COVID Transmissions for 12-8-2020

Vaccine Monday is still a thing, apparently!

Good morning! It has been 387 days since the first documented human case of COVID-19.

The tagline for today’s newsletter is in reference to an influenza virus vaccine paper that came out today in Nature Medicine, showing success in a Phase 1 clinical trial of a “universal” influenza vaccine design. If it continues to succeed in clinical trials, this new design could turn the flu shot into something that you only need to get once every 5 to 10 years. It’s not, however, COVID-related. But I’m happy to share a link to the paper if folks are interested.

As for COVID-19, we will cover some reader comments and headlines in today’s issue.

As usual, bolded terms are linked to the running newsletter glossary.

Keep the newsletter growing by sharing it! I love talking about science and explaining important concepts in human health, but I rely on all of you to grow the audience for this:

Now, let’s talk COVID.

---

Pfizer won’t have more doses of vaccine for the US until June

Apparently, so many other countries have purchased vaccine doses from Pfizer that they have exhausted their supply and manufacturing capacity through June or July of 2021. That means that the US won’t be receiving more doses until then, of that particular vaccine.

The Washington Post has the story here: https://www.washingtonpost.com/health/2020/12/07/pfizer-vaccine-doses-trump/

Now, the US has access to doses of other vaccine candidates as well, and did purchase a small stockpile of the Pfizer vaccine, so this may not be as big a deal as it sounds initially. Later on in 2021 we may start to see vaccine supplies get a little more thin, but it’s possible that Operation Warp Speed will help us deal with that via other vaccines. We shall see.

Children are not usually the source of household COVID-19 clusters

A study published in Clinical Infectious Diseases looked at 213 reports of household COVID-19 clusters: https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1825/6024998

Of these, only 3.8% had a pediatric case of COVID-19 as the “index case”; that is, the case that started the cluster. This suggests that children are only rarely the source of household COVID-19 outbreaks, but we should be cautious because children are less frequently outside the home independently, at least in many countries.

However, the study also shows that the “secondary attack rate” in children was also lower than in adults. That means that the odds were lower that a child would become infected if there was a cluster in their household than the comparable odds for an adult in such a household. This offers some indication that children are less susceptible to infection as well.

This isn’t the first time we’ve seen evidence of this, but this gets more interesting to me the more I see it. Why is this the case? I suppose we will find out.

---

What am I doing to cope with the pandemic? This:

Dr. Atomic

Tonight, December 8th, the Metropolitan Opera’s free live stream will include the contemporary opera Dr. Atomic, by John Adams and libretto by Peter Sellars. It happens to be the first opera that I ever saw at the Met, thanks to a friend who I know reads this newsletter.

Image is a poster for Doctor Atomic, in black and white, showing a mushroom cloud explosion. In a military-style stencil font, the name “John Adams” appears at the top, with the title “Doctor Atomic” appearing in the lower third of the image. Below the title, the phrase “Opera in two acts” is written in a typewriter font.

Dr. Atomic is an opera about the Manhattan Project that invented the first nuclear weapons. It’s quite an experience, and I recommend checking it out.

---

Lots of comments in response to yesterday’s newsletter!

First, we have Carl Fink again:

So, as long as you encourage questioning ...

You wrote, "This has a lot of implications. If the vaccine prevents disease in 95% of people, but it cannot impact transmission, what is the effect on the 5% of people in whom the vaccine isn’t all that effective? Must they remain inside…forever?"

There's a big assumption in there ... that you know you are one of the 5%. It might be possible in principle (by measuring antibody and t-memory cell levels) but in practice, almost nobody outside research studies will get those tests after a vaccination.

So in practice ... the 5% will get SARS-CoV-2. And a fraction of that 1/20 (say, 1%) will get serious disease. It's an imperfect world. Note that the Moderna vaccine, at least, seems to prevent nearly 100% of serious disease in the tested population--all the serious cases were in the placebo arm.

I think Carl makes some great points here, so a lot of my reply is just adding some elucidation of them:

I totally agree with you that this is a big assumption. From early on in the vaccine studies, I have kept a close eye on--and frequently mentioned here--the need for an understanding of "correlates of protection," the measured quantities that are correlated with protection against disease. These are not known for COVID-19, however we do have a sense of the totality of the natural immune response from several studies, some of which I've covered here.

Understanding the correlates of protection will also be an essential piece of information that should appear in papers from these vaccine trials, though it may not be totally apparent at first.

That said, let's assume that we do get a clear picture of them. Tests to detect correlates of protection won't be difficult to administer, and I have a feeling they will be widely offered due to popular demand. People who get this vaccine will want to know if it worked for them, and it should be possible to confirm that with a simple blood draw. Such tests are pretty routine for assessing protection against viruses like measles; you may have had one done at some point in your life and not even remember it.

