SARS-CoV-2 and COVID-19 (26...)

"...we summarize emerging evidence for the importance of the germinal centre (GC) response in the establishment of durable and broad immunity against SARS-CoV-2 and discuss new approaches to modulate the GC response to better protect against newly emerging SARS-CoV-2 variants...the GC B cell response persists in the draining lymph nodes for at least 6 months in some individuals following vaccination with SARS-CoV-2 mRNA-based vaccines..."

Florian Krammer @florian_krammer | 10:05 AM · Dec 6, 2021
Great review by the @TheBcellArtist

Quote Tweet
Nature Rev Immunol @NatRevImmunol · 37m
The germinal centre B cell response to SARS-CoV-2
Infographic ( https://twitter.com/NatRevImmunol/status/1467871965075492872/photo/1 )

Brian J. Laidlaw & Ali H. Ellebedy. 2021.The germinal centre B cell response to SARS-CoV-2. Nature Reviews Immunology (Dec 6, 2021) http://dlvr.it/SDrb8Z https://www.nature.com/articles/s41577-021-00657-1

Abstract
The germinal centre (GC) response is critical for the generation of affinity-matured plasma cells and memory B cells capable of mediating long-term protective immunity. Understanding whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination elicits a GC response has profound implications for the capacity of responding B cells to contribute to protection against infection. However, direct assessment of the GC response in humans remains a major challenge. Here we summarize emerging evidence for the importance of the GC response in the establishment of durable and broad immunity against SARS-CoV-2 and discuss new approaches to modulate the GC response to better protect against newly emerging SARS-CoV-2 variants. We also discuss new findings showing that the GC B cell response persists in the draining lymph nodes for at least 6 months in some individuals following vaccination with SARS-CoV-2 mRNA-based vaccines."

...Concluding remarks and perspective
... developing vaccination approaches that induce dimeric IgA at mucosal surfaces may be an important tool to limit reinfection.

:(

Michael Bang Petersen (prof poli sci) @M_B_Petersen | 10:12 AM · Dec 7, 2021
There is now officially community transmission with omicron in Denmark. ~50 % increase per day for the past few days.
Remember: Denmark has a very high capacity for testing and variant detection and, hence, is without blindfolds.
The spread is likely similar in your country.

Graph-confirmed # cases omicron, Denmark, Nov 28-Dec 6, 2021
https://twitter.com/M_B_Petersen/status/1468237024939360273/photo/1

How does the government count COVID-19 deaths?
USA Facts | October 25, 2021

Medical conditions or injuries at an individual’s time of death are not automatically official causes of death for the purpose of government statistics. That includes COVID-19...

https://usafacts.org/articles/how-does-the-government-count-covid-19-deaths/
----------------------------------------------------

Guidance for Certifying Deaths Due to Coronavirus Disease 2019 (COVID–19)
U.S. Department of Health and Human Services
Centers for Disease Control and Prevention
National Center for Health Statistics
National Vital Statistics System
Vital Statistics Reporting Guidance Report No. 3 ▪ April 2020
7p
https://www.cdc.gov/nchs/data/nvss/vsrg/vsrg03-508.pdf

"On average, singing produced 77% more aerosol than talking, adults produced 62% more aerosol than minors, and males produced 34% more aerosol than females. After accounting for participant voice volume and exhaled CO2 (both of which were positively correlated with aerosol emissions) in linear models, the age and sex differences were attenuated and no longer statistically significant."

Nicholas Good etal. 2021. Respiratory Aerosol Emissions from Vocalization: Age and Sex Differences Are Explained by Volume and Exhaled CO2. Environ. Sci. Technol. Lett. Publication Date:November 9, 2021 https://doi.org/10.1021/acs.estlett.1c00760 https://pubs.acs.org/doi/10.1021/acs.estlett.1c00760

Abstract
Evidence suggests that airborne transmission of infectious respiratory aerosol plays an important role for the SARS-CoV-2 virus. This work characterized respiratory aerosol emissions from a panel of healthy individuals of varying age and sex while talking and singing in a controlled laboratory setting. Particle number concentrations between 0.25 and 33 μm were measured from 63 participants aged 12–61 years with concurrent monitoring of voice volume and exhaled CO2 levels. On average, singing produced 77% (95% CI: 42,109%) more aerosol than talking, adults produced 62% (CI: 27,98%) more aerosol than minors, and males produced 34% (CI: 0,70%) more aerosol than females. After accounting for participant voice volume and exhaled CO2 (both of which were positively correlated with aerosol emissions) in linear models, the age and sex differences were attenuated and no longer statistically significant. These results support further investigation of voice volume and CO2 as indicators of infection risk indoors.

Uh oh? Preliminary, but get your vaxx & boosters, and grab your N95 respirators, boys and girls(?)

Florian Krammer (virologist Icahn) @florian_krammer | 3:56 PM · Dec 7, 2021:
First look at Omicron neutralization from @sigallab. That is a huge drop.

Quote Tweet
Rupert Beale @bealelab · 13m
https://twitter.com/bealelab/status/1468323168892895238
First neutralisation data from @sigallab. Live virus, small number of sera (but obviously very important study). That's 40 fold drop compared to D614G (spike protein ((ancestral type??))), essentially variant against which original vaccine efficacy was determined
(NB does *not* mean 40 fold drop in efficacy).
Graph ( https://twitter.com/bealelab/status/1468323168892895238/photo/1 )
(see entire figure at *)

Florian Krammer @florian_krammer
Whats orange and green?

Dr. H @1900HO
Green: vaccinated and infected
Orange: vaccinated only
But apparently without a booster. So boosters might help a bit

Björn Meyer @_b_meyer
First data on Omicron neutralization by @sigallab
* Fig 1. ACE2 dependence and partial neutralization of the Omicron variant by Pfizer BNT162b2 elicited immunity
( https://twitter.com/_b_meyer/status/1468319835012673549/photo/1 )

Prof Ed Wild @ProfEdWild
Sorry - for amateurs, in what *is* it a 40-fold drop? Thx

Rupert Beale @bealelab
Neutralisation titres. For example, if neut titre was 1:4000 for D614G (spike protein on ancestral type?), on average would be 1:100 for Omicron. Suppose threshold for protection was 1:50 (oversimplification!), you'd need 1:2000 to start with, etc.

Milltown Friedman @Booze_Fags_Mags
You take blood and dilute in increasingly more dilute amounts. With every dilution you check if there are enough antibodies to neutralise the virus…the more dilute you go and get a response the greater antibody effect. With omicron the effect faded after fewer dilutions vs delta (ancestral type?)

Victor Grubsky (physics) @VGrubsky
I think we can all agree that the current wild-type spike vaccines will not be effective against #Omicron transmission, correct? (no answer)

>5 margd: contd.

Alex Sigal (South Africa virologist) @sigallab | 4:02 PM · Dec 7, 2021
We have completed our first experiments on neutralization of Omicron by Pfizer BNT162b2 vaccination elicited immunity
Manuscript available at https://sigallab.net
and should be available on medRxiv in the coming days

There are a few results:
1. Omicron still uses ACE2
2. There is a very large drop in neutralization of Omicron by BNT162b2 immunity relative to ancestral virus
3. Omicron escape from BNT162b2 neutralization is incomplete. Previous infection + vaccination still neutralizes

This is our first set of data and is not corrected for values going below the lowest dilution used - we present the raw fold change, which is likely to be adjusted as we do more experiments. (In later tweet he says his amount of virus is limiting at this point.)

Just be be clear on something as I'm still awake, this was better than I expected of Omicron. The fact that it still needs the ACE2 receptor and that escape is incomplete means its a tractable problem with the tools we got

Florian Krammer (Icahn virologist) @florian_krammer | 4:49 PM · Dec 7, 2021:
Thanks for making this so freely available Alex! And thanks for the quick and great work. The world owes you and your team a lot.

Eric Topol @EricTopol | 7:31 PM · Dec 7, 2021:
Why would a 3rd shot (booster) likely override Omicron's immune evasiveness?
(if you missed it, Omicron led to a ~40-fold reduction in nAbs, via @sigallab >5 margd: >6 margd:)

Take a look at the 40-fold rise of neutralizing antibodies (NAbs)
https://medrxiv.org/content/10.1101/2021.12.02.21267198v1 *
Graph--antibody titer increase 0, 2, 4 weeks after Pfizer booster ( https://twitter.com/EricTopol/status/1468377695666855938/photo/1 )
----------------------------------------------------------------

C. Sabrina Tan et al. 2021. Ad26.COV2.S or BNT162b2 Boosting of BNT162b2 Vaccinated Individuals. MedRxiv Dec 5, 2021.
doi: https://doi.org/10.1101/2021.12.02.21267198 https://medrxiv.org/content/10.1101/2021.12.02.21267198v1 https://www.medrxiv.org/content/10.1101/2021.12.02.21267198v1.full.pdf

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

ABSTRACT

Previous studies have reported that a third dose of the BNT162b2 (Pfizer) COVID-19 vaccine increased antibody titers and protective efficacy. Here we compare humoral and cellular immune responses in 65 individuals who were vaccinated with the BNT162b2 vaccine and were boosted after at least 6 months with either Ad26.COV2.S (Johnson & Johnson; N=41) or BNT162b2 (Pfizer; N=24).

Eric Feigl-Ding @DrEricDing
Bad early signal—The 7-day average coronavirus level found in Boston-area wastewater has now reached their highest levels since the start of the pandemic. Wastewater always precedes a wave.

Graph-Boston SARS CoV-2 RNA/ml last 30 days ( https://twitter.com/DrEricDing/status/1468481169280970759/photo/1 )

Weekly averages of COVID-19 detected in Boston wastewater reach highest levels yet
Amanda Kaufman | Updated December 7, 2021
https://bostonglobe.com/2021/12/07/nation/weekly-averages-covid-19-detected-bost...

Jason Abaluck et al. 2021. Impact of community masking on COVID-19: A cluster-randomized trial in Bangladesh. Science • 2 Dec 2021. DOI: 10.1126/science.abi9069 https://www.science.org/doi/10.1126/science.abi9069

Abstract
We conducted a cluster-randomized trial to measure the effect of community-level mask distribution and promotion on symptomatic SARS-CoV-2 infections in rural Bangladesh from November 2020 to April 2021 (N = 600 villages, N = 342,183 adults). We cross-randomized mask type (cloth vs. surgical) and promotion strategies at the village and household level. Proper mask-wearing increased from 13.3% in the control group to 42.3% in the intervention arm (adjusted percentage point difference = 0.29 ...). The intervention reduced symptomatic seroprevalence (adjusted prevalence ratio = 0.91...), especially among adults 60+ years in villages where surgical masks were distributed (adjusted prevalence ratio = 0.65 ...). Mask distribution and promotion was a scalable and effective method to reduce symptomatic SARS-CoV-2 infections.

...Our intervention increased mask-wearing...
Our intervention increased physical distancing...
Our intervention had no impact on social distancing...
Our intervention reduced symptomatic seroprevalence...
Our intervention reduced WHO COVID-19 symptoms...
In-person reinforcement is crucial to our intervention...
Our intervention yields persistent increases in mask-wearing...
Women wear masks more but men respond more to the intervention...
The effect on symptomatic seroprevalence is especially large among the elderly...
The effect on WHO COVID-19 symptoms is larger among the elderly...
Men and women have similar reductions in symptoms and symptomatic seroprevalence...

...In summary, we found that mask distribution, role modeling, and promotion in a LMIC (low- and middle-income countries) setting increased mask-wearing and physical distancing, leading to lower illness, particularly in older adults. We find especially robust evidence that surgical masks prevent COVID-19. Whether people with respiratory symptoms should generally wear masks to prevent respiratory virus transmission—including for viruses other than SARS-CoV-2—is an important area for future research. Our findings suggest that such behavior may benefit public health...

Candidate for “highest-stakes question of the next several months” (rare hot take)
Holden Karnofsky | Dec 6, 2021

Will the FDA (A) treat Omicron-specific booster vaccines like flu shots, or will it (B) impose more requirements and slow them down?

So far, it looks like the default is (B), and it also looks like Omicron has a significant chance of making the coming months at least as painful as the debut of COVID-19 (due to its high infectiousness and potential for major vaccine escape). The hypothesis here is that switching to (A) is the most promising single way to reduce that chance, by getting a fully effective vaccine for Omicron ASAP.

There's lots of uncertainty - Omicron might turn out to be mild (at least in vaccinated people), might turn out to be less scary than expected in other ways (less infectiousness, less vaccine escape), or manufacturing might be a big enough bottleneck that we're too slow even under option (A). But still, when you think about how bad a redux of early 2020 would be, (A) vs. (B) seems to have massive stakes riding on it. If there’s anything you can imagine yourself doing to move us from a default of (B) to a world of (A), I think it would be good to drop whatever else is on your plate long enough to do that....

...Michael Mina...
" We should do the least necessary checks of the new variant vaccines. Put them into 20 people and make sure they elicit the desired immune responses. Do NOT do any sort of efficacy study and these vaccines should be fast tracked like flu shots.

Unfortunately FDA has essentially no ability to balance the cost of slowness and the cost of inaction with the benefit of action. The FDA viewpoint is that inaction and whatever cost comes from that is not on them. They are used to a system where it’s better to do nothing than act with any uncertainty. But that’s Bc the FDA is not designed for emergencies. It just isn’t. It is horribly inefficient and unable to effectively make calculations around public health vs medicine.

To this day we still do not have a regulatory framework for products that have as a base use one of public health. Vaccines elicit ideas of public health but ultimately are evaluated and regulated as medicine. As far as safety this is important. But as far as efficacy and the regulatory approaches and data required, it’s entirely around individual benefit. Which at this point I hope everyone recognizes that’s the wrong angle in a pandemic.

For example, we knew that a single dose vaccine would yield 90% or more protection from severe disease for at least a few months, yet we withheld first doses in order to give people second doses and importantly we have those second doses in a suboptimal manner just Bc that’s the hard data we had. But the soft data (the data from decades of immunology research across the world) allowed us to know that spacing the vaccines months apart would have been better both for individuals and for public health. We didn’t do that."...

https://www.cold-takes.com/candidate-for-highest-stakes-question-of-the-next-sev...

>5 margd: >6 margd: contd. Omicron, previous infections, & vaccines

Florian Krammer ( Professor at the Department of Microbiology Icahn School of Medicine at Mount Sinai) @florian_krammer | 8:51 PM · Dec 7, 2021
https://twitter.com/florian_krammer/status/1468397677562011650
https://threadreaderapp.com/thread/1468397677562011650.html

1) What do I think about Omicron now that some neutralization data is available? My impression hasn't change. We seem to see a drastic reduction in neutralizing activity, far more than with previous variants. Little activity was left in vaccinated individuals and it is likely...

2)....that very little activity is left in convalescent individuals. However, people who were infected and then vaccinated did have residual neutralizing activity despite a drastic reduction. This certainly also bodes well for vaccinated individuals who received their....

3)...booster dose. While we have no data for them yet, it is likely that they will have residual neutralizing activity. So, my guess - and at this point it is really just a guess - is that vaccine effectiveness against infection in convalescent or 2x vaccinated individuals....

4)....will take a hit and will be strongly reduced. I think protection against infection will remain higher in convalescent vaccinated and 3x vaccinate individuals. I would also speculate, that protection against severe disease may remain reasonably high in all...

5)...individuals with baseline immunity. This is speculation, and this protection may in the end be reduced as well, we will see. The reason why I am saying this is because there are several safety nets. These include residual neutralizing activity (maybe below detection),....

6)...non-neutralizing antibodies (which often target more conserved spots), T-cells and an anamnestic memory B-cell response. The last point is very important, also for potential Omicron specific boosters. It is very likely that the memory B-cell compartment includes B cells....

7)...that target neutralizing epitopes conserved between wild type SARS-CoV-2 and Omicron. The fact that we find residual neutralizing activity in some individuals with high titers can also be seen as evidence for this. Now, when Omicron spike is encountered, either due to a....

8)...breakthrough infection or through an Omicron specific booster vaccine, exactly these cells will likely be activated, they will become antibody secreting cells and increase antibody levels that may neutralize Omicron efficiently within days.

9) All of the above may also depend on the vaccine that was used. Some vaccines will likely provide better protection than others. I am most worried about inactivated vaccines and 'one-shot' vaccines.

10) Now having said all of this, I still think Omicron is highly problematic. If it spreads widely - and the signs are that it will do that - we will likely see another wave. The wave may be less severe in terms of number of deaths because many people will have....

11)...partial immunity. But as we see now with the Delta wave, even in relatively highly vaccinated populations the virus finds those who are vulnerable (because of medical conditions or because they chose to stay unvaccinated) and does a lot of damage. And currently the....

12)...vaccination rate in the US is pretty low. My speculation is that this variant will significantly prolong the pandemic. We have to take it serious. And we need much more data to better understand it.

PS: We are all tired. The health care workers are tired, the researchers are tired, everybody is tired of the pandemic. We all want our lives back. Unfortunately, the virus doesn't care. And we can only get through this together.

PPS: I do not know what all of this means for long COVID.

Florian Krammer @florian_krammer | 5:52 AM · Dec 8, 2021:
Data from @CiesekSandra confirms @sigallab's data (>5 margd: >6 margd:). And 2x Moderna is not saving the day.
Anyways, there are still a lot of questions, these are all preliminary data sets with low n
(that's not a criticism, just the reality of generating data fast). Thanks Sandra!!!

Quote Tweet
Sandra Ciesek @CiesekSandra · 6h
See thread at https://twitter.com/CiesekSandra/status/1468465347519041539 ,
https://threadreaderapp.com/thread/1468465347519041539.html

Translated from German by Google:
our first dates (data?) for Neutralization of Omicron versus Delta is done:
2x Biontech,
2x Moderna,
1xAZ / 1x Biontech after 6 months
0% neutralization with Omicron,
also 3x Biontech 3 months after booster only 25% NT (neutralization?) versus 95% with Delta.
Up to 37 times the reduction in Delta vs. Omicron

Fig 1-Antibody-neutralisation efficiency against Delta and Omicron (in English)
( https://twitter.com/CiesekSandra/status/1468465347519041539/photo/1 )

From Dean of Brown U's School of Public Health:
Ashish K. Jha, MD, MPH @ashishkjha · 1h

With early data rolling in, here’s where we currently stand with Omicron
First, we have plenty of evidence that Omicron will spread easily, quickly, and far
We should expect, globally, relatively large waves of infections
How will people fare? Depends on who you are

I think of 3 groups of people
(1) Immunologically naïve
(2) Somewhat protected
(3) Highly protected
Depending on which group you are in Your risk of infection varies As does your risk of bad outcomes
So let's talk about each of them

Group 1
Immunologically naïve: Who are they? Unvaccinated and not recently infected
How will they fare? They are likely to get infected with Omicron at very, very high rates Many of them will get sick.
I hope...but doubt... that the virus will be mild for them 3/6

Group 2
Somewhat protected Who are they? Folks with 1-2 shots of a vaccine OR a recent infection
How will they fare? Large numbers will see breakthrough infections Severe illness should largely be preventable High risk folks in this group still at risk of bad outcomes 4/6

Group 3
Highly protected Who are they? Folks boosted or have hybrid immunity (infection + 2 shots)
How will they fare? Relatively high degree of protection against infection but probably some breakthroughs Severe illness very rare Will look like “mild” disease 5/6

So when you hear Omicron no big deal Because "this is a mild disease" Understand that for some, that is true But not for all
That's why critical to get 1st/2nd shots for as many unvaccinated as quickly as possible And 3rd shots for everyone else

Fin

Isaac Bogoch (MD scientist Ont) @BogochIsaac | 8:56 AM · Dec 8, 2021
More arrows pointing toward 2 #COVID19 vaccine doses as helpful for Omicron, but better with 3 doses.
3 doses of Pfizer's vaccine "increases the neutralizing antibody titers by 25-fold compared to two doses against the Omicron variant."
(*small lab-based study, press-release*)

Photo of Pfizer BioNTech Dec 8, 2021 press release ( https://twitter.com/BogochIsaac/status/1468580152267452416/photo/1 )
__________________________________________________
ETA
Pfizer says COVID booster offers protection against omicron
LAURAN NEERGAARD | Dec 8, 2021

...Pfizer and its partner BioNTech said that while two doses may not be protective enough to prevent infection, (small, unpublished) lab tests showed a booster increased by 25-fold people’s levels of virus-fighting antibodies against the omicron variant.

Blood samples taken a month after a booster showed people harbored levels of omicron-neutralizing antibodies that were similar to amounts proven protective against earlier variants after two doses...

Pfizer’s findings, announced in a press release, are preliminary and haven’t yet undergone scientific review. But they’re the first from a vaccine maker examining whether the booster doses that health authorities are urging people to get may indeed make an important difference...

https://apnews.com/article/coronavirus-pandemic-science-business-health-coronavi...

>5 margd: >6 margd: Sigal study on omicron, previous infection, Pfizer vaxx

Sandile Cele...Alex Sigal. 2021. SARS-CoV-2 Omicron has extensive but incomplete escape of Pfizer BNT162b2 elicited neutralization and requires ACE2 for infection. MedRxiv 2021-267417v1-sigal. 9p. Contributed by STAT. https://www.documentcloud.org/documents/21150195-medrxiv-2021-267417v1-sigal

COVID-19 Breakthrough: Scientists Discover How the SARS-CoV-2 Virus Evades Our Immune System
Gracie Blackwell, Texas A&M College of Medicine | December 8, 2021

...discovery...could lead to new therapies to prevent the virus from proliferating in the human body.

...“We found that the SARS-CoV-2 virus carries a suppressive gene that acts to inhibit a human gene in the immune system that is essential for destroying infected cells,” said Dr. Koichi Kobayashi, adjunct professor at the College of Medicine and lead author of the paper.

Naturally, the cells in a human’s immune system are able to control virus infection by destroying infected cells so that the virus cannot be replicated. The gene that is essential in executing this process, called NLRC5, regulates major histocompatibility complex (MHC) class I genes, which are genes that create a pathway that is vital in providing antiviral immunity. Kobayashi and his colleagues discovered this in 2012.

“During infection, the amount and activity of NLRC5 gene become augmented in order to boost our ability of eradication of viruses,” Kobayashi said. “We discovered that the reason why SARS-CoV-2 can replicate so easily is because the virus carries a suppressive gene, called ORF6, that acts to inhibit the function of NLRC5, thus inhibiting the MHC class I pathway as well.”...

https://scitechdaily.com/covid-19-breakthrough-scientists-discover-how-the-sars-...

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Ji-Seung Yoo et al. 2021. SARS-CoV-2 inhibits induction of the MHC class I pathway by targeting the STAT1-IRF1-NLRC5 axis15. Nature Communications. November 2021. DOI: 10.1038/s41467-021-26910-8 https://www.nature.com/articles/s41467-021-26910-8 https://www.nature.com/articles/s41467-021-26910-8

...Discussion
...Altogether, our study provides mechanistic insight into ORF6-mediated SARS-CoV-2 immune evasion via targeting the MHC class I antigen-presenting pathway (Fig. 7e). Moreover, our study indicates that SARS-CoV-2 possesses impressive immune evasion strategies targeting two critical host antiviral defense programs, the MHC class I and IFN signaling pathways, that result in successful viral adaptation to human hosts. The mechanistic findings in this study may provide potential molecular targets for developing the therapeutics against COVID-19.

New ‘stealth’ form of omicron discovered in Australia
Frances Vinall | Dec 8, 2021

Authorities in the Australian state of Queensland say they have identified a new lineage of the omicron variant, which has been dubbed “omicron-like.”

The new sub-classification has 14 mutations of the original coronavirus, compared with 30 in the omicron variant, the state’s acting chief health officer, Peter Aitken, said Wednesday.

Researchers have since identified cases in South Africa and Canada with the same genomic sequences as the Queensland case, with some researchers informally calling it a “stealth version” of omicron, the Guardian reported.

Omicron-like doesn’t have the “S-gene dropout” used to differentiate omicron from other coronavirus strains in quickly processed PCR tests, which could make it harder to track.

But Catherine Bennett, epidemiology chair at Australia’s Deakin University, said PCR testing didn’t always work to detect omicron, as opposed to other variants.

“The reason they’re using the term ‘stealth’ is just because we were quite excited that one version of the PCR test could pick up this dropout … otherwise you’ve got to wait for your genomic testing,” she said. She added that genomic sequencing picks up the known omicron variant as well as the new lineage.

The omicron-like lineage was identified in a traveler with covid-19 who had come from South Africa to Queensland and remains in hotel quarantine. The state’s mandatory measure for most new overseas arrivals keeps them isolated for 14 days.

