Advertisement
Mayo Clinic Proceedings Home

How Safe Is COVID-19 Convalescent Plasma?

      To the Editor:
      We read with interest the systematic review and meta-analysis by Klassen and colleagues,
      • Klassen S.A.
      • Senefeld J.W.
      • Johnson P.W.
      • et al.
      The effect of convalescent plasma therapy on mortality among patients with COVID-19: systematic review and meta-analysis.
      recently published in Mayo Clinic Proceedings. The investigators included in their analysis 30 randomized clinical trials (RCTs) and matched control studies, documenting that COVID-19 convalescent plasma (CP) transfusion, especially when it is given within 3 days of hospital admission, is associated with lower mortality of patients with COVID-19 compared with standard treatment. Adverse events analysis, in combination with benefits analysis, is essential to make an informed decision about health intervention. For this reason, we would like to add safety data to the analysis of Klassen and coworkers.
      • Klassen S.A.
      • Senefeld J.W.
      • Johnson P.W.
      • et al.
      The effect of convalescent plasma therapy on mortality among patients with COVID-19: systematic review and meta-analysis.
      Through an online systematic search on PubMed and MEDLINE (range, January 1, 2020, to May 15, 2021), we identified 30 studies (14 RCTs and 16 non-RCTs with matched control group) that were downloaded and analyzed for safety data (Supplemental Table, available online at http://www.mayoclinicproceedings.org). Overall, severe (serious and grade 3-4) and thromboembolic adverse reactions were recorded and analyzed. In addition, we collected and evaluated the prevalence of overall and severe adverse reactions to CP transfusion in the selected studies. The study weight was calculated using the Mantel-Haenszel method, and statistical heterogeneity was assessed using the I2 statistic. Measures of treatment effect were risk difference (RD) together with 95% CI. All calculations were conducted using Review Manager, version 5.4 software (Cochrane Collaboration).
      The mean prevalence (standard deviation) of all and severe CP infusion–related adverse events was 2.1% (2.6%) and 0.7% (1.4%), respectively. As reported in Figure A and B, treatment with CP did not increase the risk of overall adverse events (RD, 0.01; 95% CI, −0.02 to 0.03; P=.65) and severe adverse events (RD, 0.00; 95% CI, −0.03 to 0.03; P=.81) compared with standard treatment. Similarly, the rate of thromboembolic events did not differ between the study groups (1.4% in the CP arm vs 1.7% in the control arm; RD, 0.00; 95% CI, −0.01 to 0.00; P=.24; Figure C). In addition, the funnel plot of comparison of all 3 outcomes (all, severe, and thromboembolic adverse reactions; Supplemental Figure, available online at http://www.mayoclinicproceedings.org) appeared to be symmetric, suggesting a substantial homogeneity among the included studies and the lack of publication bias.
      Figure thumbnail gr1a
      FigureForest plots of comparison of convalescent plasma (CP) vs standard treatment. A, Outcome: all adverse reactions. Data are from 8 randomized clinical trials (RCTs) and 1 non-RCT. B, Outcome: severe adverse reactions.
      Data are from 9 RCTs and 1 non-RCT. C, Outcome: thromboembolic adverse reactions. Data are from 7 RCTs and 2 non-RCTs. MH, Mantel-Haenszel. Figure continued on next page.
      Figure thumbnail gr1bc
      FigureForest plots of comparison of convalescent plasma (CP) vs standard treatment. A, Outcome: all adverse reactions. Data are from 8 randomized clinical trials (RCTs) and 1 non-RCT. B, Outcome: severe adverse reactions.
      Data are from 9 RCTs and 1 non-RCT. C, Outcome: thromboembolic adverse reactions. Data are from 7 RCTs and 2 non-RCTs. MH, Mantel-Haenszel. Figure continued on next page.
      In conclusion, the results of this updated meta-analysis confirm the safety of CP transfusion and, in particular, document the very low rate (0.7%) of CP transfusion–related serious adverse reactions, similar to that reported in the large US Expanded Access Program.
      • Joyner M.J.
      • Bruno K.A.
      • Klassen S.A.
      • et al.
      Safety update: COVID-19 convalescent plasma in 20,000 hospitalized patients.
      Differing from the previous systematic reviews, we have focused our analysis on the CP-related thromboembolic risk, considering the particular critical setting of COVID-19, with a hyperinflammatory and hypercoagulative state, and the concerns from some clinicians.
      • Marwah V.
      • Choudhary R.
      • Peter D.
      • Bhati G.
      Pulmonary thromboembolism post-COVID convalescent plasma therapy: adding fuel to a smoldering fire!.
      After a careful analysis of the published literature, we can conclude that the addition of CP to the COVID-19 treatment does not increase the patients’ thromboembolic risk. Finally, we personally think that considering the lack of valid anti–COVID-19 therapies, the relatively low costs, and the high safety profile, CP collection and use should be endorsed and implemented by governments of developing and developed countries, without waiting for conclusive evidence of its efficacy.
      • Cruciani M.
      • Bongiovanni G.
      • Franchini M.
      High-titer convalescent plasma therapy for COVID-19 and mortality.

