Thread by @profshanecrotty

A thread on current understanding of natural immunity to SARS-CoV-2 🧵

Immunity to SARS-CoV-2 is a key issue for global society. Natural immunity to SARS-CoV-2 (obtained by infection) and vaccine-generated immunity to SARS-CoV-2 are two different paths to immunity.

Based on our team’s SARS2 immune memory measurements (memory T and B cells & antibodies) we predicted natural immunity against serious cases of SARS2 reinfection would last multiple years in most people, against the original SARS2 strain. Back in Nov-Jan.

science.sciencemag.org/content/371/65…

It looked like natural immunity wasn't perfect, but it was probably good and was likely to last a long time for protection against serious COVID, for the original strain.

https://twitter.com/apoorva_nyc/status/1328751557719040001?s=20

Our summary of that paper is in the linked thread.

https://twitter.com/profshanecrotty/status/1346846639160365056?s=20

What have we learned since January?
In brief:
🔵 Antibodies are present for over a year
🔵 Immune memory begins to stabilize by six months
🔵 Memory B cells possess a diversity of specificities against SARS2 variants

Luckily, pro @apoorva_nyc wrote on this!  (and wrote better and got great quotes from @TheBcellArtist @NussenzweigL @JenGommerman @SCOTTeHENSLEY @PepperMarion!). Read her excellent article.

https://twitter.com/apoorva_nyc/status/1397604475125354496?s=20

My brief summary of all of these updates since the beginning of 2021 is below.

1st: Antibodies are present for over a year post-infection. Several studies, include one with >95% antibody positive.

dx.doi.org/10.1101/2021.0…
dx.doi.org/10.1101/2021.0…

And a beautiful study by Ali Ellebedy @TheBcellArtist provides a clear mechanism for the longevity of the antibody responses, as long-lived plasma cells are detected in patients.
dx.doi.org/10.1038/s41586…

2nd: Ahmed and McElrath have an outstanding study of longitudinal memory kinetics, showing stabilization over time.

https://twitter.com/profshanecrotty/status/1389310300038463490?s=20

3rd: Memory B cells possess a diversity of specificities against SARS2 variants.
Your immune system is highly evolved to deal with variants. Memory B cells are part of that.

People who have had COVID don’t have great antibodies against the variants with the most antibody escape (e.g. B.1351, P.1). That is definitely a hole in the natural immunity armor.

Memory B cells are quiescent and have two major functions. One is to produce identical antibodies upon reinfection with the same virus. The second function is that memory B cells encode a library of antibody mutations—immunological variants.

These diverse memory B cells, created in response to infection, look to be pre-emptive guesses by the immune system as to what variants may emerge in the future. This brilliant evolutionary strategy is observed clearly for SARS-CoV-2 with antibodies from human memory B cells.

This outstanding study from @NussenzweigL shows this well.  A substantial frequency of memory B cells encode antibodies capable of binding or neutralizing VOCs. And the quality of those memory B cells increases over time.
dx.doi.org/10.1101/2021.0…

Also, the dramatic increase in variant-neutralizing antibodies after vaccination of previously SARS-CoV-2—infected persons reflects recall of diverse + high quality memory B cells generated after the original infection. The Wherry lab study supports this.

https://twitter.com/rishirajgoel/status/1382788093107867648?s=20

All of that immune memory data above, after SARS2 infections, is consistent with a range of observational cohort studies that have reported natural immunity against symptomatic infection (COVID-19) to be 93-100% over 7-8 months.