It is too soon to tell what the new sub-classification means for “clinical severity or vaccine effectiveness,” Aitken said.

Bennett said variations within new variants are to be expected. “It might not be an issue,” she said. “You’re getting this microevolution all the time. We have lots of variants circulating, and we don’t hear about them at all because they didn’t become variants of interest.”

https://www.washingtonpost.com/nation/2021/12/08/covid-omicron-variant-live-upda...

Dorry Segev (Johns Hopkins transplant surgeon) @Dorry_Segev | 3:39 PM · Dec 8, 2021:
FDA authorizes long-acting pre-exposure monoclonal antibodies for immunocompromised/transplant patients!!
Game-changer!! (that said, vaccination is still important for everyone, including immunocompromised) Spread the word!

FDA News Release
Coronavirus (COVID-19) Update: FDA Authorizes New Long-Acting Monoclonal Antibodies for Pre-exposure Prevention of COVID-19 in Certain Individuals
Dec 8, 2021
https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-...

Entire 22-post, plain-language thread is worth a read, IMHO--evolving consensus on omicron transmissibility, immune evasiveness, severity...and what to expect this winter.

Andy Slavitt* @ASlavitt | 9:18 PM · Dec 8, 2021:
https://twitter.com/ASlavitt/status/1468767014881677315
https://threadreaderapp.com/thread/1468767014881677315.html

COVID Update: 2 weeks ago we said we would know a lot more about Omicron in 2 weeks.
I’ve rounded up the best scientific opinions to share a consensus. 1/ ...

A third shot on top of 2 prior shots works well against Delta and appears to make a big difference with Omicron. 20/

Rapid tests. Therapeutics. Ventilation. n-95 masks.
All help on top of vaccines. 21/

And this is how the winter of 2021-2022 is different from last winter.
As bad a storm as comes, we have the tools to stay safe. If we use them. /end

* Andy Slavitt @ASlavitt -- Former Biden White House Sr Advisor for COVID Response, past head of Medicare/Medicaid for Obama. Author “Preventable” and host: @inthebubblepod

Pre-Omicron Israeli research: People 50+ who got 3rd shot had 90% lower death rate
TOI staff | Dec 9, 2021

...Researchers looked at data of over 840,000 people who got booster; paper co-author says study ‘unequivocally’ shows value of extra dose against Delta strain

...Researchers studied the data of 843,208 individuals, of whom 758,118 (90%) received the booster (the third dose) during the period of the study.

In that group, there were 65 deaths due to COVID-19 — 0.16 per 100,000 persons per day.

In the group of vaccinated individuals who did not receive the booster, 137 died — 2.98 per 100,000 persons per day...

https://www.timesofisrael.com/pre-omicron-israeli-research-people-50-who-got-3rd...

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Ronen Arbel et al. 2021. BNT162b2 Vaccine Booster and Mortality Due to Covid-19. NEJM December 8, 2021
DOI: 10.1056/NEJMoa2115624 https://www.nejm.org/doi/full/10.1056/NEJMoa2115624

Natalie E. Dean, PhD (biostat, Emory U) @nataliexdean | 11:57 AM · Dec 9, 2021
(8-post thread at https://twitter.com/nataliexdean/status/1468988180032589825 )

A sketch to explain how a new variant may appear milder even with no change in underlying virulence.
This can occur because, when calculating the fraction of cases that are severe,
the denominator now includes many re-infections that had previously been averted. A thread. 1/8
Sketch ( https://twitter.com/nataliexdean/status/1468988174693289994/photo/1 )

...

Kids Vaccines Aren’t Reaching the Toronto Neighbourhoods That Need Them Most
Tai Huynh | December 9, 2021

Data from the first weeks of the rollout reveals low vaccine uptake in areas with the largest school outbreaks.

...Analysis...using unreleased data downloaded from Toronto Public Health’s website shows a wide disparity in vaccination rates for kids, with some Toronto neighbourhoods at nearly 70 percent vaccinated with a first dose and others sputtering along in the single digits...Those rates break along familiar socio-economic lines.

...The latest projections from the Ontario COVID-19 Science Advisory Table (which did not account for the more transmissible Omicron) show that, with the current suite of public health measures and assuming 50 percent of kids aged five to 11 are vaccinated by the end of December, daily cases in the province would rise above 1,700 by January, once again straining ICUs. Crank up the percentage of kids vaccinated and the curves flatten; decrease it and the curves shoot up...

https://thelocal.to/kids-vaccines-arent-reaching-the-toronto-neighbourhoods-that...

Where did ‘weird’ Omicron come from?
Mutations could have accumulated in a chronically infected patient, an overlooked human population, or an animal reservoir
Kai Kupferschmidt | 1 Dec 2021

...Omicron clearly did not develop out of one of the earlier variants of concern, such as Alpha or Delta. Instead, it appears to have evolved in parallel—and in the dark. Omicron is so different from the millions of SARS-CoV-2 genomes that have been shared publicly that pinpointing its closest relative is difficult, says Emma Hodcroft, a virologist at the University of Bern. It likely diverged early from other strains, she says. “I would say it goes back to mid-2020.”

...In one case (Richard Lessells, an infectious disease researcher at the University of KwaZulu-Natal) and his colleagues described in a preprint, a young woman in South Africa with an uncontrolled HIV infection carried SARS-CoV-2 for more than 6 months. The virus accumulated many of the same changes seen in variants of concern, a pattern also seen in another patient whose SARS-Cov-2 infection persisted even longer.

To head off one possible source of future variants, Lessells says, “What we need to do is close the gaps in the HIV treatment cascade. So we need to get everybody diagnosed, we need to get everybody on to treatment, and we need to get those that are currently on ineffective treatment on to effective treatment regimens.”

...Aris Katzourakis, an evolutionary biologist at the University of Oxford, is skeptical of the animal scenario, given the sheer number of human infections. ...

Many global health leaders have used the emergence of Omicron to focus the world’s attention on the huge gap between COVID-19 vaccinations in richer and poorer countries. Richard Hatchett, head of the Coalition for Epidemic Preparedness Innovations, opened his remarks at the World Health Assembly on 29 November by saying low vaccine coverage in South Africa and Botswana had “provided a fertile environment” for the variant’s evolution. “The global inequity that has characterized the global response has now come home to roost,” he said.

Yet there is little evidence to support that statement, some scientists say. “The idea that if we had vaccinated more in Africa, we wouldn't have this: I'd like that to be true, but we have literally no way of knowing,” Katzourakis. For now, the lessons to be drawn from Omicron remain as unknown as its origin.

https://www.science.org/content/article/where-did-weird-omicron-come

Interesting. I approached with skepticism, but found myself surprised to be agreeing with, US Sen Ron Johnson's (R-WI) suggestions for Listerine: “Standard gargle, mouthwash, has been proven to kill the coronavirus...If you get it, you may reduce viral replication. Why not try all these things?” My thought was that LISTERINE® Antiseptic IS available OTC, and there is some very preliminary indication that LISTERINE® Original Antiseptic Mouthwash may work on COVID (below)--why NOT gargle, if one has a sore throat and is home diagnosed with COVID?

Even better than Listerine was "Betadine Antiseptic Sore Throat Gargle", a small, unreviewed study (registered as a clinical trial) found. Who knew there was an iodine throat gargle?? (Don't swallow!)

Made me wonder about hydrogen peroxide formula for oral use. A few years ago, my dental hygienist scolded me for using H2O2 (just a splash to prevent mold growth in my irrigator!), because, apparently, CDC worried it mows down entire oral microbiome, good & bad. A couple visits later, however, I was offered a small amount of H2O2 to swish, per recommendation of CDC--I assume to minimize COVID risk to dental staff. Because it mows down entire oral microbiome, good & bad!

Then there are zinc lozenges that I use for sore throat to head off colds, 20% of which are caused by human coronavirus... ( https://www.snopes.com/fact-check/zinc-lozenges-coronavirus/ )

I'm vaxxed, etc., but am willing to also use OTC remedies for sore throat if some small indication that OTC stuff that may fight COVID early on in the nose and throat...

The Stupid Times Are Killing Us: Listerine Forced to Debunk Ron Johnson’s COVID Cure Claims
Tara Dublin | December 9, 2021
https://hillreporter.com/the-stupid-times-are-killing-us-listerine-forced-to-deb...
------------------------------------------------

LISTERINE COVID-19 Information for Health Care Professionals

...Our understanding of the course of COVID-19 disease transmission continues to evolve. Overall, more research is needed to understand whether use of mouthwashes can impact viral transmission, exposure, viral entry, viral load and ultimately affect meaningful clinical outcomes or have a public health impact. This is why Johnson & Johnson Consumer Health will continue to be active and consider further investment in lab and clinical studies with trusted collaborators, playing an important role in understanding the interaction between oral care and the COVID-19 virus in the mouth....

...in vitro studies have shown that LISTERINE® mouthwashes inactivate COVID-19 and its surrogate viruses. However, no evidence-based clinical conclusions can be drawn with regards to the anti-viral activity of LISTERINE® Antiseptic mouthwash at this time...

...in vivo...gargling with Betadine or LISTERINE® Original Antiseptic three times per day for seven days in early COVID-19 positive patients may reduce viral load in the oropharyngeal and nasopharyngeal regions...study called Povidone-Iodine* Vs Essential Oil** Vs Tap Water Gargling For COVID-19 Patients (GARGLES)*** has not yet been published in a peer-reviewed journal and, given its small size (N=20), it cannot be used to draw conclusions...

https://www.listerineprofessional.com/covid-19-update

* Betadine Antiseptic Sore Throat Gargle?

** I assumed it was the alcohol in Listerine, not "essential oils" that might clear SARS-CoV-2(?). I need to read ingredient label, I guess.
___________________________________________

*** Nurul Azmawati Mohamed et al. 2020. EARLY VIRAL CLEARANCE AMONG COVID-19 PATIENTS WHEN GARGLING WITH
POVIDONE-IODINE Betadine Antiseptic Sore Throat Gargle? AND ESSENTIAL OILS Listerine® Original Antiseptic Mouthwash? – A CLINICAL TRIAL. MedRxiv Sept 9, 2020. (15 p) https://doi.org/10.1101/2020.09.07.20180448

Preprint. Not reviewed.

Abstract
Background: Gargling had been reported to have significant roles in the prevention and treatment of respiratory tract infections. The purpose of this study was to assess the ability of regular gargling to eliminate SARS-CoV-2 in the oropharynx and nasopharynx.

Methodology: This pilot, open labeled, randomized, parallel study compared the effect of 30 seconds, 3 times/day gargling using 1% povidone-iodine (PVP-I), essential oils and tap water on SARS-CoV-2 viral clearance among COVID-19 patients in a tertiary hospital in Kuala Lumpur. Progress was monitored by day 4,6 and 12 PCR (Ct value), gargling and symptoms diary as well as clinical observations.

Results: Five confirmed Stage 1 COVID-19 patients were recruited for each arm. The age range was from 22 to 56 years old. The majority were males. Two respondents had co-morbidities, which were asthma and obesity. Viral clearance was achieved at day 6 in 100%, 80%, 20% and 0% for 1% PVP-I, essential oils, tap water and control group respectively. Analysis of 1% PVP-I group versus control group showed significant p-value for comparison of PCR results on Day 4, Day 6 and Day 12.

Conclusions: This preliminary study showed that gargling with 1% PVP-I and essential oils show great potential to be part of the treatment and management of Stage 1 COVID-19. Larger studies are required to ascertain the benefit of gargling for different stages of COVID-19 patients. This study was registered in clinicaltrial.gov (NCT04410159).

Michigan leads the US in # COVID cases per capita. Below, U Michigan hospitals issue an urgent call for vaccination, mask-wearing, and safe holiday celebrations: https://www.youtube.com/watch?v=CH1Q8dQ2UOw -- 4 x 5-min presentations + 20 min Q&A

COVID-19 Surge at Michigan Medicine - December 8, 2021 Press Conference (41:49)
Dec 8, 2021

Michigan Medicine
With COVID-19 cases high for months, and rising rapidly in recent weeks, leaders from Michigan Medicine held a press conference on Wednesday, Dec. 8, 2021 to share with the news media and community an update on how patients with and without COVID-19, and staff, are being affected. They issued an urgent call for vaccination and mask-wearing, and safe holiday celebrations. Speaking in the press conference were:

• Marschall Runge, M.D., Ph.D., CEO of Michigan Medicine, dean of U-M Medical School and executive vice president for medical affairs at the University of Michigan
• David Miller, M.D., M.P.H., president of University of Michigan Health
• Nancy May, D.N.P., RN-BC, chief nurse executive
• John Carethers, M.D., chair of the department of internal medicine
• Laraine Washer, M.D., professor of infectious diseases and medical director of infection prevention and epidemiology
• Tony Denton, J.D., senior vice president and chief operating officer
• Brad Uren, M.D., clinical associate professor of emergency medicine

The event was moderated by Mary Masson, director of public relations. For information about COVID-19 impacts and response at Michigan Medicine, visit https://www.uofmhealth.org/covid-19-u...

https://www.youtube.com/watch?v=CH1Q8dQ2UOw

Adam Fischer (Twitter social media) @afischer71 | 12:48 AM · Dec 9, 2021:
I put together this chart of Omicron antibody study results
- ~5-40x fold reduction
- 2 doses waned likely has little efficacy
- Booster likely retains some efficacy
Many thanks to @erlichya , @EricTopol, @BarakRaveh, @profshanecrotty, @DrEricDing, @DiseaseEcology for info.

Table--Omicron antibody neutralization studies as of Dec 8, 2021
https://twitter.com/afischer71/status/1468819932389392386/photo/1

Study shows benefit of regular classroom ventilation
SWI | December 9, 2021

...The research by the Swiss Federal Laboratories for Materials Science and Technology (EMPA) analysed data from CO2 sensors in 150 classrooms in canton Graubünden, before checking the results against the regular Covid tests run by the schools.
The correlation is clear: “more students and teaching staff were infected with the corona virus in classrooms with poor air quality than in rooms that are regularly ventilated”, EMPA https://www.empa.ch/web/s604/covid-and-co2 . The badly ventilated rooms – 60% of those studied, said canton Graubünden – came out with six times as many cases as the better ventilated ones.

The researchers recommend airing out classrooms more than usual, even when outside temperatures are low; they say three times each hour, for five minutes at a time, is best...

https://www.swissinfo.ch/eng/society/study-shows-benefit-of-regular-classroom-ve...

Brian E. McGarry et al. 2021. Nursing Home Staff Vaccination and Covid-19 Outcomes. NEJM December 8, 2021. DOI: 10.1056/NEJMc2115674

...Figure 1. Cumulative Adjusted Covid-19 Outcomes, According to Nursing Home Staff Vaccination Coverage and County-Level Prevalence of Covid-19.)...

...In the presence of high community prevalence of Covid-19, nursing homes with low staff vaccination coverage had higher numbers of cases and deaths than those with high staff vaccination coverage. These findings show the extent to which staff vaccination protects nursing home residents, particularly in communities with high Covid-19 transmission.

https://www.nejm.org/doi/full/10.1056/NEJMc2115674

>24 margd: Listerine contd.

FactCheck Posts › SciCheck
Researchers Studying Whether Mouthwashes Can Reduce Viral Load, COVID-19 Transmission
Lori Robertson | December 9, 2021
https://www.factcheck.org/2021/12/scicheck-researchers-studying-whether-mouthwas...

COVID-19: Do windy days reduce transmission?
Jonathan W. Raymond on December 9, 2021

A recent study investigated the role of wind speed in SARS-CoV-2 transmission in outdoor spaces.

Reduced wind speed had associations with transmission rates during warmer spells.

However, below a certain temperature, wind speed made little difference to transmission rates, possibly because people were more likely to socialize indoors...

https://www.medicalnewstoday.com/articles/covid-19-do-windy-days-reduce-transmis...
------------------------------------------------

Sean A. P. Clouston et al. 2021. A wind speed threshold for increased outdoor transmission of coronavirus: an ecological study.
BMC Infectious Diseases volume 21, Article number: 1194 (Nov 27, 2021) https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06796-z

Abstract
Background
To examine whether outdoor transmission may contribute to the COVID-19 epidemic, we hypothesized that slower outdoor wind speed is associated with increased risk of transmission when individuals socialize outside.

Methods
Daily COVID-19 incidence reported in Suffolk County, NY, between March 16th and December 31st, 2020, was the outcome. Average wind speed and maximal daily temperature were collated by the National Oceanic and Atmospheric Administration. Negative binomial regression was used to model incidence rates while adjusting for susceptible population size.

Results
Cases were very high in the initial wave but diminished once lockdown procedures were enacted. Most days between May 1st, 2020, and October 24th, 2020, had temperatures 16–28 °C and wind speed diminished slowly over the year and began to increase again in December 2020. Unadjusted and multivariable-adjusted analyses revealed that days with temperatures ranging between 16 and 28 °C where wind speed was less than 8.85 km per hour (KPH) had increased COVID-19 incidence (aIRR (Multivariable-adjusted incidence rate ratio) = 1.45...) as compared to days with average wind speed  8.85 or more KPH.

Conclusion
Throughout the U.S. epidemic, the role of outdoor shared spaces such as parks and beaches has been a topic of considerable interest. This study suggests that outdoor transmission of COVID-19 may occur by noting that the risk of transmission of COVID-19 in the summer was higher on days with low wind speed. Outdoor use of increased physical distance between individuals, improved air circulation, and use of masks may be helpful in some outdoor environments where airflow is limited.

>30 margd:

We live at the top of the escarpment overlooking the Great Rift Valley, where there are very strong winds most of the time and nothing between us and Tanzania. We always reckon that if anyone coughs up here any COVID aerosol will immediately be whisked away to Tanzania a hundred kms away!

>31 John5918: What a stunning view you must have--and sunrise/sets!
________________________________________________

Will Covid Evolve to Be Milder?
Andrew Pekosz | Dec. 10, 2021

(Dr. Pekosz investigates the replication and disease potential of respiratory viruses, including SARS-CoV-2, influenza and other emerging viruses.)

...Will Covid-19 become milder over time? The answer to that question is most likely yes, but it may not have anything to do with the virus evolving to induce milder disease.

Scientists now know that SARS-CoV-2 can, at least to some degree, reinfect people who were previously infected or vaccinated. The combination of prior infections and vaccinations are building immunity in the population. This immunity isn’t perfect because it can’t block infection completely, but it does dampen the disease the virus can induce by shortening the time of infection, reducing the amount of virus that is produced and therefore reducing the symptoms and disease.

...In December 2019, SARS-CoV-2 entered a human population that had no immunity to it. In December 2021, the Omicron variant is entering a human population that has a large amount of immunity to SARS-CoV-2. That immunity in and of itself will lessen the disease severity of the variant. But in people with limited or compromised immunity, such as the unvaccinated, the elderly or the immune compromised, SARS-CoV-2 may still be able to cause severe disease because they don’t have protection conferred by pre-existing immunity. Covid-19 becoming a milder disease is not a decision the virus will make; it’s a decision that all of us can make if we take advantage of the vaccines that can control spread and reduce the burden of this disease.

https://www.nytimes.com/2021/12/10/opinion/covid-evolve-milder.html

Good news.

The T cell response to Omicron appears to be preserved (preprint data*).
While infection/reinfection may be more frequent, a prior immune response (vaccination/recovery from infection) will still be helpful.
(& 3rd doses should help further).

- Isaac Bogoch (U Toronto MD scientist) @BogochIsaac | 8:01 AM · Dec 10, 2021:

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

* Andrew Redd et al. 2021. Minimal cross-over between mutations associated with Omicron variant of SARS-CoV-2 and CD8+ T cell epitopes identified in COVID-19 convalescent individuals. BioRxiv Dec 9, 2021. doi: https://doi.org/10.1101/2021.12.06.471446
https://www.biorxiv.org/content/10.1101/2021.12.06.471446v1

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

Abstract
There is a growing concern that ongoing evolution of SARS-CoV-2 could lead to variants of concern (VOC) that are capable of avoiding some or all of the multi-faceted immune response generated by both prior infection or vaccination, with the recently described B.1.1.529 (Omicron) VOC being of particular interest. Peripheral blood mononuclear cell samples from PCR-confirmed, recovered COVID-19 convalescent patients (n=30) infected with SARS-CoV-2 in the United States collected in April and May 2020 who possessed at least one or more of six different HLA haplotypes were selected for examination of their anti-SARS-CoV-2 CD8+ T-cell responses using a multiplexed peptide-MHC tetramer staining approach. This analysis examined if the previously identified viral epitopes targeted by CD8+ T-cells in these individuals (n=52 distinct epitopes) are mutated in the newly described Omicron VOC (n=50 mutations). Within this population, only one low-prevalence epitope from the Spike protein restricted to two HLA alleles and found in 2/30 (7%) individuals contained a single amino acid change associated with the Omicron VOC. These data suggest that virtually all individuals with existing anti-SARS-CoV-2 CD8+ T-cell responses should recognize the Omicron VOC, and that SARS-CoV-2 has not evolved extensive T-cell escape mutations at this time.

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

T cells attack infected cells, not just the virus as antibodies do in first line of defense (https://askabiologist.asu.edu/t-cell).

Omicron: Three vaccine doses key for protection against variant
James Gallagher | Dec 10, 2021

...The real-world data backs up laboratory studies that showed a 40-fold reduction in the ability of antibodies from double-vaccinated people to take out the virus.

There is optimism that vaccines will still keep many people out of hospital even if more do get Covid. Data on severity could be published next week.

However, an Omicron wave could be problematic even if it was milder. A large and sudden wave could lead to everyone who is still vulnerable needing hospital care at the same time...

Dr Mary Ramsay, head of immunisation at the UKHSA, said: "These early estimates should be treated with caution but they indicate that a few months after the second jab, there is a greater risk of catching the Omicron variant compared to Delta strain."

"We expect the vaccines to show higher protection against the serious complications of COVID-19, so if you haven't yet had your first two doses please book an appointment straight away."

https://www.bbc.com/news/health-59615005
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Eric Feigl-Ding @DrEricDing | 4:33 AM · Dec 11, 2021
Time for VE (vaccine effectiveness) data*—2 shot vaccine effectiveness against symptomatic #Omicron is not good.
UK data says 2 doses isn’t strong—
Pfizer 2 dose VE for 15+ weeks is 34-36%; AstraZeneca 2 doses VE after 25 weeks is just 5.9%.
Pfizer booster yields 71-76%.
Fig 1-VE weeks after 2-dose AZ, Pf, and both boosted by Pf
https://twitter.com/DrEricDing/status/1469601149573603328/photo/1
https://twitter.com/DrEricDing/status/1469601149573603328/photo/2

2) So how bad is the data for 2 doses? Well let’s walk through it… the table tells more about the efficacy against #Omicron beyond the figures above. 2 shots of Oxford-AstraZeneca don’t even have enough data for those

The US confirmed Covid deaths exceeds 800,000
Killed 1 of every 100 Americans over age 65
Killed 1 of every 415 Americans.
~300,000 deaths well after US vaccine rollout

Image-NYT front page ( https://twitter.com/EricTopol/status/1470409057936707585/photo/1 )
Image-graph, pace of COVID deaths in US ( https://twitter.com/EricTopol/status/1470409057936707585/photo/2 )

https://nytimes.com/2021/12/13/us/covid-deaths-elderly-americans.html
by @juliebosman @albertsun @amy_harmon

- Eric Topol (Scripps) @EricTopol | 10:03 AM · Dec 13, 2021

Denmark has published an omicron report in English (and Danish):
among 2,471 omicron cases, 27 have been hospitalized
- Nurit Baytch @NuritBaytch | 4:32 PM · Dec 12, 2021

Covid-19 Rapport om omikronvarianten (6 p)
12. dec. | 2021

...Data from 22 November to 13.00 o’clock on 12 December represent a total of 2,471 B.1.1.529 (Omicron) SARS-CoV-2 cases in Denmark.

Few test results may not be included in the report due to data delays. Furthermore, small changes in data can occur retrospectively. Data included in this report are from 22 November to 12 December 2021 unless otherwise stated.

Omicron cases are identified through variant PCR and whole-genome sequencing (WGS)...

https://files.ssi.dk/covid19/omikron/statusrapport/rapport-omikronvarianten-1212...

