SARS-CoV-2 and COVID-19 (28...)

David Fisman (U Toronto) | 8:06 PM · Feb 13, 2022
This is bonkers...global case count (log scale, blue) and CFR (Case Fatality Rate, right hand Y axis) with the emergence of omicron.
I think CFR will rebound somewhat with delayed deaths, but that's a remarkable change.

Graph--world, cases, deaths, case fatality rate, July 2020-Jan 2022
https://twitter.com/DFisman/status/1493028928956547077/photo/1
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O G (💉💉💉 + KF94/N95)@OG97921596:
They also only count deaths that happen within 28 days of a positive test.
People often die after more than 28 days (especially with Omicron).

LCAim4More@aim4more_lc:
IMH(lay)O, suggest caution in interpreting what ebb in CFR means re: Omicron.
Is it less lethal? &/Or
- better at breakthru (so x% are vaxed / prior infect)?
- more infectious to kids/young (so lower CFR demos)?
- treatment gains?
Combo I bet, but details key & seem still TBD.

caro_ottawa@crafty_caro:
Is there an instrument to measure delayed deaths… such as the people who die 6 months later of a heart attack after covid-induced heart damage?

Brenda English:
Not specifically. But I think that will show up when they calculate excess deaths. That is the number of deaths that exceed what is expected in a given time period. With large numbers of people, we die at a fairly predictable rate. So the impact of Covid is known.

Dr Zoë Hyde (epidemiologist biostatician) | 3:21 AM · Feb 13, 2022:
https://twitter.com/DrZoeHyde/status/1492775840140394497

Is the pandemic really over? What’s likely to happen over the next 12-18 months?
The UK’s Scientific Advisory Group for Emergencies (SAGE) outline four possible scenarios ranging from optimistic to pessimistic.

Here’s what they describe…🧵

Table--four scenarios, reasonable best case, central optimistic, central pessimistic, reasonable worst case
https://twitter.com/DrZoeHyde/status/1492775840140394497/photo/1

Research and analysis
Academics: Viral Evolution Scenarios, 10 February 2022
Academic paper on COVID-19 viral evolution Scenarios
From: (UK) Scientific Advisory Group for Emergencies
Published 11 February 2022
https://www.gov.uk/government/publications/academics-viral-evolution-scenarios-1...

Eric Topol (Scripps) | 12:22 PM · Feb 13, 2022:
https://twitter.com/EricTopol/status/1492912091862237185

We've learned a lot about Prior Covid ("Natural Immunity") over the past year, but the US/CDC continues to negate the abundant evidence for it providing any protection

Ground Truths on Prior Covid
How failure of the United States to acknowledge the evidence has unnecessarily fueled divisiveness and a war against mandates
Eric Topol | Feb 12, 2022
https://erictopol.substack.com/p/ground-truths-on-prior-covid

And there's substantial new data, I'll review🧵here /1 - 14

https://twitter.com/EricTopol/status/1492912091862237185/photo/1

I think I had COVID in Feb 2020, followed by long COVID. After a few hundred yards, I had to turn back from my usual 2.7 mi trail--using a cane, for heaven's sake! I kept at it, turning back as indicated by my body's response. Don't know if exercise was helping but recovery was becoming evident after six month when I could walk maybe half my usual. (Aches and pains mostly abated a day or two after first vaxx Feb 2021--don't know if causal, but not unknown experience among long COVID sufferers.)

‘I Had Never Felt Worse’: Long Covid Sufferers Are Struggling With Exercise
And experts have some theories as to why.
Melinda Wenner Moyer | Feb. 12, 2022. Updated Feb. 13, 2022

...Natalie Lambert, a biostatistician and health data scientist at the Indiana University School of Medicine, has collected self-reported data from more than a million long Covid patients through a collaboration with Survivor Corps, a Facebook support group for Covid survivors. Patients frequently report that their doctors have advised them to exercise, she said — but many say that when they do, they feel worse afterward.

...Dr. David Systrom, a pulmonary and critical care physician at Brigham and Women’s Hospital in Boston... and his colleagues... found that nobody in the study had abnormal chest CT scans, anemia or problems with lung or heart function, suggesting that organ injury wasn’t to blame for their symptoms. Yet when the long Covid patients exercised on a stationary bicycle, Dr. Systrom found that some veins and arteries were not working properly, preventing oxygen from being delivered efficiently to their muscles...long Covid patients experience damage to a certain kind of nerve fiber involved in how organs and blood vessel function.

... (Stephen J. Carter, an author of the study and an exercise physiologist at the Indiana University Bloomington School of Public Health) studied 29 women who had tested positive for Covid-19 about three months earlier. When these women underwent a six-minute-long walking test, their heart rates didn’t accelerate as much — or recover as quickly — as the heart rates of 16 similar women who had not been infected with Covid-19.

...Dr. Lambert pointed out that some patients with long Covid are also diagnosed with postural orthostatic tachycardia syndrome (or POTS), a disorder that affects blood flow. In people who have POTS, “the nervous system can’t regulate the things that it’s supposed to automatically control, like heart rate, blood pressure, sweating and body temperature,” she said. Yet “those are all things that when you’re exercising need to be regulated properly.”

...parallels between patients with long Covid and those with chronic fatigue syndrome

...should Covid patients who are having trouble with exercise continue to ramp up their physical activity? Nobody knows — and opinions differ...“That’s really the story of Covid — that for every patient, long Covid is different,” (Dr. Lambert) said. “There’s probably never going to be a one-size-fits-all recommendation for exercise.”

https://www.nytimes.com/2022/02/12/well/move/long-covid-exercise.html

Simone I Richardson et al.* 2022. SARS-CoV-2 Omicron triggers cross-reactive neutralization and Fc effector* functions in previously vaccinated, but not unvaccinated individuals. MedRxiv Feb14, 2022. doi: https://doi.org/10.1101/2022.02.10.22270789 https://www.medrxiv.org/content/10.1101/2022.02.10.22270789v1

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

Abstract
The SARS-CoV-2 Omicron variant largely escapes neutralizing antibodies elicited by vaccines or infection. However, whether Omicron triggers humoral responses that are cross-reactive to other variants of concern (VOCs) remains largely unknown. We use plasma from 20 unvaccinated and seven vaccinated individuals infected during the Omicron wave in South Africa to test binding, antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP) and neutralization against VOCs. In unvaccinated individuals, Fc effector function and binding antibodies target Omicron and other VOCs at comparable levels. However, Omicron-triggered neutralization is not extensively cross-reactive to VOCs, with 20 to 43-fold reductions in titer. In contrast, vaccination followed by breakthrough Omicron infection improved cross-neutralization of VOCs, with titers exceeding 1:2,900. This has important implications for the vulnerability of unvaccinated Omicron-infected individuals to reinfection by circulating and emerging VOCs. Further, while Omicron-based immunogens may be adequate boosters, they are unlikely to be superior to existing vaccines for priming in SARS-CoV-2 naive individuals.

* National Institute of Communicable Diseases of the National Health Services, South Africa

** https://www.ibr-inc.com/fc-mediated-effector-functions/page

A “Striking” Link Between Vitamin D Levels and Omicron
Low levels are associated with the severity of Omicron and other variants.
Richard E Cytowic MD (neurology, Geo Washington U)| February 13, 2022

A low vitamin D level "is surely a primary cause of severe COVID-19" say some researchers.
Results are equally relevant for Omicron as for previous strains, and likely those still to come.
Vitamin D affects many organs and the immune system.
A study* is the first to examine existing vitamin levels in people before they contracted COVID. “We found it remarkable, and striking”.

... Half the vitamin-deficient people developed severe, life-threatening illness compared to fewer than 10 percent of those who had normal levels. The study is the first to examine existing vitamin levels in people before they contracted COVID... (N=253. Israel)

...New data, however, indicate that even (20 nanograms per milliliter of blood) is too low: A minimum level of 50 mg/mL is now advised. Levels below this are believed to cause weak innate immune responses in patients hospitalized with COVID...

https://www.psychologytoday.com/us/blog/the-fallible-mind/202202/striking-link-b...
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References

* Pre-infection 25-hydroxyvitamin D3 levels and association with severity of COVID-19 illness. February 3, 2022. PLOS One. https://doi.org/10.1371/journal.pone.0263069

Vitamin D, an essential nutrient with versatile functions in nearly all organs. International Journal of Vitamin and Nutritional Research 10.1024/0300-9831/a000151.

Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials. The Lancet: Diabetes and Endocrinology. https://doi.org/10.1016/S2213-8587(21)00051-6

Association Between Preoperative 25-Hydroxyvitamin D Level and Hospital-Acquired Infections Following Roux-en-Y Gastric Bypass Surgery

S. A. Quraishi, et al. JAMA Surgery Vol. 149(2) Pages 112-118. DOI: 10.1001/jamasurg.2013.3176

Chauss, D. et al. Autocrine vitamin D signaling switches off pro-inflammatory programs of TH1 cells. Nature Immunol 23, 62–74 (2022). https://doi.org/10.1038/s41590-021-01080-3. According to Prof. Wright, "Th1 lymphocytes of hospitalised COVID-19 patients are continually hyper-inflammatory due to insufficient 25-hydroxyvitamin D - never switching from their pro-inflammatory startup program to their anti-inflammatory shutdown program ... This is surely a primary cause of severe COVID-19,"

Two antibiotics may have an antiviral effect against COVID-19
James Kingsland | February 14, 2022

A small study suggests that treating patients who have moderate or severe COVID-19 with ceftazidime or cefepime, plus the steroid dexamethasone, is as effective as standard care.
The antibiotic-plus-steroid treatment was associated with fewer side effects compared with standard care, which can involve seven or more different drugs.
Lab tests and computer simulations found that both antibiotics inhibit a key enzyme used by SARS-CoV-2, the virus that causes COVID-19.
However, there is currently no evidence from clinical trials that antibiotics are effective against the virus, and experts warn that overuse promotes antibiotic resistance.

...The study involved 370 patients with moderate or severe COVID-19 who were admitted to Beni-Suef University Hospital in Beni Suef, Egypt.

Researchers randomly assigned the patients to three groups:

treatment with cefepime plus dexamethasone: 124 patients
treatment with ceftazidime plus dexamethasone: 136 patients
standard COVID-19 treatment, as recommended in World Health Organization (WHO) guidelines and the Egyptian management protocol, with seven or more drugs: 110 patients

The mean recovery time for patients receiving treatment with cefepime or ceftazidime was 12 days and 13 days, respectively, while the mean recovery time with standard treatment was 19 days.

The researchers emphasize that the study was not a clinical trial and that there were insufficient numbers of patients in each group to draw firm conclusions.

However, they also conducted lab tests and computer simulations, which suggested that these two antibiotics inhibit the activity of a protease enzyme called Mpro. Mpro is an important part of a virus’s life cycle — a reduced activity of the enzyme impairs the replication rate of the virus...

https://www.medicalnewstoday.com/articles/two-antibiotics-may-have-an-antiviral-...
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Ragaey A. Eid* et al. 2022. Efficacy of Ceftazidime and Cefepime in the Management of COVID-19 Patients: Single Center Report from Egypt. Antibiotics 20 Oct 2021, 10(11), 1278; https://doi.org/10.3390/antibiotics10111278 https://www.mdpi.com/2079-6382/10/11/1278/htm

* Department of Tropical Medicine, Faculty of Medicine, Beni-Suef University, Beni-Suef 62521, Egypt

Abstract
...For Group 1 (cefepime) , the recovery time was 10, 12, and 16 days for the age groups 18–30, 30–60, and older than 60 years, respectively.
For Group 2 (ceftazidime) , the recovery time was 11, 13, and 15 days for the age groups 18–30, 30–60, and older than 60 years, respectively.
For Group 3 (control), the recovery time was 15, 16, and 17 days for the age groups 18–30, 30–60, and older than 60 years, respectively.

Both ceftazidime and cefepime showed very good inhibitory activity towards SARS CoV-2′s Mpro, with IC50 values of 1.81 µM and 8.53 µM, respectively.

In conclusion, ceftazidime and cefepime are efficient for the management of moderate and severe cases of COVID-19 due to their potential anti-SARS CoV-2 activity and low side effects, and, hence, the currently used complex multidrug treatment protocol can be replaced by the simpler one proposed in this study...

Joey Fox, P. Eng, M.A.Sc (HVAC engineer) @joeyfox85 | 3:34 PM · Feb 15, 2022:
https://twitter.com/joeyfox85/status/1493685067126030337

We stopped COVID in our home! My wife felt sick early last week and then tested positive (RAT). Everyone in our family is now negative. My kids and I never got it. We didn't resort to extreme measures like isolation or kids wearing N95s all day. This is how we did it: 1/11

We followed public health advice:
-wore comfortable cloth masks
-washed our hands frequently
-cleaned and disinfected - especially the toys
-practiced safe physical distancing
-put up plexiglass barriers as an extra precaution.

Just kidding. That's not how it's done. 2/11

#COVIDisAirborne . Focus on keeping the air clean and you can stop the spread. These are the measures we took:

Vaccines - we're all fully vaccinated (including boosters) except my 3 yo. My 4 month old had 2 doses in utero. My 6 yo has 2 doses. 3/11

Masks - I wore the CAN95 or CAN99 with ear loops. My wife wore a KN95 when she could, otherwise she wore a surgical mask + knot & tuck. It fits her well.

Filtration - We have 1 large #corsirosenthalbox in the main area and 3 minis* in the bedrooms.
https://twitter.com/joeyfox85/status/1482797730011525120?s=20&t=Pddl7vgGVluw...

* Available on amazon:
Comfort Zone CZ9BWT Portable 9-inch 2-Speed Quiet Box Fan for Home
Filterbuy 10x10x1 Air Filter MERV 13, Pleated HVAC AC Furnace Filters (6-Pack, Platinum) 4/11

The CR box is right beside where we eat and where the kids play/watch TV. We turned it up to medium speed for meals. My wife either ate in a different room or waited until we left and ate by herself. We kept windows cracked intermittently. 5/11

Humidifiers - we ran humidifiers in all the bedrooms every night. Tried to keep the home at 40% RH but because of the cold weather, it stayed around 30%.

With older kids, we could have had them stay in their rooms all day, but that wasn't possible for us. 6/11

I moved into the guest room and kept the window cracked. I made sure a room was aired out (3 air changes) before removing my mask. If the kids wanted to play in the basement, I brought one of the mini CR boxes down. 7/11

We had a disadvantage - an unmasked, unvaccinated 3 yo. It's been -10 deg C, couldn't open windows for long or go outside. But we have a 4 bedroom single family home which helped. 8/11

There's always an element of luck - how contagious someone is - but what we did worked.

-Vaccines work
-Well fitting medical masks work
-Filtration works
-Humidifiers work

My wife's case was mild - she felt fluey and achy for a few days - that's it. Many don't have that. 9/11

I've seen horror stories about how contagious this can be - e.g. across hallways in hotels with brief exposure - but those aren't the norm. Those stories do a disservice by making it seem impossible to stop this. It's not. 10/11

Focus on clean air and proper masking (N95s). It can be stopped. Vaccines, humidifiers, filtration, open windows, go outside, respirators...Infection isn't inevitable. 11/11
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Op-ed: Humidity can aid in the fight against COVID-19
https://www.hsph.harvard.edu/news/hsph-in-the-news/op-ed-humidity-can-aid-in-the...

Opinion: This winter, fight covid-19 with humidity
Joseph G. Allen, Akiko Iwasaki and Linsey C. Marr | November 18, 2020
https://www.washingtonpost.com/opinions/2020/11/18/winter-covid-19-humidity/

Marg: can't find it at the moment but article was posted earlier on temperature and humidity and infectivity

>8 margd: Here was my method:

1. Get vaccinated and boosted
2. Allow child with as-yet undiagnosed omicron to stay in the house for 48 hours
3. Breath freely without masks or other precautions
4. Obtain positive PCR for symptomatic child after 48 hours
4. No one got it outside of index case

Won’t work for everyone! ;)

>9 stellarexplorer: Pre-vaxx, and before we thought virus was in our community, DH moved into other bedroom and living room until fever broke. Then we shared vehicle (2 days) and hotel room (one night). I got whatever he had. Thinking he had flu, I did disinfect condo with hope of protecting cleaning service and next renters... Back in the day!

ETA. Our son twice had symptoms that had MDs keep him home from work, Pre-vaxx and again once vaxxed. He never did test positive. Still masking and keeping to his room, a designated bathroom, and the deck a couple times seemed to keep the rest of us safe.

Omicron is so much more contagious than what we may have been dealing with back then that today I'm happy to
ventilate and filter!

>10 margd: No argument here. While vaccines offer good protection, LC is still a concern. And I’ve known some vaccinated people who were pretty sick with Omicron though not hospitalized. No one should want to get this. What balance one chooses between safety and and activities avoided for 2 years is not an easy problem for me, so I’m taking it a step at a time

>11 stellarexplorer: Bring on summer!!

Eric Topol (Scripps) | 11:01 AM · Feb 17, 2022:
5 studies, highly consistent: 1-shot for people with Prior Covid prevents infections more than natural immunity. Across multiple variants. And additional shots provide no incremental benefit.
Table -- https://twitter.com/EricTopol/status/1494341361948000258/photo/1

This concerns me and may turn out to be the truth behind the current epidemic of “it’s over-ism”:

“ The world pre 2020 no longer exists - we may want it to, but it just doesn't. 1/13”
Worth a read.

https://twitter.com/chrischirp/status/1491891791490125825?s=21

Amazing photos: "Researchers found that the virus spreads widely during an initial infection, and that viral genetic material can remain embedded in tissues — in the intestines, lymph nodes and elsewhere — for many months."

How Long Covid Exhausts the Body
Josh Keller | Feb. 19, 2022
https://www.nytimes.com/interactive/2022/02/19/science/long-covid-causes.html

Eric Topol @EricTopol | 10:02 AM · Feb 20, 2022:
More reassuring evidence, from South Africa, that the BA.2 variant is not associated with an increase in clinical severity compared to its sister Omicron variant, BA.1

Nicole Wolter et al. 2022. Clinical severity of Omicron sub-lineage BA.2 compared to BA.1 in South Africa. MedRxiv Feb 19, 2022.
doi: https://doi.org/10.1101/2022.02.17.22271030 https://www.medrxiv.org/content/10.1101/2022.02.17.22271030v1

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

Abstract
Early data indicated that infection with Omicron BA.1 sub-lineage was associated with a lower risk of hospitalisation and severe illness, compared to Delta infection. Recently, the BA.2 sub-lineage has increased in many areas globally. We aimed to assess the severity of BA.2 infections compared to BA.1 in South Africa. We performed data linkages for (i) national COVID-19 case data, (ii) SARS-CoV-2 laboratory test data, and (iii) COVID-19 hospitalisations data, nationally. For cases identified using TaqPath COVID-19 PCR, infections were designated as S-gene target failure (SGTF, proxy for BA.1) or S-gene positive (proxy for BA.2). Disease severity was assessed using multivariable logistic regression models comparing individuals with S-gene positive infection to SGTF-infected individuals diagnosed between 1 December 2021 to 20 January 2022. From week 49 (starting 5 December 2021) through week 4 (ending 29 January 2022), the proportion of S-gene positive infections increased from 3% (931/31,271) to 80% (2,425/3,031). The odds of being admitted to hospital did not differ between individuals with S-gene positive (BA.2 proxy) infection compared to SGTF (BA.1 proxy) infection (adjusted odds ratio (aOR) 0.96, ...). Among hospitalised individuals, after controlling for factors associated with severe disease, the odds of severe disease did not differ for individuals with S-gene positive infection compared to SGTF infection (aOR 0.91, ...). These data suggest that while BA.2 may have a competitive advantage over BA.1 in some settings, the clinical profile of illness remains similar.

Bob Wachter (Chr UCSF Dept Medicine) @Bob_Wachter | 5:36 PM · Feb 19, 2022:
https://twitter.com/Bob_Wachter/status/1495165503106543618
As much as we hate externally imposed rules, they do make things easier. As masking mandates are lifted even in blue states, those of us who have been cautious will have to answer a new question. Not “must I mask?” but “should I?” Today, a 🧵on how I’m thinking about this. (1/25)

I’ve long used a threshold of 10 cases/100K/day (find your local number here @nytimes:
https://nytimes.com/interactive/2021/us/covid-cases.html ), along w/ low hospitalizations & a test positivity rate less than 2-3% as my It’s-OK-to-Ditch-the-Mask-in-Low-Risk-Settings-and-Dine-Indoors threshold. Below, I'll… (2/25)

...describe why this number hasn't budged, although the inputs into that threshold have changed quite a bit with Omicron. To me, the forces cancel each other out, landing me where I began: 10/100K/day.
This means that for most of the U.S., we’re close but not quite there. (3/25)

Where does "10 cases/100K/d" come from? Basically, it’s a low enough rate of community transmission that even vulnerable people (elders, for e.g., or unvaccinated) would have a slim chance of coming into close contact with an infected person. It’s nearly always associated…(4/25)

… with low hospitalization and death rates (both these metrics will lag behind the case & test positivity rates). It’s also associated with a low effective reproduction number (R eff less than 1.0) and low test positivity rates, the latter generally well below 5%. (5/25)

As you know by now, I’m a fan of using @UCSFHospitals' asymptomatic test positivity rate as a poor-man’s way of estimating the chance that a person near me in line at the Safeway, or at the next table in my favorite Italian restaurant, has Covid. So let’s take a look… (6/25)

…at SF numbers to see why – even with plunging rates of Covid – I’m still not ready to ditch my mask.
After that, I’ll describe why I’m sticking with the 10 cases/100K/day threshold despite all the changes in the dynamics of Covid wrought by Omicron. Here’s the latest… (7/25)...

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Should You Still Wear a Mask?
Experts weigh in on where, and when, you can safely take one off.
Amelia Nierenberg and Illustrations by Tim Peacock | Feb. 19, 2022

...Should you mask outside?...
How about indoor spaces, like supermarkets or gyms?

First and foremost, follow the norms and the rules of the business you’re entering. If the sign at the door says “Mask Required,” you don’t want to make retail workers have to enforce policies over which they have no control. Their jobs are hard enough, and everyone can wear a mask with little to no sacrifice.

If the business is mask optional, consider the space, the crowds and the airflow.

Dr. Bromage suggests a cigarette analogy: If someone were smoking, would the smell and taste of cigarettes quickly fill the air? If yes, so would the virus. You’d be smart to wear a mask. If not, it’s unlikely that you’ll get infected.

“When I walk into a space, I always do that,” Dr. Bromage said. “How high are the ceilings? Is the air moving? Can I create my own little buffer of space?”

Take a big box store with high ceilings. “Those tend to have good ventilation and because of the high ceilings, there’s a lot of dilution,” said Linsey Marr, an engineering professor at Virginia Tech who studies the airborne transmission of viruses. “The risks are pretty low, unless you’re in a crowded line waiting to check out.”

“If it’s a smaller space and crowded space, Trader Joe’s, for example, or some New York market with tiny aisles and people are really packed in there, the risk is higher,” she continued. “You might want to wear a mask.”

A hair salon might be a small space, Dr. Bromage said, but there typically won’t be that many people inside the business, so the risk of an infected person passing through will generally be low, especially as case counts fall.

At a restaurant, one person’s cigarette smoke at the next table over wouldn’t fill the air above yours. But you would smell someone smoking at your own table, so your direct dining companions pose the highest risk, Dr. Bromage said.

The gym may feel especially scary. Heavier breathing can expel more virus particles, but most gyms have excellent ventilation systems. (“If gyms did not have good air circulation, they would stink,” Dr. Bromage said.) That means any virus particles that may be floating around are also being sucked away with the sweat smell.

Dr. Bromage again uses the cigarette analogy. He’d run on the treadmill unmasked, but he’d put an extra treadmill between himself and another runner. But a spin class, in a small room with “people shouting, yelling, huffing puffing”? Probably not yet, he said.

What about on public transit or airplanes?...
What about when my child goes to school?...
What if you have the sniffles?...
And what type of mask should you wear?...

https://www.nytimes.com/article/mask-mandates-guidelines.html

Malgorzata (Gosia) Gasperowicz (developmental biologist U Calgary) @GosiaGasperoPhD | 11:47 PM · Feb 18, 2022:
‘According to the Government of Canada re #LongCovidKids

“About 58% of children had 1 or more symptoms 4 weeks or more after their initial COVID-19 infection.”...
https://canada.ca/en/public-health/services/diseases/2019-novel-coronavirus-infe...

Children
The most common symptoms that we know of in children include:
fatigue
headaches
weight loss
muscle pain
sleep disturbances
stuffy or runny nose
difficulty thinking or concentrating
About 58% of children had 1 or more symptoms 4 weeks or more after their initial COVID-19 infection.

These symptoms can be mild to severe, and can sometimes disappear and reappear. Some patients report that over-exertion (both mental and physical) may make the condition worse.

Céline Gounder, MD, ScM, FIDSA (NYU prof) @celinegounder | 10:58 AM · Feb 18, 2022:
Long COVID isn't the first "long" post-viral illness.

Also: influenza, measles, polio, Ebola, EBV...to name just a few.
Image--text "long flu" ( https://twitter.com/celinegounder/status/1494702779662798854/photo/1 )

Pandemics disable people — the history lesson that policymakers ignore
Influenza, polio and more have shown that infections can change lives even decades later. Why the complacency over possible long-term effects of COVID-19?
Laura Spinney | 16 February 2022
https://nature.com/articles/d41586-022-00414-x

>6 margd: contd.

