The benefits of lockdown

I was recently looking at mortality statistics for England and Wales in 2019 and 2020. There’s been a lot of talk about excess mortality due to Covid, but there hasn’t been much discussion of mortality reduction. Given that Covid rarely caused serious symptoms — and hardly ever death — in young people, and given the high proportion of deaths due to accidents — particularly vehicular accidents — you might expect the lockdown to have reduced their overall mortality. And this is indeed what we see.

Mortality 20193959654151474416014090
Mortality 20203758694701651474416120
Relative % excess 2020-5.2-12.84.613.412.114.014.4
Force of mortality in 2019 and 2020, in deaths/100,000

Above age 45 we see a fairly consistent 13% increase in mortality from 2019 to 2020. But there was a 13% decrease in mortality among children under 15. Even in the newborn group there was a 5% decrease. In total there were 116 fewer deaths recorded in 2020 in the 1-14 age group compared with 2019, and 200 fewer deaths in the first year of life (of which about 70 may be attributed to a 3% decrease in the number of births).

ACE2 and the variability hypothesis for Covid-19

One of the big mysteries of Covid-19 has been the difference in severity between men and women. About 2/3 of deaths have been among men, despite the fact that there are far more women than men in the most vulnerable age groups. This has been attributed to general differences between men and women in immune responses — women being generally more resistant to infection, and more susceptible to auto-immune diseases.

I recently went to look up the genetics of ACE2 — the membrane protein that SARS-Cov-2 uses to enter human cells — and discovered the basic fact (presumably known to anyone familiar with biochemistry) that the ACE2 gene is on the X chromosome. And that made me think of the infamous “variability hypothesis”. This is the notion that men are generally more variable in many characteristics than women, so will be overrepresented among the extremes at both ends of the distribution. Of course, as with any scientific fact about men and women, this has been primarily used to argue that women should mind their knitting and cannot be comparable to male geniuses like (most notoriously) Larry Summers.

Such essentialist arguments are wrong-headed and demeaning when applied to characteristics as complex as intelligence, much less to something as vaguely defined as “commitment” (Summers’s word). But this phenomenon is well grounded where it is applied to genetic traits linked to the X chromosome. Female bodies are mosaics, with each cell randomly expressing one of the two inherited versions of the X chromosome. It is extremely well known and uncontroversial in the context of X-linked Mendelian disorders, such as haemophilia and red-green colour-blindness. A single defective gene on the X chromosome causes these conditions, where a mixture of defective and healthy alleles produces a phenotype essentially indistinguishable from the healthy version alone.

The general phenomenon is superlinearity of effect: Where an average of two scores produces a markedly different outcome from one or the other extreme. Might that be the case for Covid-19? There is some evidence from Italian populations that variants in the ACE2 gene may affect individual susceptibility to severe Covid-19. Indeed, this study suggests that rare variants may play a significant role. If a mixture of half highly susceptible cells and half less susceptible is much more robust than a tissue where all cells are highly susceptible — a plausible situation, though not inevitable — then we would expect to see more severe disease in males.

Looking around, I found this paper that points out that men have generally higher levels of ACE2 circulating in blood, and argues “due to the high expression of ACE2, male patients may be more likely to develop severe symptoms and die of SARS-CoV-2”. So that’s another possibility.