A preliminary analysis of an ongoing study of more than 300 COVID-19 patients treated with convalescent plasma therapy at Houston Methodist suggests the treatment is safe and effective. The results represents one of the first peer-reviewed publications in the country assessing efficacy of convalescent plasma.
From 28 March, when Houston Methodist became the first academic medical centre in the nation to infuse critically ill COVID-19 patients with plasma donated from recovered patients, research physicians have used the treatment on 350 patients. The study tracked severely ill COVID-19 patients admitted to Houston Methodist's system of eight hospitals from 28 March through 6 July.
These latest results from Houston Methodist that now measured medical effectiveness offer valuable scientific evidence that transfusing critically ill COVID-19 patients with high antibody plasma early in their illness – within 72 hours after hospitalisation proving most effective – reduced the mortality rate.
The study was led by principal investigator Dr Eric Salazar, assistant professor of pathology and genomic medicine with the Houston Methodist Hospital and Research Institute and corresponding author Dr James M. Musser, chair of the department of pathology and genomic medicine at Houston Methodist.
"Our studies to date show the treatment is safe and, in a promising number of patients, effective," Musser said. "While convalescent plasma therapy remains experimental and we have more research to do and data to collect, we now have more evidence than ever that this century-old plasma therapy has merit, is safe and can help reduce the death rate from this virus."
The research team found that those treated early in their illness with donated plasma that has the highest concentration of anti-COVID-19 antibodies are more likely to survive and recover than similar patients who were not treated with convalescent plasma. Patients with a history of severe reactions to blood transfusions, those with underlying uncompensated and untreatable end-stage disease and patients with fluid overload or other conditions that would increase the risk of plasma transfusion were excluded.
The patients were tracked for 28 days after plasma transfusion and compared to a control group of similar COVID-19 patients who did not receive convalescent plasma. An observational propensity score-matched analysis was used to balance the characteristics of participants and allow for an objective interpretation of the results at this stage.
Several studies have measured safety, showing that the more than 34,000 COVID-19 patients in the US who have received plasma transfusions for COVID-19 experienced minimal adverse effects.
In addition to Musser and Salazar, other collaborators from Houston Methodist on this study were Paul A Christensen, Edward A Graviss, Duc T Nguyen, Brian Castillo, Jian Chen, Bevin Valdez Lopez, Todd N Eagar, Xin Yi, Picheng Zhao, John Rogers, Ahmed Shehabeldin, David Joseph, Christopher Leveque, Randall J Olsen, David W Bernard, and Jimmy Gollihar of the US Army Research Laboratory-South, University of Texas Austin.
This study was supported by funding from the Fondren Foundation, Houston Methodist Hospital, Houston Methodist Research Institute and Houston Methodist Infectious Diseases Research Fund.
Abstract
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has spread globally, and proven treatments are limited. Transfusion of convalescent plasma collected from donors who have recovered from COVID-19 is among many approaches being studied as potentially efficacious therapy. We are conducting a prospective, propensity score-matched study assessing the efficacy of COVID-19 convalescent plasma transfusion versus standard of care as treatment for severe and/or critical COVID-19. We present here the results of an interim analysis of 316 patients (n=316) enrolled at Houston Methodist hospitals from March 28 to July 6, 2020. Of the 316 transfused patients, 136 met a 28-day outcome and were matched to 251 non-transfused control COVID-19 patients. Matching criteria included age, sex, BMI, comorbidities, and baseline ventilation requirement 48 h from admission, and in a second matching analysis, ventilation status at Day 0. Variability in the timing of transfusion relative to admission and titer of antibodies of plasma transfused allowed for analysis in specific matched cohorts. The analysis showed a significant reduction (P = 0.047) in mortality within 28 days, specifically in patients transfused within 72 h of admission with plasma with an anti-spike protein receptor binding domain titer of ≥1:1350. These data suggest that treatment of COVID-19 with high anti-receptor binding domain (RBD) IgG titer convalescent plasma is efficacious in early-disease patients.
Authors
Eric Salazar, Paul A Christensen, Edward A Graviss, Duc T Nguyen, Brian Castillo, Jian Chen, Bevin Valdez Lopez, Todd N Eagar, Xin Yi, Picheng Zhao, John Rogers, Ahmed Shehabeldin, David Joseph, Christopher Leveque, Randall J Olsen, David W Bernard, Jimmy Gollihar, James M Musser
[link url="https://www.houstonmethodist.org/newsroom/preliminary-study-of-300-covid-19-patients-suggests-convalescent-plasma-therapy-effective/"]Houston Methodist material[/link]
[link url="https://ajp.amjpathol.org/article/S0002-9440(20)30370-9/fulltext"]The American Journal of Pathology abstract[/link]