Convalescent plasma for outpatients with early COVID-19

  1. Pere Millat-Martinez
  2. Arvind Gharbharan
  3. Andrea Alemany
  4. Casper Rokx
  5. Corine Geurtsvankessel
  6. Grigorios Papageourgiou
  7. Nan van Geloven
  8. Carlijn Jordans
  9. Geert Groeneveld
  10. Francis Swaneveld
  11. Ellen van der Schoot
  12. Marc Corbacho-Monné
  13. Dan Ouchi
  14. Francini Piccolo Ferreira
  15. Pierre Malchair
  16. Sebastian Videla
  17. Vanesa GarcĂ­a GarcĂ­a
  18. Anna Ruiz-Comellas
  19. Anna RamĂ­rez-Morros
  20. Joana RodrĂ­guez Codina
  21. Rosa Amado Simon
  22. Joan-Ramon Grifols
  23. Julian Blanco
  24. Ignacio Blanco
  25. Jordi Ara
  26. Quique Bassat
  27. Bonaventura Clotet
  28. BĂ rbara Baro
  29. Andrea Troxel
  30. Jaap Jan Zwaginga
  31. Oriol MitjĂ 
  32. Bart Rijnders
  33. for the ConV-ert
  34. CoV-Early and COMPILEhome study groups
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Abstract

Background

Convalescent plasma (CP) for hospitalized patients with COVID-19 has not demonstrated clear benefits. However, data on outpatients with early symptoms are scarce. We aimed to assess whether treatment with CP administered during the first 7 days of symptoms reduced the disease progression or risk of hospitalization of outpatients.

Methods

Two double-blind randomized trials ( <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT04621123">NCT04621123</ext-link> , <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT04589949">NCT04589949</ext-link> ) were merged with data pooling starting when <20% of their predefined sample size had been recruited. A Bayesian adaptive individual patient data meta-analysis was implemented. Analyses were done with Bayesian proportional odds and logistic models, where odds ratios (OR)<1.0 indicate a favorable outcome for CP. Fourteen study sites across the Netherlands and Catalonia in Spain participated in the trial. The two studies included outpatients aged ≥50 years and diagnosed with COVID-19 and symptomatic for ≤7days. The intervention consisted of one unit (200-300mL) of CP with a predefined minimum level of antibodies. The two primary endpoints were (a) a 5-point disease severity scale (fully recovered by day 7 or not, hospital or ICU admission and death) and (b) a composite of hospitalization or death.

Results

Of 797 patients included, 390 received CP and 392 placebo. At baseline, they had a median age of 58 years, 1 comorbidity, symptoms for 5 days and 93% tested negative for SARS-CoV-2 S-protein IgG antibodies. Seventy-four patients were hospitalized, 6 required mechanical ventilation and 3 died. The OR of CP for an improved disease severity scale was 0.936 (credible interval (CI) 0.667-1.311). The OR for hospitalization or death was 0.919 (CI 0.592-1.416). The effect of CP on hospital admission or death was largest in patients with ≤5 days of symptoms (OR 0.658, 95% CI 0.394-1.085). CP did not decrease the time to full symptom resolution (p=0.62).

Conclusion

Treatment with CP of outpatients in the first 7 days of symptoms did not improve the outcome of COVID-19. The possible beneficial effect in patients with ≤5 days of symptoms requires further study.

Registration

NCT04621123 and <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT04589949">NCT04589949</ext-link> on <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://www.clinicaltrials.gov">https://www.clinicaltrials.gov</ext-link>

Funding source

ZONMW, the Netherlands, grant number 10430062010001.

SUPPORT-E, grant number 101015756

YoMeCorono, <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.tomecorono.com">www.tomecorono.com</ext-link>

The Fight AIDS and Infectious Diseases Foundation with funding from the pharmaceutical company Grifols S.A

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