SARS-CoV-2 and COVID-19 (31...)

Kashif Pirzada, MD (Toronto emergency) @KashPrime | 10:27 AM · Jan 3, 2023:
This is amazing, France is going to require clean air in classrooms, aiming at CO2 levels of 800 ppm. Other countries should quickly follow suit. Aside from limiting Covid, just the benefits of lowering common respiratory viruses makes this worth it alone, as any parent knows.

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NOUS AÉRONS @nousaerons | 3:29 AM · Jan 3, 2023:
We offer a translation into English of our synoptic on the new French environmental code relating to the measurement of CO2 in schools.
A PDF version is available at http://nousaerons.fr/regulations
This is intended for foreigners who have expressed an interest in this new code.
Table in English ( https://twitter.com/nousaerons/status/1610191726924136454/photo/1 )

This New Variant Could Make You Pay for Skipping the Booster
Many Americans have been ignoring coronavirus case counts—and variants that seem to come and go every few weeks. This one is different.
Peter J. Hotez | Jan. 05, 2023

"...the new XBB.1.5 subvariant now ascending in the United States. The strain is no harbinger of a new pandemic abyss, but does pose a greater threat than a slew of variants that preceded it...

... one preliminary study published in late December in the New England Journal of Medicine suggested that those who received the bivalent booster were more likely to have virus antibodies that cross-neutralized the scrabble variants (including XBB) in the test tube. Although these studies need to be repeated specifically with XBB.1.5, the data could mean you have a better chance at fighting off the XBB.1.5 variant if you get the bivalent booster.

Unfortunately, XBB.1.5 is still too new to have clinical data in-hand to show exactly what vaccines mean in terms of warding it off. At the Texas Children’s Hospital Center for Vaccine Development, we, like other groups, are scrambling to look at our own vaccine’s effects on XBB.1.5. However, the writing is on the wall here—boosting is your best bet at protecting yourself and your loved ones..."

https://www.thedailybeast.com/this-new-variant-could-make-you-pay-for-skipping-t...
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Dr David Berger, aBsuRdiSTe cROnickLeR @YouAreLobbyLud | 7:43 AM · Jan 4, 2023
Activist doctor Remote GP Emergency doc in Australia

1/ HOW DIFFERENT IS XBB.1.5 AND HOW WORRYING IS IT?

Very. This graphic from the linked paper shows it is as different from the Wuhan variant (now known as WT = Wild Type) of SARS-COV-2 as WT is from SARS-COV (the virus which caused SARS1 in 2003).

Preprint ( https://biorxiv.org/content/10.1101/2022.11.23.517532v1.full.pdf )
Fig S3 ( https://twitter.com/YouAreLobbyLud/status/1610617921692131334/photo/1 )

2/ The briefest of explanations of the graphic, more in the paper:
It shows the degree of neutralisation of the different variants by the sera of people with a selection of vaccination options and also people who are post infection.

3/ D614G refers to a mutation on the spike protein of WT. As you can see, all the post-vaccination and post-infection sera exhibit their maximum neutralising activity against the D614G-containing WT.

4/ By contrast, their effect against both XBB and SARS-COV is equally minimal. In other words, both these entities are as antigenically distant from WT as they are from each other. That is remarkable and shows just how far SARS-COV-2 has evolved in the form of the XBB variants.

5/ They also say in the paper that:
"The extent of the antigenic drift or shift measured herein is comparable to the antigenic leap made by the initial Omicron variant from its predecessors one year ago." See next tweet for a visualisation of this.

6/ This graphic is mine. I wanted to try and make it as easy as possible to visualise the distance these variants have evolved:
XBB as far from Omicron as Omicron is from WT
XBB as far from WT as WT is from SARS-COV.a
Image ( https://twitter.com/YouAreLobbyLud/status/1610617934476632065/photo/1 )

7-10/ What do we conclude?
a) The variants are evolving at a massive rate.
b) The variants are evolving in partially immune populations to evade immunity and neutralisation by monoclonal antibodies.
c) Separate to this paper, and as per @VirusesImmunity ( Prof. Akiko Iwasaki (Yale U)* ), affinity for the ACE-2 receptor, expressed on the cell surface and the means by which the virus enters the cell, is massively increased, leading to increased likelihood of severe disease and possibly long covid.
d) That there is no scientific justification for the arbitrary decision by WHO to stop assigning Greek letters with Omicron. This is a political decision, designed to support the fiction that the virus has somehow stopped evolving so much. In fact, the opposite is true.
e) The pandemics is not "over". Rather, the signs are that it is accelerating and that we risk finding ourselves back to square one in terms of vaccine (and post-infection) immunity and effective treatments.

11/ In short, this is an emergency and we must shift immediately to both SUPPRESS TRANSMISSION and update vaccines as quickly as possible.

We have known this for a long time. We know it even more now. We must act before it is too late.

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* Prof. Akiko Iwasaki (Yale U, studies nasal vaxx, long covid) @VirusesImmunity | 10:03 AM · Jan 2, 2023:
A very important and informative thread about why the Omicron XBB.1.5 subvariant is now dominating in the Northeast US and is expected to spread. Please protect yourselves and others by wearing N95 masks. I am truly concerned about the #longCOVID wave that follows this infection.

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Yunlong Richard Cao ( Assistant Professor at Peking University ) @yunlong_cao | 8:45 PM · Dec 27, 2022:
The superior growth advantage of XBB.1.5 has been well-documented by many colleagues @JPWeiland @LongDesertTrain @EricTopol. Here I'll add some experimental data:
1) XBB.1.5 is equally immune evasive as XBB.1, but
2) XBB.1.5 has a much higher hACE2 binding affinity. 1/
Show this thread ( https://twitter.com/yunlong_cao/status/1607915567696203776 )
graphs ( https://twitter.com/yunlong_cao/status/1607915567696203776/photo/1 )
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Dr. Jeff Gilchrist @jeffgilchrist | 6:45 AM · Jan 5, 2023:
( I am an AI Data Scientist in Ottawa, Ontario, Canada collaborating on pediatric medical research projects including developing clinical decision support and prediction systems for the NICU. I'm also an Adjunct Research Professor at Carleton University. )

There hasn't been enough time to actually confirm XBB.1.5 Kraken is actually less severe, but even if that is true, this is how "more transmissible but less severe" turned out over the past year... more deaths in 2022 than 2021 or 2020, and more infected people = more Long COVID.

Chart showing Canada Annual Reported COVID Deaths were much higher in 2022 than in 2021 or 2020 (by Bill Comeau):
https://twitter.com/jeffgilchrist/status/1610965613706452993/photo/1
https://public.tableau.com/app/profile/bill.comeau/viz/CanadaCovid19_16636261617...

Darn...other nasally-administered vaxx are being studied, but nasally administered ChAdOx1 (chimpanzee adenovirus vaxx developed at Oxford U, Astrazeneca) failed to induce mucosal immunity in small Phase 1 clinical trial.

Intranasal COVID-19 vaccine fails to induce mucosal immunity
Nature Medicine explores the latest translational and clinical research news, with a clinical trial of an intranasal ChAdOx1 vaccine.
Thiago Carvalho | 03 November 2022

A team led by Oxford University’s Alexander Douglas reported disappointing phase 1 trial results for intranasal administration of the ChAdOx1 vaccine against COVID-19. Consisting of a replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 spike protein, the vaccine is usually delivered intramuscularly and has proven effective at preventing serious illness and death, but none of the current vaccines have had similar success at blocking viral transmission. Mucosal vaccines could potentially prevent SARS-CoV-2 infection at the point of viral entry in the respiratory tract, halting the spread of the virus. “We urgently need more research to develop vaccines which can block transmission of respiratory pandemic viruses using delivery routes which are safe and practical at large scale,” said Douglas in a press release...

https://www.nature.com/articles/d41591-022-00106-z
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Intranasal COVID-19 vaccine candidate’s clinical data highlights need for further development of nasal spray vaccines
(PRESS RELEASE) U Oxford | 11 October 2022
https://www.ox.ac.uk/news/2022-10-11-intranasal-covid-19-vaccine-candidate-s-cli...
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Meera Madhavan et al. 2022. Tolerability and immunogenicity of an intranasally-administered adenovirus-vectored COVID-19 vaccine: An open-label partially-randomised ascending dose phase I trial. EBioMedicine (Lancet) Volume 85, 104298, November 01, 2022. Open Access Published:October 10, 2022. DOI:https://doi.org/10.1016/j.ebiom.2022.104298 https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(22)00480-7/fullte...

Summary
...Findings - Reactogenicity was mild or moderate. Antigen-specific mucosal antibody responses to intranasal vaccination were detectable in a minority of participants, rarely exceeding levels seen after SARS-CoV-2 infection. Systemic responses to intranasal vaccination were typically weaker than after intramuscular vaccination with ChAdOx1 nCoV-19. Antigen-specific mucosal antibody was detectable in participants who received an intramuscular mRNA vaccine after intranasal vaccination. Seven participants developed symptomatic SARS-CoV-2 infection.

Interpretation - This formulation of intranasal ChAdOx1 nCoV-19 showed an acceptable tolerability profile but induced neither a consistent mucosal antibody response nor a strong systemic response.

Coronavirus found in samples from 96% of flights
Stephanie Raymond | January 3, 2023

If you believe it's now safe to fly without a protective mask, you might want to think again. New research shows the COVID-19 virus has been found on nearly every flight tested...

https://www.audacy.com/wwjnewsradio/news/national/coronavirus-found-in-samples-f...

Raymond C. Dierk et al. 2022. Efficacy of Do-It-Yourself air filtration units in reducing exposure to simulated respiratory aerosols. Building and Environment Volume 229, 1 February 2023. https://doi.org/10.1016/j.buildenv.2022.109920 https://www.sciencedirect.com/science/article/pii/S0360132322011507

Highlights
• Do-It-Yourself (DIY) air cleaners are an alternative to commercial devices.
• DIY air cleaners can reduce exposure to simulated respiratory aerosols.
• In our study, two DIY air cleaners reduced aerosol exposure up to 73%.
• Increasing fan airflow and filter depth significantly improved performance.
• Performance depends on materials, design, and construction quality.

Abstract
Many respiratory diseases, including COVID-19, can be spread by aerosols expelled by infected people when they cough, talk, sing, or exhale. Exposure to these aerosols indoors can be reduced by portable air filtration units (air cleaners). Homemade or Do-It-Yourself (DIY) air filtration units are a popular alternative to commercially produced devices, but performance data is limited. Our study used a speaker-audience model to examine the efficacy of two popular types of DIY air filtration units, the Corsi-Rosenthal cube and a modified Ford air filtration unit, in reducing exposure to simulated respiratory aerosols within a mock classroom. Experiments were conducted using four breathing simulators at different locations in the room, one acting as the respiratory aerosol source and three as recipients. Optical particle spectrometers monitored simulated respiratory aerosol particles (0.3–3 μm) as they dispersed throughout the room. Using two DIY cubes (in the front and back of the room) increased the air change rate as much as 12.4 over room ventilation, depending on filter thickness and fan airflow. Using multiple linear regression, each unit increase of air change reduced exposure by 10%. Increasing the number of filters, filter thickness, and fan airflow significantly enhanced the air change rate, which resulted in exposure reductions of up to 73%. Our results show DIY air filtration units can be an effective means of reducing aerosol exposure. However, they also show performance of DIY units can vary considerably depending upon their design, construction, and positioning, and users should be mindful of these limitations.

>4 margd: Well today at least you don't have to worry about the anti-mask people the boobs running this Gov (FAA) have managed to shut down every airport in America the new Bannana Republic....JMJ....

>6 brone:

In addition to domestic flights, 911 had troubles in Michigan, too.
I smell domestic terrorism--aided by usual suspects?

Study explores incidence, severity, and long COVID associations of SARS-CoV-2 reinfections
Dr. Chinta Sidharthan | Jan 10 2023

...Conclusions
Overall, the results indicated that the severity of SARS-CoV-2 reinfections was similar to those of the initial infection, with individuals who experienced mild to moderate symptoms during the first infection having similar symptoms during reinfection, while individuals who experienced a severe initial infection having similar reinfection symptoms or succumbing to the disease after reinfection.

Additionally, the study reported that long COVID diagnoses during the Omicron epoch occurred much closer to the index date of the infection or reinfection, and the number of long COVID diagnoses also showed an increase after reinfections with recent variants.

https://www.news-medical.net/news/20230110/Study-explores-incidence-severity-and...
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Emily Hadley et al. 2023. SARS-CoV-2 Reinfection is Preceded by Unique Biomarkers and Related to Initial Infection Timing and Severity: an N3C RECOVER EHR-Based Cohort Study. MedRxiv 5 Jan 2023
doi: https://doi.org/10.1101/2023.01.03.22284042 https://www.medrxiv.org/content/10.1101/2023.01.03.22284042v1

This article is a preprint and has not been peer-reviewed

Abstract
...We validate previous findings of reinfection incidence (5.9%), the occurrence of most reinfections during the Omicron epoch, and evidence of multiple reinfections. We present novel findings that Long COVID diagnoses occur closer to the index date for infection or reinfection in the Omicron BA epoch. We report lower albumin levels* leading up to reinfection and a statistically significant association of severity between first infection and reinfection...
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* Re albumin, if you're puffy (experiencing edema), you might want to try vitamin B6 to see if it increases your albumin production? Can't hurt?

Viki Male @VikiLovesFACS | 5:36 AM · Jan 13, 2023:
Immunologist working on pregnancy at @ImperialCollege {London}...

🇺🇸 1794 ppl giving birth in NYC Apr 20 - Nov 21, of whom 250 received #CovidVaccine in #pregnancy

👉🏻 No difference in risk of preterm birth, baby smaller than expected or needing NICU

👉🏻 Trimester of vaccination made no difference to these outcomes

Erona Ibroci et al. 2023. Impact of prenatal COVID-19 vaccination on delivery and neonatal outcomes: Results from a New York City cohort. Vaccine Volume 41, Issue 3, 16 January 2023, Pages 649-656 https://doi.org/10.1016/j.vaccine.2022.09.095 https://www.sciencedirect.com/science/article/pii/S0264410X22012269

Abstract
...In our sample, 13.7% (n = 250) received at least one prenatal dose of any COVID-19 vaccine. Vaccination was not associated with birthweight ..., gestational age ..., blood loss ..., the risks of CD {Caesarian delivery}... or NICU admission .... Trimester of vaccine initiation was also not associated with these outcomes. Our findings suggest that there is no associated risk between prenatal COVID-19 vaccination and adverse delivery and neonatal outcomes in a cohort sample from NYC.

5. Conclusion
COVID-19 vaccination during pregnancy was not adversely associated with birthweight, gestational age at delivery, blood loss at delivery, mode of delivery, and NICU admission in a prospective cohort sample from New York City. Our study adds to the growing literature on the safety of COVID-19 vaccination in pregnancy and supports the continued recommendation of vaccination of pregnant individuals against SARS-CoV-2. Thus, it may help providers counsel pregnant patients on the safety and benefits of COVID-19 vaccination during pregnancy, which is particularly important considering the higher risk of severe COVID-19 during pregnancy.

Dr. Deepti Gurdasani @dgurdasani1 | 9:56 AM · Jan 12, 2023:
Clinical epidemiologist (Queen Mary U London? Australia?)
https://twitter.com/dgurdasani1/status/1613550460576882688
https://threadreaderapp.com/thread/1613550460576882688

Interesting published in the BMJ on long COVID from Israel. Despite EHRs { electronic health records } known to underestimate long COVID (these should be considered the lower bound), it shows
-significant burden of symptoms in mostly young people with 'mild' COVID at 6mo-1 yr
- ⬆️in strep tonsillitis
🧵

Barak Mizrahi et al. 2023. Long covid outcomes at one year after mild SARS-CoV-2 infection: nationwide cohort study
BMJ 2023;380:e072529. (Published 11 January 2023) doi: https://doi.org/10.1136/bmj-2022-072529 https://www.bmj.com/content/380/bmj-2022-072529##

Abstract
...Results Covid-19 infection was significantly associated with increased risks in early and late periods for
anosmia {loss of smell} and dysgeusia {taste disorder} ...
cognitive impairment...
dyspnoea {labored breathing} ...
weakness ..., and
palpitations ... and with
significant but lower excess risk for streptococcal tonsillitis and dizziness.

Hair loss, chest pain, cough, myalgia, and respiratory disorders were significantly increased only during the early phase.

Male and female patients showed minor differences, and children had fewer outcomes than adults during the early phase of covid-19, which mostly resolved in the late period.

Findings remained consistent across SARS-CoV-2 variants.

Vaccinated patients with a breakthrough SARS-CoV-2 infection had a lower risk for dyspnoea and similar risk for other outcomes compared with unvaccinated infected patients.

Conclusions This nationwide study suggests that patients with mild covid-19 are at risk for a small number of health outcomes, most of which are resolved within a year from diagnosis.

Scientists find more evidence that breast milk of those vaccinated against COVID-19 may protect infants
Samantha Murray | 12 January 2023

A 2021 study showed that breast milk of lactating mothers vaccinated against COVID-19 contained a significant supply of antibodies that may help protect nursing infants from the illness.
A new follow-up study found these antibodies in the stool of infants who consumed the breast milk of vaccinated mothers.
These findings are another piece of evidence suggesting that the breast milk of those vaccinated against COVID-19 may help protect babies from the illness...

https://blogs.ifas.ufl.edu/news/2023/01/12/scientists-find-more-evidence-that-br...
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Lauren Stewart Stafford et al. 2023. Detection of SARS-CoV-2 IgA and IgG in human milk and breastfeeding infant stool 6 months after maternal COVID-19 vaccination. Journal of Perinatology (12 January 2023). https://www.nature.com/articles/s41372-022-01581-5

In second year of COVID, study finds fewer deaths but more years of life lost
Gabrielle Emanuel | December 01, 2022

...Although the paper doesn't delve into specific reasons for the drop in median age of people dying of COVID, {lead author of the paper, Mark Czeisler, who is a student at Harvard Medical School} hypothesizes that one factor may be the large number of people over the age of 80 who died in the early months of the pandemic.

...Other factors likely include strong vaccination rates among older adults and their adherence to mitigation strategies like mask-wearing and social distancing.

...The total number of deaths from COVID is an important data point, Czeisler said, but he added that years of life lost are also important to consider. One reason is the data may influence how public health experts try to prevent similar deaths in the future.

...Since the pandemic began, about 75% of all COVID-related deaths were among people 65 years of age and older.

https://www.wbur.org/news/2022/12/01/mortality-age-data-pandemic
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Mark É. Czeisler and Charles A. Czeisler 202. Shifting Mortality Dynamics in the United States During the COVID-19 Pandemic as Measured by Years of Life. Annals of Internal Medicine (Letters) 29 November 2022. https://doi.org/10.7326/M22-2226 https://www.acpjournals.org/doi/10.7326/M22-2226

...Discussion: In the United States, 20.8% more COVID-19–involved deaths were reported in the first 10 months of the pandemic compared with a seasonally matched interval in the pandemic's second year. Despite this, 7.4% more years of life were lost in the second pandemic year during that interval due to a 35.7% increase in YLL {years of life lost} per COVID-19 death...

CDC and FDA Identify Preliminary COVID-19 Vaccine Safety Signal for Persons Aged 65 Years and Older
US FDA | January 13, 2023

...Following the availability and use of the updated (bivalent) COVID-19 vaccines, CDC’s Vaccine Safety Datalink (VSD), a near real-time surveillance system, met the statistical criteria to prompt additional investigation into whether there was a safety concern for ischemic stroke in people ages 65 and older who received the Pfizer-BioNTech COVID-19 Vaccine, Bivalent. Rapid-response investigation of the signal in the VSD raised a question of whether people 65 and older who have received the Pfizer-BioNTech COVID-19 Vaccine, Bivalent were more likely to have an ischemic stroke {} usually blood clot} in the 21 days following vaccination compared with days 22-44 following vaccination.

This preliminary signal has not been identified with the Moderna COVID-19 Vaccine, Bivalent. There also may be other confounding factors contributing to the signal identified in the VSD that merit further investigation. Furthermore, it is important to note that, to date, no other safety systems have shown a similar signal and multiple subsequent analyses have not validated this signal...

Although the totality of the data currently suggests that it is very unlikely that the signal in VSD represents a true clinical risk, we believe it is important to share this information with the public, as we have in the past, when one of our safety monitoring systems detects a signal. CDC and FDA will continue to evaluate additional data from these and other vaccine safety systems. These data and additional analyses will be discussed at the upcoming January 26 meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee.

No change in vaccination practice is recommended. CDC continues to recommend that everyone ages 6 months of age and older stay up-to-date with COVID-19 vaccination; this includes individuals who are currently eligible to receive an updated (bivalent) vaccine. ...

https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/cdc-a...

Cool, my self-diagnosed Long COVID (early 2020, before COVID tests available) had two aspects: post-exertional malaise and body aches. I resumed my daily ~3-mile walk with few hundred yards at first, very gradually building up to distance (complicated with a couple of knee issues). The body aches seemed to resolve with my first vaxx (another story). LC mostly over within a year. (Never want to go through that again! Wearing mask, vaxxed, careful to minimize exposure to "dangerous" venues these days. Dined out for first time in winter--in a tiny greenhouse. Though on Main Street on a rainy night, it was lovely! Warm, colored lights, quiet with sound of falling rain. Our trusty CO2 monitor hovered in 600s with four people, dipping to 500s every time server opened door. We tipped her well, you bet!)

Long COVID Rehab Program Shows “Impressive” Results
University of Leeds | January 17, 2023

A rehabilitation program that helps people with long COVID reduce their symptoms and increase activity levels has shown “impressive” results, say scientists.

It is based on a gradual or paced increase in a patient’s physical activity.

Before the start of the program, the people taking part in the program were reporting on average three “crashes” a week where they were left physically, emotionally or cognitively exhausted after mild physical or mental exertion. Six weeks later, at the end of the program, that was reduced to an average of one crash a week.

The patients also experienced a “moderate improvement” in their ability to be active and better quality of life....

https://scitechdaily.com/long-covid-rehab-program-shows-impressive-results/
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Megan Parker et al. 2022. Effect of using a structured pacing protocol on post-exertional symptom exacerbation and health status in a longitudinal cohort with the post-COVID-19 syndrome. Journal of Medical Virology. 2 Dec 2022. DOI: 10.1002/jmv.28373 https://onlinelibrary.wiley.com/doi/10.1002/jmv.28373

Abstract
Post-exertional symptom exacerbation (PESE) is a characteristic symptom of post-COVID syndrome (PCS). This prospective study investigated the effect of a 6-week structured World Health Organization (WHO) Borg CR-10 5-phase pacing protocol on PESE episodes and quality of life in a cohort of individuals with long-standing PCS (average duration of symptoms was 17 months). Participants received weekly telephone calls with a clinician to complete the Leeds PESE questionnaire (LPQ) and identify the appropriate phase of the pacing protocol. EQ-5D 5L was completed at the intervention's beginning and end to measure overall health. Thirty-one participants completed the 6-week protocol, with a statistically and clinically significant reduction in the average number of PESE episodes (from 3.4 episodes in Week 1 to 1.1 in Week 6), with an average decrease of 16%... each week, and reduction across all three exertional triggers (physical, cognitive, and emotional). Physical activity levels showed moderate improvements during the intervention period. Mean EQ-5D 5L scores improved from 51.4 to 60.6 points... A structured pacing protocol significantly reduces PESE episodes and improves overall health in PCS.

WHO updates COVID-19 guidelines on masks, treatments and patient care
News release | 13 January 2023

Masks continue to be a key tool against COVID-19
Reduced isolation period for COVID-19 patients
Review of COVID-19 treatments

https://www.who.int/news/item/13-01-2023-who-updates-covid-19-guidelines-on-mask...

"..Unvaccinated women with a COVID-19 diagnosis had a greater risk of {maternal morbidity and mortality index } MMMI (RR 1·36... ). Severe COVID-19 symptoms in the total sample increased the risk of severe maternal complications ({Relative Risk} RR 2·51 ... ), perinatal complications (RR 1·84 ...), and referral, intensive care unit (ICU) admission, or death (RR 11·83 ...). Severe COVID-19 symptoms in unvaccinated women increased the risk of MMMI (RR 2·88 ...) and referral, ICU admission, or death (RR 20·82 ...)..."

"...For women with a COVID-19 diagnosis, vaccine effectiveness of all vaccines combined for women with a complete regimen was 74% (95% CI 48–87) and 91% (65–98) after a booster dose...."

Jose Villar et al. 2023. Pregnancy outcomes and vaccine effectiveness during the period of omicron as the variant of concern, INTERCOVID-2022: a multinational, observational study. The Lancet, January 17, 2023. DOI:https://doi.org/10.1016/S0140-6736(22)02467-9 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02467-9/fullt...

Summary
Background--In 2021, we showed an increased risk associated with COVID-19 in pregnancy. Since then, the SARS-CoV-2 virus has undergone genetic mutations. We aimed to examine the effects on maternal and perinatal outcomes of COVID-19 during pregnancy, and evaluate vaccine effectiveness, when omicron (B.1.1.529) was the variant of concern.

Methods--INTERCOVID-2022 is a large, prospective, observational study, involving 41 hospitals across 18 countries. Each woman with real-time PCR or rapid test, laboratory-confirmed COVID-19 in pregnancy was compared with two unmatched women without a COVID-19 diagnosis who were recruited concomitantly and consecutively in pregnancy or at delivery. Mother and neonate dyads were followed until hospital discharge. Primary outcomes were maternal morbidity and mortality index (MMMI), severe neonatal morbidity index (SNMI), and severe perinatal morbidity and mortality index (SPMMI). Vaccine effectiveness was estimated, adjusted by maternal risk profile.

Findings--We enrolled 4618 pregnant women from Nov 27, 2021 (the day after WHO declared omicron a variant of concern), to June 30, 2022: 1545 (33%) women had a COVID-19 diagnosis (median gestation 36·7 weeks IQR 29·0–38·9) and 3073 (67%) women, with similar demographic characteristics, did not have a COVID-19 diagnosis. Overall, women with a diagnosis had an increased risk for MMMI (relative risk RR 1·16...) and SPMMI (RR 1·21...). Women with a diagnosis, compared with those without a diagnosis, also had increased risks of SNMI (RR 1·23 ...), although the lower bounds of the 95% CI crossed unity. Unvaccinated women with a COVID-19 diagnosis had a greater risk of MMMI (RR 1·36... ). Severe COVID-19 symptoms in the total sample increased the risk of severe maternal complications (RR 2·51 ...), perinatal complications (RR 1·84 ...), and referral, intensive care unit (ICU) admission, or death (RR 11·83...). Severe COVID-19 symptoms in unvaccinated women increased the risk of MMMI (RR 2·88 ...) and referral, ICU admission, or death (RR 20·82 ...). 2886 (63%) of 4618 total participants had at least a single dose of any vaccine, and 2476 (54%) of 4618 had either complete or booster doses. Vaccine effectiveness (all vaccines combined) for severe complications of COVID-19 for all women with a complete regimen was 48% (95% CI 22–65) and 76% (47–89) after a booster dose. For women with a COVID-19 diagnosis, vaccine effectiveness of all vaccines combined for women with a complete regimen was 74% (95% CI 48–87) and 91% (65–98) after a booster dose.

Interpretation--COVID-19 in pregnancy, during the first 6 months of omicron as the variant of concern, was associated with increased risk of severe maternal morbidity and mortality, especially among symptomatic and unvaccinated women. Women with complete or boosted vaccine doses had reduced risk for severe symptoms, complications, and death. Vaccination coverage among pregnant women remains a priority.

How your first brush with COVID warps your immunity
The immune system responds more strongly to the strain of a virus that it first met, weakening response to other strains. Can this ‘imprinting’ be overcome?
Rachel Brazil | 18 January 2023

...imprinting does seem to have dashed the hope that the introduction of variant-targeted mRNA boosters will provide greater protection against infection than sticking with the original vaccine. Boosters introduced in Europe last September targeted the original strain and the BA.1 Omicron variant; the United States has rolled out boosters aimed at the BA.5 Omicron variant. The vaccines certainly boost antibody levels, but the antibodies produced are not Omicron specific and are unlikely to offer significantly increased protection against Omicron infection...

So what does this mean for our current vaccines? (Immunologist Rosemary Boyton at Imperial College London) says that they are “brilliant” in their ability to protect against serious illness. But, she says, now that most people are protected, scientists should focus on finding vaccines that can overcome imprinting, to halt the spread of the virus, not just the severity of disease. “Now we’re in a slightly different place, we’ve got to think slightly differently.”

(Immunologist Bob Seder, acting chief of the Vaccine Immunology Program at the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland) agrees that vaccines will need to change if they are to limit infection and transmission, rather than just prevent fatalities. He says that one approach would be to use live vaccines, which would persist in the body for 5–10 days and might produce a more effective response. But live vaccines pose greater risks, particularly for vulnerable people, owing to the dangers of even a weakened virus multiplying.

Instead, Seder is looking at nasal vaccines, which he thinks could be more effective against variants than injected vaccines. Spraying a vaccine directly into the nose could induce mucosal immunity — an immune response in the cells that make up the lining of the respiratory system and other mucous membranes. In a natural infection, the mucous membranes are the first barrier a virus will encounter. The antibody response here is prolific and designed to thwart virus entry. The response might still carry some imprint of past exposure, but its sheer strength could create better protection — even preventing infection and transmission. A study...published last year showed that the antibody response produced by injected vaccines bypasses the antibody cascade that mucosal immunity induces, whereas a breakthrough infection does induce this response.

Seder is now comparing nasal and injected mRNA vaccines in animals to see whether they can improve the response to Omicron. Data on how these vaccines perform in humans are sparse, and mixed. In October, a phase I clinical trial of a vaccine developed by Astrazeneca and the University of Oxford, UK, administered as a nasal spray, reported mucosal antibody responses in only a minority of participants, and weaker systemic responses than were obtained with intramuscular vaccination...

Another approach is the use of adjuvants — ingredients added to vaccines that help to boost the immune response. Adjuvants have been shown to alleviate imprinting in vaccination against flu... So far, their effect on imprinting in COVID-19 has not been tested.

