COVID-19 - Facts and Information Only Topic

[Hapless Bills Fan]

Really good plain-language discussion of Omicron and the above paper from "Your Local Epidemiologist", blogger Katelyn Jetelina

 

https://yourlocalepidemiologist.substack.com/p/omicron-were-getting-some-answers

 

Questions:

Is Omicron more contagious (transmissible)? 

-So far in both South Africa and UK, the answer appears to be "hell to the Yes", with an Rt of 2-3 in South Africa (limited testing) and Rt of 3.47 in UK, and Omicron went from 0.01% to 2% of the positive cases in UK in just over 2 weeks.

Is it less severe?

-That's "we don't know yet".  YLE does a good job of spelling out the possibilities:

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Are we seeing mild cases because vaccines are working or because Omicron is a less severe disease? We can have a virus that leads to mild cases, but isn’t less severe.

 

Are the majority of cases mild because South Africa has a relatively younger population than, for example, the United States? Extrapolating real-world data from one place to predict how we will do in another place is not straightforward.

 

Is Omicron growing too quickly, so we don’t have enough data yet? This may seem counterintuitive, but in a fast-growing epidemic, the proportion of cases is actually smaller than the proportion of cases in a slower growing epidemic. I tried to show this phenomenon in the figure below. At the same point in the wave, the proportion of Delta cases (orange highlight) was far higher than the proportion of Omicron cases (green highlight). This factor alone could cause an unusually low proportion of hospitalizations at first. We have to see what happens when this denominator gets bigger and bigger.

 

I'd like to point out a different way of looking at it, from Cornell president Martha Pollack in an email that was just sent regarding Cornell's Tuesday closure of in-person events and transition to online finals.  Cornell is 97% vaccinated and Omicron was spreading fast (but not causing any serious disease, sniffles or nothing). 

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While there is still much that is not known about the Omicron variant, it appears to be significantly more transmissible than Delta and other variants. There is some evidence (though far from certain) that it generally causes milder cases, particularly among vaccinated individuals. However, when you have high transmissibility, you’re going to have very high numbers of cases, and so even with lower rates of serious illness, outbreaks must be taken seriously.

 

In fact, if Cornell weren't testing every student every week, they would have no idea they had an outbreak, because most of the cases are either asymptomatic or milder than the cold/flu that is going around (in vaccinated students). 

Here is Martha Pollack's explanation of why we still care (Pollack is a computer and information science professor and knows her maths):

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The fact that we have not experienced severe illness among our student population may lead some to ask why we are imposing such serious steps. So let me share the underlying math:

Consider one variant, let’s call it A, in which each person infects two others on average, and which causes serious illness in 1% of cases. After ten iterations of transmission, you’ll have about 1,000 cases, and 10 instances of serious illness.

Now consider variant B, which is twice as infectious, so each person infects four others on average, but which causes serious illness only one-tenth as often, i.e., in only 0.1% of cases. Unchecked, over the same ten iterations of transmission, with variant B you’ll have more than a million cases, and about 1,000 individuals with serious illness.

.......the point is that higher transmissibility leads to exponential growth, which outweighs the linear decrease in percent of severe cases. To avoid this type of situation, it is imperative not to let such infections run unchecked, but to take steps that limit transmission.

It is obviously extremely dispiriting to have to take these steps. However, since the start of the pandemic, our commitment has been to follow the science and do all we can to protect the health of our faculty, staff, and students.

 

Math sez:

A Variant that is twice as infectious, but 10x less cases of serious disease, unchecked, will produce 100x more serious illness after 10 iterations of transmission.

 

 

 

 

[Hapless Bills Fan]

As promised, I'll try to explain why it's not possible that being vaccinated with a vaccine approved in the US** will give you a positive PCR test for Covid.

 

I can't find something not behind a paywall that explains it as clearly as I like, so I'm going to have to piece it together. 

 

First, the PCR test for Covid.  Here's a decent explanation of how PCR works:

https://www.genome.gov/es/node/83066

The first thing that is not well explained:

-RNA is very unstable and easily degraded.  We all have an enzyme that degrades RNA on our skin, in our sweat, in saliva, etc. (RNase)

-The RNA genome in the virus isn't eaten by the RNAse in your nose because it's all packaged up in a virus particle.

