tetano
Editor, Senior Moderator
Nat Commun
. 2024 Apr 29;15(1):3604.
doi: 10.1038/s41467-024-47941-x. Dynamic diversity of SARS-CoV-2 genetic mutations in a lung transplantation patient with persistent COVID-19
Hidetoshi Igari[SUP] #[/SUP][SUP] 1 2 3 4 [/SUP], Seiichiro Sakao[SUP] 5 6 [/SUP], Takayuki Ishige[SUP] #[/SUP][SUP] 7 [/SUP], Kengo Saito[SUP] 8 [/SUP], Shota Murata[SUP] 9 [/SUP], Misuzu Yahaba[SUP] 10 [/SUP], Toshibumi Taniguchi[SUP] 10 11 [/SUP], Akiko Suganami[SUP] 12 [/SUP], Kazuyuki Matsushita[SUP] 9 [/SUP], Yutaka Tamura[SUP] 12 [/SUP], Takuji Suzuki[SUP] 13 5 14 [/SUP], Eiji Ido[SUP] #[/SUP][SUP] 15 16 [/SUP]
Affiliations
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.
. 2024 Apr 29;15(1):3604.
doi: 10.1038/s41467-024-47941-x. Dynamic diversity of SARS-CoV-2 genetic mutations in a lung transplantation patient with persistent COVID-19
Hidetoshi Igari[SUP] #[/SUP][SUP] 1 2 3 4 [/SUP], Seiichiro Sakao[SUP] 5 6 [/SUP], Takayuki Ishige[SUP] #[/SUP][SUP] 7 [/SUP], Kengo Saito[SUP] 8 [/SUP], Shota Murata[SUP] 9 [/SUP], Misuzu Yahaba[SUP] 10 [/SUP], Toshibumi Taniguchi[SUP] 10 11 [/SUP], Akiko Suganami[SUP] 12 [/SUP], Kazuyuki Matsushita[SUP] 9 [/SUP], Yutaka Tamura[SUP] 12 [/SUP], Takuji Suzuki[SUP] 13 5 14 [/SUP], Eiji Ido[SUP] #[/SUP][SUP] 15 16 [/SUP]
Affiliations
- PMID: 38684722
- DOI: 10.1038/s41467-024-47941-x
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.