Thread by @TheMenacheryLab

Let’s talk immunity to #COVID19. I am on record saying immunity may only last 1-2 years based on serum neutralizing antibody (Ab) to MERS and common cold CoVs.

bit.ly/3dQQOJz

Does this mean we could go through this again in a few years? That I am less sure of.

First, while #SARS2 is a particularly successful pathogen, our immune system is fully capable of control.

The vast majority of people will survive because their innate immune system will limit initial damage and their adaptive immune system will provide sterilizing immunity.

This is what happens with almost all pathogens & we generate long term immunity.

While we can not say for sure for #SARS2 cause it has been 4 months since it showed up, I am not willing to say response will defy the normal rules of immunity. It might, but not a bet I’m taking.

How long will that immunity last? This is a question that we do not know the answer to because #SARS2 is new.

We can go from limited data from SARS/MERS/common CoVs. The problem is that there is little data for SARS/MERS (<20K human cases together).

For common cold CoVs, there has been less interest (aka $$$) to study them. They are also harder models to explore and takes more time.

So what do we know?

Well, my comments on 1-2 years of protection is based on serum neutralizing Ab waning in patients. Studies with SARS/MERS/Common cold CoVs finds that serum neut Ab stay high at a year and wane thereafter.

In some patients, serum Ab is no longer neutralizing virus at 3 years. This is seen with MERS-CoV patients. ncbi.nlm.nih.gov/pmc/articles/P…

With SARS1 patients, studies found most people had neutralizing Ab 3 years out, though levels had dipped from year 1. ncbi.nlm.nih.gov/pmc/articles/P…

Common cold CoV neuts wane in that 2-3 year range. Again, all of these studies with common cold CoVs are limited in size and scope.

So in the simplest term, the Ab in your blood may not be able to neutralize #SARS2 in a few years. This in theory means you can get infected with them again because there is no serum Ab to stop infection before it starts.

Does this mean #SARS2 will be back like this again in 2-3 years causing this kind of disease and damage?

Not so fast. It is clear that the neutralizing Ab response in your blood wanes. It is less clear that your immunity will forget these CoVs.

It seems clear that the long lived plasmablasts that supply CoV neut Ab to your blood are not maintained for decades like with other pathogens. This means if you were to be exposed to #SARS2 again, cells can get infected.

But your immune system hasn’t forgotten.

The immune system also stores memory B-cells around the body; some in the tissue of interest (lung), some in the draining lymph nodes, spleen, and even bone marrow. These memory B-cells have the capacity to generate same neutralzing ab as the long-lived plasmablast that wane.

They also can respond quickly, expanding themselves and becoming Ab producing cells and making even more specific Ab.This can take 2-4 days to happen.

The big difference from your first exposure? The Abs they make are already primed and specific for #SARS2.

Instead of 4-6 weeks to make very specific/powerful Ab, you can have them in < 1 week.

What this means is yes, you can be infected again. But, your immune response makes a ton of specific Ab that should limit the infection just days after it starts.

This means less damage and infection; the type of disease would be expected to be limited and much less severe. It also means these reinfected people are less likely to keep spreading the virus due to more immune control.

This in not to mention the role of T-cells, CD4 and CD8. That memory is intact as well and can also respond quickly. While neutralizing Ab is the main correlate for CoV protection, it would be foolish to discount T-cell contributions as well.

So can we be re-infected again in a few years? Yes.

But I don’t think your immunity forgets these pathogens. For CoVs, I think they still have the capacity, but take time to crank them up. This means the next time you get exposed, you might not get as sick.

This premise is discussed in challenge studies with common CoV in this thread by @jbloom_lab

https://twitter.com/jbloom_lab/status/1246547876525658112

The limitation with the assessments is the assumptions based on other CoVs & what we know about long-term immunity.

It is possible that #SARS2 is an exception, and somehow it will come back and do this again. I’m not betting on it.

Given time, my money is on host immunity