Researchers investigated the safety and efficacy of COVID-19 convalescent plasma (CCP), vs placebo, in improving the clinical status of hospitalized patients with COVID-19 requiring noninvasive supplemental oxygen.

• A randomized clinical trial including 941 patients; a unit of approximately 250 mL of CCP or equivalent volume of placebo (normal saline) was administered to the participants.

• Based on the World Health Organization 11-point Ordinal Scale for Clinical Improvement, no benefit of administering CCP was observed in 468 participants randomized to CCP compared with 473 randomized to placebo from April 2020 to March 2021.

• However, in exploratory analyses, those enrolled from April to June 2020 appeared to retrieve some benefit from CCP; this is the period when most participants received high-titer CCP and were not receiving remdesivir and corticosteroids at randomization.

• In this trial, prespecified outcomes for efficacy are not met by CCP, however, high-titer CCP may have benefited hospitalized patients with COVID-19 early in the pandemic when there were no other treatments, indicating a heterogeneous treatment effect over time.