Longitudinal analysis of genomic mutations in SARS-CoV-2 isolates from persistent COVID-19 patient

Hiroki Futatsusako; Rina Hashimoto; Masaki Yamamoto; Jumpei Ito; Yasufumi Matsumura; Hajime Yoshifuji; Kotaro Shirakawa; Akifumi Takaori-Kondo; Genotype to Phenotype Japan (G2P-Japan) Consortium; Kei Sato; Miki Nagao; Kazuo Takayama

doi:10.1016/j.isci.2024.109597

Longitudinal analysis of genomic mutations in SARS-CoV-2 isolates from persistent COVID-19 patient

iScience. 2024 Mar 29;27(5):109597. doi: 10.1016/j.isci.2024.109597. eCollection 2024 May 17.

Authors

Hiroki Futatsusako¹, Rina Hashimoto¹, Masaki Yamamoto², Jumpei Ito^{3

4

5}, Yasufumi Matsumura², Hajime Yoshifuji⁶, Kotaro Shirakawa⁷, Akifumi Takaori-Kondo⁷; Genotype to Phenotype Japan (G2P-Japan) Consortium; Kei Sato^{3

4

5

8

9

10

11}, Miki Nagao², Kazuo Takayama^{1

12}

Affiliations

¹ Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 6068507, Japan.
² Department of Clinical Laboratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto 6068507, Japan.
³ Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 1088639, Japan.
⁴ Graduate School of Medicine, The University of Tokyo, Tokyo 1138654, Japan.
⁵ International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo 1088639, Japan.
⁶ Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto 6068507, Japan.
⁷ Department of Hematology, Graduate School of Medicine, Kyoto University, Kyoto 6068507, Japan.
⁸ International Vaccine Design Center, The Institute of Medical Science, The University of Tokyo, Tokyo 1088639, Japan.
⁹ Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa 2770882, Japan.
¹⁰ Collaboration Unit for Infection, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto 8600811, Japan.
¹¹ CREST, Japan Science and Technology Agency, Kawaguchi 3320012, Japan.
¹² AMED-CREST, Japan Agency for Medical Research and Development (AMED), Tokyo 1000004, Japan.

Abstract

A primary reason for the ongoing spread of coronavirus disease 2019 (COVID-19) is the continuous acquisition of mutations by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the mechanism of acquiring mutations is not fully understood. In this study, we isolated SARS-CoV-2 from an immunocompromized patient persistently infected with Omicron strain BF.5 for approximately 4 months to analyze its genome and evaluate drug resistance. Although the patient was administered the antiviral drug remdesivir (RDV), there were no acquired mutations in RDV binding site, and all isolates exhibited susceptibility to RDV. Notably, upon analyzing the S protein sequence of the day 119 isolate, we identified mutations acquired by mutant strains emerging from the BF.5 variant, suggesting that viral genome analysis in persistent COVID-19 patients may be useful in predicting viral evolution. These results suggest mutations in SARS-CoV-2 are acquired during long-term viral replication rather than in response to antiviral drugs.

Keywords: Genomics; Microbiology and Virology.