PlagueWatch 2020-23 - Coronavirus

[rsvman]

Don’t really want to get into the origin stuff right now, but I did want to chime in on the J&J vaccine.

I know that people are underwhelmed with the numbers, but that’s a recency bias. Were it not for the amazing numbers put up by Pfizer and Moderna, we would be looking at this in an entirely different light. If someone had told us back in June of last year that J&J would make a vectored vaccine that would be anywhere near 70% protective with just a single inoculation and was refrigerator stable, we would have been ecstatic and would’ve thought it was fantastic.

Well, it still is. Truthfully, 70-ish% is about what both Pfizer and Moderna are actually achieving with a single shot in the real world (in their EUA, they counted all infections that occurred in the vaccine group, counting from receipt of the vaccine; many of those happened within the first 10 days, in which case the recipients were probably incubating the virus when they got the vaccine. In short, maybe the J&J vaccine is just as good as Pfizer and Moderna; we won’t know until they release data on the two-dose subjects.

At any rate, 70% is pretty good, and if we could get a whole bunch more people vaccinated sooner it would really pay off from the public health standpoint. I don’t know how much vaccine they will get out there and how soon it could be administered, but I strongly believe that anybody waiting for vaccine should not be picky at this point (provided the FDA reviews the data and grants the EUA). Just get whatever they have available as soon as possible. That’s the surest route to getting on the back side of this pandemic.


Now, onto a different topic...there has been a lot of questions about how long the vaccines will work and whether revaccination will be necessary, and whether variants will escape the vaccine, etc. My feeling, at this point, is that the duration of vaccine protection is likely to be a lot longer than most people think. I think it might even be possible that protection would last for a decade, or even longer. The caveat is that the virus obviously mutates quite a bit, and it is likely that eventually it will mutate away from vaccine protection. The Brazilian variant may have already done so. (As an aside, and not being political at all, I believe that whomever was in charge at the time the Brazilian variant became known should have IMMEDIATELY shut down all travel between Brazil and the United States. Once the strain gets here, it is likely to spread.)

Anyway, so here are the best-case and worst-case scenarios, as I see them today (subject to change as soon as next week, lol):

Best-case: The vaccines produce durable immunity. Herd immunity is achieved through active and rapid vaccine roll-out, and life gets back to some semblance of normal by the late fall/early winter. Repeat vaccination is not required for at least two years.

Worst-case: The vaccines produce durable immunity that has some ability to protect against slightly mutated strains, but more extreme mutations will find a way to survive and repeat vaccination will be required frequently, maybe every 8-12 months. In the meantime we have to continue living the way we are currently living, and monitoring all the new variants closely to use for making the next vaccine. Absolute worst case is that a mutant becomes undetectable by our current PCR tests, which allows a lot of infected people to be thought uninfected, allowing more rapid spread. Life doesn’t get back to some semblance of normal for years, if ever.


What will actually happen is highly likely to be somewhere between those two extremes. If I know Barney, he is probably already producing (or has already produced) a new template for a new vaccine that will protect against the UK, the South Africa, and the Brazil mutants.

[mph]

That's NYmag.com, not the New Yorker. Neither one is perfect, but I'd generally be inclined to give a story in the New Yorker more weight.

Good catch. Thank you for the correction.

[House P]

This is all readily available information, because they have to specify it in the trial design. Per clinicaltrials.gov, JnJ defined moderate and "severe" according to the FDA guidance (found here: https://www.fda.gov/media/137926/download)

Moderate: Symptoms of moderate illness with COVID-19, which could include any symptom of mild illness (fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms) or shortness of breath with exertion. Clinical signs suggestive of moderate illness with COVID-19, such as respiratory rate ≥ 20 breaths per minute, saturation of oxygen (SpO2) > 93% on room air at sea level, heart rate ≥ 90 beats per minute; No criteria for severe or critical severity

Severe: Symptoms suggestive of severe systemic illness with COVID-19, which could include any symptom of moderate illness or shortness of breath at rest, or respiratory distress; Clinical signs indicative of severe systemic illness with COVID-19, such as respiratory rate ≥ 30 per minute, heart rate ≥ 125 per minute, SpO2 ≤ 93% on room air at sea level or PaO2/FiO2 < 300; No criteria for critical severity

Basically, moderate is a pretty low bar. Definitely well shy of hospitalization. Severe is a higher bar, but below critical. So, possibly but not necessarily hospitalized, and definitely not life-altering/threatening).