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

Danish report discussed at https://twitter.com/NuritBaytch/status/1470144472063299593
Nurit Baytch @NuritBaytch:
- an underestimate of the % of omicron cases requiring hospitalization
- higher hospitalization for omicron vs delta
- age distribution of omicron cases in Denmark skew young: what will happen when omicron spreads to the elderly
- may already be seeing nosocomial (hospital) spread of omicron (9 of the omicron-related hospitalizations tested positive 48+ hours after admission)--I think we need a new letter/push for airborne precautions in hospitals

Meat Popsicle, but 3x vaccinated @Infoseepage:
- Over 85% of their total cases are less than a week old. If we assume that most of the 27 hospitalizations come from early cases which have progressed, then we are talking more like a 10% hospitalization rate, not a 1% rate.

Nurit Baytch @NuritBaytch:
I’m trying to dispel the ubiquitous notion that omicron is mild. the US is taking ~no precautions to mitigate it, and even a 1% hospitalization rate is worrisome for a virus w/ a 2-3 day doubling time
my tweet was in no way intended to be implying omicron is NBD. on the contrary

>36 margd: I'm on my way to a booster shot with Pfizer. Denmark is upscaling booster shots big time. Exactly because omicron has a very troubling doubling time. It is expected to be the dominant variant in a few days!
ETA: Mondays number of new cases (of all variants): 7799 (based on 185451 PCR tests).
I.e. record high number of cases, but still low numbers of people in hospitals and ICU.

>36 margd: Take care!
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Frederik Jørgensen, Alexander Bor, Michael Bang Petersen. 2021. Compliance without fear: Individual-level protective behaviour during the first wave of the COVID-19 pandemic. British Journal of Psychology Volume26, Issue 2 (May 2021) Pages 679-696.
https://doi.org/10.1111/bjhp.12519 https://bpspsychub.onlinelibrary.wiley.com/doi/10.1111/bjhp.12519

Abstract
Objectives
The outbreak of the COVID-19 pandemic required rapid public compliance with advice from health authorities. Here, we ask who was most likely to do so during the first wave of the pandemic.

Design
Quota-sampled cross-sectional and panel data from eight Western democracies (Denmark, France, Germany, Hungary, Italy, Sweden, the United Kingdom, and the United States).

Methods
We fielded online public opinion surveys to 26,508 citizens between 19 March and 16 May. The surveys included questions about protective behaviour, perceptions of the pandemic (threat and self-efficacy), as well as broader attitudes towards society (institutional and interpersonal trust). We employ multilevel and fixed-effects regression models to analyse the relationship between these variables.

Results
Consistent with prior research on epidemics, perceptions of threat turn out as culturally uniform determinants of both avoidant and preventive forms of protective behaviour. On this basis, authorities could foster compliance by appealing to fear of COVID-19, but there may be normative and practical limits to such a strategy. Instead, we find that another major source of compliance is a sense of self-efficacy. Using individual-level panel data, we find evidence that self-efficacy is amendable to change and exerts an effect on protective behaviour. Furthermore, the effects of fear are small among those who feel efficacious, creating a path to compliance without fear. In contrast, two other major candidates for facilitating compliance from the social sciences, interpersonal trust and institutional trust, have surprisingly little motivational power during the first wave of the COVID-19 pandemic.

Conclusions
To address future waves of the pandemic, health authorities should thus focus on facilitating self-efficacy in the public.

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

Michael Bang Petersen (coauthor of paper above) @M_B_Petersen | 4:40 PM · Dec 13, 2021
In the next days, graphs (like https://twitter.com/M_B_Petersen/status/1470508975284273157/photo/1 ) will show explosions of omicron & lockdowns will re-appear across Europe.

To motivate fatigued publics, it is key to not just appeal to fear. Communication should help people cope & envision how to pull thru.

An evidence-based Thread on how. (1/5) ... https://twitter.com/M_B_Petersen/status/1470508975284273157

Eric Topol (Scripps) @EricTopol | 8:10 PM · Dec 13, 2021:
What Denmark did to cut the booster shot interval to 4.5 months was smart.
That's when (~5 months) substantial waning shows up, not 6 months,
the US policy, which will leave many not adequately protected vs symptomatic infection
---------------------------------------------------------

Denmark cuts COVID-19 booster shot interval to 4-1/2 months
Reuters | Dec 13, 2021

...The move to offer the booster shot earlier than the six months initially planned comes amid rising infection numbers and concern over the Omicron coronavirus variant.

...About 80% of the population has received two shots and just over 20% have so far received the third booster shot...

https://www.reuters.com/article/us-health-coronavirus-denmark-vaccine/denmark-cu...

Pfizer says its Covid pill will protect against severe disease, even from Omicron.
Carl Zimmer and Rebecca Robbins | Dec. 14, 2021

...Last month, Pfizer asked the Food and Drug Administration to authorize the pill, known as Paxlovid, based on a preliminary batch of data. The new results will undoubtedly strengthen the company’s application, which could mean that Americans infected with the virus may have access to the pill within weeks.

...if given within three days of the onset of symptoms, Paxlovid reduced the risk of hospitalization and death by 89 percent. If given within five days, the risk was reduced almost as much, to 88 percent.

The results, based on an analysis of 2,246 unvaccinated volunteers at high risk of severe disease, largely match the company’s initial, smaller analysis of the clinical trial, released last month.

Pfizer said that 0.7 percent of patients who received Paxlovid were hospitalized within 28 days of entering the trial, and none died. By contrast, 6.5 percent of patients who received a placebo were hospitalized or died.

Pfizer also released preliminary data from a separate trial looking at people with a lower risk. These volunteers including vaccinated people who carried a risk factor for severe disease, as well as unvaccinated patients with no risk factors.

Among this group of 662 volunteers, Paxlovid reduced the risk of hospitalization and death by 70 percent, the company said.

...In both trials, most of the volunteers were infected with the Delta variant. But Pfizer said on Tuesday that in laboratory experiments, Paxlovid also performed well against the highly mutated Omicron variant. The drug jams into one of Omicron’s key proteins — called a protease — just as effectively as it does with other variants...

https://www.nytimes.com/2021/12/14/health/pfizer-covid-pill-paxlovid.html
_______________________________________________________

Pfizer Announces Additional Phase 2/3 Study Results Confirming Robust Efficacy of Novel COVID-19 Oral Antiviral Treatment Candidate in Reducing Risk of Hospitalization or Death
Tuesday, December 14, 2021 - 06:45am

Final data available from all high-risk patients enrolled in EPIC-HR study (n= 2,246) confirmed prior results of interim analysis showing PAXLOVID™ (nirmatrelvir PF-07321332 tablets and ritonavir tablets) reduced risk of hospitalization or death by 89% (within three days of symptom onset) and 88% (within five days of symptom onset) compared to placebo; no deaths compared to placebo in non-hospitalized, high-risk adults with COVID-19

The above data have been shared with the U.S. Food and Drug Administration (FDA) as part of an ongoing rolling submission for Emergency Use Authorization (EUA)

Separately, interim analyses of an ongoing second study in standard-risk adults (EPIC-SR) showed a 70% reduction in hospitalization and no deaths in the treated population, compared to placebo, in the secondary endpoint; the novel primary endpoint of self-reported, sustained alleviation of all symptoms for four consecutive days, as compared to placebo, was not met.

The study continues
An approximate 10-fold decrease in viral load at Day 5, relative to placebo, was observed in both EPIC-HR and EPIC-SR, indicating robust activity against SARS-CoV-2 and representing the strongest viral load reduction reported to date for a COVID-19 oral antiviral agent

Recent in vitro data confirm that nirmatrelvir is a potent inhibitor of the Omicron 3CL protease, which, combined with existing in vitro antiviral and protease inhibition data from other Variants of Concern (VoC) including Delta, indicates that PAXLOVID will retain robust antiviral activity against current VoCs as well as other coronaviruses

https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-...

Rare side effects of COVID vaccines v. substantial risk with COVID disease. Nature is a top flight science journal: "Vaccination for SARS-CoV-2 in adults was associated with a small increase in the risk of myocarditis within a week of receiving the first dose of both adenovirus (AstraZeneca) and mRNA vaccines (Moderna, Pfizer), and after the second dose of both mRNA vaccines. By contrast, SARS-CoV-2 infection was associated with a substantial increase in the risk of hospitalization or death from myocarditis, pericarditis and cardiac arrhythmia."
---------------------------------------------------------
Eric Topol (Scripps) @EricTopol | 9:47 AM · Dec 14, 2021:
https://twitter.com/EricTopol/status/1470767378745204739
Just published @NatureMedicine: The most comprehensive assessment of the rare events of
myocarditis, pericarditis, arrhythmias after COVID and AZ, mRNA vaccines

Image-abstract, highlighted ( https://twitter.com/EricTopol/status/1470767378745204739/photo/1 )
Image-no. of excess events per vaxx, disease ( https://twitter.com/EricTopol/status/1470767378745204739/photo/2 )
---------------------------------------------------------

Martina Patone et al. 2021. Risks of myocarditis, pericarditis, and cardiac arrhythmias associated with COVID-19 vaccination or SARS-CoV-2 infection. Nature Medicine (Dec 14, 2021) https://doi.org/10.1038/s41591-021-01630-0 https://nature.com/articles/s41591-021-01630-0

Abstract
Although myocarditis and pericarditis were not observed as adverse events in coronavirus disease 2019 (COVID-19) vaccine trials, there have been numerous reports of suspected cases following vaccination in the general population. We undertook a self-controlled case series study of people aged 16 or older vaccinated for COVID-19 in England between 1 December 2020 and 24 August 2021 to investigate hospital admission or death from myocarditis, pericarditis and cardiac arrhythmias in the 1–28 days following adenovirus (ChAdOx1 (AstraZeneca), n = 20,615,911) or messenger RNA-based (BNT162b2 (Pfizer), n = 16,993,389; mRNA-1273 (Moderna), n = 1,006,191) vaccines or a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test (n = 3,028,867). We found increased risks of myocarditis associated with the first dose of ChAdOx1 and BNT162b2 vaccines and the first and second doses of the mRNA-1273 vaccine over the 1–28 days postvaccination period, and after a SARS-CoV-2 positive test. We estimated an extra two ..., one ... and six ... myocarditis events per 1 million people vaccinated with ChAdOx1, BNT162b2 and mRNA-1273, respectively, in the 28 days following a first dose and an extra ten ... myocarditis events per 1 million vaccinated in the 28 days after a second dose of mRNA-1273. This compares with an extra 40 ... myocarditis events per 1 million patients in the 28 days following a SARS-CoV-2 positive test. We also observed increased risks of pericarditis and cardiac arrhythmias following a positive SARS-CoV-2 test. Similar associations were not observed with any of the COVID-19 vaccines, apart from an increased risk of arrhythmia following a second dose of mRNA-1273. Subgroup analyses by age showed the increased risk of myocarditis associated with the two mRNA vaccines was present only in those younger than 40.

DISCUSSION
...In summary, this population-based study quantifies for the first time the risk of several rare cardiac adverse events associated with three COVID-19 vaccines as well as SARS-CoV-2 infection. Vaccination for SARS-CoV-2 in adults was associated with a small increase in the risk of myocarditis within a week of receiving the first dose of both adenovirus and mRNA vaccines, and after the second dose of both mRNA vaccines. By contrast, SARS-CoV-2 infection was associated with a substantial increase in the risk of hospitalization or death from myocarditis, pericarditis and cardiac arrhythmia.

A Cdn university across the lake has suffered similar omicron wave:

Cornell shuts down its Ithaca campus after significant signs of omicron variant found
Jonathan Franklin | December 14, 2021

...Cornell University is shutting down its Ithaca, N.Y., campus and is moving to "alert level red" — its highest alert level — due to what officials say is a rapid spread of COVID-19 cases among students.

As of Tuesday afternoon, the campus reported 469 active student cases of the coronavirus and that, for the week of Dec. 6, about 3% of tests were positive among the students tested, according to Cornell's online COVID-19 dashboard.

In an online letter to students, Cornell University President Martha Pollack said the campus's COVID-19 testing lab team detected evidence of the omicron variant "in a significant number of Monday's positive student samples."

..."While I want to provide reassurance that, to date, we have not seen severe illness in any of our infected students, we do have a role to play in reducing the spread of the disease in the broader community," Pollack said.

Joel Malina, vice president for university relations, told NPR in an emailed statement that for the past 20 months, the university has developed and followed a "science-based approach" to COVID-19 decision-making.

The decisions, which involve ongoing modeling and surveillance testing, helped campus officials identify positive cases early and minimize the spread of the coronavirus on campus, Malina said.

"Virtually every case of the Omicron variant to date has been found in fully vaccinated students, a portion of whom had also received a booster shot. We have not seen evidence of significant disease in our students to date," he added.

Malina said campus officials are assisting those students who have tested positive to complete their mandated 10-day isolation periods and will help students who have tested negative to return home safely for the winter break....

https://www.npr.org/sections/coronavirus-live-updates/2021/12/14/1064197606/corn...
________________________________________________

Kali Barrett (critical care MD Toronto) @DrKaliBarrett | 10:36 AM · Dec 14, 2021
what's keeping me up at night: the # of unvaxxed in Ontario is large enough that when Omicron rips through the population, those without any immunity will get sick. Predicted # who wld need ICU large enough to overwhelm fragile system. I am most scared for the unvaxxed.

"...Severe reductions of plasma neutralizing activity were observed against Omicron compared to the ancestral pseudovirus for vaccinated six vaxxes and convalescent individuals...three mAbs (monoclonal antibodies)...that bind to the RBM (receptor binding motif)... retain(ed) unaltered potency...Broadly neutralizing sarbecovirus mAbs recognizing epitopes conserved among SARS-CoV-2 variants and other sarbecoviruses may prove key to controlling the ongoing pandemic and future zoonotic spillovers."
margd: mice-human "ping-pong" spillover?
margd: Also effective--Pfizer treatment pill Paxlovid, submitted to FDA? Omicron booster, available in 3 months? Universal Coronavirus vaxxes, being researched?

New VACCINE RANKING of ability to neutralize #Omicron—Moderna appears to be the strongest against Omicron in this study, but still big drop. Pfizer next best (but we know infection efficacy is 30-34%), AstraZeneca & Sinopharm poor. J&J & Sputnik = zero.
Natural infection immunity is on the left … “convalescent” = practically no neutralization against #Omicron in this study by itself without vaccine....
Thread ( https://twitter.com/DrEricDing/status/1471035675382358018 )
Image-neutralization drop wild to omicron 6 vaxx, convalescent ( https://twitter.com/DrEricDing/status/1471035675382358018/photo/1 )
- Eric Feigl-Ding @DrEricDing3:33 AM · Dec 15, 2021

Elisabetta Cameroni et al. 2021. Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift. BioRxiv Dec 14, 2021. https://biorxiv.org/content/10.1101/2021.12.12.472269v1

Preprint, not yet reviewed.

Abstract
The recently emerged SARS-CoV-2 Omicron variant harbors 37 amino acid substitutions in the spike (S) protein, 15 of which are in the receptor-binding domain (RBD), thereby raising concerns about the effectiveness of available vaccines and antibody therapeutics. Here, we show that the Omicron RBD binds to human ACE2 with enhanced affinity relative to the Wuhan-Hu-1 RBD and acquires binding to mouse ACE2. Severe reductions of plasma neutralizing activity were observed against Omicron compared to the ancestral pseudovirus for vaccinated and convalescent individuals. Most (26 out of 29) receptor-binding motif (RBM)-directed monoclonal antibodies (mAbs) lost in vitro neutralizing activity against Omicron, with only three mAbs, including the ACE2-mimicking S2K146 mAb, retaining unaltered potency. Furthermore, a fraction of broadly neutralizing sarbecovirus mAbs recognizing antigenic sites outside the RBM, including sotrovimab, S2X259 and S2H97, neutralized Omicron. The magnitude of Omicron-mediated immune evasion and the acquisition of binding to mouse ACE2 mark a major SARS-CoV-2 mutational shift. Broadly neutralizing sarbecovirus mAbs recognizing epitopes conserved among SARS-CoV-2 variants and other sarbecoviruses may prove key to controlling the ongoing pandemic and future zoonotic spillovers.

>43 margd: contd.
David Juurlink (Internal Medicine, U Toronto) @DavidJuurlink | 5:07 PM · Dec 14, 2021:
https://twitter.com/DavidJuurlink/status/1470878018533048326

Hugely important work from @JuliaHCox and colleagues (e.g., Martina Patone)

people 40 and younger, Pfizer carries a much lower risk of myocarditis than either Moderna **or SARS-CoV-2 infection** (annotations added)

Image ( https://twitter.com/DavidJuurlink/status/1470878018533048326/photo/1 )

Vaccine Scientists Are TIME's 2021 Heroes of the Year
Alice Park and Jamie Ducharme
Photographs by Mattia Balsamini for TIME
December 13, 2021

...Kizzmekia Corbett ( Vaccine Research Center (VRC) of the U.S. National Institute of Allergy and Infectious Diseases ), Barney Graham ( Vaccine Research Center (VRC) of the U.S. National Institute of Allergy and Infectious Diseases ), Katalin Kariko (Hungarian immigrant, U PA) and Drew Weissman (U PA)...The four were hardly alone in (vaxx development) efforts: scientists around the world have produced COVID-19 vaccines using a variety of platforms and technologies. Many—like the shots from Oxford-AstraZeneca and Johnson & Johnson–Janssen—came from more established methods, modified with impressive speed to fight a new virus. Still, Corbett, Graham, Kariko and Weissman achieved a breakthrough of singular importance, introducing an innovative and highly effective vaccine platform, based on mRNA, that will impact our health and well-being far beyond this pandemic...

...On Jan. 10, Chinese scientists (margd: they have names I bet?) published the sequence of the new virus, and the team got to work...

https://time.com/heroes-of-the-year-2021-vaccine-scientists/

News
HKUMed (Hong Kong U Scool of Medicine) finds Omicron SARS-CoV-2 can infect faster (70X) and better than Delta in human bronchus but with less severe infection in lung
15 December 2021

A study led by researchers from the LKS Faculty of Medicine at The University of Hong Kong (HKUMed) provides the first information on how the novel Variant of Concern (VOC) of SARS-CoV-2, the Omicron SARS-CoV-2 infect human respiratory tract. The researchers found that Omicron SARS-CoV-2 infects and multiplies 70 times faster than the Delta variant and original SARS-CoV-2 in human bronchus, which may explain why Omicron may transmit faster between humans than previous variants. Their study also showed that the Omicron infection in the lung is significantly lower than the original SARS-CoV-2, which may be an indicator of lower disease severity. This research is currently under peer review for publication.

https://www.med.hku.hk/en/news/press/20211215-omicron-sars-cov-2-infection
-----------------------------------------------------------------------------------

https://twitter.com/mugecevik/status/1471088942543949829/photo/1

Omicron evades Moderna vaccine too, study suggests, but boosters help
Rob Stein | December 15, 2021

...A preliminary study made public Wednesday studied blood samples in the lab from 30 people who had gotten two Moderna shots, and it found that the antibodies in their blood are at least about 50 times less effective at neutralizing the omicron variant of the coronavirus.

Previous research had indicated the Pfizer-BioNTech vaccine is less protective against omicron.

...But there was good news too. An additional 17 people in the study had received a Moderna booster. And the antibodies in their blood were highly effective at blocking the virus — essentially about as effective as they are at blocking the delta variant, (David Montefiori, a virologist at Duke University who helped conduct the study) says...

https://www.npr.org/sections/health-shots/2021/12/15/1064202754/omicron-evades-m...
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Eric Topol @EricTopol | 11:51 AM · Dec 15, 2021
New data from 3rd shot Moderna (booster, 50 μg) vs Omicron induces substantial increase in neutralization activity, presented today by @WHCOVIDResponse

https://youtube.com/watch?v=4lDuF6sMjm4
Image ( https://twitter.com/EricTopol/status/1471161030835269633/photo/1 )

Estimated (mRNA) vaccine effectiveness against (Delta) infection decreased significantly to around 20% in months 5 through 7.

Yinong Young-Xu et al. 2021. Estimated Effectiveness of COVID-19 Messenger RNA Vaccination Against SARS-CoV-2 Infection Among Older Male Veterans Health Administration Enrollees, January to September 2021 (Research Letter). JAMA Netw Open. Dec 15, 2021;4(12):e2138975. doi:10.1001/jamanetworkopen.2021.38975

Figure ( https://twitter.com/EricTopol/status/1471204582051041280/photo/1 )

Discussion

Similar to our previous findings,1 estimated vaccine effectiveness against SARS-CoV-2 infection was approximately 90% during the pre- and rising-Delta periods in the first 3 months after full vaccination. During the high-Delta period, we found a pattern similar to that observed in a study from Qatar,2 in which the estimated vaccine effectiveness against infections was significantly lower (about 60%) and the decrease in vaccine effectiveness accelerated after month 4 after full vaccination. However, the focus on older male veterans in our study could limit the generalizability of these findings.

Studies suggest that the currently approved 2-dose mRNA vaccines (mRNA-1273 and BNT162b2) seem to generate sufficient protection against COVID-19–related hospitalization despite increased transmission of the Delta variant. In this study, estimated vaccine effectiveness against SARS-CoV-2 infection decreased significantly to around 20% in months 5 through 7. This decrease could be attributable to both the passage of time (ie, a waning effect) and the increased transmission of the Delta variant.

Eric Topol @EricTopol | 4:38 PM · Dec 15, 2021:
A new report on Omicron's potency for inhibiting vaccine-induced, infection-induced, and monoclonal Ab (mAb) mediated virus neutralization. Only Sotrovimab was effective as a mAb) https://medrxiv.org/content/10.1101/2021.12.14.21267772v1
Image ( https://twitter.com/EricTopol/status/1471233251133902848/photo/1 )

Anupriya Aggarwal et al. 2021. SARS-CoV-2 Omicron: reduction of potent humoral responses and resistance to clinical immunotherapeutics relative to viral variants of concern. MedRxiv Dec 15, 2021. doi: https://doi.org/10.1101 https://www.medrxiv.org/content/10.1101/2021.12.14.21267772v1/2021.12.14.2126777...

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

Abstract
From late 2020 the world observed the rapid emergence of many distinct SARS-CoV-2 variants. At the same time, pandemic responses resulted in significant global vaccine rollouts that have now significantly lowered Covid-19 hospitalisation and mortality rates in the developed world. Unfortunately, in late 2021, the variant Omicron (B.1.1.529) emerged and it eclipsed the other variants of concern (VOC) in its number of Spike polymorphisms, and its ability to compete with and displacement of the dominant VOC Delta. Herein we accessed the impact of Omicron to humoral neutralisation in vaccinated, convalescent cohorts, in concentrated human IgG from thousands of plasma donors and also alongside many clinically used monoclonal antibodies. Overall, we observed a 17 to 22 fold drop in neutralisation titres across all donors that reached a titre to Omicron. Concentrated pooled human IgG from convalescent and vaccinated donors had greater breadth but was still reduced by 16-fold. In all therapeutic antibodies tested, significant neutralization was only observed for Sotrovimab, with other monoclonals unable to neutralize B.1.1.529.

Why Paxlovid is a Just-in-Time Breakthrough
The first potent anti-Covid pill will be a big help
Eric Topol | Dec 16, 2021

We’re desperately in need of some good news—this is it. This week the results from 2 clinical trials of Paxlovid (nirmatrelvir) became available, coinciding with the continued (second) surge of Delta in the United States and the rapid emergence of the Omicron strain. The timing for validation of the potency and safety of a whole new approach to tackling the virus couldn’t be better.

First let’s review the mechanism of action. Paxlovid, a small molecule that is orally active, was specifically designed to tackle SARS-CoV-2. It is not a repurposed drug, but actually derived from a precursor that was active against SARS. It binds to the virus’s main protease (Mpro) as shown here, a key upstream step before it gets into high gear replication (steps 4-6). Inhibiting Mpro is a choke point for the virus, making it unable to replicate...

https://erictopol.substack.com/p/why-paxlovid-is-a-just-in-time-breakthrough
----------------------------------------------------

Canada Buys 1M Initial Courses—The government of Canada said December 3 it agreed to purchase an initial 1 million courses of PAXLOVID for an undisclosed price, pending authorization by Health Canada. Pfizer submitted a rolling submission for authorization to Health Canada earlier the week of November 29, the government added.

U.S. BUYS 10M DOSES FOR $5.29B—The U.S. government agreed to buy 10 million doses of PAXLOVID for $5.29 billion beginning later this year and concluding in 2022, subject to regulatory authorization from the FDA, Pfizer said November 19. The company added that it has also entered into advance purchase agreements with several other countries and has reached out to approximately 100 countries worldwide.