The ideal immune response is strong and broad — both for disarming imprinting and for fighting a wider range of viruses and variants, says Boyton. A vaccine against SARS-CoV-2 and all its relatives — a pan-coronavirus vaccine — would induce a wider variety of antibodies that target multiple parts of the virus. Such a vaccine could prevent the virus from mutating enough to escape the immune system, and might ultimately be the key to controlling future pandemics. The hunt for such a vaccine is ongoing.

Imprinting is often presented as a problem, but it’s a fundamental part of immune memory that delivers a lightning-fast response to a viral invader, without having to start from scratch. “To me,” says (immunologist Gabriel Victora at the Rockefeller University in New York City ), “it means that the immune system is quite smart at covering its bases.”

https://www.nature.com/articles/d41586-023-00086-1

Fatal heart attacks have surged in Australia. Here’s why
Aisha Dow | January 21, 2023

...The number of excess deaths in Australia surged to 15,400 in the first part of 2022.

While the majority of these deaths were from COVID-19, the nation is also seeing significantly elevated rates of deaths from diabetes, strokes and ischemic heart disease.

Cardiologists believe the increased deaths from ischemic heart disease are likely linked to the damaging effects of COVID, but also delayed diagnoses, prevention and treatment through the pandemic...

https://www.smh.com.au/national/fatal-heart-attacks-have-surged-in-australia-her...

Analysis of seemingly recovered COVID-19 patients indicates that SARS-CoV-2 infection can persist significantly longer than suggested by PCR-negative tests
Sanchari Sinha Dutta | Jan 20 2023

...The study describes pathological lung features of COVID-19 patients who died due to progressively worsening disease, despite having persistent virus-negative PCR results for a long period. The pathological lung features of these deceased patients are similar to that observed in a patient with acute SARS-CoV-2 infection.

Interestingly, virus-infected cells have been detected in specific lung regions of these patients, including the para-bronchial glands and bronchial cartilage. As mentioned by the scientists, the long-term presence of specific virus-infected cells could cause pathological lung changes by maintaining a pro-inflammatory, immunoreactive, and pro-thrombogenic status. Further studies are required to establish the relationship between persistently infected cells and the development of long-COVID.

https://www.news-medical.net/news/20230120/Analysis-of-seemingly-recovered-COVID...
----------------------------------------------------------------------------------

Rossana Bussani eal. 2023. Persistent SARS-CoV-2 infection in patients seemingly recovered from COVID-19. J of Pathology. First published: 18 January 2023. https://doi.org/10.1002/path.6035 https://onlinelibrary.wiley.com/doi/10.1002/path.6035

Abstract
SARS-CoV-2 infection is clinically heterogeneous, ranging from asymptomatic to deadly. A few patients with COVID-19 appear to recover from acute viral infection but nevertheless progress in their disease and eventually die, despite persistent negativity at molecular tests for SARS-CoV-2 RNA. Here, we performed post-mortem analyses in 27 consecutive patients who had apparently recovered from COVID-19 but had progressively worsened in their clinical conditions despite repeated viral negativity in nasopharyngeal swabs or bronchioalveolar lavage for 11–300 consecutive days (average: 105.5 days). Three of these patients remained PCR-negative for over 9 months. Post-mortem analysis revealed evidence of diffuse or focal interstitial pneumonia in 23/27 (81%) patients, accompanied by extensive fibrotic substitution in 13 cases (47%). Despite apparent virological remission, lung pathology was similar to that observed in acute COVID-19 individuals, including micro- and macro-vascular thrombosis (67% of cases), vasculitis (24%), squamous metaplasia of the respiratory epithelium (30%), frequent cytological abnormalities and syncytia (67%), and the presence of dysmorphic features in the bronchial cartilage (44%). Consistent with molecular test negativity, SARS-CoV-2 antigens were not detected in the respiratory epithelium. In contrast, antibodies against both spike and nucleocapsid revealed the frequent (70%) infection of bronchial cartilage chondrocytes and para-bronchial gland epithelial cells. In a few patients (19%), we also detected positivity in vascular pericytes and endothelial cells. Quantitative RT-PCR amplification in tissue lysates confirmed the presence of viral RNA. Together, these findings indicate that SARS-CoV-2 infection can persist significantly longer than suggested by standard PCR-negative tests, with specific infection of specific cell types in the lung. Whether these persistently infected cells also play a pathogenic role in long COVID remains to be addressed.

The benefit of bivalent boosters for enhanced, ~80% protection from hospitalizations and deaths (vs vaccine plus prior prior booster or unvaccinated) has now been shown in 6 countries (Israel, US, Denmark, Norway, Finland, Sweden)
Graphs hospitalization w BA4-5 v. BA1 boosters ( https://twitter.com/EricTopol/status/1617553655712083969/photo/1 )
-Eric Topol @EricTopol | 11:03 AM · Jan 23, 2023

Niklas Worm Andersson et al. 2023. Comparative effectiveness of the bivalent BA.4-5 and BA.1 mRNA-booster vaccines in the Nordic countries.MedRxiv Posted January 19, 2023. doi: https://doi.org/10.1101/2023.01.19.23284764 https://www.medrxiv.org/content/10.1101/2023.01.19.23284764v1

This article is a preprint and has not been certified by peer review

ABSTRACT
...Results Compared with having received three vaccine doses, receipt of a bivalent BA.4-5 booster as a fourth dose was associated with a country-combined CVE against Covid-19 hospitalization of 80.5% (95% confidence interval, 69.5% to 91.5%). The corresponding CVE for bivalent BA.1 boosters was 74.0% (68.6% to 79.4%). CVE against Covid-19 death was 77.8% (48.3% to 100%) and 80.1% (72.0% to 88.2%) for bivalent BA.4-5 and BA.1 boosters as a fourth dose, respectively. The CVE of bivalent BA.4-5 vs. BA.1 boosters were 32.3% (10.6% to 53.9%) for Covid-19 hospitalization and 12.3% (−36.1% to 60.7%) for death (the latter estimable in Denmark only).

Conclusions Vaccination with bivalent BA.4-5 or BA.1 mRNA-booster vaccines as a fourth dose was associated with increased protection against Covid-19 hospitalization and death during a period of BA.4-5 predominance. Bivalent BA.4-5 boosters conferred moderately greater vaccine effectiveness against Covid-19 hospitalization compared with bivalent BA.1 boosters.
------------------------------------------------------------------

The bivalent vaccine booster outperforms
A review of the cumulative body of evidence
Eric Topol (MD-scientist, Scripps) | 11 Jan 2023

You may recall that I was a skeptic about the bivalent BA.5 vaccine when the FDA gave it the OK to roll out in September without any human data. At the very least, I had hoped there would be lab studies to confirm a strong immune response to this variant, and that it was superior to the original (monovalent) booster that was directed to the ancestral (Wuhan) strain. But we now have extensive data that is quite encouraging—better and broader than expected— that I’m going to briefly review here...

Lab Studies
The new Israeli study
The CDC report CDC Results Through November 2022, the BQ.1.1 wave
The Bivalent Vaccine Detractors and Naysayers
The Bottom Line Addendum re: Possible signal of risk for bivalent in age 65+

https://erictopol.substack.com/p/the-bivalent-vaccine-booster-outperforms

Elon Musk says he"felt like he was dying after his 2nd booster shot"....AMDG....

>21 brone: Yes, a second booster shot can be quite a kick in the pants, as the immune system jumps all over the invader. It doesn't, however, actually kill people, unlike COVID.

Those living with pre-existing autoimmune diseases were at least 3 times more likely to develop Long Covid after infection with SARS-CoV-2 than those who do not have these conditions.

Elizabeth T. Jacobs et al. 2023. Pre-existing conditions associated with post-acute sequelae of COVID-19. Journal of Autoimmunity
Volume 135, February 2023, 102991. https://doi.org/10.1016/j.jaut.2022.102991 https://www.sciencedirect.com/science/article/pii/S0896841122001998

Abstract
Post-acute sequelae of COVID-19 (PASC) are conditions that occur or remain at least 28 days after SARS-CoV-2 infection. While some risk factors for PASC have been identified, little is known about pre-existing conditions that render one susceptible to developing PASC. Data from participants (n = 1224) in a longitudinal COVID-19 cohort study in Arizona were used to investigate comorbid conditions associated with PASC.

After adjustment of the models for age, BMI, gender, race, and smoking, the following pre-existing conditions were statistically significantly associated with the development of PASC:
asthma (OR = 1.54;...);
chronic constipation (OR = 4.29...);
reflux (OR = 1.54...);
rheumatoid arthritis (OR = 3.69...);
seasonal allergies (OR = 1.56...); and
depression/anxiety (OR = 1.72...).

When grouping conditions together, statistically significant associations with PASC were observed for
respiratory (OR = 1.47...);
gastrointestinal (OR = 1.62), and
autoimmune conditions (OR = 4.38...).

After adjustment for severity of acute SARS-CoV-2 infection and depression/anxiety,
seasonal allergies (OR = 1.48...) and
autoimmune disease (OR = 3.78...) remained significantly associated with risk for PASC.

These findings indicate that numerous pre-existing conditions may be associated with an increased risk for the development of PASC. Patients with these conditions should consider taking extra steps to avoid infection.

Niomi Wolf a self proclaimed feminist of the third wave (?) has written a book called the New Authoritarians, covid and the war against the human. The former advisor to Bill/Hillary/Al Gore says That the first lockdown in Italy was the first strike against the foundation of western society by the Chineses (how Xenophobic). In her diverse neighborhood of the Bronx we recognized what was coming "I hhave lived in closed societies- we recognized their movements. We both knew something bad was on the way. Lockdown is an abandonment of a free society, it means a new society; totalitarian oligarchy, the fact that we allowed it means we have lost our freedom for the unseeable future. Like many Wolf believed the narrative and the facts in the beginning. The utter lack of critical thinking of the media turned the fear of the virus into a cult such as Milton's Satan. These guys running this infringment on our rights don't need a sign or secret hand shake, they simply owned the stratum, they are accountable to only one another. We the heath freedom group who oppose mandates by big Tech, Pharma, media, guv. have broken their labors to contol us therfore we are a threat to the obeying masses, you would think you guys with slogans such as "my body my life" pro choice stuff would support us....JMJ....

>24 brone: Niomi Wolf

Do you mean Naomi Wolf? Whose Wikipedia page says, near the top, "Since around 2014, Wolf has been described, by journalists and media outlets, as a conspiracy theorist."?

feminist of the third wave (?)

Are you confused about what third-wave feminism is? Have you ever thought about checking what Wikipedia says?

You complain about being categorized into left or right, and yet you think that the rest of us will be entranced by the name of Naomi Wolf. It requires more argument than that.

Lockdown is an abandonment of a free society,

Yes. There are times of emergency when we give up some of our freedoms to protect others, like wars, disasters and plagues. Proportionality is up for question, but I deny firmly that we have an unbounded right to act without concern for who we hurt.

it means a new society; totalitarian oligarchy, the fact that we allowed it means we have lost our freedom for the unseeable future.

The fact that we have allowed some restrictions for a limited period of time, as a democratic society, means that we have lost freedom forever?

they simply owned the stratum,

Or a democratic society made choices, done as a representative democracy does by letting the representatives of the people make those choices, as they needed to be done promptly.

Mini-Mini #corsirosenthalbox; DIY air filter for vehicles

My Godson is a struggling artist who drives a cab to make ends meet. For his birthday present I built this MIni-Mini #corsirosenthalbox. It uses PC fans and and 4- MERV 13 - 6X6X1 filters. Connects to a USB port. Should provide about 30 ACH {air change per hour} in his cab.
Photo ( https://twitter.com/JimRosenthal4/status/1619867327914467328/photo/1 )

- Jim Rosenthal @JimRosenthal4 | 8:17 PM · Jan 29, 2023:
CEO - Tex-Air Filters. Interested in filtration, IAQ, allergies and asthma. Lifelong learner. @jimrosenthal4@mastodon.world

Comments: https://twitter.com/JimRosenthal4/status/1619867327914467328

Study: Diminished COVID Vaccine Response in Lupus
— Immunosuppressants seem responsible; mycophenolate "holiday" may help
John Gever | January 30, 2023

...Immunoglobulin G (IgG) titers measured 2 weeks after the second dose of mRNA COVID vaccines were lower by about 20% among 342 lupus patients compared with the average for 1,887 healthcare workers...most pronounced for patients taking broad-spectrum immunosuppressants, including MMF and tacrolimus, with reductions in IgG response of about 30% relative to the healthcare workers

But holding MMF for a period of time (typically a week) after vaccination ameliorated the reduction, such that post-immunization IgG titers were down by about 20% in patients having drug "holidays" relative to the non-SLE group. And no increase in SLE flare rates were seen with the holidays...

...report adds to considerable literature showing that common therapies for rheumatologic diseases can diminish vaccine efficacyopens in a new tab or window, although not by enough to make them useless. Indeed, earlier this month, the American College of Rheumatology (ACR) published new guidance indicating that most vaccines can be given without bothering with drug holidays, albeit with some exceptions: https://www.medpagetoday.com/rheumatology/generalrheumatology/102509 .

...Those guidelines, however, deliberately excluded COVID vaccines because the evidence is still evolving. An ACR guideline issued last August on COVID vaccination for rheumatologic disease patients called for many drugs to be paused for 1 to 2 weeks. These included MMF and other broad-spectrum immunosuppressants, as well as more targeted therapies such as belimumab, rituximab (Rituxan), and Janus-activated kinase inhibitors. Holding MMF for at least 10 days was found to be optimal in a study reported at ACR's annual meeting in 2022 by a different Hopkins group...

https://www.medpagetoday.com/rheumatology/lupus/102876
----------------------------------------------------------

Michelle Petri et al. 2023. Effect of Systemic Lupus and Immunosuppressives on COVID Vaccination Antibody Response. Arthritis Care and Research. First published: 30 January 2023. https://doi.org/10.1002/acr.25094 https://onlinelibrary.wiley.com/doi/10.1002/acr.25094

ABSTRACT
...Results
The analysis was based on 365 observations from 334 different patients in the SLE (Systemic Lupus Erythematosus ) cohort, and 2235 observations from 1887 different health care workers. SLE patients on immunosuppressive medications had lower vaccine IgG levels than SLE patients who were not; but both groups had lower levels than healthcare workers. Holding mycophenolate for one week after vaccination increased post-vaccine IgG levels significantly without leading to clinical flares. In multiple variable models, mycophenolate mofetil, tacrolimus, and belimumab all significantly reduced antibody response to vaccination.

Conclusion
SLE patients, regardless of background immunosuppressive therapy, had lower vaccine IgG levels than healthcare workers. Mycophenolate, tacrolimus, and belimumab significantly reduced IgG response to vaccination. Holding mycophenolate for one week improved vaccine efficacy, providing clinical benefit on vaccine response without leading to clinical flares.

#96 in thread 26, contd.
Mutagen do what mutagens do...

Could a popular COVID-19 antiviral supercharge the pandemic?
Merck & Co.’s molnupiravir appears to be speeding evolution of SARS-CoV-2
Robert F. Service | 1 Feb 2023

...The drug, molnupiravir, produced by Merck & Co., is designed to kill the virus by inducing mutations in the viral genome. A survey of viral genomes reported in a new preprint, however, suggests some people treated with the drug generate novel viruses that not only remain viable, but spread...

doi: 10.1126/science.adg9677
https://www.science.org/content/article/could-popular-covid-19-antiviral-superch...
---------------------------------------------------------------

Theo Sanderson et al. 2022. Identification of a molnupiravir-associated mutational signature in SARS-CoV-2 sequencing databases. MedRxiv 27 Jan 2023. doi: https://doi.org/10.1101/2023.01.26.23284998 https://www.medrxiv.org/content/10.1101/2023.01.26.23284998v2

This article is a preprint and has not been peer-reviewed

Abstract
Molnupiravir, an antiviral medication that has been widely used against SARS-CoV-2, acts by inducing mutations in the virus genome during replication. Most random mutations are likely to be deleterious to the virus, and many will be lethal. Molnupiravir-induced elevated mutation rates have been shown to decrease viral load in animal models. However, it is possible that some patients treated with molnupiravir might not fully clear SARS-CoV-2 infections, with the potential for onward transmission of molnupiravir-mutated viruses. We set out to systematically investigate global sequencing databases for a signature of molnupiravir mutagenesis. We find that a specific class of long phylogenetic branches appear almost exclusively in sequences from 2022, after the introduction of molnupiravir treatment, and in countries and age-groups with widespread usage of the drug. We calculate a mutational spectrum from the AGILE placebo-controlled clinical trial of molnupiravir and show that its signature, with elevated G-to-A and C-to-T rates, largely corresponds to the mutational spectrum seen in these long branches. Our data suggest a signature of molnupiravir mutagenesis can be seen in global sequencing databases, in some cases with onwards transmission.

Jordan Walker Pfizer,s Directorof Research and Development and strategic operations for nRNA. admitted that Pfizer was doing gain of function experiments to get ahead of the game to create future vaccines. Walker calls this "directed evolution". Of course Mr Pfizer immediatly distanced himself from JW and his subsequent meltdown. Mr Pfizer spin (double talk) we routinely asscess the activity of an antiviral" by conducting computer simulations or mutations of the main protease. Translation of this tapdancing, which is it if youse guys are playing with your computer well nothing wrong with that or are you actuall mutating the virus. JW in a very talkative mood states that COVID is Pfizer's "cash cow" this is what the top R&D guy thinks of the virus that started a pandemic. My last take is that JW wont be keeping his parking space at Pfizer....AMDG....

>29 brone: So you're saying that a pharmaceutical company was doing research? Yawn.

Hannah E. Davis et al. 2023. Long COVID: major findings, mechanisms and recommendations. Nature Reviews Microbiology (13 Jan 2023)
https://www.nature.com/articles/s41579-022-00846-2

Abstract
Long COVID is an often debilitating illness that occurs in at least 10% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. More than 200 symptoms have been identified with impacts on multiple organ systems. At least 65 million individuals worldwide are estimated to have long COVID, with cases increasing daily. Biomedical research has made substantial progress in identifying various pathophysiological changes and risk factors and in characterizing the illness; further, similarities with other viral-onset illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome have laid the groundwork for research in the field. In this Review, we explore the current literature and highlight key findings, the overlap with other conditions, the variable onset of symptoms, long COVID in children and the impact of vaccinations. Although these key findings are critical to understanding long COVID, current diagnostic and treatment options are insufficient, and clinical trials must be prioritized that address leading hypotheses. Additionally, to strengthen long COVID research, future studies must account for biases and SARS-CoV-2 testing issues, build on viral-onset research, be inclusive of marginalized populations and meaningfully engage patients throughout the research process.

Sections
Introduction
Major findings
Diagnostic tools and treatments
Impact of vaccines, variants and reinfections
Challenges and recommendations
Conclusions

Anders Husby @a_husby | 4:59 PM · Feb 3, 2023:
MD, PhD from Denmark. Department of Epidemiology Research, Statens Serum Institut and Department of Pediatrics, Herlev-Gentofte Hospital Digging data.
https://twitter.com/a_husby/status/1621629436079513600

A rare side-effect of SARS-CoV-2 mRNA vaccines is myocarditis {Marg: esp in young men}. The prognosis of this side-effect is not well established.
Using information from 23+ mil. residents in four countries (🇩🇰,🇫🇮,🇳🇴,🇸🇪), we compared this kind of myocarditis to other types*

...Building on previous collaborative studies, we used combined nationwide registry data from Denmark, Finland, Norway, and Sweden to follow 7,292 individuals who where admitted with new-onset myocarditis in 2018-2022...

We categorized myocarditis patients as
- SARS-CoV-2 mRNA vaccine myocarditis,
- COVID-19 myocarditis, or
- Conventional myocarditis,
based on whether myocarditis occurred within 28 days of vaccination, covid-19, or neither.

The individuals were followed up for 90 days for heart failure, death or readmission to hospital.

Patients with vaccine myocarditis had a decreased relative risk of heart failure compared with conventional myocarditis.
The relative risk of death was 0.48 (0.21-1.09) for patients with vaccine myocarditis and 2.35 (1.06-5.19) for patients with covid-19 myocarditis.

The patterns of association also were similar when using 10-day intervals.

With regards to readmission, the estimated risk of readmission to hospital was numerically lower for patients with vaccine myocarditis compared with those with conventional myocarditis, and comparable to covid-19 myocarditis.

In a subgroup analysis of myocarditis patients, we also investigated the risk of heart failure or death among younger individuals (age 12-39 years), without predisposing comorbidities.

We found that vaccine myocarditis was associated with a non-significant reduced relative risk of heart failure or death compared with conventional myocarditis (relative risk 0.50...)

We also found that covid-19 myocarditis was associated with an increased risk of heart failure or death (relative risk 5.78...) compared with vaccine myocarditis....
-----------------------------------------------

Anders Husby et al. 2023. Clinical outcomes of myocarditis after SARS-CoV-2 mRNA vaccination in four Nordic countries: population based cohort study. bmjmedicine Volume 2, Issue 1. https://bmjmedicine.bmj.com/content/2/1/e000373

Abstract
...Conclusions Compared with myocarditis associated with covid-19 disease and conventional myocarditis, myocarditis after vaccination with SARS-CoV-2 mRNA vaccines was associated with better clinical outcomes within 90 days of admission to hospital

Viki Male @VikiLovesFACS | 1:31 AM · Feb 3, 2023:
Immunologist working on pregnancy at @ImperialCollege ...
https://twitter.com/VikiLovesFACS/status/1621395947426119680

... 👉🏻 Studies in assisted conception settings also show no effect of COVID vaccination in fertility (bear with me, there are quite a lot of these…)
https://journals.lww.com/greenjournal/Fulltext/9900/In_Vitro_Fertilization_and_E...
https://academic.oup.com/humrep/article/36/9/2506/6345462
https://medrxiv.org/content/10.1101/2021.05.30.21258079v1.full.pdf
https://sciencedirect.com/science/article/pii/S2666334121000684
https://fertstert.org/article/S0015-0282%2821%2901968-3/fulltext
https://ncbi.nlm.nih.gov/pmc/articles/PMC8116639/
https://ncbi.nlm.nih.gov/pmc/articles/PMC9111235/
https://ncbi.nlm.nih.gov/pmc/articles/PMC8872833/
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2791457
https://nature.com/articles/s41598-022-25757-3
https://sciencedirect.com/science/article/pii/S001502822200022X?ref=pdf_download...

You’ll notice that lots of those include measures of ovarian health, other than the obvious (these people are getting pregnant using their own eggs). But a couple more studies were also done looking at ovarian health (AMH) in people who were not trying to conceive… You can read those here…
https://academic.oup.com/humrep/advance-article/doi/10.1093/humrep/deab282/64782...
https://smj.org.sa/content/43/5/486

I’m most interested in vaccination effects on human fertility, and though we’ve looked and looked, we can’t find any. But since the thread also brings up the animal studies…

👉🏻 No evidence of harm to fertility in rodents
ncbi.nlm.nih.gov/pmc/articles/PMC8163337/

No evidence of intact vaccine in rodent ovaries
https://twitter.com/VikiLovesFACS/status/1407743025955094532

Finally, with respect to the risks and benefits of vaccination in pregnancy, we know that COVID infection can cause preterm birth and stillbirth…
https://www.nature.com/articles/s41577-022-00703-6

Whereas evidence from more than 360,000 people vaccinated during pregnancy in formal studies finds no increased risk of any pregnancy complications.
https://docs.google.com/document/d/1_wHIYX-tGkGBPwuax7N8BxZPR4PTTCDm/edit

That’s why obstetricians and midwives in almost every country - including yours {US} - recommend getting vaccinated or boosted if you are pregnant.
https://www.acog.org/covid-19/covid-19-vaccines-and-pregnancy-conversation-guide...
...

The people responsible for the handling of the pandemic have used two weapons popular with the Nazis, fear and propaganda. Biden announced publicly the "pandemic is over" a few months ago, yesterday he extended the COVID "emergency" till May. The Nazis murdered the disabled the elderly and the feeble by the hundreds of thousands. Leaders in the west allowed tens of thousands of elderlies in nursing homes to be quarantined neglected and devoid of any early treatment. Specifically, the actions of the disgraced Ex Gov. of N.Y. Anrew Coumo. The Nazis used technology and the co-operation of large businesses to carry out their deadly practices. Similarly Big Tech, Pharma. Media, work with Governments in the west to futher their aim of control of the population, leading us down the path of mandatory, vaccines, masks, vax passports, digital id's, digital currency centrally controlled and even implantation of such technology. Justin, the dictator of the north gave us a hint of these facist policies by confiscating bank accounts, freezing morgatages, and even removing children from the protesting truckers' families. This is Naziism, Joe Goebbel would be proud, the "BIG LIE'' keep repeating it, and it becomes the only truth that you will hear....JMJ....

>34 brone: So, do clarify. When you put "emergency" in scare quotes, are you suggesting that the recent pandemic was in some way not an emergency?
If so, I suggest you review the events of the past three years. It might be instructive for you. It might even get you to reconsider some of the nonsense you've posted above.

Yes, you run the risk of learning something in the process, but I promise, it doesn't hurt and it's actually a lot more fun than living in a state of perpetual ignorance. Go on, give it a try!

>35 kiparsky: I'm suggesting it aint one now Biden himself said it....JMJ....

>36 brone: I would definitely agree that the situation has eased substantially. Although the virus is still active in communities (I just had it last week) we have safe and effective vaccines and some effective treatments, like Paxlovid (my symptoms were relatively minor due to up-to-date vaccinations and because I live in a state that has a sane response strategy, I was able to get a course of Paxlovid within hours of getting a positive test). I wouldn't call it an emergency today, though that does not by any means suggest that it is not a public health situation that we need to continue to respond to.

Would you say that the situation was an emergency when hospitals in major cities were piling up bodies in refrigerated trucks? Does that qualify as an emergency for you?

I ask because I'm trying to take what you say seriously, and that's going to be a lot easier if you try doing that yourself.

On the other hand, big Phrama Pfizer got caught with their scubs in a tangle last week. Causing them to send out a memo to its employees to shut up. A R&D CEO spilled the mutations all over the lab floor admitting that research work on mutations of Covid is a "cash cow". Actually, saying on a recorded video that Pfizer was "preemptively developing new vaccines" what for I ask for diseases they havent created yet. Pfizer immediatly went into damage control 101, saying most of the work is done by computer simulation, blah blah, this word salad reminds me of the child kidnapping charge being spun as an impromtu adoption. Pfizer has long resisted transparency, the facts are that mounting evidence links vaccine shots to significant health problems. (VAERS) a US Gov, agency reports that 34,122 deaths, 190,833 hospitalizations, 18,413 heart attacks, 26,344 myocaditis,and pericarditis cases as of this Jan 27th. Now knowing youse guy, you will say that these reports can be submitted by anyone and are therfore not credible but wait the CDC researchers are now recognizing a "high verification rate of reports of myocarditis to VAERS after recieving shots of mRNA-based Covid 19 vaccination" the CNC reports that "under reporting is more likely". Last but not least red flags are up in the Pentagon (OMED) reports drastic spikes in Hypertention, Neurological disorders, Multiple Sclerosis, Breast Cancer, infertility, Pulmonary embolisms, Migranes, Ovarian dysfunction, Testicular Cancer, I'd hold off on the next booster if I was youse guys....JMJ....

>38 brone: I'd hold off on the next booster if I was youse guys

No. Honestly, you can repeat what you're told to repeat, but do yourself a favor and get the damned booster and lie to us about it.
If you're up to date on your shots, Covid's unpleasant enough. If you're not, I understand it's really pretty unpleasant and depending on the state of your health, can potentially have long-term health consequences. Nobody here would relish the sort of poetic justice that you're setting up here, least of all you.

>39 kiparsky: As variant Sars-Covid-2 strains have emerged, deficiencies in the (covid) vaccines have become apparent, three researchers at the NIH have determined, including a guy named Fauci that name rings a bell. Just a year ago and A Dr or researcher would have been tarred and feathered for saying this claiming they were viscous, callous, unpatriotic, and despicable anti-vax rebels. The real question the researchers present is Can we trust these guys (i never did). In fact these researchers knew before the virus hit that vaccines hardly worked even for the common flu' His Eminence Dr. Fauci now admits mRNA vaccines hardly work and might not be approvable. Does that mean that those horrible unvaxed people who have lost their jobs and all those credible doctors and scientists who disagreed with the big Pharma propaganda will be compensated for their loss of earnings and reputations....JMJ....

>40 brone: The studies that I've seen are showing numbers like 90% effectiveness, meaning that compared to the unvaccinated population, there's a 90% reduction in "serious clinical outcomes" (meaning hospitalization and death) among people who have been vaccinated. Now, for most people, that combined the the fact that the vaccines are remarkably safe (ie, essentially no side effects beyond a mild fatigue lasting less than 24 hours after treatment), would be a clear indication that it is smarter to take the vaccine than not. What are the "deficiencies" you're talking about, and what convincing studies do you have to support your claims? I'm not interested in gossip and stuff you heard on the radio, so let's go with actual facts.

(EDITED to remove formatting damage from stray less-than sign)

A chain they say is only as strong as its weakest point. AS MORE AND MORE People suffer from vaccines, mandates, masks, lockdowns, People are realizing this is emerging apartheid- as more and more people realize they are always just one booster away from being counted as unclean and unvaccinated-as the families of the enforcers begin to suffer and become divided themselves-the breaking point comes closer and closer. Catholics (under surveillance by the FBI as a national security risk) know these evil times will not stand. They have already lost and we have already won. Even in the Superbowl the kicker of the winning field goal gave the glory to God! He revealed that he was wearing the badge of Our Lady around his shoulders, The Brown Scapular....AMDG....

>42 brone: I have to feel this "poor, persecuted us" attitude is part of the reason Pope Pius XI gave the Nazis such a pass for so long. Protect the Catholics, and don't think about anyone else.

>43 prosfilaes: It's interesting, usually when people actually believe that they're "winning" something they don't whine quite this much.

Frankly, I'm not sure what this dude thinks is being lost or won here, but I'm pretty sure it only matters in his head. Like most of what he says, frankly.

Rep Nancy Mace told congress she regrets getting vaccinated because of health issues that she now has which I fear will not go away. Initially a big supporter of the shot advising everyone to get it. Many (millions) of Americans are similarly concerned about mRNA injections the safety and efficacy and ethical reservations. Alarms are being raised by the increase of heart problems, stroke, neurological issues, and widespread fertility concerns.....JMJ....

