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

Sheri Harari, Maayan Tahor, Natalie Rutsinsky, Suzy Meijer, Danielle Miller, Oryan Henig, Ora Halutz, Katia Levytskyi, Ronen Ben-Ami, Amos Adler, Yael Paran, Adi Stern*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1501-1508
Number of pages8
JournalNature Medicine
Issue number7
StatePublished - Jul 2022


FundersFunder number
Edmond J. Safra Center for Bioinformatics
European Research Council852223
Israel Science Foundation3963/19
Tel Aviv University


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