MUTATIONS in PERSISTENT SARS-CoV-2 CASES

ABSTRACT

Background: The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with decreased susceptibility to neutralizing antibodies are of clinical importance. While several demographic and clinical correlates of Coronavirus Disease 2019 (COVID-19) outcome have been identified, their relationship to virological and immunological parameters remain poorly defined. Here, we evaluate viral diversity and the accumulation of intra-host mutations over time in a population of hospitalized adults positive for SARS-CoV-2. Methods: We performed longitudinal collection of nasopharyngeal swabs and blood samples from a small cohort of hospitalized adults with COVID-19. Clinical information regarding study subject's immunocompromised status was collected. Samples were assessed for SARS-CoV-2 viral load, viral genotype, viral diversity, and antibody titer. Results: Intra-host viral genetic diversity remained constant through disease course in study subjects that were non-immunocompromised and resulted in changes in viral genotype in some participants. We report the de novo emergence of Spike mutations that have been previously associated with circulating variants of concern in two immunosuppressed patients with persistent SARS-CoV-2 infection. Conclusion: Constant rates of viral evolution suggest the emergence of variants as a function of time, emphasizing the need for effective antivirals to control viral load over long disease courses.