Pfizer also committed to offering PAXLOVID through a tiered pricing approach based on the income level of each country “to promote equity of access across the globe,” with high- and upper-middle income countries to pay more for the COVID-19 pill than lower income countries.
https://www.genengnews.com/covid-19-candidates/pfizer/

"SARS-CoV-2-infected cells treated with famotidine (TM Pepcid AC) demonstrate reduced ... drivers of the cytokine release syndrome that precipitates poor outcome for patients with COVID-19."
--------------------------------------------------------------

From the journals: JBC
Antacid may ease COVID-19 symptoms
Anand Rao | Oct. 12, 2021

Widely available vaccines have diminished the prevalence of severe illness and death due to COVID-19. However, the highly contagious delta variant has driven an increase in breakthrough infections among fully vaccinated individuals. While those vaccinated are still at lower risk for hospitalization and death, affordable and easily procurable therapeutic options remain limited for those suffering from the panoply of symptoms that accompany COVID-19. In a recent case series, the over-the-counter heartburn and ulcer medication famotidine, sold as Pepcid AC, rapidly relieved symptoms, including cough, fatigue, headaches and shortness of breath, in nonhospitalized COVID-19 patients, but researchers did not know the molecular and biological processes underlying these observations.

In recent work published in the Journal of Biological Chemistry, Rukmini Mukherjee of Goethe University and colleagues used biochemical, cellular and functional assays to assess the molecular actions of famotidine against SARS-CoV-2. While famotidine did not have an effect on viral replication or viral protease activities, the researchers showed that it does inhibit histamine-induced expression of toll-like receptor 3, or TLR3, a molecule that plays an important role in pathogen recognition and innate immune response.

...SARS-CoV-2–infected cells treated with famotidine displayed reduced expression levels of the inflammatory mediators C–C motif chemokine ligand 2 and interleukin 6, which drive cytokine storms, a potentially life-threatening symptom of COVID-19.

Pharmacokinetic studies have shown that famotidine can reach concentrations in blood sufficient to antagonize histamine H2 receptors expressed in numerous cell types, including mast cells, neutrophils and eosinophils. Thus, these findings explain how famotidine may reduce histamine-induced inflammation and cytokine release, in turn improving outcomes in COVID-19 patients.

https://www.asbmb.org/asbmb-today/science/101221/from-the-journals-jbc

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Rukmini Mukherjee et al. 2021. Famotidine inhibits toll-like receptor 3-mediated inflammatory signaling in SARS-CoV-2 infection. J of Biological Chemistry. Volume 297, ISSUE 2, 100925, August 2021. DOI:https://doi.org/10.1016/j.jbc.2021.100925 https://www.jbc.org/article/S0021-9258(21)00725-0/fulltext

"SARS-CoV-2-infected cells treated with famotidine (TM Pepcid AC) demonstrate reduced ... drivers of the cytokine release syndrome that precipitates poor outcome for patients with COVID-19."

Admissions to London hospitals starting to trend higher than you would expect from the number of cases ten days earlier, so Omicron is either putting more people in hospital than each case of Delta or doing it quicker.

Graph- projected v observed admissions London, July1-Jan 1, 2021
( https://twitter.com/OYCar/status/1471568961649086473/photo/1 )

- Dr Rob Whitehurst (ag sci ) @OYCar | 2:52 PM · Dec 16, 2021
( Discussion at https://twitter.com/OYCar/status/1471568961649086473 )
------------------------------------------------------

Meanwhile in S Africa:

Harry Moultrie (epidemiologist) @hivepi | 12:58 AM · Dec 17, 2021:
https://twitter.com/hivepi/status/1471721404747948039
Updated normalised cases, admissions and deaths for Gauteng.
Gauteng Omicron cases (incl reinfections) peaked at 97% of Delta wave.
Admissions currently at 46% of Delta wave and rate of admissions slowing. Deaths at 7% of Delta wave but still rising.
Graph-cases, admissions deaths in Gauteng, 2020 & 2021 ( https://twitter.com/hivepi/status/1471721404747948039/photo/1 )

Scientists Are Racing to Gauge the Threat of Omicron
The variant will spread quickly through the United States, experts say. What happens after that is less certain.
Emily Anthes | Dec. 16, 2021

...It spreads quickly everywhere it lands.

...Still uncertain is how serious the consequences will be, as much remains unknown about the variant, including how likely it is to cause severe disease.

...Scientists believe that the vaccines will still provide protection against the worst outcomes; there is early evidence, for instance, that T cells, which can help prevent infections from progressing to severe disease, should still recognize the variant. And boosters are likely to provide additional protection against infection, preliminary data suggests.

...Breakthrough infections are common.

...The question is how much the rapid spread of Omicron will contribute to hospitalizations and deaths...too early, and the data sets are too small, to make broad conclusions about Omicron’s severity, especially because hospitalizations and deaths typically lag several weeks behind infections.

...The Biden administration...has focused heavily on promoting vaccination and boosters, which remain critical public health tools. But in the face of a foe like Omicron, they are not enough, experts warned.

“The way we’re seeing it unfold in other places, the way we’re starting to see it take hold here, implies that a vaccination-only strategy is going to be very fragile,” Dr. Salomon said.

Experts called on officials to improve access to testing, distribute high-quality masks, promote improved ventilation and issue clearer guidelines about what activities it is safe to engage in and in what circumstances.

Local governments, schools and employers also need to begin making plans — and making those plans public — about what they will do in the event of large outbreaks or if cases or hospitalizations rise to a certain level, they noted.

Many of these steps are long overdue, experts said, and were sorely needed even before Omicron was discovered....

https://www.nytimes.com/2021/12/16/health/coronavirus-omicron-variant.html

Isabella Eckerle * @EckerleIsabella | 5:38 AM · Dec 17, 2021:

Wer noch nicht geimpft ist, der sollte spätestens ab jetzt sehr, sehr vorsichtig sein. Am besten keine Kontakte ausserhalb des eigenen Haushalts ohne FFP2. Das Narrativ, dass sich #SARSCoV2 #COVID19 mit #Omikron nun in einen milden Infekt verwandelt, ist ein gefährliches Irrlicht

Translated from German by
Anyone who has not yet been vaccinated should be very, very careful from now on at the latest.
Ideally, no contacts outside of your own household without FFP2.
The narrative that #SARSCoV2 #COVID19 turns into a mild infection with #Omikron is a dangerous will-o'-the-wisp

* Prof at Geneva Centre for Emerging Viral Diseases - Virologist, MD, DTM&H

Great news for South Africa, but UK not convinced that Omicron causes milder disease. Populations somewhat different--in age, % previously infected, % vaxxed, vaxx type, #weeks--as well as season (summer down there). Even IF milder, Omicron's increased transmissibility could still cause enough severe disease to swamp our hospitals, upping death rates--not to mention breakthrough infections keeping healthcare workers home... "Flatten the curve" should again be our cry!

Chise (Sr Scientist vaxx R&D) @sailorrooscout | 7:45 AM · Dec 17, 2021:
Encouraging news out of South Africa’s MOH this morning.
Age-controlled data regarding Omicron severity.
ACROSS ALL AGES, death rates among hospitalized patients are 2/3 LOWER in the Omicron wave.
In addition, hospitalization rates have FALLEN 91% in the Omicron wave.

Bar Graph-% deaths per age group in Tshwane, S Africa ( https://twitter.com/sailorrooscout/status/1471823759497740298/photo/1 )
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Kashif Pirzada, MD (emergency, Toronto) @KashPrime
This would be hopeful except
- Almost everyone in SA has had Delta, Beta +/- a vaccine
- 8x as many South Africans have already died of Covid compared to Canada
- Their median age (27.6) is much less than ours (41.1)
To me its more evidence that 3x vaccine may help significantly
8:51 AM · Dec 17, 2021
_________________________________________________

Eric Topol (Scripps) @EricTopol | 8:46 AM · Dec 17, 2021·
No evidence that Omicron is less severe, new @imperialcollege study reports
https://ft.com/content/020534b3-5a54-4517-9fd1-167a5db50786
Text ( https://twitter.com/EricTopol/status/1471839260068093953/photo/1 )

---------------------------------------------------------------
Modelling suggests rapid spread of Omicron in England but same severity as Delta
Emily Head, Dr Sabine L. van Elsland | 17 December 2021

Omicron largely evades immunity from past infection or two vaccine doses according to Imperial's latest report.

The new report from the Imperial College London COVID-19 response team estimates that the risk of reinfection with the Omicron variant is 5.4 times greater than that of the Delta variant. This implies that the protection against reinfection by Omicron afforded by past infection may be as low as 19%...

https://www.imperial.ac.uk/news/232698/modelling-suggests-rapid-spread-omicron-e...

Silver lining to mild breakthrough infections, esp those not resulting in long COVID?

OHSU study finds breakthrough cases provide 'super immunity'
Steve Benham | December 17th 2021

...people who had been vaccinated and had a mild breakthrough case had many more antibodies in their blood than those who had been vaccinated but had not been infected with the virus...suggest(s)...will be better able to fight off new variants as they emerge, including omicron...

The antibodies generated in those with breakthrough cases were also better antibodies and up to 1,000% more effective than antibodies produced after two doses of the Pfizer vaccine.

(co-author Marcel Curlin, with Oregon Health & Sci U’s School of Medicine) said the study did not support the idea that vaccination isn’t needed at all.

“What we’re looking at is the exceptional combination of vaccination plus infection,” he said. “So, if you’re infected alone without vaccine, the immune response is quite variable from person to person and, on average, quite a bit lower than if you’re vaccinated.”...

https://katu.com/news/local/ohsu-study-finds-breakthrough-cases-provide-super-im...
-----------------------------------------------------------

Timothy A. Bates etal. 2021. Antibody Response and Variant Cross-Neutralization After SARS-CoV-2 Breakthrough Infection ( Research Letter). JAMA. Published online December 16, 2021. doi:10.1001/jama.2021.22898 https://jamanetwork.com/journals/jama/fullarticle/2787447

Discussion
Results of this study showed substantial boosting of humoral immunity after breakthrough infection, despite predominantly mild disease. Boosting was most notable for IgA, possibly due to the differences in route of exposure between vaccination and natural infection. In addition, breakthrough sera demonstrated improved variant cross-neutralization, and Delta breakthrough infections in particular exhibited improved potency against Delta vs WA1, suggesting that the protective immune response may be broadened through development of variant boosters with antigenic inserts matching the emerging SARS-CoV-2 variants. Limitations of this study include the small number of samples and the difference in time from initial vaccination to serum collection between the breakthrough and control groups, which emerging evidence suggests may contribute to the development of variant cross-neutralizing antibody responses.

So I have been exposed to what is almost certainly Omicron by an unlucky series of events that might have been avoidable. Luck will be a major factor in not getting this variant which is SO easily transmitted, unless you are going to seriously isolate for the next 2 months. The only question Now is severity. I am early on day 3 of exposure, fully boosted, waiting to see whether my immunity will give me some protection or not.

Ironically just the night before the exposure, I was looking at the info again and realized that confirmation bias had led me prematurely to believe omicron is less severe. We shall see. I’m not currently seeing good evidence that Omicron is really less severe, but the jury is out. I hope regardless of my earlier confirmation bias that it will be milder, but very concerned for the world. I am certain that in the US this will be the largest Covid wave yet in terms of numbers of cases. In NYC area, we are seeing a monumental increase in cases and test positives. It’s just exploding

>57 stellarexplorer: Hope mild if you are infected--and that, fully boosted as you are, you will be bulletproof as a result!

p.s. I am sure you don't need advice from me, but... Of course we would call our respective MDs, but my state of mind will benefit by my throwing whatever little thing I can at the virus should it visit our house (again?). I have stash of N95 masks, a HEPA air filter for sick room (in addition to central one on furnace), rapid antigen tests, Betadine (iodine) Gargle Mouth Wash, Pepcid AC (famotidine), and pulse oximeter on hand. God forbid we should ever need the last one, but they were hard to come by last winter when son appeared to have virus. I've lent it to afflicted friends, so think of it as a neighbourhood resource. (We also take daily vitamin D, C, zinc supplements as regular fare.)

>58 margd: Thank you! Will report back. Have stocks of most of those things including the pulse ox which I hope not to need….

Denmark today: 11,194 cases (yesterday 10,000), likely now Omicron dominant, highest per capita case load in world, over 1,400/million (very high % testing country). 2nd now is Switzerland 1054/M.
Good news to date: Very low fatalities
Graph-# infections Denmark thru Dec 16, 2021 ( https://twitter.com/EricTopol/status/1471956409872904192/photo/1 )
Bar Graph-deaths per day, Nov 23-Dec 17, 2021 ( https://twitter.com/EricTopol/status/1471956409872904192/photo/2 )

- Eric Topol @EricTopol | 4:32 PM · Dec 17, 2021

Yay (from personal perspective)! Collectively, though, we can still crash the hospital systems? A smaller percentage of serious disease still a lot in a tidal wave of Omicron?

Retweet from Kashif Pirzada, MD @KashPrime, Emergency Physician in Toronto
(margd: a cousin once removed is an emergency MD in Toronto, so of course I read (re)tweets from Dr Pirzada ;)

Gupta Lab (Prof clinical microbiology, U Cambridge) @GuptaR_lab 3:33 PM · Dec 17, 2021
https://twitter.com/GuptaR_lab/status/1471941645797146628
https://threadreaderapp.com/thread/1471941645797146628.html

Sharing some potentially significant findings relating to Omicron given the current situation.
First of all huge thanks to the team working flat out- Bo Meng, @isabella_atmf and to our collaborators both in G2P, J2P along with @SystemsVirology. Findings as follows:

1. Omicron Spike protein mediates deficient cell entry and is inefficiently cleaved compared to Delta spike. We tested viral entry mediated by Wild Type, Delta and Omicron spikes using a pseudotyped virus system, infecting primary 3D lung alveolar organoids.
Image ( https://twitter.com/GuptaR_lab/status/1471941649932730368/photo/1 )

2. Omicron Spike protein induces relatively poor cell-cell fusion compared to WT and Delta. We expressed spike in cells stably expressing split GFP, so that Green signal could be measured over time upon cell-cell fusion and syncitia formation. The difference is significant.
Image ( https://twitter.com/GuptaR_lab/status/1471941653376253955/photo/1 )

3. What does this all mean? Efficient infection of lung cells could correlate with severity of lung disease. Syncitia or fused cells are often seen in respiratory tissues taken following severe disease. Delta was very good at both, in contrast to Omicron. Further work is needed

4. We also tested how well antibodies from vaccinated individuals neutralised Omicron v Delta. We found that Omicron was poorly neutralised after two doses of mRNA or Ad vectored vaccine compared to Delta, but that the third dose (mRNA vaccine) rescued this at an early time point
Image ( https://twitter.com/GuptaR_lab/status/1471941657310416896/photo/1 )

5. In summary this work suggests that Omicron does appear to have become more immune evasive, but that properties associated with disease progression *may* be attenuated to some extent. The significant growth of Omicron nevertheless represents a major public health challenge.

South Africa says vaccines and natural immunity are limiting latest Covid wave (Guardian)

Vaccines and high levels of prior exposure to coronavirus in South Africa appear to be protecting against the more severe symptoms seen in the previous three waves of the pandemic, according to the country’s health minister. The suggestion that previous exposure to another variant of coronavirus – or vaccination – might provide protection from the Omicron variant echoes analysis by South African experts earlier this week that suggested prior exposure or vaccination gave a degree of protection from serious disease...

A report from Denmark on the first 785 #Omicron cases in that country.
Most hadn't travelled abroad.
Three-quarters were vaccinated; 7% had been boosted.
Only 9 required hospitalization, with 1 ending up in the ICU.
- Helen Branswell (STAT News) @HelenBranswell | 12:06 PM · Dec 17, 2021

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

Laura Espenhain et al. 2021. Epidemiological characterisation of the first 785 SARS-CoV-2 Omicron variant cases in Denmark, December 2021 (Rapid Communication). Eurosurveillance Volume 26, Issue 50, 16/Dec/2021. https://eurosurveillance.org/content/10.2807/1560-7917.ES.2021.26.50.2101146

Conclusion
We show a rapid increase and spread of the SARS-CoV-2 Omicron variant in Denmark, a European country with high testing capacity, high vaccination coverage and limited natural immunity through SARS-CoV-2 infection. The introduction and spread occurred despite an early and comprehensive public health response. Spread was catalysed by superspreading events and challenges further epidemic control. Information from the earlier travel-related cases, with no travel history to Africa, suggests that community transmission is more widespread than reported. The high proportion of fully vaccinated Omicron cases is a concern, the implications are still being described. It is too early to draw conclusions on the severity of Omicron compared to previous SARS-CoV-2 variants, analyses on this are ongoing.

>63 margd: Matches my experiences very well. Omicron blasted its way in. From first sighting to wide spread community transmission with no travel history to Africa in two weeks. Scary! More than 12.000 cases a day and probably more than half of them Omicron. So we're trying to get booster shots into shoulders asap.
I got mine Tuesday and had a mild case of flu-like symptoms Wednesday but was fine again on Thursday. My wife is getting a booster shot later today.

Total count for Denmark (as of yesterday)
1. shot = 4.702.867 (80.1%)
2. shot = 4.505.284 (76.7%)
3. shot = 1.581.478 (26.9%)

We are aiming at vaccinating 1.000.000 a week in the next weeks!

>64 bnielsen: I had sore arm for all three Pfizer shots, but it was the first one that had me dragging all day--possibly an indication that Feb + 2020 illness WAS COVID? Then again, DH, who was as sick as I've ever seen him in late Jan 2020, had no reaction to shots other than sore arms each time(?)
____________________________________________

How Full Are (US) Hospital I.C.U.s Near You? (Interactive)
Matthew Conlen, John Keefe, Albert Sun, Lauren Leatherby and Charlie Smart
https://www.nytimes.com/interactive/2020/us/covid-hospitals-near-you.html

"...the incidence rate of post-COVID lung fibrosis can be estimated at 2–6% after moderate illness...Currently...there are no treatments..."

Evgeny Bazdyrev et al. 2021. Lung Fibrosis after COVID-19: Treatment Prospects. Pharmaceuticals 17 August 2021, 14(8), 807; https://doi.org/10.3390/ph14080807 https://www.mdpi.com/1424-8247/14/8/807

Abstract
At the end of 2019, a highly contagious infection began its ominous conquest of the world. It was soon discovered that the disease was caused by a novel coronavirus designated as SARS-CoV-2, and the disease was thus abbreviated to COVID-19 (COVID). The global medical community has directed its efforts not only to find effective therapies against the deadly pathogen but also to combat the concomitant complications. Two of the most common respiratory manifestations of COVID are a significant reduction in the diffusing capacity of the lungs (DLCO) and the associated pulmonary interstitial damage. One year after moderate COVID, the incidence rate of impaired DLCO and persistent lung damage still exceeds 30%, and one-third of the patients have severe DLCO impairment and fibrotic lung damage. The persistent respiratory complications may cause substantial population morbidity, long-term disability, and even death due to the lung fibrosis progression. The incidence of COVID-induced pulmonary fibrosis caused by COVID can be estimated based on a 15-year observational study of lung pathology after SARS. Most SARS patients with fibrotic lung damage recovered within the first year and then remained healthy; however, in 20% of the cases, significant fibrosis progression was found in 5–10 years. Based on these data, the incidence rate of post-COVID lung fibrosis can be estimated at 2–6% after moderate illness. What is worse, there are reasons to believe that fibrosis may become one of the major long-term complications of COVID, even in asymptomatic individuals. Currently, despite the best efforts of the global medical community, there are no treatments for COVID-induced pulmonary fibrosis. In this review, we analyze the latest data from ongoing clinical trials aimed at treating post-COVID lung fibrosis and analyze the rationale for the current drug candidates. We discuss the use of antifibrotic therapy for idiopathic pulmonary fibrosis, the IN01 vaccine, glucocorticosteroids as well as the stromal vascular fraction for the treatment and rehabilitation of patients with COVID-associated pulmonary damage.

>66 margd: And pulmonary fibrosis was the #1 diagnostic condition for lung transplants in the US before Covid

>67 stellarexplorer: NYET to the Great Barrington Declaration!! Vaxx. Flatten curve!

Highly vaccinated countries thought they were over the worst. Denmark says the pandemic’s toughest month is just beginning.
Chico Harlan | Dec 18, 2021

...“The next month will be the hardest period of the pandemic,” said Tyra Grove Krause, the chief epidemiologist at Denmark’s State Serum Institute, a campus of brick buildings along a canal.

Ever since the omicron variant emerged in November, the best hope has been that it might cause less severe sickness than the delta version it is competing with, which in turn might make this wave more manageable and help the transition of covid-19 into an endemic disease. But Denmark’s projections show the wave so fully inundating the country that even a lessened strain will deliver an unprecedented blow.

Scientists caution that the knowledge of omicron remains imprecise. Denmark’s virus modelers have many scenarios. But even in a middle-of-the-road scenario, Danish hospitals will soon face a daily flow of patients several times beyond what they’ve previously seen...

https://www.washingtonpost.com/world/2021/12/18/omicron-variant-denmark/

>67 stellarexplorer: But what to do in countries with strict weapons control? (I.e. a scarcity of people willing to donate their lungs.)
I'm only half joking.

>70 bnielsen: I know you’re half joking, but despite our appalling gun violence, there aren’t enough donor organs here either. Loosen the gun laws further? (Sorry, in poor taste! ;))

Why We Need to Upgrade Our Face Masks—and Where to Get Them
High-quality respirators such as N95s and KN95s are now widely available and provide the best protection against COVID, according to experts. Why aren’t more people wearing them?
Tanya Lewis | September 30, 2021

What Makes a Good Mask?
Which Masks are Best?
The Best Masks for Kids

...Where to Find Legitimate Masks
An issue with commercially available high-filtration masks is that they may not come from reputable suppliers. The CDC’s Web site warns that about 60 percent of KN95 respirators available in the U.S. are counterfeit. To find ones that are legitimate, (Kimberly Prather, an atmospheric chemist at the University of California, San Diego) recommends the Web site Project N95 ( https://shop.projectn95.org/ ). Masks can also be ordered directly from suppliers such as Bona Fide Masks ( https://bonafidemasks.com/Powecom-kn-95/ ), which sells KN95s made by Powecom. “That’s the one people swear by,” Prather says. They cost around $1 each. DemeTECH ( https://www.demetech.us/ ) sells N95s for around $4 apiece, as well as other types of masks.

Reusing Masks
Double Masking
Facial Hair

https://www.scientificamerican.com/article/why-we-need-to-upgrade-our-face-masks...

>71 stellarexplorer: Thanks! I was a bit worried if donor lungs weren't in short supply. (I think Denmark do about 30 lung transplants a year and it typically buys the patient five to eight years.)

(Of the top of my head, I'd guess the U.S. number at about 2.000 and lo and behold:
https://www.uofmhealth.org/conditions-treatments/transplant/adult-lung-transplan...
says about 2.000 a year)

What’s the timeline for kids under 5 to get a COVID vaccine?
Lauran Neergaard • December 17, 2021

On Friday, Pfizer-BioNTech announced data from its ongoing trial of children 2 to 4 indicates that the vaccine dosage used — 3 micrograms, or one-tenth of the adult dose — did not produce a potent immune response in that group after two shots. But the two-shot regimen did produce a response — comparable to the one seen in 16-to-25-year-olds — in infants between 6 months and 2 years old. Children 5 to 11 receive a 10-microgram dose, or one-third of the formulation for people 12 and older.

Pfizer said it did not plan to test a higher dose for children under 5 at this time but will test trial subjects’ immune response after administering a third dose.

...“If the three-dose study is successful,” the company said in a news release*, “Pfizer and BioNTech expect to submit data to regulators to support an Emergency Use Authorization (EUA) for children 6 months to under 5 years of age in the first half of 2022.”...

https://www.latimes.com/science/story/2021-12-17/whats-the-timeline-for-kids-und...
---------------------------------------------------

* PFIZER AND BIONTECH PROVIDE UPDATE ON ONGOING STUDIES OF COVID-19 VACCINE
Pfizer | December 17, 2021
https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-bionte...

Omnicron in UK, S Africa, etc.:

Omicron predictions (25:39)
Dr. John Campbell | Dec 17, 2021
https://www.youtube.com/watch?v=_T6C-2FNy8I

Mathew V Kiang et al. 2021. Routine asymptomatic testing strategies for airline travel during the COVID-19 pandemic: a simulation study. The Lancet Infectious Diseases Volume 21, ISSUE 7, P929-938, July 01, 2021. DOI:https://doi.org/10.1016/S1473-3099(21)00134-1 https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00134-1/fullt...

Summary
Background
Routine viral testing strategies for SARS-CoV-2 infection might facilitate safe airline travel during the COVID-19 pandemic and mitigate global spread of the virus. However, the effectiveness of these test-and-travel strategies to reduce passenger risk of SARS-CoV-2 infection and population-level transmission remains unknown.

