Evolutionary medical insights into the SARS-CoV-2 pandemic

Crespi, Bernard

I apply concepts and tools from evolutionary medicine to understanding the SARS-COV-2 pandemic. The pandemic represents a mismatched conflict, with dynamics and pathology apparently driven by three main factors: (1) bat immune systems that rely on low inflammation but high efficacy of interferon-based defences; (2) viral tactics that differentially target the human interferon system, leading to substantial asymptomatic and presymptomatic transmission; and (3) high mortality caused by hyper-inflammatory and hyper-coagulatory phenotypes, that represent dysregulated tradeoffs whereby collateral immune-induced damage becomes systemic and severe. This framework can explain the association of mortality with age (which involves immune life-history shifts towards higher inflammation and coagulation, and reduced adaptive immunity), and sex (since males senesce faster than females). Genetic-risk factors for Covid-19 mortality can be shown, from a phenome-wide association analysis of the relevant SNPs, to be associated with inflammation and coagulation; the PheWAS also provides evidence, consistent with several previous studies, that the calcium channel blocking drug amlodipine mediates risk of mortality.