Convalescent plasma as potential therapy for severe COVID-19 pneumonia

  1. Ricardo Valentini
  2. José Fernández
  3. Dardo Riveros
  4. Fernando Pálizas
  5. Jorge Solimano
  6. Pablo Saúl
  7. Juan Medina
  8. Viviana Falasco
  9. María Laura Dupont
  10. Julia Laviano
  11. Florencia Fornillo
  12. Daniela Maymó
  13. Daniel Gotta
  14. Alfredo Martinez
  15. Pablo Bonvehí
  16. Juan Dupont

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Abstract

At the beginning of the COVID-19 pandemic, there was high mortality and a lack of effective treatment for critically ill patients. Build on the experience in argentine hemorrhagic fever with convalescent plasma, we incorporated 90 patients into a multicenter study, and 87 were evaluable. We collected 397 donations from 278 convalescent donors. Patients received plasma with an IgG concentration of 0.7-0.8 (measured by Abbott chemiluminescence) for every 10 kg of body weight. Survival during the first 28 days was the primary objective. 77% were male, age 54 ± 15.6 y/o (range 27-85); body mass index 29.7 ± 4,4; hypertension 39% and diabetes 20%; 19.5% had an immunosuppression condition; 23% were healthcare workers. Plasma was administered to 55 patients (63%) on spontaneous breathing with oxygen supplementation (mainly oxygen mask with reservoir bag in 80%), and 32 patients (37%) were infused on mechanical ventilation. The 28-day survival rate was 80%, with 91% in patients infused on spontaneous breathing and 63% in those infused on mechanical ventilation (p = 0.0002). There was a significant improvement in the WHO pneumonia clinical scale at 7 and 14 days, and in PaO 2 / FiO 2 , ferritin and LDH, in the week post-infusion. We observed an episode of circulatory volume overload and a febrile reaction, both mild. Convalescent plasma infusions are feasible, safe, and potentially effective, especially before requiring mechanical ventilation, and are an attractive clinical option for treating severe forms of COVID-19 until other effective therapies become available.

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  1. ScreenIT

    SciScore for 10.1101/2020.09.01.20184390: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Protocols of donation and infusion to patients was designed by investigators at CEMIC and both approved by the Institutional Review Board.
    Consent: A written informed consent was obtained from each donor by a study authorized physician.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablePreviously pregnant women were studied for HLA antibodies.

    Table 2: Resources

    Antibodies
    SentencesResources
    Antibody testing in plasma donors and selection of units to be transfused: The SARS-COV-2 IgG antibody test was performed on donor serum samples using the Architect Plus i2000sr Analyzer (Abbott, Illinois, USA) and the CMIA SARS-COV-2 IgG kit.
    SARS-COV-2 IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    Antibody testing in plasma donors and selection of units to be transfused: The SARS-COV-2 IgG antibody test was performed on donor serum samples using the Architect Plus i2000sr Analyzer (Abbott, Illinois, USA) and the CMIA SARS-COV-2 IgG kit.
    Architect Plus
    suggested: None
    Abbott
    suggested: (Abbott, RRID:SCR_010477)

    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:
    There are several limitations of this study. The first one is that we do not have a control arm without convalescent plasma. When we designed it, there was no proven effective therapy for this disease. The mortality reported at the beginning of the pandemic in the most severe forms was high, and convalescent plasma was a possible strategy to apply in this situation (“as much as possible, without stopping” 23). The second limitation to consider is our unawareness of the neutralizing power of the infused plasma. We evaluated donor plasmas using IgG Ab against the nucleocapsid that did not establish neutralizing capacity, and in the first donors this evaluation was retrospective. When this test was available, the plasmas were selected by reading this method and most of the values were greater than 4 and never less than 3. According to some studies, the concordance between this serological response and viral neutralization suggests that a strong humoral response can be predictive of neutralizing activity, regardless of the selected target antigen 8. Furthermore, values greater than 4 had a correlation with a neutralizing titer of at least 1/320 24. Respiratory failure was the basic parameter to recruit patients in our study. In most cases it happened after several days of the onset of the initial symptoms. In a report of 4209 patients requiring admission to intensive care, the median time to onset of symptoms was 10 days 25. Although the most appropriate moment for infusion is st...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04535063RecruitingConvalescent Plasma as Potential Therapy for Severe COVID-19…

    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

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  2. Version published to 10.1101/2020.09.01.20184390v1 on medRxiv