On Aug. 18, 2021, the final results of the Clinical Trial of COVID-19 Convalescent Plasma in Outpatients (C3PO) demonstrated that COVID-19 convalescent plasma did not prevent disease progression in a high-risk group of outpatients with COVID-19, when administered within the first week of their symptoms. The trial was stopped in February 2021 due to lack of efficacy based on a planned interim analysis. The formal conclusions from the trial appeared in The New England Journal of Medicine.

COVID-19 convalescent plasma, also known as “survivor’s plasma,” is blood plasma derived from patients who have recovered from COVID-19. Last year, the U.S. Food and Drug Administration issued an Emergency Use Authorization to allow use of convalescent plasma in hospitalized patients with COVID-19. Researchers wanted to know whether administering COVID-19 convalescent plasma might also be beneficial in persons who were recently infected with SARS-CoV-2, the virus that causes the disease, but who were not severely ill and could be treated as outpatients. The objective was to prevent progression to severe COVID-19 illness.

The C3PO trial, launched in August 2020, was designed to answer that question. The randomized, controlled clinical trial involved adult outpatients who presented to emergency departments with mild COVID-19 symptoms during their first week post-infection. The trial was conducted by the SIREN clinical trials network, and enrolled more than 500 participants from 48 emergency departments across the United States. The participants were racially and ethnically diverse with a median age of 54 years, and slightly more than half were women. Participants also had at least one risk factor for progression to severe COVID-19, such as obesity, hypertension, diabetes, heart disease, or chronic lung disease. The researchers randomly assigned the participants to receive treatment with either high-titer COVID-19 convalescent plasma (containing anti-COVID-19 antibodies) or placebo (salt solution infused with multivitamins and lacking antibodies).

Researchers compared outcomes in both groups within 15 days of treatment, looking specifically at whether the patients needed to seek further emergency or urgent care, were admitted to the hospital, or died. The researchers found no significant difference in disease progression between the two groups. Of the 511 participants, disease progression occurred in 77 (30%) in the COVID-19 plasma group compared with 81 patients (31.9%) in the placebo group. The plasma intervention did not cause harm, the researchers found.

Additional studies of COVID-19 convalescent plasma are ongoing or planned in different populations. These included the Pass It On trial, a nationwide, National Institutes of Health-funded randomized clinical trial using convalescent plasma to treat hospitalized adult patients with COVID-19 infection to see if the treatment can help them recover faster. Other trials include one in outpatients who are recovering at home and one in individuals with high risk of exposure to COVID-19 to see if COVID-19 convalescent plasma can prevent infection.