Methods
In this simulation study, we developed a microsimulation of SARS-CoV-2 transmission in a cohort of 100 000 US domestic airline travellers using publicly available data on COVID-19 clinical cases and published natural history parameters to assign individuals one of five health states of susceptible to infection, latent period, early infection, late infection, or recovered. We estimated a per-day risk of infection with SARS-CoV-2 corresponding to a daily incidence of 150 infections per 100 000 people. We assessed five testing strategies: (1) anterior nasal PCR test within 3 days of departure, (2) PCR within 3 days of departure and 5 days after arrival, (3) rapid antigen test on the day of travel (assuming 90% of the sensitivity of PCR during active infection), (4) rapid antigen test on the day of travel and PCR test 5 days after arrival, and (5) PCR test 5 days after arrival. Strategies 2 and 4 included a 5-day quarantine after arrival. The travel period was defined as 3 days before travel to 2 weeks after travel. Under each scenario, individuals who tested positive before travel were not permitted to travel. The primary study outcome was cumulative number of infectious days in the cohort over the travel period without isolation or quarantine (population-level transmission risk), and the key secondary outcome was the number of infectious people detected on the day of travel (passenger risk of infection).

Findings
We estimated that in a cohort of 100 000 airline travellers, in a scenario with no testing or screening, there would be 8357 (95% uncertainty interval 6144–12831) infectious days with 649 (505–950) actively infectious passengers on the day of travel. The pre-travel PCR test reduced the number of infectious days from 8357 to 5401 (3917–8677), a reduction of 36% (29–41) compared with the base case, and identified 569 (88% 76–92) of 649 actively infectious travellers on the day of flight; the addition of post-travel quarantine and PCR reduced the number of infectious days to 1474 (1087–2342), a reduction of 82% (80–84) compared with the base case. The rapid antigen test on the day of travel reduced the number of infectious days to 5674 (4126–9081), a reduction of 32% (26–38) compared with the base case, and identified 560 (86% ...) actively infectious travellers; the addition of post-travel quarantine and PCR reduced the number of infectious days to 2518 (1935–3821), a reduction of 70% (67–72) compared with the base case. The post-travel PCR alone reduced the number of infectious days to 4851 (3714–7679), a reduction of 42% (35–49) compared with the base case.

Interpretation
Routine asymptomatic testing for SARS-CoV-2 before travel can be an effective strategy to reduce passenger risk of infection during travel, although abbreviated quarantine with post-travel testing is probably needed to reduce population-level transmission due to importation of infection when travelling from a high to low incidence setting.

"Reformulation of existing mRNA vaccines to target Omicron may not be necessary with a 3-dose regimen" and lab characterization of its spike properties (reduced receptor binding, cell-cell fusion, but increased cell-to-cell transmission)

Effectiveness of mRNA vaxx agst omicron etc. for cases, hospitalization, deaths
( https://twitter.com/EricTopol/status/1472927275934830599/photo/1 )

- Eric Topol (Scripps) @EricTopol | 8:50 AM · Dec 20, 2021
-----------------------------------------------------------

Zeng Cong etal. 2021. Neutralization and Stability of SARS-CoV-2 Omicron Variant. BioRXiv Dec 20,2021
doi: https://doi.org/10.1101/2021.12.16.472934 https://biorxiv.org/content/10.1101/2021.12.16.472934v1

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

Abstract
...Here we show that Omicron exhibits significant immune evasion compared to other variants, but antibody neutralization is largely restored by mRNA vaccine booster doses. Additionally, the Omicron spike exhibits reduced receptor binding, cell-cell fusion, S1 subunit shedding, but increased cell-to-cell transmission, and homology modeling indicates a more stable closed S structure. These findings suggest dual immune evasion strategies for Omicron, due to altered epitopes and reduced exposure of the S receptor binding domain, coupled with enhanced transmissibility due to enhanced S protein stability. These results highlight the importance of booster vaccine doses for maintaining protection against the Omicron variant, and provide mechanistic insight into the altered functionality of the Omicron spike protein.

Waning of vaccine protection over time, during the Delta wave in the US,
associated with increase in Covid cases across all age groups and increase in deaths among age 65+ shown below
but there was a 2 month delay in recommending boosters for all adults

Reduced protection by vaccine thru Sept 4, 2021 ( https://twitter.com/EricTopol/status/1472936038230151169/photo/1 )

- Eric Topol (Scripps) | @EricTopol9:24 AM · Dec 20, 2021
----------------------------------------------------------

Gabriela Paz-Bailey et al. 2021. Covid-19 Rates by Time since Vaccination during Delta Variant Predominance. NEJM Evidence. Dec 20, 2021. https://evidence.nejm.org/pb-assets/evidence-site/content/EVIDoa2100057.pdf

Abstract
...RESULTS During August 1 to September 4, 2021, case rates per 100,000 person-weeks among all vaccine recipients for the January to February, March to April, May to June, and July cohorts were 168.8 ..., 123.5 ..., 83.6 ..., and 63.1 ..., respectively.

Similar trends were observed by age group for BNT162b2 (Pfizer–BioNTech) and mRNA-1273 (Moderna) vaccine recipients. Rates for the Ad26.COV2.S (Janssen-Johnson & Johnson) vaccine were higher; however, trends were inconsistent. BNT162b2 vaccine
recipients 65 years of age or older had higher death rates among those vaccinated earlier in the year. Protection against death was sustained for the mRNA-1273 vaccine recipients.

UK

School staff more likely to catch Covid than other workers
Matilda Martin | 16th December 2021

New figures released by the (UK) Office for National Statistics (ONS) show that those working in the education sector are 37 per cent more likely to test positive for Covid-19 than other workers...15 November 15 to 28 November.

...On 1 December, ONS figures showed that people working in the education sector were 51 per cent more likely to test positive for Covid than other workers.

...On 14 December, data released by the Department for Education revealed that pupil absence due to Covid-related reasons had risen by nearly 30,000 in a fortnight, with teacher and leader absence rising by 20 per cent...

https://www.tes.com/magazine/news/general/school-staff-more-likely-catch-covid-o...

Omicron is here. What are your treatment options if you get Covid-19?
Covid-19 experts on which treatments hold up against omicron and which ones to ask a doctor about if you get sick.
Kelsey Piper | Dec 20, 2021

... (1. sotrovimab) Research currently published only in preprints suggests that based on lab studies of antibody neutralization, 18 of the 19 different specific antibody formulations examined are less effective in fighting off omicron. There’s one notable exception: , a monoclonal antibody from GlaxoSmithKline and Vir Biotechnology, seems to hold up well against omicron.

...(2) fluvoxamine, is generally used as an antidepressant and to treat obsessive-compulsive disorder. But it appears to reduce the risk of needing hospitalization or medical observation for Covid-19 by about 30 percent, and by considerably more among those patients who stick with the 10-day course of medication. Unlike monoclonal antibodies, fluvoxamine can be taken as a pill at home

...(3) budesonide asthma inhalers, was found in one randomized trial to speed at-home recovery considerably and in another to reduce risk of hospitalization. There has been no formal guidance in the US on when to consider budesonide. In the UK and Canada, health agencies have allowed doctors to prescribe it off-label on a case-by-case basis.

What does this mean in terms of concrete recommendations for a person who gets sick right now, including with omicron? “They should try to get the monoclonal antibodies,” (Angela Reiersen, a psychiatrist at Washington University in St. Louis whose research turned up fluvoxamine as a promising anti-Covid candidate) told me. “They should also consider taking fluvoxamine if appropriate, and another thing that might be useful as an outpatient would be inhaled steroids like budesonide.”

...More promising treatments...Pfizer’s Paxlovid, a protease inhibitor — which means it blocks an enzyme needed for viral replication. The drug showed an impressive 88 percent efficacy in preventing hospitalization among unvaccinated patients...not yet been approved by the FDA, however, and at this point, supply of the drug is limited.

The FDA is also considering molnupiravir, another repurposed drug that looks to be at least moderately effective, though...there are some concerns...

https://www.vox.com/future-perfect/22841852/covid-drugs-antibodies-fluvoxamine-m...

>80 margd: So a few things.

I suspect at least in the US it will not be easy to get strovimab, as it’s the only monoclonal that seems to hold up against omicron, and the adherence to the criteria for getting it have tightened accordingly. Also, a big supply was - I have heard but haven’t personally looked into it - reserved by the government for emergency use..

Fluvoxamine is probably not going to hurt, and while it may help, I would see it as one more adjunctive thing you are doing, not the sole thing. We still need larger studies on this. The exception is that this medicine may be a very bad idea for people with bipolar disorder, as it could potentially throw them into mania.

Paxlovid looks very promising, but I fear it will be available if at all in limited quantities during the Omicron wave.

The pancoronavirus vaccine would be a godsend, but we are not on the verge of that yet.

And then there’s the other important thing if you get it: don’t forget that if you are boosted your chances of severe lines are low and you have a high likelihood of being fine. If you are not boosted, get it ASAP. If you are not vaccinated, I’m doubting you are reading this.

Update to my exposure story: my son who lives in NYC had a false negative home test and came home for a visit. He had a PCR cooking, and after 48 hours, the news came that he was positive. So 48 hours sharing the same airspace while covid positive.
He left at that point so as to not further expose stellarwoman and me. We waited until day 5 and got PCRs: we are both negative. I can only assume, given the infectiousness and immune escape capability of this variant (almost certainly omicron based on incubation period and characteristic symptoms), that our boosters protected us.

>81 stellarexplorer: You didn't mention budesonide asthma inhalers--what do you think of those?

>82 stellarexplorer: An early Christmas present--not to have disease hovering over your holiday! Hope your son's doing okay?
Christmas 2021 may be a superspreader event for too many of us, though, it looks like...

Already Omicron is dominant strain in US--73.2%!
92.3% here in the Midwest (incl Michigan)...
https://covid.cdc.gov/covid-data-tracker/#variant-proportions
---------------------------------------------------------------

Omicron variant now makes up 73% of Covid infections diagnosed in U.S.
Helen Branswell | Dec. 20, 2021

...There are some hints that the virus may cause more mild disease — perhaps because it appears to prefer to replicate in the upper airways rather than descending into the lung to cause Covid pneumonia. Scientists in South Africa, which first reported the existence of the new variant, say fewer patients are requiring supplemental oxygen in this wave of infections and far fewer are ending up in intensive care.

But others caution against drawing conclusions about what level of illness the variant will trigger. For instance, scientists in South Africa are studying whether a wave of infections caused earlier this year by the Beta variant might have helped protect people there from Omicron. The Beta variant also had mutations that helped it evade the protection generated by vaccines, but it did not spread widely outside of South Africa.

https://www.statnews.com/2021/12/20/omicron-variant-now-makes-up-73-of-covid-inf...
_________________________________________________

3M™ Aura™ Particulate Respirator 9205+
https://www.3m.com/3M/en_US/p/d/b00051022/

Others
https://shop.projectn95.org/masks

Graph--Hospital & ICU occupancy of 2-3 dose vaxxed v unvaxxed, 10 Aug-Dec 21, 2021 (Ontario Science Table)
https://twitter.com/CTV_AvisFavaro/status/1472952529549938688/photo/1

To Fight Omicron, Biden Plans Aid From Military and 500 Million Tests
Sheryl Gay Stolberg | Dec. 21, 2021

WASHINGTON — President Biden will announce new steps on Tuesday to confront a staggering surge in coronavirus cases, including readying 1,000 military medical professionals to help at overburdened hospitals, setting up new federal testing sites, deploying hundreds of federal vaccinators and buying 500 million rapid tests to distribute free to the public.

...The 500 million tests that the administration intends to purchase will not be available until January, the senior officials said, adding that the government intends to create a website where people can request that tests be sent to their homes, free of charge. It was not immediately clear where the tests would come from.

The plan for new federal testing sites will debut in New York City, where several new sites will be running before Christmas. And Mr. Biden intends to invoke the Defense Production Act, officials said, to accelerate production of tests...

https://www.nytimes.com/2021/12/21/us/politics/omicron-covid-biden.html

This anti-Covid pill changes everything. So why won’t it be available for all?
Eric Topol | Dec 21, 2021

...the vital need for the (Pfizer's) Paxlovid five-day pill pack (two pills a day, and one other pill, a low dose ritonavir to help raise Paxlovid’s blood level) to be available everywhere. But there is a grossly insufficient supply of only 200,000 treatment courses now, and only 80 million expected by the end of next year.

...In the days ahead, Paxlovid will gain emergency authorization use by the US Food and Drug Administration. That’s good, but it doesn’t get us where we need to be. We must find a way to rapidly scale pill pack production for wide accessibility and use throughout the world, whether that involves enacting the Defense Production Act in the United States or other bold measures. It is not appropriate at this juncture to rely on a single company to mass produce a small molecule which companies throughout the world are fully capable of making with the highest manufacturing standards...

https://www.theguardian.com/commentisfree/2021/dec/21/paxlovid-anti-covid-pill-w...

_________________________________________________________

...Pfizer also committed to offering PAXLOVID through a tiered pricing approach based on the income level of each country “to promote equity of access across the globe,” with high- and upper-middle income countries to pay more for the COVID-19 pill than lower income countries...
https://www.genengnews.com/covid-19-candidates/pfizer/

Pfizer's Paxlovid Holds Up
Derek Lowe | 14 Dec 2021

+ high-risk patients the efficacy in preventing hospitalization is still 89%

+ the efficacy against hospitalization (or death) was basically identical if the drug was taken within five days of symptoms versus being taken within three days

- my guess is that...we have the usual situation with antivirals (and antibiotics): the more people who take this drug, the better the chances of resistance developing to it.

+ the drug "potently inhibits" the protease enzyme from all the variants of concern, including Omicron

- One hitch is that the drug is given along with Ritonavir, which is not in there for its antiviral activity (it has no antiviral activity against the coronavirus), but for its well-known ability to inhibit drug-clearing metabolic enzymes in the liver. That's fine for five days unless you're already taking some crucial medications that would normally be metabolized by those enzymes, and you'd have to think that a good number of the high-risk patients are.

- The company has been saying that they will have 200,000 courses of treatment for this year, and 80 million next year, which may sound like a lot but really isn't in the face of worldwide demand. This argues even more strongly for restricting it to high-risk cases. We're not all going to be walking around with a "Pax-pack", nor should we if there are only going to be 80 million people treated with it next year.

https://www.science.org/content/blog-post/pfizer-s-paxlovid-holds

Beware of these 5 early omicron symptoms, study says
Jeremy Tanner | Dec 20, 2021

Wondering if you have a cold or the highly transmissible omicron variant of the coronavirus?...it might be hard to tell.

...Researchers looked at symptoms reported between Oct. 3 and 10, when the delta variant was dominant, and compared those to the most recent period, Dec. 3-10, when omicron was spreading rapidly.

The top five symptoms reported in December were:
Runny nose
Headache
Fatigue (either mild or severe)
Sneezing
Sore throat

...The cold-like symptoms reported three days after a positive test were not vastly different from those of the delta variant, researchers found. The early data suggests that omicron arrives with symptoms distinct from earlier variants, which caused more flu-like, initial symptoms.

Experts warn that it’s too early to assume that omicron, which is highly transmissible and heavily mutated, will end up being a mild variant....

https://myfox8.com/news/coronavirus/beware-of-these-5-early-omicron-symptoms-stu...
-----------------------------------------------------------------------------------

The (UK) COVID Symptom Study reveals six distinct ‘types’ of COVID-19
ZOE Covid Study | July 17, 2020

Data from the COVID Symptom Study has revealed six distinct ‘types’ of COVID-19, which has major implications for treatment and monitoring.

...The six clusters are as follows:

1 (‘flu-like’ with no fever): Headache, loss of smell, muscle pains, cough, sore throat, chest pain, no fever.

2 (‘flu-like’ with fever): Headache, loss of smell, cough, sore throat, hoarseness, fever, loss of appetite.

3 (gastrointestinal): Headache, loss of smell, loss of appetite, diarrhea, sore throat, chest pain, no cough.

4 (severe level one, fatigue): Headache, loss of smell, cough, fever, hoarseness, chest pain, fatigue.

5 (severe level two, confusion): Headache, loss of smell, loss of appetite, cough, fever, hoarseness, sore throat, chest pain, fatigue, confusion, muscle pain.

6 (severe level three, abdominal and respiratory): Headache, loss of smell, loss of appetite, cough, fever, hoarseness, sore throat, chest pain, fatigue, confusion, muscle pain, shortness of breath, diarrhea, abdominal pain.

...Next, the team investigated whether people experiencing particular symptom clusters were more likely to require breathing support in the form of ventilation or additional oxygen...only 1.5% of people with cluster 1, 4.4% of people with cluster 2 and 3.3% of people with cluster 3 COVID-19 required breathing support. These figures were 8.6%, 9.9% and 19.8% for clusters 4,5 and 6 respectively. Furthermore, nearly half of the patients in cluster 6 ended up in hospital, compared with just 16% of those in cluster 1.

Broadly, people with cluster 4,5 or 6 COVID-19 symptoms tended to be older and frailer, and were more likely to be overweight and have pre-existing conditions such as diabetes or lung disease than those with type 1,2 or 3.

The researchers then developed a model combining information about age, sex, BMI and pre-existing conditions together with symptoms gathered over just five days from the onset of the illness.

This was able to predict which cluster a patient falls into and their risk of requiring hospitalisation and breathing support with a higher likelihood of being correct than an existing risk model based purely on age, sex, BMI and pre-existing conditions alone.

Given that most people who require breathing support come to hospital around 13 days after their first symptoms, this extra eight days represents a significant ‘early warning’ as to who is most likely to need more intensive care...

https://covid.joinzoe.com/post/covid-clusters

>83 margd: Thanks, he’s 24, now isolating, not boosted before exposure, very mild symptoms, has 20+ friends with what appears to be the omicron variant. Multiple people at a party he attended are positive.

As far as budesonide asthma inhalers, I think they are reasonably safe, there are some studies showing some benefit in reducing progression in severity. I wonder whether the same would be tru for other steroid inhalers? Anything specific about this one? I don’t know enough about that topic - would have to research. But seems worth knowing just because many people already have various inhalers in their possession…

>89 stellarexplorer: A hotspot I follow in Ontario (friends & family there) has highest incidence in 18-29 age group. Least vaxxed group but bad, too, at the university where students are all vaxxed. Never mind parties, they live together, eat in cafeterias, go to class together. This U is being responsible. Only wish they could quarantine the kids somehow so they didn't inadvertently didn't take the virus home with them for holidays...

The only inhalers I've ever been given was for colds going to my chest--apparently can trigger asthma in me and makes it difficult to clear my lungs(?). Anyway, takes only one or two puffs to breathe normally. (Darn thing usually expires before I need it again..) Never questioned how it worked, but if omicron has particular affiliation with bronchus (bronchi?), wonder if budesonide disinfects somehow as well as dilates airways? Sounds Trumpian! (Must read the study more closely.)

Eric Topol (Scripps) @EricTopol | 10:22 PM · Dec 21, 2021:
The first potential variant-proof, universal, beta-coronavirus vaccine, by @WalterReedArmy, soon going into clinical trials*...

Here are the impressive findings of this vaccine in non-human primates @ScienceTM published last week** Can't wait to see the Phase 1 data but big congrats to @KayvonModjarrad and team

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

* US Army Creates Single Vaccine Against All COVID & SARS Variants, Researchers Say
Tara Copp | Dec 21, 2021

...The achievement is the result of almost two years of work on the virus. The Army lab received its first DNA sequencing of the COVID-19 virus in early 2020. Very early on, Walter Reed’s infectious diseases branch decided to focus on making a vaccine that would work against not just the existing strain but all of its potential variants as well.

Walter Reed’s Spike Ferritin Nanoparticle COVID-19 vaccine, or SpFN, completed animal trials earlier this year with positive results. Phase 1 of human trials, which tested the vaccine against Omicron and the other variants, wrapped up this month, again with positive results that are undergoing final review...

Unlike existing vaccines, Walter Reed’s SpFN uses a soccer ball-shaped protein with 24 faces for its vaccine, which allows scientists to attach the spikes of multiple coronavirus strains on different faces of the protein...

https://defenseone.com/technology/2021/12/us-army-creates-single-vaccine-effecti...
--------------------------------------------------

** M. Gordon et al. 2021. A SARS-CoV-2 ferritin nanoparticle vaccine elicits protective immune responses in nonhuman primates.
Science Translational Medicine • 16 Dec 2021 • First Release • DOI: 10.1126/scitranslmed.abi5735 https://www.science.org/doi/10.1126/scitranslmed.abi5735

Abstract
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants stresses the continued need for next-generation vaccines that confer broad protection against coronavirus disease 2019 (COVID-19). We developed and evaluated an adjuvanted SARS-CoV-2 spike ferritin nanoparticle (SpFN) vaccine in nonhuman primates. High-dose (50 μg) SpFN vaccine, given twice 28 days apart, induced a Th1-biased CD4 T cell helper response and elicited neutralizing antibodies against SARS-CoV-2 wild-type and variants of concern, as well as against SARS-CoV-1 (the virus responsible for outbreaks of Severe Acute Respiratory Syndrome (SARS), which ended in 2004). These potent humoral and cell-mediated immune responses translated into rapid elimination of replicating virus in the upper and lower airways and lung parenchyma of nonhuman primates following high-dose SARS-CoV-2 respiratory challenge. The immune response elicited by SpFN vaccination and resulting efficacy in nonhuman primates supports the utility of SpFN as a vaccine candidate for SARS-causing betacoronaviruses.

Dr. Ali Nouri (Asst Sec'y Energy) @AliNouriPhD | 9:35 PM · Dec 21, 2021
Minimal neutralization of #Omicron UNLESS you experienced "Spike" at least 3 times:

2 dose vax + Boost = 3
Infxn + 2 dose vax = 3
Infxn + 2 dose vax + Boost = 4

Even then, neutralization reduced so take add'l precaution

Preprint from @florian_krammer*

Graph-convalescent neutralization agst Wuhan, Beta, Omicron
https://twitter.com/AliNouriPhD/status/1473482277409759247/photo/1

Graph-2 Pfizer neutralization agst 3 variants
https://twitter.com/AliNouriPhD/status/1473482277409759247/photo/2

Graph-3 Pfizer neutralization agst 3 variants
https://twitter.com/AliNouriPhD/status/1473482277409759247/photo/3

Graph-convalescent + 3 Pfizer agst 3 variants
https://twitter.com/AliNouriPhD/status/1473482277409759247/photo/4
-------------------------------------------------------

* Juan Manuel Carreno...Florian Krammer. 2021. Activity of convalescent and vaccine serum against a B.1.1.529 variant SARS-CoV-2 isolate. medRxiv Dec 21, 2021. doi: https://doi.org/10.1101/2021.12.20.21268134 https://www.medrxiv.org/content/10.1101/2021.12.20.21268134v1

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

Abstract
... Here, we investigated the neutralizing and binding activity of sera from convalescent, mRNA double vaccinated, mRNA boosted as well as convalescent double vaccinated and convalescent boosted individuals against wild type, B.1.351 (Beta) and B.1.1.529 (Omicron) SARS-CoV-2 isolates. Neutralizing activity of sera from convalescent and double vaccinated participants was undetectable to very low against B.1.1.529 while neutralizing activity of sera from individuals who had been exposed to spike three or four times was maintained, albeit at strongly reduced levels. Binding to the B.1.1.529 receptor binding domain (RBD) and N-terminal domain (NTD) was reduced in convalescent not vaccinated but was mostly retained in vaccinated individuals.

>91 margd: I was really excited to hear this today. The pancoronavirus vaccine would be like the silver bullet for Covid and potentially all future coronaviruses. I need to look more into this because this concept still looks like it focuses on the spike, and I had been under the impression (possibly falsely) that the plan was to attack epitopes not on the spike that were thought to be less able to mutate. Looking forward to more info!

On fluvoxamine, this PREPRINT just came out:

https://www.medrxiv.org/content/10.1101/2021.12.17.21268008v1

Supporting possible utility especially in areas without other resources. I think early, sick, and a lack of monoclonals might qualify.

Interestingly, when it comes to THEORETICAL proposed mechanisms, it looks like fluoxetine (Prozac) may have similar characteristics. This is not intended as my endorsement of any of this, just interesting new info. And I would definitely not recommend people go on these medicines without medical supervision: they are powerful medicines, and more so in some people than others.

FYI, working, vaxxed 30YO son has twice had symptoms, but never tested positive. Though MDs/employer/we gave him a few days for symptoms to recede and to see if tests turned positive, never did test pos. Might have been vaxx? Our timing? Something else?