COVID-19: Why vitamin D levels may be key
Robby Berman | February 18, 2022

Some research suggests vitamin D insufficiency has ties to worse COVID-19 outcomes.
A new study that considers pre-infection vitamin D levels confirms their link to severe COVID-19.
The researchers say their findings do not necessarily imply that vitamin D treatment will impact COVID-19 outcomes, although they suggest maintaining normal levels is wise.

Having sufficient levels of Vitamin D is important for promoting healthy bones and teeth. Too little of it has links to diabetes, autoimmune, cardiovascular, and infectious diseases. Among these is COVID-19.

Researchers at Bar Ilan University and the Galilee Medical Center in Israel have released a study that examines the links between Vitamin D levels and the severity of COVID-19 for 253 people admitted to the hospital. with COVID-19 The researchers found records indicating their vitamin D levels before they acquired a SARS-CoV-2 infection and went to the hospital.

The study concluded that people with insufficient pre-infection levels of vitamin D were 14 times more likely to develop severe COVID-19 than those with high vitamin D levels...

https://www.medicalnewstoday.com/articles/covid-19-why-vitamin-d-levels-may-be-k...

Effectiveness of Moderna vaxx against Delta and Omicron infection and hospitalization:

Tseng, H. F. et al. 2022. Effectiveness of mRNA-1273 against SARS-CoV-2 Omicron and Delta variants. Nature Medicine 21 Feb 2022. https://doi.org/10.1038/s41591-022-01753-y (2021) https://www.nature.com/articles/s41591-022-01753-y_reference.pdf

Abstract19
SARS-CoV-2 Omicron (B.1.1.529) variant is highly transmissible with potential immune escape. We conducted a test-negative case-control study to evaluate mRNA-1273 vaccine effectiveness (VE) against infection and hospitalization with Omicron or Delta. The large, diverse study population included 26,683 SARS-CoV-2 test-positive cases with variants determined by S-gene target failure status (16% Delta, 84% Omicron). The 2-dose VE against Omicron infection at 14-90 days was 44.0% ... but declined quickly. The 3-dose VE was 93.7% ... and 86.0% ... against Delta infection and 71.6% ...and 47.4% ... against Omicron infection at 14-60 days and more than 60 days, respectively. The 3-dose VE was 29.4% ... against Omicron infection in immunocompromised individuals. The 3-dose VE against hospitalization with Delta or Omicron was more than 99% across the entire study population. Our findings demonstrate high, durable 3-dose VE against Delta infection but lower effectiveness against Omicron infection, particularly among immunocompromised people. However, 3-dose VE of mRNA-1273 was high against hospitalization with Delta and Omicron variants.

NYC: research volunteers needed

Prof. Akiko Iwasaki (Yale) @VirusesImmunity | 2:42 PM · Feb 22, 2022:
https://twitter.com/VirusesImmunity/status/1496208879977390086

We need your help for some crucial #LongCOVID research!
If you live in the New York area, have FULLY recovered from COVID-19 infection and
it has been AT LEAST 12 weeks since you were first sick,
please email us at prcovid@mountsinai.org @PutrinoLab

RT highly appreciated 🙏🏼
-----------------------------------------------

Adults, and participants need to be able to come to NYC for an appointment. Thank you!

Eric Topol @EricTopol | 4:21 PM · Feb 22, 2022
The Neanderthal-derived chromosome 3 locus that has been established to be associated with risk of severe Covid
may be protective vs HIV, a 27% less risk of infection

Hugo Zeberg. 2022. The major genetic risk factor for severe COVID-19 is associated with protection against HIV. PNAS March 1, 10 Jan 2022 119 (9) e2116435119; https://doi.org/10.1073/pnas.2116435119 https://pnas.org/content/119/9/e2116435119

Abstract
There are genetic risk factors that influence the outcome of COVID-19 COVID-19 Host Genetics Initiative, Nature 600, 472–477 (2021). The major genetic risk factor for severe COIVD-19 resides on chromosome 3 and is inherited from Neandertals H. Zeberg, S. Pääbo, Nature 587, 610–612 (2020). The risk-associated DNA segment modulates the expression of several chemokine receptors, among them CCR5, a coreceptor for HIV which is down-regulated in carriers of the COVID-19 risk haplotype. Here I show that carriers of the risk variant have an ∼27% lower risk of HIV infection.

Image ( https://twitter.com/EricTopol/status/1496233792025026571/photo/1 )

zeynep tufekci (UNC) zeynep | 10:26 AM · Feb 23, 2022
The Africa CDC is asking for a pause in vaccine donations. Distribution remains a challenge (and getting too much at once makes it harder to use them before they expire), plus hesitancy is a factor.
The world should help fund distribution infrastructure.

Text, highlighted ( https://twitter.com/zeynep/status/1496506821623832582/photo/1 )
-------------------------------------------------------

Africa CDC to ask world to pause Covid-19 vaccine donations
Daniel Payne | 02/22/2022

...John Nkengasong, director of the Africa Centres for Disease Control and Prevention, said the primary challenge for vaccinating the continent is no longer supply shortages but logistics challenges and vaccine hesitancy — leading the agency and the African Vaccine Acquisition Trust to seek the delay.

“It makes sense to say, ‘Look, let’s pause and avoid the risk of sending so much that it gets expired, and then clear this and put our efforts in taking these ones up so we can now see how many people have actually been immunized — and then maybe now you can look at the next wave of donations,’” he said.

The request marks a shift in the challenges Africa faces — from not having enough doses to not being able to quickly get those doses into arms.

“It’s not to say that donations are not important,” he said. “It’s just to say let’s not just do it at once.”...

https://politico.com/news/2022/02/22/africa-asks-covid-vaccine-donation-pause-00...

Jonas R. Kunst (psych U Oslo) @KunstJonas | 8:13 AM · Feb 23, 2022
An important new study suggests that, after taking the vaccine, #LongCovid symptoms
"disappeared (30.8%) or
improved (4.7%) in 35.5% of cases,
were stable in 28.7%, and
worsened in 3.3%."
Note: The study was not randomized; bias is possible.

Image ( https://twitter.com/KunstJonas/status/1496473291103559682/photo/1 )

Mayssam Nehme et al. 2022. Symptoms After COVID-19 Vaccination in Patients with Post-Acute Sequelae of SARS-CoV-2. Journal of General Internal Medicine (2 Feb 2022) https://link.springer.com/article/10.1007/s11606-022-07443-2

...DISCUSSION
Vaccination was associated with a decreased prevalence of post-acute sequelae of SARS-CoV-2 infection compared to no vaccination...Postulated hypotheses include the potential correction of dysregulated immune or inflammatory responses, or the possible elimination of persisting viruses or viral remnants of SARS-CoV-2.6

...While acknowledging these limitations, we believe that the strength of the association, as well as a dose-response effect, could support a causal association, in addition to possible biological rationales evoked recently. If confirmed, this would mean that vaccination not only prevents infection but also can potentially improve post-acute sequelae of SARS-CoV-2.

Lauren Pelley (CBC News) @LaurenPelley | 9:48 AM · Feb 24, 2022:
BREAKING: Made-in-Canada #COVID19 vaccine from Medicago approved by Health Canada today.
Shot dubbed 'Covifenz,' and uses virus-like particles.
Background on the high efficacy against infection seen during Phase 3 clinical trials:

Canada's first homegrown COVID-19 vaccine shows high efficacy
Trial occurred before omicron variant; Health Canada submission is imminent
Lauren Pelley · CBC News | Posted: Dec 07, 2021

...Medicago, a biopharmaceutical company headquartered in Quebec City, and British-American vaccine giant GlaxoSmithKline (GSK) are now gearing up for their final regulatory submission to Health Canada.

The vaccine's overall efficacy rate against all virus variants studied was 71 per cent, with a higher efficacy rate of 75 per cent against COVID-19 infections of any severity from the dominant delta variant, the companies said in a news release.

The results followed a global, Phase 3, placebo-controlled study of the two-dose vaccine that was launched last March. The newly discovered omicron variant — recently confirmed in various countries around the world, including Canada — was not circulating during the trial period.

If licensed in this country, the shot would be the first COVID-19 vaccine using virus-like particle technology and the first plant-based vaccine ever approved for human use, Brian Ward, medical officer for Medicago, said during a recent interview with CBC News...

https://www.cbc.ca/news/health/covid-vaccine-canada-medicago-efficacy-1.6275759

As bad as COVID looked in Russia, it may be worse...

Eric Topol (Scripps) @EricTopol | 6:21 PM · Feb 24, 2022:

Russia faking Covid data
"A back-of-the-envelope calculation shows that such a low-variation week would occur by chance once every 2,747 years."

https://economist.com/graphic-detail/2022/02/25/are-some-countries-faking-their-...
... on work by @hippopedoid

Graph death rate Russia, April 2020-Jan 2022 ( https://twitter.com/EricTopol/status/1496988622150537216/photo/1 )

COVID-19 live updates: Sanofi and GSK seek approval for new vaccine
MNT News Team | February 25, 2022

Sanofi and GSK have announced positive results from late stage trials on their experimental COVID-19 vaccine. They plan to seek approval from the Food and Drug Administration (FDA) and the European Medicines Agency. As the vaccine is protein-based rather than mRNA-based, it is easier to transport and store.

According to the press release, in phase 3 efficacy trials, the vaccine was 100% effective against severe COVID-19 and hospitalization and 77% effective against moderate to severe disease.

However, it is worth noting that there were relatively few cases of severe COVID-19 among the trial participants. Once the trial is over later this year, the pharmaceutical companies plan to publish their data in a peer-reviewed journal.

https://www.medicalnewstoday.com/articles/live-updates-coronavirus-covid-19

02/24/2022 09:56 GMT — SARS-CoV-2 infection damages hamsters’ testicles

In a recent study, scientists infected hamsters with SARS-CoV-2. They compared any changes in the hamsters’ testicles with those of hamsters infected by an influenza virus.

In the hamsters with SARS-CoV-2, the team identified a “varying degree of testicular inflammation, hemorrhage, and necrosis” and a reduced ability to produce sperm.

Although this was an animal study, the authors believe that “Long term follow-up of sperm count and sex hormone profile of convalescent COVID-19 males is warranted.”

https://www.medicalnewstoday.com/articles/live-updates-coronavirus-covid-19
------------------------------------------------------------

Can Li, et al. 2022. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections by intranasal or testicular inoculation induces testicular damage preventable by vaccination in golden Syrian hamsters. Clinical Infectious Diseases 18 February 2022. https://doi.org/10.1093/cid/ciac142 https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac142/6530400

Accepted Manuscript

ABSTRACT
...Results
...Acute histopathological damage with varying degree of testicular inflammation, haemorrhage, and necrosis, degeneration of seminiferous tubules and disruption of orderly spermatogenesis were seen with increasing virus inoculum. Degeneration and necrosis of Sertoli and Leydig cells were found. Though viral loads and SARS-CoV-2 nucleocapid (N) protein expression were markedly lower in testicular than lung tissues, direct intra-testicular injection showed N expressing interstitial cells and epididymal epithelial cells. Control intranasal or intra-testicular challenge by A(H1N1)pdm09 (flu virus) showed no testicular infection or damage. From 7 to 120 dpi, degeneration and apoptosis of seminiferous tubules, immune complex deposition and depletion of spermatogenic cell and spermatozoa persisted. ...

Conclusions
SARS-CoV-2 can cause acute testicular damage with subsequent chronic asymmetric testicular atrophy and associated hormonal changes despite a self-limiting pneumonia in hamsters. Awareness of possible hypogonadism and subfertility is important in managing convalescent COVID-19 males.

Eric Topol @EricTopol | 1:02 PM · Feb 25, 2022:
You knew this, but now quantified in a new @CDCMMWR report: the very high household transmission of Omicron

Baker JM, Nakayama JY, O’Hegarty M, et al. SARS-CoV-2 B.1.1.529 (Omicron) Variant Transmission Within Households — Four U.S. Jurisdictions, November 2021–February 2022. MMWR Morb Mortal Wkly Rep. ePub: 25 February 2022. DOI: http://dx.doi.org/10.15585/mmwr.mm7109e1 https://cdc.gov/mmwr/volumes/71/wr/mm7109e1.htm?s_cid=mm7109e1_w

...In a study of household transmission in four U.S. jurisdictions, Omicron infection resulted in high transmission among household contacts, particularly among those who lived with index patients who were not vaccinated or who did not take measures to reduce the risk of transmission to household contacts.

Multicomponent COVID-19 prevention strategies, including up-to-date vaccination, isolation of infected persons, and mask use at home, are important to reduce Omicron transmission in household settings...

Fig 2. Household attack rates by characteristics household, patient ( https://twitter.com/EricTopol/status/1497270728189644802/photo/1 )

Denmark has passed all previous mortality peaks. :(

Graph--confirmed deaths per million Denmark March 2020-Feb 2022
https://twitter.com/DGBassani/status/1497235405221081088/photo/1

- Diego Bassani, PhD (Sick Kids U of Toronto) @DGBassani | Feb 25, 2022

>31 margd: But it's not painting a true picture. Covid is everywhere at the moment and so people dying from whatever reason also has covid (or had covid within the last 30 days).
Many of my colleagues and family members have had omicron in the past three weeks. All of them had something like a three day flu and took another week to get truly back in shape. No one seriously ill (i.e. seeing a doctor or anything). And all of them vaccinated at least twice.

So the graph is right, but that doesn't make omicron a killer (if you are vaccinated, that is).

Glad to hear. How is Denmark's experience with Long COVID, do you know?

>33 margd: Good question. I don't think we are seeing much of it from the Omicron wave. And the statistics from the Delta variant are still being gathered. So I haven't seen much so far. I think this is the newest I've seen:

https://www.news-medical.net/news/20220209/Danish-study-of-long-COVID-in-teens.a...

I don't know anyone with Long Covid symptoms, but that's not a scientific study :-)

>34 bnielsen: Hopefully, with good vaccination rates, Danes might be protected somewhat from Long Covid(?)

Per #25
Mayssam Nehme et al. 2022. Symptoms After COVID-19 Vaccination in Patients with Post-Acute Sequelae of SARS-CoV-2. Journal of General Internal Medicine (2 Feb 2022) https://link.springer.com/article/10.1007/s11606-022-07443-2

...DISCUSSION
Vaccination was associated with a decreased prevalence of post-acute sequelae of SARS-CoV-2 infection compared to no vaccination...Postulated hypotheses include the potential correction of dysregulated immune or inflammatory responses, or the possible elimination of persisting viruses or viral remnants of SARS-CoV-2.6

...While acknowledging these limitations, we believe that the strength of the association, as well as a dose-response effect, could support a causal association, in addition to possible biological rationales evoked recently. If confirmed, this would mean that vaccination not only prevents infection but also can potentially improve post-acute sequelae of SARS-CoV-2.

Michael Worobey (U AZ) @MichaelWorobey | 11:19 AM · Feb 26, 2022:
https://twitter.com/MichaelWorobey/status/1497607313397481472

We have just released two preprints on the origin of SARS-CoV-2:
1. "The Huanan market was the epicenter of SARS-CoV-2 emergence"
2. "SARS-CoV-2 emergence very likely resulted from at least two zoonotic events"

* Michael Worobey @MichaelWorobey
Viruses. Pandemics. Professor and Head of Ecology and Evolutionary Biology at the University of Arizona. Views are my own.
---------------------------------------------------------

Michael Worobey et al. 2022. Geographical clustering of the earliest known COVID-19 cases and the proximity of positive environmental samples to live-animal vendors suggest that the Huanan Seafood Wholesale Market in Wuhan was the site of origin of the COVID-19 pandemic. Zenodo Feb 26, 2022. DOI: 10.5281/zenodo.6299600 https://zenodo.org/record/6299600#.YhpqfWDF1ZN
Preprint

---------------------------------------------------------

Pekar, Jonathan E. et al. 2022. SARS-CoV-2 emergence very likely resulted from at least two zoonotic events. Zonodo Feb 26, 2022. DOI: 10.5281/zenodo.6291628 https://zenodo.org/record/6291628#.Yhpk0WDF1ZN
Preprint

Understanding the circumstances that lead to pandemics is critical to their prevention. Here, we analyze the pattern and origin of genomic diversity of SARS-CoV-2 early in the COVID-19 pandemic. We show that the SARS-CoV-2 genomic diversity prior to February 2020 comprised only two distinct viral lineages—denoted A and B—with no transitional haplotypes. Novel phylodynamic rooting methods, coupled with epidemic simulations, indicate that these two lineages were the result of at least two separate cross-species transmission events into humans. The first zoonotic transmission likely involved lineage B viruses and occurred in late-November/early-December 2019 and no earlier than the beginning of November 2019, while the introduction of lineage A likely occurred within weeks of the first event. These findings define the narrow window between when SARS-CoV-2 first jumped into humans and when the first cases of COVID-19 were reported. Hence, as with SARS-CoV-1 in 2002 and 2003, SARS-CoV-2 emergence likely resulted from multiple zoonotic events.

"...first evidence of a highly divergent lineage of SARS-CoV-2 in white-tailed deer and of deer-to-human transmission...From 1 November to 31 December 2021, 300 WTD were sampled from Southwestern (N=249, 83%) and Eastern (N=51, 17%) Ontario, Canada during the annual hunting season..."

Bradley Pickering et al. 2022. Highly divergent white-tailed deer SARS-CoV-2 with potential deer-to-human transmission. BioRxiv Feb 25, 2022. doi.org/10.1101/2022.02.22.481551 https://www.biorxiv.org/content/10.1101/2022.02.22.481551v1.full.pdf

Preprint not yet peer-reviewed.

Summary
Wildlife reservoirs of SARS-CoV-2 can lead to viral adaptation and spillback from wildlife to humans (Oude Munnink et al., 2021). In North America, there is evidence of spillover of SARS-CoV-2 from humans to white-tailed deer (Odocoileus virginianus), but no evidence of transmission from deer to humans (Hale et al., 2021; Kotwa et al., 2022; Kuchipudi et al., 2021). Through a multidisciplinary research collaboration for SARS-CoV-2 surveillance in Canadian wildlife, we identified a new and highly divergent lineage of SARS-CoV-2. This lineage has 76 consensus mutations including 37 previously associated with non-human animal hosts, 23 of which were not previously reported in deer. There were also mutational signatures of host adaptation under neutral selection. Phylogenetic analysis revealed an epidemiologically linked human case from the same geographic region and sampling period. Together, our findings represent the first evidence of a highly divergent lineage of SARS-CoV-2 in white-tailed deer and of deer-to-human transmission.

Pfizer vaccine's protection against COVID wanes quickly in kids ages 5-11, study says
Vanessa Romo and Rob Stein | February 28, 2022

The low-dose version of the Pfizer-BioNTech COVID-19 vaccine appears to be much less effective at protecting young children against infection than the higher-dose version of the vaccine given to older children and adults, a new study shows.

In all cases, the vaccine proved to provide strong protection against becoming seriously ill. The preprint study looked at data collected from more than 1.2 million fully vaccinated children and adolescents between the ages of 5 and 17 from Dec. 13 to Jan. 30...

https://www.npr.org/2022/02/28/1083617811/pfizer-vaccine-protection-kids
--------------------------------------------------------------

Vajeera Dorabawila et al. 2022. Effectiveness of the BNT162b2 (Pfizer) vaccine among children 5-11 and 12-17 years in New York after the Emergence of the Omicron Variant. MedRxiv Feb 28, 2022. doi: https://doi.org/10.1101/2022.02.25.22271454 https://www.medrxiv.org/content/10.1101/2022.02.25.22271454v1

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

Abstract
...Results: From December 13, 2021 to January 30, 2022, among 852,384 fully-vaccinated children 12-17 years and 365,502 children 5-11 years, VE (vaccine effectiveness) against cases declined from 66%...to 51%...for those 12-17 years and from 68%...to 12%...for those 5-11 years. During the January 24-30 week, VE for children 11 years was 11%...and for those age 12 was 67%.... VE against hospitalization declined changed from 85%...to 73%...for children 12-17 years, and from 100%...to 48%... for those 5-11 years. Among children newly fully-vaccinated December 13, 2021 to January 2, 2022, VE against cases within two weeks of full vaccination for children 12-17 years was 76%...and by 28-34 days it was 56%... For children 5-11, VE against cases declined from 65%...to 12%...by 28-34 days.

Conclusions and Relevance: In the Omicron era, the effectiveness against cases of BNT162b2 (Pfizer vaxx) declined rapidly for children, particularly those 5-11 years. However, vaccination of children 5-11 years was protective against severe disease and is recommended. These results highlight the potential need to study alternative vaccine dosing for children and the continued importance layered protections, including mask wearing, to prevent infection and transmission...

Remember COVID Toes? "Our results do not support SARS-CoV-2 as the causative agent of pandemic chilblains; however, our study does not exclude the possibility of SARS-CoV-2 seronegative abortive infections."

Jeff R. Gehlhausen...and Akiko Iwasaki. 2022. Lack of association between pandemic chilblains and SARS-CoV-2 infection. PNAS February 25, 2022 | 119 (9) e2122090119 | https://doi.org/10.1073/pnas.2122090119 | Vol. 119 | No. 9 https://www.pnas.org/doi/10.1073/pnas.2122090119

Significance
Chilblain diagnoses have increased during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and have been attributed to viral infection and a subsequent robust antiviral immune response. As a result, providers have managed these cases differently than idiopathic chilblains, which are associated with cold exposure. The relationship between pandemic chilblains and SARS-CoV-2 infection, however, remains unclear as most patients do not test positive for SARS-CoV-2–specific PCR or antibodies. To better understand this disconnect, we enrolled cases of pandemic chilblains in a study and performed detailed immune profiling of antibody and T cell responses. Additionally, we compared immunohistochemical staining of pandemic chilblains with prepandemic tissues. Our results do not support SARS-CoV-2 as the cause of the increased chilblain incidence.

Ontario opened up March 1, 2022, so following Denmark's experiences closely:

Diego Bassani, PhD (epidemiology, U Toronto) @DGBassani | 5:22 PM · Mar 1, 2022
Dear all,
Whatever is driving mortality in Denmark should be raising eyebrows.
...
Graph--excess mortality Denmark, 2016-2022 ( https://twitter.com/DGBassani/status/1498785759196815364/photo/1 )
___________________________________________________________

Eric Topol @EricTopol | 11:02 AM · Mar 1, 2022
Denmark study of #LongCovid at 6-12 months in 90,000 controls
Not seen in table below is the high rate of memory & cognitive issues reported
"The burden ...appears to be significant in the Danish population"
Graph, Fig 1--risk differences symptoms Denmark 6-12 mo post COVID

Anna Irene Vedel Sørensen et al. 2022. Post-acute symptoms, new onset diagnoses and health problems 6 to 12 months after SARS-CoV-2 infection: a nationwide questionnaire study in the adult Danish population. MedRxiv Feb 28, 2022.
doi: https://doi.org/10.1101/2022.02.27.22271328 https://medrxiv.org/content/10.1101/2022.02.27.22271328v1

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

Abstract
...Findings. Six to twelve months after the test date, the risks of 18 out of 21 physical symptoms were elevated among test-positives and one third (29.6%) of the test-positives experienced at least one physical post-acute symptom. The largest risk differences were observed for dysosmia (disorder, smell)(RD = 10.92%...), dysgeusia (distortion, taste)(RD=8.68%...), fatigue/exhaustion (RD=8.43%...), dyspnea (dyspnea) (RD=4.87%...) and reduced strength in arms/legs (RD=4.68%...). More than half (53.1%) of test-positives reported at least one of the following conditions: concentration difficulties (RD=28.34%...), memory issues (RD=27.25%...), sleep problems (RD=17.27%...), mental (RD=32.58%...) or physical exhaustion (RD=40.45%, ...), compared to 11.5% of test-negatives. New diagnoses of anxiety (RD=1.15%...) or depression (RD=1.00%...) were also more common among test-positives.

Interpretation. At the population-level, where the majority of test-positives (96.0%) were not hospitalized during acute infection, a considerable proportion experience post-acute symptoms and sequelae 6-12 months after infection.

The coronavirus invades cells in the penis and testicles of monkeys, researchers discover.
Roni Caryn Rabin | March 1, 2022

...The research demonstrated that the coronavirus infected the prostate, penis, testicles and surrounding blood vessels in three male rhesus macaques. The monkeys were examined with whole body scans specially designed to detect sites of infection.

Scientists — who expected to find the coronavirus in spots like the lungs but did not know where else they would find it — were somewhat surprised by the discovery.

“The signal that jumped out at us was the complete spread through the male genital tract,” said Thomas Hope, the paper’s senior author and a professor of cell and developmental biology at Northwestern University Feinberg School of Medicine in Chicago. “We had no idea we would find it there.”...

The researchers do not know whether the monkeys had symptoms corresponding to the viral infection of the male genital tract, such as low testosterone levels, low sperm counts, pain or sexual dysfunction, Dr. Hope said.

About 10 to 20 percent of men infected with the coronavirus have symptoms linked to male genital tract dysfunction, studies have reported.

Men infected with the virus are three to six times as likely as others to develop erectile dysfunction, believed to be an indicator of so-called long Covid.

Patients have also reported symptoms such as testicular pain, reduced sperm counts and reduced sperm quality, decreased fertility and hypogonadism, a condition in which the testes produce insufficient amounts of testosterone, leading to low sex drive, sexual dysfunction and reduced fertility...

https://www.nytimes.com/2022/03/01/health/covid-erectile-dysfunction.html
------------------------------------------------

Patrick J. Madden et al. 2022. An immunoPET probe to SARS-CoV-2 reveals early infection of the male genital tract in rhesus macaques. BioRxiv 28 Feb 2022. doi: https://doi.org/10.1101/2022.02.25.481974 https://biorxiv.org/content/10.1101/2022.02.25.481974v1

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

Diagram--virus location and signs/symptoms ( https://twitter.com/EricTopol/status/1499045263461150727/photo/1 )

I'm not sure what the "Whatever is driving mortality in Denmark should be raising eyebrows." comment means. Could someone explain?

