High-Titer Convalescent Plasma Therapy Within 72 Hours of COVID-19 Symptoms Reduced Risk for Severe Illness

Blood transfusion. Blood bag on a rack. Photo and copy space.
Study authors assessed whether convalescent plasma with high SARS-CoV-2 antibody titers would prevent progression to severe disease in older patients with COVID-19 if administered within 72 hours after the onset of mild symptoms.

Patients aged 75 or older who were mildly ill with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were less likely to progress to severe illness with early administration of high-titer convalescent plasma. These findings, from a randomized, double-blind, placebo-controlled trial were published in The New England Journal of Medicine.

Patients (N=160) aged 65 years or older were recruited for this study (ClinicalTrials.gov Identifier: NCT04479163) between June 4 and October 25, 2020, at clinical sites in Argentina. Patients were randomized to receive 1.5- to 2-hour infusions of 250 mL convalescent plasma with an immunoglobulin (Ig)G titer greater than 1:1000 against the SARS-CoV-2 spike protein (n=80) or 0.9% saline placebo (n=80) less than 72 hours after symptom onset. Patients were monitored up to day 27 for clinical outcomes. Convalescent plasma was obtained from 135 donors who had at least 10 days of symptoms of SARS-CoV-2 and had since tested negative twice.

The primary endpoint was the development of severe respiratory disease, defined as a respiratory rate of at least 30 breaths per minute and/or an oxygen saturation of less than 93% while the patient is breathing ambient air. At baseline, patients were aged mean 77.2±8.6 years and 62% were women.

A total of 16% (13/80) of convalescent plasma recipients and 31% (25/80) of placebo recipients progressed to severe disease symptoms (relative risk [RR], 0.52; 95% CI, 0.29-0.94; P =.03). Patients who received the treatment progressed to severe disease at a median of 15 days (interquartile range [IQR], 15-150, which was slower than the placebo group (median, 15; IQR, 9-15 days; P =.03).

Fewer patients receiving the convalescent plasma developed life-threatening respiratory disease (5% vs 12%), required noninvasive ventilation (1% vs 8%), admission to the intensive care unit (2% vs 8%), or developed acute respiratory failure (2% vs 6%).

At 24 hours after infusion, patients receiving the convalescent plasma had a median log anti-SARS-CoV-2 spike IgG titer of 5.7 (IQR, 4.9-6.3) and the patients receiving the placebo had titers of 3.9 (IQR, 3.9-4.7).

Among the treatment group, patients who received plasma with higher titers (median, 1:3200) showed a higher relative risk reduction of 73.3% (RR, 0.27; 95% CI, 0.08-0.68) compared with patients who had a lower titers (31.4%; RR, 0.69; 95% CI, 0.34-1.31).

This study may have been limited by premature termination of the study due to a falling infection rate in the area. The study authors felt they would no longer be able to recruit their target sample size, reducing the size of the trial by 76%, which may have limited their power.

The study authors concluded high-titer convalescent plasma administered within 72 hours of developing symptoms of mild SARS-CoV-2 among older adults reduced risk for progression to severe disease and may be a safe and inexpensive therapy for populations at high risk for poor outcomes.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Libster R, Pérez G, Wappner D, et al; for the Fundación INFANT–COVID-19 Group. Early high-titer plasma therapy to prevent severe COVID-19 in older adults. N Engl J Med. Published online January 6, 2021. doi:10.1056/NEJMoa2033700.