The next few weeks may see the worst phase of the COVID-19 pandemic. Vaccines, like the cavalry, are on the way, but will not prevent the crisis from reaching its inevitable apex. Fortunately, we have convalescent plasma available, which could take a bite out of COVID-19 by saving lives and protecting our health care system from collapse.
The FDA approved convalescent plasma for hospital use under Emergency Use Authorization last August, when it met the regulatory criteria of probable efficacy and definite safety. Unfortunately, the rollout of that authorization was marred by errors during a presidential news conference, where efficacy was mistakenly exaggerated. This created an unnecessary controversy that colors the view of plasma to this day.
Considerable evidence supports the efficacy of convalescent plasma. Studies from Mount Sinai Medical Center in New York as well as Houston Methodist Hospital have associated reductions in mortality from convalescent plasma use with early administration during the hospital course. A similar result emerged from the analysis of thousands of patients treated in the United States, and a randomized controlled trial from Argentina reports that administration of convalescent plasma with high concentrations of neutralizing antibodies within the first three days of symptoms reduces progression of disease by more than 50% in high-risk elderly outpatients. A valuable finding is the remarkable improvement in COVID-19 when convalescent plasma is used in patients unable to mount a normal immune response to COVID-19 because of immunosuppression.
Convalescent plasma is an unusual medication in that it is obtained directly from patients who have recovered from COVID-19. This feature imbues, for some people, the use of plasma with an almost mystical quality infused with altruism. However, others recoil at using a “primitive” therapy that dates from the early 20th century. Moreover, plasma is not a standard manufactured product. Units differ in antibody content but must meet minimal criteria set by the FDA. Yet convalescent plasma is safe, available and, as a donated product, costs only a few hundred dollars. Most importantly, it is associated with favorable outcomes in the majority of studies, reducing mortality on average by about 40-50%. But both physicians and the public must learn how to best use convalescent plasma.
What health care providers most need to know is that convalescent plasma is associated with reduced mortality if used early in COVID-19, but its use late in the course of disease is of little or no benefit. The same picture is emerging for monoclonal antibodies, which appear effective in outpatients, but not for inpatients. This is critically important information as we confront the difficult days ahead. If convalescent plasma is to be used, it must be used as early as possible and we must avoid wasting scarce supplies by using it in patients unlikely to benefit.
The arsenal against COVID-19 remains limited to supportive care with oxygen, careful ventilatory management, prevention of clots with anticoagulants, and just three specific therapies — antivirals (remdesivir), anti-inflammatory drugs (dexamethasone) and antibody-based treatments, such as convalescent plasma and monoclonal antibodies. Of these three options, COVID-19 convalescent plasma is the only one that is associated with reduced mortality if used early in hospitalization and that has been shown to reduce progression to severe disease when used shortly after diagnosis in outpatients.
Despite the controversies, and reluctance in some medical quarters, thousands of patients are receiving convalescent plasma each day, attesting to its acceptance by many physicians. We, as part of the leadership of the COVID-19 Convalescent Plasma Project, strongly encourage the completion of the numerous clinical trials and other studies underway, which will provide high quality information in the months ahead. However, the results of such trials will not arrive in time to inform us during the current crisis. In the meantime, the best information available is that treatment of COVID-19 with high antibody plasma early in the course of the disease reduces mortality.
The public plays a huge role in the cycle of donation and receipt of convalescent plasma. Recovered patients are the source of this precious product, and their enthusiasm for donation, as exemplified by organizations such as “The Fight is In Us” and “Survivor Corps,” can be lifesaving. Consistent use of convalescent plasma could save lives and protect our overloaded health care system by reducing ICU admissions and promoting earlier discharges. Patients and their families should ask their health care providers about convalescent plasma as a therapeutic option early in the course of illness.
Drs. Arturo Casadevall, Johns Hopkins Bloomberg School of Public Health; Michael J. Joyner, Mayo Clinic School of Medicine; and Nigel Paneth, Michigan State University, are leaders of the National COVID-19 Convalescent Plasma Project.
