Yearlong COVID-19 Infection Reveals Within-Host Evolution of SARS-CoV-2 in a Patient With B-Cell Depletion

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Abstract

B-cell–depleting therapies may lead to prolonged disease and viral shedding in individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and this viral persistence raises concern for viral evolution. We report sequencing of early and late samples from a 335-day infection in an immunocompromised patient. The virus accumulated a unique deletion in the amino-terminal domain of the spike protein, and complete deletion of ORF7b and ORF8, the first report of its kind in an immunocompromised patient. Unique viral mutations found in this study highlight the importance of analyzing viral evolution in protracted SARS-CoV-2 infection, especially in immunosuppressed hosts.

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  1. SciScore for 10.1101/2021.10.02.21264267: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsConsent: Approvals: Written consent was obtained for human research subjects, as approved by the NIH Institutional Review Board (protocol # NCT02659943).
    IRB: Approvals: Written consent was obtained for human research subjects, as approved by the NIH Institutional Review Board (protocol # NCT02659943).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Genome assembly, generation of consensus sequences and identification of variants: Following sequencing, Illumina sequencing adapters and primer sequences were trimmed with Trimmomatic v0.36 [16].
    Trimmomatic
    suggested: (Trimmomatic, RRID:SCR_011848)
    The trimmed reads were aligned to the Wuhan-Hu-1 SARS-CoV-2 reference genome (NC_045512.2) using BWA mem v0.7.17 with the -K parameter set to 100000000 for reproducibility and -Y to use soft clipping for supplementary alignments [17].
    BWA
    suggested: (BWA, RRID:SCR_010910)
    Duplicates were marked using GATK MarkDuplicatesSpark v4.1.3.0 (https://gatk.broadinstitute.org/hc/en-us/articles/360037224932-MarkDuplicatesSpark).
    GATK
    suggested: (GATK, RRID:SCR_001876)

    Results from OddPub: Thank you for sharing your code and 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: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT02659943Active, not recruitingT Cells Expressing a Fully-human AntiCD19 Chimeric Antigen R…


    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.


    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.