>45 brone: Heh. Nancy Mace, the well-known epidemiologist and medical researcher? No, Nancy Mace the cringey right-wing snowflake.
Looks like she's trying to have her cake and eat it, saying anti-vax stuff to the anti-vax crowd and then talking up the vaccines when she's talking to a general audience. Similarly, she voted against impeaching the former guy for his incitement to treason which nearly led to the murder of his vice-president and killed a number of Capitol Police officers (what happened to "Blue Lives Matter"?) but "condemned" his actions when talking to people who would be pleased by that sort of talk.
So, not someone known for integrity.

Speaking of people who expressed regrets for their positions, she mentions "natural immunity". As I recall, a number of prominent advocates for this vaccine-the-hard-way strategy expressed regret for taking this position, shortly before they died of Covid.

Think I acquired Long COVID early in 2020: exercise intolerance was a big part of it. For almost a year I could only walk a few hundred yards--with a cane--of my usual 3 miles a day. Study below might explain:

Eric Topol (MD-scientist, Scripps) @EricTopol | 6:12 PM · Feb 16, 2023:
Muscle biopsy in-depth assessment in people with #LongCovid w/ exercise symptoms compared with 2 control groups shows microvascular abnormalities with reduced capillaries, immune cell dysregulation, distinct gene expression signature...

Tom Aschman et al. 2023. Post-COVID syndrome is associated with capillary alterations, macrophage infiltration and distinct transcriptomic signatures in skeletal muscles. MedRxiv 16 Feb 2023. doi: https://doi.org/10.1101/2023.02.15.23285584 https://medrxiv.org/content/10.1101/2023.02.15.23285584v1

This article is a preprint and has not been certified by peer review

Abstract
The SARS-CoV-2 pandemic not only resulted in millions of acute infections worldwide, but also caused innumerable cases of post-infectious syndromes, colloquially referred to as long COVID. Due to the heterogeneous nature of symptoms and scarcity of available tissue samples, little is known about the underlying mechanisms. We present an in-depth analysis of skeletal muscle biopsies obtained from eleven patients suffering from enduring fatigue and post-exertional malaise after an infection with SARS-CoV-2. Compared to two independent historical control cohorts, patients with post-COVID exertion intolerance had fewer capillaries, thicker capillary basement membranes and increased numbers of CD169+ macrophages. SARS-CoV-2 RNA could not be detected in the muscle tissues, but transcriptomic analysis revealed distinct gene signatures compared to the two control cohorts, indicating immune dysregulations and altered metabolic pathways. We hypothesize that the initial viral infection may have caused immune-mediated structural changes of the microvasculature, potentially explaining the exercise-dependent fatigue and muscle pain.

Image ( https://twitter.com/EricTopol/status/1626358954640146432/photo/1 )

Study below made me wonder if B3 might help some folks with Long Covid, esp. exercise intolerance

Twin study finds form of vitamin B3 may increase mitochondria in muscle cells
Life Extension Newsletter | 21 Feb 2023
https://www.lifeextension.com/newsletter/2023/2/vitamin-b3-may-increase-mitochon...
------------------------------------------------

Helena A. K. Lapatto et al. 2023. Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study. Science Advances 13 Jan 2023
Vol 9, Issue 2. DOI: 10.1126/sciadv.add5163

Abstract
Nicotinamide adenine dinucleotide (NAD+) precursor nicotinamide riboside (NR) has emerged as a promising compound to improve obesity-associated mitochondrial dysfunction and metabolic syndrome in mice. However, most short-term clinical trials conducted so far have not reported positive outcomes. Therefore, we aimed to determine whether long-term NR supplementation boosts mitochondrial biogenesis and metabolic health in humans. Twenty body mass index (BMI)–discordant monozygotic twin pairs were supplemented with an escalating dose of NR (250 to 1000 mg/day) for 5 months. NR improved systemic NAD+ metabolism, muscle mitochondrial number, myoblast differentiation, and gut microbiota composition in both cotwins. NR also showed a capacity to modulate epigenetic control of gene expression in muscle and adipose tissue in both cotwins. However, NR did not ameliorate adiposity or metabolic health. Overall, our results suggest that NR acts as a potent modifier of NAD+ metabolism, muscle mitochondrial biogenesis and stem cell function, gut microbiota, and DNA methylation in humans irrespective of BMI.

...Discussion
...In conclusion, NR supplementation is a potential treatment option to be tested in individuals with decreased muscle mitochondrial biogenesis and dysbiosis. As possible adverse effects, we report a declining muscle satellite cell number and a possibility for impaired glucose metabolism. As patients with chronic muscle disease typically exhibit satellite cell dysfunction, muscle performance and regeneration are important endpoints to be monitored in future NR clinical trials. Overall, our data underscore the role of NR as a potent modifier of systemic NAD+ levels, muscle mitochondrial biogenesis, satellite cell function, DNA methylation, and the gut microbiota in humans. Notably, NR modulated these metabolic processes similarly in both leaner and heavier cotwins, i.e., regardless of BMI.
________________________________________________

Nicotinamide Riboside: Benefits, Side Effects and Dosage
Ryan Raman | December 10, 2018

... unlike vitamin B3 (niacin) supplements, nicotinamide riboside should not cause facial flushing...

https://www.healthline.com/nutrition/nicotinamide-riboside#benefits

J. E. Canuck, MD {Family Medicine} @DrCanuckMD | 12:02 PM · Feb 25, 2023
Study this week found full vaccination against COVID-19 is associated with a significantly lower risk of major cardiovascular events following SARS-CoV-2 infection when compared with not being vaccinated. If you’re worried about your heart get vaccinated.
---------------------------------------------------

{Behind paywall, unfortunately:}

Joy Jiang et al. 2023. Impact of Vaccination on Major Adverse Cardiovascular Events in Patients With COVID-19 Infection (Letter). J Am Coll Cardiol. Feb 20, 2023. Epublished DOI: 10.1016/j.jacc.2022.12.006 https://www.jacc.org/doi/abs/10.1016/j.jacc.2022.12.006

The Energy Department has concluded that Covid arose from a laboratory leak in China, this based on classified intelligence, really most of us knew this years ago. The science which they have all slung us is falling down around the ears of the CDC bldg. in Atlanta. So, all us conspirators and racists knew this and knew we could do nothing about things, so we became censored if we opened our mouths and whispered leak, China. Us flyover people you know us we have been in the news lately but that's another story for your fake climate post. The real crime here is the suppression of speech and of Ideas, US Academic elites who a lot of them get massive Chinese funds for their universities, jumped on us first calling us "anti-Chinese racists" or "toxic white masculinity" (true today in E Palestine OH). House democrats are on record calling for more censorship Joe called for more censorship and accused the censors of killing people for not censoring more views deemed "Covid Misinformation" Well de cat is out of the bag by suppressing alternative science and policy views we the people were denied our rights a full debate over a host of issues as censorship became widespread, no debate on the efficacy on masks, no debate or responding to doctors and scientists concerns for the side effects of a vaccine whose potency is now under fire, Fagetaboutit saying Covid was man made, Russia Collusion a hoax, The lap top Russian disinformation, this stuff is right out of Uncle Joe Stalin's note book, only these American censors are the new Fascists. Youse guys no doubt believe in this crime of denying free speech "for the good of all of us" that's good ole Joe Goebbels stuff. There are millions of us what was it Saint Hillary called us "deplorables" who believe that censorship is more likely to cost lives by protecting approved views only from challenge, censorship does not foster the truth any more than it fosters free speech. OK most likely it came from a lab the media will spin the next lie we know the LEAK came from China, but the censorship virus is much closer to home....AMDG....

>50 brone: Yes, and they made that assessment with "low confidence", which is basically saying "it's not contradicted by any known facts, but it's also not particularly supported by them, either".
The FBI reported a similar result with "moderate confidence", which is a little more persuasive - but four other departments came back with the opposite result.

The upshot: we still have no particular evidence one way or another, which makes the rest of your incontinent diatribe pretty irrelevant, so I will ignore it.

EDIT to add source: https://www.nytimes.com/2023/02/26/us/politics/china-lab-leak-coronavirus-pandem...
(yes, you too can read a newspaper - it'd help you to be less wrong, you might want to give it a shot)

>51 kiparsky: China virologist says the hedge hogs started it you would believe that before you believe it was man (sorry person) made....JMJ....

It's Time to address the other pandemic coming from China through the Mexican thug cartels at the US/Mexican non border. Fentanyl made in China killed 100,000 Americans last year alone. This is a clear and present danger. we know where it is made, we know who distributes it and we know who its killing, and most of all we know how to stop it, this pandemic we need no masks, no lockdowns, no vaccines, we need the resolve of the American people to stop it....AMDG....

>52 brone: That's a new one on me, so I have no basis to form an opinion on it. Animal origin, in general, is plausible, since we've seen it often enough, but as to hedgehogs, I have no idea whether that makes sense or not. So it's on the "dunno" pile - not obviously false yet.

However, I'm struck by the fact that you've introduced the notion of "man-made". This is a new one on me. What do you mean by suggesting that the virus was "man made"? What's the story you're asking me to evaluate here?

Moritz Gerstung @MoritzGerstung | 9:29 AM · Mar 2, 2023:
Division head @dkfz , professor @UniHeidelberg , visiting group leader @EMBLEBI. Previously @sangerinstitute and @ETH_en. We study how cancers (and 🦠) evolve.

It's been a while since the last SARS-CoV-2 variant update.
* XBB.1.5 and its cousin XBB.1.9.1 have taken over in most parts of the world.
* BQ.1* and other BA.2* variants are on the way out.
https://github.com/gerstung-lab/SARS-CoV-2-International

global maps variants ( https://twitter.com/MoritzGerstung/status/1631300790550769668/photo/1 )
graphs variants by country ( https://twitter.com/MoritzGerstung/status/1631300790550769668/photo/2 )

Vaccine may limit long-COVID impact, studies show, but controlled trials needed
Mary Van Beusekom | March 1, 2023

Vaccine tied to double remission rate*

Review shows low evidence {high study heterogenicity, however}**

https://www.cidrap.umn.edu/covid-19/vaccine-may-limit-long-covid-impact-studies-...
-----------------------------------------------

* Viet-Thi Tran et al. 2023. Efficacy of first dose of covid-19 vaccine versus no vaccination on symptoms of patients with long covid: target trial emulation based on ComPaRe e-cohort. bmjmedicine Volume 2, Issue 1 https://bmjmedicine.bmj.com/content/2/1/e000229

Abstract
...Results 910 patients were included in the analyses (455 in the vaccinated group and 455 in the control group). By 120 days, vaccination had reduced the number of long covid symptoms (mean 13.0... in the vaccinated group v 14.8 ... in the control group; mean difference −1.8,... and doubled the rate of patients in remission (16.6% v 7.5%...). Vaccination reduced the effect of long covid on patients' lives (mean score on the impact tool 24.3 ... v 27.6 (16.7); mean difference −3.3...) and the proportion of patients with an unacceptable symptom state (38.9% v 46.4%, risk difference −7.4%, ...). In the vaccinated group, two (0.4%) patients reported serious adverse events requiring admission to hospital.

Conclusion In this study, covid-19 vaccination reduced the severity of symptoms and the effect of long covid on patients' social, professional, and family lives at 120 days in those with persistent symptoms of infection.
------------------------------------------------

** Oyungerel Byambasuren et al. 2023. Effect of covid-19 vaccination on long covid: systematic review. bmjmedicine Volume 2, Issue 1 https://bmjmedicine.bmj.com/content/2/1/e000385

Abstract
...Results 1645 articles were screened but no randomised controlled trials were found. 16 observational studies from five countries (USA, UK, France, Italy, and the Netherlands) were identified that reported on 614 392 patients. The most common symptoms of long covid that were studied were fatigue, cough, loss of sense of smell, shortness of breath, loss of taste, headache, muscle ache, difficulty sleeping, difficulty concentrating, worry or anxiety, and memory loss or confusion. 12 studies reported data on vaccination before infection with the SARS-CoV-2 virus, and 10 showed a significant reduction in the incidence of long covid: the odds ratio of developing long covid with one dose of vaccine ranged from 0.22 to 1.03; with two doses, odds ratios were 0.25-1; with three doses, 0.16; and with any dose, 0.48-1.01. Five studies reported on vaccination after infection, with odds ratios of 0.38-0.91. The high heterogeneity between studies precluded any meaningful meta-analysis. The studies failed to adjust for potential confounders, such as other protective behaviours and missing data, thus increasing the risk of bias and decreasing the certainty of evidence to low.

Conclusions Current studies suggest that covid-19 vaccines might have protective and therapeutic effects on long covid. More robust comparative observational studies and trials are needed, however, to clearly determine the effectiveness of vaccines in preventing and treating long covid.

Covid notes from the other point of view, A secret I'll let you guys in on who are starting to " think" the jab leaves a lot to be desired, covidiacs will scoff at what Traditional Catholics who oppose the nRNA abortion tainted vaccine and have refused it from the beginning causing the wrath of the FBI and the pope himself. Statistics will show Traditional Catholics were not highly infected, Nasal Spray Xyitol in the corner pharmacy its patented as Xlear, also Malaria pills are very effective, neither product has any side effects. Don't let big Pharma know and the FBI and Gov."fact checkers" have effectively censored and shadow banned this info. This is the stuff they hate about Traditional Catholics Pharma, Big Gov, Big tech, big media we shun and avoid....JMJ....

Eric Topol (cardiologist, scientist, Scripps) @EricTopol | 11:01 AM · Mar 3, 2023:

Heart attacks, strokes and other major adverse outcomes doubled in people post-Covid at 1 year compared with matched uninfected controls #LongCovid, replicating previous reports ...
--------------------------------------------------------

Andrea DeVries et al. 2023. One-Year Adverse Outcomes Among US Adults With Post–COVID-19 Condition vs Those Without COVID-19 in a Large Commercial Insurance Database. JAMA Health Forum. March 3, 2023;4(3):e230010. doi:10.1001/jamahealthforum.2023.0010 https://jamanetwork.com/journals/jama-health-forum/fullarticle/2802095

Highlighted Abstract ( https://twitter.com/EricTopol/status/1631686283042111489/photo/1 )
Table 2 ( https://twitter.com/EricTopol/status/1631686961424633858/photo/1 )
---------------------------------------------------------

Eric Topol: Accompanying editorial

Mark É. Czeisler et al. 2023. Cardiovascular Risks in Patients With Post–COVID-19 Condition
(Editorial). JAMA Health Forum. March 3, 2023;4(3):e224664. doi:10.1001/jamahealthforum.2022.4664 https://jamanetwork.com/journals/jama-health-forum/fullarticle/2802097

Highlighted excerpt
https://twitter.com/EricTopol/status/1631687534005850113/photo/1
https://twitter.com/EricTopol/status/1631687534005850113/photo/2
---------------------------------------------------------

Eric Topol:
A year ago @zalaly and colleagues published an important paper @NatureMedicine on 1-year increased risk of adverse cardiovascular outcomes with #LongCovid
https://nature.com/articles/s41591-022-01689-3#Sec31
Fig 2 ( https://twitter.com/EricTopol/status/1631734860074336256/photo/1 )
It was met with skepticism

Since then it has been replicated by multiple reports such as Wang et al, in very different, younger populations https://thelancet.com/journals/eclinm/article/PIIS2589-5370(22)00349-2/fulltext
and the one today (DeVries et al. 2023 -- top of thread)
Graph ( https://twitter.com/EricTopol/status/1631734863832432641/photo/1 )

Summary table below, which includes 2 recent studies showing vaccination provides protection against major cardiovascular outcomes
Table ( https://twitter.com/EricTopol/status/1631734867083001857/photo/1 )

>58 margd: contd.

Heart attacks and strokes late after Covid
The body of evidence expands
Eric Topol | 3 March 2023

https://erictopol.substack.com/p/heart-attacks-and-strokes-late-after

hi all, just found out a friend who was here over the weekend has covid. Both of us are vaccinated and boosted, as is my family.Its been 5 days so Im watching for symptom the next ten days. In the meantim Having trouble finding updated info on what they current sypmtoms are, do I need to mask indoors, when should I get tested, when should I stay home. Any link you can send me thats not from 2022? thanks much

>57 brone: neither product has any side effects

Anti-malarial pills, like chloroquine, have nasty side effects, including death.

Complaining about the 'untested' vaccines and shilling for whatever drug someone suggested might help, sometimes drugs that have been tested and found ineffective, makes me roll my eyes.

Big Gov, Big tech, big media we shun and avoid..

Except when you're complaining that FEMA doesn't exceed its mandate. People stopped believing that whole "hating big government" thing by the four thousandth time we heard the complaints about how government isn't doing enough for fly over states.

>60 cindydavid4: If you've been exposed and you're not sure whether you're positive, that seems like a pretty good reason to take a test. Certainly if you show any cold or flu-like symptoms, then a test is a good idea. Paxlovid is pretty effective (at least it was for me and my partner) but it's meant to be taken within five days of the first symptoms, so if you think you might be positive, it sounds like you should test soon, you might still be in the effective window for that treatment.

As for masking, my advice would be if you have good reason to think you might be carrying the virus you should try to avoid places where you think it would be wise to be masked as much as possible until you can get a better sense of your status. If you must go into enclosed public spaces, certainly wear a mask and minimize your time in those spaces as much as possible - but preferably avoid those places. Masks are a good public health measure and they're a very effective way to reduce the overall rate of transmission, but they're not magic.

>60 cindydavid4: Echoing Kiparsky, I would contact my MD (pharmacist in some places https://www.cvs.com/content/covid-antiviral) right away, to make sure I could obtain Paxlovid as soon as warranted. Keep home testing if negative at first. (Because of vaxx and previous infections, many have symptoms before they test positive. Swab throat, then nose.) I would do my best to avoid spreading the virus. At home to protect family members, esp. vulnerable people--I would isolate, mask, ventilate, and filter if at all possible while I had symptoms or test positive.

In US, the predominant variant in circulation right now is XBB.1.5, a BA2 offshoot: https://covid.cdc.gov/covid-data-tracker/#variant-proportions

Johns Hopkins on the XBB.1.5: https://publichealth.jhu.edu/2023/what-you-need-to-know-about-xbb15-the-latest-o...

My *impression* is that while this variant might be a bit easier on an INDIVIDUAL, esp vaxxed and pre-infected, still, see your MD / pharmacist ASAP to get Paxlovid. (Free at the moment?) XBB.1.5 is so much more transmissible that many people in the affected POPULATION still end up in hospital or with Long COVID.*

You've got this.
---------------------------------------------------------------

* T. Ryan Gregory (U Guelph evolutionary biologist) @TRyanGregory | 8:16 AM · Mar 4, 2023:
https://twitter.com/TRyanGregory/status/1632007171956154369

Seeing a few takes about XBB.1.5 (Kraken) having been overblown because it didn't cause a big wave of infections or hospitalizations. This really misses the point of why variants (and names) matter at this stage.

To reiterate what I've been saying for months: 🧵

1) XBB.1.5 got a nickname because it had notable features. Specifically, it had the high immune escape of its recombinant ancestor XBB *and* had high ACE2 binding, which was compromised in XBB.
https://twitter.com/TRyanGregory/status/1608082277900161025

If you recall how PANGO naming works, XBB.1.5 (Kraken) is a descendant of XBB.1 (Hippogryph), itself a descendant of XBB (Gryphon).
https://twitter.com/TRyanGregory/status/1576945959824523264

The first XBB was a recombinant between two BA.2 lineages (BJ.1 x BM.1.1.1).

Here's an excellent thread by @firefoxx66 explaining recombination.
https://twitter.com/firefoxx66/status/1587762412110974976

Predictably, there was plenty of "Relax, XBB probably won't do anything" minimizing in November.
https://www.webmd.com/covid/news/20221128/new-variant-of-concern-xbb-may-lack-su...

Oops!
https://www.reuters.com/business/healthcare-pharmaceuticals/covid-variant-xbb-ac...

With transmission pretty much preceding unhindered these days, it should not surprise anyone that the variant continued to evolve.

Here's a superb thread by @yunlong_cao on what makes XBB.1.5 especially concerning.
https://twitter.com/yunlong_cao/status/1607915567696203776

Reminder that ventilation, air filtration, high quality N95 masks worn properly, and reducing crowd sizes are variant proof.

Oh, and XBB.1.5 refutes any claims that BA.2 lineages are no big deal anymore. XBBs are BA.2s. BQs are BA.5s. Both still very significant.

People really need to stop making pronouncements based only on a snapshot of the present. Evolution isn't stopping.

Kids at similar risk for long COVID as adults, study suggests
Stephanie Soucheray | November 10, 2022

A large study today from Germany shows that kids and adolescents are at the same relative risk of experiencing COVID-19 symptoms 90 days or more after acute infection as adults are, according to findings in PLOS Medicine.

And a new systematic review by researchers from the World Health Organization (WHO) in the same journal shows that likely two thirds of the world's population has SARS-CoV-2 antibodies.
About a third of kids, adults have long COVID

Though kids and adolescents have far fewer deaths or severe outcomes from COVID-19 infections compared to adults, little is known about long or post COVID symptoms in this age-group, or symptoms that persist for more than 12 weeks after acute infection...

https://www.cidrap.umn.edu/covid-19/kids-similar-risk-long-covid-adults-study-su...
------------------------------------------------------------

Martin Roessler et al. 2022. Post-COVID-19-associated morbidity in children, adolescents, and adults: A matched cohort study including more than 157,000 individuals with COVID-19 in Germany. PLOS Published: November 10, 2022. https://doi.org/10.1371/journal.pmed.1004122 https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004122

Abstract
...Methods and findings
We used routine data from German statutory health insurance organizations covering the period between January 1, 2019 and December 31, 2020. The base population included all individuals insured for at least 1 day in 2020. Based on documented diagnoses, we identified individuals with polymerase chain reaction (PCR)-confirmed COVID-19 through June 30, 2020. A control cohort was assigned using 1:5 exact matching on age and sex, and propensity score matching on preexisting medical conditions. The date of COVID-19 diagnosis was used as index date for both cohorts, which were followed for incident morbidity outcomes documented in the second quarter after index date or later.Overall, 96 prespecified outcomes were aggregated into 13 diagnosis/symptom complexes and 3 domains (physical health, mental health, and physical/mental overlap domain). We used Poisson regression to estimate incidence rate ratios (IRRs) with 95% confidence intervals (95% CIs). The study population included 11,950 children/adolescents (48.1% female, 67.2% aged between 0 and 11 years) and 145,184 adults (60.2% female, 51.1% aged between 18 and 49 years). The mean follow-up time was 236 days ... in children/adolescents and 254 days ... in adults. COVID-19 and control cohort were well balanced regarding covariates. The specific outcomes with the highest IRR (incidence rate ratio) and an incidence rate (IR) of at least 1/100 person-years in the COVID-19 cohort in children and adolescents were malaise/fatigue/exhaustion (IRR: 2.28...IR COVID-19: 12.58, IR Control: 5.51), cough (IRR: 1.74...IR COVID-19: 36.56, IR Control: 21.06), and throat/chest pain (IRR: 1.72... IR COVID-19: 20.01, IR Control: 11.66). In adults, these included disturbances of smell and taste (IRR: 6.69..., IR COVID-19: 12.42, IR Control: 1.86), fever (IRR: 3.33..., IR COVID-19: 11.53, IR Control: 3.46), and dyspnea (IRR: 2.88..., IR COVID-19: 43.91, IR Control: 15.27). For all health outcomes combined, IRs per 1,000 person-years in the COVID-19 cohort were significantly higher than those in the control cohort in both children/adolescents (IRR: 1.30..., IR COVID-19: 436.91, IR Control: 335.98) and adults (IRR: 1.33..., IR COVID-19: 615.82, IR Control: 464.15). The relative magnitude of increased documented morbidity was similar for the physical, mental, and physical/mental overlap domain. In the COVID-19 cohort, IRs were significantly higher in all 13 diagnosis/symptom complexes in adults and in 10 diagnosis/symptom complexes in children/adolescents. IRR estimates were similar for age groups 0 to 11 and 12 to 17. IRs in children/adolescents were consistently lower than those in adults. Limitations of our study include potentially unmeasured confounding and detection bias.

Conclusions
In this retrospective matched cohort study, we observed significant new onset morbidity in children, adolescents, and adults across 13 prespecified diagnosis/symptom complexes, following COVID-19 infection. These findings expand the existing available evidence on post-COVID-19 conditions in younger age groups and confirm previous findings in adults.

>60 cindydavid4:

XBB.1.5 Omicron subvariant: Questions patients may have
Sara Berg | Feb 2, 2023

...What are the symptoms of XBB.1.5?
Symptoms with XBB.1.5 appear to be similar to the earlier Omicron subvariants. Those can range from typical cold symptoms such as cough and congestion to shortness of breath and low oxygen levels that require emergency medical attention.

But as XBB.1.5 continues to spread, the signs and symptoms of COVID-19 may seem different than what was seen earlier in the pandemic with Alpha or Delta variants. Symptoms such as the temporary loss of taste and smell can still happen in some instances, but it has become less common with the Omicron variant and subvariants.

Other symptoms may include fever, chills, fatigue, muscle or body aches, sore throat, nausea or vomiting and diarrhea. Symptoms can last between five to seven days but vary from person to person.

Is XBB.1.5 infection more severe than other COVID-19 variants?
“The experts generally believe that the symptoms of COVID have become less severe over time,” Garcia explained. “That could be because they tend to remain in the upper respiratory tract and don't affect the lungs as much as earlier variants.”

“But it could also be because people in the U.S. have some level of immunity from vaccines or prior infection,” she said, noting that “many people who are infected now are reporting those mild symptoms like cough, congestion and a headache that could be confused with symptoms of the cold or flu.”

“Although XBB.1.5 is one of the most antibody-resistant variants, it doesn't seem to carry any mutation known to be associated with a potential change in severity. However, studies of disease severity are now ongoing,” said Dr. Fryhofer who also serves as the AMA’s liaison to the CDC’s Advisory Committee on Immunization Practices (ACIP) and is a member of ACIP’s COVID-19 Vaccine Work Group...

https://www.ama-assn.org/delivering-care/public-health/xbb15-omicron-subvariant-...

>65 margd: this was very helpful, thanks. Hers is a mild case and I have had no symptoms so I missed the bullet.

Preprint was post #88 in thread 28:

Shocking Report Reveals 59% of Long COVID Patients Suffer From Organ Damage a Year Later
University College London (UCL) | March 5, 2023

https://scitechdaily.com/shocking-report-reveals-59-of-long-covid-patients-suffe...
---------------------------------------------------------------

Andrea Dennis et al. 2023. Multi-organ impairment and long COVID: a 1-year prospective, longitudinal cohort study. Journal of the Royal Society of Medicine, 14 February 2023. DOI:10.1177/01410768231154703 https://journals.sagepub.com/doi/10.1177/01410768231154703

Abstract
Objectives
To determine the prevalence of organ impairment in long COVID patients at 6 and 12 months after initial symptoms and to explore links to clinical presentation.

...Results
... Extreme breathlessness (38% and 30%), cognitive dysfunction (48% and 38%) and poor health-related quality of life (EQ-5D-5L 

Eric Topol (cardiologist, scientist, Scripps) @EricTopol | 1:35 PM · Mar 6, 2023:

Very good news
Metformin significantly helped prevent #LongCovid in a placebo-controlled randomized trial, a 42% relative reduction
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4375620 by @BramanteCarolyn and colleagues
Graph ( https://twitter.com/EricTopol/status/1632812104200908800/photo/1 )

Worked consistently across key subgroups
Table ( https://twitter.com/EricTopol/status/1632812109041119232/photo/1 )
-----------------------------------------------

Carolyn Bramante et al. 2023. Outpatient Treatment of COVID-19 and the Development of Long COVID Over 10 Months: A Multi-Center, Quadruple-Blind, Parallel Group Randomized Phase 3 Trial. SSRN,
24 Pages Posted: 6 Mar 2023. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4375620

PREPRINT. Not yet peer-reviewed.

Abstract
Background: Post-acute sequelae of COVID, termed “Long COVID”, is an emerging chronic illness potentially affecting ~10% of those with COVID-19. We sought to determine if outpatient treatment with metformin, ivermectin, or fluvoxamine could prevent Long COVID.

Methods: COVID-OUT (NCT04510194) was a decentralized, multi-site trial in the United States testing three medications (metformin, ivermectin, fluvoxamine) using a 2x3 parallel treatment factorial randomized assignment to efficiently share placebo controls. Participants, investigators, care providers, and outcomes assessors were masked to randomized treatment assignment. Inclusion criteria included: age 30 to 85 years with overweight or obesity, symptoms less than 7 days, enrolled within 3 or fewer days of documented SARS-CoV-2 infection. Long COVID diagnosis from a medical provider was a pre-specified secondary outcome assessed by monthly surveys through 300 days after randomization and confirmed in medical records.

Findings: Of 1323 randomized trial participants, 1125 consented for long-term follow up, and 95.1% completed more than 9 months of follow up. The median age was 45 years ..., and 56% were female (7% pregnant). The median BMI was 30 kg/m2 ... Overall, 8.4% reported a medical provider diagnosed them with Long COVID; cumulative incidence: 6.3% with metformin and 10.6% with matched placebo. The hazard ratio (HR) for metformin preventing Long COVID was 0.58...versus placebo. The metformin effect was consistent across subgroups, including viral variants. When metformin was started within less than 4 days of symptom onset, the HR for Long COVID was 0.37... No statistical difference in Long COVID occurred in those randomized to either ivermectin (HR=0.99...) or fluvoxamine (HR=1.36...).

Interpretations: A 42% relative decrease and 4.3% absolute decrease in the Long COVID incidence occurred in participants who received early outpatient COVID-19 treatment with metformin compared to exact-matching placebo.

...Conclusions
Outpatient treatment with metformin at the time of SARS-CoV-2 infection decreased the development of Long Covid by 42% in a phase 3 randomized trial, and by over 50% when started less than 4 days from symptom onset. This finding is consistent with the 42% reduction in healthcare utilization for severe Covid-19 with metformin in the first 14 days of the trial. Fluvoxamine and ivermectin did not decrease the development of Long Covid, which is consistent with outcomes in the first 14 days of the trial. These results are hihly {sic} relevant to the current state of the pandemic because the study sample was approximately half vaccinated, and despite the 10-month follow-up of these outcome, the trial enrolled during Omicron wave. Long Covid is a significant public health emergency that may have lasting health, mental health, and economic sequelae, especially in socioeconomically marginalized groups, and metformin is safe, low-cost, and widely available.

