Drop in Convalescent Plasma Use at Hospitals Linked to Higher COVID-19 Mortality Rate

The decrease may have led to as many as 29K COVID-19 deaths, new study suggests.

The decreased use of convalescent plasma to treat hospitalized COVID-19 patients might have led to more than 29,000 excess deaths during the winter surge, a new study suggests.

Researchers at Johns Hopkins Bloomberg School of Public Health, Michigan State University and the Mayo Clinic, noted that as plasma use was declining late last year, COVID-19 patient mortality rate was rising, leading them to speculate that the two phenomena were related.

"Clinical trials of convalescent plasma use in COVID-19 have had mixed results, but other studies, including this one, have been consistent with the idea that it does reduce mortality," study senior author Arturo Casadevall, MD, PhD, Alfred and Jill Sommer Professor and Chair of the Department of Molecular Microbiology and Immunology at the Bloomberg School, said in a press release.

Hospitals began treating COVID-19 patients with convalescent plasma therapy—which uses antibody-rich blood from recovered COVID-19 patients—in summer 2020 when doctors were looking to identify treatments for the emerging disease.

By spring 2021, U.S. doctors had treated more than 500,000 COVID-19 patients with convalescent plasma, but its use started declining late in 2020 after several large clinical trials showed no apparent benefit, according to the study, Convalescent plasma use in the United States was inversely correlated with COVID-19 mortality, published online June 4 in the journal eLife.

The researchers compared the number of units of plasma distributed to U.S. hospitals from blood banks, on a per-patient basis, to the number of reported COVID-19 deaths per hospital admission across the country.

They found that while the total use of plasma peaked last December and January during the winter COVID-19 surge, the use per hospitalized patient peaked in early October 2020—just as deaths per COVID-19 hospital admission bottomed. Thereafter, in the wake of reports of negative results from clinical trials, use of plasma per hospitalized patient fell sharply—and deaths per COVID-19 hospital admission rose.

The researchers analyzed the relationship between these two datasets and found a strong negative correlation, with higher use rate being associated with lower mortality and vice versa. They also grouped periods of plasma use into five “quintile” groupings from lowest-use weeks to highest and found a graded relationship between less use and higher mortality.

A model the researchers generated to fit the data suggested that the COVID-19 case fatality rate decreased by 1.8 percentage points for every 10-percentage point increase in the rate of plasma use, according to the study.

That model implied that there would have been 29,018 fewer deaths from November 2020 to February 2021, if the peak use rate of early October had held. It also suggested that the use of plasma overall, as limited as it was, prevented about 95,000 deaths through early March of this year.

The researchers considered, but rejected, the possibility that other factors—changes in the average age of hospitalized patients and the emergence of new COVID-19 variants—could explain away the link between less plasma use and more mortality.

Regarding those clinical trials that found no benefit for plasma use, many of them had used plasma—mainly considered an antiviral treatment—relatively late in the course of COVID-19, when patients may have been too ill to benefit, and when the disease is driven mainly by immune-related responses rather than the coronavirus itself, the study says.

Convalescent plasma remains under FDA Emergent Use Authorization in the U.S., and is readily available, Casadevall says.

"We hope that physicians, policymakers, and regulators will consider the totality of the available evidence, including our findings," Casadevall says, "when making decisions about convalescent plasma use in individual COVID-19 patients."