It’s the T-cells, Not the Antibodies

By June 30, 2020 Commentary

Hot off the presses yet another T-cell paper that confirms what the one I reported on yesterday says.   (T-cell Paper)   This paper is from Sweden and involved 203 persons, some who currently had coronavirus disease, some who had recovered, family members of confirmed cases who had not tested positive and blood donors who did not have coronavirus infections, some who had donated before the epidemic.  The researchers were looking specifically at T-cell responses.   They also compared those with moderate to severe disease to those with mild or asymptomatic illness.  There was a clear different pattern in T-cell activation between the group with moderate and severe acute disease and the other groups, but all had strong T-cell responses.  For patients with more severe disease, during the disease, T-cells were focused on actually engaging and killing virus.  For other groups, the focus was on developing memory T-cells, which prevent reinfection.  The longer a patient had been recovered from an infection, the stronger the memory T-cell response was.

Among the group who had donated blood before the epidemic, there was a cross-reactive T-cell response aimed at the spike and membrane proteins.  All other groups also showed T-cell activity against COVID-19 proteins, and the strongest response came from those who had experienced severe disease.  When the blood from convalescent patients, exposed family members and health blood donors was tested against the virus fragments, most demonstrated T-cell reactivity, with greater helper T-cell responses than killer T-cell responses.  The researchers then compared antibody and T-cell responses.  Most patients who did not have a detectable antibody response, did have a T-cell response.  The authors summarized “Potent memory T cell responses were therefor elicited in the absence or presence of circulating antibodies, consistent with a non-redundant role as key determinants of immune protection against COVID-19.”  Some of the donors were found to have these T cell responses months after exposure.  The researchers further note that only surveying a population for antibodies will underestimate the extent of population-level immunity.  A very important and positive paper.

This paper tracked the antibody prevalence in New York City during the epidemic.  (Medrxiv Paper)   The researchers were from one hospital system and tracked over 5000 samples from two groups, one of which was representative of the community and one which was more representative of people with confirmed infections.  Positive tests began as early as February and accelerated in both groups in late March.  Almost 20% of the community group was positive by April 19, which the authors said was well below population immunity, but which we know actually probably significantly understates the infection rate, since it does not include T cell responses, which if the recent papers are right, would at least double the prevalence shown by antibody studies, and since it doesn’t take into account variation in susceptibility or infectiousness.  Astoundingly, however, the positive rate in the  likely exposed group for the week ending April 19 was 58%.  (not the cumulative rate, just the rate that week)  This suggests a very large number of infected people who didn’t realize they had been infected several weeks earlier.  I think NYC probably is not seeing any resurgence of cases because it has enough population immunity and pre-existing cross-reactivity to drastically slow transmission.

So just as I have hypothesized about the course of the epidemic in Minnesota and in general, let me hypothesize about New York.  The virus was almost certainly circulating in that state, especially the NYC metro area by December and January.  It was largely affecting working age and young people, who simply don’t have many cases of serious illness.  A large percent were likely infected, and T cells, not antibodies, were the predominant adaptive immune response.  Then, as awareness of the potential epidemic was arising, the virus started getting into nursing homes and other group living settings and reached other frail elderly and panic set in.  The virus ripped through these vulnerable groups, raising hospitalization and death rates.  The lockdown and policies like putting recovering patients in nursing homes actually exacerbated the situation.  The lockdowns almost certainly had little to do with stopping spread because the virus had already peaked and was finding fewer and fewer targets.  And today, even if NYC fully opened up, I would suspect no significant surge in cases would occur.  So Governor Cuomo, another verbose buffoon like a similar leader we may be familiar with here in Minnesota, did a horrific job, ignoring the potential epidemic and encouraging visitors for weeks longer than he should have, leaving mass transit open, does nothing for long-term care residents and actually jeopardizing their safety, but lucks into population immunity faster than most other states.  And he is taking bows for having the highest death rate in the country.  Nice work if you can get it.

And here is another study which can now be recognized as flawed for failure to consider the role of T cells.  (Medrxiv Paper)   The authors wanted to see if prior infection with seasonal coronavirus in children provided antibody protection against the current strain.  The looked to see if antibodies to those common strains were more prevalent in children who didn’t get COVID infection than in those who did.  They said they weren’t.  Since we know that T cells are more common adaptive or lasting immune system protection for coronavirus infection, they have likely missed the differentiator.  They also likely missed some antibodies, as they tested a limited set of protein fragments.

Join the discussion One Comment

  • Matt R says:

    Very interesting, thanks for the continued great work! Hopefully Sweden get’s back in the news and revisits the concerns about tracking towards population immunity. Looking at Worldometers, they look basically ‘done’ with the disease; if they top out at around 550 deaths per million, will be less than many U.S. States and Euro Countries that went full on lock down. As other jurisdictions keep catching up on that metric, hopefully a lesson will be learned and remembered… at least for a generation or two. I wish I could say I’m optimistic that it will.

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