Zain Chagla (McMaster U infectious disease MD) @zchagla | 8:56 AM · Dec 23, 2021:
Is anyone seeing late PCR / RAT positives amongst symptomatic cases?
i.e. people who have symptoms and exposures but have negative PCR up front, but retest positive in a day or two?

Discussed at
https://twitter.com/zchagla/status/1474016042896744452

Eric Topol @EricTopol
https://twitter.com/EricTopol/status/1474099769265975303

Just published @ScienceTM on the Merck pill, Molnupiravar, which got FDA cleared today.
https://science.org/doi/10.1126/scitranslmed.abl7430

Unlike Remdesvir, which did not reduce viral load, Molnupiravar did.
Another potential use of these pills is to reduce infectiousness and transmission

2:29 PM · Dec 23, 2021

(Some discussion follows on mutagenic nature, i.e. possibility of generating new variants.)

Eric Topol @EricTopol · 1h
The link to the paper on the discovery of Paxlovid in this issue. It's the first non-repurposed drug vs #SARSCoV2 to have clinical efficacy and FDA clearance. It may be the fastest small molecule from discovery to completion of clinical trials in history

Dafydd R. et al. 2021. An oral SARS-CoV-2 Mpro inhibitor clinical candidate for the treatment of COVID-19. Science • 2 Nov 2021 • Vol 374, Issue 6575 • pp. 1586-1593 • DOI: 10.1126/science.abl4784 https://www.science.org/doi/10.1126/science.abl4784

Path to another drug against COVID-19
The rapid development of vaccines has been crucial in battling the ongoing COVID-19 pandemic. However, access challenges remain, breakthrough infections occur, and emerging variants present increased risk. Developing antiviral therapeutics is therefore a high priority for the treatment of COVID-19. Some drug candidates in clinical trials act against the viral RNA-dependent RNA polymerase, but there are other viral enzymes that have been considered good targets for inhibition by drugs. Owen et al. report the discovery and characterization of a drug against the main protease involved in the cleavage of polyproteins involved in viral replication. The drug, PF-07321332, can be administered orally, has good selectivity and safety profiles, and protects against infection in a mouse model. In a phase 1 clinical trial, the drug reached concentrations expected to inhibit the virus based on in vitro studies. It also inhibited other coronaviruses, including severe acute respiratory syndrome coronavirus 1 and Middle East respiratory syndrome coronavirus, and could be in the armory against future viral threats. —VV

Abstract
The worldwide outbreak of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. Alongside vaccines, antiviral therapeutics are an important part of the healthcare response to countering the ongoing threat presented by COVID-19. Here, we report the discovery and characterization of PF-07321332, an orally bioavailable SARS-CoV-2 main protease inhibitor with in vitro pan-human coronavirus antiviral activity and excellent off-target selectivity and in vivo safety profiles. PF-07321332 has demonstrated oral activity in a mouse-adapted SARS-CoV-2 model and has achieved oral plasma concentrations exceeding the in vitro antiviral cell potency in a phase 1 clinical trial in healthy human participants.

No time to even skim this one, but I intend to! A tour through the weeds, I'm afraid...

Ravindra K. Gupta and Eric J. Topol. 2021. COVID-19 vaccine breakthrough infections (Perspective). Science • 23 Dec 2021 • Vol 374, Issue 6575 • pp. 1561-1562 • DOI: 10.1126/science.abl8487 https://www.science.org/doi/10.1126/science.abl4784

Eric Topol @EricTopol | 8:49 AM · Dec 23, 2021
2. And throughout Europe, + graph of staffing vs US
https://ft.com/content/43ba23b5-7dc3-435d-9d6a-201dbc038451
by @labboudles @SarahNev
Graph-infected healthcare workers by country... ( https://twitter.com/EricTopol/status/1474014181418360833/photo/1 )

Someone in my home has COVID. How do we isolate safely?

When someone in your household needs to quarantine at home, you want them to be isolated from others as much as possible. Remember that the virus transmits predominantly through the air, so sanitizing surfaces is not enough.

Visit www.healthyheating.com for tips on how to reduce the risk of transmission from one household member to another.
Part I: How to set up an emergency isolation room inside a home or apartment for a suspected infected occupant.
Part II. How to Isolate a Full Basement Renovation from Occupied Upper Floors During a Pandemic

https://cleanaircrew.org/someone-in-my-home-has-covid-how-do-we-isolate-safely/

" In broad terms, our estimates suggest that individuals who have received at least 2 vaccine doses remain substantially protected against hospitalisation, even if protection against infection has been largely lost against the Omicron variant..."

Report 50 - Hospitalisation risk for Omicron cases in England
Neil Ferguson1, Azra Ghani, Wes Hinsley and Erik Volz on behalf of the Imperial College COVID-19 response team | 22 December 2021

Summary
...Overall, we find evidence of a reduction in the risk of hospitalisation for Omicron relative to Delta infections, averaging over all cases in the study period. The extent of reduction is sensitive to the inclusion criteria used for cases and hospitalisation, being in the range 20-25% when using any attendance at hospital as the endpoint, and 40-45% when using hospitalisation lasting 1 day or longer or hospitalisations with the ECDS discharge field recorded as “admitted” as the endpoint (Table 1). These reductions must be balanced against the larger risk of infection with Omicron, due to the reduction in protection provided by both vaccination and natural infection. A previous infection reduces the risk of any hospitalisation by approximately 50% (Table 2) and the risk of a hospital stay of 1+ days by 61% (95%CI:55-65%) (before adjustments for under ascertainment of reinfections).

(Past infection) High historical infection attack rates and observed reinfection rates with Omicron mean it is necessary to correct hazard ratio estimates to accurately quantify intrinsic differences in severity between Omicron and Delta and to assess the protection afforded by past infection. The resulting adjustments are moderate (typically less than an increase of 0.2 in the hazard ratio for Omicron vs Delta and a reduction of approximately 0.1 in the hazard ratio for reinfections vs primary infections) but significant for evaluating severity overall. Using a hospital stay of 1+ days as the endpoint, the adjusted estimate of the relative risk of reinfections versus primary cases is 0.31, a 69% reduction in hospitalisation risk (Table 2).

(Vaxx status) Stratifying hospitalisation risk by vaccination state reveals a more complex overall picture, albeit consistent with the unstratified analysis. This showed an apparent difference between those who received AstraZenca (AZ) vaccine versus Pfizer or Moderna (PF/MD) for their primary series (doses 1 and 2). Hazard ratios for hospital attendance with Omicron for PF/MD are similar to those seen for Delta in those vaccination categories, while Omicron hazard ratios are generally lower than for Delta for the AZ vaccination categories. Given the limited samples sizes to date, we caution about over-interpreting these trends, but they are compatible with previous findings that while protection afforded against mild infection from AZ was substantially reduced with the emergency of Delta, protection against more severe outcomes was sustained... We emphasise that these are estimates which condition upon infection; net vaccine effectiveness against hospital attendance may not vary between the vaccines, given that PF/MD maintain higher effectiveness against symptomatic infection with Omicron than AZ...

Our estimates will assist in refining mathematical models of potential healthcare demand associated with the unfolding European Omicron wave. The hazard ratios provided in Table 3 can be translated into estimates of vaccine effectiveness (VE) against hospitalisation, given estimates of VE against infection.... In broad terms, our estimates suggest that individuals who have received at least 2 vaccine doses remain substantially protected against hospitalisation, even if protection against infection has been largely lost against the Omicron variant...
----------------------------------------------------------

Yaneer Bar-Yam* @yaneerbaryam | 1:54 PM · Dec 23, 2021
https://twitter.com/yaneerbaryam/status/1474091037861761026
https://threadreaderapp.com/thread/1474091037861761026.html

UK data: Omicron is as severe as Delta for cases that would be infected by Delta, and infects people who would not be infected by Delta (due to immunity of prior infection or vaccination). Those cases are less severe. By Simpsons paradox Omicron seems less severe, but is more. 1/...5/ (and discussion)

* Yaneer Bar-Yam @yaneerbaryam -- Complex Systems Physicist | President of @NECSI | Studying pandemics since 2005 | For progressive elimination http://worldhealthnetwork.global

How do we study the severity of a new variant?
A (very short, plain language) guide to help you organize your thinking
Natalie E. Dean, PhD* |Dec 23, 2021
https://nataliexdean.substack.com/p/how-do-we-study-the-severity-of-a

* Natalie E. Dean, PhD @nataliexdean -- Asst Professor of Biostatistics at @EmoryRollins, specializing in emerging infectious diseases and vaccine study design. Previously UF @HarvardBiostats.

Update to 64:

Total count for Denmark (as of today)
1. shot = 4.784.341 (81.4%)
2. shot = 4.536.523 (77.2%)
3. shot = 2.461.244 (41.9%)

If it goes as expected, this will revolutionize Covid prevention and stop the march of variants. Been waiting for this

https://yourlocalepidemiologist.substack.com/p/pan-coronavirus-super-vaccine?jus...

>104 stellarexplorer: Brilliant. Can't come soon enough.

>104 stellarexplorer: Hope this second generation of vaccines can sport enough spikes to stop all coronaviruses--current and future!

Also hope that research continues to produce vaxx that prompts broadly cross-binding and neutralizing antibodies like those produced by some convalescents: nice to have in world's armentarium going forward--in case unexpected coronavirus epidemic.

So much learned that may be deployed as vaxxes against other diseases, e.g., HIV, bird flu. Surely world won't forget importance of research and public health funding going forward? :/
_____________________________________________________________

Israel said delaying rollout of 4th COVID shots amid signs Omicron less severe
TOI staff | 23 December 2021

TV report also says Health Ministry DG may not endorse panel’s recommendation to offer additional booster shots if further data suggests hospitalizations lower from new variant

The Health Ministry has reportedly decided that Israel will not begin offering fourth doses of the COVID-19 vaccine starting on Sunday as planned for Israelis over 60 and others at risk.

The decision was made at a meeting held by the ministry Thursday evening...

https://www.timesofisrael.com/israel-said-to-delay-rollout-of-4th-covid-shots-am...

_____________________________________________________________

ETA:
Op-Ed: How can we avoid second winter of despair with Omicron ($1 pay wall)
Should we offer HCW an emergency 4th booster to get us through an Omicron surge?
Peter Hotez* | Dec 17, 2021
https://www.latimes.com/opinion/story/2021-12-17/op-ed-averting-a-second-winter-....

* Prof Peter Hotez MD PhD @PeterHotez --
Vaccine Scientist-Author-Combat Antiscience @bcmhouston
Professor Pediatrics Molecular Virology, @bcm_tropmed
Dean, TexasChildrens
Chair in Tropical Pediatrics

BNO Newsroom @BNODesk | 8:30 PM · Dec 26, 2021:
China reports 162 new coronavirus cases, the biggest one-day increase in 21 months, as officials work to contain Xian outbreak

China battles Covid-19 surge in Xian with mass disinfection, more testing
Guo Rui | 12:09pm, 27 Dec, 2021

Clouds of disinfectant covered the city to combat the outbreak, with 150 new cases reported on Sunday
Local officials have described the situation as ‘dire and complex’ with case numbers expected to remain high in coming days

...Virologist Jin Dong-Yan, a professor at the University of Hong Kong, said lockdowns and mass testing would help bring the situation under control, but a mass disinfection campaign was likely to be “of little use”.

Jin said the authorities were grappling with a situation where it appeared contact tracing had “fallen far, far behind” transmission, raising the challenge of containing the situation.

“They overdo everything, but they are worried because they don’t know the source of some of the active transmission … there are indications that some of the cases are not linked or have no contact, so that’s why they worry that the virus might be in the air, but that should not be true,” he said of the disinfection programme.

“There might be airborne transmission, but that would be under very specific circumstances.” While it is thought to be possible to pick up an infection from a contaminated surface, this would not be driving most transmission, he added.

The widespread disinfection in Xian appears to be in direct violation of the State Council’s Covid-19 response guidelines. Issued in March last year, these state that disinfection should be carried out in a “precise and scientific” manner to cut off the transmission.

According to the guidelines, “excessive” disinfection should be avoided, including spraying into the air in outdoor environments.

Lu Ye, deputy director of the Environmental Health Institute of the Zhejiang Centre for Disease Control and Prevention, told reporters earlier this month that disinfecting the outdoor environment was a “waste of resources” and improved ventilation was more important in preventing Covid-19.

“Catching Covid-19 from the environment depends on the viral load and the temperature and humidity of the environment. Most importantly, it requires a certain contact time to be able to cause infection, so we advocate opening windows to improve ventilation to dilute the quantity of virus in the indoor environment,” Lu said.

“Virus discharged to the outdoors can easily die, so there is no need to conduct large-scale disinfection outdoors, which is ineffective and a waste of limited resources.”

Instead, the recommendation is to open windows and doors to improve indoor ventilation in public places like supermarkets, shopping malls, offices and schools, and where possible to install air disinfection equipment that meets the relevant national standards, Lu said.

He added that air conditioning and ventilation systems should be cleaned and disinfected regularly, and the number of exhaust air fans increased in bathrooms, basements, lifts and other enclosed spaces.

...residents told to stay home unless they are getting tested. Those in less risky areas can leave home to buy supplies if they have tested negative and follow the rules, while travel curbs are also in place...

https://www.scmp.com/news/china/science/article/3161133/chinas-covid-19-surge-co...

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

South China Morning Post @SCMPNews | 7:35 AM · Dec 27, 2021:
China’s city of Xian has conducted a mass disinfection operation and more rounds of coronavirus testing as Covid-19 cases continue to surge.

Mass testing and disinfection in Xian (0:58)
https://twitter.com/SCMPNews/status/1475445105540706306

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

Xi'an locks down as China races to zero-Covid for Olympics
China is on high alert as it fights local Covid-19 outbreaks in several cities (AFP/STR)
AFP | Dec 22, 2021

...The country has stepped up already-strict measures as it braces for the arrival of thousands of international athletes for the Olympics in February.

The capital Beijing is demanding negative Covid-19 tests from all visitors and limiting flights from other cities.

And once they arrive and enter the Olympic "bubble", all participants -- who must be fully vaccinated -- will undergo daily virus tests.

Officials have strongly urged athletes to get booster jabs due to the rapid global spread of the Omicron variant, but also warned of the "certain" possibility of infections inside the bubble.

"There could be a chance of a small-scale cluster outbreak happening," said Games virus control official Huang Chun at a Thursday briefing, adding that the large number of people involved will have a "very high risk of transmission".

Officials also provided guidelines for a limited number of domestic spectators, including encouraging athletes by clapping, but not singing or shouting.

Athletes with symptoms will be sent to Beijing hospitals designated for treating Covid-19 patients, said Huang.

https://news.yahoo.com/xian-locks-down-china-races-022054860.html

>106 margd: it’s interesting. Apparently there are two approaches, one that focuses on multiple geometries of spikes, and the other (which sounded theoretically more efficient) which focused on nonspike areas of the virus which have less possibility of mutation and where any mutation in those spots looks unlikely to leave a viable virus. But exciting stuff!

Extended interview with home tests' biggest proponent. (He recently left Harvard, but continues his quest.)

Michael Mina: Rapid Testing, Viruses, and the Engineering Mindset | Lex Fridman Podcast #146 (2:14:10)
Dec 18, 2020

Michael Mina is an immunologist, epidemiologist, and physician at Harvard.

https://www.youtube.com/watch?v=L-RuvUkcyJI

>94 stellarexplorer: Interesting! (Lee et al. 2021) Maybe worth asking one's MD about possible off-label fluvoxamine Rx--if one is sick under special circumstances, and antibodies and/or Paxlovid are not available? (A FB correspondent, apparently ill with COVID, is single mom alone with 3, whose 3YO has congenital heart condition. She is terrified that the 3YO will catch the virus*, and that she will have to leave them for hospital. Sounds special to me!)

* Dunno about Omicron, but, anecdotally, Tetralogy of Fallot moms seem to be reporting their young heart warriors are suffering worse complications with RSV (Respiratory Synctial Virus) than with COVID.

Todd Lee et al. 2021. Fluvoxamine for Outpatient COVID-19 to Prevent Hospitalization: A Systematic Review and Meta-Analysis. MedRxiv (PREPRINT--NOT YET PEER-REVIEWED) Dec 21, 2021. doi: https://doi.org/10.1101/2021.12.17.21268008 https://www.medrxiv.org/con.../10.1101/2021.12.17.21268008v1

"...fluvoxamine shows a high probability of preventing hospitalization in outpatients with COVID-19..."
-----------------------------------------------------------.

Earlier publication:

Gilmar Reis et al. 2021. Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial. The Lancet Published:October 27, 2021. https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(21)00448-4/fullt... DOI:https://doi.org/10.1016/S2214-109X(21)00448-4

"...Treatment with fluvoxamine (100 mg twice daily for 10 days) among high-risk outpatients with early diagnosed COVID-19 reduced the need for hospitalisation defined as retention in a COVID-19 emergency setting or transfer to a tertiary hospital..."

Eric Topol @EricTopol | 9:38 AM · Dec 28, 2021:
Big congrats to my friend @PeterHotez and TexasChildrens for the approval of Corbevax, their low cost, recombinant protein subunit Covid vaccine in India

As India approves Corbevax, here’s all you need to know about the new COVID-19 vaccine
Prasad Bhosekar | Dec 28, 2021

According to Biological E. Limited, the CORBEVAX COVID-19 vaccine will be effective both in scale and affordability, providing sustainable access to low-and middle-income countries...

• In the pivotal phase III study conducted with an endpoint of immunogenic superiority, CORBEVAX demonstrated superior immune response in comparison with COVISHIELD vaccine when assessed for Neutralising Antibody (nAb) Geometric Mean Titers (GMT) against the Ancestral-Wuhan strain and the globally dominant Delta variant. CORBEVAXTM vaccination also generated significant Th1 skewed cellular immune response.

• CORBEVAX nAb GMT against Ancestral-Wuhan strain is indicative of vaccine effectiveness of greater than 90% for prevention of symptomatic infections based on the Correlates of Protection assessment performed during Moderna and Astra-Zeneca vaccine Phase III studies.

• CORBEVAX nAb GMT against the Delta strain indicates a vaccine effectiveness of greater than 80 percent for the prevention of symptomatic infections based on published studies.

• While none of the subjects who took CORBEVAX or COVISHIELD had serious adverse events, CORBEVAX had 50 percent fewer adverse events than COVISHIELD.

In the continuous monitoring of phase II studies, CORBEVAX showed high persistence of immune response as indicated by less than 30% drop in nAb GMT till six months second dose as compared to more than 80% drop observed with majority of the vaccines.

Vaccine Rollout Timeline:
Biological E. Limited plans to complete production at a rate of 75 million doses per month, anticipating 100+ million doses per month from February 2022. These capacities will enable the Hyderabad-based company to deliver 300 Million doses as promised to the Government of India.

Soon, the company plans to deliver more than one billion additional doses globally...

https://zeenews.india.com/india/india-approves-corbevax-here-s-all-you-need-to-k...
_________________________________________________
ETA
Texas Children’s Hospital and Baylor College of Medicine COVID-19 Vaccine Technology Secures Emergency Use Authorization in India

Mass Distribution of “The World’s COVID-19 Vaccine” to be Deployed to India with Other Underserved Countries to Follow

HOUSTON, TX (December 28, 2021) – Texas Children’s Hospital and Baylor College of Medicine announced today that CORBEVAX™, a protein sub-unit COVID-19 Vaccine, whose technology was created and engineered at its Center for Vaccine Development (CVD), has received Emergency Use Authorization (EUA) approval from the Drugs Controller General of India (DCGI) to launch in India with other underserved countries to follow.

Dubbed “The World’s COVID-19 Vaccine”, it uses a traditional recombinant protein-based technology that will enable its production at large scales making it widely accessible to inoculate the global population. The initial construct and production process of the vaccine antigen was developed at Texas Children’s Hospital CVD, led by co-directors Drs. Maria Elena Bottazzi and Peter Hotez and in-licensed from BCM Ventures, Baylor College of Medicine’s integrated commercialization team, to Hyderabad-based vaccine and pharmaceutical company Biological E. Limited (BE)...

https://www.texaschildrens.org/texas-children%E2%80%99s-hospital-and-baylor-coll...

Birgit Umaigba RN *, MEd @birgitomo | 8:52 PM · Dec 27, 2021:
https://twitter.com/birgitomo/status/1475643671378808836

Seems like no one in govt is seeing the disaster that's happening in health-care . The ER was SIX nurses short on Christmas day, even with triple time and half pay. Tonight, there's only ONE Registered Nurse on the cardiology floor. ONE. ONE nurse people. Only one showed up.

The morgue is full. Patient's been dead since 5pm but nowhere to put the body. 3 ICU patients waiting in the ER. No ICU nurses to take new critically ill patients. There are empty beds but no nurses. The nursing crisis is harming every aspect of healthcare. Urgent help needed!

My heart is really hurting because I know patients are suffering. I see it. The nurses showing up are broken and tired. Yes I sound like a broken record but this is because nothing has been done. These are human beings for crying out loud. Help us save lives. Pleaseeeeeee

Let's start by utilizing the Internationally Educated Nurses we have on ground. They can help. Someone do something. Stop ignoring the outcry to save whatever is left of the healthcare system.
@fordnation
@celliottability
@ONgov
@JustinTrudeau
@collegeofnurses
@RNAO

*Birgit Umaigba RN, MEd--Wife. Mom. ICU/ER Nurse. Clinical Practice Instructor...a 34-year-old ICU nurse working in the GTA (Greater Toronto Area); she also teaches in the bachelor of nursing program at Centennial College and is the clinical course director for internationally trained nurses at York University. (https://torontolife.com/city/the-deaths-were-seeing-in-this-third-wave-were-preventable-what-its-like-to-work-as-an-icu-nurse-right-now/)

_____________________________________________________
ETA

‘I don’t know how much more we can take’: Northeast Ohio health care providers reveal what’s happening within hospital walls
cleveland.com | Dec. 24, 2021

https://www.cleveland.com/news/2021/12/i-dont-know-how-much-more-we-can-take-nor...

CDC Updates and Shortens Recommended Isolation and Quarantine Period for General Population
Media Statement | December 27, 2021

Given what we currently know about COVID-19 and the Omicron variant, CDC is shortening the recommended time for isolation from 10 days for people with COVID-19 to 5 days, if asymptomatic, followed by 5 days of wearing a mask when around others. The change is motivated by science demonstrating that the majority of SARS-CoV-2 transmission occurs early in the course of illness, generally in the 1-2 days prior to onset of symptoms and the 2-3 days after. Therefore, people who test positive should isolate for 5 days and, if asymptomatic at that time, they may leave isolation if they can continue to mask for 5 days to minimize the risk of infecting others.

Additionally, CDC is updating the recommended quarantine period for those exposed to COVID-19. For people who are unvaccinated or are more than six months out from their second mRNA dose (or more than 2 months after the J&J vaccine) and not yet boosted, CDC now recommends quarantine for 5 days followed by strict mask use for an additional 5 days. Alternatively, if a 5-day quarantine is not feasible, it is imperative that an exposed person wear a well-fitting mask at all times when around others for 10 days after exposure. Individuals who have received their booster shot do not need to quarantine following an exposure, but should wear a mask for 10 days after the exposure. For all those exposed, best practice would also include a test for SARS-CoV-2 at day 5 after exposure. If symptoms occur, individuals should immediately quarantine until a negative test confirms symptoms are not attributable to COVID-19.

Isolation relates to behavior after a confirmed infection. Isolation for 5 days followed by wearing a well-fitting mask will minimize the risk of spreading the virus to others. Quarantine refers to the time following exposure to the virus or close contact with someone known to have COVID-19. Both updates come as the Omicron variant continues to spread throughout the U.S. and reflects the current science on when and for how long a person is maximally infectious...

https://www.cdc.gov/media/releases/2021/s1227-isolation-quarantine-guidance.html

Small study, not peer-reviewed, but looks like a possible answer to how one variant can suppress/outcompete another.

Mechanism could help end runaway pandemic? :D Not good, though if it encourages people to intentionally catch the virus--even if relatively less risky for individuals, collectively we risk crashing our hospitals...and long COVID has not been ruled out.

Look, though, at 2nd preprint posted on Sigal Llab website--looks like convergent evolution in advanced HIV patient? Convergent is good if it means limited number of options for SARS-CoV-2 to escape immune system? A reminder, though, that our collective failure to adequately treat HIV patients can result in new variants?

