Researchers working on COVID-19 therapy with plasma from convalescent patients have found that it is safe and effective and improves the chances of survival among those who are severely ill. The new study titled, “Safety Update: COVID-19 Convalescent Plasma in 20,000 Hospitalized Patients,” is published as a preprint for the journal Mayo Clinic Proceedings.
What was the study about?
The SARS-CoV-2 has resulted in a worldwide pandemic. Almost all countries have been affected by the pandemic, which has affected 8.74 million individuals and killed 460,000 persons around the world as of today. As of now, there are no definitive treatments that could be used to treat COVID-19 disease nor vaccines to neutralize the causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The risk of death due to the infection ranges from 4 to 50 percent, wrote the researchers. Risk of death rises among critically ill patients.
Several small studies have shown the benefits of using plasma from convalescent COVID-19 patients for the treatment of those who are critically ill with the infection. The U.S. Food and Drug Administration (FDA), in collaboration with the Mayo Clinic and the national blood banking community, developed a national Expanded Access Program (EAP), wrote the researchers. The EAP was formed to “collect and distribute COVID-19 convalescent plasma”. Convalescent plasma is said to contain “anti-viral antibodies and other bioactive elements,” which could help those with the active infection.
The objective of this study was to see the safety and effectiveness of the use of convalescent plasma among hospitalized COVID-19 patients. This study was a continuation of their previous study, which included 5,000 critically ill COVID-19 patients.
“In this regard, it is remarkable that there was no system in place for convalescent plasma use in March 2020, and yet within months, the nation is now able to meet most of the demand, despite complex logistics,” the team wrote.
What was done?
For this study, hospitalized patients with severe COVID-19 were recruited between 3rd April and 2nd June 2020 under the U.S. FDA Expanded Access Program for COVID-19 convalescent plasma transfusion. A total of 20,000 patients were recruited. All participants were allowed access to convalescent plasma. The patients were over the age of 18 years and were all confirmed cases of SARS-CoV-2 infection. Their attending physicians had judged them to be “at high risk of progression to severe or life-threatening COVID-19”.
As part of the study, they were administered convalescent plasma that was ABO compatible. It was donated by “recently-recovered, COVID-19 survivors”. To the patients, around 200 to 500 ml of convalescent plasma was administered intravenously. Patients were assessed for improvement at 4 hours and seven-days after the transfusion of the plasma.
What was found?
Serious Adverse Events (SAE)
SAE is defined as an adverse event after administration of a drug or treatment that results in death, is life-threatening, needs hospitalization or prolongs hospitalization, results in persistent or significant disability, leads to a congenital defect, or necessitates intervention to prevent permanent damage or impairment.
Results showed that there was a low incidence of SAE after plasma administration. A total of 146 SAEs were reported at four hours after the transfusion. Of these 83 were non-fatal, 37 were due to overload of transfusion (transfusion-associated circulatory overload or TACO), 27 were lung damage due to transfusion (transfusion-related acute lung injury TRALI), and 26 were allergic reactions. There were 63 deaths at 4 hours. Of these, 13 were related to the plasma transfusion.
At seven days after transfusion, there were 1,136 SAEs. These were of different causes as follows;
- Thromboembolic or thrombotic events were seen in 87.
- Severe fall in BP necessitating intervention and support in 406 patients.
- Cardiac event in 643 patients.
The team wrote that 569 cardiac events and 55 thrombotic complications respectively were not related to the plasma transfusion.
Risk of death
The team wrote that the mortality rate at seven days was 8.6 percent. It was more significant for critically ill patients compared to those who were less severely ill. Death rates of different groups were as follows:
- Death rates of 10.5 percent and 6 percent respectively for those admitted to or not admitted to intensive care respectively.
- Death rates of 12.1 percent and 6.2 percent respectively for those mechanically ventilated or not ventilated respectively.
- Death rates of 14 percent and 7.6 percent respectively for those with or without septic shock or multi-organ failure respectively.
Conclusions and implications
The authors wrote, “Convalescent plasma has a strong historical record of some efficacy during acute infectious pandemics.” They called for more research to search for explanations regarding how the convalescent plasma works.
The team wrote in conclusion, “These updated data provide robust evidence that transfusion of convalescent plasma is safe in hospitalized patients with COVID-19, and support the notion that earlier administration of plasma within the clinical course of COVID-19 is more likely to reduce mortality.”
This research aligns with a recent systematic review by the Karolinska Institutet that showed using convalescent plasma in patients with COVID-19 to be well-tolerated, prompting clearance of severe SARS-CoV-2, as well as decreasing disease severity; especially in younger patients.