Emergence of multiple SARS-CoV-2 mutations in an immunocompromised host

TLDR

Immunosuppressed patients can shed infectious SARS‑CoV‑2 for extended periods, as recently reported. In a B‑cell depleted patient, replication‑competent virus persisted for 154 days with 11 new spike mutations and a Y144 deletion, and viral diversification accelerated after convalescent plasma and respiratory decline, underscoring the need for real‑time genomic surveillance in such hosts.

Abstract

Abstract Prolonged shedding of infectious SARS-CoV-2 has recently been reported in a number of immunosuppressed individuals with COVID-19. Here, we describe the detection of high levels of replication-competent SARS-CoV-2 in specimens taken from the respiratory tract of a B-cell depleted patient up to 154 days after initial COVID-19 diagnosis concomitant with the development of high mutation rate. In this patient, a total of 11 nonsynonymous mutations were detected in addition to the Y144 deletion in the spike protein of SARS-CoV-2. Virus evolution studies revealed a dramatic diversification in viral population coinciding with treatment with convalescent plasma and clinical respiratory deterioration. Our findings highlight the urgent need for continuous real-time surveillance of genetic changes of SARS-CoV-2 adaptation alongside immunological investigations in patients with severely compromised humoral responses who may shed infectious virus over prolonged periods of time.