Impact of Convalescent Plasma Transfusion (CCP) In Patients With Previous Circulating Neutralizing Antibodies (nAb) to COVID-19

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Abstract

INTRODUCTION

COVID-19 convalescent plasma (CCP) transfusion has emerged in the past months as an alternative approach to treat pneumonia cases of SARS-CoV-2. Current evidence regarding characteristics of the plasma product, the titer of neutralizing antibodies (nAbs) in the transfused units, time to onset of intervention, and impact of nAbs produced by the patient are limited and heterogeneous.

MATERIAL AND METHODS

We describe the preliminary results of 104 patients with severe pneumonia due to SARS-CoV-2 transfused with CCP at three medical centers in Brazil. All enrolled patients were transfused with doses between 200 mL through 600mL of ABO compatible CCP on days 0-2 after enrolment. Clinical parameters were monitored and nAbs titration was performed using the cytopathic effect-based virus neutralization test with SARS-CoV-2 (GenBank MT126808.1 ).

RESULTS

Forty-one patients achieved clinical improvement on day 14, and multivariable logistic regression showed that nAbs T (from CCP units transfused) (p= 0.001), nAbs P0 (on day of enrolment) (p=0.009) and use of other supportive therapies (p<0.001) were associated with higher odds for this clinical improvement. Considering ICU length of stay (LOS) and length of mechanical ventilation, in our analysis, nAbs P0 were associated with a significant reduction in ICU LOS (p=0.018) and duration of mechanical ventilation (p<0.001). Administration of CCP after 10 days of symptom onset was associated with increases in ICU length of stay (p<0.001).

DISCUSSION/CONCLUSION

Despite the study limitations, our data have shown an association between patients’ previously acquired nAbs and clinical outcomes. The potential value of timely administration of CCP transfusion before day 10 of disease onset was demonstrated and nAbsP0, but not nAbsT, were associated with ICU LOS, and duration of mechanical ventilation on the improvement of clinical outcomes was also demonstrated. In conclusion, we consider these data are useful parameters to guide future CPP transfusion strategies to COVID-19.

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  1. SciScore for 10.1101/2020.12.08.20246173: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: It was approved by the Brazilian National Commission for Research Ethics (CONEP), CAAE 30922420.6.2002.0071, and the Ethics Committees of each participating site.
    Consent: Informed Consent was obtained from all study participants or their legal representatives.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablePatients with preexisting history of anaphylactic transfusion reaction, pregnant or lactating women were excluded.

    Table 2: Resources

    Antibodies
    SentencesResources
    , neutralizing antibody titers from patients on Day 5 (NAbsP5), the total volume of CP transfused, age, gender, weight, ABO group, severity organ failure assessment score on admission day (SOFA D0), use of other supportive therapies for COVID-19 (azithromycin, hydroxychloroquine, steroids, tocilizumab, human immunoglobulin, antiviral therapies), and comorbidities.
    human immunoglobulin,
    suggested: None
    Software and Algorithms
    SentencesResources
    For the analysis, we used IBM SPSS Statistics for Windows, Version 24.0. 2016, R package [18], and ggplot2 [19].
    SPSS
    suggested: (SPSS, RRID:SCR_002865)
    ggplot2
    suggested: (ggplot2, RRID:SCR_014601)

    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: We detected the following sentences addressing limitations in the study:
    Despite the study limitations such as the size of the cohort and the fact that it is a one-arm prospective study, our data have shown an association between patients’ previously acquired nAbs and clinical outcomes. Our analysis also suggests that nAbsT was associated with clinical improvements on day 14. Besides, nAbsP0 but not nAbsT have an impact on ICU LOS and duration of mechanical ventilation. The potential value of timely administration of CCP transfusion before day 10 of disease onset on the improvement of clinical outcomes was also demonstrated. In conclusion, we consider these data are useful parameters to guide future CPP transfusion strategies to COVID-19.

    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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