Characterization of SARS-CoV-2 ORF6 deletion variants detected in a nosocomial cluster during routine genomic surveillance, Lyon, France
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Abstract
Through routine genomic surveillance of the novel SARS-CoV-2 virus (n=229 whole genome sequences), 2 different frameshifting deletions were newly detected in the open reading frame (ORF) 6, starting at the same position (27267). While the 26-nucleotide deletion variant was only found in one sample in March 2020, the 34-nucleotide deletion variant was found within a single geriatric hospital unit in 5/9 patients sequenced and one health care worker with samples collected between April 2 nd and 9 th , 2020. Both the presence of the 34-nucleotide deletion variant limited to this unit and the clustering of the corresponding whole genome sequences by phylogeny analysis strongly suggested a nosocomial transmission between patients. Interestingly, prolonged viral excretion of the 34-nucleotide deletion variant was identified in a stool sample 14 days after initial diagnosis for one patient. Clinical data revealed no significant difference in disease severity between patients harboring the wild-type or the 34-nucleotide deletion variants. The in vitro infection of the two deletion variants on primate endothelial kidney cells (BGM) and human lung adenocarcinoma cells (Calu-3) yielded comparable replication kinetics with the wild-type strain. Furthermore, high viral loads were found in vivo regardless of the presence or absence of the ORF6 deletion. Our study highlights the transmission and replication capacity of two newly described deletion variants in the same ORF6 region.
Importance
While the SARS-CoV-2 genome has remained relatively stable since its emergence in the human population, genomic deletions are an evolutionary pattern previously described for the related SARS-CoV. Real-time genomic monitoring of the circulating variants is paramount to detect strain prevalence and transmission dynamics. Given the role of ORF6 in interferon modulation, further characterization, such as mechanistic interactions and interferon monitoring in patients, is crucial in understanding the viral-host factors driving disease evolution.
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SciScore for 10.1101/2020.08.07.241653: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: This study was presented by the ethics committee of the Hospices Civils de Lyon (HCL), Lyon, France and registered on the HCL database of RIPHN studies (AGORA N°41). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Virus replication kinetics: Replication kinetics was performed on both confluent buffalo green monkey (BGM) (BioWhittaker Europe) and human lung adenocarcinoma (Calu-3) cells (ATCC® HTB-55™, Calu-3suggested: ATCC Cat# HTB-55, RRID:CVCL_0609)Software and Algorithms Sentences Resources P… SciScore for 10.1101/2020.08.07.241653: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: This study was presented by the ethics committee of the Hospices Civils de Lyon (HCL), Lyon, France and registered on the HCL database of RIPHN studies (AGORA N°41). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Virus replication kinetics: Replication kinetics was performed on both confluent buffalo green monkey (BGM) (BioWhittaker Europe) and human lung adenocarcinoma (Calu-3) cells (ATCC® HTB-55™, Calu-3suggested: ATCC Cat# HTB-55, RRID:CVCL_0609)Software and Algorithms Sentences Resources Phylogeny: Multiple sequence alignment was performed using the DECIPHER package in R (45). DECIPHERsuggested: (DECIPHER, RRID:SCR_006552)Statistical analysis was performed by two-way ANOVA with Tukey multiple comparisons between both factors of comparison (virus strain and cell line) on GraphPad Prism (software version 8.4.3). GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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SciScore for 10.1101/2020.08.07.241653: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement This study was presented by the ethics committee of the Hospices Civils de 256 Lyon (HCL), Lyon, France and registered on the HCL database of RIPHN studies (AGORA N°41). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources 237 Virus replication kinetics 238 Replication kinetics was performed on both confluent buffalo green monkey (BGM) (BioWhittaker 239 Europe) and human lung adenocarcinoma (Calu-3) cells (ATCC® HTB-55™, Calu-3sug…SciScore for 10.1101/2020.08.07.241653: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement This study was presented by the ethics committee of the Hospices Civils de 256 Lyon (HCL), Lyon, France and registered on the HCL database of RIPHN studies (AGORA N°41). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources 237 Virus replication kinetics 238 Replication kinetics was performed on both confluent buffalo green monkey (BGM) (BioWhittaker 239 Europe) and human lung adenocarcinoma (Calu-3) cells (ATCC® HTB-55™, Calu-3suggested: ATCC Cat# HTB-55, RRID:CVCL_0609)Software and Algorithms Sentences Resources 228 Phylogeny 229 Multiple sequence alignment was performed using the DECIPHER package in R (45). DECIPHERsuggested: (DECIPHER, RRID:SCR_006552)Statistical analysis was 245 performed by two-way ANOVA with Tukey multiple comparisons between both factors of comparison 246 (virus strain and cell line) on GraphPad Prism (software version 8.4.3). GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
About SciScore
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