Fig. 5: Hypotheses for the emergence of SARS-CoV-2 variants of concern.

Hypothesis 1: the virus can circulate, causing acute infections within a region lacking adequate genomic surveillance for a sustained period of time and gradually acquiring adaptive changes without being detected until it reaches another region with stronger genomic surveillance. Hypothesis 2: people in close contact with farmed or wild animals such as mink or deer can transmit the virus to these populations, where severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can acquire further adaptive changes on circulation in those animal populations before a spillback into humans, leading to the emergence of variants of concern (VOCs). Hypothesis 3: if the virus persists in an individual who is chronically infected for a long period, it may acquire changes that are adaptations to host immune responses. Further adaptive changes may occur if the patient is under treatment to clear the infection (for example, monoclonal antibodies or convalescent plasma) that may accelerate selection for antibody evasion mutations.