Transfusion of human plasma.
Transfusion of human plasma.

Whether plasma from people who have had COVID-19 can be used to treat the disease is a question that has lingered from almost the start of the pandemic. At least six trials of convalescent plasma are ongoing and over 1,200 research articles and reviews on this have been published.

Now two recent reports add to the debate about convalescent plasma transfusion (CPT) for COVID-19. One study reports on “ultrapotent” antibodies, that are found in few patients but may have big effects. The other shows “no significant benefit” of convalescent plasma for COVID-19 patients with early symptoms.

It’s an age-old idea, that many were particularly hopeful for in treating COVID-19.

Some of the first US patients to recover from COVID-19 donated blood samples to the National Institute of Allergy and Infectious Diseases (NIAID), where researchers studied convalescent serum samples for antibody responses to SARS-CoV-2 infection. When viral variants began to emerge late last year, the researchers used 22 samples from people infected with the SARS-CoV-2 Washington-1 (WA1) strain to investigate how those early patients would have fared against the evolving pathogen.

As reported by JAMA Network: “At least a few of the patients, all of whom had mild to moderate disease, produced 4 particularly potent antibodies against the strain that infected them and a diverse range of variants that since have been detected.”

Two of the antibodies were deemed “ultrapotent” at across all 23 of the variants the scientists tested, including B.1.1.7 (alpha), B.1.351 (beta), and B.1.617.2 (delta) variants.

The original research was published in Science, earlier this month.  (Wang et al. Science, Aug. 13. 2021.)

Abbasi writes, “The discovery comes at a critical moment. After plummeting earlier this year, SARS-CoV-2 cases are rising again with the spread of the delta variant, relaxed restrictions, and pockets of low vaccination uptake. Just months after the first vaccine doses became available in the US, talk of boosters is dominating the public conversation.”

Further, she points out, two monoclonal antibody therapies (Mabs) have already failed against this virus. Despite aggressive development, only two other products are authorized for use in mild to moderate COVID-19 patients:  Regeneron’s casirivimab plus imdevimab cocktail and sotrovimab from GlaxoSmithKline and Vir Biotechnology.

However, another study, released by the National Institutes of Health (NIH), found that convalescent plasma was useless, at least in early-stage patients.

According to the NIH: “The final results of the Clinical Trial of COVID-19 Convalescent Plasma in Outpatients (C3PO) demonstrate that COVID-19 convalescent plasma did not prevent disease progression in a high-risk group of outpatients with COVID-19, when administered within the first week of their symptoms.”

In fact, this trial was stopped in February 2021 “due to a lack of efficacy based on planned interim analysis.”

“We were hoping that the use of COVID-19 convalescent plasma would achieve at least a 10% reduction in disease progression in this group, but instead the reduction we observed was less than 2%,” said Clifton Callaway, MD., Ph.D., the contact principal investigator for the C3PO trial and professor of emergency medicine at the University of Pittsburgh. “That was surprising to us. As physicians, we wanted this to make a big difference in reducing severe illness and it did not.”

The researchers randomly assigned the participants to receive treatment with either high-titer COVID-19 convalescent plasma (containing anti-COVID-19 antibodies) or placebo (salt solution infused with multivitamins and lacking antibodies). Researchers compared outcomes in both groups within 15 days of treatment There was no significant difference in disease progression between the two groups.

“The results show that convalescent plasma does not appear to benefit this particular group,” said Nahed El Kassar, M.D., Ph.D., one of the study’s co-authors and medical officer in the Blood Epidemiology and Clinical Therapeutics branch of the NHLBI’s Division of Blood Diseases and Resources.

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