The impact of host genetics and viral variation on SARS‐CoV‐2 infection and COVID‐19 severity. Individuals in the population harbor single nucleotide polymorphisms (SNPs) across a variety of genes (eg, ACE2, TMPRSS2, HLA, CD147, MIF, IFNG, IL6) that have been implicated in the pathology and immunology of SARS‐CoV‐2 and other pathogenic coronaviruses. These and other genetic variants may modulate disease susceptibility, increase or decrease disease severity, alter the variety of symptoms developed, and affect the magnitude and/or quality of the immune responses against SARS‐CoV‐2. In addition to host genetic variation, genetic variants of SARS‐CoV‐2 (and other pathogenic coronaviruses) can exhibit differences in biological activity. Single amino acid mutations in the spike glycoprotein can modulate ACE2 binding or alter B cell epitopes to promote immune escape or render monoclonal antibodies ineffective, while mutations in non‐structural/accessory proteins can promote the development of resistance to antivirals, alter T cell epitopes, disrupt cell mediated immunity, and modulate host cellular interactions with viral particles