Dr. Deepti Gurdasani @dgurdasani1 | 2:27 AM · Mar 7, 2023:
Clinical epidemiology, machine learning, global health. {Formerly UK, now Australia?}

Um, yeah, Swedish COVID policy was really not a success... you can try to rewrite history, but the facts don't change. Swedish policy was a disaster with 1.5-2x higher cumulative deaths/million from COVID compared to other Nordic countries... completely predictable too.

{Graph. COVID deaths in Sweden v Finland, Denmark, Norway, Iceland (March 2020-March 2023)}
https://twitter.com/dgurdasani1/status/1633006535562653696/photo/1
https://twitter.com/dgurdasani1/status/1633006535562653696/photo/2

Oh, and for those wondering about excess deaths - yeah, these don't show anything different either. Sweden having the highest cumulative excess deaths.
Graphs ( https://twitter.com/dgurdasani1/status/1633020919731068928/photo/1
------------------------------------------------------------

Compute My Head Strap N95 🖲 @MixtUpMixy | 2:29 AM · Mar 7, 2023:
And compared to the US and UK….PER MILLION!!! 😬
Yep, a real winning strategy 😒
https://twitter.com/MixtUpMixy/status/1633007035292991489/photo/1

Covid Virus did not come from nature it was made and leaked from a lab which was receiving gain of function funds from US taxpayers in Wuhan China. Fentanyl does not come from nature it is made and produced in China killing 200 people a day in the US....AMDG....

>70 brone: Covid Virus did not come from nature it was made and leaked from a lab which was receiving gain of function funds

You don't know what "gain of function" means, do you? Look it up and then decide whether you think that the two halves of that sentence go together.

Just to review: of the reports that have been done on this, two have weakly concluded that it was maybe a lab leak, and four have concluded that it wasn't. So, if I'm adding your assertion to the stack, I'm left with two US government agencies that have qualified people who spent paid time looking into it and think it was maybe a lab leak and four that have assigned qualified people who know what they're talking about to look into it and are kinda thinking it wasn't a lab leak, and then there's this random dude who thinks he knows everything who I don't really care what he says. So, if you care about evidence, you still don't really have anything conclusive either way. And if you decided that it was a lab leak before you knew anything at all and still think that, then you still think that and, again, nobody cares because you literally never cared about the evidence to begin with.

But hey, it's nice to hear from you.

>70 brone: Covid Virus did not come from nature it was made and leaked from a lab which was receiving gain of function funds from US taxpayers in Wuhan China.

And you know this how? The argument is still live about whether or not it mutated in animals or was leaked from a lab. Details are either extremely technical or classified, so I don't think you or I can have any useful opinion on it beyond citing the differing experts.

There was a small grant to the Wuhan lab, but it specifically was not for gain of function use.

Fentanyl does not come from nature it is made and produced in China killing 200 people a day in the US.

The DEA thinks it's produced in Mexico from non-fentanyl chemicals sourced from China. I'm sure that if the chemicals can't be sourced from China, they'll be sourced from India, or some other nation. What do you want to do about it? As people have said, drugs come into the US in trucks with all the other goods produced or shipped through Mexico.

A clinician's guide to Long Covid:

Day 2 - Keynote David Putrino (31:06)
Premiered Nov 1, 2022 Long COVID Physio International Forum #LCPForum

In this Keynote presentation Dr David Putrino will present latest research findings on mechanisms and causes of Long COVID that can guide safe rehabilitation interventions.

Dr David Putrino, Director of Rehabilitation Innovation for the Mount Sinai Health System, and Associate Professor of Rehabilitation and Human Performance at the Icahn School of Medicine at Mount Sinai, USA

https://longcovid.physio/forum-programme/keynote-david-putrino
https://www.youtube.com/watch?app=desktop&v=F8usNOELJdQ&feature=share&am...

Future of the COVID pandemic: Scientists say there is still a lot to learn
March 13, 20237:20 AM ET
Heard on Morning Edition (4 min)
(Transcript to come?)

NPR's Sacha Pfeiffer speaks with immunologist Akiko Iwasaki {Yale, studies Long COVID} about the future of COVID research as the pandemic enters its fourth year.

https://www.npr.org/2023/03/13/1163028287/future-of-the-covid-pandemic-scientist...

Study finds exhaled breath could enhance detection, diagnosis of COVID-19 and variants
Research suggests volatile organic compounds in breath could mark distinction between COVID-19, variants and non-COVID illnesses
Megan VanStratt | March 6, 2023 2:10 PM

The emergence of new COVID-19 variants has led to reduced accuracy across current rapid testing methods, but a recent University of Michigan study suggests that a patient’s breath might hold the key to a more precise diagnosis.

Investigators from the University of Michigan’s Max Harry Weil Institute for Critical Care Research and Innovation, including faculty and students from the College of Engineering and Michigan Medicine, used portable gas chromatography to examine breath samples collected during the pandemic’s Delta surge and its transition to Omicron (from April 2021 to May 2022.)

Their results, published February 28 in JAMA Network Open, showed that the GC technology could diagnose COVID-19 with a high level of accuracy. They also revealed that the volatile organic compounds contained in the breath of patients with Omicron differed from those in patients with Delta and earlier variants—molecular-level differences which, according to the team, could potentially be used to distinguish between COVID-19, its variants and non-COVID illnesses...

https://www.michiganmedicine.org/health-lab/study-finds-exhaled-breath-could-enh...
--------------------------------------------------

Ruchi Sharma et al. 2023. Portable Breath-Based Volatile Organic Compound Monitoring for the Detection of COVID-19 During the Circulation of the SARS-CoV-2 Delta Variant and the Transition to the SARS-CoV-2 Omicron Variant. JAMA Network Open. DOI: 10.1001/jamanetworkopen.2023.0982 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2801785

Abstract
...Results Overall, 205 breath samples from 167 adult patients were analyzed. A total of 77 patients (mean ... age, 58.5 ... years; 41 (53.2%) male patients; 13 (16.9%) Black and 59 (76.6%) White patients) had COVID-19, and 91 patients (mean...age, 54.3 ... years; 43 (47.3%) male patients; 11 (12.1%) Black and 76 (83.5%) White patients) had non–COVID-19 illness. Several patients were analyzed over multiple days. Among 94 positive samples, 41 samples were from patients in 2021 infected with the Delta or other variants, and 53 samples were from patients in 2022 infected with the Omicron variant, based on the State of Michigan and US Centers for Disease Control and Prevention surveillance data. Four VOC biomarkers were found to distinguish between COVID-19 (Delta and other 2021 variants) and non–COVID-19 illness with an accuracy of 94.7%. However, accuracy dropped substantially to 82.1% when these biomarkers were applied to the Omicron variant. Four new VOC biomarkers were found to distinguish the Omicron variant and non–COVID-19 illness (accuracy, 90.9%). Breath analysis distinguished Omicron from the earlier variants with an accuracy of 91.5% and COVID-19 (all SARS-CoV-2 variants) vs non–COVID-19 illness with 90.2% accuracy.

Conclusions and Relevance The findings of this diagnostic study suggest that breath analysis has promise for COVID-19 detection. However, similar to rapid antigen testing, the emergence of new variants poses diagnostic challenges. The results of this study warrant additional evaluation on how to overcome these challenges to use breath analysis to improve the diagnosis and care of patients.

Putrino Lab @PutrinoLab | 8:16 AM · Mar 14, 2023
We make people (and technology) better at Mount Sinai http://putrinolab.net

Friends, we are once again putting out a big call for ANYONE who has had COVID and FULLY RECOVERED (no persistent symptoms) in the NEW YORK CITY area to assist us with a #LongCovid study. If this sounds like you, please contact us at prcovid@mountsinai.org

Rosemary J Boyton and Daniel M Altmann 2023. Imprinted hybrid immunity against XBB reinfection (Comment). The Lancet Infectious Diseases. Published:March 13, 2023. DOI:https://doi.org/10.1016/S1473-3099(23)00138-X https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(23)00138-X/fullt...

In the fourth year of the COVID-19 pandemic, the picture of population immunity has become increasingly complex and the certainties have become less certain.1

Since the start of 2022, many countries have had sequential waves of infection with emerging subvariants of the SARS-CoV-2 omicron (B.1.1.529) variant. Clinical phenotypes associated with these waves in different settings have been diverse. In the USA and the UK, in which relatively high proportions of the population have received three or more doses of an mRNA vaccine, some large waves of breakthrough infections saw more than 8% of the population infected with SARS-CoV-2 (reported in weekly estimates of the rate of COVID-19 infections by the UK Office of National Statistics Coronavirus {COVID-19} Infection Survey), although sufficient protective immunity prevented a commensurate peak in deaths. However, in China, the consequences of the relaxation of physical distancing rules and poorer vaccine coverage reminded us that omicron subvariants can cause severe disease. Since the omicron variant was first detected, more than one year ago, the term omicron subvariant now encompasses considerable sequence diversity, with associated implications for differential transmission and immune evasion. In terms of sequence and epitope expression, the XBB omicron subvariant is now as distant from wild-type SARS-CoV-2 as SARS-CoV-2 is from SARS-CoV, such that XBB should probably be called SARS-CoV-3.2, 3 However, as virus sequencing surveillance has become less frequent and there are competing variants with different prevalence at any given moment in time, knowledge of which omicron subvariant is responsible for a given infection is usually not known with any confidence. In the UK, for example, the period since early 2022 has seen large, sequential waves of infection, each lasting a few months, caused by BA.1, BA.2, BA.4, BA.5, BQ1.1, and now XBB subvariants. Why do these details matter? Societal attempts to live with the virus have relied on hybrid immunity—the qualitative and quantitative boost to immunity that is imparted by a combination of infection and vaccination.4, 5, 6 Analysis by Celine Tan* and colleagues 7 of the national dataset during the XBB wave in Singapore provides a real-world picture of how well hybrid immunity holds up in this context. The answers are concerning with respect to protection from infection, although less so in terms of severe disease and death. This important study,7 which assesses epidemiological data on breakthrough infections by BA.4, BA.5, and XBB subvariants, reminds us that the details of differential immune imprinting following different combinations of infection and vaccination matter. The first, key point of relevance is that hybrid immunity from the pre-2022, antigenically distant, pre-omicron variants did not confer protection against XBB reinfection. A new biomedical interface arose during the pandemic from the iterative rapid exchanges between real-world, national cohort epidemiology and laboratory, mechanistic immunology. The analysis by Tan and colleagues 7 includes epidemiological observations supporting the concept of differentially imprinted hybrid immunity conferred by previous infections during the period in which the omicron variant was dominant. For example, previous BA.2 infection provided hybrid immunity against subsequent BA.4 and BA.5 infection, but less protection against XBB infection. Differences were also seen in the imputed kinetics of immune waning, with accelerated waning of BA.2 hybrid immunity against XBB. Far from being nuanced footnotes in the pandemic response, these subvariant datasets provide great challenges to scientists, public health clinicians, policy makers, and vaccinologists. High prevalence of breakthrough infections are evidence of us failing in our war of attrition against the virus, measurable by increased caseload, hospitalisations and health-care provision, lost days from work, chronic disability from persistent symptoms, and an inability to simply return to normal life. Among the immunological challenges is the imperative to better define the rules underpinning the differential immune imprinting exemplified by these findings. 8 , 9
We now have a global population in which very diverse previous exposures to vaccines and SARS-CoV-2 infections—which shape antibody and T-cell-receptor repertoires—have imparted differential quantity and quality of protective immunity. This dataset from Singapore reminds us not only how far we are from understanding these imprinting rules but also how great would be the benefits of understanding them better. We are arguably even further from decoding the details of differentially imprinted immune waning. Coming into the pandemic, immunity to reinfection by the human common cold coronaviruses was understood to be short-lived and fragile; 10 however, in the case of SARS-CoV-2, it was hoped that protection would be increased by highly effective vaccine platforms. If we now appreciate that even hybrid immunity to SARS-CoV-2 infection is (differentially, depending on previous immune experience) poorly durable 11
and annual debates on booster strategy are required, how should we move forward? The dataset from Singapore reminds us that suggesting the booster strategy will simply involve tweaking vaccines annually, as for influenza, seriously underestimates the complexity of the current challenge. The long-term strategy will require considerable effort towards the development of both next-generation vaccines (targeting neutralising epitopes that are truly conserved and disadvantageous for viral mutations) and vaccine platforms that provide durable, local protection in the nasal mucosa, thereby blocking viral transmission.12

* Tan C, Chiew CJ, Pang D et al. 2023. Protective immunity of natural SARS-CoV-2 infection and vaccines against medically attended symptomatic omicron BA.4, BA.5, and XBB reinfections in Singapore: a national cohort study.
Lancet Infect Dis. 2023; (published online March 13.) https://doi.org/10.1016/S1473-3099(23)00060-9 https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(23)00060-9/fullt...

ABSTRACT
...Findings
2 456 791 individuals were included in the study, contributing 53·1 million person-days of observation for the SARS-CoV-2-naive group, 3·4 million person-days for the pre-omicron group, 6·6 million person-days for the BA.1 group, and 13·7 million person-days for the BA.2 group between Oct 1, 2022, and Nov 1, 2022. Compared with SARS-CoV-2-naive individuals, first infections with pre-omicron variants did not confer protection against reinfection with BA.4 or BA.5 (IRR 0·87 ... for pre-omicron infection with booster vaccination) or XBB (IRR 1·29 ... for pre-omicron infection with booster vaccination). Previous BA.2 infection with booster provided the greatest protection against reinfection, but this was lower against reinfection with XBB (protective immunity 51%...) than against reinfection with BA.4 or BA.5 (78%...). Protection conferred by previous BA.2 infection against XBB reinfection waned faster over time from first infection (from 74% ... at 3–6 months to 49% ... at 7–8 months) than protection against BA.4 or BA.5 reinfection (from 87% ... at 3–6 months to 74% ... at 7–8 months).

Interpretation
Protection against XBB reinfection conferred by a previous omicron infection with vaccination was lower and waned faster than protection against BA.4 or BA.5 reinfection, which is indicative of the greater immune evasiveness of the XBB sublineage. Although severe COVID-19 is uncommon, populations remain vulnerable to future reinfection waves from emerging SARS-CoV-2 variants despite high rates of vaccination and infection, as reflected by substantially higher reinfection rates during Singapore's XBB wave than during the previous BA.5-driven wave. Policy makers could consider emerging public health interventions, such as omicron-adapted bivalent vaccines, to maintain population immunity against COVID-19.

A bit of good news?

Eric Topol (Scripps MD-scientist) @EricTopol | 4:48 PM · Mar 16, 2023:
Loss of smell after Covid: by 3-years (the longest follow-up study to date) more than >95 margd:% fully recovered

Jingwen Li et al. 2023. Persisting Olfactory Impairments in Recovered COVID-19 Patient: A Three-Year Follow-Up. SSRN (Lancet preprint) 19 Pages Posted: 16 Mar 2023. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4389596

ABSTRACT
...Results: The median duration of COVID-19 from symptom onset to hospital discharge was 30 days. Only 7 cases (4.5%) still had smell loss and all of them were older than 50 years. The results showed more than 30% of them had emotional and sleep problems, which were more likely to happen in women and older patients. Insomnia ... and anxiety ... were the two risk factors for OD (olfactory dysfunction) in recovered COVID-19 patients.

Interpretation: The majority of recovered COVID-19 patients had normal olfactory function based on a three-year follow-up. We recommend reassuring patients with SARS-COV-2 infection for good prognosis.

How Does COVID-19 Affect the Heart? (Review)

Lorenzo R. Sewanan et al. 2023. How Does COVID-19 Affect the Heart? Current Cardiology Reports volume 25, pages 171–184 (10 March 2023) https://link.springer.com/article/10.1007/s11886-023-01841-6

Part of...Topical Collection on Heart Failure, incl. one on pediatric heart failure ( https://link.springer.com/journal/11886/topicalCollection/AC_cdf27bde6c3f4228155... )

Abstract
Purpose of Review
Cardiac consequences occur in both acute COVID-19 and post-acute sequelae of COVID-19 (PASC). Here, we highlight the current understanding about COVID-19 cardiac effects, based upon clinical, imaging, autopsy, and molecular studies.

Recent Findings
COVID-19 cardiac effects are heterogeneous. Multiple, concurrent cardiac histopathologic findings have been detected on autopsies of COVID-19 non-survivors. Microthrombi and cardiomyocyte necrosis are commonly detected. Macrophages often infiltrate the heart at high density but without fulfilling histologic criteria for myocarditis. The high prevalences of microthrombi and inflammatory infiltrates in fatal COVID-19 raise the concern that recovered COVID-19 patients may have similar but subclinical cardiac pathology. Molecular studies suggest that SARS-CoV-2 infection of cardiac pericytes, dysregulated immunothrombosis, and pro-inflammatory and anti-fibrinolytic responses underlie COVID-19 cardiac pathology. The extent and nature by which mild COVID-19 affects the heart is unknown. Imaging and epidemiologic studies of recovered COVID-19 patients suggest that even mild illness confers increased risks of cardiac inflammation, cardiovascular disorders, and cardiovascular death. The mechanistic details of COVID-19 cardiac pathophysiology remain under active investigation.

Summary
The ongoing evolution of SARS-CoV-2 variants and vast numbers of recovered COVID-19 patients portend a burgeoning global cardiovascular disease burden. Our ability to prevent and treat cardiovascular disease in the future will likely depend on comprehensive understanding of COVID-19 cardiac pathophysiologic phenotypes.

XBB.1.5 ("Kraken") wins US--for now.

Eric Topol @EricTopol | 1:18 PM · Mar 17, 2023:·

All remains quiet on the new variant front
https://covid.cdc.gov/covid-data-tracker/#variant-proportions

Variants US Dec 2022-March 2023 ( https://twitter.com/EricTopol/status/1636778952554590208/photo/1 )

Preprint coming from U of Toronto prof on cost-effective model for forecasting COVID and excess mortality.
Reinfections matter: "essentially I'm finding from Canadian data that at least in people older than 40 reinfections are associated with an additional 70% risk of mortality (30% less than risk of first). It may be as high as 100%, and this is tougher to answer because death reporting is still really incomplete for the Omicron era past April 2022, when reinfections of older people ramped up. On a whole population level, risk of death from an additional infection may be 50% on top of the risk from the first infection."

Tara Moriarty @MoriartyLab | 9:12 PM · Mar 20, 2023:
Assoc Prof @UofT . Bloodborne infections, Lyme disease, misinfo. @COVID_19_Canada @ScienceUpFirst. Opinions mine. @MoriartyLab@med-mastodon.com

Dear Canadians,
I know many of you have been waiting for COVID forecasts for the last 2 weeks.
I'm really, really sorry, and will explain in this thread.
But in the meantime...world, please welcome the validation of the Canadian COVID Forecast plotted against excess mortality.

Graph ( https://twitter.com/MoriartyLab/status/1637985377674821633/photo/1 )

I cannot tell you how proud I am of how well the COVID Forecast index predicts excess mortality.

The graph shown here is for the Canadian provinces that report all causes mortality fastest: NL, QC, AB and BC. The aggregate % excess mortality scores are population weighted.

At a very simple level, this graph shows that the score on the COVID Forecast very closely approximates excess mortality...

For a long time, I've needed to modify the model underlying our forecasts to take into account two variables: incidental (with, not from) COVID deaths, and deaths from reinfections.

Once I started tinkering with the model it ended up taking longer than expected (when is it ever faster than expected?).

And because the model was in construction mode, I couldn't do the COVID forecasts.

...I really hope we can use this model and the forecast to keep predicting the Canadian COVID situation in the longterm. There's no sign of it going away fast.

Plus, I now know a couple of key things that provinces and/or @GovCanHealth can do.

We need weekly seroprevalence data, which we have courtesy of @COVIDimmunityTF .

We need weekly survey data, which we have, thanks to @INSPQ and @CIRANOMTL. Other provinces need the same.

We need to estimate hospitalization under-reporting rates in each province, which we can do courtesy of @CIHI_ICIS .

We need excess mortality data, courtesy of @StatCan_eng .

Plus waste water data (we use mainly PHAC but are trying to bring others on line).

If there's one thing every province could start doing, it's the weekly sampled surveys asking people if they've tested positive by RAT or PCR.

The weekly data from CIRANO/INSPQ show trends and prevalence rates that are strikingly similar to the more expensive testing-based surveys conducted weekly in the UK.
{ CIRANO https://cirano.qc.ca }
{ INSPQ https://www.inspq.qc.ca }

I still can't get over how useful the CIRANO/INSPQ survey program and data are.

A beautiful researcher-driven program that was developed at breakneck speed at the start of Omicron to provide visibility on where things were in Quebec. The skill it took to build something then that has held up so well is awe-inspiring.

Using the CIRANO/INSPQ survey data and seroprevalence data we can estimate rates of reinfection (and we calibrate our model to both datasets to make sure the outputs make sense).

Once we have decent estimates of primary and reinfection rates for each wave, we can then start asking if excess mortality patterns can be explained by first-time infections alone, and/or first-time plus reinfections.

The short answer is that reinfections matter, and have a fairly big influence on excess mortality in Canada, as I'm sure they do in other parts of the world.

I don't have time to explain now, and need to write it properly in a manuscript instead of here, but essentially I'm finding from Canadian data that at least in people older than 40 reinfections are associated with an additional 70% risk of mortality (30% less than risk of first)

It may be as high as 100%, and this is tougher to answer because death reporting is still really incomplete for the Omicron era past April 2022, when reinfections of older people ramped up.

On a whole population level, risk of death from an additional infection may be 50% on top of the risk from the first infection.

I'm trying to detangle some of this for younger people, which is tougher.

I'll update the excess mortality tracker in the coming week, once I get some data tables I need from StatsCan (one crucial one is not displaying/downloading correctly from their website, so I can't do that yet).

But all of this also means we can predict how much excess mortality directly due to COVID would be expected in each province in the Omicron era, then compare to reported COVID deaths.

Being able to do this matters for the Forecast--we need to distinguish reported from real...

Could getting Covid raise cholesterol?
Two recent studies show a link between Covid and higher cholesterol levels in the following year.
Erika Edwards | 23 Jan 2023
https://www.nbcnews.com/health/health-news/getting-covid-raise-cholesterol-rcna6...
------------------------------------------------------------

Evan Xu et al. 2023. Risks and burdens of incident dyslipidaemia in long COVID: a cohort study. Lancet Diabetes Endocrinol 2023; 11: 120–28. Published Online January 6, 2023. https://doi.org/10.1016/S2213-8587(22)00355-2 https://www.thelancet.com/pdfs/journals/landia/PIIS2213-8587(22)00355-2.pdf

ABSTRACT
...Findings In the post-acute phase of the SARS-CoV-2 infection, compared with the non-infected contemporary control
group, those in the COVID-19 group had higher risks and burdens of incident dyslipidaemia, including total
cholesterol greater than 200 mg/dL (hazard ratio HR 1·26...; burden 22·46...per 1000 people at 1 year), triglycerides greater than 150 mg/dL ..., LDL cholesterol greater than 130 mg/dL ..., and HDL cholesterol lower than 40 mg/dL ... The risk and burden of a composite of these abnormal lipid laboratory outcomes were 1·24 ... and 39·19 ... respectively. There was also increased risk and burden of incident lipid-lowering medications use (HR 1·54...; burden 25·50...
A composite of any dyslipidaemia outcome (laboratory abnormality or lipid-lowering medications use) yielded an
HR of 1·31 ... and a burden of 54·03 ... The risks and burdens of these post-acute outcomes increased in a graded fashion corresponding to the severity of the acute phase of COVID-19 infection (ie, whether patients were non-hospitalised, hospitalised, or admitted to intensive care). The results were consistent in analyses comparing the COVID-19 group to the non-infected historical control group.

Interpretation Our findings suggest increased risks and 1-year burdens of incident dyslipidaemia and incident lipid-
lowering medications use in the post-acute phase of COVID-19 infection. Post-acute care for those with COVID-19
should involve attention to dyslipidaemia as a potential post-acute sequela of SARS-CoV-2 infection
-------------------------------------------------------------

Jeremy Werner Deuel et al. 2022. Persistence, prevalence, and polymorphism of sequelae after COVID-19 in unvaccinated, young adults of the Swiss Armed Forces: a longitudinal, cohort study (LoCoMo). Lancet Infect Dis 2022 Dec;22(12):1694-1702. DOI: 10.1016/S1473-3099(22)00449-2 https://pubmed.ncbi.nlm.nih.gov/36030795/

Abstract
...We found a significant trend towards metabolic disorders in participants of the non-recent COVID-19 group compared with those in the control group: higher BMI (median 24·0 kg/m2 ... vs 23·2 kg/m2 ...), lower aerobic threshold (39% ... vs 41% ...), and higher blood cholesterol (4·2 μM ... vs 3·9 μM ...) and LDL concentrations (2·4 μM ...vs 2·2 μM ...). The only significant psychosocial difference was found in the results of the Chalder Fatigue scale with the non-recent COVID-19 group reporting higher fatigue scores than the control group (median 12 points ... vs 11 ...). No significant differences in other psychosocial questionnaire scores, ophthalmological outcomes, and sperm quality or motility were reported between the control group and non-recent COVID-19 group.

Interpretation: Young, previously healthy, individuals largely recover from SARS-CoV-2 infection. However, the constellation of higher BMI, dyslipidaemia, and lower physical endurance 180 days after COVID-19 is suggestive of a higher risk of developing metabolic disorders and possible cardiovascular complications. These findings will guide future investigations and follow-up management.

Hope nasal spray survives clinical trials! :D

delthia ricks 🔬@DelthiaRicks | 3:04 PM · Mar 24, 2023:
Award-winning science writer. Author. Citizen Scientist. Bylines: Newsday, Discover Magazine, Journal of the Nat'l Cancer Institute, Ms Magazine, Medical Xpress

In the lab: A nasal spray developed in Finland protects against #SARSCoV2 infection, including recent immune-evasive variants. When administered nasally the experimental molecule—TriSb92—developed at Univ of Helsinki blocks transmission & spread of #SARS2...
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Jette's on Mastodon White_Bite@mas.to 😊 @white_bite | 11:38 PM · Mar 24, 2023:
Monbusho scholar. Oral pathologist. Mol biol. Cancer research-Tumor suppressors & oncogenes. Dent. Oral Immunol. Cranio genetics.

Looks promising. The spray targets an area of the spike that is conserved (doesn't mutate) so that the region "changes its shape". This change prevents attachment of the virus to the host cell. 🤞🤞
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Anna R. Mäkelä et al. 2023. Intranasal trimeric sherpabody inhibits SARS-CoV-2 including recent immunoevasive Omicron subvariants. Nature Communications volume 14, Article number: 1637 (24 March 2023) https://www.nature.com/articles/s41467-023-37290-6

Abstract
The emergence of increasingly immunoevasive SARS-CoV-2 variants emphasizes the need for prophylactic strategies to complement vaccination in fighting the COVID-19 pandemic. Intranasal administration of neutralizing antibodies has shown encouraging protective potential but there remains a need for SARS-CoV-2 blocking agents that are less vulnerable to mutational viral variation and more economical to produce in large scale. Here we describe TriSb92, a highly manufacturable and stable trimeric antibody-mimetic sherpabody targeted against a conserved region of the viral spike glycoprotein. TriSb92 potently neutralizes SARS-CoV-2, including the latest Omicron variants like BF.7, XBB, and BQ.1.1. In female Balb/c mice intranasal administration of just 5 or 50 micrograms of TriSb92 as early as 8 h before but also 4 h after SARS-CoV-2 challenge can protect from infection. Cryo-EM and biochemical studies reveal triggering of a conformational shift in the spike trimer as the inhibitory mechanism of TriSb92. The potency and robust biochemical properties of TriSb92 together with its resistance against viral sequence evolution suggest that TriSb92 could be useful as a nasal spray for protecting susceptible individuals from SARS-CoV-2 infection.

Audray Fortin et al. 2023. Detection of viable SARS-CoV-2 in retrospective analysis of aerosol samples collected from hospital rooms of patients with COVID-19 (Letter to the Editor|Articles in Press). Clinical Microbiology & Infection. Published:March 22, 2023 DOI:https://doi.org/10.1016/j.cmi.2023.03.019 https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(23)00135-0/f...

...Alpha variant...before vaccines...2-3m from the patient's bed...The samples had been stored 14 months before carrying out the cell culture experiments. We first confirmed that our cell culture design clearly differentiated between replicating and non-replicating virus...No aerosol generating procedure occurred during air sampling...

...In conclusion, we provide much needed additional evidence for the presence of replicating SARS-CoV-2 virions in bioaerosols. Our results highlight the possibility to recover replicative virus particles in air samples after freezing at -80°C in VTM and storage for several months. Our results are important as they provide rationale for retrospective evaluation of the presence of infectious SARS-CoV-2 in samples collected during the different waves since 2020.

Lucy Adams: Three years and no magic bullet. I am doing things now that were unimaginable to me two years ago. I’ve even joined a choir. This wasn’t fun to write but I hope (in) some small way it might be helpful to some.

Long Covid: Three years and no magic bullet
Lucy Adams, BBC Scotland social affairs correspondent | 25 March 2023

I have had long Covid for three years. Even though I have made huge progress I still suffer most days with chronic pain in my joints, a rolling sense of vertigo, fatigue and brain fog...I'm thankful that I can do so much more than I could in those early stages. But on the bad days I feel remarkably frustrated I am nowhere near 100%...

...A collective amnesia has crept in. People want to get on with their lives.

The latest ONS figures from February 2023 indicate about two million people in the UK have long Covid. But the collection of such figures and the Covid figures more generally has been paused.

