WHO Advises Against Convalescent Plasma as COVID-19 Treatment

A laboratory technician prepares to process a bag of blood plasma as part of a research project on plasma from recovered patients for the treatment of COVID-19 patients, on Oct. 5, 2020. Jaime Reina/AFP via Getty Images

The World Health Organization (WHO) late Monday advised against using convalescent plasma to treat COVID-19.

“For non-severe COVID-19 patients, WHO recommends against its use, while it should only be used within clinical trials for severe and critical COVID-19 patients,” the WHO announced.

Convalescent plasma therapy involves using the blood plasma of patients who recovered from COVID-19 to treat others actively ill with the disease, in an effort to prevent disease progression and help them recover more quickly.

It was believed that the antibodies contained in the blood plasma of recovered COVID-19 patients may provide passive immunity for those taken ill with the disease, by neutralizing the SARS-CoV-2 virus.

“Despite its initial promise, current evidence shows that [convalescent plasma therapy] does not improve survival nor reduce the need for mechanical ventilation, and it is costly and time-consuming to administer,” the British Medical Journal (BMJ) said in a press release late Monday.

Based on 16 Randomized Controlled Trials

The new recommendation has been published in the BMJ and was developed by the WHO Guideline Development Group (GDG), a panel of international scientists, which said their decision was informed by 16 randomized controlled trials (RCTs) involving 16,236 patients with non-severe, severe, and critical COVID-19.

“The included RCTs enrolled non-pregnant women and men,” the GDG said in the medical journal. “The GDG had no reason to think that children or pregnant women with covid-19 would respond any differently to treatment with convalescent plasma, and the GDG therefore inferred that children and pregnant women should not receive the intervention either.”

The GDG said “there was no benefit demonstrated in any of the critical or important outcomes for non-severe covid-19” cases that had convalescent plasma therapy, and thus the group “did not see any justification for the resources (including time and cost) that would be associated with administration of convalescent plasma.”

It added, “The GDG believed that, although convalescent plasma should not be used in any severity subgroups as part of routine care, there was sufficient uncertainty in patients with severe and critical illness to warrant continuation of RCTs.”

The panel of scientists noted that “although it is not demonstrated in the evidence summary, there is always a potential for harms with blood product transfusion.”

Those with severe or critical COVID-19 should receive both corticosteroids and IL-6 receptor blockers, the GDG recommended. And in select cases, severe or critical COVID-19 may be treated with neutralizing monoclonal antibodies, the panel said.

Previous Papers

Some previous studies have suggested that COVID-19 convalescent plasma therapy was not effective in reducing disease progression, and sometimes not effective in reducing mortality, but a recent meta-analysis of 23 RTCs found some benefit in reducing mortality risk.

In August, a large, randomized, placebo-controlled trial funded by the National Institutes of Health found that convalescent plasma administered to high-risk outpatients within one week after symptoms onset “did not prevent disease progression.”

The trial—the Covid-19 Convalescent Plasma in Outpatients (C3PO) trial—results of which were published in the New England Journal of Medicine, enrolled 511 patients. COVID-19 disease progression occurred in roughly 30 percent in either group, and five patients in the plasma group and one patient in the placebo group died, reported the study authors.

The trial was halted in February, the authors wrote, citing lack of efficacy. Clifton Callaway, the contact principal investigator for the trial, said researchers were hoping the therapy “would achieve at least a 10% reduction in disease progression ... but instead the reduction we observed was less than 2%.”

A lab technician freeze packs donated convalescent plasma donated by recovered COVID-19 patients for shipping to local hospitals at Inova Blood Services, in Dulles, Va., on April 22, 2020. Alex Edelman/AFP/Getty Images

Separately, in a UK trial of patients hospitalized with COVID-19—the RECOVERY trial published in May—authors found “the risk of death after the administration of high-titer plasma was not different from the standard of care.” The trial involved 11,558 patients.

Another study, published in Nature Medicine in September, found that convalescent plasma did not lower the risk of intubation or death. However, the researchers did note that the varied antibody content of the convalescent plasma may have changed the response to the treatment.

However, in a recent meta-analysis of 23 RTCs published in September, researchers analyzed the variables that affected the efficacy of convalescent plasma in the studies and found that although there were mixed data on clinical efficacy, convalescent plasma did reduce mortality in many of the studies. The paper, titled “COVID-19 convalescent plasma and randomized clinical trials: rebuilding confidence by explaining failures and finding signals of efficacy,” is yet to be peer-reviewed and was published as a pre-print.

“Focusing only on the results from the 23 available RTC we noted that these were more likely to show signals of efficacy, including reductions in mortality if the plasma neutralizing titer was ≥ 160 and the time to randomization was ≤ 9 days, consistent with passive antibody therapy efficacy requiring dosing with sufficient antibody,” the authors wrote.

“The fact that most studies revealed signals of efficacy despite variability in [COVID-19 convalescent plasma] and its use suggest robust therapeutic effects that become apparent despite the data noise,” the authors added.

The authors also noted that several studies they reviewed “have reported overall negative results [regarding convalescent plasma therapy] ... despite the presence of positive signals of efficacy just barely missing statistical significance.”

FDA Emergency Use Authorization

The U.S. Food and Drug Administration (FDA) authorized convalescent plasma therapy for emergency use to treat COVID-19 in August 2020.

The federal regulator narrowed the EUA’s scope in February to only allow for blood plasma with high levels of antibodies—referred to as “high-titer convalescent plasma”—and for hospitalized COVID-19 patients before they went into respiratory failure, or to patients with impaired immunity.

“Plasma with low ranges of antibodies has not been proven to be useful in COVID-19,” the FDA stated in its revised EUA at the time. It told health care providers in a fact sheet (pdf), “Based on the totality of scientific evidence available at this time, the known and potential benefits of high titer COVID-19 convalescent plasma outweigh the known and potential risks when administered early in the course of the disease, and those hospitalized with impaired humoral immunity.”

Dr. Paul Marik, professor of medicine and chief of the Division of Pulmonary and Critical Care Medicine at the Eastern Virginia Medical School, who has been treating COVID-19 patients since the beginning of the pandemic, previously told The Epoch Times convalescent plasma is only effective in patients who are “severely immunocompromised.”

Shmuel Shoham, associate professor of medicine at Johns Hopkins University, told Endpoints News late Monday that “when used at the right time and with high enough titers,” convalescent plasma therapy to treat COVID-19 is “effective and generally safe.”

The American Red Cross had stopped collecting convalescent plasma from recovered COVID-19 patients since June 2021 due to low hospital demand and because blood industries have enough supply in storage.

Meiling Lee contributed to this report.