Adaptive evolution of SARS-CoV-2 during a persistent infection for 521 days in an immunocompromised patient

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Abstract
Immunocompromised patients struggle to adequately clear viral infections, offering the virus the opportunity to adapt to the immune system in the host. Here we present a case study of a patient undergoing allogeneic hematopoietic stem cell transplantation with a 521-day follow-up of a SARS-CoV-2 infection with the BF.7.21 variant. Virus samples from five time points were submitted to whole genome sequencing. Between the first detection of SARS-CoV-2 infection and its clearance, the patient’s virus population acquired 34 amino acid substitutions and 8 deletions in coding regions. With 11 amino acid substitutions in the receptor binding domain of the virus’ spike protein, substitutions were 15 times more abundant than expected for a random distribution in this highly functional region. Amongst them were the substitutions S:K417T, S:N440S, S:K444R, S:V445A, S:G446N, S:L452Q, S:N460K, and S:E484V at positions that are notorious for their resistance-mediating effects. The substitution patterns found indicate ongoing adaptive evolution.
Funding Information
  • Ministry of Science and Health of the State of Rhineland-Palatinate, Germany

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