-The first step in the PCR test for virus is to extract the RNA from the virus particle, wearing gloves and a clean labcoat and haircover and using specially treated labware, water and buffers that are certified free from RNAse contamination

-So then you get the viral RNA, and the RT-PCR reaction reverse transcribes it to DNA, then amplify it using primers that match two (or more) different viral genes.

 

The key point to remember is that RNA does not safely bop around the body on its own.  It needs to be carefully packaged up to protect it from being degraded.  mRNA, the instructions used to translate a protein, is even less stable and its normal life in a cell is minutes to hours.  Your body uses this feature to "turn on" or "turn off" expression of different genes.

 

Second, the mRNA vaccine:

https://www.cdc.gov/coronavirus/2019-ncov/downloads/vaccines/COVID-19-mRNA-infographic_G_508.pdf

It only contains information to make one of the Sars-Cov2 proteins, the Spike protein.

The second thing that is not well explained:

-mRNA in the cell has a one-way ticket from the cell nucleus to the cytoplasm.  It doesn't exit the cell, and it can't get back into the nucleus and become part of the cell's genome.  If the cell is lysed (broken up), any RNA released is immediately degraded by RNAse outside the cell.  The mRNA from the vaccine gets into the cell cytoplasm and stays there. 

-It has been stabilized, but still has a lifetime of days.  Here's a paper which followed where mRNA in an mRNA vaccine went:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5475249/

It mostly stays in the lymph nodes right in the arm where you got your shot, but a bit of it traveled to more distant lymph nodes.  (See Table 1).  The longest half-life was 28 hrs, meaning in a12 days at most, it's down to 0.1% of the original level (0.001 of original level)

-so even if you get vaccinated, and then get tested for Covid the next day when you still have vaccine mRNA in your cells, there isn't going to be Covid RNA hanging out in your nose waiting to be swabbed up

-even if it were, the vaccine only contains the information to make one protein, the spike protein.  The PCR test amplifies several different genes.

 

PM me if questions, I'll do my best.

 

**there are vaccines in use in other countries that use actual Covid virus that has been chemically inactivated.  It is theoretically possible this could cause a positive covid test, although highly unlikely.

 

 

 

[Hapless Bills Fan]

New pre-print (not yet peer reviewed) paper on Omicron immunity.  Seems to be solid work.

 

Bottom line: Omicron evades immunity from both prior infection, and vaccination, even with 2 doses of mRNA vaccines, and if you received 1 dose of J&J might as well have injected water.  Best results are vaccination plus prior infection; upthread some data that a booster of one of the mRNA vaccines substantially raises immunity.

 

https://www.biorxiv.org/content/10.1101/2021.12.12.472269v1

Summary.  "RBD" = receptor binding domain, where the Spike protein binds to the ACE2 receptor to get inside the cells.

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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 mAb1, retaining unaltered potency. Furthermore, a fraction of broadly neutralizing sarbecovirus mAbs recognizing antigenic sites outside the RBM, including sotrovimab2, S2X2593 and S2H974, 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.

 

Key figure: (Figure 2).  Click to embiggen.  They took plasma from infected, recovered individuals and from vaccinated individuals, and looked at the ability of their antibodies to neutralize different variants of Sars-CoV2, the virus that causes Covid-19.

 

mRNA-1273 is Moderna, BNT162.b2 is Pfizer, AZ1222 is AstraZeneca, Ad26Cov2.s is J&J. 

 

The first thing to notice is there's a pretty big spread in each condition.  That's very typical; the human immune system is highly variable.  Looking at the variability, to my eyeball I'm not sure Pfizer and Moderna are different on a "statistically significant" level, but it's pretty clear they're different from convalescent or J&J or Sputnik.

 

The second thing to know (and this is very important) is that neutralizing antibodies are only one aspect of human adaptive immune response.  T cells are another.  Neutralizing antibodies are less effective, which means infection may still occur, but the rest of the adaptive immune response may still protect against severe infection.

