WHO recommends against the use of convalescent plasma for Covid-19
The World Health Organization said late today that it’s not recommending the use of convalescent plasma as a treatment for Covid-19 for mild or severe cases, but some US experts disagree with the recommendations and say there are patients who can benefit from the plasma of those who’ve recovered from Covid-19.
The recommendation is informed by a review of 16 RCTs and a “meta-analysis on antibodies and cellular therapies for covid-19,” the WHO said, adding in a statement:
Despite its initial promise, current evidence shows that it [convalescent plasma] does not improve survival nor reduce the need for mechanical ventilation, and it is costly and time-consuming to administer. As such, the WHO makes a strong recommendation against the use of convalescent plasma in patients with non-severe illness, and a recommendation against its use in patients with severe and critical illness, except in the context of a randomised controlled trial (RCT).
The WHO wrote in the BMJ that, “Most importantly, given there was no benefit demonstrated in any of the critical or important outcomes for non-severe covid-19, the GDG [Guideline Development Group] did not see any justification for the resources (including time and cost) that would be associated with administration of convalescent plasma.”
The announcement builds on recently published data showing that while convalescent plasma has proven to be generally safe, it also failed to show signs of efficacy in some large RCTs of outpatients, including on mortality in a UK trial of those hospitalized with Covid, published in The Lancet in May, and another for outpatients in August in the New England Journal of Medicine.
In the results published in the NEJM, the NIH-funded trial enrolled more than 500 patients, randomized to receive either plasma or placebo within one week after the onset of symptoms. Covid-19 progression occurred in 77 patients (30%) in the convalescent plasma group and in 81 patients (31.9%) in the placebo group. Five patients in the plasma group and one patient in the placebo group died, and the trial was stopped early in February due to lack of efficacy.
But experts still think there may be times when convalescent plasma could help people with Covid-19, either when it’s detected early enough and high enough titers can be used (as CBER director Peter Marks has said) or for those whose immune systems may be deficient in some way.
“Based on available data I do not agree with this conclusion” from the WHO, Shmuel Shoham, associate professor of medicine at Johns Hopkins University, told Endpoints News. “When used at the right time and with high enough titers, COVID-19 Convalescent Plasma (CCP) is effective and generally safe. The widespread availability of CCP makes it an option in places where monoclonal antibodies are not readily available. There is additional data that will soon be available from the Johns Hopkins outpatient studies.”
The FDA still maintains an EUA for convalescent plasma, which was narrowed last February to only high titer units and for hospitalized patients who are in the early stages of the disease. It remains to be seen if the WHO’s new recommendation will change the EUA.
An FDA spokesperson told Endpoints that it’s aware of but not commenting on the WHO’s announcement, and the FDA EUA for convalescent plasma remains in effect at this time. The EUA was reissued on March 9, 2021 and amended in June. The FDA does not collect data on how many people have been treated with convalescent plasma under the EUA, and about 70,000 people accessed convalescent plasma under an expanded access program at the Mayo Clinic that the FDA helped to establish.
Jeff Henderson, associate professor of medicine at Washington University School of Medicine in St. Louis, told Endpoints, “Much has been learned about COVID-19 pathogenesis in the past year and a half. Relevant to therapeutics, we have learned that SARS-CoV-2 pathogenesis proceeds through an early phase of viral replication to a later phase of inflammation-associated tissue damage. Studies that take this into account have detected efficacy signals when high titer COVID-19 convalescent plasma is administered early in disease to patients with mild to moderate COVID-19.”