Johns Hopkins researchers publish a how-to guidebook on Covid-19 plasma transfusions
The novel coronavirus’ rapid spread, far outstripping even the accelerated timelines set for new drugs and vaccines, has sent doctors turning to a therapy researchers say is promising but which hasn’t been widely used in the US in decades: blood plasma donations from recovering patients.
Yet the novelty of the procedure has left hospitals facing many questions, ranging from how effective the treatment is to the basic logistics of how to go about getting the plasma from the arm of a now-healthy person and into the arm of a still-sick one.
To fill that knowledge gap, a team of experts at Johns Hopkins Medicine has published a guidebook for convalescent plasma in the Journal of Clinical Oncology. Containing both step-by-step instructions for how to handle infusions and an overview of the evidence supporting its use, the article functions as both a manual and one of the most systematic and careful English language endorsements for the use of plasma donations in Covid-19 patients since the outbreak began.
“We’ve received many inquiries from health care providers looking to ramp up their ability to deliver this therapy,” Evan Bloch, an infectious disease professor at Hopkins and lead author, said in a statement. “There is historical precedent for its use to prevent and treat viral illness. However, during the chaos of an epidemic, the therapy is often deployed without rigorously studying its effects. Carefully conducted studies are critically needed to understand which people are most likely to benefit from this therapy and how best to apply it to optimize that benefit.”
The guidebook – which also drew from experts at Stanford, Columbia and Washington University in St. Louis, among others – explained that although data from clinical trials are still needed, convalescent plasma has been used as therapy and post-exposure prophylaxis for past infectious diseases, including the deadly coronaviruses SARS and MERS, and was used in a limited number of Covid-19 cases in China. The therapy works by taking the passive antibodies a patient naturally generated in response to the virus and transferring to a new patient, where (hopefully) it binds to the virus, halting infection.
The plasma appears to be effective at multiple stages but works better the earlier it is given, the authors wrote. They cited a Hong Kong study from the SARS outbreak, in which patients given plasma in the first 14 days recovered faster than those given later. Still, a report of five critically ill Covid-19 patients in China found that all 5 improved after transfusion, evidence that “convalescent plasma is safe, reduces viral load and may improve clinical outcomes.”
“Importantly, passive antibody administration offers the only short-term strategy to confer immediate immunity to susceptible individuals,” they wrote. “This is particularly the case in the setting of a novel, emerging infectious disease such as SARS- CoV-2/COVID-19.”
By their count, five trials have been proposed to test the therapy: As post-exposure prophylaxis, in mild cases, in moderate cases, in children and as a “rescue intervention” for those severely ill. The post-exposure trial — a Phase II being run but the Mayo Clinic — could give “direct clinical benefit” for patients while also offering “wide-ranging” social benefits such as protecting healthcare workers on the frontline. Treating moderately ill patients might help stave off ventilation and preserve the short supply of equipment. Critically ill patients may be helped by plasma, but trials on those patients may offer little conclusive data because of “confounding variables,” including other experimental therapies, the authors concluded.
There’s still much we don’t know about plasma transfusions and antibodies to Covid-19, they acknowledged. That includes which of the antibodies the body makes best to neutralize the virus, and though you can screen blood for different antibodies, it takes time. Their review of the lab data indicated most patients would have enough antibodies for donation 14 days after their symptoms ended.
For equitable access to plasma, they recommended donors be screened in a clinic for both the virus and its antibodies. If the former’s negative and the latter positive, they are then directed to donate at a blood center, which then shares it with hospitals, who distribute it according to those in clinical trials or with emergency use authorizations. They argued risks — either from contracting an infection from the donor or from a phenomena called antibody-dependent enhancement, where monoclonal antibodies can worsen the disease — were low, but cautioned time and data were needed.
“The risks of COVID-19 infection are profound,” they concluded. “Human plasma from recovered COVID-19 patients is projected to be a safe and potentially effective therapy for treatment and post-exposure prophylaxis alike. Substantial evidence of benefit with prior use for viral infections offers strong precedent for such an approach. However, it is critically important to perform well controlled clinical trials to confirm efficacy, thereby informing rational evidence-based decision-making.”
For a look at all Endpoints News coronavirus stories, check out our special news channel.