Research data suggests between 2% and 20% of people who contract Covid will go on to have longer term symptoms...

https://www.bbc.com/news/uk-scotland-65058119

Joseph Allen @j_g_allen | 5:51 PM · Mar 26, 2023
Assoc Prof @HarvardChanSPH; Lancet @CommissionCOVID (Chair Task Force on Safe Work/School/Travel); Coauthor of HEALTHY BUILDINGS @Harvard_Press; WaPo, NYT, HBR
https://twitter.com/j_g_allen/status/1640109353217736704

Current ventilation rates are not designed for Covid-19 (or any other respiratory pathogen)
That's why our Lancet Covid-19 Commission Task Force on Safe Work/School/Travel published this report*
Cover ( https://twitter.com/j_g_allen/status/1640109353217736704/photo/1 )
🧵

Task Force had widespread agreement on:
1) current targets too low
2) getting bldgs off current minimums would lead to big gains
3) coalescence around target values, across experts and metrics
4) we want to propose something that moves this convo forward
5) there is urgency
Slide ( https://twitter.com/j_g_allen/status/1640109357890248704/photo/1 )

We *intentionally* provided recs across three metrics (all have pros/cons; convo was *stuck* here) and with good/better/best (creating new minimums *and* a north star both important)
Slide ( https://twitter.com/j_g_allen/status/1640109363447705601/photo/1 )

Now that there's a target, how will you get there? We have you covered there, too. Our other report** details the First Four Strategies Every Building Should Pursue
https://twitter.com/j_g_allen/status/1640109368417959937/photo/1

Both of these reports - and others we released during the pandemic, can be found here:
https://covid19commission.org/safe-work-travel
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* Proposed Non-infectious Air Delivery Rates (NADR) for Reducing Exposure to Airborne Respiratory Infectious Diseases
The Lancet COVID-19 Commission Task Force on Safe Work, Safe School, and Safe Travel | NOVEMBER 2022
33 p
https://static1.squarespace.com/static/5ef3652ab722df11fcb2ba5d/t/637740d40f35a9...
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** The First Four Healthy Building Strategies Every Building Should Pursue to Reduce Risk from COVID-19
The Lancet COVID-19 Commission Task Force on Safe Work, Safe School, and Safe Travel | JULY 2022
7 p
https://static1.squarespace.com/static/5ef3652ab722df11fcb2ba5d/t/62c87da27d5686...

In #30 of previous thread, SARS-CoV-2 attacks mitochondria causing lung injury & impairing oxygen sensing...*. Might nicotinamide riboside help?

Helena A. K. Lapatto et al. 2023. Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study. Science Advances 13 Jan 2023. Vol 9, Issue 2. DOI: 10.1126/sciadv.add5163 https://www.science.org/doi/10.1126/sciadv.add5163
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* Stephen L. Archer @DrStephenArcher | 9:07 PM · Nov 14, 2022:
Head Dept. Medicine Queen’s University, MD-Scientist: Mitochondria, O2-sensing, Therapies for Pulmonary Hypertension and Cancer

24 scientists working since April 2020 ⁦@QueensuDOM⁩ discover virus causing COVID-19 attacks mitochondria causing lung injury & impairing oxygen sensing...

How Does COVID-19 Damage the Lungs? (TVO, 23:29)
https://twitter.com/DrStephenArcher/status/1592338360302915584
https://www.youtube.com/watch?v=o_RxKCKkV_c
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How COVID-19 damages lungs
Monday October 31, 2022
By Stephen L Archer, Professor, Head of Department of Medicine Queen's U
https://www.queensu.ca/gazette/stories/how-covid-19-damages-lungs
https://theconversation.com/how-covid-19-damages-lungs-the-virus-attacks-mitocho....

Viki Male @VikiLovesFACS | 4:56 AM · Mar 28, 2023:
Immunologist working on pregnancy at @ImperialCollege {London}
https://twitter.com/VikiLovesFACS/status/1640638952343306241

#Menstrual changes in those who received a #CovidVaccine (3,635), caught #COVID (1,802), both (1,354) or neither (5,788)...

🦠 Infected more likely to report shorter cycles, missed periods, heavier periods, spotting

💉Vaccinated only: no difference

Alvergne, A., Kountourides, G., Argentieri, M.A., Agyen, L., Rogers, N., Knight, D., Sharp, G.C, Maybin, J.A, Olszewska, Z., A retrospective case-control study on menstrual cycle changes following COVID-19 vaccination and disease, ISCIENCE (2023), doi: https://doi.org/10.1016/j.isci.2023.106401 https://cell.com/iscience/pdf/S2589-0042(23)00478-9.pdf {Journal Pre-Proof}

Summary
There has been increasing public concern that COVID-19 vaccination causes menstrual disturbance regarding the relative effect of vaccination compared to SARS-CoV-2 infection. Our objectives were to test potential risk factors for reporting menstrual cycle changes following COVID-19 vaccination and to compare menstrual parameters following COVID-19 vaccination and COVID-19 disease. We performed a secondary analysis of a retrospective online survey conducted in the UK in March 2021. In pre-menopausal vaccinated participants (n=4,989), 18% reported menstrual cycle changes after their first COVID-19 vaccine injection. The prevalence of reporting any menstrual changes was higher for women who smoke, have a history of COVID-19 disease, or are not using oestradiol-containing contraceptives. In a second sample including both vaccinated and unvaccinated participants (n=12,579), COVID-19 vaccination alone was not associated with abnormal menstrual cycle parameters while a history of COVID-19 disease was associated with an increased risk of reporting heavier bleeding, ‘missed’ periods and inter-menstrual bleeding.

Distinguishing between infection- and vaxx-acquired immunity:

Prof. Akiko Iwasaki (Yale) @VirusesImmunity | 6:01 PM · Aug 5, 2021

I ... made this figure in @BioRender to help people understand which antibody test will inform infection vs. vaccination. Hope people find this useful. Please share.

Image
https://twitter.com/VirusesImmunity/status/1423403916058845184/photo/1
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The COVID-19 Testing Toolkit
Johns Hopkins Center for Health Security
https://www.centerforhealthsecurity.org/covid-19TestingToolkit/

Long Covid: There is a lack of suitable medication and therapies
California18 / March 30, 2023
https://california18.com/long-covid-there-is-a-lack-of-suitable-medication-and-t...

Face coverings and COVID-19: statement from an expert panel
UK Health Security Agency | 14 October 2021. Last updated 30 March 2023

An expert panel statement, informed by evidence and expertise, on the role of face coverings in mitigating COVID-19 transmission.

https://www.gov.uk/government/publications/face-coverings-and-covid-19-statement...

Long COVID: Incidence, Impacts, And Implications
David Putrino | March 29, 2023

... (Long COVID is now a recognized disability* under the Americans with Disabilities Act, Section 504).

Long COVID: What’s In A Name?
How Common Is Long COVID, Who Is At Risk, And What Is The Prognosis?
Separating Out The Subtypes Of Long COVID
The Search For Biomarkers In Long COVID
Treatment And Management Of Syndromic Long COVID
The Path Forward

https://www.healthaffairs.org/content/forefront/long-covid-incidence-impacts-and...

* Guidance on “Long COVID” as a Disability Under the ADA, Section 504, and Section 1557
U.S. Department of Health Human Services Office for Civil Rights and U.S. Department of Justice Human Services Civil Rights Division Disability Rights Section
https://www.hhs.gov/civil-rights/for-providers/civil-rights-covid19/guidance-lon...

Eric Feigl-Ding (epidemiologist) @DrEricDing | 10:48 AM · Mar 25, 2023:

Staring at this graph—most striking is that the troughs of each #COVID hospitalization wave is higher and higher each wave… & broader as well. Flu may be one and done each year, but #COVID19 hospital admissions just keeps humming along. Concerning. #CovidIsNotOver

HY jneill
Graph flu COVID incidence Dec 21-March 23 England ( https://twitter.com/DrEricDing/status/1639640365660532736/photo/1 )

XBB.1.16. is new variant emerging in India: 55% of COVID samples. Severity, immune escape, response to vaxx/masks similar to other omicron variants. Sewage samples show spike in viral load

Rajeev Jayadevan @RajeevJayadevan | 9:14 PM · Apr 1, 2023:
Medical doctor/specialist 🇮🇳🇺🇸🇬🇧🇮🇪🇳🇱 Author, Educator, Co-Chairman National IMA COVID Task Force & Past President, Indian Medical Association

The first study on the clinical profile of XBB.1.16.
Thanks @r_karyakarte @NehaMadaanTOI for this

SLIDE ( https://twitter.com/RajeevJayadevan/status/1642334772809834496/photo/1 )

Study of 42 XBB.1.16 patients finds 11 had taken 3rd dose
Neha Madaan / TNN / Updated: Mar 30, 2023
https://m.timesofindia.com/city/pune/study-of-42-xbb-1-16-patients-finds-11-had-...
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Vipin M. Vashishtha @vipintukur | 12:35 AM · Apr 2, 2023
Pediatrician, ‘rational’ vaccine thinker, Editor Covid-19 Vaccines, Textbook on Vaccines & many other books on vaccines, Past-Convener IAP COI, Member-WHO-VSN

XBB.1.16 led Indian surge is not going to peak soon. Cases are still ascending—propelled by Kerala, Maharashtra, Delhi & Gujarat. Northern states have now started reporting more cases

RETWEET
Outbreak In India @outbreak_india · 6h

Day 1158, 02-Apr-23, at 8AM | 🇮🇳 #COVID19 update as per @MoHFW_INDIA

Active Cases: 18,389🔺2,035

New Cases: 3,824🔺28%
New Recovered: 1,784
New Deaths: 04 (+01 BD from KL)

Samples Tested: 1,33,153🔻7%
TPR: 2.87% | Weekly 2.24%

Explore more insights at https://outbreakindia.com/india-dashboard

Table, graphs increase in cases India ( https://twitter.com/outbreak_india/status/1642383491294986242/photo/1 )
Pie chart confirmed cases by prvince ( https://twitter.com/outbreak_india/status/1642383491294986242/photo/2 )

Xueling Yang et al. 2023. Identification of the regulatory mechanism of ACE2 in COVID-19–induced kidney damage with systems genetics approach. Journal of Molecular Medicine (23 March 2023). https://link.springer.com/article/10.1007/s00109-023-02304-9

Abstract
...Collectively, our data suggested that ACE2 (angiotensin-converting enzyme 2 ) work with RAS (renin-angiotensin system), PDGFC {a growth factor involved in regulating renal physiology and morphology}, as well as their cognate hub genes to regulate renal function, which could guide for future clinical prevention and targeted treatment for COVID-19–induced renal damage outcomes.

If nasal vaxx promise keeps being realized, reinfections could be thing of the past!

Eric Topol (Scripps) @EricTopol | 11:16 AM · Apr 3, 2023:

A nasal vaccine induced superior mucosal and systemic immunity vs #SARSCoV2 variants compared with mRNA (Pfizer) and adenovirus-vector vaccines by serology, histopathology, scRNA -seq in hamsters

{See photos of nasal mucosa infected/not infected via no vaxx, nasal vaxx, Pfizer vaxx, Adeovirus vaxx in
Fig. 6: Protective effects on the mucosa and development of local immunity after vaccination.}
https://twitter.com/EricTopol/status/1642908867410690048


Geraldine Nouailles et al. 2023. Live-attenuated vaccine sCPD9 elicits superior mucosal and systemic immunity to SARS-CoV-2 variants in hamsters. Nature Microbiology (3 April 2023) https://www.nature.com/articles/s41564-023-01352-8

Abstract
Vaccines play a critical role in combating the COVID-19 pandemic. Future control of the pandemic requires improved vaccines with high efficacy against newly emerging SARS-CoV-2 variants and the ability to reduce virus transmission. Here we compare immune responses and preclinical efficacy of the mRNA vaccine BNT162b2, the adenovirus-vectored spike vaccine Ad2-spike and the live-attenuated virus vaccine candidate sCPD9 in Syrian hamsters, using both homogeneous and heterologous vaccination regimens. Comparative vaccine efficacy was assessed by employing readouts from virus titrations to single-cell RNA sequencing. Our results show that sCPD9 vaccination elicited the most robust immunity, including rapid viral clearance, reduced tissue damage, fast differentiation of pre-plasmablasts, strong systemic and mucosal humoral responses, and rapid recall of memory T cells from lung tissue after challenge with heterologous SARS-CoV-2. Overall, our results demonstrate that live-attenuated vaccines offer advantages over currently available COVID-19 vaccines.

DISCUSSION...Due to its high safety profile, sCPD9 was recently downgraded from biosafety level (BSL) 3 to BSL 2 by the relevant German state authority... This is a key step towards clinical application of a SARS-CoV-2 LAV (live-attenuated vaccine) as it will facilitate production of a clinical grade vaccine and greatly ease clinical trials in humans.) as it will facilitate production of a clinical grade vaccine and greatly ease clinical trials in humans.

LaRovere KL, Poussaint TY, Young CC, et al; for the Overcoming COVID-19 Investigators. Changes in distribution of severe neurologic involvement in US pediatric inpatients with COVID-19 or multisystem inflammatory syndrome in children in 2021 vs 2020 https://jamanetwork.com/journals/jamaneurology/fullarticle/2798383. JAMA Neurol 2022; Epub 2022 Nov 7.

Key Points
Question What was the spectrum of SARS-CoV-2–related pediatric severe neurologic involvement in 2021?

Findings In this case series of 2168 US patients younger than 21 years hospitalized for acute COVID-19 (34%) or multisystem inflammatory syndrome in children (66%), 476 (22%) had neurologic involvement. Of these, 42 (9%) had life-threatening conditions, with 23 (55%) having acute central nervous system (CNS) infections/demyelination; 18 of 42 (43%) died or had new neurologic deficits; and most vaccine-eligible patients were unvaccinated.

Meaning In 2021, SARS-CoV-2–related severe neurologic involvement in US hospitalized children and adolescents showed a potential increase in diagnoses of acute CNS infections/demyelination.

"~60% of us who had COVID still might have lingering viral spikes in our heads!"
(My takeaway: avoid reinfection AMAP, while we await nasal vaxx and LC therapeutics!!)

Eric Topol (Scripps) @EricTopol | 10:00 AM · Apr 6, 2023:
Important new report on #LongCovid and the brain demonstrating persistence of the virus spike protein, throughout the body and particularly the skull-meninges axis, both in humans and the mouse model...

Ali M. Erturk @erturklab | 5:02 AM · Apr 6, 2023:
@HelmholtzMunich , prof LMU, generating technologies to treat major health problems.

😮~60% of us who had COVID still might have lingering viral spikes in our heads! Our new study reveals SARS-CoV-2 spike accumulation in the skull-meninges-brain axis & its implications in long COVID. ...
https://biorxiv.org/content/10.1101/2023.04.04.535604v1.full.pdf *
1:26 ( https://twitter.com/erturklab/status/1643902019088908289 )

2/n Summary:
We found SARS-CoV-2 spike protein in the skull-meninges-brain axis in mouse models and human post-mortem tissues long after their COVID, which was associated with vascular and inflammatory changes in the brain along with neuronal damage.
Graphical Summary ( https://twitter.com/erturklab/status/1643902020783308800/photo/1 )

* Zhouyi Rong et al. 2023. SARS-CoV-2 Spike Protein Accumulation in the Skull-Meninges-Brain Axis: Potential Implications for Long-Term Neurological Complications in post-COVID-19. BioRxiv 5 April 2023. 26 p. https://doi.org/10.1101/2023.04.04.535604 https://www.biorxiv.org/content/10.1101/2023.04.04.535604v1.full.pdf

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Meanwhile at Yale:

Participant-centric Trial Will Test if Antiviral Paxlovid Can Help With Long COVID
Isabella Backman | April 03, 2023

...Harlan Krumholz, MD, Harold H. Hines, Jr. Professor of Medicine (Cardiology) and professor in the Institute for Social and Policy Studies, of investigative medicine, and of public health (health policy) and Akiko Iwasaki, PhD, Sterling Professor of Immunobiology and professor of dermatology, of molecular, cellular & developmental biology, and of epidemiology (infectious diseases) have been leaders in unraveling the mysteries of long COVID and advocating for those who are suffering. Through their clinical trial, they plan to combine their expertise in the clinic and lab to understand the biological mechanisms that occur throughout the course of receiving Paxlovid. The trial will be held through a unique decentralized format designed to boost accessibility for its participants.

...The team hopes that its study will not only help those struggling with long COVID, but also provide a greater understanding of other post-infectious syndromes. “Infectious triggers are responsible for a whole lot of downstream suffering among people,” says Krumholz. “This study will help us begin to understand this phenomenon diagnostically and start identifying targets to help relieve the widespread suffering.”

“There are a number of other similar post-acute infection syndromes that happen after many different virus infections and some bacteria and parasitic infections,” says Iwasaki. “The fact that the downstream consequences, including myalgic encephalomyelitis, are so similar to each other makes us believe that once we figure out one of these syndromes, we can apply a similar insight into other post-acute phase diseases.”...

https://medicine.yale.edu/news-article/participant-centric-trial-will-test-if-an...

>98 margd: contd. Rong et al 2023

Jette's Not A 📚 😊 @white_bite | 10:40 PM · Apr 5, 2023:
Monbusho scholar. Oral pathologist. Mol biol. Cancer research-Tumor suppressors & oncogenes. Dent. Oral Immunol. Cranio genetics.

Interesting to note how spike proteins of SARS2 are able to bind to almost the entire body in mice when infected with the virus. The red dye shows areas of infection. Take note of the difference between the flu virus and SARS2 spike. (It's not the flu!) (2/n)
{1st photo is Wuhan strain, second is B1.117, 3rd is flu}
Photo ( https://twitter.com/white_bite/status/1643805751121674240/photo/1 )

It was also noted that SARS2 may have gained access through the marrow and meninges in the human skull. (Meninges are the protective layer right under the skull) This was in comparison to samples negative of SARS2 infection. (3/n)

8 of 16 skull samples had SARS2 and 6 of 12 had SARS2 spike protein in the meninges.
Blue areas indicate presence of SARS2. Ctrl= SARS2 negative (4/n)
photos ( https://twitter.com/white_bite/status/1643805763494871044/photo/1 )

Noted too were changes in protein structures i the brain caused by infection -- some being indicative of ongoing inflammation.
Study further elucidated injury in brain cells due to presence of spike proteins in the skull and meninges.
Study further proves persistence of (5/n)

Spike proteins in the skull and meninges.
These all result in continuous inflammation as well as injury to the blood vessels which may lead to blood clots and damage to the area.
This shows a new http://mechanism.as to how brain injury is incurred in COVID post infection.
Graphical and short summary ( https://twitter.com/white_bite/status/1643805775410905089/photo/1 )

>98 margd: contd. (Yale studies efficacy of pavlovid on Long Covid) "Currently people in CT, NY, and FL can enroll. "

Prof. Akiko Iwasaki (Yale) @VirusesImmunity | 3:30 PM · Apr 6, 2023:

We are now enrolling in the #PaxLCTrial; randomizing people with #longCOVID to 15 days of Paxlovid (nirmatrelvir/ritonavir) or placebo (placebo/ritonavir). Currently people in CT, NY, and FL can enroll. Hope to expand to other states soon. For more info 👉🏼 https://kindred.hugo.health/pax-lc

Image ( https://twitter.com/VirusesImmunity/status/1644059997767098370/photo/1 )

Virological characteristics of new SARS-CoV-2 lineage of concern, XBB.1.16, which is rapidly spreading in India. "XBB.1.16 had an effective reproductive number (R e) that was 1.27- and 1.17-fold higher than the parental XBB.1 and XBB.1.5,58 respectively, suggesting that XBB.1.16 will spread worldwide in the near future."

The Sato Lab (Kei Sato) {U Tokyo} @SystemsVirology | 11:51 PM · Apr 6, 2023:
https://twitter.com/SystemsVirology/status/1644186056160583681
BREAKING🔔 A new preprint from G2P-Japan🇯🇵 is out @biorxivpreprint. We illuminated the virological characteristics of new SARS-CoV-2 lineage of concern, XBB.1.16, which is rapidly spreading in India🇮🇳 Please RT🔥 1/...
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Daichi Yamasoba et al. 2023. Virological characteristics of the SARS-CoV-2 Omicron XBB.1.16 variant. BioRxiv 6 April 2023. doi: https://doi.org/10.1101/2023.04.06.535883 https://www.biorxiv.org/content/10.1101/2023.04.06.535883v1

This article is a preprint and has not been certified by peer review

Abstract

At the end of March 2023, XBB.1.16, a SARS-CoV-2 omicron XBB subvariant, emerged and was detected in various countries. Compared to XBB.1.5, XBB.1.16 has two substitutions in the S protein: E180V is in the N-terminal domain, and T478K in the receptor-binding domain (RBD). We first show that XBB.1.16 had an effective reproductive number (Re) that was 1.27- and 1.17-fold higher than the parental XBB.1 and XBB.1.5, respectively, suggesting that XBB.1.16 will spread worldwide in the near future. In fact, the WHO classified XBB.1.16 as a variant under monitoring on March 30, 2023. Neutralization assays demonstrated the robust resistance of XBB.1.16 to breakthrough infection sera of BA.2 (18-fold versus B.1.1) and BA.5 (37-fold versus B.1.1). We then used six clinically-available monoclonal antibodies and showed that only sotrovimab exhibits antiviral activity against XBB subvariants, including XBB.1.16. Our results suggest that, similar to XBB.1 and XBB.1.5, XBB.1.16 is robustly resistant to a variety of anti-SARS-CoV-2 antibodies. Our multiscale investigations suggest that XBB.1.16 that XBB.1.16 has a greater growth advantage in the human population compared to XBB.1 and XBB.1.5, while the ability of XBB.1.16 to exhibit profound immune evasion is comparable to XBB.1 and XBB.1.5. The increased fitness of XBB.1.16 may be due to (1) different antigenicity than XBB.1.5; and/or (2) the mutations in the non-S viral protein(s) that may contribute to increased viral growth efficiency.

Rare but horrifying brain damage in babies whose mothers tested SARS-CoV-2 positive several weeks before delivery...

Ralf Wittenbrink @RWittenbrink | 9:00 AM · Apr 8, 2023:
Translated from German by Google

Maternal #SARSCoV2 , placental changes and brain damage in newborns

"Long-term neurodevelopmental abnormalities in newborns exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in utero...
Photos ( https://twitter.com/RWittenbrink/status/1644686720686759936/photo/1 )

is the fetal brain. Future longitudinal studies are needed to investigate the effects of the timing of #SARSCoV2 infection on placental inflammation, as well as the long-term consequences for the developing brain.”
Photos ( https://twitter.com/RWittenbrink/status/1644686763347124224/photo/1 )
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Merline Benny et al. 2023. Maternal SARS-CoV-2, Placental Changes and Brain Injury in 2 Neonates.
Pediatrics e2022058271. April 06 2023. https://doi.org/10.1542/peds.2022-058271 https://publications.aap.org/pediatrics/article/doi/10.1542/peds.2022-058271/191...

...This report summarizes severe neurologic injury in 2 infants born in the third trimester, whose mothers tested SARS-CoV-2 positive several weeks before delivery. Both infants displayed ongoing neurologic injury and developmental deficits. One infant, with sudden death at 13 months of age, had extensive loss of brain white matter, gliosis, and vacuolization at autopsy...

"SARS-CoV-2 awakens ancient retroviral genes and the expression of proinflammatory HERV-W envelope protein in COVID-19 patients"

Charvet, B., et al. 2023. SARS-CoV-2 awakens ancient retroviral genes and the expression of proinflammatory HERV-W envelope protein in COVID-19 patients, ISCIENCE (2023), journal Pre-proof. doi: https://doi.org/10.1016/j.isci.2023.106604. https://www.cell.com/action/showPdf?pii=S2589-0042%2823%2900681-8

Abstract
Patients with COVID-19 may develop abnormal inflammatory response, followed in some cases by severe disease and long-lasting syndromes. We show here that in vitro exposure to SARS-CoV-2 activates the expression of the human endogenous retrovirus* (HERV) HERV-W proinflammatory envelope protein (ENV) in peripheral blood mononuclear cells from a subset of healthy donors, in ACE2 receptor and infection-independent manner. Plasma and/or sera of 221 COVID-19 patients from different cohorts, infected with successive SARS-CoV-2 variants including the Omicron, had detectable HERV-W ENV, which correlated with ENV expression in T-lymphocytes and peaked with the disease severity. HERV-W ENV was also found in post-mortem tissues of lungs, heart, gastrointestinal tract, brain olfactory bulb and nasal mucosa from COVID-19 patients. Altogether, these results demonstrate that SARS-CoV-2 could induce HERV-W envelope protein expression and suggest its involvement in the immunopathogenesis of certain COVID-19-associated syndromes and thereby its relevance in the development of personalized treatment of patients.

Discussion
In spite of rapid advances in basic and translational science, COVID-19 continues to pose an important global health threat. This new disease revealed heterogeneous clinical profiles in the evolution of acute and post-acute COVID-19, with symptoms not directly related to the viral infection. In the present study we have analyzed the induction of HERV expression during COVID-19 disease. Our initial in vitro results showed that SARS-CoV-2 can trigger both HERV-W and HERV-K ENV RNA transcription after a single exposure to SARS-CoV-2 virus, but only HERV-W ENV protein
expression in short-term PBMC cultures from about 30% of healthy donors, suggesting heterogeneity in the healthy population for SARS-CoV-2-induced HERV activation.

...Since all severe COVID-19 cases were tested positive for HERV-W ENV protein in plasma, this points to a potential marker of disease severity as already shown with blood T-lymphocytes. We also found HERV-W ENV in plasma of about 20% of early COVID-19 cases who were included after positive SARS-CoV-2 PCR result, independently of disease severity. This percentage is similar to that of healthy donors who showed HERV-W ENV positivity in PBMC exposed to SARS-CoV-2 challenge in vitro. Altogether, these data suggest that a percentage of individuals with an underlying susceptibility to more symptomatic and/or severe evolution may be linked to the activation of HERV-W ENV expression. In PBMC cultures non-responding to SARS-CoV-2 exposure, we had observed HERV RNA levels below the levels of non-exposed controls, which may be explained by the activation of HERV-inhibitory pathways and effectors. Thus, an inter-individual variability in the potency of HERV inhibitory mechanisms, possibly with an (epi)genetic origin, may provide an explanation for non-universal activation of HERV-W ENV upon SARS-CoV-2 challenge, similarly to individuals with COVID-19. Indeed, most SARS-CoV-2 RT-PCR positive individuals do not develop major symptomatology after infection, including asymptomatic cases who may represent about 35% of PCR-positive cases. Moreover, since patients from different geographic areas and time periods of the pandemic, infected by different variants of SARS-CoV-2 were analyzed, the global results of this study are not expected to be influenced by such variables.

...Moreover, given the known HERV-W involvement in the microglia-driven pathogenesis of multiple sclerosis or of certain psychoses associated with inflammatory biomarkers, the presently observed HERV-W ENV expression in microglia strongly suggests a role in neurological symptoms and cognitive impairment mostly occurring or persisting during the post-acute COVID-19 period

...In acute primary infection, the pathogenic effects of HERV-W ENV on immune cells needs to be further considered to better understand COVID-19 immunopathogenesis. HERV-W ENV production may result in a hyperactivation of the innate immunity via HERV-W ENV-mediated TLR4 activation and in a possible contribution to the frequently observed lymphopenia along with an adaptive immune defect. The induction of autoimmune manifestations64-67 as previously shown to be provoked with HERV-W ENV, initially called MSRV,21 as well as the capacity of HERVs to modulate innate immunity should also be considered.

Altogether, these data indicate that HERV-W ENV does not simply represent a biomarker of COVID-19 severity or evolution but is also likely to be a superimposed pathogenic player contributing to the disease severity and may help to explain the inter-individual variability in COVID-19 manifestations. In addition, it may play a role in the clinical evolution with possible long-term pathology as seen with the now emerging post-COVID secondary pandemic representing
millions of patients suffering from various symptoms and long-term disabling pathology for which no rationalized understanding nor therapeutic perspective can be proposed to date. In face of this challenging situation, data from the present study strongly suggest HERV-W ENV as a marker of severity and as a potential therapeutic target for personalized medical approaches in in COVID-19 associated syndromes.

*Endogenous retroviruses ( ERVs) are endogenous viral elements in the genome that closely resemble and can be derived from retroviruses. They are abundant in the genomes of jawed vertebrates, and they comprise up to 5-8% of the human genome (lower estimates of ~1%). https://en.wikipedia.org/wiki/Endogenous_retrovirus

Tatiana Prowell, MD @tmprowell | 7:02 PM · Apr 9, 2023
Internist/oncologist serving people w/ #cancer @ #bcsm clinic, #MedEd, #Regulatory & #COVID19. #ASCO20 Ed Chair.

A study from #Brazil finds 1 in 4 adults who had mild #COVID19 demonstrated cognitive deficits. The average age of study participants was 38. See what happened when they were asked to copy a diagram. We are not prepared for this. #MedTwitter #LongCovid https://brainfacts.org/diseases-and-disorders/covid-19/2023/the-risks-of-even-mi... *

Text excerpt and copied diagrams ( https://twitter.com/tmprowell/status/1645200506518740993/photo/1 )
---------------------------------------------------------------------------------

The Risks of Even Mild COVID-19: 1 in 4 Showing Cognitive Deficits After Mild Case, Brazilian Study Finds
Christine Won | 17 Jan 2023

...In one study, researchers in Brazil found people who had mild COVID-19 symptoms showed “persistent cognitive impairment” months post-infection, where some were complaining of bumping into things or not being able to park the car due to altered depth perception and visual processing. “Everybody was worried about severe COVID, but the number of people with mild COVID is four times higher,” says Marco Romano-Silva, of the Federal University of Minas Gerais in Brazil and senior author of the study published in June in Molecular Psychiatry.

...Researchers found 1 in 4 showed significant cognitive impairment in visuoconstruction skills — the visual ability to spatially reproduce designs or patterns — matching the increased levels of inflammation they were seeing on blood panels as well as in neuroimaging.

...They discovered the sensorimotor brain regions of children who had contracted severe COVID-19 months ago were using more resources compared with healthy children. “Our hypothesis is that if there is a dysfunction in these specific areas, other areas have to be connected that have to compensate for ideal functioning,” Hidalgo-Tobon says, remarking their findings suggest the affected areas ultimately manifested a cognitive profile similar to attention-deficit/hyperactivity disorder (ADHD). “In addition, it is important to note this activation of supplementary motor areas in a general dysfunctional way…that has an impact on executive processes.”...

