Emergence of Multiple SARS-CoV-2 Antibody Escape Variants in an Immunocompromised Host Undergoing Convalescent Plasma Treatment

  1. Liang Chen
  2. Michael C. Zody
  3. Clara Di Germanio
  4. Rachel Martinelli
  5. Jose R. Mediavilla
  6. Marcus H. Cunningham
  7. Kaelea Composto
  8. Kar Fai Chow
  9. Milena Kordalewska
  10. André Corvelo
  11. Dayna M. Oschwald
  12. Samantha Fennessey
  13. Marygrace Zetkulic
  14. Sophia Dar
  15. Yael Kramer
  16. Barun Mathema
  17. Soren Germer
  18. Mars Stone
  19. Graham Simmons
  20. Michael P. Busch
  21. Tom Maniatis
  22. David S. Perlin
  23. Barry N. Kreiswirth

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Abstract

Over a year of the COVID-19 pandemic, distinct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages have arisen in multiple geographic areas around the world. SARS-CoV-2 variants of concern (VOCs), i.e., B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma), and B.1.617.2 (delta), harboring mutations and/or deletions in spike protein N-terminal domain (NTD) or receptor-binding domain (RBD) regions showed evidence of increased transmissibility and disease severity and possible reduced vaccine efficacy.

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  1. Version published to 10.1128/msphere.00480-21
  2. ScreenIT

    SciScore for 10.1101/2021.04.08.21254791: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Informed consent: Informed consent was obtained from this patient and the study was approved by Hackensack Meridian Health Institutional Review Board (IRB) under protocol Pro2018-1022.
    IRB: Informed consent: Informed consent was obtained from this patient and the study was approved by Hackensack Meridian Health Institutional Review Board (IRB) under protocol Pro2018-1022.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Libraries were quantified using fluorescent-based assays including PicoGreen (Life Technologies),
    PicoGreen
    suggested: None
    Adapter sequences and low quality (Q < 20) bases were trimmed from the remaining reads, using Cutadapt v2.1017
    Cutadapt
    suggested: (cutadapt, RRID:SCR_011841)
    Processed reads were then mapped to the SARS-CoV-2 genome reference using BWA-MEM v0.7.1728 and only read pairs with at least one alignment spanning a minimum of 42 bp in the reference and starting before position 29,862 (to exclude polyadenine-only alignments) were kept.
    BWA-MEM
    suggested: (Sniffles, RRID:SCR_017619)
    Genome sequences were determined by alignment pileup consensus calling with a minimum support of 5 reads using Samtools v1.11 and bcftools v1.11 9.
    Samtools
    suggested: (SAMTOOLS, RRID:SCR_002105)
    SNP and InDels were called using FreeBayes v1.3.5 (https://github.com/freebayes), followed by annotation using SnpEff v4.510.
    FreeBayes
    suggested: (FreeBayes, RRID:SCR_010761)
    SnpEff
    suggested: (SnpEff, RRID:SCR_005191)
    In addition, 2,282 SARS-CoV-2 genomes with E484K mutation were downloaded from GISAID database12 (date as 2/12/2021), and the genomes with less than 1% ambiguous nucleotides (Ns) and > 28,900 bp were aligned using MAFFT v7.475 12 using default setting.
    MAFFT
    suggested: (MAFFT, RRID:SCR_011811)
    A maximum likelihood phylogenetic tree was constructed using IQ-TREE v2.1.213 with automatic model selection and 1000-bootstrap replicates.
    IQ-TREE
    suggested: (IQ-TREE, RRID:SCR_017254)

    Results 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.

    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.

  3. Version published to 10.1101/2021.04.08.21254791 on medRxiv