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

Hidetoshi Igari (), Seiichiro Sakao, Takayuki Ishige (), Kengo Saito, Shota Murata, Misuzu Yahaba, Toshibumi Taniguchi, Akiko Suganami, Kazuyuki Matsushita, Yutaka Tamura, Takuji Suzuki and Eiji Ido ()
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Hidetoshi Igari: Department of Infectious Diseases, Chiba University Hospital
Seiichiro Sakao: Department of Respiratory Medicine, Chiba University Hospital
Takayuki Ishige: Chiba University Hospital
Kengo Saito: Department of Molecular Virology, Graduate School of Medicine, Chiba University
Shota Murata: Chiba University Hospital
Misuzu Yahaba: Department of Infectious Diseases, Chiba University Hospital
Toshibumi Taniguchi: Department of Infectious Diseases, Chiba University Hospital
Akiko Suganami: Department of Bioinformatics, Graduate School of Medicine, Chiba University
Kazuyuki Matsushita: Chiba University Hospital
Yutaka Tamura: Department of Bioinformatics, Graduate School of Medicine, Chiba University
Takuji Suzuki: Chiba University Hospital
Eiji Ido: Department of Infectious Diseases, Chiba University Hospital

Nature Communications, 2024, vol. 15, issue 1, 1-11

Abstract: Abstract Numerous SARS-CoV-2 variant strains with altered characteristics have emerged since the onset of the COVID-19 pandemic. Remdesivir (RDV), a ribonucleotide analogue inhibitor of viral RNA polymerase, has become a valuable 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 transplantation of the left lung, developed COVID-19 caused by Omicron BA.5 strain with persistent chronic viral shedding, showing viral fusogenicity. Genome-wide sequencing analyses revealed the occurrence of several viral mutations after RDV treatment, followed by dynamic changes in the viral populations. The C799F mutation in nsp12 was found to play a pivotal role in conferring RDV resistance, preventing RDV-triphosphate from entering the active site of RNA-dependent RNA polymerase. The occurrence of diverse mutations is a characteristic of SARS-CoV-2, which mutates frequently. Herein, we describe the clinical case of an immunosuppressed host in whom inadequate treatment resulted in highly diverse SARS-CoV-2 mutations that threatened the patient’s health due to the development of drug-resistant variants.

Date: 2024
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DOI: 10.1038/s41467-024-47941-x

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