All convalescent plasma may not have protective antibodies

There are at least three kinds of antibodies produced in an infection: IgG, IgA, IgB but the neutralising effect was most visible only in the case of the IgGs

Not all plasma from those who’ve recovered from COVID-19 in India may contain enough protective antibodies, says a multi-institutional study led by researchers in the country and the United States.

Also read: Coronavirus | Plasma therapy may look promising in treating COVID-19, but it is no magic bullet

When scientists checked the antibodies from 42 persons who had mild to moderate infection and had recovered, 38 of them expressed IgG (Immunoglobulin G) responses — the antibodies that are produced a week or two of the infection. However, only “half of them had appreciable neutralising antibody titres,” say the scientists in a paper uploaded on BioArxiv, an online repository of scientific papers and are usually yet to be peer-reviewed.

Plasma therapy, the administration of filtered serum from the blood of those who had recovered from the infection to those who are battling it, is among the permitted off-label interventions recommended by the Indian Council of Medical Research (ICMR) in patients with moderate disease but whose oxygen saturation levels aren’t improving despite the use of steroids.

However, in the PLACID trial, among the largest studies of its kind and spread across 39 hospitals and 464 participants, the ICMR concluded that plasma therapy neither helped reduce mortality nor prevented moderately ill patients from manifesting severe COVID-19 disease.

Also read: Coronavirus | Plasma therapy didn’t help COVID-19 patients: ICMR

Director General of ICMR Dr. Balram Bhargava said on Wednesday that the PLACID results hadn’t been ‘peer-reviewed’ and only after that would the organisation consider changes to recommendations in plasma use as therapy. Several hospitals in India continue to advise caregivers — frequently through their own means — to procure plasma for ailing patients.

“Neutralising response”

The latest study underscored that only those IgG antibodies that bound to the receptor binding region of the coronavirus spike protein, which attaches itself to the body’s healthy cells and infiltrates, had a “neutralising response.” Antibodies that bound to other parts of the virus didn’t succeed in provoking such a response. Thus, doctors, when assessing plasma therapy, would be well served to evaluate the quality of the plasma via an assay, or a chemical test, that specifically evaluates the levels of RBD (receptor-binding domain)-specific IgG titres and not just crude IgG levels.

Also read: Experts question FDA nod for emergency use of plasma therapy

There are at least three kinds of antibodies produced in an infection: IgG, IgA, IgB but the neutralising effect was most visible only in the case of the IgGs, the authors noted.

“It’s important to note that many Indian government agencies and institutions are already making efforts to bring these RBD-based IgG assays more widely available, and thus this study is very relevant and timely to scientifically validate these efforts,” the ICGEB-Emory said in a statement.

The ICMR-funded study is led by Anmol Chandele and Kaja Murali Krishna of the ICGEB-Emory Vaccine Center at the International Centre for Genetic Engineering and Biotechnology. Done in collaboration with ICMR-National Institute of Malaria Research, Dept of Biotechnology and the Emory Vaccine Center, Atlanta, it doesn’t explain why many with antibodies didn’t express neutralising responses, but conjectured that it could have to do with inter-individual differences in human immune responses associated with variants of the virus, the initial viral loads that those infected were exposed to, genetic factors and disease severity.

Previous studies have shown that there are relatively higher neutralising antibodies in COVID-19 hospitalised patients during the acute febrile phase, or in recovered individuals that were previously hospitalised with severe COVID-19 disease.

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