Article (Scientific journals)
Intrahost evolution leading to distinct lineages in the upper and lower respiratory tracts during SARS-CoV-2 prolonged infection
El Moussaoui, Majdouline; Bontems, Sébastien; Meex, Cécile et al.
2024In medRxiv preprint
 

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Abstract :
[en] Accumulating evidence points to persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in immunocompromised individuals as a source of genetically divergent, novel lineages, generally characterised by increased transmissibility and immune escape. While intrahost evolutionary dynamics of the virus in chronically infected patients have been previously reported, existing knowledge is primarily based on samples obtained from the nasopharyngeal compartment. In this study, we investigate the intrahost evolution and genetic diversity that accumulated during a prolonged SARS-CoV-2 infection with the Omicron sublineage BF.7, estimated to have persisted for over one year in an immunosuppressed patient. Based on the sequencing of eight viral genomes collected from the patient at six time points, we identified 86 intrahost single-nucleotide variants (iSNVs), two indels, and a 362 bp deletion. Our analysis revealed distinct viral genotypes in the nasopharyngeal (NP), endotracheal aspirate (ETA), and bronchoalveolar (BAL) samples. Notably, while significant divergence was observed between NP and BAL samples, most of the iSNVs found in ETA samples were also detected in NP or BAL samples. This suggests that NP samples may not offer a comprehensive representation of the overall intrahost viral diversity. Nonsynonymous mutations were most frequent in the spike and envelope genes, along with loss-of-function mutations in ORF8, generated by a frameshift mutation and a large deletion detected in the BAL and NP samples, respectively. Using long-range PCR on SARS-CoV-2 samples sequenced as part of routine surveillance, we validated that similar deletions causing ORF8 loss of function can be carried by SARS-CoV-2 during acute infection. Our findings not only demonstrate that the Omicron sublineage BF.7 can further diverge from its already exceptionally mutated state but also highlight that patients chronically infected with SARS-CoV-2 can develop genetically specific viral populations across distinct anatomical compartments. This provides novel insights into the intricate nature of viral diversity and evolution dynamics in persistent infections.
Disciplines :
Immunology & infectious disease
Author, co-author :
El Moussaoui, Majdouline  ;  Université de Liège - ULiège > Département des sciences cliniques > Immunopathologie - Maladies infectieuses et médecine interne générale
Bontems, Sébastien ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Bactériologie, mycologie, parasitologie, virologie et microbiologie
Meex, Cécile ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Bactériologie, mycologie, parasitologie, virologie et microbiologie
Hayette, Marie-Pierre ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Bactériologie, mycologie, parasitologie, virologie et microbiologie
LEJEUNE, Marie ;  Centre Hospitalier Universitaire de Liège - CHU > > Service d'hématologie clinique
Hong, Samuel L. 
Dellicour, Simon  ;  Université de Liège - ULiège > Département de morphologie et pathologie (DMP)
Moutschen, Michel  ;  Université de Liège - ULiège > GIGA > GIGA I3 - Immunology & Infectious Diseases
CAMBISANO, Nadine ;  Centre Hospitalier Universitaire de Liège - CHU > > Service de génétique
Renotte, Nathalie ;  Université de Liège - ULiège > GIGA > GIGA Cancer - Human Genetics
Bours, Vincent ;  Université de Liège - ULiège > GIGA > GIGA Cancer - Human Genetics
Darcis, Gilles ;  Université de Liège - ULiège > Département des sciences cliniques
Artesi, Maria  ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Génétique humaine
Durkin, Keith   ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques
More authors (4 more) Less
 These authors have contributed equally to this work.
Language :
English
Title :
Intrahost evolution leading to distinct lineages in the upper and lower respiratory tracts during SARS-CoV-2 prolonged infection
Publication date :
04 March 2024
Journal title :
medRxiv preprint
Available on ORBi :
since 01 June 2024

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