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Older adults hospitalized with milder COVID-19 who received convalescent plasma showed lower risk of developing severe respiratory disease versus patients who received placebo, a randomized trial found.

In an intention-to-treat analysis, severe respiratory disease occurred in 16% of COVID-19 patients ages 65 and older receiving convalescent plasma within 72 hours after symptom onset versus 31% of patients receiving placebo (relative risk 0.52, 95% CI 0.29-0.94, P=0.03), reported Fernando Polack, MD, of Fundación INFANT–COVID-19 Group in Buenos Aires, Argentina, and colleagues, in the .

However, the trial was stopped early at about three-quarters of its projected sample size due to a decline in COVID-19 cases in the region, the authors noted.

Evidence for convalescent plasma in COVID-19 has been conflicting from the beginning. Some observational studies showed promise, while more recent research found no benefit among patients with severe COVID-19. But previous studies may have administered them too late, as authors noted antibodies in plasma "must be administered soon after infection in order to be effective." The FDA authorized its use in hospitalized COVID-19 patients in August.

Polack and colleagues pointed up how their trial differed from others: it focused on older adults, who are most affected by the pandemic, and convalescent plasma was given "in a mild stage" with the aim of preventing progression.

"Our primary endpoint" -- severe respiratory illness -- "was an enrollment criterion in previous studies," the group noted.

Patients were enrolled in Argentina from June 4 to Oct. 25. They included patients ages 65-74 with at least one comorbidity, and patients ages 75 and older irrespective of pre-existing conditions. They had tested positive for SARS-CoV-2 and had symptoms including fever, unexplained sweating or chills and dry cough for less than 48 hours.

Severe respiratory disease was defined as respiration at 30 breaths per minute or more or oxygen saturation of less than 93% on ambient air. They were assessed from 12 hours after infusion to day 15 of trial participation.

Overall, 160 patients underwent randomization. Mean age was 77, and 62% were women. A little more than half were 75 or older. Most patients had pre-existing conditions, with over two-thirds of both groups being treated for hypertension.

An intention-to-treat analysis found severe respiratory disease developed in 13 of 80 patients in the intervention group and 25 of 80 in the placebo group, for a relative risk reduction of 48% and a number needed to treat of 7 to avert one episode of severe respiratory disease.

There were no solicited adverse events observed. Four convalescent plasma recipients had life-threatening respiratory disease. Two patients in the intervention group and four patients in the placebo group died.

Polack's group noted that while the trial "lacked the statistical power to discern long-term outcomes," their findings underscored "the need to return to the classic approach of treating viral infections early."

An exploratory finding of the trial was a dose-dependent IgG effect, where donated plasma with IgG titers of 1:3,200 or higher reduced severe respiratory disease by 73% and a number needed to treat of 4. Among the plasma donors in the trial, 71% with titers of 1:3,200 or higher were previously hospitalized.

"'Super donors' with IgG titers of 1:12,800 or higher and perhaps immunized persons in the future could contribute to build a therapeutic arsenal," Polack and colleagues wrote.

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