Promising early plasma tx in adults 65+ with milder COVID-19

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

In an intention-to-treat analysis, severe respiratory disease occurred in 16% of COVID-19 patients aged 65 years and older receiving convalescent plasma within 72 hours of symptom onset versus 31% of patients receiving COVID-19. 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 New England Journal of Medicine.

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

Evidence of convalescent plasma in COVID-19 has been conflicting from the start. Some observational studies have shown promise, while more recent research has found no benefit in patients with severe COVID-19. But previous studies may have given them too late, as the authors noted that antibodies in plasma “must be given soon after infection to be effective.” The FDA cleared its use in COVID-19 hospital patients in August.

Polack and his colleagues highlighted how their trial differed from others: it focused on the elderly, who are most affected by the pandemic, and convalescent plasma was given “at a mild stage” with the aim of preventing the disease. progression.

“Our primary endpoint” – severe respiratory disease – “was a recruiting criterion in previous studies,” the group noted.

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

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

A total of 160 patients were randomized. The average age was 77 and 62% were female. Just over half were 75 years of age or older. Most patients had pre-existing conditions, with more than two-thirds of both groups treated for hypertension.

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

No solicited adverse events were observed. Four recovering plasma recipients had life-threatening respiratory illness. 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 results underscored “the need to revert to the classic approach of treating viral infections early.”

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

“’Super donors’ with IgG titers of 1: 12,800 or higher and perhaps people with immunity in the future could help build a therapeutic arsenal,” Polack and colleagues wrote.

Last updated on January 7, 2021