Patients with immunosuppression are at risk for prolonged infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

In several case reports, investigators have indicated that multimutational SARS-CoV-2 variants can arise during the course of such persistent cases of coronavirus disease 2019 (Covid-19).

These highly mutated variants are indicative of a form of rapid, multistage evolutionary jumps (saltational evolution; see Glossary), which could preferentially occur in the milieu of partial immune control.

The presence of a large number of mutations is also a hallmark of the variants of concern — including B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma), and B.1.617.2 (delta)5 — which suggests that viral evolution in immunocompromised patients may be an important factor in the emergence of such variants.

Since a large number of persons globally are living with innate or acquired immunosuppression, the association between immunosuppression and the generation of highly transmissible or more pathogenic SARS-CoV-2 variants requires further delineation and mitigation strategies.

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