COVID Transmissions for 7-23-2020

Jul 23, 2020

Greetings from an undisclosed location in my apartment. Everything outside is rain.

It has been 249 days since the first documented human case of COVID-19.

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Now, let’s talk COVID.

Naturally, vaccines are at the top of the list for today’s headlines once again. Later on, the in-depth piece looks at some evidence that vaccines will actually be able to protect us against infection.

Who will be vaccinated first:

STAT news reports that there is mounting confusion over who is responsible for identifying the groups in the US that should be prioritized for vaccination when a vaccine becomes available. Several different entities are making recommendations, as reported here: https://www.statnews.com/2020/07/22/confusion-spreads-over-system-to-determine-priority-access-to-covid-19-vaccines/

US commits to buying vaccine doses:

Buried under a bunch of other stuff in this article from CIDRAP is some useful information: https://www.cidrap.umn.edu/news-perspective/2020/07/covid-deaths-climbing-us-inks-deal-vaccine-doses

Specifically, that the US has made an agreement—which when I was a public health person was called an “advance market commitment”—to purchase 100 million doses of the Pfizer-BioNTech vaccine, in the event the vaccine proves both safe and effective. The deal offers the option to purchase an additional 500 million doses as well.

Inside the coronavirus:

Scientific American put together a really, truly excellent animated walk through of the structure and life cycle of SARS-CoV-2. It explains a lot of the basic biology of the virus-host interactions, from entry to replication and exit, as well as the immune responses. It also walks through which parts of this process are potential drug targets. Highly recommended: https://www.scientificamerican.com/interactive/inside-the-coronavirus

Making indoor air safer:

FiveThirtyEight ran an article on filtration methods for air movement systems that might make it safer to have indoor, in-person get togethers without causing virus outbreaks. I don’t know exactly what I think about their recommendations, but I do think the topic is something we need to be talking about: https://fivethirtyeight.com/features/how-to-make-indoor-air-safer/

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

Reading

I just got the next two books in the Southern Reach trilogy by Jeff Vandermeer. In an earlier issue I recommended the first book, Annihilation. I’ll let you know how the other two shape up.

Cooking

I played around with the idea of beet fritters, to this result:

It’s not the prettiest thing I’ve ever made in my life, but the flavoring came out nicely. I shredded about 2 pounds of beets and pureed one sweet potato for the mix. Added some garbanzo flour as a binder, salt, paprika, and five spice, then formed little patties and pan fried these in oil for about 3-4 minutes a side. I thought I could get away without egg as an additional binding agent because the beets and sweet potato would be sugary enough to caramelize and hold together; I was right, they did…until I attempted flipping them. So next time, I think egg is going to go in. I’ll keep working on these, I think, until I have a reliable result to share. That said, these tasted great, especially topped with horseradish.

What does “immune” look like?

A key problem that we’ve touched on in a previous in-depth article is the lack of correlates of protection for COVID-19.

Some of our best evidence regarding immunity right now comes from work done in monkeys. Specifically, rhesus macaques, a model animal that is commonly used in virology and other biological studies. Before describing this work, I have to remind you of an old saying in biological sciences: “Mice lie, monkeys exaggerate.”

This is not a human. Image is of a rhesus macaque monkey sitting on a low concrete wall, in side view, with its head turned slightly to face the camera. Vegetation fills the background. Image from Md. Tareq Aziz Touhid on Wikimedia commons: https://commons.wikimedia.org/wiki/File:Rhesus_Macaque_monkey_look.jpg

Model animal systems are just models. Humans are not the same as monkeys, and we should expect differences between how each species mounts an immune response to the virus. That said, animal model experiments can be very informative and they allow us to do experiments that wouldn’t be ethical in humans.

For example, we can infect or immunize monkeys, allow them to develop an immune response, and then “challenge” them with new exposure to the virus to see if they are protected. This type of experiment has been performed, in fact. In a paper published in Science in May: https://science.sciencemag.org/content/early/2020/05/19/science.abc4776

In this paper, the researchers first challenged 9 “naïve” macaques; this means they hadn’t been exposed to the virus before, and then measured their immune responses. They found that the subjects in the study mounted noticeable neutralizing antibody responses. They also did pathology investigation on the lungs of some of their subjects, showing that infection with the virus resulted in meaningful evidence of pneumonia. In other words, they saw that monkeys got a COVID-like illness when infected, and that they also had an immune response to the virus. Those are two very important points.

