A systematic review of convalescent plasma treatment for COVID19

  1. Ville N. Pimenoff
  2. Miriam Elfström
  3. Joakim Dillner

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Abstract

Background

Transfusion of convalescent immune plasma (CP) is commonly used in epidemics. Several articles now describe clinical report data of CP for treatment of SARS-CoV-2-induced COVID-19 disease.

Methods

A systematic literature review was conducted using the NCBI curated COVID-19 related open-resource literature database LitCovid to identify studies using CP as treatment for COVID-19 patients. We retrieved and curated all COVID-19 related patient and treatment characteristics from previously reported studies. A Poisson model was developed to evaluate the association between age of the patients, older age being the most common risk factor for COVID-19 mortality, and recovery time since CP treatment using data extracted from the literature.

Results

From 18,293 identified COVID-19 related articles, we included ten studies reporting results of CP treatment for COVID-19 from a total of 61 patients. Decreased symptoms of severe COVID-19 and clearance of SARS-CoV-2 RNA were the most direct observations. We found that patients over the age of sixty who received CP treatment for COVID-19 had a significantly prolonged recovery estimated by viral clearance (from 10 to 29 days since first dose of CP) compared to younger patients, who recovered from the infection in less than a week after receiving CP treatment.

Conclusions

Limited published results on plasma transfusion treatment for COVID-19 disease with concomitant treatments suggest that CP therapy for COVID-19 is well tolerated and effective. First randomized clinical trial results, however, revealed no improvements in recovery time for elderly patients with severe COVID-19 between standard treatment alone and added with convalescent plasma. Accordingly, we argue that older patients may need a significantly longer time for recovery. Further randomized clinical trial data for COVID-19 with rigorous ethical standards is urgently needed.

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  1. ScreenIT

    SciScore for 10.1101/2020.06.05.20122820: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablePrevious reports also suggest that male gender and comorbidities such as hypertension and cardiovascular disease are risk factors for mortality for patients with COVID-1918–21, and thus were included in our model.

    Table 2: Resources

    No key resources detected.

    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:
    Another important caveat related to plasma transfusion treatment for COVID-19 patients, which warrants future evaluation, is the possible transfusion-associated circulatory overload, a common serious adverse effect of transfusion11. Furthermore, it is suggested that there may be a risk for complement-mediated tissue damage in convalescent plasma treatment11. Lastly, the risk for antibody-dependent disease enhancement during CP treatment for COVID-19 requires further evaluation using randomized clinical trial data11,39. Taken together, current reports on convalescent plasma for treating COVID-19 is limited by lack of representation of patients in the early phase of infection, as well as confounding from multiple overlapping therapies and small patient numbers34. Randomized clinical trial data is needed for comprehensive evaluation of CP treatment safety and feasibility, however, not treating patients with severe COVID-19 for clinical trial purposes may need a rigorous ethical evaluation. Limitations: Despite the significance of our results, our study has a number of limitations. There is only limited data available, thus far, for a comprehensive analysis of the safety and feasibility of CP therapy for COVID-19. A massive number of large scale clinical trials are ongoing, but preliminary data is still not available33–36,46. Ideally, all the patients would have been followed with the same criteria for the COVID-19 onset and recovery. However, we have curated all eligible studies...

    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.

  2. Version published to 10.1101/2020.06.05.20122820v2 on medRxiv
  3. Version published to 10.1101/2020.06.05.20122820v1 on medRxiv