The significance of recurrent de novo amino acid substitutions that emerged during chronic SARS-CoV-2 infection: an observational study.
EBioMedicine
; 107: 105273, 2024 Aug 14.
Article
en En
| MEDLINE
| ID: mdl-39146693
ABSTRACT
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).
Texto completo:
1
Bases de datos:
MEDLINE
Idioma:
En
Revista:
EBioMedicine
Año:
2024
Tipo del documento:
Article
País de afiliación:
China