 

"Fully vaccinated" people (by the current definition) are getting infected with Omicron quite readily, as are people who have had a prior infection with an earlier strain.  So far, the infections in these people are mild, but "pump the brakes" on saying that Omicron will universally be mild in all populations - we just don't know yet, and as outlined up-thread, even if it causes 10x or 100x fewer serious disease,  if it is more infectious it can result in a larger overall number of very sick people.

 

 

[Hapless Bills Fan]

Cardiology and Covid vaccine

 

https://www.acc.org/latest-in-cardiology/ten-points-to-remember/2021/09/03/14/37/myocarditis-with-covid19-mrna

 

Myocarditis With COVID-19 mRNA Vaccines. Circulation 2021;144:471-484.

 

1. The overall rates of myocarditis/pericarditis after the second dose of mRNA vaccines for COVID-19 are approximately 12.6 per million doses in individuals 12-39 years of age. (note: that's 0.00126%)
7. The risk-benefit assessment appears to continue to favor vaccination, even for patients in the highest risk group for myocarditis. For example, in males aged 12-17, in which there have been 56-69 myocarditis cases per million doses, those vaccines would be expected to prevent 8,500 COVID-19 cases, 183 hospitalizations, 38 intensive care unit (ICU) admissions, and one death. For older males (24-29 years), the 15-18 myocarditis cases would be compared against 936 hospitalizations, 215 ICU admissions, and 13 deaths.

9. Myocarditis after vaccination has generally been mild, with almost all patients having resolution of symptoms and signs and improvement in diagnostic markers and imaging with or without treatment.

 

Because of these data, the American College of Cardiology recommends vaccination for patients with cardiac conditions.

 

If you have a clotting or cardiac condition, the best thing is to discuss risks and benefits fully with your cardiologist/hematologist.

 

[PastaJoe]

 

[Hapless Bills Fan]

More Omicron - R-values

UK Chief Medical Adviser to UK Health

https://www.theguardian.com/world/video/2021/dec/16/omicron-r-number-covid-variant-estimated-3-5-dr-susan-hopkins-video

 

The Lancet, top tier journal

https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00559-2/fulltext

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The original strain of SARS-CoV-2 has an R0 of 2·5, while the delta variant (B.1.617.2) has an R0 of just under 7. Martin Hibberd, professor of emerging infectious diseases at London School of Hygiene & Tropical Medicine (London, UK), reckons omicron's R0 could be as high as 10. In the UK, cases of omicron are doubling every 2–3 days, which puts it on track to supplant delta as the dominant variant in the country by mid-December. It also complicates control efforts. “Contact tracing works well if you have about a week between one infection and the next”, explained Hibberd, “But it is almost impossible to make it work if you only have 2 or 3 days between infections. We may have to rely on other measures, like daily testing.”

 

[Hapless Bills Fan]

On 12/22/2021 at 7:19 AM, PastaJoe said:

 

 

Here's some more about spike ferritin nanoparticle vaccines

 

This vaccine in particular.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651551/

 

Essentially, this is a technology that allows a multi-valent vaccine to be put on a single particle.

It's cool technology, and I hope it proves out in phase 2 and 3 trials.

 

But Feigl-Ding's "all its variants" is IMO a bit misleading - it makes it sound as though this vaccine will protect against future variants.

It won't.  It's a cool technology that will allow a single vaccine to protect against multiple variants in the same shot, but as the article on which Feigl-Ding's tweet is based points out,

https://www.defenseone.com/technology/2021/12/us-army-creates-single-vaccine-effective-against-all-covid-sars-variants/360089/

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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.

You have to put the spike protein from known, identified coronavirus strains into the shot.

 

In theory (ahem), one could do the same thing with an adenovirus or mRNA vaccine by combining a "payload" of nucleic acids from different variants into a single vaccination.

