Public Health Watch: Study Finds No Benefit for Convalescent Plasma in Severe COVID-19

Does convalescent plasma work as a treatment for COVID-19?

The answer to this all-important question, particularly in the context of now-surging Omicron variant, is: It depends.

A study published by JAMA Network Open concluded that the treatment did not reduce the progression to severe respiratory failure or death in patients with moderate to severe COVID-19 pneumonia—at least not within 30 days of initiation. Notably, the regimen used in the study was high-titer convalescent plasma (≥1:160, by microneutralization test; at a dose 200 mL given in 1 to 3 infusions) plus standard therapy, while patients in the control group received standard therapy—remdesivir, glucocorticoids, and low–molecular weight heparin—alone.

The primary outcome, a composite of worsening acute respiratory failure or death within 30 days, occurred in 25.5% of patients who received convalescent plasma plus standard therapy compared with 28% of those who received standard therapy alone, the researchers found. Worse, the 30-day mortality rate was similar between the 2 groups, at 6.1% and 7.9%, respectively. In addition, the researchers found no significant differences in mechanical ventilation, death, virological cure, and time from hospitalization to discharge between the 2 groups.

“It has been suggested that the benefits of [convalescent plasma] may depend on the plasma NAb titer and that using [it] with a low titer could explain negative results,” wrote the researchers, from Pisan University Hospital, University of Pisa, Italy, who did not respond to requests for comment from Contagion. “To our knowledge, [this] was among the first and few randomized controlled trials using qualified convalescent plasma with a NAb titer of at least 1:160 assessed with microneutralization test.”

This prospective, open-label, randomized clinical trial enrolled 487 adults hospitalized with COVID-19 pneumonia (median age: 64 years; 64.1% men) with a partial pressure of oxygen-to-fraction of inspired oxygen ratio between 350 mm Hg and 200 mm Hg. Study participants were randomly assigned to receive either convalescent plasma plus standard therapy (n = 241) or standard therapy alone (n = 246) at 27 sites in Italy and the modified intent-to-treat population was 473, which the researchers acknowledge “was inadequate for the analysis of subgroups, such as patients with mild pneumonia, early disease onset (<72 hours), and negative serology.”

“Therefore, further studies are needed to evaluate the role of high-titer [convalescent plasma] therapy in these groups of patients,” they wrote.

However, another strike against the treatment is that 5% of those who received it experienced adverse events compared with 1.6% of the standard therapy group.

Still, as the Italian researchers also note, theirs is far from the only study to assess convalescent plasma as a treatment for COVID-19—and results have been mixed across the board. In the RECOVERY trial, for example, the mortality rate among participants who received the treatment was 24.1% vs 24.4% in the control group, though recipients of the experimental treatment with no detectable anti–SARS-CoV-2 IgG antibodies at the time of their transfusions had improved outcomes (OR, 0.90).

More recently, a JAMA Internal Medicine study published earlier this month found that convalescent plasma (at a dose of 250 mL) was effective in patients who develop serious symptoms from the virus, provided it is initiated early in the course of the disease, in hospitalized patients, before they require high levels of supplemental oxygen or become hypoxic, and before they have been treated with remdesivir. Patients given high-titer convalescent plasma were up to 70% more likely to meet the World Health Organization's criteria for clinical improvement within 28 days compared with those given the placebo.

The lack of clear-cut answers on convalescent plasma is frustrating, particularly as the world waits for other treatment options to come online. However, the treatment should remain in the armamentarium for as long as the fight against SARS-CoV-2 continues