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Plasma Tx Improved COVID-19 Outcomes in Sickest Patients

— Three of five patients in China treated with convalescent plasma later discharged from hospital

MedpageToday
A bag of blood plasma with a COVID-19+ label

Three of five critically ill patients from China with COVID-19 treated with convalescent plasma recovered enough to be discharged from the hospital, and the other two did not deteriorate further, a small case series found.

Patients with COVID-19 infection and acute respiratory distress syndrome (ARDS), who were receiving mechanical ventilation at the time of treatment, .

Three were weaned from ventilation within 2 weeks, reported Yingxia Liu, MD, and Zheng Zhang, MD, both of Second Hospital Affiliated to Southern University of Science and Technology in Shenzhen, China, and colleagues, writing in a preliminary communication in JAMA.

However, this was not a randomized controlled trial, and the authors added that it is unclear if patients would have improved without the use of convalescent plasma, as they were treated with multiple other agents, including antiviral medications.

Use of convalescent plasma was recommended as an "empirical treatment" during outbreaks of Ebola, as well as MERS, and other research in SARS and H1N1 influenza suggested "transfusion of convalescent plasma is effective," they said.

This uncontrolled case series examined five patients with laboratory-confirmed COVID-19, treated with plasma from five donors, ages 18 to 60, who had recovered from the infection, and tested negative for this and other respiratory and bloodborne viruses. The donors had been asymptomatic for at least 10 days, with a SARS-CoV-2 -- the virus causing COVID-19 infection -- specific ELISA antibody titer greater than 1,000 and a neutralizing antibody titer greater than 40, they said.

Five critically ill COVID-19 patients at Shenzhen Third People's Hospital, ranging from age 36 to 73, two of whom were women, had all received antiviral agents and steroids. None were smokers and four of five had no pre-existing medical conditions (one had hypertension and mitral insufficiency). Complications prior to plasma transfusion included severe ARDS, and bacterial pneumonia in two of five patients and one patient was receiving extracorporeal membrane oxygenation (ECMO).

Convalescent plasma was administered from 10 to 22 days after admission, the authors said. Outcomes of interest included the Sequential Organ Failure Assessment score, viral load, serum antibody titer, and ventilatory and ECMO supports before and after transfusion.

The authors found that viral load, as assessed by cycle threshold value, declined within days of treatment, and clinical conditions of patients improved from a variety of assessments, including body temperature reduction and chest imaging. Notably, they said four patients receiving mechanical ventilation did not need respiratory support 9 days after plasma transfusion.

The patient receiving ECMO at the time of plasma treatment did not require ECMO on day 5 following transfusion, the researchers said, adding that as of March 25, two patients remained hospitalized, with a 37-day length of stay apiece.

In an accompanying editorial, John Roback, MD, PhD, and Jeannette Guarner, MD, both of Emory University School of Medicine in Atlanta, said that while "the and neutralized the virus in in vitro cultures," because the plasma was administered up to 3 weeks after hospital admission, "it is unclear whether this timing is optimal or if earlier administration might have been associated with different clinical outcomes."

Scaling may also be an issue with this approach, with the editorialists noting, "the deployment of convalescent plasma will have limited reach because transfusions are typically performed in hospital settings and may require large infusion volumes."

The researchers said that while the limited sample size and study design "preclude a definitive statement about the potential effectiveness," they suggested evaluating the treatment further in clinical trials.

Disclosures

This study was supported by the National Science and Technology Major Project, Sanming Project of Medicine in Shenzhen, Shenzhen Science and Technology Research and Development Project, National Natural Science Foundation of China, Shenzhen Science and Technology Research and Development Project, and The Key Technology R&D Program of Tianjin.

The authors disclosed no conflicts of interest.

Roback disclosed being a member of the American Red Cross Biomedical Services Medical Advisory Council and support from CSL Plasma, Secure Transfusion Services, and Cambium Medical Technologies.

Guarner disclosed no conflicts of interest.

Primary Source

JAMA

Shen C, et al "Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma" JAMA 2020; DOI: 10.1001/jama.2020.4783.

Secondary Source

JAMA

Roback JD, Guarner J "Convalescent Plasma to Treat COVID-19: Possibilities and Challenges" JAMA 2020; DOI: 10.1001/jama.2020.4940.