COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

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Treatment Libster R, Perez Marc G, Wappner D, et al. Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults. N Engl J Med. 2021 Feb 18;384(7):610-618. doi: 10.1056/NEJMoa2033700. Epub 2021 Jan 6.

BACKGROUND: Therapies to interrupt the progression of early coronavirus disease 2019 (Covid-19) remain elusive. Among them, convalescent plasma administered to hospitalized patients has been unsuccessful, perhaps because antibodies should be administered earlier in the course of illness.

METHODS: We conducted a randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adult patients within 72 hours after the onset of mild Covid-19 symptoms. The primary end point was severe respiratory disease, defined as a respiratory rate of 30 breaths per minute or more, an oxygen saturation of less than 93% while the patient was breathing ambient air, or both. The trial was stopped early at 76% of its projected sample size because cases of Covid-19 in the trial region decreased considerably and steady enrollment of trial patients became virtually impossible.

RESULTS: A total of 160 patients underwent randomization. In the intention-to-treat population, severe respiratory disease developed in 13 of 80 patients (16%) who received convalescent plasma and 25 of 80 patients (31%) who received placebo (relative risk, 0.52; 95% confidence interval [CI], 0.29 to 0.94; P = 0.03), with a relative risk reduction of 48%. A modified intention-to-treat analysis that excluded 6 patients who had a primary end-point event before infusion of convalescent plasma or placebo showed a larger effect size (relative risk, 0.40; 95% CI, 0.20 to 0.81). No solicited adverse events were observed.

CONCLUSIONS: Early administration of high-titer convalescent plasma against SARS-CoV-2 to mildly ill infected older adults reduced the progression of Covid-19. (Funded by the Bill and Melinda Gates Foundation and the Fundación INFANT Pandemic Fund; Dirección de Sangre y Medicina Transfusional del Ministerio de Salud number, PAEPCC19, Plataforma de Registro Informatizado de Investigaciones en Salud number, 1421, and number, NCT04479163.).

Discipline / Specialty Area Score
Hospital Doctor/Hospitalists
Internal Medicine
Infectious Disease
Comments from MORE raters

Geriatrics rater

There is no significant effect in admission to ICU, mechanical ventilation or death for a treatment available in short supply. In this sense, the results are similar to other trials with convalescent plasma.

Hospital Doctor/Hospitalists rater

Due to the ongoing pandemic and paucity of truly effective treatments, further data on convalescent plasma is always useful and appreciated. My concern with this article is that; although it is a signal to useful effect, the small numbers may be influencing the results. The subgroup analysis of antibody titer w/r/t reaching the endpoint and K-M curves were solid evidence of benefit (though with such wide CI, I am not sure if further studies would be different). Of note, the convalescent plasma group was slightly younger and more female than the placebo group (though it also had more comorbidities than placebo). Overall, I feel that this study could be used to justify an aggressive approach in this age group, though not necessarily demand it.

Infectious Disease rater

The presented study is well done in terms of craftsmanship. Unfortunately, the number of patients is not sufficient to show significant results regarding the long-term outcome, however, the authors were able to "shed light into the darkness" of convalescent plasma therapy. However, the presented intervention is highly interesting for all physicians involved in the treatment of COVID-19 sufferers, as a relatively inexpensive (early) treatment option for high-risk patients is described here. With a possible decrease in severe courses, the pressure on intensive care units can be reduced. Summarized from the perspective of the intensive care therapist; the article worth reading.