Alex Sigal @sigallab | 4:48 PM · Dec 27, 2021:
We have submitted new results to medRxiv:
Omicron infection enhances neutralizing immunity against the Delta variant*
The preprint can be found here: https://sigallab.net

We studied people who were infected with Omicron close to when they had symptoms and about 2 weeks later:
Graphs ( https://twitter.com/sigallab/status/1475584479540486148/photo/1 )

The increase neutralizing immunity against Omicron was expected - that is the virus these individuals were infected with.
However, we also saw that the same people - especially those who were vaccinated - developed enhanced immunity to the Delta variant.

If, as it currently looks like from the South African experience, Omicron is less pathogenic, then this will help push Delta out, as it should decrease the likelihood that someone infected with Omicron will get re-infected with Delta.

If that's true, then the disruption Covid-19 has caused in our lives may become less...

Discussed at https://twitter.com/sigallab/status/1475584463941914635 , e.g., chris pepperdine @cpepp "but increased infections also come with increased variants. Mask up peeps. Get boosted if you can. Nobody needs this virus, or any variant lurking in their body."
--------------------------------------------------
* Khadija Khan...Alex Sigal. 2021. Omicron infection enhances neutralizing immunity against the Delta variant. 8 p. Manuscript. https://secureservercdn.net/50.62.198.70/1mx.c5c.myftpupload.com/wp-content/uplo...

Omicron has been shown to be highly transmissible and have extensive evasion of neutralizing antibody immunity elicited by vaccination and previous SARS-CoV-2 infection. Omicron infections are rapidly expanding worldwide often in the face of high levels of Delta infections. Here we characterized developing immunity to Omicron and investigated whether neutralizing immunity elicited by Omicron also enhances neutralizing immunity of the Delta variant. We enrolled both previously vaccinated and unvaccinated individuals who were infected with SARS-CoV-2 in the Omicron infection wave in South Africa soon after symptom onset. We then measured their ability to neutralize both Omicron and Delta virus at enrollment versus a median of 14 days after enrollment. Neutralization of Omicron increased 14-fold over this time, showing a developing antibody response to the variant. Importantly, there was an enhancement of Delta virus neutralization, which increased 4.4-fold. The increase in Delta variant neutralization in individuals infected with Omicron may result in decreased ability of Delta to re-infect those individuals. Along with emerging data indicating that Omicron, at this time in the pandemic, is less pathogenic than Delta, such an outcome may have positive implications in terms of decreasing the Covid-19 burden of severe disease.

________________________________________________________

Sandile Cele...Alex Sigal. 2021. SARS-CoV-2 evolved during advanced HIV disease immunosuppression has Beta-like escape of vaccine and Delta infection elicited immunity. MedRxiv Dec 7, 2021. doi: https://doi.org/10.1101/2021.09.14.21263564 https://www.medrxiv.org/content/10.1101/2021.09.14.21263564v2

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

Summary
Characterizing SARS-CoV-2 evolution in specific geographies may help predict the properties of variants coming from these regions. We mapped neutralization of a SARS-CoV-2 strain that evolved over 6 months from the ancestral virus in a person with advanced HIV disease. Infection was before the emergence of the Beta variant first identified in South Africa, and the Delta variant. We compared early and late evolved virus to the ancestral, Beta, Alpha, and Delta viruses and tested against convalescent plasma from ancestral, Beta, and Delta infections. Early virus was similar to ancestral, whereas late virus was similar to Beta, exhibiting vaccine escape and, despite pre-dating Delta, strong escape of Delta-elicited neutralization. This example is consistent with the notion that variants arising in immune-compromised hosts, including those with advanced HIV disease, may evolve immune escape of vaccines and enhanced escape of Delta immunity, with implications for vaccine breakthrough and reinfections.

Highlights
A prolonged ancestral SARS-CoV-2 infection pre-dating the emergence of Beta and Delta resulted in evolution of a Beta-like serological phenotype

Serological phenotype includes strong escape from Delta infection elicited immunity, intermediate escape from ancestral virus immunity, and weak escape from Beta immunity

Evolved virus showed substantial but incomplete escape from antibodies elicited by BNT162b2 vaccination

DC!

Eric Topol @EricTopol | 11:25 AM · Dec 28, 2021
Omicron and an expanded Y-axis

Graph-# case rates DC, NY, Puerto Rico thru Dec 28, 2021
https://twitter.com/EricTopol/status/1475865492732538881/photo/1

Scott Gottlieb, MD @ScottGottliebMD | 10:39 AM · Dec 28, 2021:

London and New York City: New Covid cases and New Covid Hospitalizations - #Omicron versus prior waves. On a relative basis, Hospitalizations are well below what was seen in prior Covid waves.

Graph- case and hospitalization rates in London and NYC
https://twitter.com/ScottGottliebMD/status/1475853849684586497/photo/1

>113 margd: I wonder whether they will have to lengthen the time again after Omicron blows through?

>117 stellarexplorer: Public health can't be an easy place to be these days...

>118 margd: Nope. I can’t tell you how often I end up explaining to people why it’s completely expectable for the CDC to modify their guidance as we learn more about this emerging virus. {headbang}

Joseph Allen* @j_g_allen | 8:03 AM · Dec 29, 2021
https://twitter.com/j_g_allen/status/1476176934568611843
17 tweets ( https://threadreaderapp.com/thread/1476176934568611843.html )

I see a lot of people - on both "sides" - making simple mistakes about masks. I've studied PPE, taught PPE, and overseen PPE programs, including teams implementing fit testing in hospitals, long before covid.

A thread...

* Joseph Allen @j_g_allen -- Assoc Prof @HarvardChanSPH; Lancet @CommissionCOVID (Chair Task Force on Safe Work/School/Travel); Coauthor of HEALTHY BUILDINGS @Harvard_Press; WaPo, NYT, HBR

"...the rapid spread of the Omicron VOC primarily can be ascribed to the immune evasiveness rather than an inherent increase in the basic transmissibility...the non-pharmaceutical interventions that were used to control the previous variants of SARS-CoV-2 are also likely to be effective against the Omicron VOC...(while) booster vaccines did offer some protection against household transmission, the reduced level of protection (compared to Delta) means that vaccination is less likely to be sufficient to curb transmisssion within a population...the current vaccines are unlikely to mitigate the spread of the Omicron VOC to the extent that has been achieved for previous variants on the long term...adapted or improved vaccines may be necessary to mitigate the spread of the Omicron VOC. However, both a primary series and a booster dose is likely to play an important role in reducing transmission on a short term (flatten the curve) and modifying the outcome of infection by reducing severity...existing circulating immunity within a country is of major importance in limiting the severity of the epidemic with the Omicron VOC..."

Eric Topol @EricTopol | 10:22 AM · Dec 29, 2021:
https://twitter.com/EricTopol/status/1476212140956553222
A study of nearly 12,000 households in Denmark shows
a marked reduction of Omicron transmission among people who had a 3rd (booster) shot*
Table-susceptibility transmissibility unvaxxed, vaxxed, boosted households
https://twitter.com/EricTopol/status/1476212140956553222/photo/1
---------------------------------------------------

* Frederik Plesner Lyngse et al. 2021. SARS-CoV-2 Omicron VOC Transmission in Danish Households. MedRxiv Dec 27, 2021.
doi: https://doi.org/10.1101/2021.12.27.21268278 https://medrxiv.org/content/10.1101/2021.12.27.21268278v1

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

Abstract
The Omicron variant of concern (VOC) is a rapidly spreading variant of SARS-CoV-2 that is likely to overtake the previously dominant Delta VOC in many countries by the end of 2021. We estimated the transmission dynamics following the spread of Omicron VOC within Danish households during December 2021. We used data from Danish registers to estimate the household secondary attack rate (SAR). Among 11,937 households (2,225 with the Omicron VOC), we identified 6,397 secondary infections during a 1-7 day follow-up period. The SAR was 31\% and 21\% in households with the Omicron and Delta VOC, respectively. We found an increased transmission for unvaccinated individuals, and a reduced transmission for booster-vaccinated individuals, compared to fully vaccinated individuals. Comparing households infected with the Omicron to Delta VOC, we found an 1.17 ... times higher SAR for unvaccinated, 2.61 times ... higher for fully vaccinated and 3.66 ... times higher for booster-vaccinated individuals, demonstrating strong evidence of immune evasiveness of the Omicron VOC. Our findings confirm that the rapid spread of the Omicron VOC primarily can be ascribed to the immune evasiveness rather than an inherent increase in the basic transmissibility.
...
5 Discussion and Conclusion
Our results show that the Omicron VOC (variant of concern) is generally 2.7-3.7 times more infectious than the Delta VOC among vaccinated individuals... Furthermore, we show that fully vaccinated and booster-vaccinated individuals are generally less susceptible to infection compared to unvaccinated individuals... We also show that booster-vaccinated individuals generally had a reduced transmissibility (OR (order of risk): 0.72...), and that unvaccinated individuals had a higher transmissibility (OR: 1.41...), compared to fully vaccinated individuals.

Surprisingly, we observed no significant difference between the SAR (secondary attack rate, i.e., within household) of Omicron versus Delta among unvaccinated individuals... This indicates that the increased transmissibility of the Omicron VOC primarily can be ascribed to immune evasion rather than an inherent increase in the basic transmissibility...Our data indicate that the non-pharmaceutical interventions that were used to control the previous variants of SARS-CoV-2 are also likely to be effective against the Omicron VOC. On the other hand, although we showed that booster vaccines did offer some protection against household transmission, the reduced level of protection means that vaccination is less likely to be sufficient to curb transmisssion within a population. Furthermore, the duration of the protective effect is currently unknown, and the rapidly waning effectiveness of the second dose against the Omicron VOC as well as data from neutralization assays... do raise some concerns about the
longevity of the booster response. This means that the current vaccines are unlikely to mitigate the spread of the Omicron VOC to the extent that has been achieved for previous variants on the long term...adapted or improved vaccines may be necessary to mitigate the spread of the Omicron VOC. However, both a primary series and a booster dose is likely to play an important role in reducing transmission on a short term and modifying the outcome of infection by reducing severity. ...

...note that the existing circulating immunity within a country is of major importance in limiting the severity of the epidemic with the Omicron VOC...

There are some potential biases in this study...

There are also a number of other confounding variables that might lead to biases within our study...

To conclude, we found an increased susceptibility for unvaccinated individuals, and a reduced susceptibility for booster-vaccinated individuals, compared to fully vaccinated individuals in households infected with the Delta VOC. Additionally, we found a reduced
susceptibility for booster-vaccinated individuals in households infected with the Omicron VOC. Furthermore, we found an increased transmissibility from unvaccinated individuals, and a reduced transmissibility from booster-vaccinated individuals, compared to fully
(v)accinated individuals. Lastly, we we found a general higher transmission in households infected with the Omicron VOC relative to the Delta for both unvaccinated, fully vaccinated and booster-vaccinated individuals. The Omicron VOC showed immune evasiveness
for fully vaccinated and booster-vaccinated individuals. Our results confirm that booster vaccination has the potential to reduce Omicron VOC transmission in households, although vaccination as a strategy for epidemic control is increasingly challenged by the
immune evasiveness of the Omicron VOC.

Comparing Omicron VOC to Delta VOC, we found an 1.17 ... times higher SAR for unvaccinated, 2.61... times higher for fully vaccinated and 3.66... times higher for booster-vaccinated individuals, demonstrating strong evidence of immune evasiveness of the Omicron VOC.

"...despite Omicron's extensive mutations and reduced susceptibility to neutralizing antibodies, the majority of T cell response, induced by vaccination or natural infection, cross-recognises the variant. Well-preserved T cell immunity to Omicron is likely to contribute to protection from severe COVID-19, supporting early clinical observations from South Africa."

Eric Topol @EricTopol | 10:09 AM · Dec 29, 2021:
Our T cells appear to be ready, willing and able to defend vs Omicron*
CD4+ and CD8+ ** cells hold up well in people vaccinated or prior Covid

Graphs- J&J, Pfizer, Convalescent T cells v. ancestral, omicron variants
( https://twitter.com/EricTopol/status/1476208683835002880/photo/1 )
-----------------------------------------------------------------------

Roanne Keeton et al. 2021. SARS-CoV-2 spike T cell responses induced upon vaccination or infection remain robust against Omicron. MedRxiv Dec 28, 2021. doi: https://doi.org/10.1101/2021.12.26.21268380 https://medrxiv.org/content/10.1101/2021.12.26.21268380v1

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

Abstract
The SARS-CoV-2 Omicron variant has multiple Spike (S) protein mutations that contribute to escape from the neutralizing antibody responses, and reducing vaccine protection from infection. The extent to which other components of the adaptive response such as T cells may still target Omicron and contribute to protection from severe outcomes is unknown. We assessed the ability of T cells to react with Omicron spike in participants who were vaccinated with Ad26.CoV2.S (J&J) or BNT162b2 (Pfizer), and in unvaccinated convalescent COVID-19 patients (n = 70). We found that 70-80% of the CD4 and CD8 T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar to that of the Beta and Delta variants, despite Omicron harbouring considerably more mutations. Additionally, in Omicron-infected hospitalized patients (n = 19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those found in patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n = 49). These results demonstrate that despite Omicron's extensive mutations and reduced susceptibility to neutralizing antibodies, the majority of T cell response, induced by vaccination or natural infection, cross-recognises the variant. Well-preserved T cell immunity to Omicron is likely to contribute to protection from severe COVID-19, supporting early clinical observations from South Africa.

** What is the Difference Between CD4 and CD8 T Cells ... The main difference between CD4 and CD8 T cells is that the CD4 T cells are the helper T cells, which assist other blood cells to produce an immune response, whereas the CD8 T cells are the cytotoxic T cells that induce cell death either by lysis or apoptosis. https://pediaa.com/what-is-the-difference-between-cd4-and-cd8-t-cells/

Eric Topol @EricTopol | 12:05 PM · Dec 29, 2021:
High rate of asymptomatic carriers noted with Omicron as compared with prior variants,
with high viral nasal titers in many carriers, adds to its rapid spread capability
--------------------------------------------------

Nigel Garret et al. 2021. High Rate of Asymptomatic Carriage Associated with Variant Strain Omicron. MedRxiv Dec 27, 2021.
doi: https://doi.org/10.1101/2021.12.20.21268130

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

Abstract
... findings strongly suggest that Omicron has a much higher rate of asymptomatic carriage than other VOC and this high prevalence of asymptomatic infection is likely a major factor in the widespread, rapid dissemination of the variant globally, even among populations with high prior rates of SARS-COV-2 infection.

>122 margd: contd.

Eric Topol @EricTopol
A 2nd report today from @ljiresearch also demonstrates vaccination induced T-cells vs Omicron (B.1.1,519) well preserved compared with all variants and with 3 different vaccines...

Figure 1. Impact of variant associated mutations on spike -specific CD4 + and CD8 + T cell
responses to SARS-CoV-2 variants (8 variants v. 3 vaccines)
https://twitter.com/EricTopol/status/1476242703717257221/photo/1

Alison Tarke et al. 2021. SARS-CoV-2 vaccination induces immunological memory able to cross-recognize variants from Alpha to Omicron. BioRxiv Dec 28, 2021. doi: https://doi.org/10.1101/2021.12.28.474333 https://biorxiv.org/content/10.1101/2021.12.28.474333v1

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

Abstract

We address whether T cell responses induced by different vaccine platforms (mRNA-1273 (Moderna), BNT162b2 (Pfizer), Ad26.COV2.S (J&J), NVX-CoV2373 (Novavax) cross-recognize SARS-CoV-2 variants. Preservation of at least 83% and 85% for CD4+ and CD8+ T cell responses was found, respectively, regardless of vaccine platform or variants analyzed. By contrast, highly significant decreases were observed for memory B cell and neutralizing antibody recognition of variants. Bioinformatic analyses showed full conservation of 91% and 94% of class II and class I spike epitopes*. For Omicron, 72% of class II and 86% of class I epitopes were fully conserved, and 84% and 85% of CD4+ and CD8+ * T cell responses were preserved. In-depth epitope repertoire analysis showed a median of 11 and 10 spike epitopes recognized by CD4+ and CD8+ T cells from vaccinees. Functional preservation of the majority of the T cell responses may play an important role as a second-level defense against diverse variants.

* There are two classes of MHC (Major Histocompatibility Complex) molecules, MHC class I, which are expressed on all nucleated cells and activate cytotoxic T cell lymphocytes (CD8+ T cells), and MHC class II, which are expressed on antigen presenting cells and activate helper T cell lymphocytes (CD4+ T cells). ( https://www.biorxiv.org/content/10.1101/2021.09.11.459907v1.full.pdf )

_________________________________________

ETA -- now published

Alison Tarke et al. SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to Omicron. Cell Published:January 23, 2022. DOI:https://doi.org/10.1016/j.cell.2022.01.015 https://www.cell.com/cell/fulltext/S0092-8674(22)00073-3

David Fisman* @DFisman | 4:07 PM · Dec 29, 2021:
Endlessly confronted by how frankly miraculous covid vaccines have been.
I've spent most of today finishing a paper on covid in pregnancy.
Had to drop a bunch of analyses related to vaccines because vaccinated pregnant people don't go to ICU in Ontario.
Like: at all.

We have been looking at 2009 women with Covid in pregnancy, to mid November.
Pregnancy increases icu risk 6-fold after adjustment for other factors.

Preprint will be up soon...

* David N. Fisman is a University of Toronto professor in the area of epidemiology at the Dalla Lana School of Public Health. He also works as an infectious disease specialist.

Encouraging: reduced severity overall (in Gauteng, S Africa), but would be nice to see a few more data points in December?
Discouraging: more (largely unvaxxed) children and teens under 20 years were hospitalized with omicron than other variants. :(

Eric Topol @EricTopol | 10:50 AM · Dec 30, 2021:
A good omen for Omicron from its 1st epicenter in Gauteng, South Africa*
The reduced clinical severity compared with the 1st 3 waves, and vs Beta and Delta variants

Graph-#cases, hospitalizations, deaths in Gauteng S Africa, 6 March 2020-6 Dec 2021
https://twitter.com/EricTopol/status/1476581435322421252/photo/1
-------------------------------------------------------------------

* Jassat, Waasila and Karim, Salim Abdool and Mudara, Caroline and Welch, Richard and Ozougwu, Lovelyn and Groome, Michelle and Govender, Nevashan and von Gottberg, Anne and Wolter, Nicole and Group, DATCOV Author and Blumberg, Lucille and Cohen, Cheryl, Clinical Severity of COVID-19 Patients Admitted to Hospitals in Gauteng, South Africa During the Omicron-Dominant Fourth Wave (December 29, 2021). Available at SSRN: https://ssrn.com/abstract=3996320 https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3996320

Preprints with The Lancet

Abstract
...Results: There were 41,046, 33,423, and 133,551 SARS-CoV-2 cases in the second, third and fourth waves respectively. About 4.9% of cases were admitted to hospital during the fourth wave compared to 18.9% and 13.7% during the second and third waves ... During the fourth wave, 28.8% of admissions were severe disease compared to 60.1% and 66.9% in the second and third waves .... Admitted patients in the omicron-dominated fourth wave were 73% less likely to have severe disease than patients admitted during the delta-dominated third wave (adjusted odds ratio (aOR) 0.27...).

Conclusion: The proportion of cases admitted was lower and those admitted were less severe during the first four weeks of the Omicron-dominated fourth wave in Gauteng province of South Africa. Since any combination of a less-virulent virus, comorbidities, high immunity from prior infection(s) or vaccination may be important contributors to this clinical presentation, care should be taken in extrapolating this to other populations with different co-morbidity profiles, prevalence of prior infection and vaccination coverage.

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

Also in Jassat et al 2021 preprint:

Scott Gottlieb, MD @ScottGottliebMD | 10:52 AM · Dec 30, 2021:
New preprint on Covid impact in Gauteng.
During #Omicron wave 17.68% of all recorded hospital admissions were children and teens under 20 years, vs
3.97% during second wave,
3.52% during third (Delta) wave.
5.8% of children and teens are vaxxed in Gauteng

Table 1: Summary of SARS-CoV-2 cases, COVID-19 admissions and in-hospital deaths in the Beta-
(29 Nov-26 Dec 2020), Delta- (2 May-29 May 2021) and Omicron-dominated waves (14 Nov-11 Dec
2021), Gauteng Province, South Africa
https://twitter.com/ScottGottliebMD/status/1476581879524564995/photo/1

>126 margd: I don’t know anything personally about the increase in child hospitalizations, but I heard Dr Fauci say there were two main reasons, and neither was that omicron is more dangerous to kids. First, since some very small number of infected kids will be hospitalized, the sheer number of children being infected right now necessarily means more kids hospitalized. Second, he says few of the hospitalized kids are being hospitalized due to Covid, but rather hospitalizations in which a Covid positive is found are being counted as Covid hospitalizations. Fwiw.

Uh oh?

Jorge A. Caballero, MD @DataDrivenMD | 8:01 PM · Dec 29, 2021
544 children with #COVID19 were admitted to U.S. hospitals yesterday—
this shattered the previous single-day record that was set 2 days ago (421)

source: HHS (https://healthdata.gov/Hospital/COVID-19-Reported-Patient-Impact-and-Hospital-Capa/g62h-syeh)

Graph: pediatric admissions ( https://twitter.com/DataDrivenMD/status/1476357620550148100/photo/1 )

Time to "flatten the curve", people!

Benjy Renton (VT reporter) @bhrenton | 12:06 AM · Dec 30, 2021:
Tonight's Circuit Breaker Dashboard update:
- 250 counties projected to be at hospital capacity (up from 160 yesterday)
- 296 counties are at high risk of hitting capacity within the next 10 days (up from 145 yesterday).
- 510 as "unsustainable"

County map of US ( https://twitter.com/bhrenton/status/1476419380607176714/photo/1 )
Explore (by state): http://alexanderjxchen.github.io/circuitbreaker/
---------------------------------------------------

The Omicron Plan: “Circuit breakers” and other short-term strategies to get us through the next wave.
We’ve learned a lot. Now is the time to apply those lessons.
Jeremy Faust MD MS (ER physician) | Dec 19, 2021

...•Circuit breakers must be introduced in some areas. Circuit breakers are short-term restrictions, regardless of vaccination status, designed to slow the spread of Covid-19. The goal of these circuit breakers is specifically to “flatten curves,” so that hospitals do not become overwhelmed. To accomplish this, restrictions need not last long. In fact, tremendous impact can be achieved in just a matter of days (or perhaps a week or two), if adhered to sufficiently. Such restrictions are familiar and should include eliminating indoor dining or limiting seating capacity drastically. ... Other large gatherings like concerts should go virtual temporarily or should limit their capacity dramatically. Working from home should be encouraged when possible.

...•Provide US residents with free or inexpensive KN94, KN95, or N95 masks. These masks should be routinely used in crowded indoor settings. Less effective (surgical or some cloth) masks might be acceptable for low density settings where the risk of encountering someone at the peak of contagiousness is statistically far lower. (While using the best masks all the time would be “optimal,” we are human; let’s reduce harm rather than pretending we can eliminate it by striving for a perfection that nobody can achieve). Insisting on the best masks in crowded high-risk conditions will limit “superspreading” events.

•Send every US resident free rapid antigen tests. Rapid tests should be readily available to the public and free. While rapids don’t rule out infection, they identify almost all of the contagious ones. However, it’s possible that Omicron’s transmission dynamics will render rapid tests somewhat less useful because the “warranty” on the information they provide may turn out only to be good for several hours, rather than a day or two. This is something we are watching and waiting for the FDA to comment on soon.

•Go big on vaccination and boosting by re-opening mass vaccination sites. These sites provided vaccines to communities that now lack vaccine access.

•Go small on vaccination and boosting by going door-to-door to reach people in need. EMS workers can do this. We need to lower the bar for those finally considering vaccinating due to Omicron...

https://insidemedicine.bulletin.com/the-omicron-plan-circuit-breakers-and-other-...

>61 margd: contd.

Omicron may cause milder disease. A lab study hints at why.
Nicoletta Lanese published 5 days ago (Dec 25, 2021?)

Omicron appears to be less efficient at entering lung cells.

https://www.livescience.com/omicron-less-severe-disease-early-evidence

Prior infection by non-Omicron variants *without 2-3 vaxx* provides very low protection against infection by Omicron.
--------------------------------------------------------------------

Juan Manuel Carreño. 2021. Activity of convalescent and vaccine serum against SARS-CoV-2 Omicron (Research Briefing) Nature 31 Dec 2021. doi: https://doi.org/10.1038/d41586-021-03846-z https://www.nature.com/articles/d41586-021-03846-z

The Omicron (B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)...Here, we investigated the neutralizing and binding activity of sera from convalescent, mRNA double vaccinated, mRNA boosted, convalescent double vaccinated, and convalescent boosted individuals against wild type, B.1.351 (Beta) and B.1.1.529 (Omicron) SARS-CoV-2 isolates. Neutralizing activity* of sera from convalescent and double vaccinated participants was undetectable to very low against B.1.1.529 while neutralizing activity of sera from individuals who had been exposed to spike three or four times was maintained, albeit at significantly reduced levels. Binding to the B.1.1.529 receptor binding domain (RBD) and N-terminal domain (NTD) was reduced in convalescent not vaccinated individuals, but was mostly retained in vaccinated individuals.

