Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial

Abstract

Importance: Convalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19), but further data from randomized clinical trials are needed.

Objective: To evaluate the efficacy and adverse effects of convalescent plasma therapy for patients with COVID-19.

Design, setting, and participants: Open-label, multicenter, randomized clinical trial performed in 7 medical centers in Wuhan, China, from February 14, 2020, to April 1, 2020, with final follow-up April 28, 2020. The trial included 103 participants with laboratory-confirmed COVID-19 that was severe (respiratory distress and/or hypoxemia) or life-threatening (shock, organ failure, or requiring mechanical ventilation). The trial was terminated early after 103 of a planned 200 patients were enrolled.

Intervention: Convalescent plasma in addition to standard treatment (n = 52) vs standard treatment alone (control) (n = 51), stratified by disease severity.

Main outcomes and measures: Primary outcome was time to clinical improvement within 28 days, defined as patient discharged alive or reduction of 2 points on a 6-point disease severity scale (ranging from 1 [discharge] to 6 [death]). Secondary outcomes included 28-day mortality, time to discharge, and the rate of viral polymerase chain reaction (PCR) results turned from positive at baseline to negative at up to 72 hours.

Results: Of 103 patients who were randomized (median age, 70 years; 60 [58.3%] male), 101 (98.1%) completed the trial. Clinical improvement occurred within 28 days in 51.9% (27/52) of the convalescent plasma group vs 43.1% (22/51) in the control group (difference, 8.8% [95% CI, -10.4% to 28.0%]; hazard ratio [HR], 1.40 [95% CI, 0.79-2.49]; P = .26). Among those with severe disease, the primary outcome occurred in 91.3% (21/23) of the convalescent plasma group vs 68.2% (15/22) of the control group (HR, 2.15 [95% CI, 1.07-4.32]; P = .03); among those with life-threatening disease the primary outcome occurred in 20.7% (6/29) of the convalescent plasma group vs 24.1% (7/29) of the control group (HR, 0.88 [95% CI, 0.30-2.63]; P = .83) (P for interaction = .17). There was no significant difference in 28-day mortality (15.7% vs 24.0%; OR, 0.59 [95% CI, 0.22-1.59]; P = .30) or time from randomization to discharge (51.0% vs 36.0% discharged by day 28; HR, 1.61 [95% CI, 0.88-2.95]; P = .12). Convalescent plasma treatment was associated with a negative conversion rate of viral PCR at 72 hours in 87.2% of the convalescent plasma group vs 37.5% of the control group (OR, 11.39 [95% CI, 3.91-33.18]; P < .001). Two patients in the convalescent plasma group experienced adverse events within hours after transfusion that improved with supportive care.

Conclusion and relevance: Among patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment, compared with standard treatment alone, did not result in a statistically significant improvement in time to clinical improvement within 28 days. Interpretation is limited by early termination of the trial, which may have been underpowered to detect a clinically important difference.

Trial registration: Chinese Clinical Trial Registry: ChiCTR2000029757.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Liu reports holding a pending patent on COVID-19 testing. Dr Wu reports consulting for Verax Medical and Grifols, receiving royalties from UptoDate and AABB, and being a volunteer visiting professor and receiving travel support for giving medical education from the Chinese Institute of Blood Transfusion. No other disclosures were reported.

Figures

Figure 1.. Patient Enrollment and Treatment Assignment

PCR indicates polymerase chain reaction; CHF, congestive heart failure; COVID-19, coronavirus disease 2019.

Figure 2.. Time to Clinical Improvement in Patients With COVID-19

The cumulative improvement rate is the percentage of patients who experienced a 2-point improvement or were discharged alive from the hospital. Ticks on the curves indicate censored events. All patients who did not reach clinical improvement were observed for the full 28-day period or until death. COVID-19 indicates coronavirus disease 2019. The median (IQR) follow-up times for the convalescent plasma group and control group, respectively, were 15 (10-28) days and 24 (13-28) days overall; 13 (10-16) and 18.5 (11-26) days among those with severe COVID-19; and 28 (12-28) and 26 (15-28) days among those with life-threatening COVID-19.