SARS‐CoV‐2 intrahost evolution in immunocompromised patients in comparison with immunocompetent populations after treatment

Abstract

Many evidence suggests that long‐lasting infection can develop with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). This occurrence has been widely described in immunocompromised individuals. In these patients, ineffective clearance of virus infection provides an opportunity for developing immune escape mutants. This study aimed to characterize SARS‐CoV‐2 intrahost evolution in five immunocompromised in comparison with five immunocompetent COVID‐19 patients during treatment. We performed next‐generation sequencing (NGS) on collected two oropharyngeal samples from immunocompromised and immunocompetent COVID‐19 patients before and after treatment. In this study, we detected alpha and delta variants of SARS‐CoV‐2. The most common substitutions in structural proteins in patients with alpha variant were S‐ΔY143‐144, A570D, D614G and D1118H, and N‐R203K and G204R, and in delta variant S‐T19R, G142D, E156G, 157‐158del, L452R, T478K, D614G, D950N and N‐D63G, R203M and D377Y were dominant. The common variations in nonstructural and accessory proteins including nsp3‐A488S, P1228L, nsp6‐T77A, nsp12‐P323L, G671S, nsp13‐P77L, NS3‐S26L, and NS7a‐T120I were detected. Also some infrequent substitutions were seen in immunocompromised and immunocompetent patients. After treatment, nsp12‐V166A was emerged as a remdesivir resistance and S‐L452M in a patient with common variable immunodeficiency. S‐E484Q was detected in a patient with acute lymphoma leukemia. This study showed the possibility of the genetic diversity and development of some new mutations in immunocompromised patients. Therefore, surveillance of these patients to characterize any new variants is necessary.