An extensive overview of convalescent plasma therapeutic use in Covid-19 has just been published on JAMA 30 April.

The analysed points are the following:

  1. need of randomised controlled trials: Without randomized controlled trials, researchers can’t be sure whether patients recovered because of an experimental therapy or in spite of it. Yet virtually everything that’s known about the use of convalescent plasma against infectious diseases comes from studies in which every patient received the treatment.
  2. under which umbrella to perform clinical trials: One way to administer convalescent plasma is by conducting a clinical trial, as Bennett-Guerrero and Brown have opted to do, under the traditional investigational new drug (IND) regulatory pathway. Another is expanded access, also called “compassionate use,” which enables patients with a serious or life-threatening disease to obtain an investigational medical product outside of a clinical trial when there is no alternative treatment available. If such patients can’t obtain convalescent plasma through clinical trials or an expanded-use protocol, their physician can request a single-patient emergency Investigational New Drug Application (eIND). Houston Methodist Hospital reported that on March 28, it became the first US hospital to provide convalescent plasma to a patient with COVID-19, in this case under an eIND.
  3. supply and demand: The AABB (formerly the American Association of Blood Banks) and the New York Blood Center and several other community-based blood centers have partnered with Survivor Corps—a grassroots organization of COVID-19 survivors whose mission is to support research into developing a cure and a vaccine—to increase convalescent plasma donations.
  4. timing and dosing: For patients with COVID-19, convalescent plasma seems more effective if it’s given earlier in the course of the disease, according to Beth Shaz, MD, New York Blood Center’s chief medical officer. “It appears to slow progression of disease and keep people out of the ICU. Some are getting extubated shortly after transfusion,” she said on April 15 in an email to Hillyer and other colleagues. In patients critically ill with acute respiratory distress syndrome, though, convalescent plasma doesn’t seem to be as effective, wrote Shaz, who also is president of AABB. Stanford University researchers will soon begin testing convalescent plasma in emergency department patients with COVID-19 respiratory symptoms who aren’t yet sick enough to be admitted to the hospital.
  5. next steps: Convalescent plasma is like a bridge, it’s a stopgap measure until more refined treatments and a vaccine can be mass-produced. One of those treatments is intravenous (IV) immunoglobulin, made of pooled IgG from convalescent plasma. The NIAID has been working to develop and launch a placebo-controlled trial of IV IgG to treat COVID-19, Lane said. Unlike convalescent plasma, IV IgG can be standardized and used to treat anyone, no matter their blood type. Further down the road is the development of monoclonal antibodies targeting SARS-CoV-2. The Gates Foundation, Wellcome, and Mastercard have launched a COVID-19 Therapeutics Accelerator, which will screen new monoclonal antibodies for possible anti–COVID-19 activity. 
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