Covid-19 seems to be on the decline here. It is certainly not over yet, but it is more of a nuisance than a danger.
(Over 20000 new cases today, so there's a lot of people staying at home for a week or so until they test negative again. But very very few get seriously ill.)

Here's the newest numbers on mortality, that I could find:
https://en.ssi.dk/news/news/2022/mortality-is-declining-in-denmark

>42 bnielsen: Looks like both Johns Hopkins and SSI data are from same time frame. I think SSI graph is also measuring excess mortality? I've seen another graph that had high mortality rates for Denmark compared to other countries, I think--will post if I can locate it again.

Below is Johns Hopkins data for Canada, showing uptick just as Ontario etc open up:

Malgorzata (Gosia) Gasperowicz (U Calgary) @GosiaGasperoPhD | 8:49 PM · Mar 1, 2022:
🙋‍♀️Excuse me, Canada?
Does anyone* pay attention? 👇
We are initiating the 6th wave right now. As always: it can be prevented; the spread can be stopped; & relative normalcy can be brought back.
*anyone = anyone with power to make decisions or influence decisions.
Graph--case rate Canada Nov 2021-Feb 2022 (https://twitter.com/GosiaGasperoPhD/status/1498837842025324551/photo/1)

Trust testing will take place in some fashion (drive-through?) to protect other shoppers from infection.

President Biden @POTUS | 9:47 PM · Mar 1, 2022
We’re launching the “Test to Treat” initiative, so people can get tested at a pharmacy and if they’re positive, receive antiviral pills on the spot at no cost.

Michael Mina (frmrly Harvard, proponent of DIY tests) @michaelmina_lab
This is a terrific advance
@POTUS making rapid testing a priority & linking it to treatment!
Now let’s make sure Test-to-Treat is not ONLY in pharmacies but can be done equitably at home.
1. @POTUS has already provided the at-home tests
2. Link those to telemedicine & fast Rx

The lesson from here - according to me :-) - is to get vaccinated - the booster shot is especially a good idea. And then BA-2 will make sure something like 50% of the population will get a relatively mild infection lasting a week or two for each affected person. You will definitely want to spread that out as much as possible, but I don't think you can avoid it. Having say 20% of all school teachers in a given area sick at the same time is no fun, but again I don't think it's possible to avoid it.

>44 margd: contd.

National COVID-⁠19 Preparedness Plan (10p)
White House | (March 1, 2022?)
https://www.whitehouse.gov/covidplan/

Only authorized monoclonal antibody therapy that adequately covers all sublineages of the Omicron variant (including BA.2) is the recently authorized LY-CoV1404 (bebtelovimab). Sotrovimab does not work well vs BA.2.

Eric Topol @EricTopol | 11:08 AM · Mar 3, 2022:
Just out Nature:
The monoclonal antibody Bebtelovimab works well against the Omicron sublineages BA.1 and BA.2 via lab assessment;
Sotrovimab not well vs BA.2

Iketani, S., Liu, L., Guo, Y. et al. Antibody evasion properties of SARS-CoV-2 Omicron sublineages. Nature (2022). https://doi.org/10.1038/s41586-022-04594-4 https://nature.com/articles/s41586-022-04594-4

Hong Kong

Eric Topol @EricTopol | 12:34 PM · Mar 4, 2022
Still vertical. Dreadful.
Graph--death rate Hong Kon Feb 2020-March 2022 ( https://twitter.com/EricTopol/status/1499800518452936705/photo/1 )
------------------------------------------------

Hong Kong’s covid death rate has surpassed the US’s worst day
Mary Hui | March 2, 2022

...A key driver of the soaring death rates in Hong Kong appears to be the severely under-vaccinated status among its elderly. According to data released by the government this past weekend, 91% of the city’s deaths (pdf) since the latest Omicron-driven wave took hold were of people who had not been fully vaccinated.

...For much of 2021, Hong Kong had almost no local Covid cases, in large part because the city kept the virus out with some of the world’s most stringent travel and quarantine restrictions. The government bet fully on a policy of “zero covid,” wagering that travel restrictions and contact tracing could quickly snuff out any local transmission chain. That worked on earlier variants—but the far more transmissible omicron foiled a strategy primarily premised on policing the city’s borders...

https://qz.com/2136230/hong-kongs-covid-death-rate-surpasses-uss-worst-day/

>45 bnielsen: New estimates say that about 2/3 of all adult Danes has had Covid since november 2021. But the number of Covid-patients in ICU is lower than during the first wave. The 2/3 number is based on tests on blood donors, so there's quite a lot of guesses involved.

How a nondescript box has been saving lives during the pandemic – and revealing the power of grassroots innovation
Douglas Hannah | March 3, 2022 3.55pm EST

https://theconversation.com/how-a-nondescript-box-has-been-saving-lives-during-t...

>49 bnielsen: Also Long-Covid seems to be minimal here with the Omicron variant. But that statistics won't be available any time soon.

Michael Mina @michaelmina_lab
1/ This is absolutely critical
Despite all we know of immunity from infection -we keep failing to account for it when discussing if Omicron is actually much less deadly or did it spread amidst a backdrop of widespread immunity from infection+vax

Hong Kong's Covid Death Rate Is Now One of the World's Highest
Linda Lew | February 28, 2022. Updated on March 1, 2022,
https://www.bloomberg.com/news/articles/2022-03-01/hong-kong-virus-deaths-among-...

2/ Why does it matter?? Because of exactly what is happening in Hong Kong, for example.
The mantra quickly became that Omicron is a “weak virus” so don’t worry too much. Which is crazy considering we still have massive deaths, particularly in US.

3/ That mantra of Omicron being much less deadly began in S Africa and was quickly adopted by the world.
However, as I’ve said before, Omicron spread on tail end of a massive global Delta wave. Providing protective pre existing immunity to a large fraction of the planet

4/ So once Omicron came around & mortality was lower, there was an incomplete accounting for role of immunity derived from natural infection. Largely bc too many scientists have, unfortunately, not even wanted to recognize that immunity from infection is powerfully beneficial

5/ This all, in my view, has led to a miscalculation of risk associated w variants like Omicron, such that when Omicron enters a place that did not have widespread build up of immunity, people are dying at very high rates.

6/ We can’t underestimate both the virulence and pathogenicity of new variants, nor the benefit of immunity derived through infection, nor the extent to which the human species has already been infected (not to mention vaccinated too!)

7/ I fear what we see in Hong Kong - v high mortality associated w Omicron - is partly a consequence of us seeing what we want to see - and not fully accounting for things like massive undocumented spread and immunity from infection that impacts estimates of risk w new variants

8/ Eventually the entire globe will have at least partial immunity to this virus + new variants, but amount of protection will vary by both vax and exposure history. When new variants occur and estimates of mortality are made, we must more fully consider the immune landscape

Eric Reinhart (MD anthropologist) @_Eric_Reinhart
The rush to dismiss discussion of immunity due to infxn for fear of abetting anti-vax discourses has had harmful unintended consequences. To effectively navigate public health, we need to better account for longer-term ramifications of our strategies for battling disinformation.

Michael Mina @michaelmina_lab
Exactly. And of course this isn’t to discount long term impacts nor to say that people should get infected just to get immunity for their future selves (hope that’s obvious). But we can’t undo the past… so we should at the least account, immunologically, for global transmission

Eric Topol @EricTopol | 11:01 AM · Mar 7, 2022
Just published nature
The impact of #Covid on the brain: the 1st longitudinal imaging study before and after infection, with controls
https://nature.com/articles/s41586-022-04569-5

Reduction of grey matter, brain size, cognitive decline
Image ( https://twitter.com/EricTopol/status/1500864330354475008/photo/1 )
---------------------------------------------------------

Gwenaëlle Douaud et al. 2022. SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Nature (7 March 2022) https://nature.com/articles/s41586-022-04569-5

Unedited manuscript g.

Abstract
...401 cases who tested positive for infection with SARS-CoV-2 between their two scans, with 141 days on average separating their diagnosis and second scan... The availability of pre-infection imaging data reduces the likelihood of pre-existing risk factors being misinterpreted as disease effects. We identified significant longitudinal effects when comparing the two groups, including: (i) greater reduction in grey matter thickness and tissue-contrast in the orbitofrontal cortex and parahippocampal gyrus, (ii) greater changes in markers of tissue damage in regions functionally-connected to the primary olfactory cortex, and (iii) greater reduction in global brain size. The infected participants also showed on average larger cognitive decline between the two timepoints. Importantly, these imaging and cognitive longitudinal effects were still seen after excluding the 15 cases who had been hospitalised. These mainly limbic brain imaging results may be the in vivo hallmarks of a degenerative spread of the disease via olfactory pathways, of neuroinflammatory events, or of the loss of sensory input due to anosmia. Whether this deleterious impact can be partially reversed, or whether these effects will persist in the long term, remains to be investigated with additional follow up.

See Table of Contents for chapters devoted to Testing, Worker Safety, and everything in between:

Prof. Akiko Iwasaki (Yale) @VirusesImmunity | 1:05 PM · Mar 7, 2022:
After over two years of COVID pandemic, we need a vision for how to navigate the #NextNormal.
Honored to contribute to this roadmap led by @ZekeEmanuel with many colleagues - including @hmkyale @ktkadakia @PutrinoLab on #LongCOVID, with patients’ input...

Getting to and Sustaining the Next Normal: A Roadmap for Living with COVID
136 p
https://www.covidroadmap.org/

Eric Topol @EricTopol | 1:36 PM · Mar 7, 2022:
A 1-year prospective, multi-center study of #LongCovid moderate-severe symptoms in adults, teens, and children with controls: persistence in adults and in teen girls, not in children less than age 14

Tables-persistence of moderate/severe symptoms by age and gender ( https://twitter.com/EricTopol/status/1500903215319060481/photo/1 )

Anneke Haddad et al. 2022. Long COVID Symptoms in a Prospective Cohort of Exposed and Infected Children and Adolescents and Their Parents One Year After SARS-CoV-2 Infection. The Lancet Preprint 22 Pages Posted: 3 Mar 2022. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4048831

Abstract
...Findings: The prevalence of moderate or severe persistent symptoms was significantly higher elevated in infected than in exposed women (36.4% vs 14.2%), infected men (22.9% vs 10.3%) and infected adolescent girls (32.1% vs 8.9%). However, moderate or severe persistent symptoms were not more common in infected adolescent boys aged 14-18 or in children younger than 14 years than in their exposed counterparts. The number of persistent symptoms reported by individuals was associated with the number of persistent symptoms reported by their household members.

Interpretation: In this well-controlled, multi-centre study, infected men, women and adolescent girls were at increased risk of negative outcomes 11-12 months after SARS-CoV-2 infection. Amongst non-infected adults, prevalence of negative outcomes was also high. Prolonged symptoms tended to cluster within families, suggesting family-level interventions for long COVID could prove useful.

Genetic study reveals causal link between blood type and COVID severity
Rich Haridy | March 06, 2022

...One of the key findings was a causal association between COVID-19 severity and an enzyme known as ABO, which determines a person’s blood type.

Christopher Hübel from King’s College London said the new research did not interrogate the relationship between specific blood types and COVID-19 severity. However, he does point out the ABO findings do validate prior observational studies linking type A blood with an increased COVID-19 risk.

...Of course, there are a number of risk factors beyond blood type known to play a role in COVID-19 severity, from age to pre-existing illness. So these findings should not be a cause for concern to those with type A blood.

Instead, as co-last author on the study Gerome Breen explains, these findings help researchers investigate novel therapeutic pathways to help treat COVID-19. For example, several blood proteins were identified in the study as causally linked to a decreased risk of severe disease.

These proteins, known as adhesion molecules, play a role in the interactions between immune cells and blood vessels. The researchers hypothesize these adhesion molecules may be helping moderate the severity of late-stage COVID-19 and it may be possible to turn this discovery into a therapy to prevent sick patients deteriorating in hospital....

https://newatlas.com/health-wellbeing/causal-link-blood-type-covid19-severity-ge...
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Alish B. Palmos et al. 2022. Proteome-wide Mendelian randomization identifies causal links between blood proteins and severe COVID-19. PLOS x. Published: March 3, 2022 . https://doi.org/10.1371/journal.pgen.1010042

Scientists find 16 'Covid genes' that raise your risk of falling critically ill and having just ONE could be difference between a runny nose or trip to hospital
John Ely Senior Health Reporter For Mailonline | 7 March 2022:

UK scientists analysed the genes of 7,500 Brits who were critically ill with Covid
The study found 16 genetic variants which made people more likely to need care
These genes govern how well the body can fight Covid and deal with symptoms
Scientists hope new treatments could one day be developed to help patients

...some genes were linked to a doubling of the risk of severe illness from Covid...

https://www.dailymail.co.uk/news/article-10585787/Scientists-16-Covid-genes-rais...
---------------------------------------------------------------

Athanasios Kousathanas et al. 2022. Whole genome sequencing reveals host factors underlying critical Covid-19. Nature (7 March 2022) https://www.dailymail.co.uk/news/article-10585787/Scientists-16-Covid-genes-rais...

Unedited version of manuscript

(U.S.)
ORDER SECOND TEST KITS NOW—starting today, everyone in US can order a second set of 4 #COVID19 tests. Hopefully no glitches with apartment or condominium addresses this time. ➡️Also don’t forget to report in your positive tests if your state/city allows.

https://special.usps.com/testkits

- Eric Feigl-Ding 💙💛@DrEricDing🧪 | 2:29 PM · Mar 7, 2022

US: Don't ditch those masks yet, folks, get vaxxed if you aren't already, and order second set free testkits... https://special.usps.com/testkits
The US has a little more natural immunity + higher vaxx rate (esp srs), and more effective vaxx(?) than Hong Kong, but could be tough sledding for un(der)vaxxed and immune compromised...

Eric Feigl-Ding 💙💛@DrEricDing | 1:22 AM · Mar 8, 2022:
https://twitter.com/DrEricDing/status/1501080810694365185
📍Not good—the #BA2 subvariant is doubling and tripling very quickly.
New York State is reporting 7.7% BA2, up from 2.3% two weeks prior.
Regionally, NY/NJ/PR/VI up to 12.4% BA2. And these data are 2 weeks behind!
Epidemiologists regard this as Omicron 2.0

Excerpt of text w 7.7% and 12.4% data ( https://twitter.com/DrEricDing/status/1501080810694365185/photo/1 )

COVID-19 Variant Data
Monitoring the Prevalence of SARS-CoV-2 Variants
https://coronavirus.health.ny.gov/covid-19-variant-data

2) Nationally, #Ba2 is now 8.3%. But this data is from the final week of February— the CDC doesn’t release numbers every week — often when they just feel like it. This graph is log-scale ➡️ which means #BA2’s linear surge is exponential.

Graph by @DrWilliamKu using CDC data.
% Delta & 3 strains Omicron, US, May 2021-Feb 2022 ( https://twitter.com/DrEricDing/status/1501082001561899013/photo/1 )

...England ( https://twitter.com/DrEricDing/status/1501083805490331648 )
...Hong Kong ( https://twitter.com/DrEricDing/status/1501084315135926272 )

Scott Gottlieb, MD (frmr FDA cmr) @ScottGottliebMD | 8:48 AM · Mar 8, 2022
New study finds risk of a second person in household getting Covid when one person had infection was
25.1% when variant of initial index case was Omicron,
19.4% when it was Delta,
17.9% when it was nonclassified.
Was higher for unvaxxed and those over 30

Text excerpt ( https://twitter.com/ScottGottliebMD/status/1501193105516765186/photo/1 )
Table secondary household attack by variant, age, gender, vaxx status etc.
https://twitter.com/ScottGottliebMD/status/1501193105516765186/photo/2

Silje B. Jørgensen et al. 2022. Secondary Attack Rates for Omicron and Delta Variants of SARS-CoV-2 in Norwegian Households (Research Letter) JAMA. Published online March 7, 2022. doi:10.1001/jama.2022.3780 https://jamanetwork.com/journals/jama/fullarticle/2789920

How ventilation, filtration, and humidity may prevent coronavirus transmission
Corrie Pelc | March 2, 2022

Researchers from the University of Oregon measured the amount of virus particles that 11 students with COVID-19 released during certain activities.
The research team found higher ventilation, filtration, and humidity levels decreased the amount of virus particles in the air.
Scientists believe their findings can assist building operators with creating safer indoor environments...

https://www.medicalnewstoday.com/articles/how-ventilation-filtration-and-humidit...
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Hooman Parhizkar et al. 2022. Quantifying Environmental Mitigation of Aerosol Viral Load in a Controlled Chamber With Participants Diagnosed With Coronavirus Disease 2019. Clinical Infectious Diseases, ciac006, Published: 06 January 2022. https://doi.org/10.1093/cid/ciac006 https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac006/6498295

Abstract
...Methods
We recruited 11 participants diagnosed with COVID-19 to individually occupy a controlled chamber and conduct specified physical activities under a range of environmental conditions; we collected human and environmental samples over a period of 3 days for each participant.

Results
Here we show that increased viral load, measured by lower RNA cycle threshold (CT) values, in nasal samples is associated with higher viral loads in environmental aerosols and on surfaces captured in both the near field (1.2 m) and far field (3.5 m). We also found that aerosol viral load in far field is correlated with the number of particles within the range of 1–2.5 µm. Furthermore, we found that increased ventilation and filtration significantly reduced aerosol and surface viral loads, while higher relative humidity resulted in lower aerosol and higher surface viral load, consistent with an increased rate of particle deposition at higher relative humidity. Data from near field aerosol trials with high expiratory activities suggest that respiratory particles of smaller sizes (0.3–1 µm) best characterize the variance of near field aerosol viral load.

Conclusions
Our findings indicate that building operation practices such as ventilation, filtration, and humidification substantially reduce the environmental aerosol viral load and therefore inhalation dose, and should be prioritized to improve building health and safety.

...Discussion
In summary, we found the following statistically significant relationships:

Positive relationships between viral load (RNA) found in human specimens and paired aerosol and surface samples at ~0 ACH and ambient conditions for sitting and standing trials (routine trials) as well as trials with high expiratory activities (coughing, speaking, and speaking loudly).

Positive relationship between viral load in near field aerosols captured during periods of higher expiratory activity and near field particles of 0.3–1 µm, 1–2.5 µm, and 10–25 µm in size, but no statistical significance for 2.5–10 µm particles.

Increased CO2 concentrations and particle counts in the range of 1–5 µm measured in the near field as compared to the far field for routine trials.

Positive relationship between aerosol viral load in the far field and the number of corresponding far field particles detected in the range of 1–2.5 µm.

Inverse relationships between viral load found in aerosols and degree of ventilation, as well as in-room filtration.

Relationships between viral load and degree of relative humidity; whereby higher RH is associated with lower viral load in aerosol samples and higher viral load in select surface samples, consistent with increased particle deposition on surfaces.

Immunity + improved treatments + less virulent SARS-CoV-2 variant = less fatality risk than flu (individual risk, England)
Don't think long COVID and hospital capacity taken into account? Still!

Eric Topol (Scripps) @EricTopol | 11:13 PM · Mar 9, 2022:
This represents phenomenal progress, folks.
The immunity wall in England has now led to Covid carrying (slightly) *less* fatality risk than seasonal flu

Graph fatality ratio flu v COVID England July 2020-Jan 2022
( https://twitter.com/EricTopol/status/1501773203261165570/photo/1 )

That's even the case for people of advanced age
Graph ( https://twitter.com/EricTopol/status/1501773208323706881/photo/1 )

Consider that Covid started with a ~18-fold increased mortality compared with influenza for people age 60+
Graph ( https://twitter.com/EricTopol/status/1501773213990273024/photo/1 )

Financial Times: Vaccines and Omicron mean Covid now less deadly than flu in England (Paywall)
https://ft.com/content/e26c93a0-90e7-4dec-a796-3e25e94bc59b

Eric Topol @EricTopol | 4:52 PM · Mar 10, 2022:
Reduction of 2° Covid transmission via universal masking (vs optional) in schools among 1.1+ million student students and 150,000+ staff attending 61 K–12 districts across 9 states

Table- primary secondary infections w universal, partial masking schools
https://twitter.com/EricTopol/status/1502039598456664067/photo/1

Angelique E. Boutzoukas et al. 2022. School Masking Policies and Secondary SARS-CoV-2 Transmission. Pediatrics (March 9, 2022)
https://doi.org/10.1542/peds.2022-056687 https://publications.aap.org/pediatrics/article/doi/10.1542/peds.2022-056687/185...

(Abstract)
...RESULTS
1,112,899 students and 157,069 staff attended 61 K–12 districts across 9 states that met inclusion criteria. The districts reported 40,601 primary and 3,085 secondary infections. Six districts had optional masking policies, 9 had partial masking policies, and 46 had universal masking. Districts that optionally masked throughout the study period had 3.6 times the rate of secondary transmission as universally masked districts. For every 100 community-acquired cases, universally masked districts had 7.3 predicted secondary infections, while optionally masked districts had 26.4.

CONCLUSIONS
Secondary transmission across the cohort was modest (fewer than 10% of total infections) and universal masking was associated with reduced secondary transmission compared to optional masking.

Ayurvedic compound may serve as ‘starting point’ for COVID-19 treatment
Erika Watts | March 10, 2022

Researchers in Colorado and India are researching the bark of the neem tree as a way to treat COVID-19.
They learned that an extract from the tree bark, Azadirachta indica, may have antiviral benefits and help reduce symptoms in people with a SARS-CoV-2 infection.
The scientists believe Azadirachta indica may act as a pan-antiviral, capable of treating future emerging variants of SARS-CoV-2.

A preclinical study, which appears in the journal Virology, examines how the extract from the bark of Azadirachta indica affects human lung cells and mice with a SARS-CoV-2 infection...

https://www.medicalnewstoday.com/articles/ayurvedic-compound-may-serve-as-starti...
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LuckySarkara et al. 2022, Azadirachta indica A. Juss bark extract and its Nimbin isomers restrict β-coronaviral infection and replication. Virology Volume 569, April 2022, Pages 13-28 https://doi.org/10.1016/j.virol.2022.01.002 https://www.sciencedirect.com/science/article/pii/S0042682222000022

Highlights
• What is already known:

i. Azadirachta indica bark extract restricts HSV-1 and murine-β-Coronavirus replication, spread, and fusion in vitro.
ii. m-CoV-MHV-A59/RSA59 when preincubated with Azadirachta indica bark extract (NBE) restricts viral infectivity in vivo.

• What this study adds:

i. NBE significantly restricts newly emerged human β-Coronavirus SARS-CoV-2 infection and replication in vitro.
ii. Nimbin/Epinimbin significantly inhibits m-CoV-infectivity, cell-to-cell fusion, spread, and replication in vitro like NBE.

• Clinical significance:

i. NBE/it's isolated Nimbin/Epinimbin isomers significantly reduces coronaviral-induced clinical outcome, acute and chronic inflammatory pathology.
ii. The Triterpenoids compounds of NBE inhibit SARS-CoV-2, HSV-1 and m-CoV infectivity, suggesting pan-β-anti-coronaviral/pan-antivirals.

Abstract
Emerging mutations in the SARS-CoV-2 genome pose a challenge for vaccine development and antiviral therapy. The antiviral efficacy of Azadirachta indica bark extract (NBE) was assessed against SARS-CoV-2 and m-CoV-RSA59 infection. Effects of in vivo intranasal or oral NBE administration on viral load, inflammatory response, and histopathological changes were assessed in m-CoV-RSA59-infection. NBE administered inhibits SARS-CoV-2 and m-CoV-RSA59 infection and replication in vitro, reducing Envelope and Nucleocapsid gene expression. NBE ameliorates neuroinflammation and hepatitis in vivo by restricting viral replication and spread. Isolated fractions of NBE enriched in Nimbin isomers shows potent inhibition of m-CoV-RSA59 infection in vitro. In silico studies revealed that NBE could target Spike and RdRp of m-CoV and SARS-CoV-2 with high affinity. NBE has a triterpenoids origin that may allow them to competitively target panoply of viral proteins to inhibit mouse and different strains of human coronavirus infections, suggesting its potential as an antiviral against pan-β-Coronaviruses.

Study joins search for variant-proof approach to SARS-CoV-2 treatment
Robby Berman | March 10, 2022

Rapidly mutating spike proteins in SARS-CoV-2 threaten to thwart mRNA vaccines and other COVID-19 medications.
Researchers have identified some other targets within the virus and are seeking existing drugs that might be of use in disrupting them.
A study led by Penn State researchers that uses a new screening methodology proposes a list of existing drugs worthy of further investigation.

https://www.medicalnewstoday.com/articles/study-joins-search-for-variant-proof-a...
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Anoop Narayanan et al. 2022. Identification of SARS-CoV-2 inhibitors targeting Mpro and PLpro using in-cell-protease assay.
Communications Biology volume 5, Article number: 169 (25 Feb 2022)

Eric Topol (Scripps) @EricTopol | 10:58 AM · Mar 12, 2022:

The next wave in Europe has begun
Graph-daily confirmed case rate European countries, March 2020-March 2022
https://twitter.com/EricTopol/status/1502675479077130240/photo/1

https://www.mediaite.com/news/new-poll-cnn-and-msnbc-viewers-got-covid-much-less...
NEW POLL: CNN and MSNBC Viewers Got Covid Much Less Than People Who Watch Fox News — By a Whopping 17 Points

***
It appears that the comments/rants made by FOX News hosts and guests actually presented a danger to the lives of its viewers. Is this really a surprise???

Countries that relied on public health measures challenged by omicron variant. China is worrisome example, especially since one of its vaccines at least is less effective with the new variant.