Thanks for digging though Clintrials.gov for this information. It is reassuring that "moderate disease" appears to be the type of stuff that doesn't typically require medical attention (unless I am missing something as I am not a doctor).

They did not have a category for "mild" disease in the trial protocol.

After reading your post, I skimmed the full protocol posted by J&J. It seems that they have a secondary endpoint to "assess the effect of [the vaccine] on molecularly confirmed mild COVID-19".

Mild disease is defined as any case which does not meet the definition of moderate or severe disease, but has one of the following symptoms:

"fever (≥38.0°C or ≥100.4°F [but less than 38.5°C or 101.2°F]), sore throat, malaise (loss of appetite,generally unwell, fatigue, physical weakness), headache, muscle pain (myalgia), gastrointestinalsymptoms, cough, chest congestion, runny nose, wheezing, skin rash, eye irritation or discharge, chills,new or changing olfactory or taste disorders, red or bruised looking feet or toes, or shaking chills orrigors. "

As many others have pointed out, it is much more important that a vaccine prevents severe disease than mild disease.

Either way, I am not sure why they didn't mention mild cases in their press release. I could be because this was a secondary endpoint and/or it could be because the efficacy was less than 66% for mild cases. I guess we will learn more when the full study results are published.

They said near 100% protection against hospitalizations and 100% protection against deaths. So we can infer that there were 0 deaths on the vaccine arm (as you state, no clue how many total deaths), and very few hospitalizations in the vaccine arm compared with the placebo arm (no clue on the scale, but it's COVID so likely a decent number in a trial with 30,000 participants.

If I understand the protocol correct, J&J planned to stop when there were 154 cases of moderate or severe disease in their population. Based on the results released to date, we could probably expect that they had ~115 cases in the placebo group vs ~40 cases in the vaccine group. I am not sure how many hospitalizations would be expected in a group of 154 moderate or severe cases, but I suspect the error bars are pretty wide for comparing hospitalizations between the placebo and vaccine group.

[budwom]

I’ll have to rewatch but I remember them saying that is was 90% likely that it was created in a lab. The leading experts in the field believe there really isn’t any evidence to back this up from what I’ve read. They strongly believe that it occurred naturally and I’m way more inclined to believe the scientific community as a whole. Just my two cents. Maybe others on this board who are closer to this than me can chime in.

Biological warfare is pretty scary stuff though.

One thing I know that is not helpful is that China continues to obfuscate the origins (I don't mean to imply a lab had anything to do with it). NBC news interviewed one of their top "investigators" who will be working with the WHO (?) team that is trying to find the origin of the disease and when asked if he thought Covid originated in China, he emphatically said no. I would have thought that a true investigator would have offered up an "I don't know." Seems like he may have his marching orders.

[cato]

I'm hopeful that vaccines will be available to most adults by this spring at the latest. Sadly, many who can get the vaccine will choose not to do so. But that will increase supply for those who want it in the upcoming months.

I'm optimistic, but I'm still hopeful vaccines will be available to kids 12 and over by very late summer (bigger maybe there).

What is the late spring date based on? I’m in SoCal and will be at the end of the line (well, end of the adult line. My under-12 kids aren’t getting a vaccine any time soon).

The most optimistic prediction I have seen for me and my wife is sometime by the fall. But I’m skeptical. There are a lot of people ahead of us in line.

[MChambers]

Good article, based on a Lancet article, summarizing the possible causes and implications of the new outbreak of the Brazil variant: https://nymag.com/intelligencer/2021...questions.html

[MChambers]

Scary FT story (not paywalled) by a writer who ended up in the ICU for 10 days or so. https://www.ft.com/content/2b0dbba3-...a-90e87261d436

[rsvman]

Scary FT story (not paywalled) by a writer who ended up in the ICU for 10 days or so. https://www.ft.com/content/2b0dbba3-...a-90e87261d436

Um, wow. That is a fascinating read.

[CDu]

Another good day yesterday on the dosing front. Up to 29.6 million doses administered, a 1.7 million increase from yesterday. 24 million people have gotten at least 1 dose. Two straight days of 50 million per month pace. That is fantastic if we can maintain it.