 

Both will have the same limitation: you need to identify a critical variant that may escape vaccine coverage and produce a vaccine that targets it

 

[Hapless Bills Fan]

BIG NEWS

 

https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-first-oral-antiviral-treatment-covid-19

 

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Today, the U.S. Food and Drug Administration issued an emergency use authorization (EUA) for Pfizer’s Paxlovid (nirmatrelvir tablets and ritonavir tablets, co-packaged for oral use) for the treatment of mild-to-moderate coronavirus disease (COVID-19) in adults and pediatric patients (12 years of age and older weighing at least 40 kilograms or about 88 pounds) with positive results of direct SARS-CoV-2 testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death. Paxlovid is available by prescription only and should be initiated as soon as possible after diagnosis of COVID-19 and within five days of symptom onset. 

 

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Paxlovid consists of nirmatrelvir, which inhibits a SARS-CoV-2 protein to stop the virus from replicating, and ritonavir, which slows down nirmatrelvir’s breakdown to help it remain in the body for a longer period at higher concentrations. Paxlovid is administered as three tablets (two tablets of nirmatrelvir and one tablet of ritonavir) taken together orally twice daily for five days, for a total of 30 tablets. Paxlovid is not authorized for use for longer than five consecutive days. 

 

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Paxlovid is not authorized for the pre-exposure or post-exposure prevention of COVID-19 or for initiation of treatment in those requiring hospitalization due to severe or critical COVID-19. Paxlovid is not a substitute for vaccination in individuals for whom COVID-19 vaccination and a booster dose are recommended.

 

https://apnews.com/article/coronavirus-pandemic-pfizer-medication-f5f65e7e61d6aa9c7dfa193053e8878a?fbclid=IwAR3Zxzm5fFdLqWfpiodmI0mMDFUAXWrf83q3JzM_llCrR7O9gsX1t6iO3kM

 

Pfizer's drug Paxaloid has received emergency use authorization from the FDA.

This is a pill - no injection, infusion etc

 

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The drug, Paxlovid, is a faster way to treat early COVID-19 infections, though initial supplies will be extremely limited. All of the previously authorized drugs against the disease require an IV or an injection.

 

An antiviral pill from Merck also is expected to soon win authorization. But Pfizer’s drug is all but certain to be the preferred option because of its mild side effects and superior effectiveness, including a nearly 90% reduction in hospitalizations and deaths among patients most likely to get severe disease.

 

“The efficacy is high, the side effects are low and it’s oral. It checks all the boxes,” said Dr. Gregory Poland of the Mayo Clinic. “You’re looking at a 90% decreased risk of hospitalization and death in a high-risk group — that’s stunning.”

 

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Pfizer currently has 180,000 treatment courses available worldwide, with roughly 60,000 to 70,000 allocated to the U.S. The company said it expects to have 250,000 available in the U.S. by the end of January.

 

Federal health officials are expected to ration early shipments to the hardest hit parts of the country. Pfizer said the small supply is due to the manufacturing time — currently about nine months. The company says it can halve production time next year.

 

The U.S. government has agreed to purchase enough Paxlovid to treat 10 million people, and it will be provided free to patients. Pfizer says it’s on track to produce 80 million courses globally next year, under contracts with the U.K., Australia and other nations.

 

On Dec 16, it was approved for use in EU member states, although full review is still underway:

https://www.reuters.com/world/europe/eu-regulator-says-pfizers-anti-covid-pill-can-be-used-by-member-states-2021-12-16/

 

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European Union countries can use Pfizer's (PFE.N) antiviral COVID-19 pill Paxlovid early after diagnosis of an infection even though its full review for regulatory approval has not been completed, the bloc's drugs regulator said on Thursday.

 

Patients at risk of suffering severe forms of the infection should start the five-day course of Paxlovid as soon as possible after diagnosis or within 5 days of symptom onset but not when supplemental oxygen is already required.

 

"The Agency's advice can now be used to support national recommendations on the possible use of the medicine before marketing authorisation," the European Medicines Agency (EMA) said in a statement.

 

This was expected after Pfizer released data from its clinical trial

https://www.reuters.com/business/healthcare-pharmaceuticals/pfizer-says-covid-19-pill-near-90-effective-final-analysis-2021-12-14/

 

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NEW YORK, Dec 14 (Reuters) - Pfizer Inc (PFE.N) on Tuesday said its antiviral COVID-19 pill showed near 90% efficacy in preventing hospitalizations and deaths in high-risk patients, and recent lab data suggests the drug retains its effectiveness against the fast spreading Omicron variant of the coronavirus.

