COVID Transmissions for 2-25-2021

Feb 25, 2021

Good morning and welcome to COVID Transmissions.

It has been 465 days since the first documented human case of COVID-19. We are 100 days into the second year of the COVID-19 pandemic.

Please note this will be the last issue of COVID Transmissions for this week. The Jewish holiday of Purim is on Friday, and I am taking the day off from work, including the work I do on this newsletter. I will be back on Monday, which I am told will be part of the month of March, a month that I’m not sure we ever really left, back in 2020. Hopefully this March will be a month of renewal and new growth, as it should be, as we gain increasing control over the pandemic.

Today we’re going to be science wonks, and look into some interesting scientific topics about COVID-19. Also, a reader comment that applies some critical review—a key scientific process—to a story I shared yesterday.

I’ve also included a headline that has some practical applications—where the author reviews research into whether a person who has had COVID-19 still needs a full two-dose course of certain vaccinations.

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

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Now, let’s talk COVID.

Understanding virus evolution in Austria

OK, I will begin by confessing I am still reading through this preprint. I am sharing it because I think it is interesting, but I am not endorsing its content scientifically. That said, I don’t think it has much practical impact. It’s just cool.

The authors here looked at sequence information to figure out the “size” of the “genetic bottleneck” in SARS-CoV-2 transmission. What they mean is this: how many different genome sequences are involved in the typical transmission event from an infected patient to establish a new infection?

The answer they come to is that it is, typically, fewer than 10 different genome sequences. Considering that a drop of fluid from an infected person’s lungs may contain 10,000 or more virus particles, this is quite a restriction upon the diversity of virus that establishes infections.

OK, John, that’s interesting, but what’s the point?

Well, the point is that each transmission event involves selection, from a potentially large population of input virus particles, of the specific virus particles that will manage to establish the new infection. This is a “genetic bottleneck,” and every virus experiences one. A narrow genetic bottleneck means a lot of selective pressure is applied to the SARS-CoV-2 virus during transmission events. This fact will help us to understand how and why the virus evolves during its transmission chain. It is quite basic science, and may seem arcane, but I foresee potential applications down the road.

Specifically, there may be applications in forecasting the need for vaccine redesigns, or there may be applications in trying to identify common genetic features that make a specific virus particle more likely to be the “founder” of a new infection, versus the other thousands of particles that may make the trip into a new host along with it.

You can read this preprint here: https://www.biorxiv.org/content/10.1101/2021.02.22.432096v1

If you’ve had COVID-19, do you still need as many doses of vaccine as someone who hasn’t?

On Tuesday, Dr. Frances Collins, director of the National Institutes of Health, explored a simple but important question on his blog: is a past immune response to COVID-19 enough to ensure that just one dose of certain COVID-19 vaccines will give you lasting protection?

In this blog post, he cited research by a member of my PhD committee (Dr. Viviana Simon, MD) and a colleague of mine during my PhD, who has since risen to great scientific achievement (Dr. Florian Krammer, PhD).

The results cited are early evidence that one dose of an mRNA vaccine may be enough for patients who have already recovered from SARS-CoV-2 infection. I think Dr. Collins describes it well in his post, so I will just point you over there: https://directorsblog.nih.gov/2021/02/23/is-one-dose-of-covid-19-vaccine-enough-after-covid-19-infection/

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

Reading: Lease Documents

We found a new apartment! This means reading about 80 pages of lease, lease riders, and information that NYC requires landlords to make us read about how to react to various disasters, potentially including terrorism, fires, building explosions, and/or God deciding to punish the sins of humanity, or something to that effect.

Yeah, not exactly a fun update! But, we’re excited to have a new place to live.

Carl Fink made an excellent comment on yesterday’s newsletter that I think is worth all of our attention, regarding the results from SIREN that I shared yesterday:

"The tests performed here were done fortnightly, as mentioned. It is possible to have a full clinical course of COVID-19 in less than 14 days, and I’m sure it’s also possible to have an asymptomatic infection that resolves in less than 14 days."
I tend to read CT early in the morning, while finishing my first cup of coffee. As a result, reading this I thought, "Why didn't they do antibody tests to see if someone was infected?"
And then, "Oh, right, vaccinated."
'However, the really disappointing part is where gender, age, ethnicity, IMD (“index of multiple deprivation", a measure of socioeconomic status/poverty) and staff group also impacted likelihood of getting the vaccine. Basically, this tells me that societal inequality, as well as potentially a false impression of invincibility among younger people, led to disparities in vaccine uptake.'
There's also a frequently-written-about phenomenon that members of some ethnic groups simply distrust the medical system. I have no idea if the UK experiences this to the same extent as the US, with our atrocious (in the literal sense--these were atrocities) history of things like the Tuskeegee Experiment and the Doctor J. Marion Sims inventing gynecology by experimenting on slaves without anesthetic.
Another wrinkle here: everyone in this study (if I read your summary correctly) was employed by the NHS. They certainly varied by SES, but that would inevitably correlate with educational level--in the healthcare business, physicians get paid more than nurses get paid more than nurses' assistants, to name three jobs. Did they correct for that?

I think Carl’s on the money in every single point mentioned here, actually more than he thinks he is, as I note in my reply:

Actually, interestingly enough, the vaccines should not interfere with a person's ability to be tested for COVID-19 antibodies. Specifically, there are antibody tests that target the virus nucleoprotein (N), which is not a vaccine component. So you can specifically differentiate natural immunity from vaccine-induced immunity by this method.
As it happens, SIREN participants are antibody-tested every 30 days. However, this does not appear to have been part of the case definition in the trial and wasn't used for the efficacy data reported here. I don't know why and it is not explained in the paper. I hope it comes up on peer review, because you raise an important point! I wonder if The Lancet accepts public comment on preprints and considers it during peer review. It may be worth communicating this question to them.
On to other matters in your comment: it's quite a shame that the systemic racism in past medical practice has reinforced mistrust. I think you make a very important point there, too.
Indeed, everyone in SIREN is a staff member at a publicly funded UK hospital. The study covers workers from every walk of life; this includes porters and security guards as well. You're right to think about how their monetary compensation and educational level may impact their vaccine hesitancy. The study authors, in the methods section, note that they examined the dataset for potential bias based on demographic factors, but they do not go into detail. I think that your point here, as well, is one that should be raised during peer review.
We see here that it is important to interrogate the content of preprints, because they do contain undetected flaws in logic or omissions. These two comments would likely require "minor revisions" to the piece, because it seems some of the work being requested has already been done, but the authors have not commented upon it in sufficient detail. Minor revisions are what one hopes for when submitting something for publication.

This is good citizen science right here—applying critical thinking to a preprint to understand its limitations.

You might have some questions or comments! 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.

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