Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.
Convalescent plasma was found to be safe and effective in 19 of 25 (76%) severely ill COVID-19 patients in the first peer-reviewed study of the treatment in the United States.
The treatment, which involves infusing patients with the plasma from people who have recovered from COVID-19 and have developed antibodies, has been used in the treatment of severe microbial infections for more than 100 years, with varied success.
The findings by Eric Salazar, MD, PhD, of the Department of Pathology and Genomic Medicine at Houston Methodist Hospital in Texas, and colleagues were published on May 26 in the American Journal of Pathology.
The observational study was conducted at Houston Methodist from March 28 to April 28. Patients were eligible for the infusions if they had severe and/or life-threatening COVID-19 disease. The participants, who ranged in age from 19 to 77 years (median, 51 years; interquartile range, 42.5 – 60 years), underwent transfusion once with 300 mL of convalescent plasma.
Safety was the primary outcome; status at day 14 after transfusion was the secondary outcome. Clinical improvement was gauged on a modified World Health Organization six-point scale and on laboratory values.
Researchers found that at day 7 post transfusion, nine patients demonstrated at least a one-point improvement in clinical status; seven of those patients were discharged. By day 14, 19 patients (76%) had at least a one-point improvement, and 11 were discharged.
Salazar told Medscape Medical News he was glad to see that none of the problems that can happen with transfusions occurred in this study. Potential problems include allergic reactions ranging from mild reaction to anaphylaxis, fluid overload, and transfusion-related acute lung injury.
The findings regarding safety were consistent, he said, with other findings, including the Mayo Clinic’s expanded access protocol; the findings were published in an article on the preprint server medRxiv. In that study, which involved 5000 patients, the treatment appeared to be safe.
"It seems to be pretty well tolerated," he said.
Additionally, the authors write, "The patient outcomes in our study are similar to those recently published describing treating COVID-19 patients with remdesivir on a compassionate-use basis."
Potential There, but RCTs Still Needed
Now Salazar's team and others are working to answer other questions, including how much plasma COVID-19 patients need and how many doses should be administered. Other questions concern at which point in the illness treatment is most effective, at which point it is too late, and whether it should be used as prophylaxis or after exposure.
"The other very important question is what titer of antibody in the units is the most effective?" he said.
What Salazar does know is that people who have recovered from COVID-19 are eager to help others with donations.
"There's been a tremendous outpouring of support from the Houston community from patients that have recovered from COVID-19. That's been very inspiring," he said. The amount of plasma drawn from one donor can serve two patients, he said.
The COVID-19 Expanded Access Program, led by the Mayo Clinic, tracks plasma donations and transfusions nationally. As of June 1, more than 18,500 infusions had been performed at nearly 2400 sites across the United States.
Kyle Annen, DO, assistant professor in the Department of Pathology at the University of Colorado in Denver, told Medscape Medical News she found the results of the Houston study "encouraging," though she said she had expected the positive safety findings. The strength of this study, she said, is that it is the first to meet the demands of peer review.
"This study is more evidence toward confirming our suspicion that convalescent plasma is both safe and efficacious," she said.
Annen, who is also medical director of transfusion services at Children's Hospital Colorado, added that if convalescent plasma proves to be effective in fighting COVID-19, the antibody titer question will be especially important. In addition, time may be of the essence in collecting the plasma.
"We don't know how long antibodies stick around, and not everyone makes the same titer level," she said. If they don't last long, supplies will decrease as fewer people become infected.
The question is not only whether convalescent plasma could be donated in sufficient quantities, Annen said.
"It's also, will there be enough that's of the appropriate quality — the number of antibodies present in the plasma to have the desired level of impact," she said.
Previous Small Case Studies Also Positive
Small studies conducted in China of the use of convalescent plasma in the treatment of COVID-19, though not peer reviewed, have shown positive results. One involved five patients who improved with the plasma.
Another study of 10 severely ill patients suggests that convalescent plasma was associated with improved clinical symptoms within 3 days and with disappearance of the virus from the blood in 7 days.
A limitation of the current study is that, not having a control group, it is unclear whether the 25 patients would have improved had they not received the treatment. Also, most patients were treated with several other medications, so it is unclear what role plasma transfusion had in patients' improvement.
The use of convalescent plasma has a long history dating back to the Spanish Flu pandemic in 1918, Annen noted. Although it was tested during the SARS, H1N1, and Ebola pandemics, its effectiveness has not been definitively proven in large randomized controlled trials.
Because so many centers are collecting and testing use of the plasma for patients with COVID-19, scientists may be able to get that answer, she said.
Whether the answer would be the same for other pandemics remains to be seen.
"I think if we can definitely prove that it is an effective treatment for COVID-19, that will only help us to jump on it faster in the future for other viruses," she said.
Funding for the study was provided by the National Institutes of Health, the Fondren Foundation, the National Institute of Allergy and Infectious Diseases, the Army Research Office, Houston Methodist Hospital, and the Houston Methodist Research Institute. The authors and Annen have disclosed no relevant financial relationships.
Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune and Nurse.com and was an editor at the Chicago Sun-Times, the Cincinnati Enquirer, and the St. Cloud (Minnesota) Times. Follow her on Twitter at @mfrellic.
Medscape Medical News © 2020
Cite this: Convalescent Plasma Safe, Promising in Small COVID-19 Study - Medscape - Jun 04, 2020.