Recurrent SARS-CoV-2 mutations in immunodeficient patients

TLDR

Long‑term SARS‑CoV‑2 infections in immunodeficient patients are a key source of viral variation yet remain understudied, and existing case reports have not been consolidated into a comprehensive dataset. The study aims to compile and analyze SARS‑CoV‑2 genomic data from immunodeficient patients using literature searches and the COG‑UK dataset. The authors combined literature reviews with extraction of new case series from the COG‑UK database to assemble a unified genomic dataset. Spike receptor‑binding domain and N‑terminal domain were mutation hotspots, with recurrent emergence of variants‑of‑concern mutations—including the envelope T30I mutation—and many recurrent changes in immunodeficient patients enhance ACE2 affinity, immune escape, or viral packaging, reflecting selective pressure for mutations that promote cell‑cell transmission and persistence.

Abstract

Long-term severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in immunodeficient patients are an important source of variation for the virus but are understudied. Many case studies have been published which describe one or a small number of long-term infected individuals but no study has combined these sequences into a cohesive dataset. This work aims to rectify this and study the genomics of this patient group through a combination of literature searches as well as identifying new case series directly from the COVID-19 Genomics UK (COG-UK) dataset. The spike gene receptor-binding domain and N-terminal domain (NTD) were identified as mutation hotspots. Numerous mutations associated with variants of concern were observed to emerge recurrently. Additionally a mutation in the envelope gene, T30I was determined to be the second most frequent recurrently occurring mutation arising in persistent infections. A high proportion of recurrent mutations in immunodeficient individuals are associated with ACE2 affinity, immune escape, or viral packaging optimisation. There is an apparent selective pressure for mutations that aid cell-cell transmission within the host or persistence which are often different from mutations that aid