Randomised double-blinded placebo-controlled trial (Orange)
Early administration of convalescent plasma obtained from blood donors who have recovered from coronavirus disease 2019 (COVID-19) may prevent disease progression in acutely ill, high-risk patients with COVID-19. In this randomized, multicenter, single-blind trial, the authors assigned patients who were being treated in an emergency department for COVID-19 symptoms to receive either one unit of convalescent plasma with a high titer of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or placebo. All the patients were either 50 years of age or older or had one or more risk factors for disease progression. In addition, all the patients presented to the emergency department within 7 days after symptom onset and were in stable condition for outpatient management. The primary outcome was disease progression within 15 days after randomization, which was a composite of hospital admission for any reason, seeking emergency or urgent care, or death without hospitalization. Secondary outcomes included the worst severity of illness on an 8-category ordinal scale, hospital-free days within 30 days after randomization, and death from any cause.
A total of 511 patients were enrolled in the trial (257 in the convalescent-plasma group and 254 in the placebo group). The median age of the patients was 54 years; the median symptom duration was 4 days. In the donor plasma samples, the median titer of SARS-CoV-2 neutralizing antibodies was 1:641. Disease progression occurred in 77 patients (30.0%) in the convalescent-plasma group and in 81 patients (31.9%) in the placebo group (risk difference, 1.9 percentage points; 95% credible interval, −6.0 to 9.8; posterior probability of superiority of convalescent plasma, 0.68). Five patients in the plasma group and 1 patient in the placebo group died. Outcomes regarding worst illness severity and hospital-free days were similar in the two groups. The authors concluded that the administration of COVID-19 convalescent plasma to high-risk outpatients within 1 week after the onset of symptoms of COVID-19 did not prevent disease progression.
Korley FK, Durkalski-Mauldin V, Yeatts SD, Schulman K, Davenport RD, Dumont LJ, El Kassar N, Foster LD, Hah JM, Jaiswal S, Kaplan A, Lowell E, McDyer JF, Quinn J, Triulzi DJ, Van Huysen C, Stevenson VLW, Yadav K, Jones CW, Kea B, Burnett A, Reynolds JC, Greineder CF, Haas NL, Beiser DG, Silbergleit R, Barsan W, Callaway CW; SIREN-C3PO Investigators. Early Convalescent Plasma for High-Risk Outpatients with COVID-19. N Engl J Med. 2021 Aug 18. doi: 10.1056/NEJMoa2103784.