Covid-19: Do many people have pre-existing immunity?
https://www.bmj.com/content/370/bmj.m3563/rr-6
Thank you to Dr Doshi for raising the profile of T-cells. Incidentally, German researchers found that a staggering 81% of individuals had pre-existing T-cells that cross-react with SARS-CoV-2 epitopes [1]. This fits with modelling in May by Imperial College’s Professor Friston, a world authority in mathematical modelling of complex dynamic biological systems, indicating that around 80% and 50% of the German and UK populations, respectively, are resistant to COVID-19: https://unherd.com/2020/06/kar…0-not-even-susceptible-to...
Antibodies can only latch onto and help destroy pathogens outside cells and may also occasionally, paradoxically, enhance a pathogen’s ability to infect cell instead by antibody dependent ”enhancement” or ADE. It is only the T-cell that can cleverly sense and destroy pathogens inside infected cells using “sensors” which detect foreign protein fragments.
In the late 60’s the Lancet described a case of a child with agammaglobulinemia, a condition in which absence of B cells prevent them from producing antibodies, who overcame a measles infection quite normally and did not become re-infected thereafter. We now know that, although this condition can compromise immunity, in that particular case the rest of the immune functions, including T-cells, must have been perfectly up to the job of clearing infection and establishing immune memory without help from antibodies. The importance of T-cells in fighting SARS-CoV-1 and establishing immune memory has also been well documented and discussed in a number of pre-COVID papers from 2017 and earlier [2].
Then, early in April, it was reported that two patients with agammaglobulinemia overcame COVID-19 infections without requiring ventilation [3], prompting the Italian authors to write: “This observation suggests that T‐cell response is probably important for immune protection against the virus, while B‐cell response might be unessential”.
All this should have shifted the focus of efforts towards T-cells at an early stage - the real question is why mainstream media and others continued to focus efforts and narrative on antibodies. Is it because vaccines are good at provoking antibody responses but not so great at generating T-cells? Some of the vaccines presently under trial do elicit some T-cells but it seems that neither the quantity nor variety are hugely impressive.
Does this matter? Apparently so: Research establishments including Yale found that in mild or asymptomatic cases, many T-cells are produced. These were highly varied, responding not just to parts of the Spike, S protein or Receptor Binding Domain but to many other parts of the virus [1, 4-6]. Notably, in these mild cases there were few or no detectable antibodies. Conversely, the severely ill produced few T-cells with less variety but had plenty of antibodies. What is also of interest is that men produced fewer T-cells than women, and unlike women, their T-cell response reduced with age [7].
So why are some people unable to mount a good protective T-cell response? The key to this question might be a 10-year-old Danish study led by Carsten Geisler, head of the Department of International Health, Immunology and Microbiology at the University of Copenhagen [8]. Geisler noted that "When a T cell is exposed to a foreign pathogen, it extends a signalling device or 'antenna' known as a vitamin D receptor, with which it searches for vitamin D,", and if there is an inadequate vitamin D level, "they won't even begin to mobilize." In other words, adequate vitamin D is critically important for the activation of T-cells from their inactive naïve state. The question of whether T-cells might also need a continuing supply of vitamin D to prevent the T-cell exhaustion and apoptosis observed in some serious COVID-19 cases [9] deserves further research
