Early high-titer plasma therapy may reduce progression of COVID-19 in older patients

1. Patients aged 65 years or greater who received convalescent plasma within 72 hours of symptom onset were less likely to develop severe respiratory disease compared to those who received placebo.

2. These benefits appeared to be dose-dependent, with higher donor antibody concentrations conferring greater protection upon the recipients.

Evidence Rating Level: 1 (Excellent)

Study Rundown: While many potential treatments for COVID-19 have been examined, few have shown conclusive evidence of benefit in the early stages of the disease. Convalescent plasma is inexpensive and readily available, and infusions have been found to be safe and effective against other contagious diseases. However, their utility in treating COVID-19 remains ambiguous, potentially due to administration only after symptoms had already worsened. This study aimed to determine whether earlier treatment with convalescent plasma against SARS-CoV-2 would prevent disease progression in older individuals. Those who received convalescent plasma had higher concentrations of anti–SARS-CoV-2 serum Spike IgG at 24 hours relative to placebo. These patients were half as likely to develop severe respiratory disease compared to those who received placebo and also had a significantly longer median time to such an event versus placebo. Numerically fewer patients in the convalescent plasma group reached each of the secondary end points including life-threatening respiratory disease, critical systemic illness, and death. These effects were noted to be dose-dependent, as those who received donor plasma at a titer above the median concentration had a roughly two-fold reduction in relative risk compared to those who received plasma at a titer below the median concentration. While further research is needed to evaluate long-term outcomes, these results suggested that early treatment using convalescent plasma may reduce the risk of severe COVID-19 in older patients.

Click here to read the study in NEJM

Relevant Reading: Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19

In-Depth [randomized controlled trial]: This double-blind, multicenter trial was conducted in Argentina from June 4 to October 25, 2020 and involved 160 patients with laboratory-confirmed COVID-19 that were either over 75 years of age or between 65 and 74 years of age with at least one prespecified coexisting condition such as hypertension, diabetes, obesity, CVD, or COPD. Randomization was completed in a 1:1 ratio, and 250 ml of either high-titer convalescent plasma (IgG titer > 1:1000 against SARS-CoV-2 spike protein) or placebo (0.9% normal saline) was administered within 72 hours of symptom onset. 24 hours after infusion, patients in the convalescent plasma group had greater concentrations of antibody titers (median log anti–SARS-CoV-2 S IgG titer, 5.7; interquartile range [IQR], 4.9 to 6.3) than in those in the placebo group (median log anti–SARS-CoV-2 S IgG titer, 3.9; IQR, 3.9 to 4.7). The primary endpoint, severe respiratory disease by day 15, occurred in 13 of 80 patients (16%) who received convalescent plasma and in 25 of 80 patients (31%) who received placebo (relative risk [RR], 0.52; 95% confidence interval [CI], 0.29 to 0.94). This effect was dose-dependent; those who received plasma at a titer at median concentration (1:3200) or greater had a RR of 0.27 (CI, 0.08–0.68), whereas those who received plasma at a titer below this concentration had an RR of 0.69 (CI, 0.34–1.31). Further, the median time to the primary endpoint was longer in the convalescent plasma group than in the placebo group (both P=0.03). A composite of life-threatening respiratory disease, critical systemic illness, or death occurred in 7 patients (9%) who received convalescent plasma and 12 patients (15%) who received placebo.

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