Abstract
Objectives: The potential benefit of convalescent plasma (CP) therapy for coronavirus disease 2019 (COVID-19) is highest when administered early after symptom onset. Our objective was to determine the effectiveness of CP therapy in improving the disease course of COVID-19 among high-risk outpatients. Methods: A multicentre, double-blind randomized trial was conducted comparing 300 mL of CP with non-CP. Patients were ≥50 years, were symptomatic for <8 days, had confirmed RT-PCR or antigen test result for COVID-19 and had at least one risk factor for severe COVID-19. The primary endpoint was the highest score on a 5-point ordinal scale ranging from fully recovered (score = 1) or not (score = 2) on day 7, over hospital admission (score = 3), intensive care unit admission (score = 4) and death (score = 5) in the 28 days following randomization. Secondary endpoints were hospital admission, symptom duration and viral RNA excretion. Results: After the enrolment of 421 patients and the transfusion in 416 patients, recruitment was discontinued when the countrywide vaccination uptake in those aged >50 years was 80%. Patients had a median age of 60 years, symptoms for 5 days, and 207 of 416 patients received CP therapy. During the 28 day follow-up, 28 patients were hospitalized and two died. The OR for an improved disease severity score with CP was 0.86 (95% credible interval, 0.59–1.22). The OR was 0.58 (95% CI, 0.33–1.02) for patients with ≤5 days of symptoms. The hazard ratio for hospital admission was 0.61 (95% CI, 0.28–1.34). No difference was found in viral RNA excretion or in the duration of symptoms. Conclusions: In patients with early COVID-19, CP therapy did not improve the 5-point disease severity score.
| Original language | English |
|---|---|
| Pages (from-to) | 208-214 |
| Number of pages | 7 |
| Journal | Clinical Microbiology and Infection |
| Volume | 29 |
| Issue number | 2 |
| Early online date | Aug 2022 |
| DOIs | |
| Publication status | Published - Feb 2023 |
Bibliographical note
Funding Information:The CoV-Early study (clinical registry number: NCT04589949) was a phase 3, multicentre, randomized, double-blind, placebo-controlled trial conducted in the Netherlands The study was funded by ZonMw (grant-number 10430062010001) and supported by Sanquin (Dutch blood supply), which provided the plasma. A complete list of participating sites is available in our online protocol. This study was approved by the medical ethical review board of the Erasmus MC (METC-2020-0682).
Funding Information:
The authors thank the following: the Data Safety Monitoring Board (DSMB) members for CoV-Early study (Prof. P.M. Bossuyt, Dr. J.L. Nouwen, Prof, M.C. de Vries); all Public Health Service contact tracers who informed potential study candidates; all infectiologists at Erasmus MC who worked even harder during the COVID-19 times to let the study team focus on the COVID-19 trials (Adam Anas, Hannelore Bax, Mariana de Mendonça-Melo, Els van Nood, Jan Nouwen, Karin Schurink, Lennert Slobbe, Dorine de Vries-Sluijs and Annelies Verbon) and the emergency department physicians and colleagues from the department of internal medicine who referred patients and facilitated patient recruitment; the medical students who contacted the patients (Romée Land, Eva Pruijt, Silje Taal, Liselotte Jeletich, Willem Sebrechts, Femke de Vries and Tia Rijlaarsdam); the many research assistants, research nurses and other participants who helped in facilitating the study (Maartje Wagemaker, Ayten Karisli, René van Engen, Marita Tjauw Joe Kim – Amadmoestar, Diane Struik, Denise Heida-Peters, Sabine Harinck, Marjo van der Poel, Greetje van Asselt, Danielle Orij – Westerhof, Marloes Romeijn, Marlies Bouterse, Pepita de Vries, Dewi Dubbelaar, Cynthia Oud, Jo Anne den Ouden, Milly Haverkort); Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON) for building the electronic case report form (eCRF) and providing real-time support with the eCRF on very short notice (Henk Hofwegen, Ronnie van der Holt, Mirjam Stomp, Marleen Luten and Monique Steijart); all the persons involved in the blinding and distribution of plasma products at the sites; and last but certainly not least, all patients who participated in the trial, the thousands of plasma donors and the COVID-19 test centres that informed patients across the Netherlands about the study.
Publisher Copyright:
© 2022 The Authors
