Indian Study Shows No Survival Benefit of Plasma in COVID-19

n the absence of a vaccine or an efficient antidote to SARS-CoV-2, the utilization of convalescent plasma therapy is hip globally. It involves the infusion of plasma from patients who have recovered from COVID-19 and thus carry protective antibodies into patients who are currently infected with the coronavirus. The US Food and Drug Administration (FDA) recently granted emergency use authorization (EUA) for its use, although the absence of randomized controlled trials (RCTs), the gold standard of research project , has led to skepticism about its effectiveness among experts.

In light of this, the PLACID (PLAsma Convalescent InDia) trial helps fill this gap. Recently conducted by the Indian Council of Medical Research (ICMR), the apex medical research body in India, it’s the primary RCT for plasma in COVID-19 patients to be completed within the world. The study included 464 hospitalized, moderately ill COVID-19 patients—they were on supplemental oxygen but not critically ill with organ damage—across 39 medical centers between April 22 and July 14. The trial had two arms: an intervention arm, during which patients received two doses of 200 ml of convalescent plasma, 24 hours apart, along side standard of care, and an impact arm that received standard of care alone.

The results, posted as a preprint on September 8 with a revision posted two days later, signal that the utilization of convalescent plasma in COVID-19 patients didn’t forestall progression to severe disease or mortality.

Study coauthor Pankaj Malhotra, a clinical hematologist at the Postgraduate Institute of Medical Education and Research in Chandigarh, India, says that these results won’t have much effect on clinical practice in India where convalescent plasma therapy is hugely popular and where the entire number of COVID-19 cases has crossed 4.9 million. In June, the Indian health ministry recommended off-label use of plasma in COVID-19 patients who showed no improvement despite standard of care. Malhotra adds that the study could perhaps cause a decline within the burgeoning illegal trade plasma within the country.

Arturo Casadevall, an immunologist at Johns Hopkins Bloomberg School of Public Health, tells The Scientist, “It’s the primary RCT that was completed for convalescent plasma and that i think that’s a big accomplishment.” An RCT in China was halted prematurely in late March thanks to dwindling cases and another within the Netherlands was discontinued as antibody titers in recipients were found to be like that of donors, raising questions on the potential advantage of convalescent plasma. within the US currently, there are quite 20 RCTs that are actively recruiting patients, but none are completed. an outsized Mayo Clinic study that was a part of the US Expanded Access Program for COVID-19 convalescent plasma which led to the FDA’s EUA was nonrandomized.

Despite the shortage of survival benefit shown within the ICMR study, some positives gleaned from the trial include improved symptoms and oxygenation and faster viral clearance in patients within the intervention arm compared with the control arm.

Michael Joyner, the lead author of the Mayo Clinic study that prompted the FDA to grant EUA for convalescent plasma therapy to treat COVID-19 within the US, tells The Scientist that the authors, the Indian research council, and therefore the country deserve tons of credit for doing this trial under very difficult circumstances. “I think that’s most impressive. . . . So, high compliments there.”

“I see the cup being half full in terms of the viral load data and therefore the improved oxygenation then forth,” Joyner says. The half empty part, he adds, is that the majority of the plasma had low titers of antibodies and was given relatively late during the course of the disease—a median of eight days after onset of symptoms. “Those are the 2 main limitations of the study.”

See “The look for Immune Responses that Stop COVID-19”
The Mayo Clinic investigators found that early treatment with plasma in hospitalized COVID-19 patients, within three days of diagnosis, with high levels of protective antibodies decreases mortality compared with later treatment using plasma with low titers of antibodies. Since this study didn’t include an impact arm, however, the researchers can’t say if the reduced mortality was thanks to plasma treatment.

Casadevall, who is involved in two clinical trials at Hopkins to check whether plasma therapy is effective in COVID-19, finds the results of the Indian study encouraging, and contends that the low titers, likely because many of the donors were younger and fitter and had only mild disease, and therefore the late use of plasma could perhaps account for the shortage of survival benefit.

Adrian Newland, a hematologist at Barts Health NHS Trust, tells The Scientist in an email, “It has also been seen that the antibody titers often fall off quite quickly therefore the chances of only 200 ml of serum (given twice) of providing any significant protection is little .”

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