The impact of environmental mycobiomes on geographic variation in COVID-19 mortality

Mortality rates during the COVID-19 pandemic have varied by orders of magnitude across communities in the United States. Individual, socioeconomic, and environmental factors have been linked to health outcomes of COVID-19. It is now widely appreciated that the environmental microbiome, composed of microbial communities associated with soil, water, atmosphere, and the built environment, impacts immune system development and susceptibility to immune-mediated disease. The human microbiome has been linked to individual COVID-19 disease outcomes, but there are limited data on the influence of the environmental microbiome on geographic variation in COVID-19 across populations. To fill this knowledge gap, we used taxonomic profiles of fungal communities associated with 1,135 homes in 494 counties from across the United States in a machine learning analysis to predict COVID-19 Infection Fatality Ratios (the number of deaths caused by COVID-19 per 1000 SARS-CoV-2 infections; 'IFR'). Here we show that exposure to increased fungal diversity, and in particular indoor exposure to outdoor fungi, is associated with reduced SARS-CoV-2 IFR. Further, we identify seven fungal genera that are the predominant drivers of this protective signal and may play a role in suppressing COVID-19 mortality. This relationship is strongest in counties where human populations have remained stable over at least the previous decade, consistent with the importance of early-life microbial exposures. We also assessed the explanatory power of 754 other environmental and socioeconomic factors, and found that indoor-outdoor fungal beta-diversity is amongst the strongest predictors of county-level IFR, on par with the most important known COVID-19 risk factors, including age. We anticipate that our study will be a starting point for further integration of environmental mycobiome data with population health information, providing an important missing link in our capacity to identify vulnerable populations. Ultimately, our identification of specific genera predicted to be protective against COVID-19 mortality may point toward novel, proactive therapeutic approaches to infectious disease.