[Mtn.Devil.91.92.01.10.15]

I’ll have to rewatch but I remember them saying that is was 90% likely that it was created in a lab. The leading experts in the field believe there really isn’t any evidence to back this up from what I’ve read. They strongly believe that it occurred naturally and I’m way more inclined to believe the scientific community as a whole. Just my two cents. Maybe others on this board who are closer to this than me can chime in.

Biological warfare is pretty scary stuff though.

Just watched the interview. They weren't stating it as biological warfare necessarily. They acknowledged that there is a perspective in science that advocates for studying these possibilities to be prepared for them, and that it could easily have "escaped." To my limited knowledge, they made a strong case for why it seemed likely to not be a naturally occurring virus.

And, they prefaced the discussion by saying it's very difficult to have a rational scientific discussion on the topic because it has been politicized into oblivion. BUT that it is important to learn where it originated in order to know how to best combat it.

I thought it was a good discussion.

[Bostondevil]

Just watched the interview. They weren't stating it as biological warfare necessarily. They acknowledged that there is a perspective in science that advocates for studying these possibilities to be prepared for them, and that it could easily have "escaped." To my limited knowledge, they made a strong case for why it seemed likely to not be a naturally occurring virus.

And, they prefaced the discussion by saying it's very difficult to have a rational scientific discussion on the topic because it has been politicized into oblivion. BUT that it is important to learn where it originated in order to know how to best combat it.

I thought it was a good discussion.

I remain highly skeptical. I will not go so far to say Bill Maher is an anti-vaxxer, but he's not particularly pro-vaccine. I would have pushed back against Weinstein and Heying much, much harder had I been the interviewer. (Ain't nobody getting by me saying something has a 90% chance of being correct without much better evidentiary support. "Because you say so" don't fly with me.) I agree that politics have made it nearly impossible to have a legitimate debate about the origins of this virus, at least for now, but when they said that the marked difference between indoor spread and outdoor spread supported a lab origin, I started to wonder about their expertise. I came here mostly to hear what rsvman had to say about it! What I've found so far by googling about this pair is not exactly confidence boosting.

[Mtn.Devil.91.92.01.10.15]

I remain highly skeptical. I will not go so far to say Bill Maher is an anti-vaxxer, but he's not particularly pro-vaccine. I would have pushed back against Weinstein and Heying much, much harder had I been the interviewer. (Ain't nobody getting by me saying something has a 90% chance of being correct without much better evidentiary support. "Because you say so" don't fly with me.) I agree that politics have made it nearly impossible to have a legitimate debate about the origins of this virus, at least for now, but when they said that the marked difference between indoor spread and outdoor spread supported a lab origin, I started to wonder about their expertise. I came here mostly to hear what rsvman had to say about it! What I've found so far by googling about this pair is not exactly confidence boosting.

I am also waiting to hear him chime in.

[Bostondevil]

As for the J&J vaccine? I'll take it!!!!!! It was studied in South Africa AND Brazil and still had high prevention of disease rates. Also - it had very high prevention of hospitalization and death. At the end of the day, that's what we're really going for, keeping people alive and out of the hospital. I'm good with their prevention of severe disease/death rates.

[Bluedog]

Interesting that in a recent NY Times article about the JnJ vaccine, it quotes two experts who have a different take on if taking both vaccines would be okay...for the record, they do all agree that taking one now vs waiting is absolutely worth it and also note what rsvman said above in that the numbers are still great, it was at a disadvantage because more variants have come into play, and they're still testing to see if a second booster will further increase the efficacy.

Dr. Paul Offit, a vaccine expert at Children’s Hospital of Philadelphia: "People who take the Johnson & Johnson vaccine should be able to safely receive a Pfizer-BioNTech or Moderna vaccine later if a booster shot is needed"

Dr. William Schaffner, an infectious disease expert at Vanderbilt University: "It is not yet known whether it would be safe to take one type of vaccine now and then another later, Dr. Schaffner said, adding, “We haven’t studied this.”"

Which Covid Vaccine Should You Get? Experts Weigh the Effect Against Severe Disease https://nyti.ms/36paxxM

[MChambers]

Interesting that in a recent NY Times article about the JnJ vaccine, it quotes two experts who have a different take on if taking both vaccines would be okay...for the record, they do all agree that taking one now vs waiting is absolutely worth it and also note what rsvman said above in that the numbers are still great, it was at a disadvantage because more variants have come into play, and they're still testing to see if a second booster will further increase the efficacy.

