Initial experience in Mexico with convalescent plasma in COVID-19 patients with severe respiratory failure, a retrospective case series

  1. Michel F. Martinez-Resendez
  2. Fernando Castilleja-Leal
  3. Alejandro Torres-Quintanilla
  4. Augusto Rojas-Martinez
  5. Gerardo Garcia-Rivas
  6. Rocio Ortiz-Lopez
  7. Victor Trevino
  8. Reynaldo Lara-Medrano
  9. Hiram Villanueva-Lozano
  10. Teresa Ramirez-Elizondo
  11. Victor M. Sanchez-Nava
  12. Francisco Moreno-Hoyos
  13. Alfonso Martinez-Thomae
  14. Martin Hernández-Torre
  15. Carlos Diaz-Olachea
  16. Servando Cardona-Huerta
  17. Sylvia de la Rosa-Pacheco
  18. Carlos Diaz-Garza
  19. Paola Reynoso-Lobo
  20. Alma R. Marroquin-Escamilla
  21. Jessica G. Herrera-Gamboa
  22. Fatima M. Alvarado-Monroy
  23. Claudia D. Aguayo-Millan
  24. Francisco F. Villegas-Macedo
  25. Jesus Efrain Flores-Osorio
  26. Daniel Davila-Gonzalez
  27. María Eugenia Diaz-Sanchez
  28. Guillermo Torre-Amione

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Abstract

Introduction

Hospital mortality due to COVID-19 in Mexico is high (32%) and as of today, effective treatment options are limited. More effective treatments that shorten hospital stay and reduce mortality are needed. Initial reports for the use of convalescent plasma (CP) therapy for COVID-19 appear promising. We describe a case series of eight patients with impending respiratory failure, who underwent CP therapy.

Methods

Six male and two female (ages 31 to 79) patients that were admitted to the intensive-care unit for severe COVID-19 were transfused with two doses of CP (250 mL per dose, anti-SARS-CoV-2 IgG titers > 1:100). Donors were six SARS-CoV-2 infected males who remained asymptomatic for > 7 days and were negative for two nasopharyngeal RT-PCR tests. Clinical characteristics, inflammatory and cellular injury markers, chest X-ray findings and viral loads were analyzed before and after CP administration. Viral load association to disease severity was further analyzed on a separate cohort of asymptomatic vs hospitalized patients with COVID-19.

Results

Eight patients with respiratory failure were successfully discharged with a median length of stay of 22.5 (IQR 18.25-29.00). After CP therapy, we observed a reduction of C-reactive protein (CRP) (median, 22.80 mg/dL vs. 1.63 mg/dL), and of procalcitonin (median, 0.27 ng/mL vs. 0.13 ng/mL). High-Sensitivity Cardiac Troponin I (hs-cTnI), Brain Natriuretic Peptide (BNP) and Lactate Dehydrogenase (LDH) were lower, and a mild reduction of pulmonary infiltrates by chest X-ray was observed. Lastly, a reduction of viral load was after CP therapy was found. (log, median [IQR], 1.2 [0.70-2.20] vs. 0.25 [0.00-1.78]). We observed no adverse effects.

Conclusions

CP could potentially be an effective therapeutic option for patients with severe COVID-19. Clinical benefit needs to be studied further through randomized controlled trials.

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  1. ScreenIT

    SciScore for 10.1101/2020.07.14.20144469: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: This study was approved by the Clinical Research Ethics Committee of the School of Medicine at Tecnológico de Monterrey (P000353-COVID-19 TecSalud-CEIC-CR001).
    Consent: Written informed consent was obtained from all patients.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableDonors: We obtained CP from 6 male donors who were between the ages of 22 and 57 years.

    Table 2: Resources

    Antibodies
    SentencesResources
    Donors showed anti-SARS-CoV-2 IgG antibody titers higher than 1:100 as determined by ELISA.
    anti-SARS-CoV-2 IgG
    suggested: None
    Serology Test: Antibody titers for IgG and IgM antibodies against SARS-CoV-2 were obtained using the EDI™ Novel Coronavirus COVID-19 IgG and IgM ELISA Kits (Epitope Diagnostics, San Diego, CA) following manufacturer instructions.
    SARS-CoV-2
    suggested: None
    IgM ELISA Kits (Epitope Diagnostics, San Diego, CA
    suggested: None
    The cutoffs for IgG antibodies were calculated using the following formulas: Positive cutoff = 1.1 X (xNC + 0.18) and negative cutoff = 0.9 × (xNC + 0.18).
    IgG
    suggested: None
    The cutoffs for IgM antibodies were calculated using the following formulas: Positive cutoff = 1.1 X (xNC + 0.10) and negative cutoff = 0.9 × (xNC + 0.10).
    IgM
    suggested: None
    Software and Algorithms
    SentencesResources
    RT-PCR Test: We used the Applied Biosystems™ TaqMan™ 2019-nCoV Assay Kit v1 (Cat. No. A47532) for the qualitative detection and characterization of 2019-nCoV RNA.
    Applied Biosystems™
    suggested: (Applied Biosystems, RRID:SCR_005039)
    GraphPad Prism 7.0 was used for plotting graphs and statistical analysis.
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    There are limitations to our present study. Patients were receiving standard care, which could interact with the course of illness or with CP therapy. Neutralizing antibodies were not determined. However, our preliminary results support the completion of randomized larger trials. In summary, the present study supports the observations of others and reaffirms the importance of conducting prospective clinical studies aimed to define not only the best timing and cohort of patients in which CP should be used, but also to improve our understanding of the mechanisms of action.

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

    IdentifierStatusTitle
    NCT04333355TerminatedSafety in Convalescent Plasma Transfusion to 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

    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 10.1101/2020.07.14.20144469v1 on medRxiv