Health & Environmental Research Online (HERO)


Print Feedback Export to File
8630759 
Journal Article 
Characterization of SARS-CoV-2 ORF6 deletion variants detected in a nosocomial cluster during routine genomic surveillance, Lyon, France 
Quéromès, G; Destras, G; Bal, A; Regue, H; Burfin, G; Brun, S; Fanget, R; Morfin, F; Valette, M; Trouillet-Assant, S; Lina, B; Frobert, E; Josset, L 
2021 
Emerging Microbes & Infections
EISSN: 2222-1751 
10 
1 
167-177 
English 
33399033 
WOS:000613523200001 
During routine molecular surveillance of SARS-CoV-2 performed at the National Reference Center of Respiratory Viruses (Lyon, France) (n = 229 sequences collected February-April 2020), two frameshifting deletions were detected in the open reading frame 6, at the same position (27267). While a 26-nucleotide deletion variant (D26) was only found in one nasopharyngeal sample in March 2020, the 34-nucleotide deletion (D34) was found within a single geriatric hospital unit in 5/9 patients and one health care worker in April 2020. Phylogeny analysis strongly suggested a nosocomial transmission of D34, with potential fecal transmission, as also identified in a stool sample. No difference in disease severity was observed between patients hospitalized in the geriatric unit infected with WT or D34. In vitro D26 and D34 characterization revealed comparable replication kinetics with the wild-type (WT), but differential host immune responses. While interferon-stimulated genes were similarly upregulated after infection with WT and ORF6 variants, the latter specifically induced overexpression of 9 genes coding for inflammatory cytokines in the NF-kB pathway, including CCL2/MCP1, PTX3, and TNFα, for which high plasma levels have been associated with severe COVID-19. Our findings emphasize the need to monitor the occurrence of ORF6 deletions and assess their impact on the host immune response. 
Cytokines; ORF6 protein, SARS-CoV-2; Viral Proteins; Index Medicus; SARS-CoV-2; nosocomial cluster; deletion; inflammation; genomic surveillance; Sequence Deletion; Frameshift Mutation; Hospitalization; Cytokines -- immunology; Phylogeny; France -- epidemiology; Immunity; Base Sequence; Aged, 80 and over; Genetic Variation; Cross Infection -- virology; Genome, Viral; Viral Proteins -- immunology; COVID-19 -- virology; Cross Infection -- immunology; COVID-19 -- immunology; COVID-19 -- epidemiology; Cross Infection -- epidemiology; SARS-CoV-2 -- genetics; Viral Proteins -- genetics