What Makes Me Sick Makes You Stronger: Convalescent Plasma as Treatment for COVID-19
Investigations in the US and China make a case for using convalescent plasma, a “last resort” for SARS, as an early treatment for COVID-19.
Survivors of COVID-19 could help with providing early treatment to other afflicted patients and even with protecting at risk family members and health care workers, if their immunoglobulin rich "convalescent" plasma or serum was donated and utilized as some medical investigators in China and the US are calling for.
"...human convalescent serum is an option for prevention and treatment of COVID-19 disease that could be rapidly available when there are sufficient numbers of people who have recovered and can donate immunoglobulin-containing serum," declared Arturo Casadevall, MD, PhD, of the Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, MD, and Liise-anne Pirofski, MD, of Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, in their viewpoint column in The Journal of Clinical Investigation.
"Evidence shows that convalescent plasma from patients who have recovered from viral infections can be used as a treatment without the occurrence of severe adverse events," stated Yuan Shi, PhD, MD, of the Chongqing Key Laboratory of Pediatrics, Chongqing, China, and colleagues in their comment column in The Lancet Infectious Diseases. "Therefore, it might be worthwhile to test the safety and efficacy of convalescent plasma transfusion in SARS-CoV-2 infected patients."
Convalescent plasma has already been administered in small series of patients in the current outbreak in China, according to a report from the Xinhua news agency. Although clinical data has not yet been published, anecdotal descriptions suggest that the procedure reduced viral load and was well tolerated.
The evidence of benefit from convalescent plasma in earlier viral diseases is compelling, and the precedents for passive antibody therapy that Casadevall and Pirofski, and Shi cited date back to the 1918 H1N1 influenza virus pandemic.
In that early case of administering blood products when, Casadevall and Pirofski pointed out, there were no means to measure antibody titers or knowledge about viral serotypes or studies that met modern criteria for randomization or blinding, a meta-analysis credits the procedure for a 21% reduction in overall crude case-fatality rate.
More contemporary examples include convalescent serum antibody preparations obtained by apheresis for patients with severe H1N1 2009 infection requiring intensive care; and use of convalescent plasma in the 2013 West African Ebola epidemic and in the H5N1 and H7N9 avian flu outbreaks.
"Although every viral disease and epidemic is different, these experiences provide important historical precedents that are both reassuring and useful as humanity now confronts the COVID-19 epidemic," Casadevall and Pirofski observed.
Shi points out that convalescent plasma or immunoglobulins was used as a last resort to improve survival of patients with SARS, when they continued to deteriorate despite treatment with pulsed methylprednisonlone.
Rather than relegate the treatment to last resort, however, Casadevall and Pirofski emphasized that it would be most effective when administered shortly after the onset of symptoms.
"The reason for temporal variation in efficacy is not well understood but could reflect that passive antibody works by neutralizing the initial inoculum, which is likely to be much smaller than that of established disease," Casadevall and Pirofski explain. "Another explanation is that antibody works by modifying the inflammatory response, which is also more easily achieved during the initial immune response."
In addition to recommending the intervention early in disease onset, the investigators urged considering it as a preventative for healthcare workers, and possibly family members caring for the patient. They noted that prophylactic doses of passive antibody therapy are smaller than therapeutic doses.
"Today, nurses, physicians, and first responders exposed to known cases of COVID-19, some of whom have developed disease, are being quarantined, which threatens to collapse the healthcare system," Casadevall and Pirofski warned.
The researchers recognized that convalescent plasma would be a stop-gap until other treatments are proven effective and made widely available. Until then, they call for mobilizing donation programs; coordinating blood banking facilities; conducting assays, including serological assays to detect SARS-CoV-2 in serum and virological assays to measure viral neutralization; and implementing therapeutic and prophylaxis protocols.
"Even local deployment will entail considerable coordination between different entities, such as infectious disease specialists, hematologists, blood banking specialists, and hospital administrators," Casadevall and Pirofski indicate. "Hence, as we are in the midst of a worldwide pandemic, we recommend that institutions consider the emergency use of convalescent sera and begin preparations as soon as possible."