NEJM Journal Watch
Carlos del Rio, MD reviewing
In a multicenter, open-label study in patients with severe or life-threatening COVID-19, convalescent plasma did not provide added clinical benefit to standard treatment.
Convalescent plasma has been suggested as a possible treatment option for COVID-19. Now, investigators from China have conducted a multicenter, open-label, randomized clinical trial of convalescent plasma added to standard of care among patients with confirmed SARS-CoV-2 infection, stratified into severe or life-threatening disease. Convalescent plasma was obtained from persons who had recovered from COVID-19 and were more than 2 weeks out from hospital discharge. Only plasma with an IgG titer against the S protein-receptor binding domain of at least 1:640 was used, at a dose of 4 to 13 mL/kg (median infusion, 200 mL). The primary endpoint was time to clinical improvement within 28 days, defined as discharge or a reduction of 2 points on a 6-point disease severity scale.
Although a 200-participant study was planned, early termination for lack of patients in Wuhan after March 27 occurred, with 103 participants enrolled, 52 (23 with severe and 29 with life-threatening disease) in the convalescent-plasma group and 51 (22 with severe and 29 with life-threatening disease) in the control group. Median age was 70 years; 58.3% male. Clinical improvement occurred in 27 convalescent-plasma recipients (51.9%) and 22 control patients (43.1%), a nonsignificant difference. Among those with severe disease, the primary outcome occurred in 91.3% versus 68.2%, suggesting a possible benefit, but the test for interaction by disease severity was not significant. Convalescent plasma treatment was associated with higher rates of negative SARS-CoV-2 polymerase chain reaction tests from nasopharyngeal swabs, suggesting antiviral activity. The early termination could have underpowered the study, the authors note.
This well-conducted randomized clinical trial of convalescent plasma in patients with COVID-19 suggests that this treatment is not of benefit in all patients but may have a role in some patients with severe disease. The study only included patients with advanced disease, and most had symptoms for more than 14 days, so it did not address the possible impact of convalescent plasma on less-severe disease. Future studies are needed to further define the role of convalescent plasma in the management of COVID-19.