Signal promising but efficacy needs to be confirmed

Covid-19 convalescent plasma appears safe for use in patients with severe or life-threatening Covid-19 disease, according to a report that looked at the first 20,000 patients infused with convalescent plasma.

“The overall frequency of [severe adverse events (SAE)] classified as attributable or likely secondary to convalescent plasma transfusion continued to be low (<1% of all transfusions) and the seven-day mortality rate in this extremely high risk cohort was 8.6%,” Michael J. Joyner, MD, from the department of Anesthesiology and Perioperative Medicine, at the Mayo Clinic, Rochester, and colleagues reported in the Mayo Clinic Proceedings. “Despite the potential risks associated with plasma transfusion in critically-ill patients, these data provide continued optimism for the safety of Covid-19 convalescent plasma.”

They also pointed out several other notable findings in their study:

  • In the first seven days following convalescent plasma transfusion, there was a very low rate (<1%) of thrombotic and thromboembolic events.
  • Aggregate, adverse cardiac events occurred in about 3% of patients receiving convalescent plasma, and 88% were determined to not be caused by the transfusion.
  • The incidence of transfusion related acute lung injury (TRALI) and transfusion associated circulatory overload (TACO) was 0.18% and 0.10% respectively, which they noted “is significantly lower than those reported in previous studied, which ranged from 5-8% and 1-4%, respectively.”

The study authors noted that while the low mortality rate of 8.6% is encouraging and lower than the 12% found in the first 5,000 infused patients, the study was not designed as an efficacy study.

“While the mortality rate has fallen, we note that the clinical characteristics of the transfused patients in the [FDA Expanded Access Program (EAP)] have shifted toward less critically-ill patients and lower proportions of apparent ’rescue therapy’. No therapy has been introduced into clinical use during this time period which reduces (to our knowledge) mortality in hospitalized patients with Covid-19,” Joyner and colleagues wrote.

That said, they proffered several possibilities that may explain the decline in mortality that they observed:

  • The ability to manage Covid-19 patients in improving in the U.S.
  • Blood banks have more availability of convalescent plasma now and thus more patients are receiving it earlier in their hospital stay than the first 5,000 recipients, due particularly to “improved logistics for the collection, deployment, and use of convalescent plasma,” plus more recovered potential donors.
  • There is historic evidence that antibody therapies are more effective the earlier they are given, and mortality is subsequently lower, “the lower mortality in more recently treated patients would be consistent with greater efficacy from earlier use.”
  • Recovered Covid-19 patients are now being recruited sooner for convalescent plasma donation and therefore “the plasma may contain higher levels of neutralizing antibodies or other bioactive elements.

Joyner and colleagues add, however, that more data are needed to evaluate their theory.

The U.S. Covid-19 Convalescent Plasma EAP is a pragmatic study to enable “local acute care facilities to use the emerging best evidence for care while allowing for administration of convalescent plasma. It was conducted within a modified clinical trial framework,” Joyner and colleagues wrote.

Patients 18 years or older hospitalized with a laboratory confirmed diagnosis of SARS-CoV-2 and who were determined to have — or who would progress to — severe or life-threatening Covid-19 were eligible for participation.

“…ABO-compatible Covid-19 convalescent plasma had no minimum neutralizing-antibody titer level and was donated by recently-recovered, Covid-19 survivors. Approximately 200 – 500 mL of convalescent plasma was administered intravenously according to institutional transfusion guidelines,” Joyner and colleagues reported.

More than 30,000 patients were enrolled from April 3 to June 11, 2020, and of these 21,987 received Covid-19 convalescent plasma transfusion — 20,000 had been transfused by June 1. Twenty percent of the patients were African American, about 35% were Hispanic, and 5% were Asian. Forty percent were women. Most participants were overweight and had severe or life-threatening Covid-19, about 66% had respiratory failure and dyspnea as a primary symptom, most were hypoxic, and nearly 50% had pulmonary infiltrates. There were about a third with severe respiratory compromise. Multi-organ failure or septic shock affected a small percent of the population.

  1. Covid-19 convalescent plasma appears safe for use in patients with severe or life-threatening Covid-19 infection, according to a report that looked at the first 20,000 patients infused with convalescent plasma, with a very low rate (<1%) of thrombotic and thromboembolic events.
  2. Be aware that while the study showed a low mortality rate, this study was not designed to be an efficacy study.

Candace Hoffmann, Managing Editor, BreakingMED™

This study was supported in part by a US Department of Health and Human Services (HHS), Biomedical Advanced Research and Development Authority (BARDA), National Center for Advancing Translational Sciences (NCATS) grant, National Heart, Lung, and Blood Institute (NHLBI), Natural Sciences and Engineering Research Council of Canada (NSERC), National Institute of Allergy and Infectious Disease (NIAID) grants, National Heart Lung and Blood Institute, National Institute of Aging (NIA), Schwab Charitable Fund, United Health Group, National Basketball Association (NBA), Millennium Pharmaceuticals, Octapharma USA, Inc, and the Mayo Clinic.

The study authors disclosed no relevant relationships.

 

Cat ID: 151

Topic ID: 88,151,730,933,125,190,926,192,927,151,928,195,929,925,934