Substack cometh, and lo it is good. (Pricing)

A possible reason for inter-regional differences in COVID-19 prevalence?


There have been striking differences in COVID-19 severity/penetration by region. There are all sorts of reasons posited. This post from Derek Lowe at In The Pipeline, New Data on T Cells and the Coronavirus, suggests a possibility:

And turning to patients who have never been exposed to either SARS or the latest SARS CoV-2, this new work confirms that there are people who nonetheless have T cells that are reactive to protein antigens from the new virus. As in the earlier paper, these cells have a different pattern of reactivity compared to people who have recovered from the current pandemic (which also serves to confirm that they truly have not been infected this time around). Recognition of the nsp7 and nsp13 proteins is prominent, as well as the N protein. And when they looked at that nsp7 response, it turns out that the T cells are recognizing particular protein regions that have low homology to those found in the “common cold” coronaviruses – but do have very high homology to various animal coronaviruses.

Very interesting indeed! That would argue that there has been past zoonotic coronavirus transmission in humans, unknown viruses that apparently did not lead to serious disease, which have provided some people with a level of T-cell based protection to the current pandemic. This could potentially help to resolve another gap in our knowledge, as mentioned in that recent post: when antibody surveys come back saying that (say) 95% of a given population does not appear to have been exposed to the current virus, does that mean that all 95% of them are vulnerable – or not? I’ll reiterate the point of that post here: antibody profiling (while very important) is not the whole story, and we need to know what we’re missing.

It seems that later we will find out that perhaps the Vietnamese benefited from some immunity conferred by a previous asymptomatic coronavirus outbreak? If you’ve been following Spencer Wells (more specifically, here, here, and here on the general hypotheses) on Twitter you know he’s been suggesting this for several months. The pattern seems to extend to neighboring nations too.

8 thoughts on “A possible reason for inter-regional differences in COVID-19 prevalence?

  1. Could cat owners have milder SARS-CoV-2 infections due to their prior contact with feline corona viruses !?

  2. In my country (Argentine) I’ve seen some doctors on tv say that apparently countries in which the BCG vaccine is mandatory seem to be having less problems with Covid19.

    We are in the worst moment right now, we haven’t reached the peak of the curve yet, but in the biggest shanty town of Buenos Aires more than 50% of the population has antibodies, hopefully it will disappear soon like a fire that run out of trees to burn.

  3. The study is from Singapore, so their hypothetical “wild viruses” may be endemic to SE Asia. They mention a bat virus, but their alignment (Ext Fig 2) sadly doesn’t include any zoonotics.

    Importantly, the peptides from ORF1 and N were selected for the study precisely because of their conservation. The study didn’t even look at other peptides to find out what else may be “remembered” by the immune system about these pre-COVID infections.

    And sometimes crossreactive T-cells might be a problem rather than a solution? At least for SARS and MERS, Th2 overreaction pathologies are listed in the literature, and a weakly specific T cell may cause a disproportionately strong but ultimately ineffective response to a pathogen…

  4. Walter Sobchak — From a June 18th post on the blog NextGenerationTechnologist:

    “A large international GWAS has yet to conclusively identify variants in the population of affected individuals they have data from that determine COVID-19 disease severity. Work is ongoing with a project called The COVID-19 Host Genetics Initiative, a worthwhile effort; another effort to keep track of is what 23andMe is doing with their dataset, recently reporting susceptibility by ABO bloodtype.”

    A few more leads come from this search: “COVID-19 Host Susceptibility GWAS”.

  5. Walter, here is a link to the July 9th Escobar et al. PNAS paper that looked at BCG vaccination and Covid-19 mortality rates.

    BCG vaccine protection from severe coronavirus disease 2019 (COVID-19).

    The data are coarse (inter-country comparisons) and messy, so the statistical approach is complex. The authors conclude that “every 10% increase in the BCG index was associated with a 10.4% reduction in COVID-19 mortality. [These results] suggest that BCG could have a protective effect.”

  6. So we’re discussing possible beneficial (to us) immune interactions between related coronaviruses. I wonder whether dengue-like interactions are also possible, and in particular whether they could partially explain the increasing likelihood of severe cytokine storms with age. Not sure how this could be tested in anything less than a large-scale prospective study, though.

  7. I wonder about whether people get really immune and how long they being protected after an infection.
    Its looking bad for both and I don’t see an effective longer term vaccination coming any time soon.

Comments are closed.