This is a really big deal. The picture is starting to become clearer. Since I first read the details and early studies from the Diamond Princess I was baffled by the failure of so many people to become “infected”, when they had to have been exposed and by so many people who were asymptomatic and had mild illness. I thought right away that this meant the susceptible population couldn’t be close to 100%. The most likely explanation would be some immune defense. We have seen evidence for this coming to light–particularly the papers on T cell cross-reactivity from infection with other strains of coronavirus. This paper now gives some clear evidence that for the current strain T cells are also a main defense and surveys that only look for antibodies are missing lots of infections. (Medrxiv Paper) You may recall in the last couple of weeks I have suggested that surveys need to start looking for T cell activity as well as antibodies.
I think I have explained before, very likely inartfully, the big picture of the immune system. This is very simplified. In terms of combatting known pathogens, including their close relatives, we rely on “memory” immune cells. These cells include B cells, which mature in bone marrow, and T cells which originate in bone marrow but mature in the thymus. Through a complicated process, these cells are taught to recognize fragments of pathogen proteins when we are originally infected. We maintain a large library of unique B cells and T cells that have that capability, each recognizing certain proteins. When prompted, the applicable unique B cells are capable of producing antibodies to battle a renewed infection by the same pathogen, or a new strain that has the same or similar protein fragments. T cells can both help prompt B cells and, some T cells, appropriately called killer T cells, can actually destroy the pathogen themselves. Both B and T cells can also call other kinds of immune system cells in to help with the fight. We generally think of antibodies as the main weapon, but the fact is that T cells can be equally or more important in some cases. That appears to be so for many coronavirus infections.
The researchers in this study were intrigued by several cases where an index patient was part of a family in which other individuals had symptoms, but were negative for antibodies. They tested the nine index patients and the eight contacts, as well as ten unexposed controls. Three different antibody tests and one assay for T cells were used. Cross-reactive T cells to earlier coronavirus strains were also looked for. The index patients all had a mild illness and all had antibodies and a significant T cell response detectable for the duration of the study, up to 69 days later. Six of the eight contacts reported symptoms, but non had detectable antibodies. These persons did, however, develop a strong T cell response against multiple coronavirus proteins, that lasted up to 80 days after symptom onset. Their T cell response was as strong as that of the index patients, but directed toward fewer protein fragments.
It gets cooler (okay, I am a science nerd). All the patients and all but one of the healthy donors also had T cells reactive to two common pre-existing coronavirus strains. This confirms recent studies finding this cross-reactivity. The biggest implication is that antibody tests alone are likely missing a large number of infections. So not only do we need widespread antibody testing, we need some population T cell testing as well. And, there are likely many people who are not getting infected because they have a pre-existing immune defense.
And once again, the authors reference prior similar results in regard to other viruses, which makes me ask, what is wrong with most of our epidemiologists and immunologists that they seem incapable of bringing this knowledge to bear early in the epidemic, when it could have been used to do very fast studies that would have told us the susceptible population was not 100%?