| Autor: |
Jonathan Daniel Ip, Wing-Ming Chu, Wan-Mui Chan, Allen Wing-Ho Chu, Rhoda Cheuk-Ying Leung, Qi Peng, Anthony Raymond Tam, Brian Pui-Chun Chan, Jian-Piao Cai, Kwok-Yung Yuen, Kin-Hang Kok, Yi Shi, Ivan Fan-Ngai Hung, Kelvin Kai-Wang To |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
EBioMedicine, Vol 107, Iss , Pp 105273- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2352-3964 |
| DOI: |
10.1016/j.ebiom.2024.105273 |
| Popis: |
Summary: Background: De novo amino acid substitutions (DNS) frequently emerge among immunocompromised patients with chronic SARS-CoV-2 infection. While previous studies have reported these DNS, their significance has not been systematically studied. Methods: We performed a review of DNS that emerged during chronic SARS-CoV-2 infection. We searched PubMed until June 2023 using the keywords “(SARS-CoV-2 or COVID-19) and (mutation or sequencing) and ((prolonged infection) or (chronic infection) or (long term))”. We included patients with chronic SARS-CoV-2 infection who had SARS-CoV-2 sequencing performed for at least 3 time points over at least 60 days. We also included 4 additional SARS-CoV-2 patients with chronic infection of our hospital not reported previously. We determined recurrent DNS that has appeared in multiple patients and determined the significance of these mutations among epidemiologically-significant variants. Findings: A total of 34 cases were analyzed, including 30 that were published previously and 4 from our hospital. Twenty two DNS appeared in ≥3 patients, with 14 (64%) belonging to lineage-defining mutations (LDMs) of epidemiologically-significant variants and 10 (45%) emerging among chronically-infected patients before the appearance of the corresponding variant. Notably, nsp9-T35I substitution (Orf1a T4175I) emerged in all three patients with BA.2.2 infection in 2022 before the appearance of Variants of Interest that carry nsp9-T35I as LDM (EG.5 and BA.2.86/JN.1). Structural analysis suggests that nsp9-T35I substitution may affect nsp9-nsp12 interaction, which could be critical for the function of the replication and transcription complex. Interpretation: DNS that emerges recurrently in different chronically-infected patients may be used as a marker for potential epidemiologically-significant variants. Funding: Theme-Based Research Scheme [T11/709/21-N] of the Research Grants Council (See acknowledgements for full list). |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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