Then they re-challenged their macaques after they recovered from the initial virus infection, and they saw that virus genome counts recovered from the lungs of re-challenged monkeys were a lot lower overall than when the monkeys were first exposed to the virus:

Image is three charts, each showing copies of virus RNA per mL in monkeys; the leftmost chart shows levels over time in the primary challenge (the first time the monkeys were exposed); in this chart there are high levels of virus RNA present in the first 7 days, they fall by day 14, and by day 21 have mostly resolved. The middle chart shows levels of virus RNA in the same type of sample from the same monkeys, on their second exposure to the virus. Here, levels of RNA drop to zero before Day 7. The rightmost chart shows an average (red line) of the peak RNA level during the primary challenge and then the re-challenge. The re-challenge levels are significantly lower. Image adapted from Science magazine.

This is a very important experiment because it is definitive evidence that the monkeys were protected following their recovery from initial infection. It’s possible that this isn’t true in humans, but so far what was seen in the monkeys aligns with what we have seen in humans—evidence of lung pathology, evidence of an immune response upon recovery.

The same group published a vaccination study in rhesus macaques in the same issue of Science: https://science.sciencemag.org/content/early/2020/05/19/science.abc6284

This offers us the opportunity to look at whether vaccination produces similar results as infection, in terms of protection from a future challenge with the virus. We can’t do this study in humans for ethical reasons; people could, maybe even would, die.

In these experiments, the authors had 7 conditions for their experimental monkeys. One group of monkeys received a “sham” vaccine that had no SARS-CoV-2 components. The other 6 groups received DNA-based vaccines based on parts of the SARS-CoV-2 S protein. The fact that these are DNA-based vaccines is very interesting because this is similar to the mRNA-based strategy that is being used by companies like Moderna in their quest for a human vaccine.

Here’s what the sham group looked like, in the same kind of data as I showed from the other paper:

Image shows virus genome copies in sham-vaccinated rhesus macaques over time; an early increase in copies per mL is followed by a slow decline. Image adapted from Science magazine.

No surprises there—we see a jump in the number of virus genome copies early on that slowly drops off. These monkeys are not protected; this graph looks a lot like the “primary challenge” graph from the other paper.

What about the vaccinated monkeys? Let’s look at them:

Image shows, again, virus genome copies in rhesus macaques over time. In this image there are 6 graphs, all representing a different vaccination group that received an active, anti-SARS-CoV-2 DNA vaccine. Each graph shows a smaller overall count of virus genome copies (by at least 1 order of magnitude), as well as a faster time until virus genome copy levels are negligible. Image adapted from Science magazine.

I’m skipping over what each of the different vaccine options were; it’s not really important to the point we are trying to understand here. Instead, let’s just notice that these graphs all look a lot more similar to the “rechallenge” graph from the other paper than they do to the “primary challenge” graph. These monkeys were protected.

The reason I am walking through all of this is that these two studies showed immune responses in their subjects, and showed that these immune responses were correlated with protection. In the vaccine papers that we looked at earlier this week, similar types of immune responses were documented in humans, but as mentioned, it would not be ethical to intentionally infect people with COVID-19 to produce data like the above in humans.

However, we know this:

Rhesus monkeys have an immune response to infection, and an immune response to vaccination, that look similar
Rhesus monkeys that were vaccinated appear to be protected in a similar fashion as rhesus monkeys that were previously infected
Humans also have an immune response to infection and an immune response to vaccination that look similar

It would be reasonable, then, to have the hypothesis that human beings who are vaccinated might be protected in a similar fashion as humans that were previously infected. Note that I say “hypothesis” because we have not demonstrated any real protection yet in humans. However, we can use the animal model data to make the educated guess that humans are likely able to acquire vaccine-induced protective immunity against COVID-19.

The next big question is this: “How long does immunity last?” I’ll be covering that in a future in-depth piece. For now, let’s take comfort in the fact that our close monkey relatives have given us a reason to be hopeful for the prospect of a successful vaccine trial.

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

Also, I welcome any feedback on structure and content. I want this to be as useful as possible, and I can only make that happen with constructive comments.

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