COVID-19 Analysis from Jennifer Christian, M.D., M.P.H.

September 21st, 2020 by Tom Lynch

I have written before of my great admiration for Dr. Jennifer Christian and for her Work Fitness and Disability Roundtable (WFDRoundtable@groups.io). The Roundtable is a mainstay for clinicians and other health care professionals.

I thought this morning’s Roundtable post by Jennifer to be particularly thoughtful and thought-provoking, so I asked her if she would allow us to republish the post in its entirety here at the Insider. She very kindly gave permission.

I think Jennifer is one of those brilliant three or four folks I’m lucky enough to know who think around corners. Her mind makes intuitive leaps where others (like mine) plod along.

Here is Jennifer’s post:

How many people have some pre-existing immunity to COVID-19

There is growing uncertainty about what this fall and winter is going to look like with regard to the COVID-19 pandemic.  Are we going to have a second, and possibly even bigger wave of worldwide infections — or is the biggest part of this pandemic over and done with once each geographic area has had its first wave?

A new review from the British Medical Journal says researchers may have been paying too much attention to antibodies and too little attention to a second part of the human immune system that protects against and reacts to infections:  T cells.   More on this in a moment…..

But first, a reminder.  We are in the middle of the first large-scale pandemic with a new and highly contagious respiratory pathogen since the field of immunology was born!   Immunology is still quite young compared to other specialty areas in biological science and medicine.  It was only in the mid-20th century that advances in cell biology started making it possible to study the detailed processes that make up the immune response in detail.  That has led to much deeper understanding of the mechanisms by which vaccines work, to the development of the first cancer chemotherapy agents that selectively killed rapidly-proliferating immune cells, and to the development of immune-modulating drugs, which enable the transplantation of organs by muting the body’s natural rejection of foreign tissues.

The appearance of HIV/AIDS in the 1980’s again precipitated huge leaps in funding for research to increase our understanding of the immune system, which in turn highlighted the function of T cells and other previously unrecognized aspects of it.   However, in comparison to other bodily systems and organs, our knowledge of the human immune system is still primitive — it’s obvious there is much left to learn — and some of what we don’t know may seem very basic!

If you’re an immunologist, virologist, epidemiologist — or a public health officer trying to figure out how to protect and guide your local population — this is the overwhelming challenge of a lifetime.  Personally, I hope that the media and the general public will remember that this pandemic has attacked our society at the very edge of what is known.  All of those professionals are working at a feverish pace to observe carefully, assemble enough data to be confident they have enough to detect a real pattern if it’s actually there, make sense of what they are seeing, and then figure out the implications for action.  Let’s agree to be forgiving of the fact that “the facts” have not all been revealed to us yet, and “the scientists” simply don’t yet know everything we wish they did.

Back to the T cell story.   Researchers have shown that people with the most severe cases of COVID-19 (the ones in ICU and who are most likely to die) often have low T cell levels.  But some other puzzling data has appeared. For example:

  • some countries — and especially some areas within those countries that had bad initial outbreaks — have not seen widespread new infections despite having relaxed protective restrictions; and,
  • blood tests in a noticeable fraction of people with no record of exposure to SARS-CoV-2 virus show some of the T cells reacting weakly to it anyway — indicating a potentially partial immune response.

This has led scientists to start wondering whether we really know enough about the human immune system’s ability to develop partial T cell “cross-reactivity” to families of closely-related viruses and whether that might predictably and reliably reduce the severity of illness or even reduce the likelihood of getting ill at all when a new-but-related virus appears.   And, that, of course, raises some possibilities that need to be investigated:

  1. Does cross-reactivity explain why some geographic areas that had first pandemic peaks are not seeing second ones — because the people who got sick had no immunity and were more susceptible, and most of the remaining ones have some limited immunity which is protecting them?
  2. Does cross-reactivity explain some of the disparity between people who get deathly sick from COVID-19 and people who are exposed to the virus but never get infected, or, if they do, remain asymptomatic or have only mild illness?  Note that there are two  possibilities:  Cross-reactivity could be making the illness worse or it might be making it less severe — we don’t know yet.
  3. How could cross-reactivity be protective if it develops after prior exposure to coronaviruses, because children are the least likely to get a severe case of the disease and adults are the most susceptible to severe COVID-19 illness and death?  (Children have not had a lifetime of colds, and thus less opportunity to be exposed to coronavirus and develop partial-immunity to SARS-CoV-2)

In short, my best advice as of 21 September 2020 is:

  1. Stay tuned for further developments in the factual realm – both changes in case counts and new research results;
  2. Hope for the best but prepare for the worst as autumn approaches and we all retreat indoors.

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