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Determinants of immune evasion evolved by SARS-CoV-2 during long-term persistent infection of an immunocompromised individual

Chronic SARS-CoV-2 infections of immunocompromised individuals is thought to be a major factor in the evolution of new SARS-CoV-2 variants of concern (VOC). We characterised a pathway by which a wave 1 SARS-CoV-2 virus gradually evolved mechanisms of evasion from both adaptive and innate immune responses redolent of major VOCs during a single chronic infection. This provides one of the strongest pieces of evidence for the involvement of long-term infections in the evolution of new variants that resist antibody-mediated immunity. We also suggest adaptations that resist innate immunity occur early in a chronic infection to promote viral persistence.