I do think you're right that most people won't pursue getting such a test, but the reality is we can only make it available, we can't force its use to confirm vaccination success. Should such a test come about, it will probably become mandatory as a condition of employment for some workers, though--likely hospital workers at the least. Still, if the test is at least available, it offers the opportunity for people who are at risk for a weak immune response to pursue testing to understand if their vaccination succeeded or not. That should, at least, create the opportunity to make an informed choice.

Ultimately though this is all predicated on us figuring out the correlates of protection. I have faith we'll get there, but it may not be so quick.

Regarding the prevention of severe disease...given the small number of events in the trials, I'm a little skeptical of their ability to predict impact on severe disease. We are talking about very small numbers of severe disease cases compared across the trial arms, so it is quite difficult to be certain if those results will bear out across billions of patients. I do expect some protective effect but I don't think 100% is realistic. Systemically, that protective effect will make a huge difference, but somehow I do not think that fact will be a great comfort to any vaccinated patient who ends up getting severe disease anyway.

Anyway, you're 100% correct that I'm making an assumption here--that in some way we'll be able to profile and identify the patients who do not obtain protection via this vaccine. It could be we'll never figure it out. We'll have to see.

Next, we have a comment from frequent commenter Robert Berger:

You note that the CDC recommendation regarding mask wearing is long overdue, and should have happened in April. You "imagine that there were political reasons that it did not." I believe you may have forgotten that there were technical and logistical, not political, reasons that it did not. First, back in April, the general consensus was that only N95 masks could effectively protect people from getting infected. Second, there was no published premise, as yet, that wearing masks could prevent the wearer from infecting others. And finally, there was a concern that if a mask mandate or recommendation were issued, it would result in a rush to horde whatever N95 masks remained in what was, at that time, a very limited supply that was sorely needed by front line workers.

I don’t agree with Robert’s narrative here, and you’ll see that in my reply, but I still appreciate his comment. He’s not wrong that there were issues of shortages of medical-grade masks. But I don’t think that’s what stopped a national mask mandate in April. Here’s my reply:

Hi Robert. Thanks for your comment as always, but I think you've overinterpreted the statement.

There was no logistical consideration that interfered with the ability of cloth masks to be deployed in April. I chose that timing deliberately, because it was in April that it became apparent that makeshift cloth masks were a viable measure for limiting the transmission of disease. For what it's worth, this was apparent before, but for a variety of reasons some wrong-headed thinking was applied to the question of mask-wearing by folks inside the public health community before this time.

On April 15th, 2020, Governor Andrew Cuomo of New York issued an order that required mask-wearing, based on examples from Southeast Asia where such policies were correlated with control of COVID-19 outbreaks. It's not correct that there "was no published premise." By April 16th, there was sufficient published evidence to support this commentary on mask-wearing, published in The Lancet: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30918-1/fulltext

That's only one example of the various scientific arguments that were made for masking in April; there were many, and all of them based on evidence. I agree the evidence was limited.

While the evidence collected in that commentary was not definitive, the benefit-risk calculation pointed to an obvious and immediate need for such a mandate. There was no cost to a mask wearing requirement in any meaningful way, and the potential for benefit was quite high. This mask mandate did not call for universal use of N95 masks, but rather the use of any face covering. Face coverings are readily available and haven't had any supply limitations that I am aware of, particularly since the requirement is satisfied by even a makeshift cloth covering.

Supply concerns regarding N95 masks were an issue during the months of April and March in NYC. That doesn't impact the need for a mask mandate going back to April. In fact, we needed that mask mandate even longer than that, but we were painfully unaware of that fact until April, and I do consider population-wide ignorance in the absence of evidence to be a valid excuse. However, I do not consider ignorance in the face of evidence to be a valid excuse, and by April it was apparent that mask-wearing satisfied the simple risk-benefit analysis that forms the basis of evidence-based healthcare policy.

I love to see this level of conversation happening in the comments thread. It’s great to see and it stimulates a better quality of newsletter for everyone. Thank you again for your comments, Carl and Robert.

You might have some questions or comments of your own! Send them in. As several folks have figured out, you can also email me if you have a comment that you don’t want to share with the whole group.

Join the conversation, and what you say will impact what I talk about in the next issue.

Also, let me know any other thoughts you might have about the newsletter. I’d like to make sure you’re getting what you want out of this.

---

This newsletter will contain mistakes. When you find them, tell me about them so that I can fix them. I would rather this newsletter be correct than protect my ego.

Though I can’t correct the emailed version after it has been sent, I do update the online post of the newsletter every time a mistake is brought to my attention.

No corrections since last issue.

See you all next time.

Always,

JS