China Focus: China takes strict, swift measures to stem new COVID-19 infections
Source: Xinhua
Editor: huaxia
2022-03-13 17:10:15

BEIJING, March 13 (Xinhua) -- China is taking strict and swift measures to stem new COVID-19 infections that have emerged in multiple regions recently.

The Chinese mainland on Saturday reported 1,807 locally transmitted COVID-19 cases in 19 provincial-level regions, the National Health Commission (NHC) said Sunday.

Chinese Vice Premier Sun Chunlan on Saturday urged regions experiencing severe epidemic outbreaks to clear COVID-19 cases among the general public in the shortest time possible.

Efforts should be made to expand the coverage of nucleic acid testing, accelerate epidemiological screening and patient transportation and isolation, and apply quarantine measures in a strict way, said Sun.

As part of the swift COVID-19 responses, China has added antigen detection as an option for COVID-19 testing among the public, in efforts to boost the early discovery of COVID-19 cases, the NHC said Friday.

...Shanghai on Saturday required citizens not to leave the city if not necessary and those who do must hold a certificate for a negative nucleic acid test results taken 48 hours before departure.

In the first two months of 2022, the megacity, with a population of nearly 25 million, has logged 1,243 confirmed COVID-19 cases arriving from outside the Chinese mainland, accounting for about 38 percent of total such cases on the mainland. The number is also roughly equivalent to 80 percent of Shanghai's total imported cases last year.

The city has required primary and secondary schools to switch to online classes and temporarily closed kindergartens and nurseries from Saturday after 11 locally transmitted COVID-19 cases and 32 imported cases were reported Thursday.

In northeast China's Jilin Province, which reported 1,412 local cases Saturday, local authorities have conducted multiple rounds of mass nucleic acid testing in face of the Omicron variant, which spreads easily and is hard to detect.

The city of Jilin conducted six rounds of mass nucleic acid testing and the Jiutai district in the provincial capital Changchun completed three rounds, while the rest of the city conducted two rounds...

In face of the surging cases, the city of Changchun is building a makeshift hospital at an exhibition center that can provide more than 1,500 beds. In the city of Jilin, local authorities have built three makeshift hospitals, which can offer over 1,200 beds. The fourth one with over 2,000 beds is under construction...

http://www.xinhuanet.com/english/20220313/37bead17cc3841a391838deca0cac8e2/c.htm...

Countries with immunity from previous infections + vaxx are also seeing rise, e.g. England:

Eric Feigl-Ding (epidemiologist) @DrEricDing | 4:44 PM · Mar 10, 2022
CASES SPIKING UP ⬆️52.9% in one week in England 🏴󠁧󠁢󠁥󠁮󠁧󠁿—
Clear trend now there is new wave happening, despite 98% with antibodies.
Hospitalizations also across 🏴󠁧󠁢󠁥󠁮󠁧󠁿. #BA2 subvariant 50%+ too.

10-Mar—371,662
09-Mar—346k
08-Mar—323k
07-Mar—300k
…
04-Mar—256k
03-Mar—243,057
...
Graph-positive tests Oct 2021-March 2022 England ( https://twitter.com/DrEricDing/status/1502037691126497283/photo/1 )

Pfizer's COVID vaccine less effective against Omicron in younger children, new study suggests
Alexander Tin | March 11, 2022

...Figures published late Thursday by the CDC from its COVID-NET hospital surveillance* show that rates of COVID-19 hospitalizations were lower through the end of January among vaccinated Americans of any age, compared to the unvaccinated.

However, the smallest gaps were among children ages 5 to 17 years old. Hospitalization rates were six times higher in unvaccinated adults compared to the vaccinated. Rates were three times higher in unvaccinated 5- to 11-year-olds and two times higher in unvaccinated 12- to 17-year-olds...

...The CDC also published a new study Friday in its Morbidity and Mortality Weekly Report** estimating that two shots of the Pfizer vaccine was 31% effective against Omicron variant infections in children ages 5 to 11.

Vaccine effectiveness among adolescents ages 12 to 15 against Omicron was virtually double that, at 59%, though the study's authors cautioned that "wide and overlapping" statistical uncertainty around the two figures suggested that they "might not be significantly different." ....

https://www.cbsnews.com/news/covid-vaccine-less-effective-against-omicron-infect...
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* Graph- Rates of COVID-19-Associated Hospitalizations by Vaccination Status in Children Ages 5–11 Years, January 2022–January 2022. Rates of laboratory-confirmed COVID-19 hospitalizations by vaccination status. https://covid.cdc.gov/covid-data-tracker/#covidnet-hospitalizations-vaccination
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** Fowlkes AL, Yoon SK, Lutrick K, et al. Effectiveness of 2-Dose BNT162b2 (Pfizer BioNTech) mRNA Vaccine in Preventing SARS-CoV-2 Infection Among Children Aged 5–11 Years and Adolescents Aged 12–15 Years — PROTECT Cohort, July 2021–February 2022. MMWR Morb Mortal Wkly Rep. ePub: 11 March 2022. DOI: http://dx.doi.org/10.15585/mmwr.mm7111e1 https://www.cdc.gov/mmwr/volumes/71/wr/mm7111e1.htm

...Children and adolescents aged 5–15 years were tested for SARS-CoV-2 weekly, irrespective of symptoms, during July 2021–February 2022. Approximately one half of Omicron infections in unvaccinated children and adolescents were asymptomatic. Two doses of Pfizer-BioNTech COVID-19 vaccine reduced the risk of Omicron infection by 31% among children aged 5–11 years and by 59% among persons aged 12–15 years.

All eligible children and adolescents should remain up to date with recommended COVID-19 vaccinations...

She's 25!

Hailey Bieber Hospitalized with Brain Issues Calls It 'Stroke Like' Blood Clot
Exclusive | 3/12/2022

HB explains that this happened on Thursday morning, at which point she started having "stroke like symptoms," and was then taken to the hospital where docs found a small blood clot in her brain ... causing a lack of oxygen...a brain condition that doctors think may be COVID-related ...

...Hailey was admitted to a Palm Springs area hospital a few days ago after suffering a "medical emergency." We're told it affected the way she moved, and the symptoms are typical for much older people. Hailey is 25...

https://www.tmz.com/2022/03/12/hailey-bieber-hospitalized-brain-covid/?adid=soci...

Eric Feigl-Ding @DrEricDing | 5:52 PM · Mar 14, 2022:
SEWER SIGNALS—there is a sharp reversal in wastewater #SARSCoV2–many now rising across the US / plateauing and no longer falling, says CDC data. This parallels surge in Europe, just a few weeks behind. A #BA2 wave is coming—how soon/big is the question

Map-change virus in US sewer water, March 1-10 ( https://twitter.com/DrEricDing/status/1503469939797151753/photo/1 )
https://www.bloomberg.com/news/articles/2022-03-14/are-covid-cases-going-back-up...

Peter V. Markov et al. 2022. Antigenic evolution will lead to new SARS-CoV-2 variants with unpredictable severity. Nature Reviews Microbiology (14 March 2022) https://www.nature.com/articles/s41579-022-00722-z

The comparatively milder infections with the Omicron variant and higher levels of population immunity have raised hopes for a weakening of the pandemic. We argue that the lower severity of Omicron is a coincidence and that ongoing rapid antigenic evolution is likely to produce new variants that may escape immunity and be more severe...

John Burn-Murdoch (Financial Times) @jburnmurdoch | 1:19 PM · Mar 14, 2022
NEW: I’m not sure people appreciate quite how bad the Covid situation is in Hong Kong, nor what might be around the corner.
First, an astonishing chart.
After keeping Covid at bay for two years, Omicron has hit HK and New Zealand, but the outcomes could not be more different.
Graph-case fatality rate, HK v NZ, Feb-March 2022 ( https://twitter.com/jburnmurdoch/status/1503420660869214213/photo/1 )
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Eric Feigl-Ding @DrEricDing | Eric Feigl-Ding | 3:32 AM · Mar 14, 2022:
7) This is why building 6000-bed isolation hospitals in just 6 days is an immediate priority for China. It knows what is coming. China last did this only in Wuhan in Jan 2020 because they know it is that bad and serious again.

How serious is China about what is happening in Jilin? It has begun building a 6000-bed hospital isolation center… with work crews working 24 hours around the clock— scheduled completion is in 6 days from groundbreaking. Live camera of construction:
https://weibo.com/l/wblive/p/show/1022:2321324746875155906656
Photo--construction ( https://twitter.com/DrEricDing/status/1503272773745094661/photo/1 )
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Eric Feigl-Ding @DrEricDing | 2:01 PM · Mar 14, 2022
6) I want folks to pay attention to also the BOOSTER rates, since you need boosters in order to fully protect against #BA2 (or BA1 old #Omicron). China has just under 40% boosted, which while more than HK’s 28%, far lags many other EU countries. And again, a lot of weaker shots.
Graph-booster rate by country ( https://twitter.com/DrEricDing/status/1503431234114007040/photo/1 )

FACT SHEET: Biden Administration Launches Effort to Improve Ventilation and Reduce the Spread of COVID-⁠19 in Buildings
White House | March 17, 2022

...The Clean Air in Buildings Challenge is a call to action for leaders and building owners and operators of all types to assess their indoor air quality and make ventilation and air filtration improvements to help keep occupants safe. As part of the Challenge, today, the Environmental Protection Agency (EPA) published a best practices guide for improving indoor air quality and reducing the risk of spreading dangerous airborne particles.* This guide – developed in collaboration with the Department of Energy, Centers for Disease Control and Prevention, and other federal agencies – contains a set of clear recommendations organized into four groups:

Create a clean indoor air action plan that assesses indoor air quality, plans for upgrades and improvements, and includes HVAC inspections and maintenance.
Optimize fresh air ventilation by bringing in and circulating clean outdoor air indoors.
Enhance air filtration and cleaning using the central HVAC system and in-room air cleaning devices.
Engage the building community by communicating with building occupants to increase awareness, commitment, and participation.

Under each of these recommendation areas, EPA’s best practices guide lays out clear-cut actions building owners and operators can implement. The best practices guide is designed to serve as a menu of improvements to choose from. The guide includes quick steps that all organizations can take right away as a starting place, as well as resources to help plan for longer-term investments and improvements.

The Biden Administration and Congress have provided hundreds of billions of dollars in federal funds that can be used in schools, public buildings, and other settings to improve indoor air quality. The American Rescue Plan provided $350 billion for state and local governments, as well as $122 billion for schools, that can be used to support making ventilation and filtration upgrades. These American Rescue Plan dollars are being put to work in communities around the country in improving Heating, Ventilation, and Air Conditioning (HVAC) systems. Funding within the State and Local Fiscal Recovery Fund program and the Elementary and Secondary School Education Relief program can be spent on inspection, testing, and maintenance of current ventilation systems; purchasing portable air filtration units, with HEPA air filters; purchasing MERV-13 (or higher) filters for HVAC system and air conditioners; purchasing fans; repairing windows and/or doors; servicing, upgrading, or replacing HVAC systems consistent with industry standards; and more.

As detailed in the National COVID-19 Preparedness Plan, the Administration will continue to advance indoor air quality in buildings in additional ways, including:

Supporting state, local, and Tribal governments as well as school districts to make ventilation improvements and upgrades using American Rescue Plan (ARP) and Bipartisan Infrastructure Law funds. The Administration will work closely with public sector partners like schools to provide guidance and technical assistance to make these improvements and connect them to agency resources on indoor air quality.
Building public awareness around ventilation and filtration improvements to reduce disease spread in buildings. The Administration will build public awareness and communicate with the public on how ventilation and good indoor air quality are key factors in keeping Americans safe while inside buildings. The Administration will launch efforts to explain what good ventilation and air filtration look like as an important component of helping to reduce disease spread, and how buildings of any kind can pursue improvements to their ventilation and air filtration strategies.
Highlighting actions taken by buildings to achieve clean, healthy air quality through a recognition program. While the Administration invites all buildings to take actions from the Clean Air in Buildings Challenge, the Administration will also foster ways to recognize steps taken by buildings to improve indoor air quality and protect their communities. Similar to how programs like LEED, Fitwel, and WELL recognize buildings for their environmental and health impacts, this new effort between the federal government and external experts will develop ways to recognize steps taken by building owners for the health and safety of their communities and their achievements in improving air filtration and ventilation systems to protect and promote public health.
Catalyzing science and technology innovation to reduce indoor disease transmission. The Office of Science and Technology Policy (OSTP), in coordination with other partners through the Pandemic Innovation Task Force, is identifying opportunities to drive innovation and implementation of technologies to support clean indoor air in buildings and reduce disease transmission. OSTP will also host a series of public engagements to provide the latest science, tools, and best practices on improving indoor air quality.

https://www.whitehouse.gov/briefing-room/statements-releases/2022/03/17/fact-she...
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* Clean Air in Buildings Challenge
Guidance to Help Building Owners and Operators Improve Indoor Air Quality and Protect Public Health
EPA | March 17, 2022
https://www.epa.gov/indoor-air-quality-iaq/clean-air-buildings-challenge

Scientists explore potential connection between Covid and diabetes
Emerging evidence shows that the coronavirus can attack insulin-producing cells in the pancreas.
AP | March 16, 2022

A Centers for Disease Control and Prevention report* looked at two large U.S. insurance databases that included new diabetes cases from March 2020 through June 2021. Diabetes was substantially more common in kids who’d had Covid-19. The report didn’t distinguish between Type 1, which typically starts in childhood, and Type 2, the kind tied to obesity.

Rates of both types of diabetes have risen in U.S. kids in recent years, but reports from Europe and some U.S. hospitals suggest the pace may have accelerated during the pandemic.

“I think we’re all a little worried,” said Dr. Inas Thomas, a specialist at the University of Michigan’s Mott Children’s Hospital.

Her hospital has seen a 30 percent increase in Type 1, compared with pre-pandemic years, Thomas said. It is not known how many had Covid-19 at some point, but the timing raises concerns that there could be a connection, she said.

https://www.nbcnews.com/health/health-news/diabetes-covid-scientists-explore-pot...
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Barrett CE, Koyama AK, Alvarez P, et al. Risk for Newly Diagnosed Diabetes 30+ Days After SARS-CoV-2 Infection Among Persons Aged 18 (or fewer) Years — United States, March 1, 2020–June 28, 2021. MMWR Morb Mortal Wkly Rep 2022;71:59–65. DOI: http://dx.doi.org/10.15585/mmwr.mm7102e2external icon https://www.cdc.gov/mmwr/volumes/71/wr/mm7102e2.htm

Summary
...Persons aged 18 (or fewer) years with COVID-19 were more likely to receive a new diabetes diagnosis 30+ days after infection than were those without COVID-19 and those with prepandemic acute respiratory infections. Non–SARS-CoV-2 respiratory infection was not associated with an increased risk for diabetes.

...The increased diabetes risk among persons aged 18 (or fewer) years following COVID-19 highlights the importance of COVID-19 prevention strategies in this age group, including vaccination for all eligible persons and chronic disease prevention and treatment...
__________________________________________________

Eric Topol @EricTopol | 6:04 PM · Mar 16, 2022:
The association of predominantly mild Covid and subsequent Type 2 diabetes

Matched pair analysis of 35,000+ people who develop diabetes vs controls with acute URI, ~28% increase
Graph-diabetes incidence over 12 months after infection w COVID v upper respiratory tract infection ( https://twitter.com/EricTopol/status/1504217090005241856/photo/1 )


Wolfgang Rathmann et al. 2022. Incidence of newly diagnosed diabetes after Covid-19 (Short Communication). Diabetologia (16 March 2022) https://link.springer.com/article/10.1007/s00125-022-05670-0

Abstract
...Results
There were 35,865 individuals with documented Covid-19 in the study period. After propensity score matching, demographic and clinical characteristics were similar in 35,865 AURI (acute upper respiratory tract infections) controls (mean age 43 years; 46% female). Individuals with Covid-19 showed an increased type 2 diabetes incidence compared with AURI (15.8 vs 12.3 per 1000 person-years). Using marginal models to account for correlation of observations within matched pairs, an IRR (incidence rate ratios) for type 2 diabetes of 1.28 (95% CI 1.05, 1.57) was estimated. The IRR was not increased for other forms of diabetes.

Conclusions/interpretation
Covid-19 confers an increased risk for type 2 diabetes. If confirmed, these results support the active monitoring of glucose dysregulation after recovery from mild forms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Staff at teaching hospital in Michigan where son's employed IS overworked, sounds like, but he is given N95 for routine patients and (respirator?) for potentially infected patients. Vaxx was condition of employment. Rooms, if not elevators, are well-ventilated according to his CO2 monitor. Haven't seen COVID numbers for hospital, but it seems to be doing its best for its vulnerable patients?

Teaching hospital in Ontario--an older one where I was born-- seemed to suffer a number of omicron outbreaks in hospital, but hospital and public health were on top of them right away. Ten years ago an elderly uncle died there of MRSA after a minor surgical procedure, and I was somewhat appalled by the palm-touch door-openers into ICU (where he was after his two surgeries attempting to suction bacteria out of his shoulder joint), though we were freshly gowned and masked each time we later entered his room.

Nowhere is safe: Record number of patients contracted Covid in the hospital in January
Rachael Levy and Allan James Vestal | 02/19/2022

...During the January Covid-19 surge a year ago, hospitals reported around 2,000 patients each week on average had contracted Covid during their stay, compared to roughly 3,000 this year.

The total number of people who contract Covid-19 while in the hospital remains unclear because these figures only count patients who were in the hospital at least 14 consecutive days and don’t account for people who test positive after leaving. The government’s figures are likely a fraction of the total.

Hospital-acquired infections have long been one of the most serious risks for patients, especially those who stay for weeks or months. But the recent data show that more than two years into the pandemic, hospitals still have a long way to go to prevent transmission within their walls.

Michael Osterholm, an epidemiologist at the University of Minnesota...said hospitals aren’t doing enough to prevent transmission, allowing visitors and staff to wear surgical masks rather than more protective N-95 masks. The Centers for Disease Control and Prevention hasn’t recommended that all health care workers and visitors wear N-95s at all times.

...One potential factor, several public health experts said, is the CDC’s decision in December to allow health workers who had tested positive for Covid to return without first isolating or testing to ensure they were no longer infectious.

...U.S. health officials are considering changing how hospitals report the number of patients who contract Covid-19 in-house, POLITICO has reported, a change that could set off concerns from hospital lobbyists and associations that say such transmission is rare....

https://www.politico.com/news/2022/02/19/covid-hospitals-data-00010283

Covid-19 Can Cause Severe Croup In Young Children Says New Study
Victoria Forster (PhD cancer researcher)| March 16, 2022

Although young children with Covid-19 generally experience mild illness, the omicron coronavirus variant has led to more children being hospitalized with Covid-19 in recent months at a rate five times higher than with the Delta variant.

Now a new paper* from researchers at Boston Children’s Hospital has described 75 cases of croup in children with Covid-19, a previously uncommonly reported manifestation of Covid-19 in this age group. Croup is a common illness in babies and young children characterized by a bark-like cough and sometimes noisy, high pitched breathing. It can be caused by a number of different respiratory viruses and causes swelling around the voice box and windpipe and bronchial tubes leading to the lungs.

Croup is generally mild in children with fewer than 5% of children requiring hospitalization prior to the pandemic. But worryingly, in the 75 patients with croup caused by Covid-19 infection in the new study, 12% of the children needed hospital care, with just under half of these needing intensive care. All of the affected children in the paper were under 5 and therefore not yet eligible for Covid-19 vaccination.

Although the information about the croup cases was collected between March 2020 and January 2022, 80% of the cases in the study occurred during a period of time where omicron was the dominant coronavirus variant and the study authors suggest that omicron may be more likely to cause croup than previous variants.

......The authors urge parents to be aware that although croup can be caused by many different viruses, parents should consider testing for Covid-19 if their child develops croup.

https://www.forbes.com/sites/victoriaforster/2022/03/16/covid-19-can-cause-sever...
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Ryan C.L. Brewster et al. 2022. COVID-19-Associated Croup in Children. Pediatrics (March 8, 2022)
https://doi.org/10.1542/peds.2022-056492 https://publications.aap.org/pediatrics/article/doi/10.1542/peds.2022-056492/185...

Release prior to publication
__________________________________________

Andy Slavitt 💙💛 @ASlavitt | 10:35 AM · Mar 16, 2022:
(Former Biden White House Sr Advisor, past head of Medicare/Medicaid for Obama)
NEW: CDC report says omicron hospitalized children 0-5 at 5 times the rate of Delta.
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Marks KJ, Whitaker M, Agathis NT, et al. Hospitalization of Infants and Children Aged 0–4 Years with Laboratory-Confirmed COVID-19 — COVID-NET, 14 States, March 2020–February 2022. MMWR Morb Mortal Wkly Rep 2022;71:429–436. DOI: http://dx.doi.org/10.15585/mmwr.mm7111e2

Summary
...During Omicron variant predominance beginning in late December 2021, U.S. infants and children aged 0–4 years were hospitalized at approximately five times the rate of the previous peak during Delta variant predominance. Infants aged 6 months (or younger) had the highest rates of hospitalization, but indicators of severity (e.g., respiratory support) did not differ by age group.

Important strategies to prevent COVID-19 among infants and young children include vaccination of currently eligible populations such as pregnant women, family members, and caregivers of infants and young children.

A covid surge in Western Europe has U.S. bracing for another wave
Lenny Bernstein and Joel Achenbach | March 16, 2022

...CDC data shows that, as of last week, BA.2 accounted for 23.1 percent of all new coronavirus infections in the United States, the largest percentage yet — up from 13.7 percent the week before. But BA.2 accounted for more than 38 percent of cases last week in parts of the Northeast and New England.

The seven-day average of cases in the United States fell 17.9 percent in the past week, according to data tracked by The Washington Post, while the number of deaths dropped 17.2 percent and hospitalizations declined 23.2 percent.

Predicting the future course of the virus has proved difficult throughout the pandemic, and the current circumstances in Europe elicited a range of opinions from people who have closely tracked the pathogen and the disease it causes.

In the United States, just 65.3 percent of the population, 216.8 million people, are fully vaccinated, and only 96.1 million have received a booster shot, according to data tracked by The Post. In Germany, nearly 76 percent are fully vaccinated, according to the Johns Hopkins data, and Britain has fully vaccinated 73.6 percent.

That lower vaccination rate is very likely to matter as BA.2 spreads further in the United States, especially in regions where it is significantly lower than the national rate, several experts said. And even for people who are fully vaccinated and have received a booster shot, research data is showing that immunity to the virus fades over time. Vaccine-makers Pfizer and BioNTech asked the Food and Drug Administration on Tuesday for emergency authorization to offer a fourth shot to people 65 and older.

...Similarly, as the public sheds masks — every state has dropped its mask mandate or announced plans to do so — another layer of protection is disappearing, several people tracking the situation said.

...Yet BA.2 appears to be spreading more slowly in the United States than it has overseas, for reasons that aren’t entirely clear, Debbie Dowell, chief medical officer for the CDC’s covid-19 response, said in a briefing Saturday for clinicians sponsored by the Infectious Diseases Society of America.

...One reason for that may be the immunity that millions of people acquired recently when they were infected with the BA.1 variant, which generally caused less-severe illness than previous variants. Yet no one really knows whether infection with BA.1 offers protection from BA.2.

...Topol said the United States needs to improve its vaccination and booster rates immediately to protect more of the population against any coming surge...

https://www.washingtonpost.com/health/2022/03/16/covid-ba2-omicron-surge/

Scott Gottlieb, MD (frmr FDA director) @ScottGottliebMD | 9:27 PM · Mar 16, 2022
1.19% of South Korea’s population tests positive for COVID in one day

Quote Tweet
BNO Newsroom @BNODesk · 16h
BREAKING: South Korea reports 621,328 new coronavirus cases, by far the biggest one-day increase so far, and a record 429 new deaths
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Graph-confirmed COVID mortalities S Korea March 2022 ( https://twitter.com/EricTopol/status/1504264955964497922/photo/1 )

John-Arne Røttingen (Ambassador Global Health Norway) @jarottingen | 11:05 AM · Mar 17, 2022:
35 generic manufacturers sign agreements with @MedsPatentPool to produce generic versions of Pfizer’s oral COVID-19 treatment
World map ( https://twitter.com/jarottingen/status/1504474008418279428/photo/1 )

Young athletes (esp. males?) will be heartened by 6.3.1. (below), I think? We should all consult our MDs re any heart issues associated with COVID, BUT... "...myocardial and pericardial involvement in some (U.S. collegiate athletes) recovering from COVID-19... Data from large registries have demonstrated, however, an overall low prevalence of clinical myocarditis,...without a rise in reported acute adverse cardiac events.... Cognizant of additional data that has accrued over the past year, we provide updated guidance related to resumption of athletics and intense exercise training after SARS-CoV-2 infection..."

New ACC (American College of Cardiology) Guidance on Cardiovascular Consequences of COVID-19
Sue Hughes | March 17, 2022

The document makes the following recommendations in regard to COVID-related myocarditis:

When there is increased suspicion for cardiac involvement with COVID-19, initial testing should consist of an ECG, measurement of cardiac troponin, and an echocardiogram. Cardiology consultation is recommended for those with a rising cardiac troponin and/or echocardiographic abnormalities. Cardiac MRI is recommended in hemodynamically stable patients with suspected myocarditis.

Hospitalization is recommended for patients with definite myocarditis, ideally at an advanced heart failure center. Patients with fulminant myocarditis should be managed at centers with an expertise in advanced heart failure, mechanical circulatory support, and other advanced therapies.