      Supplemental Online Material

      Supplemental material can be found online at http://www.mayoclinicproceedings.org. Supplemental material attached to journal articles has not been edited, and the authors take responsibility for the accuracy of all data.

      References

        • Klassen S.A.
        • Senefeld J.W.
        • Johnson P.W.
        • et al.
        The effect of convalescent plasma therapy on mortality among patients with COVID-19: systematic review and meta-analysis.
        Mayo Clin Proc. 2021; 96: 1262-1275
        • Joyner M.J.
        • Bruno K.A.
        • Klassen S.A.
        • et al.
        Safety update: COVID-19 convalescent plasma in 20,000 hospitalized patients.
        Mayo Clin Proc. 2020; 95: 1888-1897
        • Marwah V.
        • Choudhary R.
        • Peter D.
        • Bhati G.
        Pulmonary thromboembolism post-COVID convalescent plasma therapy: adding fuel to a smoldering fire!.
        Adv Resp Med. 2021; 89: 347-349
        • Cruciani M.
        • Bongiovanni G.
        • Franchini M.
        High-titer convalescent plasma therapy for COVID-19 and mortality.
        Transfusion. 2021; 61: 1988-1990

      Linked Article

      • In Reply—How Safe Is COVID-19 Convalescent Plasma?
        Mayo Clinic ProceedingsVol. 96Issue 8
        • Preview
          We would like to thank Franchini and Cruciani for their letter in response to our systematic review and meta-analysis studying the effect of convalescent plasma therapy on the mortality of patients diagnosed with coronavirus disease 2019 (COVID-19).1 This letter highlights important new meta-analytical data based on 30 controlled studies (including 14 randomized clinical trials) demonstrating that convalescent plasma transfusion does not increase the risk of adverse events, including thromboembolic events, compared with patients diagnosed with COVID-19 who either were not transfused or were transfused with standard fresh frozen plasma.
        • Full-Text
        • PDF
      • The Effect of Convalescent Plasma Therapy on Mortality Among Patients With COVID-19: Systematic Review and Meta-analysis
        Mayo Clinic ProceedingsVol. 96Issue 5
        • Preview
          To determine the effect of COVID-19 convalescent plasma on mortality, we aggregated patient outcome data from 10 randomized clinical trials, 20 matched control studies, 2 dose-response studies, and 96 case reports or case series. Studies published between January 1, 2020, and January 16, 2021, were identified through a systematic search of online PubMed and MEDLINE databases. Random effects analyses of randomized clinical trials and matched control data demonstrated that patients with COVID-19 transfused with convalescent plasma exhibited a lower mortality rate compared with patients receiving standard treatments.
        • Full-Text
        • PDF
        Open Access