The promise of plasma in the COVID-19 fight

Hundreds of thousands of people around the world are getting sick with COVID-19 every few days. Hospitals are becoming overwhelmed. There's no vaccine, and no drug known to work to reverse the illness cause by the novel coronavirus.

But we do have one potentially promising treatment to help people infected with the coronavirus: infusions of antibody-rich plasma from other patients who have had the disease and recovered.

One early look reported in the Journal of the American Medical Association last month showed that five critically ill coronavirus patients on ventilators in Shenzen, China, rapidly improved after treatment with plasma. Within a few days, they started getting better. Eventually, three of them were discharged and two were still hospitalized in stable condition.

The concept is an old one. Doctors first used the basic technique of convalescent plasma in the 1890s against diphtheria. It's called "passive antibody therapy" because antibody-rich plasma is transferred from someone who has successfully recovered from an infection into a patient suffering from the same disease. The lives of an estimated 45,000 diphtheria patients were saved annually in that pre-antibiotic era.

Results from more recent studies have been promising, too. In a 2011 study of 93 patients with severe H1N1 influenza, only 20% of patients who received convalescent plasma died, compared with 54% of a control group (made up of patients who declined the treatment). In 2003, 1,775 patients with severe acute respiratory syndrome enrolled in a study; 12.5% of those who received convalescent plasma died, compared with the overall SARS-related 17% mortality rate for admitted patients. A detailed analysis of 32 studies, using convalescent plasma on patients with diseases caused by SARS and other viruses, revealed a consistent trend of reduction in mortality — up to 75% — in the treatment group.

None of these studies were double-blind, randomized control trials (RCTs), in which the patients are divided into two comparable groups. In a typical drug trial, one group receives the drug while the other gets a placebo, unbeknown to the treating physician. That wasn't what happened with the five coronavirus patients in Shenzen, either. So how do we know that these results are reproducible in 500 or 5,000 patients? How do we know whether the patients who got better weren't going to improve on their own in due course? How do we know that patients didn't respond to one of the other antiviral medications that they were on at the same time?

Despite these questions, doctors should aggressively pursue plasma therapy. We urgently need therapeutic interventions. It's too painful to see patients — sometimes in their 30s — become confused with air hunger and end up on a ventilator. It's too painful to FaceTime their families and explain why we don't have an effective treatment option.

The reasons were promising enough that on Friday, the Food and Drug Administration allowed physicians to use convalescent plasma on their COVID-19 patients. A multistate consortium of physicians and scientists from 34 institutions had already gone live with a detailed website to help interested doctors and patients. Blood across the nation have started collecting convalescent plasma from test-positive coronavirus donors who have recovered. Donors must be symptom-free for 14 days with a negative follow-up test. Each donor could provide up to three plasma doses, which would be screened for other infectious agents before being infused into the host.

Almost 19,000 patients have recovered from COVID-19 in the U.S., and this allows scientists to conduct robust randomized clinical trials that would give us a lot of insight. Could convalescent plasma be used early in the disease to prevent a patient from getting sick enough to require scarce resources such as ventilators? Could it be used even earlier, like when a health care worker is exposed to a coronavirus-positive patient who has not yet become symptomatic? Offering convalescent plasma in this scenario may protect yet another scarce resource, our front-line workers, from falling.

We can seize this opportunity by providing funding to expand plasma collection capabilities throughout the nation and develop concentrated forms of convalescent plasma. Hyperimmune globulin (H-Ig) is one such option, which allows for the administration of a standardized dose of immunoglobulin in an injection form. That's one way to scale this treatment nationwide, in far-flung community hospitals, ambulatory settings and drive-through clinics. Imagine how that would change the resolve of a nation that is hunkered down, scared of an invisible enemy.

Americans are already elated over the idea. They are rolling up their sleeves, literally. One of the coronavirus survivors from New York started a Facebook group called "Survivor Corps" and has amassed more than 20,000 members. Miami's mayor, also a coronavirus survivor, donated his plasma last week. One of my patients, who had a miserable hospitalization, was supercharged about donating his plasma even before being discharged.

Every crisis can present an opportunity. Right now, we have the opportunity to study convalescent plasma therapy in robust clinical trials. If they work, the treatment could be the bridge the world needs between now and the day we have an effective COVID-19 vaccine.