REFERENCES
de Paula, J. J., et al. 2022. Selective visuoconstructional impairment following mild COVID-19 with inflammatory and neuroimaging correlation findings. Molecular psychiatry, 1–11. Advance online publication. https://doi.org/10.1038/s41380-022-01632-5

Díez-Cirarda, M., et al. 2022. Predominance of visuoconstructive impairment after mild COVID-19?. Molecular psychiatry, 1–2. Advance online publication. https://doi.org/10.1038/s41380-022-01797-z

Long-term study of children with COVID-19 begins. (2021, November 15). National Institutes of Health. https://www.nih.gov/news-events/news-releases/long-term-study-children-covid-19-...

https://www.brainfacts.org/diseases-and-disorders/covid-19/2023/the-risks-of-eve...

:)

Eric Topol (Scripps) @EricTopol | 4:25 PM · Apr 10, 2023:

This is big, folks. The WhiteHouse is supporting next generation—nasal and variant-proof Covid vaccines —and therapies with a $5 billion program https://washingtonpost.com/health/2023/04/10/operation-warp-speed-successor-proj... by ddiamond

Thanks to the relentless efforts of @AshishKJha46 and @WHCOVIDResponse 👍

White House launching $5 billion program to speed coronavirus vaccines
‘Project Next Gen’ would succeed ‘Operation Warp Speed’ with a mission to develop next-generation vaccines and therapies.
Dan Diamond | 10 April 2023
https://washingtonpost.com/health/2023/04/10/operation-warp-speed-successor-proj...

>101 margd: contd.

Covid wastewater levels in Bengaluru, a southern India capital city, have just reached their all time high, topping even the original Omicron surge. This variant is screaming to us that something is different. We have a legit covid catastrophe waiting to go global.

Graphs Bengalaru sewer virus-trend, Bangalore cases-lagging indicator ( https://twitter.com/Derek_a_Franks/status/1645437827537154052/photo/1 )

- Derek Franks @Derek_a_Franks | 10:45 AM · Apr 10, 2023

:) Good news: "no association between prenatal exposure to mild maternal SARS-CoV-2 infection and infant neurodevelopment". COVID infection may be risky for pregnant mom, and may invade placenta, but born babies are proving normal neurodevelopmentally.

Sarah B. Mulkey 2023. Use of Telehealth Methods to Track Infant Neurodevelopment After In Utero SARS-CoV-2 Exposure (Invited Commentary). JAMA Netw Open. 2023;6(4):e237403. doi:10.1001/jamanetworkopen.2023.7403 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2803648

...The results of this study provide needed reassurance to the many mothers who have experienced SARS-CoV-2 infection during pregnancy. Pregnant patients continue to be exposed to SARS-CoV-2 despite their efforts to avoid infection, so the findings of this study can help mothers have less worry about potential consequences on their infants’ early neurodevelopment.

---------------------------------------------------------
Morgan R. Firestein et al. 2023. Assessment of Neurodevelopment in Infants With and Without Exposure to Asymptomatic or Mild Maternal SARS-CoV-2 Infection During Pregnancy (Original Investigation). JAMA Netw Open. 10 April 2023;6(4):e237396. doi:10.1001/jamanetworkopen.2023.7396 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2803646

Abstract
...Main Outcomes and Measures Infant neurodevelopment was assessed using the Developmental Assessment of Young Children, second edition (DAYC-2), adapted for telehealth assessment. The primary outcome was age-adjusted standard scores on 5 DAYC-2 subdomains: cognitive, gross motor, fine motor, expressive language, and receptive language.

Results Among 403 mothers, the mean (SD) maternal age at delivery was 32.1 (5.4) years; most mothers were of White race (240 {59.6%}) and non-Hispanic ethnicity (253 {62.8%}). Among 407 infants, 367 (90.2%) were born full term and 212 (52.1%) were male. Overall, 258 infants (63.4%) had no documented prenatal exposure to SARS-CoV-2 infection, 112 (27.5%) had confirmed prenatal exposure, and 37 (9.1%) had exposure before pregnancy or at an indeterminate time. In adjusted models, maternal SARS-CoV-2 infection during pregnancy was not associated with differences in cognitive (β = 0.31...), gross motor (β = 0.82...), fine motor (β = 0.36...), expressive language (β = −1.00...), or receptive language (β = 0.45...) DAYC-2 subdomain scores. Trimester of exposure and maternal symptom status were not associated with DAYC-2 subdomain scores.

Conclusions and Relevance In this study, results of a novel telehealth-adapted observational neurodevelopmental assessment extended a previous finding of no association between prenatal exposure to maternal SARS-CoV-2 infection and infant neurodevelopment. Given the widespread and continued high prevalence of COVID-19, these data offer information that may be helpful for pregnant individuals who experience asymptomatic or mild SARS-CoV-2 infections.

President Biden signed a bipartisan congressional resolution to end the national emergency for the COVID-19 pandemic, weeks before it was set to expire with the public health emergency. (AP)

https://apnews.com/article/joe-biden-covid19-coronavirus-national-emergency-e3a5...

>106 margd: upcoming variants, contd.

Vipin M. Vashishtha @vipintukur | 11:17 PM · Apr 11, 2023:
Pediatrician, ‘rational’ vaccine thinker, Editor Covid Vaccines, TB on Vaccines & many others, Past-Convener IAP COI, Member-WHO-VSN (http://vaccinesafetynet.org)

#Arcturus XBB.1.16 & its progenies are still the fastest, but many new variants are fast approaching it. The nearest in growth potential is XBC.1.6-a recombinant of Delta & Omicron, growing quickly in Australia & few other countries

Table, variants ( https://twitter.com/vipintukur/status/1645989569362563072/photo/1 )

Quote Tweet
Federico Gueli 🇺🇳 @siamosolocani · 11h
#Collection24 maintained and run by @wolfeagle1989 shows the game as it is
XBB.1.16 likely still the fastest but now less lonely, i would call XBC.1.6 as main contender but FP.1 / XBB.2.3.2 / XBB.2.3.4 / XBB.1.28.1 / XBB.1.31 /XBB.1.22.2 are NOT out of the game.

>98 margd: >100 margd: contd (Paxlovid study on Long COVID)

Prof. Akiko Iwasaki (Yale) @VirusesImmunity | 8:44 AM · Apr 11, 2023:
We study innate and adaptive immunity against viruses and study disease pathogenesis.
https://twitter.com/VirusesImmunity/status/1645769873174196228

Our study showing that Omicron subvariants are even more capable than other VOCs {variants of concern} in suppressing MHC I expression to evade CD8 T cell immunity is just published.*

For a detailed explanation of our findings, please read my thread below. (2/)
https://twitter.com/VirusesImmunity/status/1607446922599763968

Our data showed that MHC I suppression is mediated by a number of viral gene products and affects only the infected cells (S+). Such a mechanism will not lead to generalized immunodeficiency but reflects a specific survival mechanism for SARS-CoV-2. (3/)
https://twitter.com/VirusesImmunity/status/1645769873174196228/photo/1

What does this mean? Immune evasion from CD8 T cells could allow infected cells to survive better in the host. The virus could establish a safe niche for prolonged replication. To eliminate such persistent reservoirs, we need to employ antivirals or antibody therapy. (4/)

To see if eliminating such a viral reservoir could lead to recovery from #longCOVID, @hmkyale and a team of @YaleMed @YaleCII scientists have started #PaxLCTrial. Learn more about this trial here. (5/)
https://www.kindred.hugo.health/pax-lc

Ending this thread with a great description of our #PaxLCTrial by @IzzyBackman. This trial is decentralized, patient-centric, and intended to uncover biological features associated with symptom improvement with Paxlovid. (end) 🙏🏼
https://medicine.yale.edu/news-article/participant-centric-trial-will-test-if-an...

------------------------------------------------
* Miyu Moriyama et al. 2023. Enhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants. PNAS
April 10, 2023. Vol. 120 | No. 16. https://doi.org/10.1073/pnas.2221652120 https://www.pnas.org/doi/10.1073/pnas.2221652120

Significance
Numerous pathogenic viruses have developed strategies to evade host CD8+ T cell-mediated clearance. Here, we demonstrated that SARS-CoV-2 encodes multiple viral factors that can modulate major histocompatibility complex class I (MHC-I) expression in the host cells. We found that MHC-I upregulation was strongly suppressed during SARS-CoV-2, but not influenza virus infection, in vivo. Notably, the Omicron subvariants showed an enhanced ability to suppress MHC-I compared to the original strain and the earlier SARS-CoV-2 variants of concern (VOCs). We identified a mutation in the E protein shared by the Omicron subvariants that further suppressed MHC-I expression. Our results point to the inherently strong ability of SARS-CoV-2 to hinder MHC-I expression and demonstrated that Omicron subvariants have evolved an even more optimized capacity to evade CD8 T cell recognition.

Koji Matsuo et al. 2023. Severe Maternal Morbidity and Mortality of Pregnant Patients With COVID-19 Infection During the Early Pandemic Period in the US. JAMA Netw Open. 7 April 2023;6(4):e237149. doi:10.1001/jamanetworkopen.2023.7149

"The mortality of pregnant patients with COVID at time of delivery was 14 times greater than delivering patients without"

"SARS-CoV-2 infection is linked to a substantially increased risk of developing a diverse spectrum of new-onset autoimmune diseases."

Chetan Sharma & Jagadeesh Bayry 2023. High risk of autoimmune diseases after COVID-19. Nature Reviews Rheumatology (12 April 2023) 2p https://www.nature.com/articles/s41584-023-00964-y

Eric Topol's highlighted text ( https://twitter.com/EricTopol/status/1646507680272642050/photo/1 )

Human coronaviruses (HCoVs) cause ~20% colds) replication "significantly attenuated" at 37C (98.6F). "In contrast, SARS-CoV-2 and MERS-CoV replicate at both temperatures (33C, 37C), though SARS-CoV-2 replication is enhanced at 33 °C late in infection."

"following infection...the seasonal HCoVs as well as SARS-CoV-2 cause cellular cytotoxicity {toxic to cells} as well as epithelial barrier disruption, while MERS-CoV does not."

"IL-13 treatment {mimics asthma} enhances MERS-CoV and HCoV-229E replication but reduces that of SARS-CoV-2 and HCoV-NL63..."
---------------------------------------------------------------

Clayton J. Otter et al. 2023. Infection of primary nasal epithelial cells differentiates among lethal and seasonal human coronaviruses. PNAS April 6, 2023. 120 (15) e2218083120. https://doi.org/10.1073/pnas.2218083120 https://www.pnas.org/doi/10.1073/pnas.2218083120

Abstract
The nasal epithelium is the initial entry portal and primary barrier to infection by all human coronaviruses (HCoVs {cause of ~20% of "colds"}). We utilize primary human nasal epithelial cells grown at air–liquid interface, which recapitulate the heterogeneous cellular population as well as mucociliary clearance functions of the in vivo nasal epithelium, to compare lethal {Severe acute respiratory syndrome (SARS)-CoV-2 and Middle East respiratory syndrome-CoV (MERS-CoV)} and seasonal (HCoV-NL63 and HCoV-229E) HCoVs.
...This study highlights diversity among HCoVs during infection of the nasal epithelium, which is likely to influence downstream infection outcomes such as disease severity and transmissibility.

Harry Spoelstra @HarrySpoelstra | 10:54 AM · Apr 14, 2023:
CardioVascular Surgeon, international clinical research...

Study reports that #SarsCoV2 can cause a significant deficiency in the phagocytic activity of monocytes, which is a critical effector mechanism for the antifungal host defence:
➡️Opening possibilities for opportunistic fungal infections....... a "mystery" if it ever was, solved? 🤔
➡️CAM(COVID-19-associated mucormycosis)

https://journals.asm.org/doi/10.1128/mbio.00590-23 *
------------------------------------------------------

* Bishnu Prasad Sinha et al. 2023. Deficient Phagocytosis in Circulating Monocytes from Patients with COVID-19-Associated Mucormycosis. (Assoc Soc Microbio) mBio 13 April 2023 DOI: https://doi.org/10.1128/mbio.00590 https://journals.asm.org/doi/10.1128/mbio.00590-23

ABSTRACT
...Compared to monocytes from healthy individuals, peripheral blood CD14+ monocytes from CAM {COVID-19-associated mucormycosis, esp. in India} patients were significantly deficient in phagocytic function. The monocyte transcriptome also revealed that pathways related to endocytic pathways, phagosome maturation, and the cytoskeletal regulation of phagocytosis were significantly downregulated in CAM patients. Thus, the study reports a significant deficiency in the phagocytic activity of monocytes, which is a critical effector mechanism for the antifungal host defense, in patients with CAM. This result is in concordance with results regarding the specific cytokine signature and monocyte transcriptome.
_________________________________________

Everything you need to know about the rare fungal infection that's infected nearly 100 people in Michigan
The outbreak occurred at a paper mill on the Upper Peninsula of Michigan.
Mary Kekatos | April 15, 2023
https://abcnews.go.com/Health/rare-fungal-infection-infected-100-people-michigan...
__________________________________________

ETA:
New York had record-high cases of ‘diabolical’ fungal infection last year
Jacob Geanous | April 15, 2023
https://nypost.com/2023/04/15/new-york-had-record-high-cases-diabolical-fungal-i...

Carmen Scheibenbogen @C_Scheibenbogen | 9:10 AM · Apr 18, 2023:
Immunologist and ME/CFS researcher @ChariteBerlin

Translated from German by google
Preprint to the follow-up data of our #Charite post covid study, which unfortunately shows that most #PCS #MECFS are persistently seriously ill.

medrxiv.org
Symptom persistence and biomarkers in post-COVID-19/chronic fatigue syndrome - results from a...
Introduction: Post-COVID-19 syndrome (PCS) is characterized by a wide range of symptoms, predominantly fatigue and exertional intolerance. While disease courses during the first year post infection...

Anna Franziska Legler et al. 2023. Symptom persistence and biomarkers in post-COVID-19/chronic fatigue syndrome - results from a prospective observational cohort. MedRxiv 17 April 2023. doi: https://doi.org/10.1101/2023.04.15.23288582 https://www.medrxiv.org/content/10.1101/2023.04.15.23288582v1

This article is a preprint and has not been certified by peer review

Abstract
Introduction: Post-COVID-19 syndrome (PCS) is characterized by a wide range of symptoms, predominantly fatigue and exertional intolerance. While disease courses during the first year post infection have been repeatedly described, little is known about long-term health consequences.

Methods: We assessed symptom severity and various biomarkers at three time points post infection (3-8 months (mo), 9-16mo, 17-20mo) in 106 PCS patients with moderate to severe fatigue and exertional intolerance. A subset of patients fulfilled diagnostic criteria of myalgic encephalomyelitis/chronic fatigue syndrome (PCS-ME/CFS) based on the Canadian Consensus Criteria.

Results: While PCS-ME/CFS patients showed persisting symptom severity and disability up to 20mo post infection, PCS patients reported an overall health improvement. Inflammatory biomarkers equally decreased in both groups. Lower hand grip force at onset correlated with symptom persistence especially in PCS-ME/CFS.

Discussion: Debilitating PCS may persist beyond 20mo post infection, particularly in patients fulfilling diagnostic criteria for ME/CFS.

COVID during pregnancy may alter brain development in boys
Jon Hamilton | April 18, 2023
Heard on Morning Edition (3 min)

Boys born to mothers who got COVID-19 while pregnant appear nearly twice as likely as other boys to be diagnosed with subtle delays in brain development...

In the study, boys, but not girls, were more likely to be diagnosed with a range of developmental disorders in the first 18 months of life. These included delays in speech and language, psychological development and motor function, as well as intellectual disabilities.

In older children, these differences are often associated with autism spectrum disorder, says Dr. Roy Perlis, a co-author of the study and a psychiatrist at Massachusetts General Hospital.

But for the young children in this study, "it's way too soon to reliably diagnose autism," Perlis says. "All we can hope to detect at this point are more subtle sorts of things like delays in language and speech, and delays in motor milestones."

The finding is just the latest to suggest that a range of maternal infections can alter fetal brain development, especially in male offspring. For example, studies have found links between infections like influenza and cytomegalovirus, and disorders like autism and schizophrenia.

"Male fetuses are known to be more vulnerable to maternal infectious exposures during pregnancy," says Dr. Andrea Edlow, the study's lead author and a maternal-fetal medicine specialist at Massachusetts General Hospital...

But the effect from COVID-19 appears to be modest, Perlis says. "Most children of moms who have COVID during pregnancy won't have neurodevelopmental consequences even if there is some increase in risk."...

https://www.npr.org/sections/health-shots/2023/04/18/1170087779/covid-pregnancy-...
-------------------------------------------------------------

Andrea G. Edlow et al. 2023. Sex-Specific Neurodevelopmental Outcomes Among Offspring of Mothers With SARS-CoV-2 Infection During Pregnancy. JAMA Netw Open. 23 March 2023;6(3):e234415. doi:10.1001/jamanetworkopen.2023.4415 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2802745

Key Points
Question Is in utero exposure to maternal SARS-CoV-2 infection associated with greater rates of neurodevelopmental disorder diagnoses in male or female offspring, compared with controls with no such exposure?

Findings This cohort study of 18 355 infants delivered after February 2020 found that male but not female offspring born to mothers with a positive SARS-CoV-2 polymerase chain reaction test result during pregnancy were more likely to receive a neurodevelopmental diagnosis in the first 12 months after delivery, even after accounting for preterm delivery.

Meaning These findings suggest that male offspring exposed to SARS-CoV-2 in utero may be at increased risk for neurodevelopmental disorders.

Abstract
Importance Prior studies using large registries have suggested a modest increase in risk for neurodevelopmental diagnoses among children of mothers with immune activation during pregnancy, and such risk may be sex-specific.

Objective To determine whether in utero exposure to SARS-CoV-2 is associated with sex-specific risk for neurodevelopmental disorders up to 18 months after birth, compared with unexposed offspring born during or prior to the COVID-19 pandemic period.

Design, Setting, and Participants This retrospective cohort study included the live offspring of all mothers who delivered between January 1 and December 31, 2018 (born and followed up before the COVID-19 pandemic), between March 1 and December 31, 2019 (born before and followed up during the COVID-19 pandemic), and between March 1, 2020, and May 31, 2021 (born and followed up during the COVID-19 pandemic). Offspring were born at any of 8 hospitals across 2 health systems in Massachusetts.

Exposures Polymerase chain reaction evidence of maternal SARS-CoV-2 infection during pregnancy.

Main Outcomes and Measures Electronic health record documentation of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnostic codes corresponding to neurodevelopmental disorders.

Results The COVID-19 pandemic cohort included 18 355 live births (9399 boys 51.2%), including 883 (4.8%) with maternal SARS-CoV-2 positivity during pregnancy. The cohort included 1809 Asian individuals (9.9%), 1635 Black individuals (8.9%), 12 718 White individuals (69.3%), and 1714 individuals (9.3%) who were of other race (American Indian or Alaska Native, Native Hawaiian or other Pacific Islander, more than 1 race); 2617 individuals (14.3%) were of Hispanic ethnicity. Mean maternal age was 33.0 (IQR, 30.0-36.0) years. In adjusted regression models accounting for race, ethnicity, insurance status, hospital type (academic center vs community), maternal age, and preterm status, maternal SARS-CoV-2 positivity was associated with a statistically significant elevation in risk for neurodevelopmental diagnoses at 12 months among male offspring (adjusted OR, 1.94 ...; P = .01) but not female offspring (adjusted OR, 0.89 ...; P = .77). Similar effects were identified using matched analyses in lieu of regression. At 18 months, more modest effects were observed in male offspring (adjusted OR, 1.42 ...; P = .10).

Conclusions and Relevance In this cohort study of offspring with SARS-CoV-2 exposure in utero, such exposure was associated with greater magnitude of risk for neurodevelopmental diagnoses among male offspring at 12 months following birth. As with prior studies of maternal infection, substantially larger cohorts and longer follow-up will be required to reliably estimate or refute risk.

New diabetes post-acute Covid (PASC, Long Covid), an inconvenient truth
A new study adds to 11 others for increased risk of Type 2 diabetes
Eric Topol | Apr 18, 2023

...Back in 2020, when the first signals that diabetes (particularly Type 2) was showing up more than a month out from Covid, the hope was that it was spurious. But then study after study have been confirming this sequelae. Today a new study* from the province of British Columbia in Canada, a comprehensive population assessment, is the 12th report of a heightened risk of Type 2 diabetes after Covid. This cohort was younger than most (mean age 32 years) and the increased risk of 17% was less than most of the previous publications...The increased risk compared with controls ranges widely from 17% to 235% with only 1 of these {12} studies not showing a significant increase in a subgroup (among women in a Veterans Affairs report)...people can develop diabetes after Covid without the typical symptoms of Long Covid... {See table of studies}

https://erictopol.substack.com/p/new-diabetes-post-acute-covid-pasc
------------------------------------------------------------------------

* Zaeema Naveed etal. 2023. Association of COVID-19 Infection With Incident Diabetes (Original Investigation). JAMA Netw Open. 18 April 2023;6(4):e238866. doi:10.1001/jamanetworkopen.2023.8866 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2803938

Pamela B. Davi and Rong Xu 2023. COVID-19 and Incident Diabetes—Recovery Is Not So Sweet After All (Invited Commentary). JAMA Netw Open. 2023;6(4):e238872. doi:10.1001/jamanetworkopen.2023.8872 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2803946

"the oldest patients {26-64y} were found to maintain their cognitive functions relatively preserved, with only a mild impairment in attention and speed processing, while the youngest showed the most marked and heterogeneous cognitive impairment"

Elena Herrera et al. 2023. Cognitive impairment in young adults with post COVID-19 syndrome. Scientific Reports volume 13, Article number: 6378 (19 April 2023) https://www.nature.com/articles/s41598-023-32939-0

Abstract
In this study, we aimed to examine different cognitive domains in a large sample of patients with post COVID-19 syndrome. Two hundred and fourteen patients, 85.04% women, ranged 26 to 64 years (mean = 47.48 years) took part in this investigation. Patients’ processing speed, attention, executive functions and various language modalities were examined online using a comprehensive task protocol designed for this research. Alteration in some of the tasks was observed in 85% of the participants, being the attention and executive functions tests the ones that show the highest percentage of patients with severe impairment. Positive correlations were observed between the age of the participants in almost all the tasks assessed, implying better performance and milder impairment with increasing age. In the comparisons of patients according to age, the oldest patients were found to maintain their cognitive functions relatively preserved, with only a mild impairment in attention and speed processing, while the youngest showed the most marked and heterogeneous cognitive impairment. These results confirm the subjective complaints in patients with post COVID-19 syndrome and, thanks to the large sample size, allow us to observe the effect of patient age on performance, an effect never reported before in patients with these characteristics.

Shingles.

Yi-Chen Chen and Chung-Han Ho et al. 2023. Long-term risk of herpes zoster following COVID-19: A retrospective cohort study of 2 442 686 patients. J of Medical Virology. First published: 18 April 2023. https://doi.org/10.1002/jmv.28745 https://onlinelibrary.wiley.com/doi/10.1002/jmv.28745

Abstract
"...During the 1-year follow-up period, patients with COVID-19 had a higher risk of HZ (Herpes zoster) compared with those without COVID-19 (HR: 1.59...). In addition, compared with the control group patients, those with COVID-19 had a higher risk of HZ ophthalmicus (HR: 1.31...), disseminated zoster (HR: 2.80...), zoster with other complications (HR: 1.46...), and zoster without complications (HR: 1.66...)... regardless of vaccine status, age, or sex...importance of carefully monitoring HZ in this population and suggests the potential benefit of the HZ vaccine for patients with COVID-19..."

Dr. Deepti Gurdasani @dgurdasani1 | 9:20 PM · Apr 23, 2023:
Clinical epidemiology, machine learning, NLP, global health. {Australia, formerly UK}

Important study showing significantly poorer IgG* response in both saliva (18% post-infection) and plasma with omicron infection (70%) in children compared with previous variants (68% - saliva, 100% in a small plasma sample). By contrast, all vaxxed children had IgG Abs in saliva.

Fig 1. Saliva IgG Levels in Children and Adolescents Following SARS-CoV-2 Infection
https://twitter.com/dgurdasani1/status/1650308808063987717/photo/2

* Immunoglobulin G (IgG) – About 70-80% of the immunoglobulins in the blood are IgG. Specific IgG antibodies are produced during an initial infection or other antigen exposure, rising a few weeks after it begins, then decreasing and stabilizing. The body retains a catalog of IgG antibodies that can be rapidly reproduced whenever exposed to the same antigen. IgG antibodies form the basis of long-term protection against microorganisms. In those with a normal immune system, sufficient IgG is produced to prevent re-infection. Vaccinations use this process to prevent initial infections and add to the catalog of IgG antibodies, by exposing a person to a weakened, live microorganism or to an antigen that stimulates recognition of the microorganism. IgG is the only immunoglobulin that can pass through the placenta. The mother’s IgG antibodies provide protection to the fetus during pregnancy and to the baby during its first few months of life. There are four subclasses of IgG: IgG1, IgG2, IgG3, and IgG4. https://www.testing.com/tests/immunoglobulins-iga-igg-igm/
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Constanze Heinzel et al. 2023. Saliva and Plasma Antibody Levels in Children and Adolescents After Primary Infection With Omicron Variants of SARS-CoV-2 Infection in Germany (Research Letter). JAMA Pediatr. Published online April 17, 2023. doi:10.1001/jamapediatrics.2023.0631 https://jamanetwork.com/journals/jamapediatrics/fullarticle/2804012

ABSTRACT
...Results
Saliva was collected from youth aged 1 to 18 years in spring 2021 (n = 1474) and spring 2022 (n = 1194) (groups not exclusive). Of these, 54 participants were infected with SARS-CoV-2 between April 2020 and December 2021 (defined as pre-Omicron infection), and 173 were infected from January 2022 to May 2022 (defined as Omicron infection). Either no symptoms or mild coldlike symptoms were reported, and none of the participants were hospitalized for COVID-19. While 37 of 54 youth with pre-Omicron infection had RBD-WT {receptor binding domain of the index/Wuhan type} reactive IgG in their saliva, considerably fewer (32 of 173) were IgG positive after an Omicron infection (Figure 1). This proportion did not increase when assessing IgG reactivity toward RBD-BA.1 (14 of 64) or RBD-BA.2 (9 of 64). {BA.1 and BA.2 are Omicron variants.} All participants who experienced 2 infections were positive for salivary IgG (reactive to RBD-WT = 11 of 13; BA.1 = 12 of 13; BA.2 = 12 of 13) and at levels higher than after a single Omicron infection. Almost all vaccinated participants (324 of 325) were positive for anti-RBD-WT IgG and had the highest IgG levels. Thirty-five of 45 participants with pre-Omicron infection had IgG reactive to Tri-WT in saliva, while only 14 and 16 of 51 with Omicron infection had IgG against Tri-WT and Tri-BA.1, respectively. Again, individuals who were twice infected had salivary IgG reactive to spike trimer** at relatively high levels.

For a subgroup of participants, plasma was sampled in addition to saliva. All participants with pre-Omicron infection had IgG reactive to RBD-WT and to Tri-BA.1 at high levels. For the Omicron-infected cohort, IgG reactive to RBD-WT, to RBD-BA.1, and to RBD-BA.2 and to the spike protein complex (Tri-BA.1) reflected the salivary IgG levels: only a fraction were IgG positive and IgG levels were low (Figure 2). Antibody levels reactive to NCP-BA.1 {nucleocapsid-protein of an omicron variant} showed a similar pattern and consolidated spike protein–based findings (Figures 1 and 2).

Discussion
SARS-CoV-2 Omicron reinfections within short periods are increasingly reported...Our data suggest that this might be explained by a weak humoral immune response to Omicron. In contrast to pre-Omicron variants, a primary Omicron infection elicited only a poor IgG antibody response, possibly resulting in insufficient infection prevention by salivary IgG. The observed neutralization escape of recurrent Omicron variants may be due to the absence of antibodies rather than reduced binding affinity. As a result, first-time SARS-CoV-2 infections with the Omicron variant may remain also largely undetected by seroprevalence studies. Further work on cellular immune responses and viral loads is needed to draw conclusions on the immunogenicity of Omicron and to test whether the results of this study are generalizable a larger population, including adults.

Fig 1. Saliva IgG Levels in Children and Adolescents Following SARS-CoV-2 Infection
https://twitter.com/dgurdasani1/status/1650308808063987717/photo/2

** The trimeric spike (S) protein of SARS-CoV-2 is the primary focus of most vaccine design and development efforts. nature.com

Charge for COVID home tests commence 11 May in US. Few more days to pick up free tests?

These benefits will disappear when Biden ends the Covid national and public health emergencies in May (11)
Tami Luhby Phil Mattingly Jeremy Diamond | January 31, 2023

...Most Americans covered by Medicare, Medicaid and private insurance plans have been able to obtain Covid-19 tests and vaccines at no cost during the pandemic. Those covered by Medicare and private insurance have been able to get up to eight at-home tests per month from retailers at no charge. Medicaid also picks up the cost of at-home tests, though coverage can vary by state...

https://www.cnn.com/2023/01/30/politics/may-11-end-of-covid-and-public-health-em...
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FIRST ON CNN: CDC set to stop tracking community levels for Covid-19
Brenda Goodman | April 28, 2023

As the nation’s public health emergency expires on May 11, the United States Centers for Disease Control and Prevention will stop reporting its color-coded Covid-19 Community Levels as a way to track the spread of the infection.

Instead, the CDC will keep tabs on Covid-19 largely by tracking hospitalizations in some areas...

This is much the same way the agency tracks other respiratory infections, such as the flu.

Hospitalizations are a lagging indicator: it generally takes a person a week to 10 days to be hospitalized with a Covid-19 infection. So the switch may mean that the nation is losing its capacity for the earliest warning of an uptick in spread.

However, wastewater testing in communities and for air travelers will continue and is expected to close some of those early warning gaps...

https://www.cnn.com/2023/04/28/health/cdc-covid-community-levels

Hopefully new (nasal) vaccines will break pattern of waning immunity and emergence of new variants... In mean time, previous-infection and recent vaxx should stave off severe, critical or fatal COVID--unless/until variant w new immune escape evolves. Doesn't say below, but masks, ventilation, filtration, (UV disinfection?) also helpful in preventing re-infection by new variants.

