Convalescent plasma ineffective for COVID-19

A recent Singapore meta-analysis of randomized controlled trials (RCT) has found no clear clinical benefit to using convalescent plasma (CP) for patients with the coronavirus disease 2019 (COVID-19), especially in those with severe disease.

“Nonetheless, its therapeutic use in patients unable to mount an adequate immune response remains undetermined,” they said. “Rather than determining its effectiveness in COVID-19 in general, further research on CP should be directed in highly select patient groups and determining which subgroup of patients is most likely to benefit.”

A total of 18 RCTs were deemed eligible for quantitative analysis after searching through six online databases. In aggregate, 8,702 COVID-19 patients received CP and were compared against 7,906 controls who were not given CP. In terms of quality, six included trials were deemed to have low risk of bias while only one had a high risk for such. Certainty of evidence was classified as high according to the Grading of Recommendations, Assessment, Development, and Evaluations tool. [Transfus Med Rev 2021;doi:10.1016/j.tmrv.2021.09.001]

Pooled analysis of the 18 studies showed that there were 2,121 and 1,984 deaths in the CP and control arms, yielding comparable mortality rates of 24.4 percent and 25.1 percent, respectively. In turn, there was no significant difference in risk estimates between arms (risk ratio [RR], 0.95, 95 percent confidence interval [CI], 0.86–1.04 p=0.27).

The null effect of CP on mortality remained true even after trim-and-fill corrections for small-study effects (RR, 0.98, 95 percent CI, 0.86–1.11; p=0.71).

Moreover, a subsequent futility analysis showed that the cumulative Z-curve was unable to cross the boundaries for either benefit or harm and fell within the boundaries of futility. This suggested that even with further enrolment and randomization of patients, CP was unlikely to demonstrate significant clinical benefit over the control.

Similarly, CP failed to demonstrate significant clinical benefit even in subgroup analyses according to timing of administration and geographical location. There was also no between-arm difference in terms of the need for mechanical ventilation (RR, 1.00, 95 percent CI, 0.91–1.10; p=0.99) and hospital length of stay (difference, 1.32 days, 95 percent CI, –1.86 to 4.51; p=0.33).

“The added value of our study lies in the finding that further recruitment of patients is futile in eliciting the effect of CP in patients with severe COVID-19, which previous meta-analyses have not investigated,” the researchers said.

“More importantly, the finding of futility holds massive public health implications, particularly when the delta variant becomes increasingly prevalent,” they added, pointing out that in favour of CP, “[i]mmense amounts of resources are diverted away from other potentially beneficial therapies, as well as vaccine production.”

Establishing futility of CP could help prevent such diversion.