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We read with interest the COVID-19 Forecasting Team's description of the variation in COVID-19 infection–fatality ratio,1 confirming that differences in COVID-19 mortality between geographies are largely explained by the age structures of their populations. However, we fear that the lower than anticipated burden of severe COVID-19 in most of sub-Saharan Africa gets lost in estimations from models based on data from the few African countries that have reliable excess mortality data but are not representative of sub-Saharan Africa. Moreover, country-level estimates of COVID-19 infection–fatality ratio hide the observation that COVID-19 mortality in sub-Saharan Africa is highly concentrated in sections of the population with a more western lifestyle—usually wealthier individuals in urban centres.2 Such disparity is obvious for most people living in sub-Saharan Africa, where COVID-19 is sometimes popularly called “VIP disease” or “rich person disease”. We suspect that, besides a higher prevalence of obesity, hypertension, and diabetes among wealthier people, immunological factors are at play. Several studies associate chronic parasitic infection (more prevalent among people living in poverty with a less westernised lifestyle) with less severe clinical presentation of COVID-19.3, 4 Such findings are consistent with the importance of a diverse microbiome and chronic immune stimulation in maintaining a well trained immune system that is less likely to cause hyperinflammation, which is critical in severe COVID-19.

a less westernised lifestyle) with less severe clinical presentation of COVID-19.3, 4 Such findings are consistent with the importance of a diverse microbiome and chronic immune stimulation in maintaining a well trained immune system that is less likely to cause hyperinflammation, which is critical in severe COVID-19. Although unexplored, the notion that the better-off might fare worse is not unique to COVID-19 in sub-Saharan Africa. It is also consistently documented that autoimmune diseases, more prevalent in high-income countries, share a common pathway with severe COVID-19, linking reduced microbiome diversity to hyperinflammation, popularised as the hygiene hypothesis.5 Similar links have been documented in HIV serosurveys in the 2000s in sub-Saharan Africa, in which the better-off had higher risk of HIV infection.6 It is vital to deepen our understanding of microbiome diversity and linked immunological factors in the severity of COVID-19, and account for this when modelling COVID-19 infection–fatality ratios.