Vipin M. Vashishtha @vipintukur | 12:31 AM · Apr 30, 2023:
Pediatrician, ‘rational’ vaccine thinker, Editor Covid Vaccines, TB on Vaccines & many others, Past-Convener IAP COI, Member-WHO-VSN (http://vaccinesafetynet.org)
https://threadreaderapp.com/thread/1652531150148231168.html
With comments: https://twitter.com/vipintukur/status/1652531150148231168

How long population immunity induced by natural infection, primary-series vaccination, and booster vaccination against SARS-CoV-2 lasts?
A new study from Qatar offers some clues. 1/ ...

Takeaways:
1-Both previous-infection and vaccine population immunities vary rapidly at a national level creating fertile grounds for repeated waves of infection to occur even within months of each other. 9/
2-High levels of population immunity may not be sustained for more than a year or so.
3-So, preventing infection/reinfection, transmission, or future waves of infection cannot sustainably be done with current vaccines nor by the entire population being infected. 10/
4-Timely administration of boosters for those vulnerable to severe COVID-19 may remain essential for years to come.
5-Repeated waves of infection may also facilitate further evolution of the virus and continual immune evasion. 11/
6-Emergence of a new variant that is substantially different from circulating variants can suddenly and immensely reduce population immunity leading to large epidemic wave. 12/
7-However, the durability of population immunity against severe COVID-19 will likely curtail the severity of future waves. 13/13
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Suelen H. Qassim et al. 2023. Population immunity of natural infection, primary-series vaccination, and booster vaccination in Qatar during the COVID-19 pandemic: An observational study. MedRxiv 29 April 2023. doi: https://doi.org/10.1101/2023.04.28.23289254 https://www.medrxiv.org/content/10.1101/2023.04.28.23289254v1

This article is a preprint and has not been certified by peer review

Abstract
... Findings:
Previous-infection effectiveness against reinfection was strong before emergence of Omicron, but declined with time after a wave and rebounded after a new wave. Effectiveness dropped immediately after Omicron emergence from 88.3% ... in November 2021 to 51.0% ... in December 2021.

Primary-series effectiveness against infection was 84.0% ... in April 2021, soon after introduction of vaccination, before waning gradually to 52.7% ... by November of 2021. Effectiveness declined linearly by ~1 percentage point every 5 days. After Omicron emergence, effectiveness dropped suddenly from 52.7% ... in November 2021 to negligible levels in December 2021.

Booster effectiveness dropped immediately after Omicron emergence from 83.0% ... in November 2021 to 32.9% ... in December 2021, and continued to decline thereafter.

Effectiveness of previous infection and vaccination against severe, critical, or fatal COVID-19 were generally more than 80% throughout the study duration.

Interpretation:
High population immunity may not be sustained beyond a year. This creates fertile grounds for repeated waves of infection to occur, but these waves may increasingly exhibit a benign pattern of infection.

The Biden-⁠Harris Administration Will End COVID-⁠19 Vaccination Requirements for Federal Employees, Contractors, International Travelers, Head Start Educators, and CMS-Certified Facilities
White House | 1 May 2023

...Today, we are announcing that the Administration will end the COVID-19 vaccine requirements for Federal employees, Federal contractors, and international air travelers at the end of the day on May 11, the same day that the COVID-19 public health emergency ends. Additionally, HHS and DHS announced today that they will start the process to end their vaccination requirements for Head Start educators, CMS-certified healthcare facilities, and certain noncitizens at the land border. In the coming days, further details related to ending these requirements will be provided...

https://www.whitehouse.gov/briefing-room/statements-releases/2023/05/01/the-bide...

Martin Achleitner et al. 2023. Clinical improvement of Long-COVID is associated with reduction in autoantibodies, lipids, and inflammation following therapeutic apheresis (Immediate Communication). Molecular Psychiatry (2 May 2023) https://www.nature.com/articles/s41380-023-02084-1

Open Access

Abstract
In the aftermath of the COVID-19 pandemic, we are witnessing an unprecedented wave of post-infectious complications. Most prominently, millions of patients with Long-Covid complain about chronic fatigue and severe post-exertional malaise. Therapeutic apheresis has been suggested as an efficient treatment option for alleviating and mitigating symptoms in this desperate group of patients. However, little is known about the mechanisms and biomarkers correlating with treatment outcomes. Here, we have analyzed in different cohorts of Long-Covid patients specific biomarkers before and after therapeutic apheresis. In patients that reported a significant improvement following two cycles of therapeutic apheresis, there was a significant reduction in neurotransmitter autoantibodies, lipids, and inflammatory markers. Furthermore, we observed a 70% reduction in fibrinogen, and following apheresis, erythrocyte rouleaux formation and fibrin fibers largely disappeared as demonstrated by dark field microscopy. This is the first study demonstrating a pattern of specific biomarkers with clinical symptoms in this patient group. It may therefore form the basis for a more objective monitoring and a clinical score for the treatment of Long-Covid and other postinfectious syndromes.

Method
...A cohort of 27 patients with Long-Covid was treated with a filtration-based (TKM58) therapeutic apheresis approach, specifically INUSpheresis, which is known to remove autoantibodies, inflammatory cytokines, oxidated LDLs, environmental toxins, and large molecules, contributing to plasma viscosity 5. The patients were treated twice at an interval of 3 weeks. Each treatment lasted an average of 114 min and the patients received 8000E Heparin per treatment.

Discussion
...Discussion
Extracorporeal apheresis has the potential to improve symptoms of Long-Covid. Consistent with the clinical experience of several centers that have administered this treatment in a cohort of more than 1000 patients, 70% of patients with ME/CFS, including Long-Covid patients, reported a significant improvement in their symptoms... In the current study, we analyzed those biomarkers that play a role in the pathogenesis of postinfectious syndromes, such as Long-Covid, in 27 patients who showed clinical improvement after extracorporeal therapeutic apheresis and found that the biomarkers were significantly reduced after the treatment.

...In conclusion, this study clearly shows that extracorporeal apheresis is a powerful technology to reduce biomarkers that have been implicated in the pathogenesis of post-infectious syndromes such as Long-Covid. This, however, describes only an association and not causality and a clear correlation with symptoms and improvement of patients. Therefore, an additional limitation of our and similar studies is the current lack of hard endpoints for clearly defining and measuring improvements in Long-Covid symptoms objectively. Nevertheless, the study provides some guidance for monitoring treatment success and for establishing a larger patient cohort with a score of several of these parameters that will correlate with the immediate and long-term outcomes of the procedure. We believe that in the acute situation of such a mass number of desperate individuals suffering from a multifaceted disorder such as Long-Covid entirely relying on the most stringent criteria of evidence-based medicine did not and will not fully meet the needs of these patients.

This therapeutic option has to be presented honestly and transparently to patients seeking help and improvement of their current situation. It needs to be acknowledged that this treatment will not be successful in every patient and that we do not fully understand the exact mechanisms of treatment success or failure at this point. There has to be room for practice-oriented medicine that allows providing this treatment to those patients in need while the performance of controlled randomized evidence-based trials is needed. Private centers engaged in this type of treatment have to be involved in the monitoring of their patients. In such a complex disorder with a combination of diverse pathological mechanisms, individualized trials with different treatment protocols will be necessary. Extracorporeal therapeutic apheresis has been used for many decades and is an extremely safe method but nevertheless an invasive procedure and patients have to be informed about rare complications. Modern artificial intelligence-based technologies involving machine learning will be ideally suited to design and define individual treatment protocols with specific markers for the different patient groups of post-infectious syndromes in the future...

Esther Wei-Yun Landhuis 2023. How Primary Care Physicians Can Recognize and Treat Long COVID. JAMA. Published online May 3, 2023. doi:10.1001/jama.2023.6604 https://jamanetwork.com/journals/jama/fullarticle/2804697

... {Bateman Horne Center*}’s videos and ... guidance for ME/CFS-related postexertional malaise...drink electrolyte fluids...wear... compression socks...pace activity...exercise protocol developed for postural orthostatic tachycardia syndrome (POTS)...a graded program of horizontal exercise.

...Last August, the US Department of Health and Human Services launched a research action plan for long COVID that includes the National Institutes of Health–funded Researching COVID to Enhance Recovery, or RECOVER, Initiative. Some have criticized RECOVER as inadequate and slow—to the extent that its principal investigators recently published a Call to Action urging Congress to include $37.5 million in fiscal year 2024 to speed research and disseminate learnings to other physicians.

The first RECOVER clinical trials are expected to launch in the coming months, a spokesperson from the National Heart, Lung, and Blood Institute told JAMA in an email, and will evaluate multiple interventions focused on 5 symptom types: viral persistence, autonomic dysfunction, sleep disturbances, cognitive dysfunction, and exercise intolerance or fatigue. Details of the interventions will appear on ClinicalTrials.gov once finalized...

...guidance on managing long COVID in patients is available from the CDC, the VA, and the American Academy of Physical Medicine and Rehabilitation.**

Experts interviewed for this story offered some basic guidance for primary care physicians:
Believe the patient.
Go beyond symptoms.
Address fatigue.
Look to familiar conditions... long COVID can share symptoms with ME/CFS, fibromyalgia, posttreatment Lyme disease syndrome, dysautonomia, and mast cell activation syndrome. Approaches to managing these conditions can help some patients with long COVID. For example, POTS can be alleviated with fluids, compression garments, and graded horizontal exercise...

* https://batemanhornecenter.org/education/long-covid/

** https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/post-covid-condition...
https://www.publichealth.va.gov/n-coronavirus/docs/Whole-Health-System-Approach-...
https://www.aapmr.org/members-publications/covid-19/pasc-guidance

Improving Ventilation In Buildings
CDC | Updated May 11, 2023

To improve ventilation in your building, keep your system operating as designed. Aim for at least 5 air changes each hour and upgrade to MERV-13 filters....

https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/Improving-Ventila...
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Flying Lady Doctor Says | تقول الطبيبة | 🇮🇶 @LadyDoctorSays | 4:29 PM · May 12, 2023
Emergency MD

CDC now recommending adequate ventilation - changing all the air in an occupied room every 12 minutes - and quietly reaffirms that covid is harmful to children so masks at school should be considered.

For everyone asking "why now?"

Basically CDC couldn't "recommend" this during the emergency because then the government would be obligated to pay for part or all of it. Employers who failed to achieve this standard could also be held liable for workplace injury caused by covid.

New research sheds light on the causes of fatigue after COVID 19
Unlocking the secrets of long COVID
Newcastle University | 11-May-2023

...individuals suffering from post-Covid exhaustion had three crucial areas of their nervous system functioning insufficiently. Tiredness is a prevalent long Covid symptom.

This development may result in improved treatment and diagnostic methods for the condition, and the group is already making headway in their research...commenced the recruitment of participants to assess the efficacy of a TENS machine, which is frequently employed for pain management during childbirth, in mitigating exhaustion in individuals with long Covid...

https://www.newswise.com/coronavirus/covid-19-fatigue-causes-revealed-in-new-res...
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Anne M E Baker et al. 2023. Neural dysregulation in post-COVID fatigue. Brain Communications, Volume 5, Issue 3, 12 April 2023, fcad122, https://doi.org/10.1093/braincomms/fcad122 https://academic.oup.com/braincomms/article/5/3/fcad122/7115845

Abstract

Following infection with SARS-CoV-2, a substantial minority of people develop lingering after-effects known as ‘long COVID’. Fatigue is a common complaint with a substantial impact on daily life, but the neural mechanisms behind post-COVID fatigue remain unclear. We recruited 37 volunteers with self-reported fatigue after a mild COVID infection and carried out a battery of behavioural and neurophysiological tests assessing the central, peripheral and autonomic nervous systems. In comparison with age- and sex-matched volunteers without fatigue (n = 52), we show underactivity in specific cortical circuits, dysregulation of autonomic function and myopathic change in skeletal muscle. Cluster analysis revealed no subgroupings, suggesting post-COVID fatigue is a single entity with individual variation, rather than a small number of distinct syndromes. Based on our analysis, we were also able to exclude dysregulation in sensory feedback circuits and descending neuromodulatory control. These abnormalities on objective tests may aid in the development of novel approaches for disease monitoring.

Long COVID: New research, common symptoms, long-term effects and treatments with Akiko Iwasaki, PhD {Yale}
Todd Unger, AMA | May 22, 2023 (16:03 audio + transcript)

... people who were given Paxlovid within the first five days of symptom onset during the acute phase of the COVID did reduce the risk for developing long COVID about 26% over a six-month period. Whether Paxlovid can treat an existing long COVID is currently unclear. We've actually started a clinical trial with Paxlovid to see if that can relieve symptoms in an already existing long COVID patients.

...We are still investigating for possible root causes of long COVID, including persistent virus infection as well as autoimmunity and reactivation of latent viruses, like the Epstein-Barr virus, as well as chronic changes that happen in tissues due to inflammation.

...there are common symptoms that are reported, such as extreme fatigue, post-exertional malaise, cognitive dysfunction, tachycardia, loss of smell and taste. ...It is also now understood that new onset conditions can happen as a result of COVID infection, such as myalgic encephalomyelitis, dysautonomia, small fiber neuropathy, diabetes, heart conditions, stroke and many others. So these are also potential sequela of acute COVID infection.

...The first {finding} is that people with long COVID had reduced circulating levels of cortisol. The second is that we detected recent reactivation of Epstein-Barr virus in people who have long COVID compared to those who recover. EBV may or may not be directly responsible for the symptoms, but this is a feature we're detecting. Third, we found that the immune cells are differentially activated. We see more activated B cells and T cells, and T cells in particular, that secrete type 2 cytokines that are elevated in the people with long COVID.

And, finally, we find that antibody levels to the SARS-CoV-2 viral antigens are elevated in people with long COVID. This may indicate a persistent antigen for which these people are developing more and more antibodies against.

...Yale LISTEN study {Listen to Immune, Symptom and Treatment Experiences Now} ... First, we're collecting information about their symptoms and medical records, history from participants. And then we are also inviting some of these participants to provide blood and saliva for immune phenotyping, just as what we're doing with the Mount Sinai cohort. We are applying this deep immune phenotyping to both groups of patients {Long COVID & vaccine adverse events} in order to better understand the underlying disease pathogenesis. So far, we are finding some similarities between long COVID and post-vaccine adverse events. But we've just begun analysis. ...

LISTEN study is also carrying out the Paxlovid trial. This Paxlovid is an antiviral agent that can hopefully remove the persistent virus reservoir if there is such a reservoir in people with COVID. So we are doing this phase II trial, which is decentralized and it's a one-to-one, randomized, double blind, placebo-controlled trial...

...we're hoping to learn who responds positively to Paxlovid and what are their biomarkers before the treatment so that we can potentially enroll people with such biomarkers for Paxlovid treatment who might benefit more than, say, those without the biomarkers...

...the long COVID is pandemic after the pandemic. I mean, the pandemic is still not over. We still have COVID circulating around and there are people still getting long COVID from infection and potentially reinfection.

We are nowhere near equipped to deal with this. We urgently need several things. First, ... accurate diagnosis and treatment...Second, long COVID patients need financial assistance. ...We also need social support... we also need more public awareness. Many people are still not aware of long COVID. And there is a need for physicians as well as patients so that they can get the best treatment and best therapy possible and to support them through this process...

https://www.ama-assn.org/delivering-care/public-health/long-covid-new-research-c...

https://fortune.com/well/2023/05/23/covid-deaths-one-person-every-four-minutes-v...
COVID still kills 1 person every 4 minutes despite the global emergency being officially over

As long COVID turns three, Americans play disability roulette
As an ICU physician, I’ve had a front-row seat to the heartbreak of the past three years.
Wes Ely* | Updated May 26, 2023

While society yawns, impatient to move on from the COVID-19 pandemic, Americans still play disability roulette. About 1 in 10 of the 110,000 people who catch COVID this week in the United States, many for a second or third time, will be left lastingly ill. Even some vaccinated people; even some young, previously healthy people, after only mild cases.

No longer a mass death event, COVID-19 is an ongoing mass disability event. Every seven days, 25,000 more people join the 10 million in our country suffering memory loss, heart problems, dizziness, extreme fatigue, and more owing to the virus. Globally an estimated 65 million people have this new chronic health condition. One recent long COVID study showed organ damage in more than half of a group of outpatients one year on....

https://www.bostonglobe.com/2023/05/26/opinion/long-covid-turns-three-americans-...
(Photo, highlighted article: https://twitter.com/WesElyMD/status/1662061662935957505/photo/1 )

*Dr. Wes Ely is a professor of medicine and critical care at Vanderbilt University and the Nashville VA Medical Center. He is codirector of the Critical Illness, Brain Dysfunction, and Survivorship Center and author of “Every Deep-Drawn Breath.” He can be found on Twitter and TikTok @WesElyMD.

"Alzheimer's disease can be initiated or deteriorated in COVID-19 patients due to reduced hippocampal neurogenesis"

Ali Nouraeinejad 2023. The functional and structural changes in the hippocampus of COVID-19 patients (Review). Acta Neurologica Belgica (25 May 2023) https://link.springer.com/article/10.1007/s13760-023-02291-1#Sec12

Abstract
Since the hippocampus is predominantly susceptible to injuries caused by COVID-19, there are increasing data indicating the likelihood of post-infection memory loss and quickening neurodegenerative disorders, such as Alzheimer’s disease. This is due to the fact that the hippocampus has imperative functions in spatial and episodic memory as well as learning. COVID-19 activates microglia in the hippocampus and induces a CNS cytokine storm, leading to loss of hippocampal neurogenesis. The functional and structural changes in the hippocampus of COVID-19 patients can explain neuronal degeneration and reduced neurogenesis in the human hippocampus. This will open a window to explain memory and cognitive dysfunctions in “long COVID” through the resultant loss of hippocampal neurogenesis.

The hippocampus
COVID-19 activates microglia in the hippocampus and induces a CNS cytokine storm, leading to loss of hippocampal neurogenesis
COVID-19 results in neuronal degeneration and reduced neurogenesis in the human hippocampus
Changes in gray matter volumes in neuropsychiatric long COVID syndrome
Longitudinal neurocognitive profile of “long COVID”
Neurogenesis is disturbed in human hippocampal progenitor cells when they are exposed to serum samples from hospitalized COVID-19 patients with neurological complaints
Hippocampal-prefrontal connectivity prior to the COVID-19 pandemic may be used to predict stress reactivity
The explanation of memory and cognitive dysfunctions in “long COVID” through the loss of hippocampal neurogenesis
Alzheimer's disease can be initiated or deteriorated in COVID-19 patients due to reduced hippocampal neurogenesis
The high rate of “long COVID” symptoms, especially cognitive impairment, can justify the need for therapeutic interventions in affected individuals

Conclusion
The hippocampus, which is important in memory, spatial working memory through transient high gamma synchrony, executive functions, path integration, and spatial processing, is recognized as one of the earliest and most distressed configurations of the brain throughout acute or chronic inflammatory circumstances owing to its specific susceptibility to neuroinflammatory incidents. This is also the case in COVID-19, which activates microglia in the hippocampus and induces a CNS cytokine storm, leading to the loss of hippocampal neurogenesis. The details of functional and structural changes of the hippocampus in COVID-19 patients, which were explored in this review, explain memory and cognitive dysfunctions in “long COVID” through the loss of hippocampal neurogenesis. The initial results of a longitudinal investigation on the assessment of episodic verbal memory have also practically illustrated weaker performance in COVID-19 patients than in healthy controls. This clinical outcome additionally confirms the role of the hippocampus in cognitive function in COVID-19 patients.

A better perspective of the cellular features of COVID-19 brain injury could assist in interventions to ease long-term neuropsychiatric complaints. These therapeutic aids may include antagonists of cytokines or other pathway modulators. Alleviating the long-term post–COVID-19 complications of cognition, emotion, and behavior would help reduce the disease burden. The neuropathology of COVID-19 may provide a replica for decoding the neurodegenerative mechanisms related to neuroinflammation in other brain diseases and for developing new therapeutic methods.

Eric Feigl-Ding @DrEricDing | 11:53 AM · May 27, 2023:

📍Holy crap—51 elite cyclists have dropped out of the major @giroditalia 🚵‍♀️tournament so far, including **3 top race contenders**, amid an outbreak of #COVID19 and variety of illnesses. Now only 71% racers remaining. ➡️more cyclists have dropped out this tournament than even in 2020 amid Italy🇮🇹’s first COVID wave. Let that sink in. But hey, pAnDeMiC-iS-OvER??? #COVIDisNotOver.

https://cyclingnews.com/features/giro-ditalia-abandons-the-full-list-of-riders-w...
Image ( https://twitter.com/DrEricDing/status/1662487252621049857/photo/1 )
Image ( https://twitter.com/DrEricDing/status/1662487252621049857/photo/2 )
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Eric Feigl-Ding @DrEricDing | 4:20 PM · May 26, 2023:

Welp—Remember how @CDCgov claimed there was no “outbreak” at their CDC conference 3 weeks ago? ➡️Now we learn 181 cases of #COVID19 arose of 1800+ CDC staffers/guests…. So basically 1 in 10 folks at a single CDC conference caught COVID. Yet @CDCDirector Walensky dismantles reporting and they gaslight us it was nothing. #CovidIsNotOver

https://washingtonpost.com/health/2023/05/26/cdc-covid-outbreak/
Image ( https://twitter.com/DrEricDing/status/1662192084722360325/photo/1 )

Eric Feigl-Ding @DrEricDing | 3:26 AM · Jun 2, 2023:
...there are 4 different levels of “high”. NYC is in the top 2 levels of high wastewater #COVID so far already across most of its boroughs.
Map ( https://twitter.com/DrEricDing/status/1664534026483277825/photo/1 )

More than 70% of US household COVID spread started with a child, study suggests
Mary Van Beusekom | 2 June 2023

...A team led by Boston Children's Hospital researchers gave smartphone-connected thermometers to 848,591 households with 1,391,095 members, who took 23,153,925 temperature readings from October 2019 to October 2022. Fevers were a proxy for infection...

...The authors concluded that children had an important role in the spread of SARS-CoV-2 and that in-person school also resulted in substantial spread...

https://www.cidrap.umn.edu/covid-19/more-70-us-household-covid-spread-started-ch...
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Yi-Ju Tseng et al. 2023. Smart Thermometer–Based Participatory Surveillance to Discern the Role of Children in Household Viral Transmission During the COVID-19 Pandemic (Original Investigation). JAMA Netw Open. 1 June 2023;6(6):e2316190. doi:10.1001/jamanetworkopen.2023.16190 . https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2805468

Key Points
Question What role did children play in household viral transmission during the COVID-19 pandemic, when enveloped virus rates were low and relative proportions of COVID-19 were at a high?

Findings In a cohort study of 166 170 households with adults and children using smart thermometers, among 38 787 inferred household transmissions over 3 years, 70.4% had a pediatric index case. Rates dropped during school breaks.

Meaning These results suggest that children were important viral vectors in households during the pandemic, particularly when school was in session.

Abstract
Importance Children’s role in spreading virus during the COVID-19 pandemic is yet to be elucidated, and measuring household transmission traditionally requires contact tracing.

Objective To discern children’s role in household viral transmission during the pandemic when enveloped viruses were at historic lows and the predominance of viral illnesses were attributed to COVID-19.

Design, Setting, and Participants This cohort study of a voluntary US cohort tracked data from participatory surveillance using commercially available thermometers with a companion smartphone app from October 2019 to October 2022. Eligible participants were individuals with temperature measurements in households with multiple members between October 2019 and October 2022 who opted into data sharing.

Main Outcomes and Measures Proportion of household transmissions with a pediatric index case and changes in transmissions during school breaks were assessed using app and thermometer data.

Results A total of 862 577 individuals from 320 073 households with multiple participants (462 000 female (53.6%) and 463 368 adults (53.7%)) were included. The number of febrile episodes forecast new COVID-19 cases. Within-household transmission was inferred in 54 506 (15.4%) febrile episodes and increased from the fourth pandemic period, March to July 2021 (3263 of 32 294 (10.1%)) to the Omicron BA.1/BA.2 wave (16 516 of 94 316 (17.5%)...). Among 38 787 transmissions in 166 170 households with adults and children, a median (IQR (Interquartile range)) 70.4% ... had a pediatric index case; proportions fluctuated weekly from 36.9% to 84.6%. A pediatric index case was 0.6 to 0.8 times less frequent during typical school breaks. The winter break decrease was from 68.4% ... to 41.7% ... at the end of 2020 ... At the beginning of 2022, it dropped from 80.3% ... to 54.5%... During summer breaks, rates dropped from 81.4% ... to 62.5% ... by August 2021 ... and from 83.8%... to 62.8% ... by July 2022.... These patterns persisted over 2 school years.

Conclusions and Relevance In this cohort study using participatory surveillance to measure within-household transmission at a national scale, we discerned an important role for children in the spread of viral infection within households during the COVID-19 pandemic, heightened when schools were in session, supporting a role for school attendance in COVID-19 spread.

Daniele Focosi, MD PhD MSc @dfocosi | | 2:31 AM · Jun 3, 2023:
MD, specialist in Hematology, PhD in Virology, MSc in clinical trials in oncohematology, transfusion physician.

Very important paper by ⁦(Bart Rijnders @bjarijn--infectious diseases physician, living in Antwerp, working in Rotterdam, Professor of Medicine at Erasmus MC) ⁩ showing how Paxlovid + high-titer convalescent plasma can clear persistent COVID-19 in immunocompromised patients, including Evusheld failures ...
⁩
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Sammy Huygens et al. 2023. High-titer convalescent plasma plus nirmatrelvir/ritonavir treatment for non-resolving COVID-19 in six immunocompromised patients. Journal of Antimicrobial Chemotherapy, dkad144, 30 May 2023. https://doi.org/10.1093/jac/dkad144

Abstract
...Results
Five immunocompromised patients were treated with high-titer CP (convalescent plasma) and 5 days of nirmatrelvir/ritonavir. One patient received nirmatrelvir/ritonavir monotherapy. Median duration of SARS-CoV-2 PCR positivity was 70 (range 20–231) days before nirmatrelvir/ritonavir treatment. In four patients receiving combination therapy, no viral genome of SARS-CoV-2 was detected on day 7 and 14 after treatment while the patient receiving nirmatrelvir/ritonavir monotherapy, the day 7 Ct value* increased to 34 and viral genome was undetectable thereafter. Treatment was unsuccessful in one patient. In this patient, sequencing after nirmatrelvir/ritonavir treatment did not show protease gene mutations.

Conclusions
In immunocompromised patients with non-resolving COVID-19, the combination of nirmatrelvir/ritonavir and CP may be an effective treatment. Larger prospective studies are needed to confirm these preliminary results and should compare different treatment durations.

{* The total number of amplification cycles required to detect the virus' genetic material or viral RNA is defined as the 'CT' value or Cycle Threshold. https://www.homage.com.my/resources/covid-19-ct-value/}

...Results
...Four patients had an underlying B-cell malignancy, one patient a T-cell malignancy and one patient a common variable immune deficiency. All patients had received at least two vaccinations. Three patients had SARS-CoV-2 antibodies (646, 1660 and 5660 BAU/mL) around the time of nirmatrelvir/ritonavir initiation following previous unsuccessful treatment with CP or tixagevimab/cilgavimab, two were antibody negative and in one patient, SARS-CoV-2 antibodies were not measured before treatment. One patient was treated while hospitalized for worsening of respiratory symptoms and all other patients were treated as outpatients.

Table 1 and Figure 1 provide an overview on the treatment and follow-up for all patients...

On Covid, the past is being erased and the present ignored
Guardian Letters | 1 Jun 2023

‘Don’t mention the virus’ has become a mantra, says Joan Twelves, while Joe Sim and Steve Tombs say the government is silencing discussion about the disease. Plus one reader describes how her husband’s death was not recorded as caused by Covid...

https://www.theguardian.com/world/2023/jun/01/on-covid-the-past-is-being-erased-...

Daria A. Pawlak and Arash Sahraie 2023. Lost time: Perception of events timeline affected by the COVID pandemic (Research Article). PLOS May 31, 2023. https://doi.org/10.1371/journal.pone.0278250 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0278250

Abstract...As expected, the findings showed more errors for distant events than those in 2020, but surprisingly we found a large error for estimating the timing of events that occurred in 2021 matching in the extent to those 3 to 4 years earlier. The findings show that participants were less able to recall the timeline of very recent events coinciding with COVID lockdowns. This increased error in perception of event timeline correlated positively with reported levels of depression & anxiety as well as physical and mental demands during the pandemic, but negatively correlated with measures of resilience. Although measures of boredom showed significant correlations with reported depression & anxiety and physical/mental load, they did not correlate with errors in the perception of the event timeline for 2021. The findings are consistent with poor perception of event timeline reported previously in prison inmates. It is likely that an accurate perception of an event timeline relies on a collection of life events such as birthdays, holidays, travels, etc., anchoring our experiences in the time domain, which was largely absent during COVID restrictions.

...Discussion
...In conclusion, although the direct adverse effect on the health of a population by a pathogen can be well documented and the optics of disease such as reported hospital admissions can largely underpin the management decisions in a pandemic, the resultant interventions can also have dramatic hidden adverse effect on a variety of cognitive processes. Here we have demonstrated such influences on the perception of event timelines in individuals.

https://twitter.com/RajeevJayadevan/status/1665262885298216960/photo/1
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Rajeev Jayadevan @RajeevJayadevan | 4:36 AM · Jun 4, 2023:
Medical doctor/specialist 🇮🇳🇺🇸🇬🇧🇮🇪🇳🇱 Author, Co-Chairman National IMA COVID Task Force & Past President, Indian Medical Association, Cochin

It’s similar to the difference between driving along a boring 100 mile road with corn fields on either side, VS driving 100 miles along a scenic road, stopping in small towns. We remember the latter better...

>137 margd: attributes lost perception of timelines to interventions such as lockdowns, but study below also names the virus itself for memory and cognitive problems:

Dutch Survey Data Shows Significant Increase In Memory And Concentration Problems Among Adults Since Start Of Covid-19 Pandemic
Joshua Cohen | 4 June 2023

...Recently published data from the Netherlands suggests that among people ages 25 and up, memory and concentration problems have risen by 24% since the beginning of the Covid-19 pandemic. According to an ongoing large-scale research survey conducted by the Dutch National Institute for Public Health and the Environment (RIVM) and the Netherlands Institute for Health Care Research (NIVEL), there has been a 31% increase in primary care visits by adults ages 25 to 44 for “memory and concentration problems” in the past three years. Among the 45 to 74 year-old group, there was a 40% jump in visits to the doctor for these specific complaints. And, in the 75 and up age group, there was an 18% rise in physician visits.

