番茄社区

Neither clinical status nor overall mortality was improved in COVID-19 patients with severe pneumonia treated with convalescent plasma in a randomized trial, researchers in Argentina said.

At 30 days in the 333-patient trial, the convalescent plasma group and the placebo group showed no significant difference in distribution of clinical outcomes on a 6-point ordinal scale ranging from recovery to death (OR 0.83, 95% CI 0.52-1.35, P=0.46), reported Ventura Simonovich, MD, of Hospital Italiano de Buenos Aires, and colleagues in the . Odds ratios less than one in this analysis reflect poorer outcomes with convalescent plasma versus placebo.

Moreover, there was no significant difference in between group mortality rates (10.96% with plasma vs 11.43% for placebo), the authors wrote in an early edition of the .

The FDA authorized convalescent plasma in August to treat patients hospitalized with COVID-19 on the basis of observational data. Since then, guideline authors have been wary of the treatment: the National Institutes of Health called then-current data to recommend for or against its use given a lack of "well-controlled, adequately powered, randomized clinical trials." The Infectious Diseases Society of America (IDSA) recommended to within the context of a clinical trial. The IDSA noted that only one randomized trial had been completed at that time, showing no benefit. Two other randomized trials came to opposite conclusions, one indicating a benefit while the other found none; both were stopped early.

The current study, , was a multi-center double-blind, placebo-controlled trial at 12 sites in Argentina, where participants were assigned 2:1 to receive convalescent plasma or placebo. Hospitalized adults were eligible if they tested positive for SARS-CoV-2, had radiologically confirmed pneumonia and no previous directives rejecting advanced life support, and at least one of the criteria for severity, such as oxygen saturation below 93%. Data were collected May 28-August 27.

Primary outcome was clinical status 30 days after intervention, as measured by an adapted version of the World Health Organization (WHO) clinical scale, ranging from 1 (death) to 6 (discharged with full return to baseline physical function).

Overall, 228 patients were randomized to receive convalescent plasma, while 105 were randomized to placebo. Median age of patients was 62, about 68% of patients were men and 65% had a pre-existing condition at trial entry. Median time of onset of COVID-19 symptoms to enrollment was 8 days. More than 90% of patients were receiving oxygen and glucocorticoids at trial entry.

In addition to no between-group differences in clinical status at day 30, there was no difference in clinical status on day 7 or day 14. Median time from enrollment to hospital discharge was 13 days in the plasma group and 12 days in the placebo group.

Examining safety, infusion-related adverse events were more common with plasma than placebo (4.8% vs 1.9%, respectively), and five patients in the plasma group had nonhemolytic febrile reactions. However, there was no significant between group difference in incidence of adverse events or severe adverse events.

"Our trial ensured that more than 95% of the transfused plasma units had a total anti-SARS-CoV-2 antibody titer of at least 1:800," the authors wrote.

Limitations to the data include that all enrolled patients had severe COVID-19 pneumonia, so conclusions cannot be extrapolated to mild and moderate cases. They also noted it was difficult to differentiate post-infusion reactions, including transfusion-associated cardiac overload and transfusion-related acute lung injury, from COVID-19 progression.

They suggested further research in other populations or alternative interventions, such as intravenous immunoglobulin or anti-SARS-CoV-2 monoclonal antibodies.

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