Dr. Paul Offit, a vaccine expert at Children’s Hospital of Philadelphia: "People who take the Johnson & Johnson vaccine should be able to safely receive a Pfizer-BioNTech or Moderna vaccine later if a booster shot is needed"

Dr. William Schaffner, an infectious disease expert at Vanderbilt University: "It is not yet known whether it would be safe to take one type of vaccine now and then another later, Dr. Schaffner said, adding, “We haven’t studied this.”"

Which Covid Vaccine Should You Get? Experts Weigh the Effect Against Severe Disease https://nyti.ms/36paxxM

Yesterday, I spoke to someone who works in a nursing home in the DC suburbs, who told me she had gotten both vaccines. I thought that was strange, and not a good thing, from a public policy perspective, but it did not occur to me that it could be risky.

[MChambers]

Here's an interesting article in Wired about why the coronavirus is mutating, what it says about the world response to the pandemic, and the implications: https://www.wired.com/story/worrisom...rging-why-now/

[Bluedog]

Yesterday, I spoke to someone who works in a nursing home in the DC suburbs, who told me she had gotten both vaccines. I thought that was strange, and not a good thing, from a public policy perspective, but it did not occur to me that it could be risky.

I assume that person got Pfizer and Moderna given those are the only two authorized in the U.S. The above quote says "different types" together haven't been studied yet. That is, adenovirus and mRNA. Pfizer and Moderna are both the same "type" (i.e. mRNA). At least, that's how I read it. Still, yes, seems odd to mix and match Pfizer/Moderna and I'm sure that's not recommended simply because it hasn't been studied and they have slightly different timings and the like. But I wouldn't think it's much risky from a health perspective really...just the efficacy hasn't been studied.

[tbyers11]

I remain highly skeptical. I will not go so far to say Bill Maher is an anti-vaxxer, but he's not particularly pro-vaccine. I would have pushed back against Weinstein and Heying much, much harder had I been the interviewer. (Ain't nobody getting by me saying something has a 90% chance of being correct without much better evidentiary support. "Because you say so" don't fly with me.) I agree that politics have made it nearly impossible to have a legitimate debate about the origins of this virus, at least for now, but when they said that the marked difference between indoor spread and outdoor spread supported a lab origin, I started to wonder about their expertise. I came here mostly to hear what rsvman had to say about it! What I've found so far by googling about this pair is not exactly confidence boosting.

I am also highly skeptical about this virus coming from a lab. I have not watched the Bill Maher clip but I did read the NYMag article linked up thread. To me the article is a bit disingenuous because it presents the 2 ideas (natural vs lab) in the first paragraph as equally likely. In fact, the author actually states that he thinks there was lab manipulation. As someone who works in this field I think that this disingenuous and I call hogwash. This whole article basically has the false premise that because we can't rule out something that is highly unlikely that it should treated with equal likelihood to occur as the much more likely explanation. A reverse Occam's Razor if you will. This article is written by someone with an agenda toward an OPINION that there was a lab origin.

Is there risk? Yes, of course. But I believe that this article is greatly skewed toward this risk having equal footing with the much more likely natural explanation. IMO, that is what conspiracy theorists do. Twist the plausible explanations for things and greatly amplify the very small likelihood that their theory is real. And amplify the fact that scientists will never rule anything out even if it has a 1% chance.

FULL DISCLOSURE: I have collaborated with Ralph Baric (on dengue not coronaviruses). The work that he does and that others do in this area are key to learning about pandemic preparedness in my professional opinion.
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More detailed rebuttal

IMO, it is MUCH more likely that the coronavirus combines with other coronaviruses in bats or pangolins and a variant that can then effectively infect humans occurs. Virologists and epidemiologists study this for viruses all the time. It is well documented for influenza that this occurs between waterfowl, pigs, and humans in a regular manner. And live wet markets are the perfect breeding ground for this.

The author fails to note that the lab accidents that might occur - a dropped flask, a needle prick, a mouse bite, an illegibly labeled bottle would also need about 10 other highly unlikely steps to occur for anyone of those accidents with a virulent virus to actually infect a human in the BSL3 or BSL4 lab conditions in which they are handled. Every one these incidents that occur are tracked and reported (the 1100 incidents cited in the US from 2008 and 2012 resulted in only 5 cases of workers actually being infected or sickened and all were properly quarantined and recovered).