...The possible causes of the increase in memory and concentration problems are unclear. A plausible explanation is that the isolation brought about by Covid-19 restrictions contributed to accelerated cognitive decline among people who were already starting to have problems with memory and concentration.

Experts posit, however, that long Covid is likely to blame for the majority of sufferers. Since 2020, numerous investigations have shown that memory and concentration problems are common post-Covid symptoms. Other infectious diseases, such as flu, can also cause these symptoms. But studies have demonstrated that long-term memory and concentration problems are much more common after being infected with Covid-19 than following a bout with influenza. Specifically, people struggling with the effects of long Covid can exhibit problems with attention, memory, and executive function...

https://www.forbes.com/sites/joshuacohen/2023/06/04/dutch-survey-data-shows-sign...

Harry Spoelstra @HarrySpoelstra | 2:41 AM · Jun 8, 2023:
Vascular Surgeon and Medical Director Therapeutisch Vasculair Centrum, Aalter Halle-Brussels

IMPORTANT:
❗New evidence that the #SARSCoV2 S-protein
➡️may have a direct pathogenic action on cardiac pericytes* with subsequent damaging of the heart’s microvasculature, through pericyte detachment, death, and decreased vascular coverage, thus disrupting the coronary microcirculation.
➡️Furthermore the S-protein shows signs that it modifies the transcriptional program of human cells to the virus’ advantage! #micemodel
➡️More study needed, but this is potentially very concerning.......again! #Heart

* Pericytes are multi-functional mural cells of the microcirculation that wrap around the endothelial cells that line the capillaries throughout the body. Pericytes are embedded in the basement membrane of blood capillaries, where they communicate with endothelial cells by means of both direct physical contact and paracrine signaling. (Wikipedia)
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Elisa Avolio et al. 2023. Murine studies and expressional analyses of human cardiac pericytes reveal novel trajectories of SARS-CoV-2 Spike protein-induced microvascular damage (Letter). (Nature) Signal Transduction and Targeted Therapy volume 8, Article number: 232 (2 June 2023). https://nature.com/articles/s41392-023-01489-2

...Findings summarized in Fig. 1q https://twitter.com/HarrySpoelstra/status/1666696879298445312/photo/1 provide novel evidence of the SARS-CoV-2 S-protein’s direct pathogenic action on cardiac pericytes and the heart’s microvasculature. It is plausible that the harmful effects observed in healthy mice three days after a single systemic injection of the S-protein might be intensified in the presence of cardiovascular risk factors and prolonged exposure. These possibilities merit further investigation. Moreover, we showed that the S-protein modifies the transcriptional program of human cells to the virus’ advantage. This new information could have significant implications for the treatment of COVID-19, for instance, using anti-S-protein engineering approaches to protect vascular cells.

COVID spike protein causes brain cells to fuse together, resulting in synchronous firing, possibly causing brain fog and facilitating spread of virus via fused axons. Current vaccines use spike protein S-2P (two consecutive prolines are added at positions 986 and 987) and so lack fusogenicity, but "critical to consider the fusogenic potential when designing any future vaccines in which viral fusogens are to be expressed in mammalian cells" (COVID, Herpes simplex? Epstein-Barr virus? Zika virus? Japanese encephalitis virus?) {Marg: My understanding is that current COVID vaxx use far fewer spike proteins, non-replicating, compared to those produced by the SARS-CoV-2 virus itself.}

Could fused neurons explain COVID-19’s ‘brain fog’?
Studies in dish suggest SARS-CoV-2 causes brain cells to stick together, but more research is needed to determine the significance
Claudia Lopez Lloreda | 7 Jun 2023

...The key appears to be angiotensin-converting enzyme 2 (ACE2), the protein expressed on the surface of mammalian cells that SARS-CoV-2 is known to target. The virus uses a surface protein called spike to bind to ACE2, triggering the virus to fuse to a cell and release its genetic material inside. Seemingly, the spike protein in infected cells may also make other ACE2 on a cell trigger fusion to a neighboring cell. When the team engineered neurons to express the spike protein, only cells that also expressed ACE2 were able to fuse with each other. The findings parallel previous work in lung cells: The ACE2 receptor seems to be critical in mediating their fusion during SARS-CoV-2 infection.

However, the neuronal syncytia seen in the lab dishes and organoids also had some peculiarities that made them stand out from those seen in lungs. When lung cells fused, only the main parts of the cell body connected to each other. Among neurons, in contrast, the fusion happened farther away from the cell body, at long, thin extensions known as dendrites and axons, which are critical for cell-cell communication.

The fusions seemed to disrupt this communication. Neurons typically fire independently, propagating signals throughout the brain. But 90% of the fused neurons fired at the same time, whereas the remaining 10% stayed silent. This massive amount of synchronous activity “is almost like a seizure,” (co-author Massimo Hilliard, a neuroscientist at the University of Queensland) says. Brain fog could result when this delicate communication is disrupted, he says. Hillard’s group has previously shown that inducing neurons to fuse in the nervous system of the worm Caenorhabditis elegans blunted their ability to sense odors...

https://www.science.org/content/article/could-fused-neurons-explain-covid-19-s-b...
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Ramón Martínez-Mármol et al. 2023. SARS-CoV-2 infection and viral fusogens cause neuronal and glial fusion that compromises neuronal activity. Science Advances, 7 Jun 2023, Vol 9, Issue 23. DOI: 10.1126/sciadv.adg2248 https://www.science.org/doi/10.1126/sciadv.adg2248

Abstract
Numerous viruses use specialized surface molecules called fusogens to enter host cells. Many of these viruses, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can infect the brain and are associated with severe neurological symptoms through poorly understood mechanisms. We show that SARS-CoV-2 infection induces fusion between neurons and between neurons and glia in mouse and human brain organoids. We reveal that this is caused by the viral fusogen, as it is fully mimicked by the expression of the SARS-CoV-2 spike (S) protein or the unrelated fusogen p15 from the baboon orthoreovirus. We demonstrate that neuronal fusion is a progressive event, leads to the formation of multicellular syncytia, and causes the spread of large molecules and organelles. Last, using Ca2+ imaging, we show that fusion severely compromises neuronal activity. These results provide mechanistic insights into how SARS-CoV-2 and other viruses affect the nervous system, alter its function, and cause neuropathology.

...DISCUSSION
Neuroinfectious diseases transmitted by viruses represent an emerging public health threat due to the increasing appearance of new zoonotic neurotropic viruses...

Fused neurons can result in compromised neuronal circuitry and altered animal behavior...

... Our results demonstrate the formation of neuronal bridges that can extend hundreds of micrometers, allowing the exchange of small proteins and large mitochondria between interconnected neurons. Given the diverse range of structures that can be transported through these viral fusogen-mediated cellular structures, it is tempting to speculate that infecting viruses and other toxic aggregates may also use these pathways to spread to neighboring cells. In the case of SARS-CoV-2, the potential of fusion-mediated spreading of infection would be determined by the delivery of viral fusogen to the cell surface, which we have shown to occur, and by the pattern of ACE2-expressing neurons...that are in contact with a single infected neuron, even at large distances from their respective cell somas {bulbous body of a neuron}. The neuropathological consequences of virus-induced neuronal fusion events could underlie the remarkable association between herpes simplex virus infection and Alzheimer’s disease..., HIV and Parkinson’s disease..., Epstein-Barr virus and multiple sclerosis..., and Zika virus or Japanese encephalitis virus with epileptic seizures.... An important consideration that emerges from our results is that fused neurons remain viable albeit with altered circuitry and function. This uncharacterized, difficult-to-detect event could explain some of the neurological consequences of viral infections of the nervous system.

Most of the current immunization approaches for COVID-19 are based on expressing the spike S protein in the host cells as an epitope to trigger the immune system response.... These nucleic acid-based vaccines deliver the antigen encoded as mRNA, such as in the Pfizer-BioNTech BNT162b2 and the Moderna mRNA-1273 vaccines..., or as adenovirus-enclosed DNA, such as in the Oxford-AstraZeneca ChAdOx1 nCoV-19/AZD1222 ... and Johnson & Johnson Ad26.COV2.S ... vaccines. The current versions of the Moderna, Pfizer-BioNTech, and Johnson & Johnson SARS-CoV-2 vaccines encode the full-length spike S protein with two mutations (spike S-2P) that stabilize the prefusion conformation and inactivate its fusogenicity ... We used this same mutant form of spike S-2P as a negative control, demonstrating the complete lack of fusogenicity when two consecutive prolines were added at positions 986 and 987. However, our findings demonstrate that it will be critical to consider the fusogenic potential when designing any future vaccines in which viral fusogens are to be expressed in mammalian cells...

"...early outpatient COVID-19 treatment with metformin decreased the subsequent risk of long COVID by 41·3% during 10-month follow-up. This finding is consistent with the 42·3% reduction in health-care utilisation for severe COVID-19 with metformin in the first 14 days of the trial..."

{margd: especially effective in patients under 45, unvaxxed, overweight, female, etc., although one commenter noted that study wasn't set up for robust analysis of sub-groups. "More study needed." Reportedly safe for heart failure, kidney, pregnant patients?}
---------------------------------------------------------

Carolyn T Bramante et al. 2023. Outpatient treatment of COVID-19 and incidence of post-COVID-19 condition over 10 months (COVID-OUT): a multicentre, randomised, quadruple-blind, parallel-group, phase 3 trial. The Lancet Infectious Diseases June 08, 2023 DOI:https://doi.org/10.1016/S1473-3099(23)00299-2 https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(23)00299-2/fullt...

Summary
...Findings
...The cumulative incidence of long COVID by day 300 was 6·3% (95% CI 4·2–8·2) in participants who received metformin and 10·4% (7·8–12·9) in those who received identical metformin placebo (hazard ratio (R) 0·59...). The metformin beneficial effect was consistent across prespecified subgroups. When metformin was started within 3 days of symptom onset, the HR was 0·37 ... There was no effect on cumulative incidence of long COVID with ivermectin (HR 0·99) or fluvoxamine (1·36) compared with placebo.

...Discussion
In this investigator-initiated, decentralised, multicentre, randomised, quadruple-blind, placebo-controlled, phase 3 trial of outpatient treatment for COVID-19, treatment with metformin during acute COVID-19 infection reduced the risk of long COVID by day 300 by 41·3% compared with placebo, with an estimated cumulative incidence of 6·3% in the metformin group and 10·6% in the placebo group. This finding is consistent with the results for the primary outcome of the trial, in which metformin reduced the risk of emergency department visits, hospitalisations, and death due to COVID-19 by day 14 of study drug by 42·3% compared with placebo (odds ratio (OR) 0·58...

Participants who received metformin were also less likely to be hospitalised by day 28 than those who received placebo (eight (1·3%) of 596 vs 19 (3·2%) of 601). Ivermectin and fluvoxamine did not reduce the risk of long COVID in this trial, and this finding was consistent with their lack of efficacy to reduce severe COVID-19 outcomes by day 14.6...

....Although the effect sizes for metformin to reduce the risk of severe COVID-19 and long COVID were similar, the number of cases of long COVID was higher than the number of emergency department visits or hospitalisations for acute COVID-19 in this trial. This difference supports the current understanding that long COVID also occurs in people who did not have severe COVID-19.23

The exact pathophysiology of long COVID is unknown but is likely to be multifactorial, including the inflammatory cascade during acute infection and persistent viral replication...

Larger effects for therapies started earlier in the course of infection support an antiviral mechanism...fewer than 4 days after symptom onset...

The point estimate for the vaccinated subgroup showed a weaker effect than in the unvaccinated subgroup and its 95% CI (Confidence Interval) crossed 1·00... Further study is needed to understand the efficacy in people who have received SARS-CoV-2 vaccination...

...Metformin has also been shown to be safe in adults with kidney disease and should not be withheld from people with glomerular filtration rates of greater than 30 mL/min per 1·73 m2 (and perhaps even lower)

Metformin treats diabetes largely by preventing hepatic gluconeogenesis, not by lowering blood glucose concentrations; therefore, the risk of hypoglycaemia is very low, including in people without diabetes. The safety of metformin has also been shown in children and in women who are lactating or pregnant.

Guidelines recommend that metformin should no longer be stopped upon hospital admission or for surgery....

...In conclusion, early outpatient COVID-19 treatment with metformin decreased the subsequent risk of long COVID by 41·3% during 10-month follow-up. This finding is consistent with the 42·3% reduction in health-care utilisation for severe COVID-19 with metformin in the first 14 days of the trial. Fluvoxamine and ivermectin did not decrease the risk of long COVID, which was also consistent with the findings for severe COVID-19 outcomes by day 14. As the COVID-19 pandemic continues to evolve, all therapeutics require further prospective, interventional trials to assess long COVID incidence, including among people who have received vaccination and booster vaccination, and people with previous SARS-CoV-2 infection. Long COVID is an important public health emergency that might have lasting health, mental health, and economic sequelae, particularly in socioeconomically marginalised groups, and metformin is safe and widely available at low cost.

Bernal and Whitehurst 2023. Incidence of Epstein-Barr virus reactivation is elevated in COVID-19 patients. Virus Research Volume 334, September 2023, 199157. https://doi.org/10.1016/j.virusres.2023.199157 https://www.sciencedirect.com/science/article/pii/S0168170223001193

Highlights

• COVID-19 patients have increased incidence of Epstein-Barr Virus reactivation.
• Detection of EBV DNA is greater among COVID-19 positive patients (27.1% vs 12.5%).
• No statistical difference in CRP (C-reactive protein, biomarker of inflammation) levels of COVID-19 positive vs. negative patients.
• No statistical difference in amount of EBV genomes in reactivated patient groups.

...Our samples were collected when the Omicron variant was the most dominant in NYC cases

...Meng et al (2022) found that patients experiencing EBV reactivation due to COVID showed increased survival outcomes when treated with the EBV inhibitor, ganciclovir

Eric Topol (Scripps mD scientist) @EricTopol | 1:12 PM · Jun 27, 2023:
A third of people are Blood Group A.
SARSCoV2 preferentially infects these cells "providing a direct link between ABO blood group expression and (Covid) infection"

@ASH_hematology
Graphs, Delta v Omicron ( https://twitter.com/EricTopol/status/1673741129047760897/photo/1 )

Shang-Chuen Wu et al. 2023. Blood Group A Enhances SARS-CoV-2 Infection (Brief Report).
Blood 27 June 2023. blood.2022018903. https://doi.org/10.1182/blood.2022018903 https://ashpublications.org/blood/article/doi/10.1182/blood.2022018903/496471/Bl...

The receptor binding domain (RBD) of SARS-CoV-2 bears sequence and overall ABO blood binding similarity with human galectins. (an ancient family of carbohydrate binding proteins)

SARS-CoV-2 preferentially infects blood group A cells, providing a direct link between blood group A expression and increased infection.

Eric Topol (Scripps cardiologist scientist) @EricTopol | 6:58 PM · Jun 26, 2023:
Persistence of #SARSCoV2 virus, or parts of it, in 11 studies of children for weeks to months after acute infection, independent of severity...

Highlighted text ( https://twitter.com/EricTopol/status/1673465697249431554/photo/1 )
Proposed followup childhood Covid, LC ( https://twitter.com/EricTopol/status/1673465697249431554/photo/2 )
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Danilo Buonsenso et al. 2023. Viral persistence in children infected with SARS-CoV-2: current evidence and future research strategies (Personal View). The Lancet Microbe. June 26, 2023. DOI:https://doi.org/10.1016 https://thelancet.com/journals/lanmic/article/PIIS2666-5247(23)00115-5/fulltext/...

Summary
In this Personal View, we discuss current knowledge on SARS-CoV-2 RNA or antigen persistence in children infected with SARS-CoV-2. Based on the evidence that the virus can persist in adults, we have done a literature review and analysed studies that looked for SARS-CoV-2 RNA or antigens in children undergoing autopsy, biopsy, or surgery for either death from COVID-19 or multisystem inflammatory syndrome, or assessments for long COVID-19 or other conditions. Our analysis suggests that in children, independent from disease severity, SARS-CoV-2 can spread systemically and persist for weeks to months. We discuss what is known about the biological effects of viral persistence for other viral infections and highlight new scenarios for clinical, pharmacological, and basic research exploration. Such an approach will improve the understanding and management of post-viral syndromes.

Illinois study: 14% of cats had COVID antibodies

Chi Chen et al. 2023. Spatial and temporal clustering of anti-SARS-CoV-2 antibodies in Illinois household cats, 2021- 2023. MedRxiv 27 June 2023. doi: https://doi.org/10.1101/2023.06.21.23291564 https://www.medrxiv.org/content/10.1101/2023.06.21.23291564v1

This article is a preprint and has not been certified by peer review

Abstract
In this study, we evaluated the seroprevalence of SARS-CoV-2 antibodies in Illinois household cats from October 2021 to May 2023. Among 1,715 samples tested by serological assays, 244 samples (14%) tested positive. High-rate temporal, spatial, and space-time clusters of SARS-CoV-2 cases were assessed within 63 counties in Illinois. Three space-time clusters with higher than expected seroprevalence rates were identified in the northeastern, central-east, and southwest regions of Illinois, occurring between June and October 2022. Young cats had a higher rate of seropositivity compared to older cats, and the third quarter of the year had the highest seropositivity rate. This study provides an in-depth analysis of SARS-CoV-2 epidemiology in Illinois household cats, which will aid in COVID-19 control and prevention.

RSV linked to previous COV'ID infection...

Dr. Blome aka Dr. Strange @BlomeChristine | 2:02 AM · Jun 29, 2023:
Research Group Patient-Reported Outcomes @pros_research_ | Post-Covid research | no MD | @hche_uhh | Associate Editor @BrJDermatol

Preprint: RSV linked to previous COV'ID infection.
2021 RSV wave delayed, but as high as expected ⬇️. Catch-up infections do not appear to be a good explanation for the all-time RSV high in 2023. Also, not plausible for 0-1 year olds anyway (bottom figure)
Graphs ( https://twitter.com/BlomeChristine/status/1674297245628354560/photo/1 )

Lindsey Wang et al. 2023. Disrupted seasonality and association of COVID-19 with medically attended respiratory
syncytial virus infections among young children in the US: January 2010–January 2023. MedRxiv 16 May 2023. https://medrxiv.org/content/10.1101/2023.05.12.23289898v1.full.pdf

Abstract
Respiratory syncytial virus (RSV) infections and hospitalizations surged sharply in 2022 among young children. To assess whether COVID-19 contributed to this surge, we leveraged a real-time nation-wide US database of electronic health records (EHRs) using time series analysis from January 1, 2010 through January 31, 2023, and propensity-score matched cohort comparisons for children aged 0–5 years with or without prior COVID-19 infection. Seasonal patterns of
medically attended RSV infections were significantly disrupted during the COVID-19 pandemic. The monthly incidence rate for first-time medically attended cases, most of which were severe RSV-associated diseases, reached a historical high rate of 2,182 cases per 1,0000,000 person-days in November 2022, corresponding to a related increase of 143% compared to expected peak rate (rate ratio: 2.43...). Among 228,940 children aged 0–5 years, the risk for first-time medically attended RSV during 10/2022–12/2022 was 6.40% for children with prior COVID-19 infection, higher than 4.30% for the matched children without COVID-19 (risk ratio or RR: 1.40...); and among 99,105 children aged 0–1 year, the overall risk was 7.90% for those with prior COVID-19 infection, higher than 5.64% for matched children without
(RR: 1.40...). These data provide evidence that COVID-19 contributed to the 2022 surge of severe pediatric RSV cases.

1/1000 infections become chronic = millions worldwide = enormous latent pool of viral diversity = more unpredictability in emergence of new variants

Marc Johnson @SolidEvidence | 5:59 PM · Jun 29, 2023:
Molecular virologist, Professor, sewage sage and wastewater wizard. {U Missouri?}

How common are chronic SARS-CoV-2 infections?
I think that at least 1 in 1,000 infections lead to long term (more than 4 month) chronic infection.
This is how I came up with that number. 1/

https://threadreaderapp.com/thread/1674538153347276801.html
With comments: https://twitter.com/SolidEvidence/status/1674538153347276801
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Arijit Chakravarty @arijitchakrav | 7:57 PM · Jun 29, 2023
Biologist who knows some math, working in pharma R&D. Day job-helping companies make drugs more efficiently. Night “job”- publishing on covid.

Fascinating 🧵 on a crucial question. Long-term SC2 infections are a major driver of viral evolution at this point. This 🧵 suggests that there may be millions of these infections present in the global population at any given time (1/)

Our modeling projects 1-2 infections a year on average, which translates to 8-16 billion infections worldwide annually. If 1/1000th of those lead to chronic infections, you’re looking at many millions of such infections. (2/)

The existence of such an enormous latent pool of viral diversity has major implications for what happens next in the pandemic. Simply put, we can expect more unpredictability over time, as the emergence of new variants distantly related to current ones is facilitated. (3/3)

Alex H @nuisancefilter: And to think, we nearly had it within traceable-grasp the summer ‘21– to think we threw all that effort and the effort of so many years to come away. For a cheap. Political. Point.

Arijit Chakravarty @arijitchakrav: 🔥🔥🔥

Don Ford - The People's Strategist - @DonEford: ...The number of people with cryptic infections is much higher, but these are just the people with it in their digestive tract.

COVID Infection May Impair Semen Quality, Even After Mild Cases
— Jury still out on whether infection can cause permanent seminal damage, however
Ingrid Hein, Staff Writer, MedPage Today June 30, 2023

Semen quality remained impaired more than 3 months after a mild COVID-19 infection, according to a small study from Spain involving unvaccinated men.

... Seminal volume reduced by 20% (from 2.5 to 2 mL)
Sperm concentration was 26.5% lower (from 68 to 50 million/mL of ejaculate)
Sperm count reduced 37.5% (from 160 to 100 million/mL of semen)
Semen total motility reduced 9.1% (49.5% to 45%)
Number of live sperm reduced about 5% (80% to 76%)

Researchers found no differences when comparing semen samples taken less than 100 days after infection to those more than 100 days later.

(Rocio Núñez-Calonge, PhD, with the UR International Group in Madrid) noted in a press release that it takes approximately 78 days to create new sperm. "We assumed that semen quality would improve once new sperm were being generated, but this was not the case. We do not know how long it might take for semen quality to be restored, and it may be the case that COVID has caused permanent damage, even in men who suffered only a mild infection," she said. "There are patients whose semen quality still does not improve after 500 days, but we would need to monitor them in the long term"...

Parviz Kavoussi, MD, of the University at the Texas Health Science Center at San Antonio, commented that seminal quality should be expected to return in about 6 months after mild COVID. He pointed to a study performed in Belgium that showed unvaccinated men with mild illness had impaired seminal values that returned to baseline 3 to 6 months later. {OTOH} an autopsy study in men with more severe COVID-19 infections did reveal damage in the testicles related to infection.

"Luckily, in Spanish} group's men, the decline observed still put them within range for natural conception," said Tung-Chin Hsieh, MD, a urologist at the University of California San Diego...

Primary Source
European Society of Human Reproduction and Embryology
Source Reference: Núñez-Calonge R, et al "What is the recovery time for sperm parameters in men who have suffered a mild Covid-19 infection?" ESHRE 2023. https://www.eshre.eu/ESHRE2023

https://www.medpagetoday.com/infectiousdisease/covid19/105312?xid=nl_mpt_DHE_202...

>100 margd:

Stanford Study of Paxlovid for Long COVID* Stopped Early
— Enrollment was halted earlier than planned after interim analysis
Kristina Fiore, Director of Enterprise & Investigative Reporting, MedPage Today June 30, 2023

...trial enrollment had been halted... a study coordinator that a preliminary review found "inconclusive evidence" for the primary outcome of the study. Another {source} said their first appointment was canceled just a few days before it was supposed to take place, and they were later told that all future enrollment had been halted.

...Stanford Medicine spokesperson Lisa Kim confirmed that "new enrollment is closing slightly earlier than original projections based on a planned interim analysis reviewed by an external monitoring committee."

"There are no safety concerns with the study and enrolled participants are encouraged to complete follow-up activities as planned," she added.

Kim did not provide further comment on what was found during the interim analysis and did not comment on the "inconclusive" results mentioned by the study coordinator to the source.

In May, MedPage Today reported that some participants were concerned that some investigators were not wearing masks during clinic visits, potentially putting the participants at risk...Neither Stanford nor study sponsor Pfizer would comment on whether or not the masking issue factored into the decision to stop the study early...

https://www.medpagetoday.com/special-reports/exclusives/105295?xid=nl_mpt_DHE_20...

* https://stanfordhealthcare.org/trials/p/NCT05576662.html

Federal Survey*: 11% of Previously Infected U.S. Adults Report Long COVID Symptoms
Cecelia Smith-Schoenwalder | June 30, 2023

As of June 2023, about 11% of adults who had ever had COVID reported that they were currently experiencing symptoms of long COVID, down from nearly 19% one year ago.

...55% of Americans report ever having the coronavirus. The Centers for Disease Control and Prevention estimates the true number is about 70% based on blood donation samples. The gap could likely be explained by asymptomatic infections that didn’t prompt testing for many Americans.

Nearly 16% of adults said they had long COVID symptoms at some point in time. The rate would mean that more than 40 million Americans have experienced long COVID....

https://www.usnews.com/news/health-news/articles/2023-06-30/federal-survey-11-of...
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* National Center for Health Statistics: Long COVID
Household Pulse Survey
https://www.cdc.gov/nchs/covid19/pulse/long-covid.htm

As part of an ongoing partnership with the Census Bureau, the National Center for Health Statistics (NCHS) recently added questions to assess the prevalence of post-COVID-19 conditions (long COVID), on the experimental Household Pulse Survey...

>150 margd: Happy to see that some LC may resolve after three months, but some damage lingers apparently... ;( Still premature to let guard down. (Previous post)

Heart-disease risk soars after COVID — even with a mild case
Massive study shows a long-term, substantial rise in risk of cardiovascular disease, including heart attack and stroke, after a SARS-CoV-2 infection.
Saima May Sidik | 2022

Even a mild case of COVID-19 can increase a person’s risk of cardiovascular problems for at least a year after diagnosis, a new study* shows. Researchers found that rates of many conditions, such as heart failure and stroke, were substantially higher in people who had recovered from COVID-19 than in similar people who hadn’t had the disease... {PAYWALL}

Nature 602, 560 (2022)
doi: https://doi.org/10.1038/d41586-022-00403-0
https://www.nature.com/articles/d41586-022-00403-0
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* Xie, Y., Xu, E., Bowe, B. & Al-Aly, Z. Long-term cardiovascular outcomes of COVID-19. Nature Med. volume 28, pages 583–590 (7 Feb. 2022)https://www.nature.com/articles/s41591-022-01689-3 (2022).

Nate Bear @NateB_Panic | 7:13 AM · Jul 6, 2023:
The union that represents doctors and medical students in the UK just called the continued spread of covid in hospitals "outrageous" and demanded the re-introduction of infectious disease controls. The media ignored it

UK doctors demand re-introduction of infectious disease controls
Nate Bear | 6 July 2023
https://ko-fi.com/Post/UK-doctors-demand-the-re-introduction-of-infectiou-U7U0MY...
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First major survey of doctors with Long Covid reveals debilitating impact on health, life and work (Press Release)
BMA media team | 4 July 2023

...Dr Kelly Fearnley, Long Covid Doctors for Action chair, said: “From the start of this pandemic, UK healthcare workers have been risking their lives and health caring for Covid patients without adequate protection. A significant number are now disabled following preventable occupational exposure to SARS-CoV-2 and are being managed out of the door with no support system in place and without means to financially support themselves and their families. Not only have they lost their health and independence, they have lost their careers and livelihoods, with many now facing financial destitution.

“One would think, given the circumstances under which we fell ill and current workforce shortages, NHS employers would be eager to do everything to facilitate the return to work of people with Long Covid. However, NHS employers are legally required to implement only ‘reasonable adjustments’, and so things such as extended phased return or adjustments to shift patterns, are not always being facilitated. Instead, an increasing number of employers are choosing to terminate contracts. We feel betrayed and completely abandoned.

“Infection control guidelines are fundamentally flawed: SARS-CoV-2 is airborne. It is outrageous that three-and-a-half years into this pandemic, staff and patients are still, knowingly and repeatedly, being exposed to a level-3 biohazard – a virus known to cause brain damage and significantly increased risk of life-threatening blood complications even in those recovered. Healthcare workers must be provided with respiratory protection and the air quality in hospitals be monitored and improved through the installation of ventilation systems and air filter units.”

https://www.bma.org.uk/bma-media-centre/first-major-survey-of-doctors-with-long-...

Gabrielle M. Katz et al. 2023. Understanding How Post–COVID-19 Condition Affects Adults and Health Care Systems (Special Communication). JAMA Health Forum. 7 July 2023;4(7):e231933. doi:10.1001/jamahealthforum.2023.1933 https://jamanetwork.com/journals/jama-health-forum/fullarticle/2807048

Abstract
Importance. Post–COVID-19 condition (PCC), also known as long COVID, encompasses the range of symptoms and sequelae that affect many people with prior SARS-CoV-2 infection. Understanding the functional, health, and economic effects of PCC is important in determining how health care systems may optimally deliver care to individuals with PCC.

Observations. A rapid review of the literature showed that PCC and the effects of hospitalization for severe and critical illness may limit a person’s ability to perform day-to-day activities and employment, increase their risk of incident health conditions and use of primary and short-term health care services, and have a negative association with household financial stability. Care pathways that integrate primary care, rehabilitation services, and specialized assessment clinics are being developed to support the health care needs of people with PCC. However, comparative studies to determine optimal care models based on their effectiveness and costs remain limited. The effects of PCC are likely to have large-scale associations with health systems and economies and will require substantial investment in research, clinical care, and health policy to mitigate these effects.

Conclusions and Relevance. An accurate understanding of additional health care and economic needs at the individual and health system levels is critical to informing health care resource and policy planning, including identification of optimal care pathways to support people affected by PCC.