Antibody response and intra‐host viral evolution after plasma therapy in COVID ‐19 patients pre‐exposed or not to B‐cell‐depleting agents

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Abstract

Administration of plasma therapy may contribute to viral control and survival of COVID‐19 patients receiving B‐cell‐depleting agents that impair humoral immunity. However, little is known on the impact of anti‐CD20 pre‐exposition on the kinetics of SARS‐CoV‐2‐specific antibodies. Here, we evaluated the relationship between anti‐spike immunoglobulin G (IgG) kinetics and the clinical status or intra‐host viral evolution after plasma therapy in 36 eligible hospitalized COVID‐19 patients, pre‐exposed or not to B‐cell‐depleting treatments. The majority of anti‐CD20 pre‐exposed patients (14/17) showed progressive declines of anti‐spike IgG titres following plasma therapy, contrasting with the 4/19 patients who had not received B‐cell‐depleting agents ( p  = 0.0006). Patients with antibody decay also depicted prolonged clinical symptoms according to the World Health Organization (WHO) severity classification ( p  = 0.0267) and SARS‐CoV‐2 viral loads ( p  = 0.0032) before complete virus clearance. Moreover, they had higher mutation rates than patients able to mount an endogenous humoral response ( p  = 0.015), including three patients with one to four spike mutations, potentially associated with immune escape. No relevant differences were observed between patients treated with plasma from convalescent and/or mRNA‐vaccinated donors. Our study emphasizes the need for an individualized clinical care and follow‐up in the management of COVID‐19 patients with B‐cell lymphopenia.

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  1. SciScore for 10.1101/2022.04.24.22274200: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablePlasma collection and preparation: Convalescent plasma was collected from 32 male donors (CP), who had fully recovered for at least 28 days after COVID-19 onset and presented an anti-S protein-specific IgG response, ranging from 29.4-135.6 ratio, with an average ratio of 79 using an in-house developed Luminex assay (42), correlating to neutralizing titers (43, 44).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Variant calling was performed with Freebayes (parameters: –min-alternate-fraction 0.1 –min-coverage 10 –min-alternate-count 9) (48).
    Freebayes
    suggested: (FreeBayes, RRID:SCR_010761)

    Results from OddPub: Thank you for sharing your code.


    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.


    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.