Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 28, Number 5—May 2022

High-Dose Convalescent Plasma for Treatment of Severe COVID-19 (response)

Cite This Article

In Response: We thank Focosi and Casadevall for their comments (1). One strong contribution of our study was the high dose (i.e., 1,800 mL in 3 days) of coronavirus disease (COVID-19) convalescent plasma (CCP), which, in our opinion, would be more likely to benefit patients than a lower dose (e.g., 200–600 mL in 1 or 2 doses), as is the protocol in most CCP studies (including but not limited to COVID-19 treatment) (2).

The weak point of our study was the relatively large therapeutic window (up to 10 days of signs/symptoms) for CCP transfusion, which may have included the later inflammatory process of illness. One early trial suggested benefit for COVID-19 patients who received CCP within the first 14 days (3). Nevertheless, subsequent trials showed that CCP (or serum) administration could be most beneficial for COVID-19 patients when administered as prophylaxis or within the first days of infection (4,5), ideally, within the first 3 days (6) but perhaps not later (7,8). We emphasize that CCP transfusion was considered experimental at the beginning of the pandemic, and inclusion criteria comprised only patients with severe illness, for whom >7 days of infection are needed for illness to become evident.

We think that applying the suggested formula to identify which COVID-19 patients are likely to benefit from CCP (higher risk for progression to severe disease) would not be applicable to our study because it was envisaged for patients not receiving mechanical ventilation (9), whereas the patients in our study had severe disease (90% receiving mechanical ventilation).

In summary, our study emphasizes that CCP should not be transfused late in the course of disease, when the clinical course is driven by inflammation. This conclusion does not exclude the possibility of transfusing CCP as soon as patients are identified for potential benefit, as suggested by other studies (6,7).


Gil C. De SantisComments to Author  and Rodrigo T. Calado
Author affiliation: University of São Paulo, São Paulo, Brazil



  1. De Santis  GC, Oliveira  LC, Garibaldi  PMM, Almado  CEL, Croda  J, Arcanjo  GGA, et al. High-dose convalescent plasma for treatment of severe COVID-19. Emerg Infect Dis. 2022;28:54855; Epub ahead of print. DOIPubMedGoogle Scholar
  2. Bloch  EM, Shoham  S, Casadevall  A, Sachais  BS, Shaz  B, Winters  JL, et al. Deployment of convalescent plasma for the prevention and treatment of COVID-19. J Clin Invest. 2020;130:275765. DOIPubMedGoogle Scholar
  3. Cheng  Y, Wong  R, Soo  YO, Wong  WS, Lee  CK, Ng  MH, et al. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis. 2005;24:446. DOIPubMedGoogle Scholar
  4. Focosi  D, Franchini  M, Pirofski  LA, Burnouf  T, Fairweather  D, Joyner  MJ, et al. COVID-19 convalescent plasma is more than neutralizing antibodies: a narrative review of potential beneficial and detrimental co-factors. Viruses. 2021;13:1594. DOIPubMedGoogle Scholar
  5. Casadevall  A, Scharff  MD. Serum therapy revisited: animal models of infection and development of passive antibody therapy. Antimicrob Agents Chemother. 1994;38:1695702. DOIPubMedGoogle Scholar
  6. Libster  R, Pérez Marc  G, Wappner  D, Coviello  S, Bianchi  A, Braem  V, et al.; Fundación INFANT–COVID-19 Group. Early high-titer plasma therapy to prevent severe Covid-19 in older adults. N Engl J Med. 2021;384:6108. DOIPubMedGoogle Scholar
  7. Korley  FK, Durkalski-Mauldin  V, Yeatts  SD, Schulman  K, Davenport  RD, Dumont  LJ, et al.; SIREN-C3PO Investigators. SIREN-C3PO Investigators. Early convalescent plasma for high-risk outpatients with Covid-19. N Engl J Med. 2021;385:195160. DOIPubMedGoogle Scholar
  8. Simonovich  VA, Burgos Pratx  LD, Scibona  P, Beruto  MV, Vallone  MG, Vázquez  C, et al.; PlasmAr Study Group. PlasmAr Study Group. A randomized trial of convalescent plasma in Covid-19 severe pneumonia. N Engl J Med. 2021;384:61929. DOIPubMedGoogle Scholar
  9. Park  H, Tarpey  T, Liu  M, Goldfeld  K, Wu  Y, Wu  D, et al. Development and validation of a treatment benefit index to identify hospitalized patients with COVID-19 who may benefit from convalescent plasma. JAMA Netw Open. 2022;5:e2147375. DOIPubMedGoogle Scholar


Cite This Article

DOI: 10.3201/eid2805.220363

Original Publication Date: April 11, 2022

Related Links


Table of Contents – Volume 28, Number 5—May 2022

EID Search Options
presentation_01 Advanced Article Search – Search articles by author and/or keyword.
presentation_01 Articles by Country Search – Search articles by the topic country.
presentation_01 Article Type Search – Search articles by article type and issue.



Please use the form below to submit correspondence to the authors or contact them at the following address:

Gil C. De Santis, Rua Tenente Catão Roxo, 2501 Ribeirão Preto, 14051-140 SP, Brazil

Send To

10000 character(s) remaining.


Page created: March 23, 2022
Page updated: April 19, 2022
Page reviewed: April 19, 2022
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.