Patients with myocarditis and COVID-19 pneumonia (with an ongoing need for supplemental oxygen) should be treated with corticosteroids. For patients with suspected pericardial involvement, treatment with NSAIDs, colchicine, and/or prednisone is reasonable. Intravenous corticosteroids may be considered in those with suspected or confirmed COVID-19 myocarditis with hemodynamic compromise or MIS-A (multisystem inflammatory syndrome in adults). Empiric use of corticosteroids may also be considered in those with biopsy evidence of severe myocardial infiltrates or fulminant myocarditis, balanced against infection risk.

As appropriate, guideline-directed medical therapy for heart failure should be initiated and continued after discharge.

The document notes that myocarditis following COVID-19 mRNA vaccination is rare, with highest rates seen in young males after the second vaccine dose. As of May 22, 2021, the US Vaccine Adverse Event Reporting System noted rates of 40.6 cases per million after the second vaccine dose among male individuals aged 12-29 years and 2.4 cases per million among male individuals aged 30 and older. Corresponding rates in female individuals were 4.2 and 1 cases per million, respectively.

But the report says that COVID-19 vaccination is associated with "a very favorable benefit-to risk ratio" for all age and sex groups evaluated thus far.

In general, vaccine-associated myocarditis should be diagnosed, categorized, and treated in a manner analogous to myocarditis following SARS-CoV-2 infection, the guidance advises...

https://www.medscape.com/viewarticle/970467#vp_2
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Ty J. Gluckman et al. 2022. 2022 ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19 in Adults: Myocarditis and Other Myocardial Involvement, Post-Acute Sequelae of SARS-CoV-2 Infection, and Return to Play: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. Mar 16, 2022. Epublished DOI: 10.1016/j.jacc.2022.02.003 https://www.jacc.org/doi/10.1016/j.jacc.2022.02.003

... 6.3.1 (Return to Play, RTP) Overview
Observation of myocardial injury among patients hospitalized with COVID-19,... coupled with uncertainty around cardiovascular sequalae after mild illness,... fueled early apprehension regarding the safety of competitive sports for athletes recovering from SARS-CoV-2 infection. Several consensus screening recommendations have followed,... including 2 by the ACC’s Sports and Exercise Cardiology Council,... endorsing a conservative RTP screening approach consisting of so-called triad testing... with a 12-lead ECG, cTn (preferably using a high-sensitivity assay), and an echocardiogram. Subsequent protocols incorporating universal CMR in U.S. collegiate athletes identified myocardial and pericardial involvement in some recovering from COVID-19... Data from large registries have demonstrated, however, an overall low prevalence of clinical myocarditis,... without a rise in reported acute adverse cardiac events.... Cognizant of additional data that has accrued over the past year, we provide updated guidance related to resumption of athletics and intense exercise training after SARS-CoV-2 infection. Included below is a summary of literature related to athletes with COVID-19 and a practical, evidence-based framework to guide RTP evaluation...

Ahmed Mushfiq et al. 2022. End COVID-19 in low- and middle-income countries (Policy Forum). Science • 10 Mar 2022 • Vol 375, Issue 6585 • pp. 1105-1110 • DOI: 10.1126/science.abo4089 https://www.science.org/doi/10.1126/science.abo4089

Vaccines are changing the course of the COVID-19 pandemic, but in grossly uneven ways. Low- and middle-income countries (LMICs) face considerable obstacles in both receiving and distributing doses. To limit virus transmission, its devastating impacts, and opportunities for further mutations, this must change. Until it does, nonpharmaceutical interventions such as masking must remain a priority. Science invited global experts to highlight research and innovations aimed at quickening the end of COVID-19 in LMICs. —Brad Wible

Contributions to COVID-19 research and innovation
Lessons from India in April 2021
The economic impact of COVID-19
Scale up production of COVID-19 vaccines in LMICs
Is vaccine hesitancy a problem?
Overcoming last-mile vaccine delivery challenges
Optimizing vaccine dosing in pandemics
Mobile phone messaging to promote preventive behaviors
Promoting mask wearing to reduce COVID-19 infections

https://www.science.org/doi/10.1126/science.abo4089

John Burn-Murdoch* @jburnmurdoch | 12:39 PM · Mar 17, 2022:
See entire lo-ong thread with comments at https://twitter.com/jburnmurdoch/status/1504497732039413765

NEW: time for a Covid situation update
Cases and hospitalisations are rising again across much of the western world.
What’s driving the rise, and should we be worried?
Graphs ( https://twitter.com/jburnmurdoch/status/1504497732039413765/photo/1 )
...

* John Burn-Murdoch @jburnmurdoch
Stories, stats & scatterplots for @FinancialTimes | Mainly Covid for now | Visiting senior fellow @LSEdataScience ...

U.S. Has Far Higher Covid Death Rate Than Other Wealthy Countries
Benjamin Mueller and Eleanor Lutz | Feb. 1, 2022

Two years into the pandemic, the coronavirus is killing Americans at far higher rates than people in other wealthy nations, a sobering distinction to bear as the country charts a course through the next stages of the pandemic...

https://www.nytimes.com/interactive/2022/02/01/science/covid-deaths-united-state...

Why the AstraZeneca vaccine is linked with rare blood clots: New insights
Anna Guildford, Ph.D. | March 17, 2022

Healthcare professionals have administered over 11 billion COVID-19 vaccine doses globally so far.
However, there have been reports of a low risk of blood clotting complications linked to adenovirus-based COVID-19 vaccines.
A recent study offers a possible explanation as to why this happens in some people.
The research found that the electrical charge of the adenovirus promotes the adhesion of blood-based proteins associated with blood clotting...

... thrombosis with thrombocytopenia (TTS), a potentially life threatening blood clotting disorder...they think that vaccination with an adenovirus causes platelet factor 4 (PF4), a protein in the blood (protein stored inside the blood’s platelets released when platelets are activated), to bind to the adenovirus, forming a complex. Platelets are the tiny blood cells that help the body form clots to stop bleeding. Some people form antibodies against this antigen-PF4 complex, which causes the platelets to aggregate, leading to an increased risk of blood clots.

https://www.medicalnewstoday.com/articles/why-the-astrazeneca-vaccine-is-linked-...
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* Alexander T. Baker et al. 2022. ChAdOx1 interacts with CAR and PF4 with implications for thrombosis with thrombocytopenia syndrome. Science Advances • 1 Dec 2021 • Vol 7, Issue 49 • DOI: 10.1126/sciadv.abl8213 https://www.science.org/doi/epdf/10.1126/sciadv.abl8213 https://www.science.org/doi/10.1126/sciadv.abl8213

Abstract
Vaccines derived from chimpanzee adenovirus Y25 (ChAdOx1), human adenovirus type 26 (HAdV-D26), and human adenovirus type 5 (HAdV-C5) are critical in combatting the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic. As part of the largest vaccination campaign in history, ultrarare side effects not seen in phase 3 trials, including thrombosis with thrombocytopenia syndrome (TTS), a rare condition resembling heparin-induced thrombocytopenia (HIT), have been observed. This study demonstrates that all three adenoviruses deployed as vaccination vectors versus SARS-CoV-2 bind to platelet factor 4 (PF4), a protein implicated in the pathogenesis of HIT. We have determined the structure of the ChAdOx1 viral vector and used it in state-of-the-art computational simulations to demonstrate an electrostatic interaction mechanism with PF4, which was confirmed experimentally by surface plasmon resonance. These data confirm that PF4 is capable of forming stable complexes with clinically relevant adenoviruses, an important step in unraveling the mechanisms underlying TTS.

New BioAge Drug Prevents Death From COVID-19 in Old Mice by Reversing Immune Aging
BioAge Labs March 21, 2022

A Phase 2 clinical trial is testing the new drug’s ability to reduce mortality in older people hospitalized with COVID-19. By directly targeting immune aging, BGE-175 could effectively treat emerging COVID variants that evade vaccine-based immunity.

The immune system deteriorates with age, making COVID-19 particularly deadly in older people — but to date, no clinically available medication addresses this key risk factor. A study published today (March 21, 2022) in Nature shows that an oral drug that reverses multiple aspects of immune aging effectively prevents death in a mouse model of COVID-19, suggesting that the medication could be used to protect the elderly patients who are at greatest risk in the pandemic.

In the study, daily doses of BGE-175 (asapiprant) protected aged mice from a lethal dose of SARS-CoV-2, the virus that causes COVID-19. Ninety percent of mice that received the drug survived, whereas all untreated control mice died. BGE-175 treatment was initiated two days after infection, when the mice were already ill, a time-frame relevant to real-life clinical situations in which patients would receive medication only after becoming symptomatic.

The mouse model used in the study closely mirrored the pathological progression of human COVID-19. The mouse-adapted strain of SARS-CoV-2 generated by the researchers caused a disease that shared many of the hallmarks of human COVID-19: accumulation of fluid in the air sacs of the lungs, extensive infiltration of lung tissue by immune cells, and high levels of pro-inflammatory factors called cytokines.

BGE-175 is currently in a Phase 2 clinical trial to test whether it can prevent disease progression and mortality in older patients hospitalized with COVID-19. BGE-175 is being clinically developed by BioAge Labs, a California-based biotechnology company devoted to creating drugs that treat human disease and extend healthspan by targeting the molecular mechanisms of aging.

“The COVID-19 pandemic has devastated elderly populations around the world,” said Kristen Fortney, PhD, CEO of BioAge and an author of the study. “The promising preclinical data in this paper show that BGE-175 almost completely protects aged mice from lethality in a compelling model of human COVID-19. By reversing age-related declines in critical immune mechanisms, BGE-175 could allow older patients to more effectively fight off this disease.”
Reversing immune aging via a dual mechanism

As we age, a biochemical pathway involving the signaling molecule PGD2 becomes more active, impairing immunity in two major ways: First, antigen-presenting cells called dendritic cells migrate less efficiently, slowing the adaptive T-cell and antibody responses. Second, white blood cells called neutrophils infiltrate infected tissues more aggressively, leading to damaging inflammation. Thus, the aged immune system is both slower to respond to new infections and more likely to overreact once it does mount a response.

BGE-175 inhibits this pathway by blocking the interaction between PGD2 and its receptor, a protein called DP1. BioAge’s AI-based drug discovery platform identified the PGD2-DP1 pathway as a key target for immune aging. In the study described in the Nature paper, BGE-175 increased migration of dendritic cells from the lungs into the lymph nodes, decreased the levels of neutrophils in lung tissue, and dramatically improved overall survival. From the standpoint of PGD2 pathway activity, the drug restored the immune system to a more youthful state.

As with the drug-treated animals, genetically engineered mice that were unable to synthesize PGD2 or lacked DP1 had lower viral loads, exhibited less inflammation and tissue damage, and were less susceptible to death from viral infection, confirming that BGE-175 acts through the PGD2 pathway.

“Our findings clearly show that the therapeutic target of BGE-175 plays a key role in making the aged lung environment conducive for optimal immune function, and thereby counters immune aging,” said Stanley Perlman, MD, PhD, Professor of Microbiology and Immunology and Pediatric Infectious Physician at the University of Iowa, who was an author of the Nature paper. “The drug’s protective effect in mice supports the idea that BGE-175 corrects age-related declines in immunity, providing a strong rationale for testing in older patients who are hospitalized with COVID-19.”...

https://scitechdaily.com/new-bioage-drug-prevents-death-from-covid-19-in-old-mic...
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Lok-Yin Roy Wong et al. 2022. Eicosanoid signaling blockade protects middle-aged mice from severe COVID-19. Nature (21 March 2022) https://www.nature.com/articles/s41586-022-04630-3

unedited version of this manuscript...will undergo further editing.

Abstract
...Using our mouse-adapted SARS-CoV-2, we show that middle-aged mice lacking expression of PTGDR, or PLA2G2D are protected from severe disease. Further, treatment with a PTGDR antagonist, asapiprant, protected aged mice from lethal infection. PTGDR antagonism is one of the first interventions in SARS-CoV-2-infected animals that specifically protects aged animals, suggesting that the PLA2G2D-PGD2/PTGDR pathway is a useful target for therapeutic interventions.

"In a prospective study of 536 mainly non-hospitalised individuals, symptom burden decreased, but single organ impairment persisted in 59% at 12 months post-COVID-19."

Andrea Dennis et al. 2022. Multi-organ impairment and Long COVID: a 1-year prospective, longitudinal cohort study. MedRxiv
March 21, 2022. doi: https://doi.org/10.1101/2022.03.18.22272607 https://www.medrxiv.org/content/10.1101/2022.03.18.22272607v1

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

Abstract
...Main outcome: Prevalence of single and multi-organ impairment at 6 and 12 months post-COVID-19.

Results: Extreme breathlessness (36% and 30%), cognitive dysfunction (50% and 38%) and poor health-related quality of life (EQ-5D-5L less than .7; 55% and 45%) were common at 6 and 12 months, and associated with female gender, younger age and single organ impairment. At baseline, there was fibro-inflammation in the heart (9%), pancreas (9%), kidney (15%) and liver (11%); increased volume in liver (7%), spleen (8%) and kidney (9%); decreased capacity in lungs (2%); and excessive fat deposition in the liver (25%) and pancreas (15%). Single and multi-organ impairment were present in 59% and 23% at baseline, persisting in 59% and 27% at follow-up.

Conclusion and Relevance: Organ impairment was present in 59% of individuals at 6 months post-COVID-19, persisting in 59% of those followed up at 1 year, with implications for symptoms, quality of life and longer-term health, signalling need for prevention and integrated care of Long COVID. Trial Registration: ClinicalTrials.gov NCT04369807

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...The long-term consequences of COVID-19 include increased risk of:
Heart disease https://nature.com/articles/s41591-022-01689-3
Kidney disease https://jasn.asnjournals.org/content/32/11/2851
and now diabetes https://thelancet.com/journals/landia/article/PIIS2213-8587(22)00044-4/fulltext

- Ziyad Al-Aly, MD @zalaly | 7:36 PM · Mar 21, 2022

Italian study shows ventilation can cut school COVID cases by 82%
Reuters | March 22, 2022
https://www.reuters.com/world/europe/italian-study-shows-ventilation-can-cut-sch...

Wastewater is our COVID early warning system. 35% of monitoring sites are showing a rise in SARS-CoV-2 RNA. In the last week there’s been a 26% increase in the number of sites (red dots) noting 1000% incr in wastewater levels. Here are the places where RNA levels are rising.
US map ( https://twitter.com/JReinerMD/status/1505611645954973698/photo/1 )

-Jonathan Reiner @JReinerMD |2:26 PM · Mar 20, 2022
Prof, The George Washington University School of Medicine & Health Sciences

Eric Topol @EricTopol | 3:54 PM · Mar 21, 2022:
"The (neutralizing antibody) response against Omicron declined 6.3-fold over the same 6-month time frame after the boost."

Graph-waning neutralizing response of doses 1-4 against Wuhan, Delta, Omicron ( https://twitter.com/EricTopol/status/1505996380023652355/photo/1 )
---------------------------------------------------------

Xiaoying Shen . 2022. Boosting immunity to Omicron. Nature Medicine volume 28, pages 445–446 (24 Feb 2022). https://nature.com/articles/s41591-022-01727-0

New data confirm that the COVID-19 vaccine booster dose is crucial for the generation of neutralizing antibody responses against Omicron, while better therapeutic antibodies are needed for this and future variants....

>88 margd:, contd.

COVID-19 Increases Risk of Type 2 Diabetes
Deutsches Zentrum für Diabetesforschung (DZD) | March 23, 2022

...relative risk of developing type 2 diabetes was 28% higher in the Covid-19 group than in the AURI group ( acute upper respiratory tract infections )

https://scitechdaily.com/covid-19-increases-risk-of-type-2-diabetes/
-------------------------------------------------------------

Wolfgang Rathmann et al. 2022. Incidence of newly diagnosed diabetes after Covid-19. 16 March 2022, Diabetologia.
DOI: 10.1007/s00125-022-05670-0

Abstract
...Results
There were 35,865 individuals with documented Covid-19 in the study period. After propensity score matching, demographic and clinical characteristics were similar in 35,865 AURI controls (mean age 43 years; 46% female). Individuals with Covid-19 showed an increased type 2 diabetes incidence compared with AURI (15.8 vs 12.3 per 1000 person-years). Using marginal models to account for correlation of observations within matched pairs, an IRR (Incidence Rate Ratio) for type 2 diabetes of 1.28 ... was estimated. The IRR was not increased for other forms of diabetes.

Conclusions/interpretation
Covid-19 confers an increased risk for type 2 diabetes. If confirmed, these results support the active monitoring of glucose dysregulation after recovery from mild forms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

News in brief: mRNA made in Africa
Nature Biotechnology volume 40, page 284 ( 16 March 2022)
https://www.nature.com/articles/s41587-022-01268-4

BioNTech, the drug company that produced an mRNA vaccine for COVID-19 with Pfizer, has developed a new type of vaccine factory for Africa. The biotech has miniaturized all the processes needed to manufacture mRNA vaccines into a modular unit. The factory, made up of two groups of six 40-foot containers, can be loaded on trucks, planes, boats or trains. Once on site, the so-called ‘bioNTainer’, containing the 50,000 steps needed to manufacture a mRNA vaccine, can be assembled for plug-and-play manufacturing. The first containers will arrive in Rwanda and Senegal in the second half of 2022 and potentially also in South Africa...

Photo-bioNTainer ( https://twitter.com/NatureBiotech/status/1506765231753728000/photo/1 )

Philip Schellekens (Sr Advisor World Bank Group) @fibke | 3:22 AM · Mar 21, 2022
US tends to lag Europe.
We can expect a reversal in US cases very soon (below).
And we can expect the wave to be far more lethal than the European one (see next tweet).
Graph--Eur & US case rates Apr 2020-Apr 2022 ( https://twitter.com/fibke/status/1505807130363895811/photo/1 )
1/

If the past provides any guidance, we can expect a greater mortality impact of the upcoming BA.2 wave in the US than in Europe
Graph--Eur & US mort rates Apr 2020-Apr 2022 ( https://twitter.com/fibke/status/1505807134595944451/photo/1 )
2/

Let’s look at Europe without stacking the trend. Reversal of cases is the biggest in Western Europe. Eastern Europe is starting to turn around.
Graphs-case & death rates by Eur regions ( https://twitter.com/fibke/status/1505807137603297280/photo/1 )
3/

No such patterns yet in the US, apart from a tiny upward blip for the Midwest region
Graphs-case & death rates by US region ( https://twitter.com/fibke/status/1505807140761571328/photo/1 )
4/

For more details, read this post

Data insight. COVID waves: Europe and US compared
Comparisons of cases and fatalities at the regional and subnational levels
March 26, 2022
https://pandem-ic.com/covid-waves-europe-and-us-compared/

5/
----------------------------------------------------------
ETA
Eric Topol @EricTopol | 1:40 PM · Mar 23, 2022
Thread on the BA.2 wave in England. This is not just about cases.
—Hospital admissions increased 22% past week, may be decelerating
—Need for mechanical ventilation up 10%
—Deaths up 14%

Quote Tweet
COVID-19 Actuaries Response Group @COVID19actuary · Mar 23
Hospital admissions with COVID continue to increase across England. The rate of increase appears to be slowing, but admissions are still up by 22% in the last week.

See below for a breakdown by region and age. Also bed occupancy and hospital deaths. 1/6
Graph-hospitalizations England Jan-March 2022 ( https://twitter.com/COVID19actuary/status/1506667555016089612/photo/1 )

Show this thread ( https://twitter.com/COVID19actuary/status/1506667555016089612 )

Eric Topol @EricTopol | 11:03 AM · Mar 24, 2022:
Nearly 200,000 Covid hospitalizations are estimated to have been prevented by boosters, age 25+, since mid-December
Fig 16. No. hospitalizations averted by boosters Dec 2021- March 2022 ( https://twitter.com/EricTopol/status/1507010122177863681/photo/1 )

Jonas R. Kunst (U Oslo) @KunstJonas | 4:34 AM · Mar 25, 2022
🚨A new study suggests that antiviral cytotoxic activity together with other clinical features and demographic information can identify people with #LongCovid with 100% accuracy. If this replicates, it could lead to the first biomarkers for the condition.

Miguel Galán et al. 2022. Persistent Overactive Cytotoxic Immune Response in a Spanish Cohort of Individuals With Long-COVID: Identification of Diagnostic Biomarkers. Front. Immunol., 25 March 2022 | https://doi.org/10.3389/fimmu.2022.848886

Long-COVID is a new emerging syndrome worldwide that is characterized by the persistence of unresolved signs and symptoms of COVID-19 more than 4 weeks after the infection and even after more than 12 weeks. The underlying mechanisms for Long-COVID are still undefined, but a sustained inflammatory response caused by the persistence of SARS-CoV-2 in organ and tissue sanctuaries or resemblance with an autoimmune disease are within the most considered hypotheses. In this study, we analyzed the usefulness of several demographic, clinical, and immunological parameters as diagnostic biomarkers of Long-COVID in one cohort of Spanish individuals who presented signs and symptoms of this syndrome after 49 weeks post-infection, in comparison with individuals who recovered completely in the first 12 weeks after the infection. We determined that individuals with Long-COVID showed significantly increased levels of functional memory cells with high antiviral cytotoxic activity such as CD8+ TEMRA cells, CD8±TCRγδ+ cells, and NK cells with CD56+CD57+NKG2C+ phenotype. The persistence of these long-lasting cytotoxic populations was supported by enhanced levels of CD4+ Tregs and the expression of the exhaustion marker PD-1 on the surface of CD3+ T lymphocytes. With the use of these immune parameters and significant clinical features such as lethargy, pleuritic chest pain, and dermatological injuries, as well as demographic factors such as female gender and O+ blood type, a Random Forest algorithm predicted the assignment of the participants in the Long-COVID group with 100% accuracy. The definition of the most accurate diagnostic biomarkers could be helpful to detect the development of Long-COVID and to improve the clinical management of these patients.

Biden Administration Plans to Offer Second Booster Shots to Those 50 and Up
Sharon LaFraniere | March 25, 2022

After fraught discussions, officials decided that another shot might save thousands of lives if a new coronavirus wave hit before the fall. The F.D.A. could authorize the boosters next week.

The Biden administration is planning to give Americans age 50 or older the option of a second booster of the Pfizer-BioNTech or Moderna coronavirus vaccine without recommending outright that they get one, according to several people familiar with the plan....

https://www.nytimes.com/2022/03/25/us/politics/biden-second-booster-shot-older-a...

Eric Feigl-Ding @DrEricDing | 9:19 AM · Mar 25, 2022:
⚠️Holy moly—Gosh, 6-9% of all people across England Scotland Wales N Ireland tested newly positive for #COVID19 in just 1 week!!! Wowzers. 97-99% of people in 🇬🇧 already had antibodies. #BA2 reinfection is real. Hospitalizations surging. Don’t play games.

https://ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsan...
Table 1-highlighted, estimated cases UK, 13-20 March 2022 ( https://twitter.com/DrEricDing/status/1507346360022020096/photo/1 )

CDC updates Covid-19 guidance to allow patients wear N95s
Rachael Levy | 03/24/2022

The Centers for Disease Control and Prevention on Thursday updated its guidance so that people visiting health care facilities are allowed to wear highly protective masks such as N95s.

The change comes after a POLITICO report last week found that hospitals around the country routinely ask patients and visitors to wear a surgical mask instead of their own N95...

https://www.politico.com/news/2022/03/24/cdc-updates-covid-19-guidance-to-allow-...

Gavin Yamey et al. 2022. It is not too late to achieve global covid-19 vaccine equity. BMJ 2022; 376 doi: https://doi.org/10.1136/bmj-2022-070650 (Published 24 March 2022). https://www.bmj.com/content/376/bmj-2022-070650

Gavin Yamey and colleagues say that a new, urgent push for global vaccine equity could help avert suffering and deaths, protect economies, and prevent new virus variants...

"protection against reinfection...decreased...dramatically so when Omicron appeared. Protection was lower among the elderly but appeared more pronounced following symptomatic compared to asymptomatic infections."

Michlmayr, Daniela and Hansen, Christian Holm and Gubbels, Sophie Madeleine and Valentiner-Branth, Palle and Bager, Peter Michael and Obel, Niels and Drewes, Birgitte and Holten Møller, Camilla and Møller, Frederik Trier and Legarth, Rebecca and Mølbak, Kåre and Ethelberg, Steen, Observed Protection Against SARS-CoV-2 Reinfection Following a Primary Infection: A Danish Cohort Study Using Two Years of Nationwide PCR-Test Data. Available at SSRN: https://ssrn.com/abstract=4054807 or http://dx.doi.org/10.2139/ssrn.4054807 https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4054807

Preprint, not yet peer-reviewed.

Abstract
Background: The level of protection after a SARS-CoV-2 infection against reinfection and COVID-19 disease remains important with much of the world still unvaccinated.

Methods: Analysing nationwide, individually referable, Danish register data including RT-PCR-test results, we conducted a cohort study using Cox regression to compare SARS-CoV-2 infection rates before and after a primary infection among still unvaccinated individuals, adjusting for sex, age and residency region. The prevalence of infections classified as symptomatic or asymptomatic was compared for primary infections and reinfections. The study also assessed protection against each of the main viral variants after an earlier variant primary infection by restricting follow-up time to distinct, mutually exclusive periods during which each variant dominated.

Findings: Until 1 July 2021 the estimated protection against reinfection was 83.5% (95%CI: 82.2%–84.6%); but lower for the 65+ year-olds (72.0%; 95%CI: 56.1%–82.2%). First-time cases who reported no symptoms were more likely to experience a reinfection (OR: 1.48; 95%CI: 1.36–1.62). By autumn 2021, when infections were almost exclusively by the Delta variant, the estimated protection of a recent infection was 91.3% (95%CI: 89.7%–92.7%) compared to 71.3% (95%CI: 66.8%–75.2%) after a first infection over a year earlier. With Omicron, a first infection in the past 3-6 months gave an estimated 43.1% (95%CI: 41.6%-44.4%) protection, whereas a first infection longer than 12 months earlier provided only 14.6% (12.7-16.4%) protection.

