Evolution of SARS-CoV-2 Viral Mutations in Individuals with Prolonged Infections

Objective. The world has been faced with the repeat rise of SARS-CoV-2 variants since late 2020, including Alpha, Beta, Gamma, Delta, and the latest simultaneous emergence of far-flung spawn of Omicron sub-lineages in different parts of the globe. This has brought us the challenge of determining what factor(s) have been the selective force behind these immune evasive and therapy resistant mutations. It is very possible that such variants evolved in limited host individuals with prolonged infections, or from a localized community of patients. Methods. This study surveys the GISAID time capsule of mutations found in viral genomes from patients with prolonged same lineage viral infections. We analyzed 288 SARS-CoV-2 genomes representing 113 patients who had same lineage viral genomes in two or more samples stored in GISAID. Results. Of these, thirty-five (30.9%) of the 113 patients developed mutations during their infections. Samples from patients whose viral genomes showed nucleotide changes(s) (n=35) versus those that showed no change (n=78) had a statistically significant difference (p=2.121x10^-4) in duration of infection by a median of 13 days (range 0-109 days) versus 6 days (range 0-72 days), respectively. Five highly recognizable variant-defining mutations with immune evasion properties were identified in 5 cases infected by the B.1 lineages in late 2020 and early 2021. Conclusion. This suggests the duration of infection is a contributing factor that gives rise to mutations, but not the sole factor, and individual host conditions may play a critical role in driving viral evolution.