Emerging SARS-CoV-2 mutation hotspots associated with clinical outcomes
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Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Understanding the influence of mutations in the SARS-CoV-2 gene on clinical outcomes and related factors is critical for treatment and prevention. Here, we analyzed 209,551 high-coverage complete virus sequences and 321 RNA-seq samples to mine the mutations associated with clinical outcome in the SARS-CoV-2 genome. Several important hotspot variants were found to be associated with severe clinical outcomes. Q57H variant in ORF3a protein were found to be associated with higher mortality rate, and was high proportion in severe cases (39.36%) and 501Y.V2 strains (100%) but poorly proportional to asymptomatic cases (10.04%). T265I could change nsp2 structure and mitochondrial permeability, and evidently higher in severe cases (20.12%) and 501Y.V2 strains (100%) but lower in asymptomatic cases (1.43%). Additionally, R203K and G204R could decrease the flexibility and immunogenic property of N protein with high frequency among severe cases, VUI 202012/01 and 484K.V2 strains. Interestingly, the SARS-CoV-2 genome was more susceptible to mutation because of the high frequency of nt14408 mutation (which located in RNA polymerase) and the high expression levels of ADAR and APOBEC in severe clinical outcomes. In conclusion, several important mutation hotspots in the SARS-CoV-2 genome associated with clinical outcomes was found in our study, and that might correlate with different SARS-CoV-2 mortality rates.
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SciScore for 10.1101/2021.03.31.437666: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources The overlap of mutations generated by REDItools 2 and JACUSA were considered. REDItoolssuggested: (REDItools, RRID:SCR_012133)In this study, all samples were processed through a SARS-CoV-2 reference-based assembly pipeline that involved removing non-SARS-CoV-2 reads with Kraken2[22] and aligning to the SARS-CoV-2 reference genome NC_045512.2 by using Samtools[23]. Kraken2suggested: NoneResults from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: We …SciScore for 10.1101/2021.03.31.437666: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources The overlap of mutations generated by REDItools 2 and JACUSA were considered. REDItoolssuggested: (REDItools, RRID:SCR_012133)In this study, all samples were processed through a SARS-CoV-2 reference-based assembly pipeline that involved removing non-SARS-CoV-2 reads with Kraken2[22] and aligning to the SARS-CoV-2 reference genome NC_045512.2 by using Samtools[23]. Kraken2suggested: NoneResults from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:However, this research has several limitations. First, the insufficient clinical information on these sequences may have led to missing some mutations associated with clinical outcomes. Second, given that some raw RNA-seq data were unavailable, the relationship between SARS-CoV-2 mutation and clinical outcomes at the patient level was not analyzed. Third, some hotspot mutations lacked experimental proof and thus require experimental verification.
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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