Dynamic diversity of SARS-CoV-2 genetic mutations in a lung transplantation patient with chronic persistent COVID-19

Numerous SARS-CoV-2 variant strains have emerged since the onset of COVID-19 pandemic, with altered virus characteristics. Remdesivir (RDV), a ribonucleotide analogue inhibitor of viral RNA polymerase, has become an invaluable therapeutic agent. However, immunosuppressed hosts may respond inadequately to RDV and develop chronic persistent infections. A patient with respiratory failure caused by interstitial pneumonia, who had undergone a one-lung transplant, developed Omicron BA.5 strain COVID-19 infection with persistent chronic viral shedding. Genome-wide sequencing analyses revealed that several mutations occurred after RDV treatment, followed by dynamic changes in their populations. C799F in nsp12 played a pivotal role in conferring RDV resistance.