Why Did Some Lucky People Avoid Even Mild COVID Symptoms?

Dead body’s are easy to count

Very early in the Pandemic it became clear that certain factors predisposed a person to much greater risk of severe symptoms or death from COVID. The greatest risk was conferred by advanced age, and the well-known list of other medical conditions pressing their thumb on the scale against us. Medical scientists also focused on the rare cases of seemingly healthy, relatively young people, without the usual risk factors, who either died or had terrible courses. From these patients we learned that inherited defects in the Interferon cascade, part of our immune system’s first line of defense from novel pathogens we have never before encountered, led to devastating disease from this particular virus. Those people understandably caught the attention of researchers and the public, but fortunately these cases were rare, and the knowledge gained from studying them was not widely applicable. On the other hand, enormous numbers of unvaccinated persons, some even with older age, caught the virus and remained asymptomatic. Understanding what protected these folks, has been slow in coming, but offers a more general picture of human resistance to this virus, and more realistic possibilities of developing useful therapeutics. A recent preprint referenced below offers a tantalizing hint explaining at least one aspect of their COVID armor.

A little brief background is necessary for the non-immunologists. There are proteins on the surface of our cells called HLA (human leukocyte antigen). These are the factors that must be matched for organ transplantation. One of their jobs is to identify our own cells as Self, and off limits from attack by our immune system. The other function is to latch onto and present fragments of foreign proteins to the immune system, and thus begin the process of an immune response to the invader. The other bit of background, is that the SARS2-COV19 Corona virus is related to the four endemic Corona viruses which cause common colds, and they share some important protein sequences which strongly stimulate the immune system. With those basics reviewed, let’s look at the results from this paper.

https://www.medrxiv.org/content/10.1101/2021.05.13.21257065v3

A common allele of HLA mediates asymptomatic SARS-CoV-2 infection

Our discovery cohort (n=1428) was comprised of unvaccinated, self-identified subjects who reported a positive test result for SARS-CoV-2. We tested for association of five HLA loci (HLA-A, -B, -C, -DRB1, -DQB1) with disease course and identified a strong association of HLA-B*15:01 with asymptomatic infection, and reproduced this association in two independent cohorts.

Using a data base of 30,000 people who had been screened for organ transplantation, with detailed HLA results available, the authors identified a strong relationship between asymptomatic infection and the particular HLA type B15:01. Then going a step further they looked at memory T cells from pre-pandemic specimens and found that T lymphocytes from people with this HLA type reacted strongly to a specific protein sequence which is shared by SARS2-COV19 and the routine head cold Corona viruses. These lucky folks have an HLA structure which allowed their immune system to “pre-program” a set of T cells to react to a protein found on the Corona viruses we have all been repeatedly exposed to and also the new Pandemic COVID virus. Having occasionally treated the odd 90 yo life long smoker, I decided long ago that there is no good substitute for the right set of genes.

Since we are on the subject of who lives and dies, there is another set of data I would like you to consider. Early in the Pandemic, Sweden distinguished itself among the EU nations by avoiding societal lockdowns. They never closed schools or businesses or restaurants, but instead issued “recommendations” for mask wearing, social distancing, staying home if sick, and avoiding public transportation if necessary. The Swedish government was vehemently criticized by a giant chorus of experts around the world, who of course, knew better. It is true that during the early months of the epidemic Sweden had the fifth highest COVID death rate within the EU, but then a very surprising pattern emerged. We all know that COVID death rates have been rightly criticized as a suspect data point, given the vagaries of different criteria for deciding exactly what killed a given individual with multiple co-morbidities, and the limitations of death certifications in many countries. Epidemiologists tell us that a much more accurate picture is obtained from excess deaths data—a dead body is easy to count. So although Sweden had more COVID deaths in the early months of the Pandemic than neighboring “otherwise similar” Nordic countries which perused aggressive societal lockdown policies—since the middle of 2020 Sweden has had the lowest excess death rate in the EU. Overall, Sweden’s COVID death rate puts it somewhere in the middle of the EU pack (and well below the US), but the fact remains that their overall excess deaths are currently the lowest in Europe. I would call this an Inconvenient Fact, but it’s only inconvenient for people who championed draconian lockdowns, and actually quite convenient if you are one of Swedes still kicking around and helping the national statistic. I have read some creative suggestions by non-Swedish epidemiologists and Public Health officials (for whom this truly is an inconvenient fact) trying to explain this away. None of them make any real sense, are merely guesses not backed up by data; and it certainly looks clumsy when you are forced to undermine the metric you insisted was the gold standard, simply because it reveals a result you don’t like. I could pretend to have answers for this seeming paradox, but I’ll let you formulate your own guesses.

The chart above was accurate as of the end of November 2022. Excess mortality data is a lagging indicator, but I don’t find any suggestion the situation has materially changed in the last 3 months.

There isn’t anything remarkable to report on the COVID disease front. The winter wave continues its slow descent and US weekly deaths have declined to an average of 1700. XBB.1.5 remains the only game in town, still with no new challengers, and as previously discussed I think this is a very positive sign. Greta Thunberg recently delegated a Tweet from 2018 in which she stated that unless we completely stopped burning fossil fuels the world would be uninhabitable in 5 years. I immediately breathed a sigh of relief and cancelled my burial insurance policy. I started this Substack over a year ago, during a confusing time, primarily to provide interested people with what I felt was critical scientific information without agenda or bias. As interest in COVID fades, I won’t be doing weekly blogs anymore, but less frequent updates. If you are interested in having me periodically report on other medical/infectious disease issues, let me know via the like button at the top or in the comments. It certainly seems like the COVID clouds are parting, but plenty of other opportunities for stormy weather are on the horizon.