Convalescent plasma may have benefited patients in early days of COVID-19 pandemic

Results from the CONTAIN COVID-19 trial showed that convalescent plasma did not meet prespecified efficacy endpoints in patients hospitalized with COVID-19.

However, exploratory subgroup analyses of the trial revealed that high-titer COVID-19 convalescent plasma (CCP) may have benefited patients before remdesivir and corticosteroids were available, indicating “a heterogenous treatment effect over time,” researchers wrote.

While previous matched-controlled studies of early CCP lowered mortality in hospitalized patients, randomized clinical trials have produced mixed results, Mila B. Ortigoza, MD, PhD, an assistant professor in the departments of medicine and microbiology at NYU Grossman School of Medicine, and colleagues wrote in JAMA Internal Medicine.

For the CONTAIN COVID-19 trial, Ortigoza and colleagues randomly assigned 941 hospitalized patients in an approximate 1:1 ratio (median age = 63 years, 59.1% men) to receive approximately 250 mL of CCP or placebo. All the patients had been hospitalized for 3 or fewer days or presented 7 or fewer days after their symptoms began and needed noninvasive oxygen supplementation. At the time of randomization — from April 17, 2020, to March 15, 2021 — most of the patients were not receiving remdesivir and corticosteroids, according to Ortigoza and colleagues.

The researchers reported that the cumulative adjusted odds ratio (cOR) for the primary outcome — a patient’s score on the 11-point WHO Ordinal Scale for Clinical Improvement on day 14 after randomization — was 0.94 (95% credible interval [CrI], 0.75-1.18), with posterior probability. The cOR for the secondary outcome — WHO Ordinal Scale for Clinical Improvement on day 28 — was 0.92 (95% CrI, 0.74-1.16).

In the exploratory subgroup analyses, Ortigoza and colleagues reported a potential benefit of CCP among patients who were enrolled from April 2020 to June 2020, a time when most patients received high titer CCP and were not receiving remdesivir or corticosteroids (cOR at day 28 = 0.72; 95% CrI, 0.46-1.13). In an analysis limited to those who were not administered remdesivir or corticosteroids at randomization, the cOR was 0.65 (95% CrI, 0.41-1.02). However, the researchers emphasized that these findings “cannot establish the effect of these medications on CCP efficacy; they were not randomized, the trial was not designed to investigate their effects, and the analyses were exploratory.”

“Further investigation is needed to understand the effects of corticosteroids and remdesivir on CCP efficacy,” they wrote.

Ortigoza and colleagues also noted that previous studies of hospitalized patients “identified a CCP benefit in older patients and those with less severe disease.”

“Given the absence of overall CCP benefit in our trial and randomized clinical trials of hospitalized patients with severe to life-threatening disease, it is possible that patients with less severe disease could benefit the most from CCP therapy,” they wrote.