* Neutralizing antibodies are an important specific defense against viral invaders. Neutralizing antibodies not only to bind to a virus, they bind in a manner that blocks infection. A neutralizing antibody might block interactions with the receptor, or might bind to a viral capsid in a manner that inhibits uncoating of the genome. https://www.sciencedirect.com/topics/neuroscience/neutralizing-antibody
-----------------------------------------------------------------------

Fabian Schmidt et al. 2021.
Plasma Neutralization of the SARS-CoV-2 Omicron Variant (Correspondence). NEJM December 30, 2021
DOI: 10.1056/NEJMc2119641 https://www.nejm.org/doi/full/10.1056/NEJMc2119641

...Although these findings indicate that the omicron variant shows an unprecedented degree of neutralizing antibody escape, they also suggest that boosting and promoting affinity maturation of antibodies in persons who have previously been infected or vaccinated...with the use of existing Wuhan-hu-1–based vaccine immunogens, will provide additional protection against infection with the omicron variant and subsequent disease.

Eric Topol (Scripps) @EricTopol | 1:06 PM · Dec 29, 2021:
With yet another in vivo study of Omicron infection today, it sure is looking that
this variant has less virulence, less chance of inducing Covid pneumonia*
Added to our immunity wall and T cell defense, this is all good.

List of studies showing Omicron's decreased lung infectivity
https://twitter.com/EricTopol/status/1476253179503251461/photo/1

* Eleanor G Bentley et al. 2021. SARS-CoV-2 Omicron-B.1.1.529 Variant leads to less severe disease than Pango B and Delta variants strains in a mouse model of severe COVID-19. BioRxiv 31 Dec 2021 doi: https://doi.org/10.1101/2021.12.26.474085 https://www.biorxiv.org/content/10.1101/2021.12.26.474085v2

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

Abstract

...In contrast to mice infected with Pango B and Delta variant viruses, those infected with the Omicron variant had less severe clinical signs (weight loss), showed recovery and had a lower virus load in both the lower and upper respiratory tract. This is also reflected by less extensive inflammatory processes in the lungs. Although T cell epitopes may be conserved, the antigenic diversity of Omicron from previous variants would suggest that a change in vaccine may be required to mitigate against the higher transmissibility and global disease burden. However, the lead time to develop such a response may be too late to mitigate the spread and effects of Omicron. These animal model data suggest the clinical consequences of infection with the Omicron variant may be less severe but the higher transmissibility could still place huge burden upon healthcare systems even if a lower proportion of infected patients are hospitalised.

"younger males (adolescents, 20-49) are an underrecognized group at high risk for SARS-CoV-2 infection"

David N. Fisman et al. 2021. COVID-19 Case Age Distribution: Correction for Differential Testing by Age. Annals of Internal Medicine. https://doi.org/10.7326/M20-7003 https://www.acpjournals.org/doi/full/10.7326/M20-7003

Figure 3. Observed and test-adjusted estimates of cumulative incidence of SARS-CoV-2 infection, Ontario, Canada.
(data thru Dec 8, 2021)

Discussion...adults aged 20 to 29 years and males were at higher risk for infection after adjustment for decreased testing frequency, which is also consistent with reported risk behaviors... Although younger children have seemed less likely to be infected in both PCR-based population screening studies and serologic surveys..., we caution against ascribing this apparent decrease in risk to biological or immunologic mechanisms. Younger children may have been more adherent to social distancing than adolescents with more autonomy, have been deprived of typical school-based contact networks, may have atypical presentations of SARS-CoV-2 infection (such as gastrointestinal illness) with resultant undertesting or underrecognition..., or may have had COVID-19 misidentified as a non–COVID-19 respiratory infection.... It has been suggested that only about 1% of children with SARS-CoV-2 infection are identified through clinical testing..., and seroprevalence studies have found little difference in reported symptom history between seropositive and seronegative children..., in contrast to adults... As such, surveillance data that do not include testing of asymptomatic children may result in misleading estimates of prevalence. With the emergence of novel SARS-CoV-2 variants of concern, epidemiology of infection in children in schools may have shifted further... The Alpha (B.1.1.7) and Delta (B.1.617.2) lineages emerged after December 2020 in Ontario..., and their effects would not have been captured by our data set...

David Robertson and Peter Dosh. 2021. The end of the pandemic will not be televised
BMJ 2021; 375:e068094 doi: https://doi.org/10.1136/bmj-2021-068094 (Published 14 December 2021) https://www.bmj.com/content/375/bmj-2021-068094

Problems defining pandemic endings
Interruption and resumption of social life
Dashboards—fighting or fuelling the pandemic?

The end of the pandemic will not be brought to you
History suggests that the end of the pandemic will not simply follow the attainment of herd immunity or an official declaration, but rather it will occur gradually and unevenly as societies cease to be all consumed by the pandemic’s shocking metrics. Pandemic ending is more of a question of lived experience, and thus is more of a sociological phenomenon than a biological one. And thus dashboards—which do not measure mental health, educational impact, and the denial of close social bonds—are not the tool that will tell us when the pandemic will end. Indeed, considering how societies have come to use dashboards, they may be a tool that helps prevent a return to normal. Pandemics—at least respiratory viral pandemics—simply do not end in a manner amenable to being displayed on dashboards. Far from a dramatic “end,” pandemics gradually fade as society adjusts to living with the new disease agent and social life returns to normal.

As an extraordinary period in which social life was upturned, the covid-19 pandemic will be over when we turn off our screens and decide that other issues are once again worthy of our attention. Unlike its beginning, the end of the pandemic will not be televised.

Gert Marais etal. 2021. Saliva swabs are the preferred sample for Omicron detection. MedRxiv 24 Dec 2021.
doi: https://doi.org/10.1101/2021.12.22.21268246 https://www.medrxiv.org/content/10.1101/2021.12.22.21268246v1

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

Abstract
The Omicron variant is characterised by more than 50 distinct mutations, the majority of which are located in the spike protein. The implications of these mutations for disease transmission, tissue tropism and diagnostic testing are still to be determined. We evaluated the relative performance of saliva and mid-turbinate swabs as RT-PCR samples for the Delta and Omicron variants. The positive percent agreement (PPA) of saliva swabs and mid-turbinate swabs to a composite standard was 71%... and 100%..., respectively, for the Delta variant. However, for the Omicron variant saliva and mid-turbinate swabs had a 100%... and 86%... PPA, respectively. This finding supports ex-vivo data of altered tissue tropism from other labs for the Omicron variant. Reassessment of the diagnostic testing standard-of-care may be required as the Omicron variant become the dominant variant worldwide.
________________________________________________

Ben 🕊 @1BJDJ
A virus so fiendish and deadly, you can catch it through being within 2 metres of someone without any symptoms,
yet they can’t get any samples of it without swabbing the back of your throat and nasal passages.

>135 margd: contd. Throat combined with nares specimen collection instructions (infographic, UK & Ontario videos):

https://twitter.com/tweetmommybop/status/1477475314070691843/photo/1

Prof Peter Hotez MD PhD @PeterHotez | 8:33 PM · Jan 1, 2022:
Fyi, India is the furthest along but we’re also transferring our TexasChildrens Covid vaccine technology,
helping in the co development to additional countries listed here. Again, no patent or strings attached. The country vaccine producer gets to own the vaccine…

This means the vaccine producer works with its own national regulatory authority and WHO. If they ask for our additional help we provide it at our own expense. We’re not only vaccinating the world, we’re stopping the disgusting practices around science colonialism…so here we go

Bangladesh
https://www.bcm.edu/news/baylor-college-of-medicine-and-texas-childrens-hospital...

Indonesia
https://www.texaschildrens.org/about-us/news/releases/texas-childrens-hospital-a...

South Africa
https://www.bcm.edu/news/baylor-tch-and-immunitybio-collaborate-for-covid-19-vac...

And we’re in discussions with other countries as well.
No patents, no strings attached, but also very little if any help from the G7 and global policymakers

the developing country vaccine producers work out their clinical, regulatory, clinical testing, EUA/licensure, vaccine distribution plan with their own national regulatory authority (their FDA equivalent). We don’t interfere. Everyone talks about “decolonization” we’re leading it

Cali Dreaming NaphiSoc @NaphiSoc · 11h
your homerun Hotez is to tune it to delta/omicron.
with bases loaded
we are talking call from Sweden time. (margd: Nobel Peace Prize?)

Mark D. Levine (Manhattan borough prez) @MarkLevineNYC | 5:13 PM · Jan 1, 2022

BREAKING: Another unimaginable high reached in NY today. 85,476 reported Covid cases statewide.

A stunning 49,724 in New York City alone. Positivity 22.7%.

Hospitalizations in NYC continue to climb, now at 4,326–well above last winter’s peak. 1,023 new admissions in past day.

Faheem Younus, MD @FaheemYounus | 9:40 AM · Jan 2, 2022:
Good News: Compared to Delta, Omicron causes significantly less severe disease.
A study of hospitalized COVID patients in South Africa shows that. The summary below *

Table-Omicron v Delta stats, S Africa ( https://twitter.com/FaheemYounus/status/1477651005466726409/photo/1 )
----------------------------------------------------

* Caroline Maslo et al. 2021. Characteristics and Outcomes of Hospitalized Patients in South Africa During the COVID-19 Omicron Wave Compared With Previous Waves (Research Letter). JAMA. Published online December 30, 2021. doi:10.1001/jama.2021.24868 https://bit.ly/3qIKk6y

In Canada, but also elsewhere (US), no doubt: get tested. You may need proof at some point.

David Fisman (U of T) @DFisman · 10h:
Great point. If you have occupationally-acquired covid, get tested. You’ll need that documentation if you develop long covid.

https://twitter.com/Garnet_2203/status/1477743888316002305 (2:06)

andrew kaczynski (CNN) @KFILE | 1:17 PM · Jan 2, 2022:
Glasses that fog up when you wear a mask, did we ever figure out how not to do that?

Yes. Put my mask high your glasses oover the top. Here is the video. IT WORKS
https://www.youtube.com/watch?v=4pTJzApn7cM

Barbasol original shaving cream (no scent) - rub it on your glasses and mirrors and car windows to stop the fogging up.
just rub it in. It's like a foam glass cleaner - a little dab will do you! Works great! No rinse.

If you're wearing a good mask like an N95 or authentic KN95/KF94, try to work on sealing it to your face better. If the mask folds, i.e. is not a formed cup (right), uncrimp/unfold/straighten the nose wire, put it on, and really mold the wire to your nose and cheeks.
https://twitter.com/cindymclennan/status/1477723462101786627/photo/1

Yes. Paper tape along bridge of nose to cheek. Works very well, and not irritating. MicroPore makes a good paper tape.
https://twitter.com/cindymclennan/status/1477723462101786627/photo/1

Reported six days ago on mediRxiv.org, a pre-print that yet another variant strain of SARS-CoV-2 has appeared in southern France, possibly of Cameroonian origin. Known currently as variant "IHU", the genomic analysis reveals 46 mutations and 37 deletions resulting in 30 amino acid substitutions and 12 deletions.

Fourteen amino acid substitutions, including N501Y and E484K, and 9 deletions are located in the spike protein.

No further characterization of the variant is presented, other than it is (at time of filing) restricted to the south of France in a single geographical area following screening and that the "index case returned from a traveler who came from Cameroon."

>143 Limelite: and at this point not thought to be highly concerning. Frankly at this moment it would have to be astonishingly infectious to have any chance of outcompeting Omicron. Which may, whatever its mutations, consign it to extinction.

Not only am I on vacation, it appears my computer internet is, too... Welcome news from Israel (Paul Kuodi et al. preprint, below) worth extra effort to share--hope I copied address correctly...

At least 2 doses vaxx associated w substantial decrease in reporting of most common long COVID symptoms.

--------------------------------------------------------------
ETA:

Paul Kuodi et a. 2022. Association between vaccination status and reported incidence of post-acute COVID-19 symptoms in Israel: a cross-sectional study of patients infected between March 2020 and November 2021.
doi: https://doi.org/10.1101/2022.01.05.22268800 Med Rxiv Jan 6, 2022. www.medrxiv.org/content/10.1101/2022.01.05.22268800v1

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

Abstract
...Results: Of 951 previously infected individuals who filled the survey 637(67%) were vaccinated. The most commonly reported symptoms were; fatigue (22%), headache (20%), weakness (13%), and persistent muscle pain (10%). After adjusting for follow-up time and baseline symptoms, fully vaccinated (2 or more doses) individuals were less likely than unvaccinated individuals to report any of these symptoms by 64%, 54%, 57%, and 68% respectively, (Risk ratios 0.36, 0.46, 0.43, 0.32, ... in the listed sequence).

Conclusions: Vaccination with at least two doses of COVID-19 vaccine was associated with a substantial decrease in reporting the most common post-acute COVID19 symptoms. Our results suggest that, in addition to reducing the risk of acute illness, COVID-19 vaccination may have a protective effect against long COVID.

Vaxx associated w small change in menstrual cycle length. Transient, mild.

Edelman, Alisonet al. 2022. Association Between Menstrual Cycle Length and Coronavirus Disease 2019 (COVID-19) Vaccination A U.S. Cohort. Obstetrics & Gynecology: January 5, 2022 - Volume - Issue - 10.1097/AOG.0000000000004695 doi: 10.1097/AOG.0000000000004695 https://journals.lww.com/greenjournal/Fulltext/9900/Association_Between_Menstrua...

ABSTRACT
...RESULTS:
We included 3,959 individuals (vaccinated 2,403; unvaccinated 1,556). Most of the vaccinated cohort received the Pfizer-BioNTech vaccine (55%) (Moderna 35%, Johnson & Johnson/Janssen 7%). Overall, COVID-19 vaccine was associated with a less than 1-day change in cycle length for both vaccine-dose cycles compared with prevaccine cycles (first dose 0.71 day-increase,...; second dose 0.91...; unvaccinated individuals saw no significant change compared with three baseline cycles (cycle four 0.07...; cycle five 0.12...). In adjusted models, the difference in change in cycle length between the vaccinated and unvaccinated cohorts was less than 1 day for both doses (difference in change: first dose 0.64 days, ...; second dose 0.79 days...). Change in menses length was not associated with vaccination.

CONCLUSION:
Coronavirus disease 2019 (COVID-19) vaccination is associated with a small change in cycle length but not menses length.

COVID-19 may have killed nearly 3 million in India, far more than official counts show
New analysis bolsters idea that country’s seemingly low death rate was misleading
Jon Cohen | 6 Jan 2022
https://www.science.org/content/article/covid-19-may-have-killed-nearly-3-millio...

Covid may raise the risk of diabetes in children, C.D.C. researchers reported.
Roni Caryn Rabin | Jan. 7, 2022

...C.D.C. study* is among the first to examine large insurance claim databases in the United States to estimate the prevalence of new diabetes diagnoses in children under age 18 who had Covid or were known to be infected with the coronavirus...: they found a 2.6-fold increase in new diabetes cases among children in one, and a smaller 30 percent increase in another...not yet clear whether post-Covid diabetes would be a chronic condition in these children, or a transient condition that resolves. Most of the children were only followed about four and a half months.

The finding underscores the importance of vaccinating all eligible children against Covid...and using measures like masking and distancing, especially to protect the youngest, who cannot yet be vaccinated.

Many of the children in the study were only diagnosed after having an episode of diabetic ketoacidosis, a life-threatening complication that occurs when the body doesn’t have enough insulin to allow blood sugar into cells to use for energy.

...did not distinguish between types of diabetes, including both Type 1 and Type 2 in... analysis. The increases were seen both among those who had been ill with Covid, and those who were asymptomatic but tested positive.

Another study**, also released on Friday by the C.D.C., found that two doses of the Pfizer-BioNTech vaccine protected hospitalized youngsters between the ages of 12 and 18 against severe multisystem inflammatory syndrome, or MIS-C, which can develop two to six weeks after infection with the virus...

https://www.nytimes.com/2022/01/07/health/kids-covid-diabetes-cdc.html
---------------------------------------------

* Barrett CE, Koyama AK, Alvarez P, et al. Risk for Newly Diagnosed Diabetes (more than) 30 Days After SARS-CoV-2 Infection Among Persons Aged less than) 18 years — United States, March 1, 2020–June 28, 2021. MMWR Morb Mortal Wkly Rep. ePub: 7 January 2022. DOI: http://dx.doi.org/10.15585/mmwr.mm7102e2external icon https://www.cdc.gov/mmwr/volumes/71/wr/mm7102e2.htm

...Persons aged less than) 18 years with COVID-19 were more likely to receive a new diabetes diagnosis (more than) 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 (less than) 18 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...
------------------------------------------------

** Zambrano LD, Newhams MM, Olson SM, et al. Effectiveness of BNT162b2 (Pfizer-BioNTech) mRNA Vaccination Against Multisystem Inflammatory Syndrome in Children Among Persons Aged 12–18 Years — United States, July–December 2021. MMWR Morb Mortal Wkly Rep. ePub: 7 January 2022. DOI: http://dx.doi.org/10.15585/mmwr.mm7102e1 https://www.cdc.gov/mmwr/volumes/71/wr/mm7102e1.htm

...Estimated effectiveness of 2 doses of Pfizer-BioNTech vaccine against MIS-C was 91% (95% CI = 78%–97%). Among critically ill MIS-C case-patients requiring life support, all were unvaccinated...

Scroll down to "COVID" to estimate one's risk of a positive test, hospitalization, ICU, death
(Cleveland Clinic library of risk calculation tools):

https://riskcalc.org

T-cells from common colds can provide protection against COVID-19 - study
Alistair Smout | Jan 10, 2022

High levels of T-cells from common cold coronaviruses can provide protection against COVID-19, an Imperial College London study published on Monday has found, which could inform approaches for second-generation vaccines...

https://www.reuters.com/business/healthcare-pharmaceuticals/t-cells-common-colds...
-----------------------------------------

Rhia Kundu et al. 2021. Cross-reactive memory T cells associate with protection against SARS-CoV-2 infection in COVID-19 contacts. Nature Communications volume 13, Article number: 80 (2022). January 10, 2022. https://www.nature.com/articles/s41467-021-27674-x

Abstract

Cross-reactive immune responses to SARS-CoV-2 have been observed in pre-pandemic cohorts and proposed to contribute to host protection. Here we assess 52 COVID-19 household contacts to capture immune responses at the earliest timepoints after SARS-CoV-2 exposure. Using a dual cytokine FLISpot assay on peripheral blood mononuclear cells, we enumerate the frequency of T cells specific for spike, nucleocapsid, membrane, envelope and ORF1 SARS-CoV-2 epitopes that cross-react with human endemic coronaviruses. We observe higher frequencies of cross-reactive (p = 0.0139), and nucleocapsid-specific (p = 0.0355) IL-2-secreting memory T cells in contacts who remained PCR-negative despite exposure (n = 26), when compared with those who convert to PCR-positive (n = 26); no significant difference in the frequency of responses to spike is observed, hinting at a limited protective function of spike-cross-reactive T cells. Our results are thus consistent with pre-existing non-spike cross-reactive memory T cells protecting SARS-CoV-2-naïve contacts from infection, thereby supporting the inclusion of non-spike antigens in second-generation vaccines.

Some gut bacteria may protect against SARS-CoV-2 infection
Mary McGorray, M.D. | January 6, 2022

All humans have a microbiome comprising thousands of microorganisms, such as bacteria, fungi, and viruses, which co-exist naturally in the body.
A team of scientists decided to study whether bacteria from the human microbiome could inhibit the SARS-CoV-2 virus.
They identified three bacterial metabolites from the human microbiome that inhibited SARS-CoV-2 viral infection.
Remarkably, these natural bacterial metabolites resemble drugs that the Food and Drug Administration (FDA) has approved and that clinical research is exploring as treatments for COVID-19, obsessive-compulsive disorder (OCD), or both.
... IPA is structurally similar to remdesivir, a medication that doctors use to treat some severe COVID-19 infections.
Tryptamine is similar to serotonin. The selective serotonin reuptake inhibitor fluvoxamine is a medication that doctors typically use to treat OCD.
BIP parallels central aspects of the structure of favipiravir, an oral antiviral medication that clinical trials are testing as a treatment for mild COVID-19 disease and comparing with remdesivir for treating moderate disease...

https://www.medicalnewstoday.com/.../some-gut-bacteria...
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Frank J. Piscotta et al. 2021 Metabolites with SARS-CoV-2 Inhibitory Activity Identified from Human Microbiome Commensals. Am. Soc. for Microbiology. mSphere Dec 1, 2021. DOI: https://doi.org/10.1128/mSphere.00711-21 https://journals.asm.org/doi/10.1128/mSphere.00711-21

ABSTRACT
The COVID-19 pandemic has highlighted the need to identify additional antiviral small molecules to complement existing therapies. Although increasing evidence suggests that metabolites produced by the human microbiome have diverse biological activities, their antiviral properties remain poorly explored. Using a cell-based SARS-CoV-2 infection assay, we screened culture broth extracts from a collection of phylogenetically diverse human-associated bacteria for the production of small molecules with antiviral activity. Bioassay-guided fractionation uncovered three bacterial metabolites capable of inhibiting SARS-CoV-2 infection. This included the nucleoside analogue N6-(Δ2-isopentenyl)adenosine, the 5-hydroxytryptamine receptor agonist tryptamine, and the pyrazine 2,5-bis(3-indolylmethyl)pyrazine. The most potent of these, N6-(Δ2-isopentenyl)adenosine, had a 50% inhibitory concentration (IC50) of 2 μM. These natural antiviral compounds exhibit structural and functional similarities to synthetic drugs that have been clinically examined for use against COVID-19. Our discovery of structurally diverse metabolites with anti-SARS-CoV-2 activity from screening a small fraction of the bacteria reported to be associated with the human microbiome suggests that continued exploration of phylogenetically diverse human-associated bacteria is likely to uncover additional small molecules that inhibit SARS-CoV-2 as well as other viral infections.

COVID-19: Did Omicron evolve in mice?
James Kingsland | Jan 7, 2021

The origin of the Omicron variant of SARS-CoV-2 is uncertain because it contains a large number of mutations that are rare in other known human variants.
The most popular theory is that Omicron evolved during a protracted infection of an individual with a compromised immune system.
Scientists at the Chinese Academy of Sciences now report that they have found a pattern of mutations in Omicron that is typical of a virus that has infected mice.
They believe SARS-CoV-2 jumped from a human to a mouse in mid-2020, then back into a human in late 2021.
They say it is unlikely that the intermediate host was a laboratory mouse....

https://www.medicalnewstoday.com/.../covid-19-did-omicron...
------------------------------------------------------
Changshuo Wei et al. 2021. Evidence for a mouse origin of the SARS-CoV-2 Omicron variant. Journal of Genetics and Genomics. Available online 24 December 2021 as Journal Pre-proof. https://doi.org/10.1016/j.jgg.2021.12.003 https://www.sciencedirect.com/.../pii/S1673852721003738#!

Abstract
The rapid accumulation of mutations in the SARS-CoV-2 Omicron variant that enabled its outbreak raises questions as to whether its proximal origin occurred in humans or another mammalian host. Here, we identified 45 point mutations that Omicron acquired since divergence from the B.1.1 lineage. We found that the Omicron spike protein sequence was subjected to stronger positive selection than that of any reported SARS-CoV-2 variants known to evolve persistently in human hosts, suggesting a possibility of host-jumping. The molecular spectrum of mutations (i.e., the relative frequency of the 12 types of base substitutions) acquired by the progenitor of Omicron was significantly different from the spectrum for viruses that evolved in human patients but resembled the spectra associated with virus evolution in a mouse cellular environment. Furthermore, mutations in the Omicron spike protein significantly overlapped with SARS-CoV-2 mutations known to promote adaptation to mouse hosts, particularly through enhanced spike protein binding affinity for the mouse cell entry receptor. Collectively, our results suggest that the progenitor of Omicron jumped from humans to mice, rapidly accumulated mutations conducive to infecting that host, then jumped back into humans, indicating an inter-species evolutionary trajectory for the Omicron outbreak.