Jury Still Out on Convalescent Plasma

By Jonathan Springston, Editor, Relias Media

The authors of a recent study concluded convalescent plasma did not prevent COVID-19 disease progression in a group of high-risk outpatients when the solution was administered within the first week of symptom onset.

Primarily funded by the National Heart, Lung, and Blood Institute (NHLBI), the authors of the Clinical Trial of COVID-19 Convalescent Plasma in Outpatients (C3PO) wanted to see how COVID-19 convalescent plasma, blood taken from COVID-19 patients who have recovered, could help those battling the virus. Investigators enrolled more than 500 patients (median age = 54 years; slightly more than half were women) who presented to 48 different emergency departments (EDs) across the United States. These patients had presented to EDs with mild symptoms during the first week after infection. Each also presented with at least one comorbidity associated with severe disease progression (e.g., obesity, chronic lung disease).

In this randomized, controlled trial, participants were assigned either convalescent plasma or placebo. Researchers followed participants to see who needed additional emergency care, who was admitted to the hospital, and who died. Although convalescent plasma caused no harm, it did not seem that effective either. The researchers ended their work earlier this year after disappointing early results. But in the formal report, published last week, the authors concluded convalescent plasma still could be beneficial, depending on many different factors.

On Aug. 23, 2020, the FDA issued an emergency use authorization (EUA) for convalescent plasma to treat patients hospitalized with COVID-19. After the announcement, criticism emerged — from skepticism about the data to accusations of an overly politicized process. In February 2021, the agency revised the EUA, narrowing the scope to only the high-titer dose — still for hospitalized patients, but early in the disease course.

Meanwhile, the results of real-world testing have been mixed. In addition to the recently reported results of C3PO, investigators in China last year did not find improvements in mortality or time to clinical improvement with convalescent plasma treatment in those hospitalized with COVID-19, although patients treated in that trial already had developed severe or life-threatening disease. In Argentina, convalescent plasma showed benefit in elderly patients (mean age = 77.2 years), but researchers excluded those with a long list of comorbidities.

There appear to be many factors when considering the efficacy of convalescent plasma: age, disease course, dose, timing, comorbidities, and much more. An ongoing NIH-backed study is focused on convalescent plasma for patients already hospitalized with COVID-19. Another trial involves patients who are at home recovering from the disease. Still another work in progress is about whether convalescent plasma could prevent COVID-19 infection in a high-risk population.

“Convalescent plasma may still play a role if it is administered before the development of native antibodies. The treatment may also be efficacious in preventing symptomatic COVID-19 after exposure,” the C3PO authors wrote. “Future studies may also consider whether convalescent plasma that is collected during different epochs and from different geographic locations during a pandemic will have different therapeutic potentials. Donations that are temporally and geographically proximate to their point of use may be more effective. Since convalescent plasma may be the only available therapeutic agent during the early phases of a pandemic, understanding how and when it is useful is important for public health. It is also important to consider that host factors and other aspects of the host response to the infection may be more important than humoral immunity for determining the natural history of the illness.”

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