Interpretation: SARS-CoV-2 infection offered a high level of sustained protection against reinfection, comparable with that offered by vaccines, but decreased with the introduction of new main virus variants; dramatically so when Omicron appeared. Protection was lower among the elderly but appeared more pronounced following symptomatic compared to asymptomatic infections. Decreases in protection against reinfection, seemed primarily to be driven by viral evolution.

"Memory T-cell responses to the original strain were not disrupted by new variants. This study suggests that cross-reactive SARS-CoV-2-specific T-cell responses could be particularly important in the protection against severe disease caused by variants of concern whereas neutralising antibody responses seem to reduce over time."

Eric Topol @EricTopol | 8:45 PM · Mar 23, 2022:
In a prospective cohort of over 1,000 people with moderate to critical Covid, the memory T cell response at 1 year across variants was well preserved, indicative of sustained protection vs severe disease
https://twitter.com/EricTopol/status/1506794397739880452/photo/1

Li Guo et al. 2022. SARS-CoV-2-specific antibody and T-cell responses 1 year after infection in people recovered from COVID-19: a longitudinal cohort study. The Lancet Microbe. Published:March 23, 2022DOI:https://doi.org/10.1016/S2666-5247(22)00036-2 https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(22)00036-2/fullt...

Summary
...Findings
We enrolled 1096 patients, including 289 (26·4%) patients with moderate initial disease, 734 (67·0%) with severe initial disease, and 73 (6·7%) with critical initial disease. Paired plasma samples were collected from 141 patients during the follow-up visits for the microneutralisation assay. PBMCs were collected from 92 of 141 individuals at the 12-month follow-up visit, of which 80 were analysed by ELISpot and 92 by ICS assay to detect the SARS-CoV-2-specific memory T-cell responses. N-IgG (899 (82·0%)), S-IgG (1043 (95·2%)), RBD-IgG (1032 (94·2%)), and neutralising (115 (81·6%) of 141) antibodies were detectable 12 months after initial infection in most individuals. Neutralising antibodies remained stable 6 and 12 months after initial infection in most individuals younger than 60 years. Multifunctional T-cell responses were detected for all SARS-CoV-2 viral proteins tested. There was no difference in the magnitude of T-cell responses or cytokine profiles in individuals with different symptom severity. Moreover, we evaluated both antibody and T-cell responses to the D614G, beta, and delta viral strains. The degree of reduced in-vitro neutralising antibody responses to the D614G and delta variants, but not to the beta variant, was associated with the neutralising antibody titres after SARS-CoV-2 infection. We also found poor neutralising antibody responses to the beta variant; 83 (72·2%) of 115 patients showed no response at all. Moreover, the neutralising antibody titre reduction of the recovered patient plasma against the delta variant was similar to that of the D614G variant and lower than that of the beta variant. By contrast, T-cell responses were cross-reactive to the beta variant in most individuals. Importantly, T-cell responses could be detected in all individuals who had lost the neutralising antibody response to SARS-CoV-2 12 months after the initial infection.

Interpretation
SARS-CoV-2-specific neutralising antibody and T-cell responses were retained 12 months after initial infection. Neutralising antibodies to the D614G, beta, and delta viral strains were reduced compared with those for the original strain, and were diminished in general. Memory T-cell responses to the original strain were not disrupted by new variants. This study suggests that cross-reactive SARS-CoV-2-specific T-cell responses could be particularly important in the protection against severe disease caused by variants of concern whereas neutralising antibody responses seem to reduce over time.

Co-author Shane Crotty: We compare immune memory to Moderna, Pfizer, J&J, and Novavax COVID-19 vaccines head-to-head. T cells, B cells, and antibody. We think this is the most comprehensive immunological evaluation of these four different vaccines.

Zeli Zhang et al. 2022. Humoral and cellular immune memory to four COVID-19 vaccines. BioRxiv March 21, 2022. doi: https://doi.org/10.1101/2022.03.18.484953 https://www.biorxiv.org/content/10.1101/2022.03.18.484953v1

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

SUMMARY
Multiple COVID-19 vaccines, representing diverse vaccine platforms, successfully protect against symptomatic COVID-19 cases and deaths. Head-to-head comparisons of T cell, B cell, and antibody responses to diverse vaccines in humans are likely to be informative for understanding protective immunity against COVID-19, with particular interest in immune memory. Here, SARS-CoV-2-spike—specific immune responses to Moderna mRNA-1273, Pfizer/BioNTech BNT162b2, Janssen Ad26.COV2.S and Novavax NVX-CoV2373 were examined longitudinally for 6 months. 100% of individuals made memory CD4+ T cells, with cTfh and CD4-CTL highly represented after mRNA or NVX-CoV2373 vaccination. mRNA vaccines and Ad26.COV2.S induced comparable CD8+ T cell frequencies, though memory CD8+ T cells were only detectable in 60-67% of subjects at 6 months. Ad26.COV2.S was not the strongest immunogen by any measurement, though the Ad26.COV2.S T cell, B cell, and antibody responses were relatively stable over 6 months. A differentiating feature of Ad26.COV2.S immunization was a high frequency of CXCR3+ memory B cells. mRNA vaccinees had substantial declines in neutralizing antibodies, while memory T cells and B cells were comparatively stable over 6 months. These results of these detailed immunological evaluations may also be relevant for vaccine design insights against other pathogens.

Eric Topol @EricTopol | 8:52 PM · Mar 27, 2022
No wonder BA.2 is causing so much transmissibility trouble
— ~175,000 nasopharyngeal samples analyzed for viral load
— BA.2 nearly twice as much as BA.1

Antonio Lentini et al. 2022. Monitoring of the SARS-CoV-2 Omicron BA.1/BA.2 variant transition in the Swedish population reveals higher viral quantity in BA.2 cases. MedRxiv March 27, 2022. doi: https://doi.org/10.1101/2022.03.26.22272984 https://www.medrxiv.org/content/10.1101/2022.03.26.22272984v1

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

Abstract
...Here, we tracked the remarkably rapid shift from Omicron BA.1 to BA.2 sub-variant dominance in the Swedish population during January-March 2022. By analysis of 174,933 clinical nasopharyngeal swab samples using a custom variant-typing RT-PCR assay, we uncover nearly two-fold higher levels of viral RNA in cases with Omicron BA.2. Importantly, increased viral load in the upper pharynx upon BA.2 infection may provide part of the explanation why Omicron BA.2 is more transmissible and currently outcompetes the BA.1 variant across populations.

There are a lot of drugs that interact with Paxlovid--my son's epilepsy meds apparently--so good advice to seek and follow MD and pharmacist insight and oversight for Paxlovid...

Menaka Pai, MSc MD FRCPC (McMaster U) @MPaiMD | 10:13 PM · Mar 26, 2022:
https://twitter.com/MPaiMD/status/1507903661447745539

After deliberation and a voting process to achieve quorum, this is who we felt should get paxlovid:
10/n

Ontario COVID-19 Drugs and Biologics
Clinical Practice Guidelines Working Group on behalf of the Ontario COVID-19 Science Advisory Table
Version 10.0 | https://doi.org/10.47326/ocsat.cpg.2022.10.0
February 23, 2022
https://covid19-sciencetable.ca/sciencebrief/clinical-practice-guideline-summary...

We decided that people with at least 5% risk of landing in hospital should receive paxlovid. If we treat 25 of them, we’d prevent 1 hospitalization. This decision was based on EPIC-HR, the single big published paxlovid trial, which shows it works in high risk people. 12/n

EPIC-SR—the “standard risk” trial of Paxlovid—is not published in final form. It didn’t show people with lower risk felt better. We don’t know that paxlovid keeps these lower risk folks out of hospital. 13/n

The government decided to use our Feb 23 criteria to inform the assessment centres around the province, which prescribe paxlovid and which take referrals to provide paxlovid to individuals outside major centres. 14/n

Please look at that table! Would you be eligible for paxlovid if you got COVID? Would your loved ones? Think about your elders. Those you know with other illnesses. 15/n
Table risk factors ( https://twitter.com/MPaiMD/status/1507903689603829766/photo/1 )

As you do this, note! Our decision about who should get paxlovid is NOT based on limited supply! It’s NOT based on rationing! (We have enough drug.) It’s not based on who “deserves” paxlovid. It’s based on who would BENEFIT most. 16/n...

Hope China's zero-COVD policy works against omicron, 'coz previous success (= little natural immunity) and effectiveness of Chinese vaxx doesn't sound up to this variant...esp even more transmissible BA2 subtype...

(A friend's dad died of COVID in Hong Kong last week, though family members he lived with apparently uninfected.
A strong man, he was over 100 years old and survived five days in hospital... )

Eric Feigl-Ding @DrEricDing |
Wow—China’s financial hub of Shanghai will lock down the city of 26 million in two stages to carry out #COVID19 testing over 9-days. It will enter lockdown do PCR tests. All transit will stop. All factories will close—companies will work remote if capable.
Shanghai to lock down in two stages for testing as COVID surges

China: Shanghai to lock down for testing as COVID surges
The financial hub of 26 million people has become a testing ground for China’s ‘zero-COVID’ policy.
March 27, 2022

https://www.aljazeera.com/news/2022/3/27/china-shanghai-lockdown-covid-surge

Dr Zoë Hyde (epidemiologist) @DrZoeHyde | 6:01 AM · Mar 27, 2022:
Groundbreaking new research shows a far-UVC (ultraviolet light) air purification system can reduce levels of an airborne pathogen by 98% within minutes.

This is equivalent to an incredible 184 air changes per hour - better than even HEPA air cleaners.
Infographic ( https://twitter.com/DrZoeHyde/status/1508021338845609985/photo/1 )
Graph--reduction pathogen in as few as 5 min! ( https://twitter.com/DrZoeHyde/status/1508021338845609985/photo/2 )
------------------------------------------------------------------

Ewan Eadie et al. 2022. Far-UVC (222 nm) efficiently inactivates an airborne pathogen in a room-sized chamber. Scientific Reports volume 12, Article number: 4373 (23 March 2022) https://www.nature.com/articles/s41598-022-08462-z

Abstract
Many infectious diseases, including COVID-19, are transmitted by airborne pathogens. There is a need for effective environmental control measures which, ideally, are not reliant on human behaviour. One potential solution is Krypton Chloride (KrCl) excimer lamps (often referred to as Far-UVC), which can efficiently inactivate pathogens, such as coronaviruses and influenza, in air. Research demonstrates that when KrCl lamps are filtered to remove longer-wavelength ultraviolet emissions they do not induce acute reactions in the skin or eyes, nor delayed effects such as skin cancer. While there is laboratory evidence for Far-UVC efficacy, there is limited evidence in full-sized rooms. For the first time, we show that Far-UVC deployed in a room-sized chamber effectively inactivates aerosolised Staphylococcus aureus. At a room ventilation rate of 3 air-changes-per-hour (ACH), with 5 filtered-sources the steady-state pathogen load was reduced by 98.4% providing an additional 184 equivalent air changes (eACH). This reduction was achieved using Far-UVC irradiances consistent with current American Conference of Governmental Industrial Hygienists threshold limit values for skin for a continuous 8-h exposure. Our data indicate that Far-UVC is likely to be more effective against common airborne viruses, including SARS-CoV-2, than bacteria and should thus be an effective and “hands-off” technology to reduce airborne disease transmission. The findings provide room-scale data to support the design and development of effective Far-UVC systems.

Africa’s Low Vaccination Rates Should Concern Everyone
John Nkengasong (Africa Centers for Disease Control and Prevention) | March 27, 2022

...logistical challenges and issues of vaccine hesitancy — similar to those seen in other places around the world — have momentarily outstripped shortages for the continent...Now that supply is not the primary challenge, we need to focus on better delivery.

Only about 15 percent of the population in Africa has been fully vaccinated.

On Feb. 5, President Cyril Ramaphosa of South Africa, the leader of the African Union’s Covid-19 response, presented a comprehensive report at the A.U. ...As part of this plan, which was unanimously endorsed, governments must commit to achieving more than 70 percent vaccination rates for their countries by the end of 2022. Only about 14 of the 55 A.U. member states have so far vaccinated more than 40 percent of their eligible populations.

...For vaccination campaigns to be successful, vaccine donation must be closely coordinated with either the COVAX and African Vaccine Acquisition Task Team initiatives, to ensure that countries in Africa are not overwhelmed. Too many doses without the infrastructure or coordination to distribute them could lead to vaccines expiring. Because it is very likely that repeated vaccination and boosting will be required, African countries need to be able to accelerate and strengthen their own vaccine manufacturing capacity, and need partnerships with vaccine makers....

https://www.nytimes.com/2022/03/27/opinion/africa-fight-covid.html

A new effective early treatment option against COVID-19 and emerging SARS-CoV-2 VOCs!

Tirosh Shapira et al. 2022. A TMPRSS2 inhibitor acts as a pan-SARS-CoV-2 prophylactic and therapeutic. Nature (28 March 2022) https://www.nature.com/articles/s41586-022-04661-w

Unedited. Before final publication, the manuscript will undergo further editing.

Abstract
The COVID-19 pandemic caused by the SARS-CoV-2 virus remains a global public health crisis. Although widespread vaccination campaigns are underway, their efficacy is reduced due to emerging variants of concern (VOCs)... Development of host-directed therapeutics and prophylactics could limit such resistance and offer urgently needed protection against VOCs... Attractive pharmacological targets to impede viral entry include type-II transmembrane serine proteases (TTSPs), such as TMPRSS2, whose essential role in the virus lifecycle is to cleave the viral spike protein to expose the fusion peptide for cell entry... Here, we identify and characterize a small-molecule compound, N-0385, which exhibits low nanomolar potency and a selectivity index of 106+ at inhibiting SARS-CoV-2 infection in human lung cells and in donor-derived colonoids... In Calu-3 cells it inhibits entry of SARS-CoV-2 VOCs, B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma) and B.1.617.2 (Delta). Importantly, in the K18-human ACE2 transgenic mouse model of severe SARS-CoV-2 disease, we found that N-0385 affords a high level of prophylactic and therapeutic benefit following either multiple or even a single administration. This demonstrates that TTSP-mediated proteolytic maturation of spike is critical for SARS-CoV-2 infection in vivo and suggests that N-0385 provides a novel effective early treatment option against COVID-19 and emerging SARS-CoV-2 VOCs.

Eric Topol @EricTopol | 7:31 PM · Mar 29, 2022:
New @ScienceTM The mRNA vaccines are not interchangeable.
If you got Moderna vaccines, think about getting a Pfizer booster or if you got Pfizers, a Moderna booster
Text-highlighted abstract ( https://twitter.com/EricTopol/status/1508949980727287809/photo/1 )

Paulina Kaplone et al. 2022. mRNA-1273 and BNT162b2 COVID-19 vaccines elicit antibodies with differences in Fc-mediated effector functions. Science Translational Medicine • 29 Mar 2022 • First Release • DOI: 10.1126/scitranslmed.abm2311 https://science.org/doi/10.1126/scitranslmed.abm2311

DISCUSSION
...In conclusion, both mRNA vaccines induced robust functional humoral immune responses, with differences in epitope recognition and antibody-mediated functional properties. Additionally, strong responses against VOCs, including the beta and delta variants, were observed. RBD*-specific antibody depletion highlighted the different roles of non-RBD-specific antibody effector functions induced across the mRNA vaccines (Pfizer, Moderna), which might provide insights into potential differences in protective immunity conferred by these vaccines.

*Receptor Binding Domain

Some have disparaged epidemiologist Dr. Feigl-Ding for alarmism, but others commend him for being on target. (Except maybe that P1 in BC bit, but his was a reasonable hunch, IMHO.) Unfortunately, I'm afraid he might be right on how Omicron BA2 will play out in China...

China at a COVID Tipping Point
Eric Feigl-Ding | March 15, 2022
https://medriva.com/china-at-a-covid-tipping-point/

>110 margd: contd.

BEST BOOSTER? Mix it up — but depends which you had first.
Switching vaccine for the booster seems to be the best—
Pfizer to Moderna booster,
Moderna to Pfizer for booster, and
J&J should switch to Moderna / Pfizer booster.

How do COVID boosters compare?
Table ( https://twitter.com/DrEricDing/status/1451418802416197633/photo/1 )

- Eric Feigl-Ding @DrEricDing | 1:23 AM · Oct 22, 2021
--------------------------------------------------------------------------------

Natarajan K, Prasad N, Dascomb K, et al. Effectiveness of Homologous and Heterologous COVID-19 Booster Doses Following 1 Ad.26.COV2.S (Janssen Johnson & Johnson) Vaccine Dose Against COVID-19–Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults — VISION Network, 10 States, December 2021–March 2022. MMWR Morb Mortal Wkly Rep. ePub: 29 March 2022. DOI: http://dx.doi.org/10.15585/mmwr.mm7113e2external icon https://www.cdc.gov/mmwr/volumes/71/wr/mm7113e2.htm

...These findings underscore the importance of receiving recommended COVID-19 booster doses, when eligible, to prevent moderate to severe COVID-19 during Omicron variant predominance. All adults who have received mRNA vaccines for their COVID-19 primary series vaccination should receive an mRNA booster dose when they are eligible. Adults who received a Janssen vaccine as their first dose should preferentially receive a heterologous mRNA vaccine booster dose ≥2 months later, or a homologous Janssen vaccine booster dose if mRNA vaccine is contraindicated or unavailable.

From Canada, which has higher load BA2 than the US, anecdotal report on transmission...

Purely based on anecdotes over the last month, the top 3 ways to acquire #COVID19 appear to be:
1. Have a school-aged child in your household
2. Dine more than 2x weekly at a restaurant frequented by college-aged persons
3. Participate in recreational hockey
- Gerald Evans ( Infectious Disease MD, Queen's U) @skepticalIDdoc | 5:49 PM · Mar 31, 2022

-----------------------------------------------------------

Canada is more vaxxed than US but has less immunity form previous infections, I think?

Eric Topol @EricTopol | 4:58 PM · Mar 31, 2022:
The BA.2 variant is showing up more in Canada than the US so far
Graphs - https://twitter.com/EricTopol/status/1509636353440432159/photo/1

Become a Ventilation Expert in 6 Steps
This 🧵 is your training course. It's been left to building operators to ensure good ventilation - this hasn't been successful. Time to take back control over your air. You can do it! Just read on. 1/13...

(With discussion) https://twitter.com/joeyfox85/status/1509704366353223681
https://threadreaderapp.com/thread/1509704366353223681.html

- Joey Fox, P. Eng, M.A.Sc @joeyfox85 | 9:29 PM · Mar 31, 2022
HVAC Engineer. Ventilation, Filtration, UVGI. #COVIDisAirborne . If you know how it spreads, you know how to stop it. (Toronto)

Mouse study: "Boosting with historical vaccines, variant-matched mRNA vaccines ... or possibly heterologous platforms targeting historical spike proteins ... could minimize B.1.1.529 breakthrough infections by increasing the magnitude of neutralizing anti-SARS-CoV-2 antibodies ... or expanding the breadth of the antibody repertoire to better control variant strains...While our data suggest that certain cohorts (those with lower starting antibody responses) might benefit more from an Omicron-matched vaccine, further studies evaluating the magnitude and durability of the boosted immune responses are needed, especially in key vulnerable populations including the elderly, immunocompromised and immunosuppressed."
----------------------------------------------------

Buried deep in this nice mouse study* by my friend @msdiamondlab is this data.
Omicron-specific booster *does* improve responses to Omicron relative to an OG booster. You just have to wait a bit to see it. Will bet good $ that it'll be the same in people.
Graphs-Omicron pre- and post- booster ( https://twitter.com/deeptabhattacha/status/1509733344044486656/photo/1 )

- Deepta Bhattacharya @deeptabhattacha | 11:24 PM · Mar 31, 2022
Prof. of Immunology @uarizona studying antibody responses to infections and vaccines.

* Baoling Ying et al. 2022.Boosting with Omicron-matched or historical mRNA vaccines increases neutralizing antibody responses and protection against B.1.1.529 infection in mice. BioRxiv 9 Feb 2022. doi: https://doi.org/10.1101/2022.02.07.479419 https://biorxiv.org/content/10.1101/2022.02.07.479419v1

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

...DISCUSSION
...In summary, our studies in mice show protection against B.1.1.529 infection and disease when mRNA-1273 or Omicron-matched mRNA-1273.529 boosters are administered. While the low-dose primary immunization series of mRNA-1273 protected against WA1/2020 challenge, we observed substantial loss of serum neutralizing activity against B.1.1.529, and this was associated with breakthrough infection, inflammation, and disease in the lung after B.1.1.529 10
challenge. Despite diminished cross-variant neutralization responses by Omicron-matched and historical mRNA vaccines when administered as primary series immunizations, their delivery as boosters improved neutralizing responses against B.1.1.529, with slightly better protection conferred by the matched mRNA-1273.529 booster. Boosting with historical vaccines, variant-matched mRNA vaccines (Choi et al., 2021; Ying et al., 2021) or possibly heterologous platforms targeting historical spike proteins (e.g., adenoviral vectored or protein subunit vaccines (Atmar et al., 2022)) could minimize B.1.1.529 breakthrough infections by increasing the magnitude of neutralizing anti-SARS-CoV-2 antibodies (Atmar et al., 2021; Munro et al., 2021) or expanding the breadth of the antibody repertoire to better control variant strains
(Falsey et al., 2021; Naranbhai et al., 2022; Wang et al., 2021). While our data suggest that certain cohorts (those with lower starting antibody responses) might benefit more from an Omicron-matched vaccine, further studies evaluating the magnitude and durability of the boosted immune responses are needed, especially in key vulnerable populations including the elderly, immunocompromised and immunosuppressed.

A New Wave of Covid-19 Is Coming. Here’s How to Prepare.
Taking these seven steps now can lower your risk and minimize the disruption to your family’s life.
Tara Parker-Pope and Knvul Sheikh | March 30, 2022. Updated March 31, 2022.

Pay attention to Covid indicators in your community
Have high-quality masks on hand
Order home Covid tests sooner rather than later
Get a booster (when you’re eligible)
Get a pulse oximeter
Make a plan for antiviral drug treatment
Have backup plans for social events and travel

https://www.nytimes.com/2022/03/30/well/live/ba2-omicron-covid.html

US health officials drop Covid warning for cruise ship travelers
AP| 30 March 2022

...The CDC removed the Covid-19 “cruise ship travel health notice” that was first imposed in March 2020, after virus outbreaks on several ships around the world.

However, the agency expressed reservations about cruising.

...Cruise-ship operators have complained since the start of the pandemic that their industry has been singled out for a shutdown and then tighter Covid-19 restrictions than others, including airlines.

The Cruise Lines International Association said in a statement that the CDC’s decision to remove its health warning “recognizes the effective public health measures in place on cruise ships and begins to level the playing field between cruise and similarly situated venues on land”.

https://www.theguardian.com/us-news/2022/mar/30/us-cdc-drops-covid-warning-cruis...

"Treatment with ivermectin did not result in a lower incidence of medical admission to a hospital due to progression of Covid-19 or of prolonged emergency department observation among outpatients with an early diagnosis of Covid-19."

Eric Topol @EricTopol | 5:04 PM · Mar 30, 2022:
Ivermectin: the largest randomized, double-blind trial yet conducted, with early treatment, indicates there is no difference compared with placebo. It doesn't work. Period.

Text-highlighted abstract ( https://twitter.com/EricTopol/status/1509275271274323975/photo/1 )

Table-subgroup analyses of hospitalizations and emergency observation
( https://twitter.com/EricTopol/status/1509275271274323975/photo/2 )

Gilmar Reis et al. 2022. Effect of Early Treatment with Ivermectin among Patients with Covid-19. NEJM March 30, 2022
DOI: 10.1056/NEJMoa2115869 . http://nejm.org/doi/full/10.1056/NEJMoa2115869

Abstract
Background
The efficacy of ivermectin in preventing hospitalization or extended observation in an emergency setting among outpatients with acutely symptomatic coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is unclear.

Methods
We conducted a double-blind, randomized, placebo-controlled, adaptive platform trial involving symptomatic SARS-CoV-2–positive adults recruited from 12 public health clinics in Brazil. Patients who had had symptoms of Covid-19 for up to 7 days and had at least one risk factor for disease progression were randomly assigned to receive ivermectin (400 μg per kilogram of body weight) once daily for 3 days or placebo. (The trial also involved other interventions that are not reported here.) The primary composite outcome was hospitalization due to Covid-19 within 28 days after randomization or an emergency department visit due to clinical worsening of Covid-19 (defined as the participant remaining under observation for 6+ hours) within 28 days after randomization.

Results
A total of 3515 patients were randomly assigned to receive ivermectin (679 patients), placebo (679), or another intervention (2157). Overall, 100 patients (14.7%) in the ivermectin group had a primary-outcome event, as compared with 111 (16.3%) in the placebo group (relative risk, 0.90...). Of the 211 primary-outcome events, 171 (81.0%) were hospital admissions. Findings were similar to the primary analysis in a modified intention-to-treat analysis that included only patients who received at least one dose of ivermectin or placebo (relative risk, 0.89...) and in a per-protocol analysis that included only patients who reported 100% adherence to the assigned regimen (relative risk, 0.94...). There were no significant effects of ivermectin use on secondary outcomes or adverse events.

Conclusions
Treatment with ivermectin did not result in a lower incidence of medical admission to a hospital due to progression of Covid-19 or of prolonged emergency department observation among outpatients with an early diagnosis of Covid-19.

