Convalescent plasma does not reduce mortality, disease progression in COVID-19
During the earliest days of the novel coronavirus disease (COVID-19) pandemic, convalescent plasma has generated great enthusiasm for its potential in treating the disease, but a recent study shows that its use does not lead to reduction in progression to severe COVID-19 or all-cause mortality.
“Although the use of convalescent plasma seemed to improve resolution of shortness of breath and fatigue in patients with moderate COVID-19 and led to higher negative conversion of SARS-CoV-2 RNA on day 7 postenrolment, this did not translate into a reduction in 28-day mortality or progression to severe disease,” the researchers said.
Thirty-nine public and private hospitals across India participated in this open-label, parallel arm, phase II, multicentre, randomized controlled trial (RCT). Overall, 464 adults (aged ≥18 years) with confirmed moderate COVID-19 were included in the analysis: 235 were assigned to convalescent plasma with best standard of care (intervention arm) and 229 to best standard of care only (control arm).
Patients in the intervention arm received two doses of 200 mL convalescent plasma, transfused 24 hours apart. The presence and levels of neutralizing antibodies were not measured a priori, and stored samples were assayed at end of study.
The primary outcome of a composite of progression to severe disease (PaO2/FiO2 <100 mm Hg) or all-cause mortality at 28 days after enrolment occurred in 44 patients (19 percent) in the intervention arm and 41 (18 percent) in the control arm (risk difference, 0.008, 95 percent confidence interval [CI], –0.062 to 0.078; risk ratio, 1.04, 95 percent CI, 0.71–1.54). [BMJ 2020;371:m3939]
Mortality within 28 days of enrolment occurred in 34 patients (15 percent) in the intervention arm and 31 (14 percent) in the control arm (risk ratio, 1.04, 95 percent CI, 0.66–1.63, while progression to severe disease occurred in 17 patients from each arm (risk ratio, 1.04, 0.54–1.98).
“This trial has high generalizability and approximates convalescent plasma use in real life settings with limited laboratory capacity,” the researchers said. “A priori measurement of neutralizing antibody titres in donors and participants might further clarify the role of convalescent plasma in the management of COVID-19.”
In a recent Cochrane review of 20 studies (one RCT, three controlled nonrandomized studies of intervention, and 16 noncontrolled nonrandomized studies of intervention), results showed unclear effectiveness of convalescent plasma in improving mortality or clinical improvement in COVID-19 patients. [Cochrane Database Syst Rev 2020;7:CD013600]
Furthermore, an RCT of 103 patients with severe COVID-19 in China found no effect of convalescent plasma treatment on time to clinical improvement. [JAMA 2020;324:460-470]
“Areas of future research could include effectiveness of convalescent plasma among neutralizing antibody negative patients and the use of convalescent plasma with high neutralizing antibody titres,” the researchers said. “The challenge will be to find both suitable patients and suitable plasma donors.”
In an editorial, Elizabeth B. Pathak, president of Women’s Institute for Independent Social Enquiry, stated that the desperation engendered by COVID-19 demands to “strongly resist the urge to succumb to pandemic research exceptionalism,” adding that high quality clinical research should be an integral part of a coordinated international response. [BMJ 2020;371:m4072; Science 2020;368:476-477]
“Specifically, scientific validity is a necessary component of ethical research. Low quality research not only wastes scarce resources, it is also inherently unethical,” she added. [JAMA 2000;283:2701-2711]