Convalescent plasma therapy didn't help 52 seriously ill COVID-19 patients recover in the first known randomized study of its kind, although it was stopped early because of low enrollment.
The study, published yesterday in JAMA, involved coronavirus patients with severe illness (respiratory distress and/or low oxygen levels) or life-threatening disease (shock, organ failure, or the need for mechanical ventilation) in seven medical centers in Wuhan, China, from Feb 14 to Apr 1, with final follow-up on Apr 28.
The trial was stopped early because, owing to containment of the Wuhan outbreak, researchers were able to recruit only 103 of 200 patients needed to generate a clinically meaningful result. One patient withdrew from the study, and one in the control group received convalescent plasma, a protocol violation, because of a life-threatening infection.
Convalescent plasma therapy, which dates back to the early 20th century, involves the transfusion of blood plasma collected from patients recovered from infection to improve immune response in the recipient. Although evidence supporting its use in COVID-19 patients is scarce, the US Food and Drug Administration (FDA) recently approved its emergency use in patients who have severe or life-threatening coronavirus infection.
Clinical status, death rates
Twenty-seven (51.9%) of 52 patients randomly assigned by disease severity to receive a single dose of convalescent plasma improved within 28 days, versus 22 (43.1%) of 51 given standard treatment alone (difference, 8.8 percentage points [95% confidence interval (CI), −10.4 to 28.0]; hazard ratio [HR], 1.40 [95% CI, 0.79 to 2.49]; P = .26).
Twenty-one (91.3%) of 23 patients with severe illness receiving convalescent plasma recovered (were released from the hospital or achieved a two-point reduction on a six-point illness-severity scale) within 28 days, versus 15 (68.2%) of 22 receiving standard treatment (HR, 2.15 [95% CI, 1.07 to 4.32]; P = .03).
Six (20.7%) of 29 patients with life-threatening disease receiving convalescent plasma recovered, compared with 7 (24.1%) of 29 of the control group (HR, 0.88 [95% CI, 0.30 to 2.63]; P = .83).
Death rates were not significantly different between the convalescent plasma group (15.7%) and the control group (24.0%) (odds ratio [OR], 0.65 [95% CI, 0.29 to 1.46]; P = .30). Nor were they different in terms of time to hospital release within 28 days (51.0% in the convalescent plasma group vs 36.0% in the control group; HR, 1.61 [95% CI, 0.88 to 2.93]; P = .12).
Rates of negative polymerase chain reaction results in the convalescent plasma group were all significantly higher than those of the standard treatment group (44.7% vs 15.0%, P = .003 at 24 hours; 68.1% vs 32.5%, P = .001 at 48 hours; and 87.2% vs 37.5%, P < .001 at 72 hours).
Two patients receiving convalescent plasma group experienced adverse events within hours after transfusion but improved with supportive care. Median patient age was 70 years, and 60 (58.3%) of 101 were men. Median time from symptom onset and random assignment was 30 days.
Of patients with severe disease, 2 (9.1%) in the control group and zero in the convalescent plasma group died. Of those with life-threatening disease, 8 patients (28.6%) in the convalescent plasma group died, while 10 patients (35.7%) in the control group died.
'Potentially hopeful' results
The authors noted that most previous studies on convalescent plasma lacked standardization and procedure control in donor selection and the type or level of antibodies in the convalescent plasma.
"This may explain the varied therapeutic effects seen across a variety of diseases or even across patients with the same disease," they said, adding that the World Health Organization has issued guidance on clinical trials of convalescent plasma in a pandemic.
The researchers called for further studies on optimal patient selection and timing of convalescent plasma therapy in COVID-19 patients.
In a commentary in the same journal, Arturo Casadevall, MD, PhD, of the Johns Hopkins Bloomberg School of Public Health in Baltimore and colleagues said that while convalescent plasma didn't lead to significant improvements in clinical status or death rate, the study generated "potentially hopeful signals," adding that convalescent plasma may be useful in combination with antiviral drugs.
"Given that the mechanisms of action of antiviral drugs and neutralizing antibodies are distinct, they could be synergistic," they wrote.