When the article quotes a journalist who says "I’m just asking, Is it a complete coincidence that this outbreak happened in the one city in China with a BSL-4 lab?”. He misses the point entirely. This is, IMO, an example of the recent trend to give fringe beliefs equal footing with common sense. The BSL-4 lab was built in Wuhan precisely because that region in China has a well documented history of zoonotic transmissions. Would you build a lab that studies underground oil reserves in Oklahoma or in Vermont?

The author misrepresents the context and reasoning behind lab adaption of H5N1 flu in ferrets with out of context use the word "force". This process is routinely done with pathogenic avian flu viruses because the ferret infection model has been repeatedly shown to be a strong model for human infection. It helps scientists study what factors in the avian flu viruses make them more likely to "jump" into mammals for better surveillance. Flu virus transmission and pathology in birds bears little resemblance to that of humans. Same thing for SARS virus work. The mouse adaption studies that he described from Baric and Shi in 2015 was important work showing that we should definitely be monitoring betacoronaviruses more closely for the potential of exactly what did happen in 2019. I strongly disagree with the out-of-context comment that the author ends that section with from Mark Liptsch that Gain-of-function experiments “have done almost nothing to improve our preparedness for pandemics,” he said, “yet they risked creating an accidental pandemic.”.

The author constantly refers to the people on the side that lab experiments were related to this outbreak in a positive light. Calling them "thoughtful' and treating their assertions that something bad 'could' happen as basically the same as something bad has happened. Which there is absolutely no proof that it has. The author also casts Fouchier, Baric and Shi with terms like 'force", creepy paper" and Anarchist's Cookbook.

I am going to stop now, because I could go on all day. I'll agree with Ralph Baric's quote "(that) he still thought the virus came from bats in southern China, perhaps directly, or possibly via an intermediate host, although the smuggled pangolins, in his view, were a red herring. The disease evolved in humans over time without being noticed, he suspected, becoming gradually more infectious, and eventually a person carried it to Wuhan “and the pandemic took off.” Then he said, “Can you rule out a laboratory escape? The answer in this case is probably not.” As a scientist I agree with Dr. Baric's last direct quote that you probably can't rule out a lab escape. However, that doesn't mean that a lab escape was likely or even slightly likely. To a scientist if there was a 1-2% chance (what I personally would rate a lab escape) you would always say you can't rule it out.

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[Bostondevil]

I am also highly skeptical about this virus coming from a lab. I have not watched the Bill Maher clip but I did read the NYMag article linked up thread. To me the article is a bit disingenuous because it presents the 2 ideas (natural vs lab) in the first paragraph as equally likely. In fact, the author actually states that he thinks there was lab manipulation. As someone who works in this field I think that this disingenuous and I call hogwash. This whole article basically has the false premise that because we can't rule out something that is highly unlikely that it should treated with equal likelihood to occur as the much more likely explanation. A reverse Occam's Razor if you will. This article is written by someone with an agenda toward an OPINION that there was a lab origin.

Is there risk? Yes, of course. But I believe that this article is greatly skewed toward this risk having equal footing with the much more likely natural explanation. IMO, that is what conspiracy theorists do. Twist the plausible explanations for things and greatly amplify the very small likelihood that their theory is real. And amplify the fact that scientists will never rule anything out even if it has a 1% chance.

FULL DISCLOSURE: I have collaborated with Ralph Baric (on dengue not coronaviruses). The work that he does and that others do in this area are key to learning about pandemic preparedness in my professional opinion.



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So much this. Thank you. I don't know enough about viruses to know about the likelihood of what they were claiming, but the level of their certainty in the interview made me think - y'all aren't scientists. Real scientists are much more measured.

[WillJ]

At any rate, 70% is pretty good, and if we could get a whole bunch more people vaccinated sooner it would really pay off from the public health standpoint. I don’t know how much vaccine they will get out there and how soon it could be administered, but I strongly believe that anybody waiting for vaccine should not be picky at this point (provided the FDA reviews the data and grants the EUA). Just get whatever they have available as soon as possible. That’s the surest route to getting on the back side of this pandemic.

Perhaps you've addressed this somewhere else in this thread, but can you see any good reason for the FDA not having approved the Astrazeneca vaccine yet? My current opinion that it's criminal negligence, but I'd be interested if you can convince me otherwise."