Outpatient convalescent plasma therapy for high-risk patients with early COVID-19: a randomized placebo-controlled trial

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.

Keywords: Antibodies; COVID-19; Convalescent plasma; Outpatients; Therapy.

Fig. 1

Consolidated Standards of Reporting Trials flow diagram. CP, convalescent plasma.

Fig. 2

Antibody titres over time between patients in the CP and non-CP groups using a mixed effects model. The line represents fitted log (antibodies in BAU/mL + 1), and the dotted line represents 95% CIs. Eighty-five patients had a day 1 measurement, 82 patients had a day 3 measurement, 79 patients had a day 7 measurement, 83 patients had a day 14 measurement and 82 patients had a day 28 measurement. BAU, binding antibody unit; CP, convalescent plasma.