Convalescent Plasma in Patients Admitted to Hospital With COVID-19

Quick Takes

  • RECOVERY is large, multicenter, adaptive trial of 177 NHS hospitals in the UK, which previously also investigated and published other COVID-19 treatments (dexamethasone, hydroxychloroquine, lopinavir-ritonavir, azithromycin, and tocilizumab).
  • For patients hospitalized with COVID-19, high-titer convalescent plasma has no therapeutic benefit.

Study Questions:

What is the safety and efficacy of high-titer convalescent plasma therapy in patients admitted to the hospital with coronavirus disease 2019 (COVID-19)?

Methods:

RECOVERY (Randomized Evaluation of COVID-19 Therapy) is a randomized, controlled, open-label, adaptive trial of 177 National Health Service (NHS) hospitals in the United Kingdom (UK), which previously also investigated and published other treatments (dexamethasone, hydroxychloroquine, lopinavir-ritonavir, azithromycin, and tocilizumab). After assessing for the presence of antibodies against acute respiratory syndrome coronavirus 2 (SARS-CoV-2), eligible patients were randomized (1:1) to usual care with or without high-titer convalescent plasma, defined as having a sample to cutoff ratio of ≥6.0 on the EUROIMMUN IgG ELISA for spike glycoprotein. This value had been previously shown to be associated with neutralizing titers of 1:100 or more in convalescent plasma and was nearly twice the cutoff ratio of 3.5 specified in the Emergency Use Authorization of the US Food and Drug Administration. The primary outcome was all-cause 28-day mortality. Secondary outcomes included time to discharge from hospital, need for dialysis or hemofiltration, and (in patients not already on the ventilator at time of randomization) need for mechanical ventilation (including extracorporeal membrane oxygenation). Safety outcomes were transfusion-related events.

Results:

Between May 2020 and January 2021, 11,558 (71%) of 16,287 patients enrolled in RECOVERY were randomized to either the usual care group (5,763) or plasma group (5,795). Mean age was 63.5 (standard deviation, 14.7 years); median time from symptom onset to randomization was 9 days (interquartile range, 6-12). At randomization, 5% of all patients were receiving invasive mechanical ventilation, 87% were receiving supplemental oxygen only, and 8% were receiving no oxygen; 92% of patients were receiving steroids at the time of randomization. There was no significant difference in the primary endpoint, with a 28-day mortality of 24.4% in the usual care group and 24.1% in the plasma group (rate ratio [RR], 1.0; 95% confidence interval [CI], 0.93-1.07; p = 0.95). This endpoint was similar in prespecified subgroups based on age (<70, 70-79, >80 years old), sex, ethnicity, days since symptom onset, respiratory support received, use of steroids, and presence or absence of pre-existing SARS-CoV-2 antibodies at the time of randomization. There was no difference between length of stay, with 66% of both groups discharged within 28 days (RR, 0.9; 95% CI, 0.94-1.03; p = 0.57). For patients not on invasive mechanical ventilation at the time of randomization, there was no significant difference in progression to mechanical ventilation (29% in both groups, RR, 0.99; 95% CI, 0.93-1.05; p = 0.79).

Conclusions:

For patients hospitalized with COVID-19, convalescent plasma has no therapeutic benefit.

Perspective:

RECOVERY is the largest randomized trial to date studying the effects of high-titer convalescent plasma in patients hospitalized with COVID. Their findings are consistent with several prior trials and provide the most definitive answer possible that convalescent plasma (even high-titer) has no therapeutic benefits across any subgroups. Perhaps the only remaining question is whether convalescent plasma may be able to limit disease progression in outpatients or patients with early COVID-19, a question being addressed in a recently completed randomized controlled trial (NCT 04355767).

Clinical Topics: Prevention, Novel Agents, Statins

Keywords: Azithromycin, Coronavirus, COVID-19, ACC COVID-19 Podcast, Dexamethasone, Disease Progression, Extracorporeal Membrane Oxygenation, Glycoproteins, Hydroxychloroquine, Immunoglobulin G, Lopinavir, Length of Stay, Patient Discharge, Plasma, Primary Prevention, Respiration, Artificial, Ritonavir, SARS-CoV-2, Steroids, Ventilators, Mechanical


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