Outpatients With COVID-19 Experienced No Significant Benefit From COVID-19 Convalescent Plasma


COVID-19 convalescent plasma administered within the first week of symptoms did not prevent disease progression in a high-risk group of outpatients.

COVID-19 convalescent plasma administered within the first week of symptoms did not prevent disease progression in a high-risk group of outpatients with COVID-19, according to the results of the Clinical Trial of COVID-19 Convalescent Plasma in Outpatients (C3PO) study published in the New England Journal of Medicine.

“We were hoping that the use of COVID-19 convalescent plasma would achieve at least a 10% reduction in disease progression in this group, but instead the reduction we observed was less than 2%,” said Clifton Callaway, MD, PhD, professor of emergency medicine at the University of Pittsburgh, in a press release. “That was surprising to us. As physicians, we wanted this to make a big difference in reducing severe illness and it did not.”

COVID-19 convalescent plasma is blood plasma derived from patients who have recovered from the virus. The FDA issued the treatment an Emergency Use Authorization in 2020, allowing the use of convalescent plasma in hospitalized patients with COVID-19.

The investigators sought to determine whether administering COVID-19 convalescent plasma might also be beneficial in persons who were recently infected with SARS-CoV-2 but who were not severely ill and could be treated as outpatients. The C3PO trial, a randomized, controlled clinical trial, enrolled more than 500 outpatients who presented to emergency departments with mild COVID-19 symptoms during their first week post-infection. All trial participants had at least 1 risk factor for progression to severe COVID-19, such as obesity, hypertension, diabetes, heart disease, or chronic lung disease.

Participants were split into 2 cohorts: 1 who received high-titer COVID-19 convalescent plasma and another who received a placebo of a salt solution infused with multivitamins and lacking antibodies. The investigators compared outcomes in both groups within 15 days of treatment, examining whether patients required further emergency care, were admitted to the hospital, or died from their disease.

They found that there was no significant difference in disease progression between the groups, with 30% of the convalescent plasma cohort and 31.9% of the placebo group showing disease progression.

“The results show that convalescent plasma does not appear to benefit this particular group,” said Nahed El Kassar, MD, PhD, medical officer in the Blood Epidemiology and Clinical Therapeutics branch of the NHLBI’s Division of Blood Diseases and Resources, in the release. “But the findings answer an important clinical question and may help bring researchers a step closer to finding more effective treatments against this devastating disease.”

The reason for this lack of efficacy is not currently understood. The researchers plan to examine possible explanations, including insufficient plasma dose, timing of plasma administration, host-related factors, and other aspects of the host tissue responses to the infection.


NIH study shows no significant benefit of convalescent plasma for COVID-19 outpatients with early symptoms [news release]. EurekAlert; August 18, 2021. Accessed August 19, 2021. https://www.eurekalert.org/news-releases/925830

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