Freda Kreier. 2022. Morgue data hint at COVID’s true toll in Africa. Nature 603, 778-779 (2022) doi: https://doi.org/10.1038/d41586-022-00842-9 https://www.nature.com/articles/d41586-022-00842-9

...co-author Christopher Gill, a global-health specialist at Boston University in Massachusetts...and his colleagues in Zambia tested bodies in one of Lusaka’s largest morgues for SARS-CoV-2 over several months in 2020 and 2021. Test positivity was 32% overall — and reached around 90% during the peak of the waves caused by the Beta and Delta variants. Moreover, only 10% of the people whose bodies were found to contain the virus after death had tested positive while still alive. Some had falsely tested negative, but most had never been tested at all.

Although Gill and his colleagues can’t confirm that all of these people died of COVID-19, the results still stand in sharp contrast to official numbers. So far, there have been fewer than 4,000 confirmed COVID-19 deaths in Zambia, a country of around 19 million people. Separate findings published on 10 March suggest that Zambia’s ‘excess’ deaths — those above what would usually be expected — from 1 January 2020 to the end of 2021 exceeded 80,000.

COVID’s true death toll: much higher than official records

The Lusaka numbers mesh with statistics from South Africa, where a 2021 study found that only 4–6% of SARS-CoV-2 infections in two communities were officially documented... Further study of the same communities showed that 62% of study participants had been infected at least once from July 2020 to August 2021... Co-author Cheryl Cohen, an epidemiologist at the University of the Witwatersrand in Johannesburg, South Africa, says that many of these infections were asymptomatic, but that people with symptoms might also have gone undetected because of the cost and difficulty of getting tested.

Gill suspects that a major reason for the gap between his results and official counts is that most people in Zambia who die of COVID-19 do so outside medical care. Four out of five people tested in the study were never admitted to a hospital; the majority of unreported infections were in people living in Lusaka’s lowest-income neighbourhoods...

Minor correction (and margd fixed it), so no need to keep the error alive here :-)

>120 bnielsen:. Thanks: fixed it.

"Cardiac complications were rare after SARS-CoV-2 infection or mRNA COVID-19 vaccination. However, the risks for these complications were higher after infection than after vaccination among males and females in all age groups. These findings provide important context for balancing risks and benefits of mRNA COVID-19 vaccination among eligible persons (5 years or older)." Study

Block JP, Boehmer TK, Forrest CB, et al. Cardiac Complications After SARS-CoV-2 Infection and mRNA COVID-19 Vaccination — PCORnet, United States, January 2021–January 2022. MMWR Morb Mortal Wkly Rep. ePub: 1 April 2022. DOI: http://dx.doi.org/10.15585/mmwr.mm7114e1 https://www.cdc.gov/mmwr/volumes/71/wr/mm7114e1.htm

...The study population consisted of 15,215,178 persons aged (5 years or older), including 814,524 in the infection cohort; 2,548,334 in the first dose cohort; 2,483,597 in the second dose cohort; 1,681,169 in the unspecified dose cohort; and 6,713,100 in the any dose cohort (Table 1)... Among the four COVID-19 vaccination cohorts, 77%–79% of persons were aged (30 years or older); within the SARS-CoV-2 infection cohort, 63% were aged 30 years (or older).

Among males aged 5–11 years, the incidences of myocarditis and myocarditis or pericarditis were 12.6–17.6 cases per 100,000 after infection, 0–4 after the first vaccine dose, and 0 after the second dose; incidences of myocarditis, pericarditis, or MIS (multisystem inflammatory syndrome) were 93.0–133.2 after infection (Table 2). Because there were no or few cases of myocarditis or pericarditis after vaccination, the RRs for several comparisons could not be calculated or were not statistically significant. The RRs (risk ratios) were significant when comparing myocarditis, pericarditis, or MIS in the 42 days after infection (133.2 cases per 100,000) with myocarditis or pericarditis after the first (4.0 cases per 100,000; RR 33.3) or second (4.7 cases per 100,000; RR 28.2) vaccine dose.

Among males aged 12–17 years, the incidences of myocarditis and myocarditis or pericarditis were 50.1–64.9 cases per 100,000 after infection, 2.2–3.3 after the first vaccine dose, and 22.0–35.9 after the second dose; incidences of myocarditis, pericarditis, or MIS were 150.5–180.0 after infection. RRs for cardiac outcomes comparing infected persons with first dose recipients were 4.9–69.0, and with second dose recipients, were 1.8–5.6; all RRs were statistically significant.

Among males aged 18–29 years, the incidences of myocarditis and myocarditis or pericarditis were 55.3–100.6 cases per 100,000 after infection, 0.9–8.1 after the first vaccine dose, and 6.5–15.0 after the second dose; incidences of myocarditis, pericarditis, or MIS were 97.2–140.8 after infection. RRs for cardiac outcomes comparing infected persons with first dose recipients were 7.2–61.8, and with second dose recipients, were 6.7–8.5; all RRs were statistically significant.

Among males aged ≥30 years, the incidences of myocarditis and myocarditis or pericarditis were 57.2–114.0 cases per 100,000 after infection, 0.9–7.3 after the first vaccine dose, and 0.5–7.3 after the second dose; incidences of myocarditis, pericarditis, or MIS were 109.1–136.8 after infection. RRs for cardiac outcomes among infected persons compared with first dose recipients were 10.7–67.2, and compared with second dose recipients, were 10.8–115.2; all RRs were statistically significant.

Among females aged 5–11 years, incidences of myocarditis and myocarditis or pericarditis were 5.4–10.8 cases per 100,000 after infection, and incidences of myocarditis, pericarditis, or MIS were 67.3–94.2 after infection (Table 3). No cases of myocarditis or pericarditis after vaccination were identified. The incidences of cardiac outcomes did not vary by age among females aged (12 years or older). In this group, the incidences of myocarditis and myocarditis or pericarditis were 11.9–61.7 cases per 100,000 after infection, 0.5–6.2 after the first vaccine dose, and 0.5–5.4 after the second dose; incidences of myocarditis, pericarditis, or MIS were 27.1–93.3 after infection. Among females aged 12 years (or older), RRs for cardiac outcomes comparing infected persons with first dose recipients were 7.4–42.6, and with second dose recipients, were 6.4–62.9; all RRs were statistically significant...

I’m not a medical professional and this is not advice. But onpassing this step-by-step testing sheet that I used when I did a PCR. Friends and family kept testing negative on rapid tests but tested positive after I shared this with them. Tongue and cheek swabs, followed by nose.

The Ottawa Hospital Instructions for Combined throat and nose swab
https://twitter.com/kkirkup/status/1510028918060945411/photo/1

- Kristy Kirkup (Globe & Mail) @kkirkup | 6:58 PM · Apr 1, 2022

>116 margd: I think the one that a lot of virologists and infectious disease experts will take issue with is the decision about the second booster. There’s a general feeling that the Israeli study, which is a preprint, is flawed due to vast differences in control and study populations in different arms of the study, and due to short follow up. This and the ongoing success at severe illness protection after 3 shots. I personally will wait. If I were twenty years older in my 80s perhaps I’d see it differently, not sure.

Dominique Grandjean et al. 2022. Screening for SARS-CoV-2 Persistence in Long COVID Patients using Sniffer Dogs and Scents from Axillary Sweats Samples (Research Article). Journal of Clinical Trials, Vol.12 Iss. S16 No: 1000002 (5p) https://www.longdom.org/open-access/screening-for-sarscov2-persistence-in-long-c...

ABSTRACT
Background: Dogs can be trained to identify several substances not detected by humans, corresponding to specific Volatile
Organic Compounds (VOCs). The presence of VOCs, triggered by SARS-CoV-2 infection, was tested in sweat from long
COVID patients.

Patients and methods: An axillary (armpit) sweat sample of long COVID patients and of COVID-19 negative, asymptomatic individuals was taken at home to avoid any hospital contact. Swabs were randomly placed in olfaction detection cones, and the material sniffed by at least 2 trained dogs.

Results: Forty-five long COVID patients, mean age 45 (6-71), 73.3% female, with prolonged symptoms evolving for a mean of
15.2 months (5-22) were tested. Dogs discriminated in a positive way 23/45 (51.1%) long COVID patients versus 0/188 (0%)
control healthy individuals (p less than .0001).

Conclusion: Our data provide arguments for the persistence of viral antigens at least in some long COVID patients and raise
the possibility of future therapeutic options

...CONCLUSION
These results reinforce the hypothesis of a SARS-CoV-2 antigens persistence at least for some long COVID patients, possibly with virus actively replicating. It also shows the limited utility of SARS-CoV-2 serological tests made during long COVID. Such results raise the possibility of future therapeutic options and invite to build long COVID antiviral treatments trials. In addition, with a better characterization of the detected VOCs, an improvement of odor sampling methods and the development of point-of-care instruments, this detection by dogs could also help to implement scent-based tests for other major human pathogens.

David Elfstrom @DavidElfstrom | 9:41 PM · Apr 3, 2022:
P.Eng, Energy management, measurement & verification. Born @ 327 ppm CO₂. Safer infrastructure, #ventilation, #CorsiRosenthalBox optimization

The next time someone denies the use of a portable air cleaner in a classroom on a (false) basis that it might spread infection by moving air, or interfere with the HVAC system, show them this paper.

https://onlinelibrary.wiley.com/doi/epdf/10.1111/ina.12917

zeynep tufekci (UNC) zeynep | 8:03 PM · Apr 3, 2022:

New, from BioNTech co-founders Şahin and Türeci*:
“We report here that Omicron breakthrough infection in BNT162b2 vaccinated individuals results in strong neutralizing activity not only against Omicron, but also broadly against previous SARS-CoV-2 VOCs and against SARS-CoV-1."

Yes, they looked at not just other variants but also at the 2003 SARS. Not a typo.

According to this, breakthrough Omicron infections are conferring not just additional protection, but also *broadening* the immune response.

Promising news for usefulness of an Omicron-vaccine.
---------------------------------------------------------------------

* Jasmin Quandt et al. 2022. Omicron breakthrough infection drives cross-variant neutralization and memory B cell formation. BioRxiv 1 Apr 2022. doi: https://doi.org/10.1101/2022.04.01.486695 https://www.biorxiv.org/content/10.1101/2022.04.01.486695v1

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

Abstract
Omicron is the evolutionarily most distinct SARS-CoV-2 variant (VOC) to date and displays multiple amino acid alterations located in neutralizing antibody sites of the spike (S) protein. We report here that Omicron breakthrough infection in BNT162b2 vaccinated individuals results in strong neutralizing activity not only against Omicron, but also broadly against previous SARS-CoV-2 VOCs and against SARS-CoV-1. We found that Omicron breakthrough infection mediates a robust B cell recall response, and primarily expands preformed memory B cells that recognize epitopes shared broadly by different variants, rather than inducing new B cells against strictly Omicron-specific epitopes. Our data suggest that, despite imprinting of the immune response by previous vaccination, the preformed B cell memory pool has sufficient plasticity for being refocused and quantitatively remodeled by exposure to heterologous S protein, thus allowing effective neutralization of variants that evade a previously established neutralizing antibody response.

Eric Feigl-Ding @DrEricDing | 5:59 AM · Apr 5, 2022:
I cry for England 🏴󠁧󠁢󠁥󠁮󠁧󠁿—#BA2 hospitalizations have now exceeded old #Omicron’s peak—which were **merely 3 months ago**. So much for stupid mass infection natural herd strategy.

This is @borisjohnson & @sajidjavid’s horrible British 🇬🇧 exceptionalism.

HT @Antonio_Caramia
Graph-England hospital admissions May 2021-Apr 2022
https://twitter.com/DrEricDing/status/1511282321789538313/photo/1

Michael Mina @michaelmina_lab | 1:00 AM · Apr 6, 2022:
Epidemiologist, Immunologist, Pathologist, MD,PhD. Vaccines, immunity, Infectious disease, tests, public health. Previously Harvard Faculty. CSO @eMedCertified
https://twitter.com/michaelmina_lab/status/1511569540743933961

Q:Why do Symptoms start so early with Omicron?
A:When you have a BREAKTHROUGH infection, you already have immune memory that recognizes the virus FAST & causes IMMUNE symptoms very early
The virus often still “breaks through” but your symptoms have already kicked in days ago 1/
Charting omicron infection w/ & w/o vaxx ( https://twitter.com/michaelmina_lab/status/1511569540743933961/photo/1 )

Quote Tweet
Michael Mina @michaelmina_lab · Dec 17, 2021
IMPORTANT:
RAPID TESTS DO WORK WITH OMICRON
"But why are some people staying negative in the first days they have symptoms??"
This is expected. Symptoms don't = contagious virus
This is literally a reflection of the fact that vaccines are doing their job!
Infographic--are rapid tests failing with omicron--no
https://twitter.com/michaelmina_lab/status/1472024457640394756/photo/1

"potential impact of infection on pathways relevant to cancer affecting cell proliferation, development and survival, favoring DNA degradation, preventing the repair of damaging events and impeding the translation of RNA into working proteins"

Pau Erola ET AL. 2022. The network of SARS-CoV-2-cancer molecular interactions and pathways. BioRxiv 5 April 2022
doi: https://doi.org/10.1101/2022.04.04.487020 https://biorxiv.org/content/10.1101/2022.04.04.487020v1

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

Abstract
Background: Relatively little is known about the long-term impacts of SARS-CoV-2 biology, including whether it increases the risk of cancer. This study aims to identify the molecular interactions between COVID-19 infections and cancer processes. Materials and

Methods: We integrated recent data on SARS-CoV-2-host protein interactions, risk factors for critical illness, known oncogenes, tumor suppressor genes and cancer drivers in EpiGraphDB, a database of disease biology and epidemiology. We used these data to reconstruct the network of molecular links between SARS-CoV-2 infections and cancer processes in various tissues expressing the angiotensin-converting enzyme 2 (ACE2) receptor. We applied community detection algorithms and Gene Set Enrichment Analysis (GSEA) to identify cancer-relevant pathways that may be perturbed by SARS-CoV-2 infection.

Results: In lung tissue, the results showed that 4 oncogenes are potentially targeted by SARS-CoV-2, and 92 oncogenes interact with other human genes targeted by SARS-CoV-2. We found evidence of potential SARS-CoV-2 interactions with Wnt and hippo signaling pathways, telomere maintenance, DNA replication, protein ubiquitination and mRNA splicing. Some of these pathways were potentially affected in multiple tissues.

Conclusions: The long-term implications of SARS-CoV-2 infection are still unknown, but our results point to the potential impact of infection on pathways relevant to cancer affecting cell proliferation, development and survival, favoring DNA degradation, preventing the repair of damaging events and impeding the translation of RNA into working proteins. This highlights the need for further research to investigate whether such effects are transient or longer lasting. Our results are openly available in the EpiGraphDB platform at https://epigraphdb.org/covid-cancer and the repository https://github.com/MRCIEU/covid-cancer (https://doi.org/10.5281/zenodo.6391588).

Eric Topol @EricTopol | 5:00 PM · Apr 5, 2022
Just published @NEJM
4th dose vaccine protection in >620,000 people vs 3-doses in >620,000, all age 60+, Omicron wave, Israel
—4-fold lower rate of severe disease, no waning at 6 weeks
—2-fold lower rate of infection, rapidly waned

Text-1st p and abstract, highlighted ( https://twitter.com/EricTopol/status/1511448592350908416/photo/1 )
Fig 2-adjusted risk ratios for infection, severity, weeks after 4th dose
https://twitter.com/EricTopol/status/1511448592350908416/photo/2

Yinon M. Bar-On et al. 2022. Protection by a Fourth Dose of BNT162b2 against Omicron in Israel. NEJM April 5, 2022
DOI: 10.1056/NEJMoa2201570 http://nejm.org/doi/full/10.1056/NEJMoa2201570

Abstract
Background On January 2, 2022, Israel began administering a fourth dose of BNT162b2 vaccine to persons 60 years of age or older. Data are needed regarding the effect of the fourth dose on rates of confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and of severe coronavirus disease 2019 (Covid-19).

Methods Using the Israeli Ministry of Health database, we extracted data on 1,252,331 persons who were 60 years of age or older and eligible for the fourth dose during a period in which the B.1.1.529 (omicron) variant of SARS-CoV-2 was predominant (January 10 through March 2, 2022). We estimated the rate of confirmed infection and severe Covid-19 as a function of time starting at 8 days after receipt of a fourth dose (four-dose groups) as compared with that among persons who had received only three doses (three-dose group) and among persons who had received a fourth dose 3 to 7 days earlier (internal control group). For the estimation of rates, we used quasi-Poisson regression with adjustment for age, sex, demographic group, and calendar day.

Results The number of cases of severe Covid-19 per 100,000 person-days (unadjusted rate) was 1.5 in the aggregated four-dose groups, 3.9 in the three-dose group, and 4.2 in the internal control group. In the quasi-Poisson analysis, the adjusted rate of severe Covid-19 in the fourth week after receipt of the fourth dose was lower than that in the three-dose group by a factor of 3.5 ... and was lower than that in the internal control group by a factor of 2.3 .... Protection against severe illness did not wane during the 6 weeks after receipt of the fourth dose. The number of cases of confirmed infection per 100,000 person-days (unadjusted rate) was 177 in the aggregated four-dose groups, 361 in the three-dose group, and 388 in the internal control group. In the quasi-Poisson analysis, the adjusted rate of confirmed infection in the fourth week after receipt of the fourth dose was lower than that in the three-dose group by a factor of 2.0 ... and was lower than that in the internal control group by a factor of 1.8 ... However, this protection waned in later weeks.

Conclusions Rates of confirmed SARS-CoV-2 infection and severe Covid-19 were lower after a fourth dose of BNT162b2 vaccine than after only three doses. Protection against confirmed infection appeared short-lived, whereas protection against severe illness did not wane during the study period.

Eric Topol @EricTopol | 10:34 AM · Apr 5, 2022·Twitter Web App
Getting the dose right for Covid vaccines can be tricky, as we've seen for children less than age 5 with Pfizer.
Is there a better way to do this?

Table-doses of approved vaxx ( https://twitter.com/EricTopol/status/1511351555248857098/photo/1 )

Could computer models be the key to better COVID vaccines? (NEWS FEATURE)
For vaccine dosing decisions, past experience and best guesses won the day in the mad rush to beat back the pandemic. Modelling tools might have made a difference.
Elie Dolgin | 05 April 2022
https://nature.com/articles/d41586-022-00924-8

#140 in thread 27, contd.

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 | 10 February 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 study1 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.

What’s more, the risk was elevated even for those who were under 65 years of age and lacked risk factors, such as obesity or diabetes...

https://www.nature.com/articles/d41586-022-00403-0

* * Yan Xie et al. 2022. Long-term cardiovascular outcomes of COVID-19. Nature Medicine (Feb 7, 2022) https://www.nature.com/articles/s41591-022-01689-3

Eric Topol (Scripps) @EricTopol | 7:59 PM · Apr 4, 2022:
In a prospective cohort of 500+ people with #LongCovid vs healthy controls, 1 in 5 had evidence by MRI of heart function impairment at 6 months, which persisted in half at 1 year. Would be missed by blood tests (troponin)
81% had not been hospitalized
T 2-cardiac impairment by MRI at 6&12 months ( https://twitter.com/EricTopol/status/1511131328900579333/photo/1 )

Adriana Roca-Fernández et al. 2022. Cardiac impairment in Long Covid 1-year post-SARS-CoV-2 infection. MedRxiv April 4, 2022.
doi: https://doi.org/10.1101/2022.04.03.22272610 https://medrxiv.org/content/10.1101/2022.04.03.22272610v1

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

Abstract
Background Long Covid is associated with multiple symptoms and impairment in multiple organs. Cardiac impairment has been reported to varying degrees by varying methodologies in cross-sectional studies. Using cardiac magnetic resonance (CMR), we investigated the 12-month trajectory of cardiac impairment in individuals with Long Covid.

Methods 534 individuals with Long Covid underwent baseline CMR (T1 and T2 mapping, cardiac mass, volumes, function, and strain) and multi-organ MRI at 6 months (IQR 4.3,7.3) since first post-COVID-19 symptoms and 330 were rescanned at 12.6 (IQR 11.4, 14.2) months if abnormal findings were reported at baseline. Symptoms, standardised questionnaires, and blood samples were collected at both timepoints. Cardiac impairment was defined as one or more of: low left or right ventricular ejection fraction (LVEF and RVEF), high left or right ventricular end diastolic volume (LVEDV and RVEDV), low 3D left ventricular global longitudinal strain (GLS), or elevated native T1 in 3 or more cardiac segments. A significant change over time was reported by comparison with 92 healthy controls.

Results The technical success of this multiorgan assessment in non-acute settings was 99.1% at baseline, and 98.3% at follow up, with 99.6% and 98.8% for CMR respectively. Of individuals with Long Covid, 102/534 (19%) had cardiac impairment at baseline; 71/102 had complete paired data at 12 months. Of those, 58% presented with ongoing cardiac impairment at 12 months. High sensitivity cardiac troponin I and B-type natriuretic peptide were not predictive of CMR findings, symptoms, or clinical outcomes. At baseline, low LVEF, high RVEDV and low GLS were associated with cardiac impairment. Low LVEF at baseline was associated with persistent cardiac impairment at 12 months.

Conclusion Cardiac impairment, other than myocarditis, is present in 1 in 5 individuals with Long Covid at 6 months, persisting in over half of those at 12 months. Cardiac-related blood biomarkers are unable to identify cardiac impairment in Long COVID. Subtypes of disease (based on symptoms, examination, and investigations) and predictive biomarkers are yet to be established. Interventional trials with pre-specified subgroup analyses are required to inform therapeutic options.

Eric Topol (Scripps) @EricTopol | 2:07 PM · Apr 4, 2022:
"We found no safety concerns for currently administered COVID-19 vaccines during pregnancy."
Systematic review of 71 studies* reinforces safety in a vulnerable group who derive substantial vaccine protection vs serious adverse outcomes

Table-odd of adverse outcomes with and without vaxx ( https://twitter.com/EricTopol/status/1511042885520482304/photo/1 )
----------------------------------------------------------

* Ciapponi, Agustin and Berrueta, Mabel and Bardach, Ariel and Mazzoni, Agustina and Anderson, Steven A. and Argento, Fernando J. and Ballivian, Jamile and Bok, Karin and Comandé, Daniel and Goucher, Erin and Kampmann, Beate and Parker, Edward and Rodriguez Cairoli, Federico and Santa María, María Victoria and Stergachis, Andy and Voss, Gerald and Xiong, Xu and Zamora, Natalia and Buekens, Pierre M. and Zaraa, Sabra, Safety of COVID-19 Vaccines During Pregnancy: A Systematic Review and Meta-Analysis. Available at SSRN: https://ssrn.com/abstract=4072487 or http://dx.doi.org/10.2139/ssrn.4072487

Lancet preprint. 44 Pages. Posted: 1 Apr 2022. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4072487 https://deliverypdf.ssrn.com/delivery.php

Abstract
...Interpretation: We found no safety concerns for currently administered COVID-19 vaccines during pregnancy. Further experimental and real-world evidence should expand these findings that reinforce current recommendations about vaccinating pregnant persons with approved COVID-19 vaccines. Robust safety data for non-mRNA-based COVID-19 vaccines are urgently needed.

...In summary, based on the available data, there does not appear to be any obvious safety risk associated with mRNA COVID-19 vaccines, their components, or the technological platforms used for pregnant individuals. Therefore, it is reasonable to consider COVID-19 vaccination in pregnant individuals as they are at higher risk for adverse effects, although data for non-mRNA vaccines are urgently needed.

Confidence in vaccine safety and effectiveness are known key predictors for vaccine acceptance...and the ongoing clinical trials and observational studies will provide further important data on vaccine safety and efficacy in both mothers and infants. Given the current skew in the evidence base towards mRNA-LNP vaccines, research and surveillance on other platforms, especially in low- and lower-middle-income settings, should be prioritized.

In conclusion, we found no safety concerns for currently used COVID-19 vaccines during pregnancy. Our findings support its use for vaccinating pregnant persons, and the provided evidence will hopefully assist pregnant persons and policymakers in considering COVID-19 vaccination for this vulnerable group.

Scientists divided on need for 4th Covid shot after FDA quietly approved another round of boosters
Spencer Kimball | Apr 6 2022

Key Points
The FDA and CDC OK’d a second booster shot for people age 50 and older last week.
The decision was based on data from Israel, which rolled out fourth doses months ago.
Dr. Peter Marks, who heads the FDA office responsible for vaccine safety and efficacy, said shortly after the decision that another round of boosters will likely be needed in the fall.

Leading U.S. scientists and physicians worry that the FDA and CDC are moving too fast in approving a fourth round of Covid shots, with little public debate that gives the vaccine makers too big a role in setting the pace with which the doses are distributed across the nation.

The top U.S. public health agencies last week endorsed a fourth Covid shot for older adults without holding public meetings, drawing criticism from leading vaccine experts who believe federal health officials haven’t provided enough transparency about the reasons for the decision.

The authorization of a fourth dose for adults age 50 and older comes as the scientific community is divided over whether the data is sufficient to support another round of boosters, and whether authorizing additional shots is a sustainable public health policy, especially since protection against infection simply wears off over time. There is a debate over whether the goal of the vaccines is to prevent severe illness, which they’ve largely achieved, or infection as well — a more challenging proposition...

https://www.cnbc.com/2022/04/06/scientists-divided-on-need-for-4th-covid-shot-af...

