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Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults

Our take —

This was a double-blind randomized controlled trial from Argentina with 160 elderly patients with SARS-CoV-2, which showed that early, high-titer convalescent plasma given within 72 hours of COVID-19 symptom onset significantly reduced progression to severe respiratory disease over the subsequent 15 days.

Study design

Randomized Controlled Trial

Study population and setting

This was a double-blind randomized controlled trial of 160 elderly patients early in the course of COVID-19 disease, comparing convalescent plasma (CP) to placebo, conducted across 15 institutions in Argentina. Eligible individuals were either 75 years or older, or 65-74 years of age with at least one chronic coexisting condition with <48 hours of one sign and one symptom of COVID-19 and a positive SARS-CoV-2 PCR. All participants received either CP, with an IgG titer >1:1000 of anti-spike protein, or placebo infusion within 72 hours of symptom onset. The primary endpoint was progression to severe respiratory disease, defined as tachypnea (30 breaths per minute or greater) or hypoxemia (less than 93% oxygen saturation on room air) within 15 days following the infusion with either convalescent plasma (n=80) or placebo (n=80).

Summary of Main Findings

In the intention-to-treat analysis, 13 out of 80 (16%) participants in the CP arm compared to 25 out of 80 (31%) in the placebo arm reached the primary endpoint of severe respiratory disease, a significant reduction (RR 0.52, p 0.03). The combined secondary endpoint of life-threatening respiratory disease, critical systemic illness, and/or death occurred among 7 (9%) CP arm participants and 12 (15%) placebo arm participants (not statistically significant).

Study Strengths

The study assessed early use of CP, when it is most plausibly effective. In addition, all CP units were considered high-titer. Moreover, the selected population of patients aged 75 or greater, or 65-74 with one or more comorbidities, targets a specific population at high risk of COVID-19 morbidity and mortality.

Limitations

The study stopped recruiting participants prematurely because of a lowered incidence of COVID-19 cases in the regions of Argentina available to recruit from, which made it difficult to have enough statistical power to evaluate secondary outcomes, although they appear to be better in the CP group. The trial was not powered to assess the combined severe illness or death secondary outcome.

Value added

This study is a first from a placebo-controlled RCT to demonstrate that high-titer convalescent plasma, when given very early in the course of COVID-19, can reduce progression to severe respiratory disease among a high-risk population.

This review was posted on: 14 January 2021