COVID Transmissions for 9-3-2021
Greetings from an undisclosed location in my apartment. Welcome to COVID Transmissions.
It has been 654 days since the first documented human case of COVID-19. In 654, King Reeceswinth created the Liber Judiciorum, a code of law for Visigothic Iberia that declared equality between Goths and Hispano-Romans; this was a relatively big step forward, since these nationalistic distinctions were still formalized in several other legal codes in neighboring kingdoms.
Today we’ll discuss some basic science work that may help us better understand what elements of the immune response to SARS-CoV-2 actually mean you’re protected from it. This kind of work could eventually get us a test that a person could take that would tell them if they’re really protected. Have a great weekend!
Housekeeping note: Next week’s COVID Transmissions schedule will be altered slightly to account for Labor Day and Rosh Hashana. There will be an issue out on Tuesday September 7th (prewritten and scheduled, since I will be celebrating Rosh Hashana) and another issue that goes out on Thursday September 9th. Jewish holiday-related disruptions for the remainder of the month of September will likely be minimal, but there is a possibility I will skip the September 17th issue if Yom Kippur this year hits me a little too hard.
Bolded terms are linked to the running newsletter glossary.
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Now, let’s talk COVID.
Mouse model insights into COVID-19 immunity
Earlier this week, I discussed how we do not currently have a good sense of how immunity against COVID-19 is generated from the various parts of the immune system. Now I’m happy to share some basic science work that starts to get us closer to an answer: https://www.science.org/doi/10.1126/sciimmunol.abl4509
This paper is pretty cool; its first author is someone I was in grad school with, and I’m glad to see him continuing to do great science. In this work, a mouse model for SARS-CoV-2 infection is used to probe the different parts of the immune system to see how they contribute to protection against the virus in this model.
First, we should discuss the different components of the immune system that are of importance here. There is innate immunity, which represents a set of nonspecific sensors and responses. Generally, innate immunity offers delaying action to prevent an infection from taking over, and also alerts the adaptive immune system, which includes things like antibodies and T cells.
T cells are generally divided into two broad classes, called CD4+, which are cells that modulate broader immune responses, and CD8+, which are cells that go out and kill virus-infected cells. B cells, meanwhile, produce antibodies, often working in tandem with CD4+ T cells.
This study dissected each component of the immune system I’ve just mentioned. Using mice that have no adaptive immunity at all, they showed that innate immunity alone is not enough to control SARS-CoV-2. Then, using experiments where CD8+ and CD4+ T cells were variously inhibited, they demonstrated that both of these cell types can contribute to defense against the virus. They were also able to look at a strain of mice that cannot produce antibodies; in these mice, the CD8+ T cells, which do not generally interact with the antibody system, were more important for controlling the virus than the CD4+ T cells, which have important interactions with antibody-producing cells.
This gives a picture that each component of the adaptive immune response can have an important impact on controlling SARS-CoV-2 infection. To further suss out how each component contributes, the authors tried transferring cells and antibodies from mice that were immunized to mice that were not capable of mounting an adaptive immune response. In these experiments, they found that both T cells and antibodies could provide control of SARS-CoV-2, but they also found that the antibodies were particularly effective at controlling infectious virus.
This suggested to them that immunity to SARS-CoV-2 might be driven by antibodies alone in their model. To test that, they tried immunizing mice using an mRNA vaccine, and then showed that higher antibody levels directly correlated with survival when those mice were later infected with virus. This suggested that, in their model, antibody levels are a correlate of protection. T cells, they found, were relatively dispensable in mice that had been mRNA vaccinated.
The authors suggested that the reason that antibodies were so important is that in the vaccination condition, the antibody response was so overwhelmingly good that the T cell responses were not needed. They also determined that vaccination produces a rather limited T cell response in their model.
Now, this model is a mouse model, and I don’t think we can directly relate it to humans, but it generates a solid hypothesis that antibody levels could indeed be a correlate of protection for human immunity to COVID-19 as well. In light of that, there is much work to be done, because it is not enough to know that something can serve as a correlate of protection—for it to be a useful one, we would also want to know exactly what level of antibodies correlate with protection from disease or infection.
There’s more to be learned here, but through this basic science work we can begin to understand what elements of the immune response are directly relevant in protection from COVID-19.
What am I doing to cope with the pandemic? This:
Tabletop RPGs!
Being able to have small gatherings at home with other vaccinated people is a huge step forward for quality of life, even if I still need to be masked when indoors in public. As I’ve said before, I’ve gotten back to tabletop gaming with friends. Last night I held a session for the Star Wars roleplaying game, where a group of my friends played characters who are, effectively, the Star Wars version of Nazi hunters, going after war criminals to (hopefully) bring them to justice. It was a lot of fun, and a great way to just spend some time with people—something that is incredibly precious, as we all know from our experiences throughout this pandemic.
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.
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Part of science is identifying and correcting errors. If you find a mistake, please tell me about it.
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. And don’t forget to share the newsletter if you liked it.
Always,
JS