COVID-19 and the heart: Can SARS-CoV-2 cause arrhythmia?
Marybeth Gallagher, RN | April 8, 2022

Specialized cells within the heart that regulate its rhythm can become selectively infected with SARS-CoV-2, the virus that causes COVID-19, according to a new study.

The infection of these cells, which are known as pacemaker cells and comprise the sinoatrial node (sinus node), can result in an irregular heartbeat, causing it to speed up (tachycardia) or slow down (bradycardia).

The study’s* findings offer a possible explanation as to why some COVID-19 patients report disrupted heart rhythms...

https://www.medicalnewstoday.com/articles/covid-19-and-the-heart-can-sars-cov-2-...
------------------------------------------------------------

* Yuling Han et al. 2022. SARS-CoV-2 Infection Induces Ferroptosis of Sinoatrial Node Pacemaker Cells. Circulation Research. 8 March 2022;130:963–977 https://doi.org/10.1161/CIRCRESAHA.121.320518 https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.121.320518

Abstract
...Results: Viral RNA and spike protein were detected in SAN cells in the hearts of infected hamsters. We established an efficient strategy to derive from hESCs (human Embryonic Stem Cells) functional human SAN (sinoatrial node)-like pacemaker cells, which express pacemaker markers and display SAN-like action potentials. Furthermore, SARS-CoV-2 infection causes dysfunction of human SAN-like pacemaker cells and induces ferroptosis*. Two drug candidates, deferoxamine and imatinib, were identified from the high content screen, able to block SARS-CoV-2 infection and infection-associated ferroptosis.

Conclusions: Using a hamster model, we showed that primary pacemaker cells in the heart can be infected by SARS-CoV-2. Infection of hESC-derived functional SAN-like pacemaker cells demonstrates ferroptosis as a potential mechanism for causing cardiac arrhythmias in patients with COVID-19. Finally, we identified candidate drugs that can protect the SAN cells from SARS-CoV-2 infection.

* Ferroptosis is a type of programmed cell death dependent on iron and characterized by the accumulation of lipid peroxides, and is genetically and biochemically distinct from other forms of regulated cell death such as apoptosis. (Wikipedia)

Jonathan Reiner (George Washington U) @JReinerMD | 11:17 AM · Apr 8, 2022
This is CDC’s community transmission map. This is what individuals should use to gauge individual risk. It’s not so easy to find on the CDC website. Only 24% of the country has low transmission rates.

Map ( https://twitter.com/JReinerMD/status/1512449602326351875/photo/1 )

COVID-19 Integrated County View
Maps, charts, and data provided by CDC, updates daily by 8 pm ET†

This site provides an integrated, county view of key data for monitoring the COVID-19 pandemic in the United States. It allows for the exploration of standardized data across the country.§ The footnotes describe each data source and the methods used for calculating the metrics. For the most complete and up-to-date data for any particular county or state, visit the relevant health department website. Additional data and features are forthcoming...

https://covid.cdc.gov/covid-data-tracker/#county-view?list_select_state=all_stat...

Dr. Jorge A. Caballero stands with 🇺🇦 @DataDrivenMD | 9:54 AM · Aug 2, 2021:
https://twitter.com/DataDrivenMD/status/1422194205355483136

31/Vaccines are necessary but not sufficient to prevent #LongCovid. A new study of #COVID19 breakthrough infections in vaccinated healthcare workers found that:
🔸#VaccinesWork! (only (39) breakthrough cases (among 1497 fully vaccinated health care workers0 )
🔸1 in 5 breakthrough cases developed #LongCovid

Text-highlighted abstract ( https://twitter.com/DataDrivenMD/status/1422194205355483136/photo/1 )
----------------------------------------------------

Moriah Bergwerk et al. 2022. Covid-19 Breakthrough Infections in Vaccinated Health Care Workers. October 14, 2021
N Engl J Med 14 Oct 2021; 385:1474-1484 DOI: 10.1056/NEJMoa2109072 https://nejm.org/doi/full/10.1056/NEJMoa2109072

Abstract
...Results. ... Most breakthrough cases were mild or asymptomatic, although 19% had persistent symptoms (6+ weeks)...

Conclusions. ... Most breakthrough infections were mild or asymptomatic, although persistent symptoms did occur...

At least 67 guests test positive for covid after Washington gala
More than 10 percent of attendees of (Apr 2, 2022) Gridiron dinner have been infected with the virus.
Annie Linskey | April 9, 2022
https://www.washingtonpost.com/politics/2022/04/09/least-67-guests-test-positive...

Eric Feigl-Ding @DrEricDing | 12:18 PM · Apr 11, 2022
⚠️DEATHS UP—In just 1 week, #COVID19 deaths spiked ⬆️45% in England. “Hospitals & ambulance services facing extreme pressures & high staff absences, forcing some to declare critical incidents & to warn of 12 hour waits in 🏥 ERs”.

Graph-deaths within 28 days of positive test, England ( https://twitter.com/DrEricDing/status/1513552049488764929/photo/1 )
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Elisabeth Mahase. 2022. Covid-19: Hospital and ambulance services struggle with huge demand and staff illness
BMJ 2022;377:o950 doi: https://doi.org/10.1136/bmj.o950 (Published 11 April 2022) https://bmj.com/content/377/bmj.o950

Hospitals and ambulance services in England are facing “extreme pressures” and a high volume of staff absences, forcing some to declare critical incidents and others to warn of 12 hour waits for patients in hospital emergency departments...

VFC @19_VFC | 6:56 PM · Apr 11, 2022
https://twitter.com/19_VFC/status/1513652157458919425

Approaching 3x level of previous peak in the eastern region of Ontario.

Graph-(wastewater count?) Dec 2021-Apr 2022, e Ontario
https://twitter.com/19_VFC/status/1513652157458919425/photo/1

Dave Vanness (Professor Health Policy & Admin PA) @djvanness | 7:44 AM · Apr 11, 2022:
So here's the thing about #LongCovid that keeps me up at night. If there's damage to vasculature in the heart or brain, that heart attack or stroke that you might have had at 80 now may hit you at 65; we won't have the data until it's too late.
----------------------------------------------------

Berenice Martínez-Salazar et al. 2022. COVID-19 and the Vasculature: Current Aspects and Long-Term Consequences (REVIEW article). Front. Cell Dev. Biol., 15 February 2022 | https://doi.org/10.3389/fcell.2022.824851 https://www.frontiersin.org/articles/10.3389/fcell.2022.824851/full

...Summary and Conclusion
Taken together, clinical manifestations of SARS-CoV-2 infection have been detected in several vascular beds (e.g., those of the lungs, heart, and kidneys) and are not restricted to the pulmonary system. According to current research, direct viral infection of cardiomyocytes and pericytes together with dysfunctional endothelium foster vascular dysfunction in COVID-19 patients. Endothelial cells, putatively not prone to direct viral infection through SARS-CoV-2, probably get indirectly activated via the inflammatory immune response (“cytokine storm”) mediated by the virus. In addition, pre-existing CVD (cardiovascular disease) renders COVID-19 patients particularly vulnerable for downstream vascular complications and COVID-19-associated mortality. Altogether, chronic inflammation and vascular damage contribute to the acute pathophysiology of COVID-19 but may also cause development of LCS ( Long COVID-19 syndrome ).

Currently, significant efforts are being made to decipher both the direct and indirect impact of SARS-CoV-2 on the vasculature. In vitro studies, for example of endothelial cells, pericytes and cardiomyocytes have already shed some light on how SARS-CoV-2 directly affects vascular cells and explored which downstream signaling events are involved. Yet, only limited conclusions on the contribution of immune cells to vascular dysfunction during SARS-CoV-2 infection can be drawn. More complex cell culture/organoid systems to better exploit and resemble the complex nature of cell-cell interactions need to be established in vitro. To complement these in vitro studies and allow for exploration of long-term consequences of dysfunctional vasculature in COVID-19 well-defined in vivo models need to be investigated. Hence, combined efforts are required to comprehend the varied responses to SARS-CoV-2 infection to pave the way for new treatment strategies, including those for the long-term cardiovascular effects of COVID-19.

Via Eric Topol:

Pei-Ni Jone et al. 2022. SARS-CoV-2 Infection and Associated Cardiovascular Manifestations and Complications in Children and Young Adults: A Scientific Statement From the American Heart Association. Circulation. 2022;0:10.1161/CIR.0000000000001064 .
Originally published11 Apr 2022. https://doi.org/10.1161/CIR.0000000000001064 https://www.ahajournals.org/doi/10.1161/CIR.0000000000001064 https://www.ahajournals.org/doi/epdf/10.1161/CIR.0000000000001064

Abstract
Coronavirus disease 2019 (COVID-19) resulted in a global pandemic and has overwhelmed health care systems worldwide. In this scientific statement, we describe the epidemiology, pathophysiology, clinical presentations, treatment, and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and multisystem inflammatory syndrome in children and young adults with a focus on cardiovascular manifestations and complications. We review current knowledge about the health consequences of this illness in children and young adults with congenital and acquired heart disease, the public health burden and health disparities of this infection in these populations, and vaccine-associated myocarditis.

...VACCINE-ASSOCIATED MYOCARDITIS
Vaccination is underway to prevent COVID-19 in those 5 years of age (or older). Research on the safety of vaccination in infants and young children is in progress. Myocarditis and pericarditis, presenting with chest pain and high tro-ponin levels typically 2 to 6 days after receipt of mRNA COVID-19 vaccine in young people, have been reported to the Vaccine Adverse Event Reporting System... In a series of 63 patients 21 years (or fewer) of age with myocarditis temporally associated with the COVID-19 vaccine, the mean age was 15.6 years, 92% were male, all had an elevated troponin, 7% had significant arrhythmias, 14% had decreased left ventricular systolic function (ejection fraction, 45%–54%), and 88% had evidence of myocarditis on cardiac magnetic resonance imaging... In this cohort, at a mean follow-up of 35 days, 86% of patients had resolution of symptoms and normalization of function; follow-up was not available in the remaining 14%... Treatment is largely supportive and includes primarily pain management with oral anti-inflammatory medications, although IVIG, steroids, and colchicine have been used... The mechanisms of myocarditis and pericarditis associated with mRNA COVID-19 vaccines are unknown at this time; the reasons for male predominance in these cases are also unknown... The benefit of COVID-19 vaccine outweighs the risks of rare myocarditis/pericarditis temporally associated with COVID-19 vac-cine: Per 1 million doses of COVID-19 vaccine in male individuals 12 to 29 years of age (the highest-risk group for vaccine-associated myocarditis), 11 000 COVID-19 cases, 560 hospitalizations, and 6 deaths would be prevented, whereas 39 to 47 cases of myocarditis would be expected... A study demonstrated that receipt of 2 doses of mRNA COVID-19 vaccine is highly effective in preventing MIS-C in the 12- to 18-year-old age group: the estimated effectiveness against MIS-C was 91% ... Thus, COVID-19 vaccination is still recommended to curb this pandemic, but active efforts are underway to investigate potential long-term effects of myocarditis associated with COVID-19 vaccination...

FUTURE
COVID-19 is still a relatively new disease, and our understanding of its effects, as well as the effects of the postinflammatory condition MIS-C, on the general pediatric population and on children and adolescents with acquired and congenital heart disease is evolving. We need to better understand the mechanisms, optimal treatment approach, and long-term outcomes of MIS-C. The development of novel antiviral therapies needs to be tested in children in clinical trials. Investigations focused on the long-term outcomes are needed for children with and without acquired and congenital heart disease who have had SARS-CoV-2 infection. The consequences of long COVID-19 and the impact of this disease on the heart have yet to be elucidated in children and young adults.

CONCLUSIONS
SARS-CoV-2 infection continues to infect patients worldwide, with variants circulating in different parts of the world. We have much to learn about the pathology of this disease but have gained some ground on the treat-ment of COVID-19 and management of children with MIS-C. The long-term cardiovascular manifestations of COVID-19 in children require continued clinical research trials.
-----------------------------------------------------------------

Enrico Ammirati et al. 2022. Prevalence, Characteristics, and Outcomes of COVID-19–Associated Acute Myocarditis. Circulation Vol. 145, No. 15:1123–1139. Originally published 11 Apr 2022 https://doi.org/10.1161/CIRCULATIONAHA.121.056817 . https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.056817

Abstract
...Conclusions:
AM ((acute myocarditis)) occurrence is estimated between 2.4 and 4.1 out of 1000 patients hospitalized for COVID-19. The majority of AM occurs in the absence of pneumonia and is often complicated by hemodynamic instability. AM is a rare complication in patients hospitalized for COVID-19, with an outcome that differs on the basis of the presence of concomitant pneumonia.

Eric Feigl-Ding (epidemiologist) @DrEricDing | 6:13 PM · Apr 11, 2022:
Watching—Just two new rising variants… #BA4 (yellow) and #BA5 (orange) now rising and displacing #BA2 (blue) in South Africa. Nothing to see here. Cases not rising much. Close your eyes. No hospitalizations yet. Put your heads in the sand. Go back to the parties. #CovidIsNotOver
Graph-variant prevalence Nov 2021-Apr 2022, S Africa ( https://twitter.com/DrEricDing/status/1513641429108760580/photo/1 )

Eric Topol (Scripps) @EricTopol 6:30 PM · Apr 11, 2022:

Vaccines and myocarditis/pericarditis: a new systematic review of 400+ million doses of various vaccines, from 1947 - 2021
—Overall incidence: Covid (18/M) vs non-Covid (56/M)
—Smallpox highest; Covid similar to flu shots
—mRNA risk: male, (less than) age 30, 2nd💉

Text-Ling summary, highlighted ( https://twitter.com/EricTopol/status/1513645568639254532/photo/1 )

Fig 2-table, myopericarditis cases per million vaccine dose, COVID & non-COVID
( https://twitter.com/EricTopol/status/1513645568639254532/photo/2 )

Fig 3-table, myopericarditis cases per million vaccine dose, COVID mRNA and non-mRNA ( https://twitter.com/EricTopol/status/1513645568639254532/photo/3 )

Fig 4-graph, incidence of myopericarditis by age ( https://twitter.com/EricTopol/status/1513645568639254532/photo/3 )
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Ryan Ruiyang Ling et al. Myopericarditis following COVID-19 vaccination and non-COVID-19 vaccination: a systematic review and meta-analysis. The Lancet Respiratory Medicine. Published:April 11, 2022 DOI:https://doi.org/10.1016/S2213-2600(22)00059-5 https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(22)00059-5/fullt...

...In conclusion, this meta-analysis of more than 400 million doses of vaccines suggests that the overall incidence of myopericarditis following COVID-19 vaccination is similar to that in the published literature on its incidence after influenza vaccination, and is lower than the incidence after live smallpox vaccination. The incidence of myopericarditis in younger males after mRNA COVID-19 vaccination is higher than expected by comparison with other age groups. The scale of mass global vaccination and enhanced surveillance might account for the increased reporting of this adverse event in the context of COVID-19 vaccination. Nonetheless, certain subpopulations—those of male sex or younger age and those receiving an mRNA vaccine, particularly the second dose—appear to be at increased risk of myopericarditis following COVID-19 vaccination. These findings are important additions to the conversation when weighing the risks and benefits of COVID-19 vaccination during this pandemic. Although the results of our analysis place the risks of COVID-19 vaccination into perspective, the decision to vaccinate should be informed by appropriately weighing the benefits and harms of COVID-19 vaccination, the local risk of exposure to COVID-19 infection at the time, and the risk of myopericarditis from COVID-19 infection itself.

"The Final Pandemic Betrayal: Millions of people are still mourning loved ones lost to COVID, their grief intensified, prolonged, and even denied by the politics of the pandemic." (The Atlantic article by Ed Yong, April 13)
https://www.theatlantic.com/health/archive/2022/04/us-1-million-covid-death-rate...

In just two years, COVID has become the third most common cause of death in the U.S., which means that it is also the third leading cause of grief in the U.S. Each American who has died of COVID has left an average of nine close relatives bereaved, creating a community of grievers larger than the population of all but 11 states. Under normal circumstances, 10 percent of bereaved people would be expected to develop prolonged grief, which is unusually intense, incapacitating, and persistent. But for COVID grievers, that proportion may be even higher, because the pandemic has ticked off many risk factors.

The social response in this country was horrible on many levels.

By upending the entire world, COVID could have created a shared experience that countered the loneliness of grief. But most of the people I’ve been speaking with feel profoundly lonely—detached from society, from their support network, and especially from their loved ones at the moment of their death.

Several personal stories are recounted in the article.

Vincent Rajkumar (Mayo Clinic) @VincentRK | 11:56 AM · Apr 16, 2022:

1 million deaths in the US.
A look back at how Covid has been sadly minimized:

-It's just the flu

-It's a hoax

-99.9% safe

-Only old people are dying

-We just test too much

-Docs make money saying deaths are due to Covid

-Died with not of Covid

-Nature's vaccine

A BA.2 Surge Could Wreak Unequal Havoc
— COVID's "new normal" response must target those repeatedly left behind
Anne Sosin, MPH, Lakshmi Ganapathi, MBBS, and Gavin Yamey, MD, MPH * | April 11, 2022

...there's a risk that if BA.2 does lead to a wave, it could wreak unequal havoc. We worry that the "new normal" will be plentiful boosters and rapid, easy access to antivirals for the well-off, while the least-off are left behind.

The last surge, driven by the Omicron variant, affected Americans unequally, a pattern likely to repeat itself. The share of Americans killed by the coronavirus during the Omicron surge was 63% higher than other large, wealthy nations and peak daily deaths exceeded the peak of the surge driven by the more virulent Delta variant. Deaths and hospitalizations were not evenly spread: Black adults were hospitalized at four times the rate of white adults at Omicron's peak. Children too young to be vaccinated were hospitalized at record levels, and one in five COVID deaths among children occurred during the Omicron surge.

... the U.S. must intentionally design systems to deliver testing and treatment to the individuals and communities at highest risk. The U.S. should automatically mail rapid tests to low-income households, and distribute tests as well as N95 masks via public schools and other community institutions. The "test-to-treat" programs should be expanded to include a broader range of sites and tailored to local realities, particularly in areas with limited pharmacy and primary care coverage. These strategies should be paired with a public information campaign enlisting both mass media and trusted local messengers.

Our public health strategies must also be adapted to protect those at greatest risk. An estimated 7 million Americans -- or in 1 in 37 adults -- are immunocompromised and cannot benefit fully from the protection of vaccines, and severe COVID-19 outcomes are overwhelmingly concentrated in this group. Independent analyses have demonstrated that the CDC's new community thresholds for action are too high to protect the most vulnerable members of communities and to operate schools safely. As mask mandates in schools and workplaces fall away, a potential BA.2 wave could exact a devastating toll on the lives and livelihoods of our highest risk community members. Schools, workplaces, and other essential services should reinstate masking at the earliest signs of a surge and provide accommodations to enable immunocompromised people to participate fully in daily life.

Significant investments have yielded a growing arsenal of tools to control the pandemic. It will be a moral stain on the country if we do not invest the political will and material resources to bring them to the Americans that need them most.

https://www.medpagetoday.com/opinion/second-opinions/98157

* Anne Sosin, MPH, is a policy fellow and public health researcher at the Nelson A. Rockefeller Center at Dartmouth College. Lakshmi Ganapathi, MBBS, is Instructor of Pediatrics at Harvard Medical School and Associate Director of the Pediatric Infectious Diseases Fellowship Program. Gavin Yamey, MD, MPH, is a professor of global health and public policy at Duke University, where he directs the Center for Policy Impact in Global Health.

Eric Topol (Scripps) @EricTopol | 5:49 PM · Apr 5, 2022:
A big plan to systematically study the extreme phenotype of #LongCovid via genomics and immunology, including possible superantigen and neurotoxin motifs

Fig. 1. Infographic Long Covid signs & symptoms, possible mechanisms
https://twitter.com/EricTopol/status/1511461172234493952/photo/1

Brodin, P., Casari, G., Townsend, L. et al. Studying severe long COVID to understand post-infectious disorders beyond COVID-19. Nat Med (2022). https://doi.org/10.1038/s41591-022-01766-7 https://nature.com/articles/s41591-022-01766-7

...Collectively, we believe that our genetic and immunological studies of patients with severe long COVID hold potential for better understanding of this complex condition, and by focusing on severe cases that develop after mild COVID-19, we maximize our chances of success. Our results would probably be applicable beyond COVID-19 and will hopefully provide important insights of relevance into other post-infectious disorders such as myalgic encephalomyelitis.

Andy Slavitt 💙💛 @ASlavitt | 5:06 PM · Apr 17, 2022:
Former Biden White House Sr Advisor, past head of Medicare/Medicaid for Obama. Author “Preventable” and host: @inthebubblepod .
https://twitter.com/ASlavitt/status/1515798926279946241

COVID Update: COVID may not be remembered primarily for the full hospitals, unpredictable variants, mask & vaccine controversies, or even the massive loss of life.
It may be thought of primarily as chronic disease affecting 10s of millions. 1/

Already today many are more worried about long-COVID than they are about simply getting a bout of COVID.
For good reason. If you’re vaccinated & boosted, surviving COVID is less of a concern. What comes next is. 2/

I recently talked to two people who know more about the causes & treatments for long-COVID than anybody else. Come listen. @VirusesImmunity (Akiko Awasaki, Yale) & @PutrinoLab (David Putrino, Mt Sinai). 3/
https://link.chtbl.com/InTheBubble?sid=twitter

We don’t know a lot about long COVID. And what we know can be confusing. What is clear is that 10s of millions of people maintain long-term chronic symptoms that can be diverse & debilitating.
As the # of people impacted accumulate, they could overshadow the acute stage. 4/

What we understand is that something* in the virus— or in our bodies when we get exposed— is causing a reaction in our parasympathetic nerve system.
This system that regulates involuntary functions like digestion, heart rate & immune response. 5/
*Will return to this

The vagus nerve is the main part of this system & it is a part of so many body functions from head to toe.
This is why everything from brain function to exhaustion to body temperature to skin to gut health to alertness can be impacted. 6/

About 10% of people with COVID seem to end up with these symptoms per @VirusesImmunity
which are also similar to ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome).

But this is only an estimate, made confusing by the fact that many people have lingering symptoms from acute COVID for months that eventually dissipate. 7/

We’ve interviewed many people with these symptoms. Included in them is my own 20 yo son & Senator @timkaine
as well as @dianaberrent (Tim & Diana have their own @inthebubblepod episodes, Zach does not.) 8/

The symptoms are diverse as the reach of the Vagus Nerve would indicate. Cold hands, trouble standing, blurred speech, racing heart rate, continuous pins & needles, constant stomach aches, extreme lethargy, continuous infections. 9/

On Monday, @AlbertBourla is on @inthebubblepod talking fairly exclusively about the next vaccines & current research.
He does make the comment that COVID could end up over the decades as prevalent as heart disease. 10/

Here are some things we do know from the experts.
-Chances of getting long-COVID are cut in half by being vaccinated.
-Vaccines can be taken soon after diagnosis & also help.
-There are treatments that work & those guidelines are being published. 11/

Here’s a snippet of @PutrinoLab (David Putrino, Mt Sinai) talking about the impact of effective rehabilitation & lifestyle treatments. Full dialogue on the link.
80% reduction in symptoms & a small number of people fully recovered is very promising. 12/
1:55 ( https://twitter.com/inthebubblepod/status/1514574237549445126 )

With more research, more improvements can be made. But so few can access treatment & thousands more in the US every day are coming down with what will end up as long-COVID.
As we make treatments more available, we will also need to update insurance & disability laws. 13/

There are multiple reasons we currently believe people get long-COVID per @VirusesImmunity (Akiko Iwasaki, Yale).
The virus can hide, prior exposure to Epstein-Barr, an auto-immune issue... And certain people may be more prone as she reviews in the interview (explanation in tweet 3). 14/

Many people I know still wear masks and avoid higher risk situations principally because of their fear of the risk of long-COVID.
It is an understandable reaction. 15/

We have developed many tools to make COVID survivable— vaccines, boosters, oral anti-virals, monoclonal antibodies.
But despite the progress on long-COVID, this is painstaking expensive & difficult research. 16/

We need a class of drugs focused on long-COVID, prevalent therapies, and a better understanding at how to prevent long-term illness.
Many with ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) know what it’s like to face real difficulties & feel ignored, misdiagnosed & doubted. 17/

One common website for ME/CFS says to “get better sleep.”
Some with long-COVID are mistakenly told to get in better conditioning. Not only wrong but deeply harmful advice. 18/

Fear of illness doesn’t need to dictate our lives. But a highly contagious virus that could create chronic illness at around 10,000 new people every day can’t be ignored.
Particularly as acute COVID becomes more curable, it’s one reason people will still wear masks indoors. 19/

As people move on, COVID becomes the territory of the marginalized. 20/

I’m going to keep returning to the topic on the show, keep pushing in Congress & keep the topic front & center the best I can. /end

>145 margd: Compare >143 margd: to >145 margd:
I’ve found Professor >145 margd: to be biased in that direction for a long time now. To me, for the healthy population, the main issue is >143 margd:, and it’s is not a trivial concern

>152 stellarexplorer: Agree that Long Covid is hugely concerning. Hopefully, though, we'll learn more about all manner of viral harm from research done on Long Covid.

Epidemiologist Eric Feigl Ding (sp?) is great for bringing us obscure, latest worldwide data, I think. He does seem ready to see harm in every variant, etc., which brings scorn from more cautious prognosticators, but he has support of others such as the Mayo Clinic blood cancer MD. Feigl Ding most missed it in worrying about P1's foothold in British Columbia--after it had killed so many people in Brazil. If I recall correctly, P1 was surpassed by Delta in BC? Even without Delta, BC demographics are SO different from Brazil's... Feigl Ding was born in Shanghai, so might have better insights there from his connection and knowledge of the dialect?