COVID-19 infection and transmission includes complex sequence diversity
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Abstract
SARS-CoV-2 whole genome sequencing has played an important role in documenting the emergence of polymorphisms in the viral genome and its continuing evolution during the COVID-19 pandemic. Here we present data from over 360 patients to characterize the complex sequence diversity of individual infections identified during multiple variant surges (e.g., Alpha and Delta). Across our survey, we observed significantly increasing SARS-CoV-2 sequence diversity during the pandemic and frequent occurrence of multiple biallelic sequence polymorphisms in all infections. This sequence polymorphism shows that SARS-CoV-2 infections are heterogeneous mixtures. Convention for reporting microbial pathogens guides investigators to report a majority consensus sequence. In our study, we found that this approach would under-report sequence variation in all samples tested. As we find that this sequence heterogeneity is efficiently transmitted from donors to recipients, our findings illustrate that infection complexity must be monitored and reported more completely to understand SARS-CoV-2 infection and transmission dynamics. Many of the nucleotide changes that would not be reported in a majority consensus sequence have now been observed as lineage defining SNPs in Omicron BA.1 and/or BA.2 variants. This suggests that minority alleles in earlier SARS-CoV-2 infections may play an important role in the continuing evolution of new variants of concern.
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SciScore for 10.1101/2022.04.18.488717: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The study protocol was approved by the Cleveland VA Medical Center’s Institutional Review Board (IRB protocol number 1584025) with a waiver of consent. Sex as a biological variable not detected. Randomization To perform this analysis, we randomly selected and analyzed 110 additional COVID-19 infections reported from 18 different laboratories or consortia with raw sequence data available in the sequence read archive (SRA) (Supplemental Table 4). Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources Variants were called at positions with a minimum coverage of 100 reads with a base quality score >20 using Samtools mpileup v1.8. Samtoolssuggeste…SciScore for 10.1101/2022.04.18.488717: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The study protocol was approved by the Cleveland VA Medical Center’s Institutional Review Board (IRB protocol number 1584025) with a waiver of consent. Sex as a biological variable not detected. Randomization To perform this analysis, we randomly selected and analyzed 110 additional COVID-19 infections reported from 18 different laboratories or consortia with raw sequence data available in the sequence read archive (SRA) (Supplemental Table 4). Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources Variants were called at positions with a minimum coverage of 100 reads with a base quality score >20 using Samtools mpileup v1.8. Samtoolssuggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
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.
Results from scite Reference Check: We found no unreliable references.
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