Detection and prevalence of SARS-CoV-2 co-infections during the Omicron variant circulation, France, December 2021 - February 2022
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Abstract
In Dec 2021-Feb 2022, an intense and unprecedented co-circulation of SARS-CoV-2 variants with high genetic diversity raised the question of possible co-infections between variants and how to detect them. Using 11 mixes of Delta:Omicron isolates at different ratios, we evaluated the performance of 4 different sets of primers used for whole-genome sequencing and we developed an unbiased bioinformatics method which can detect all co-infections irrespective of the SARS-CoV-2 lineages involved. Applied on 21,387 samples collected between weeks 49-2021 and 08-2022 from random genomic surveillance in France, we detected 53 co-infections between different lineages. The prevalence of Delta and Omicron (BA.1) co-infections and Omicron lineages BA.1 and BA.2 co-infections were estimated at 0.18% and 0.26%, respectively. Among 6,242 hospitalized patients, the intensive care unit (ICU) admission rates were 1.64%, 4.81% and 15.38% in Omicron, Delta and Delta/Omicron patients, respectively. No BA.1/BA.2 co-infections were reported among ICU admitted patients. Although SARS-CoV-2 co-infections were rare in this study, their proper detection is crucial to evaluate their clinical impact and the risk of the emergence of potential recombinants.
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SciScore for 10.1101/2022.03.24.22272871: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Field Sample Permit: Ethics: Samples used in this study were collected as part of an approved ongoing surveillance conducted by the NRC of HCL.
IRB: This study was approved 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).Sex as a biological variable not detected. Randomization Sample selection: The samples sequenced at the National Reference Center (NRC) of Respiratory Viruses of Hospices Civils de Lyon (HCL) selected for this study were i) samples from systematic sequencing of hospitalized patients in the Lyon area (university hospital of Lyon, HCL) and from HCL health care workers; ii) samples from … SciScore for 10.1101/2022.03.24.22272871: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Field Sample Permit: Ethics: Samples used in this study were collected as part of an approved ongoing surveillance conducted by the NRC of HCL.
IRB: This study was approved 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).Sex as a biological variable not detected. Randomization Sample selection: The samples sequenced at the National Reference Center (NRC) of Respiratory Viruses of Hospices Civils de Lyon (HCL) selected for this study were i) samples from systematic sequencing of hospitalized patients in the Lyon area (university hospital of Lyon, HCL) and from HCL health care workers; ii) samples from random sequencing performed during the weekly Flash survey conducted by the EMERGEN consortium (French consortium for the genomic surveillance of emerging pathogens). Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Following interim biosafety guidelines established by WHO, NPS were inoculated on confluent Vero E6 TMPRSS2 cells with DMEM supplemented with 2% penicillin– streptomycin, 1% L-glutamine, 2% G418 and 2% inactivated fetal bovine serum. Vero E6 TMPRSS2suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)Software and Algorithms Sentences Resources Mapped reads were processed to remove duplicates tagged by picard, then realigned by abra2 to improve indel detection sensitivity and finally clipped with samtools ampliconclip to remove read ends containing primer sequences. samtoolssuggested: (SAMTOOLS, RRID:SCR_002105)Results from OddPub: Thank you for sharing your code and data.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:This study has several limitations. First, the follow-up duration for the assessment of BA.1 /BA.2 co-infection is short, and as BA.2 detection is still increasing in France, the prevalence of BA.1 /BA.2 co-infection may be underestimated. In addition, ICU admission and vaccination status information was lacking for some Flash cases, limiting the clinical characterization of co-infected patients. Finally, additional sequencing methods were not tested, such as metagenomics or hybrid capture which are less prone to amplification-bias toward specific lineages 7. However, these techniques have lower sensitivity and lower throughput and were therefore not suitable as first-line sequencing methods in our laboratory 20. In conclusion, our findings emphasize the importance of using appropriate experimental and bioinformatic methods for the comprehensive identification of SARS-CoV-2 co-infections. Although these events are rare, SARS-CoV-2 co-infections need to be properly identified as they can lead to the emergence of new variants after a recombination event.
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.
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- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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