Drivers of adaptive evolution during chronic SARS-CoV-2 infections

In some immunocompromised patients with chronic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, considerable adaptive evolution occurs. Some substitutions found in chronic infections are lineage-defining mutations in variants of concern (VOCs), which has led to the hypothesis that VOCs emerged from chronic infections. In this study, we searched for drivers of VOC-like emergence by consolidating sequencing results from a set of 27 chronic infections. Most substitutions in this set reflected lineage-defining VOC mutations; however, a subset of mutations associated with successful global transmission was absent from chronic infections. We further tested the ability to associate antibody evasion mutations with patient-specific and virus-specific features and found that viral rebound is strongly correlated with the emergence of antibody evasion. We found evidence for dynamic polymorphic viral populations in most patients, suggesting that a compromised immune system selects for antibody evasion in particular niches in a patient's body. We suggest that a tradeoff exists between antibody evasion and transmissibility and that extensive monitoring of chronic infections is necessary to further understanding of VOC emergence. Analysis of mutations that arise in chronic SARS-CoV-2 infections shows both overlap and differences with mutations present in pandemic viral variants of concern, highlighting their distinct drivers of evolution.

Automated summary

In immunocompromised patients with chronic SARS-CoV-2 infection, adaptive evolution occurs and some mutations may lead to the emergence of variants of concern. However, certain mutations associated with global transmission are absent in chronic infections. The study also found a strong correlation between viral rebound and antibody evasion. The findings suggest a tradeoff between antibody evasion and transmissibility, highlighting the importance of monitoring chronic infections for understanding the emergence of variants of concern.