 

The U.S. drugmaker last month said the oral medicine was around 89% effective in preventing hospitalizations or deaths when compared to placebo, based on interim results in around 1,200 people. Data from its final analysis of the trial disclosed on Tuesday includes an additional 1,000 people.

 

Nobody in the trial who received the Pfizer treatment died, compared with 12 deaths among placebo recipients.

 

The Pfizer pills are taken with the older antiviral ritonavir every 12 hours for five days beginning shortly after onset of symptoms. If authorized, the treatment will be sold as Paxlovid.

 

I'll put up some stuff about the mechanism first, but long story short, unlike monoclonal antibody treatments which target spike protein regions that may mutate to maintain infectivity, this medication should not be affected by viral mutations as it targets the "business" part of an essential viral enzyme.

[Hapless Bills Fan]

 

FDA also grants Merck pill Molnupiravir emergency use authorization

 

https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-additional-oral-antiviral-treatment-covid-19-certain

 

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Molnupiravir is a medication that works by introducing errors into the SARS-CoV-2 virus’ genetic code, which prevents the virus from further replicating. Molnupiravir is administered as four 200 milligram capsules taken orally every 12 hours for five days, for a total of 40 capsules. Molnupiravir is not authorized for use for longer than five consecutive days. 

 

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Molnupiravir is not authorized for use in patients younger than 18 years of age because molnupiravir may affect bone and cartilage growth. It is not authorized for the pre-exposure or post-exposure prevention of COVID-19 or for initiation of treatment in patients hospitalized due to COVID-19 because benefit of treatment has not been observed in people when treatment started after hospitalization due to COVID-19.   

 

 

[Hapless Bills Fan]

Pretty good description of Paxlovid mechanism

https://www.acsh.org/news/2021/11/16/pfizers-covid-drug-works-wonders-heres-how-it-works-15924

 

Bottom line up front: it's a protease inhibitor specific for the protease made by the Sars-Cov-2 virus, plus a second drug that extends the life of the protease inhibitor by blocking the human enzymes that degrade it.

 

Heard of "protease inhibitor therapy" for HIV?  Similar thing...the virus makes its proteins all in one long strand-o-beads that have to be cut in the correct location to be active and able to make a new virus.  But the HIV protease uses a different mechanism, so its protease inhibitors didn't do too much for the Sars-Cov-2 protease inhibitor.

 

The "business end" of a viral protease is a great target for pharmaceutical treatment because it can't mutate much (if at all), or the mutations put it "out of business".  Omicron and its many mutations has only one mutation in the protease, and doesn't impact Paxlovid binding.

 

For those who would like something meaty, here's the paper about it:

https://www.science.org/doi/full/10.1126/science.abl4784#

 

And if you're a drinkin' kind of guy, pour one and drink a toast to all the peons in R&D at Pfizer who have been working their donkeys off for the last 22 months to develop this molecule.

 

[The Frankish Reich]

3 hours ago, BuffaninSarasota said:

So variants are possible due to unvaccinated people, huh? Any data to support that claim?

Yes. 

https://hub.jhu.edu/2021/07/19/andrew-pekosz-delta-variants/

Of course, the problem is that with a pandemic it isn't enough to vaccinate the vast majority of people in a single country; the unvaccinated throughout the world provide the laboratories for mutations.

https://www.npr.org/sections/goatsandsoda/2021/12/01/1055803031/the-mystery-of-where-omicron-came-from-and-why-it-matters

[Hapless Bills Fan]

Nice visualization of how Covid has ebbed and waned across the country

 

https://www.axios.com/year-in-covid-visual-c84387bc-ffd4-4c46-aff2-be2178a55d41.html

[Hapless Bills Fan]

The US Government will provide 4 free covid Antigen (rapid) tests per household.

 

The government has launched a website where you can get four at home tests per household, free of charge. It takes about a minute to complete the process, and I would recommend doing that now if you have not already, since it just went live today.

 

http://COVIDtests.gov

 

The tests are said to ship in late January.