Limited Benefits

UNM Researchers Find Flaws in Convalescent Therapy for COVID-19

Hospitals around the world are treating COVID-19 patients with plasma drawn from people who have recovered from the infections in hopes that their antibodies will bind to and neutralize the virus.

But in a recent study University of New Mexico researchers identify potentially serious shortcomings in the use of so-called “convalescent” plasma, reporting that none of 12 patients at UNM Hospital who received the treatment appeared to benefit from it.

“We stopped after we enrolled 13 patients [in the study] after we got some of the data back showing that most of the convalescent plasma had little to no neutralizing antibodies in it and it actually didn’t help them improve their antibody levels,” said Michelle Harkins, MD, division chief of Pulmonary, Critical Care & Sleep Medicine.

The paper, accepted online this week by the Journal of Infectious Diseases, reflects a unique collaboration between her division, the Division of Infectious Diseases and the UNM Center for Global Health, Harkins said. 

Twelve patients enrolled in the study were followed for 14 days following transfusions of convalescent plasma. The researchers were especially interested in the presence of neutralizing antibodies – immune proteins tailor-made by the body to target the SARS-CoV-2 coronavirus.

At the end of the trial period, there was no evidence the convalescent plasma had sparked a strong immune response in the hospitalized patients. And upon testing, it was determined that the plasma – collected from different donors – showed wide differences in the concentrations of these neutralizing antibodies, they found.

The team also measured levels of Immunoglobulin M (IgM) antibodies, which are the first to be produced in the body when the immune system detects an infection, and Immunoglobulin G (IgG) antibodies, which trigger a longer-lasting immune response. The presence of IgG didn’t translate to high levels of neutralizing antibodies, Harkins said.

“We were surprised,” she said. “Just because the plasma has a detectable level of IgG antibodies doesn’t mean it has enough neutralizing antibodies to be therapeutically effective.”

The use of convalescent plasma collected from recovered patients is a century-old technique that has proven effective in fighting other viral infections, and many doctors have turned to it because few other effective medical treatments are available, Harkins said.

The UNM researchers believe that concentrations of neutralizing antibodies in convalescent plasma might vary depending on the severity of the donor’s illness and how much time has elapsed prior to the donation. The study underscores the need to test for concentrations of neutralizing antibodies before administering convalescent plasma to patients.

They also point out that each of the patients received a standardized 200 milliliters of plasma, although the patients varied greatly in age and weight, suggesting that the amount of plasma administered must matched to each patient’s body size.

The findings underscore how much remains to be learned about the novel coronavirus and its effects in the body – which is why it is important to share with the broader scientific community potential shortcomings with convalescent plasma therapy, Harkins said.

It’s way early in the pandemic,” Harkins said. “Everybody wants to have an answer. Our study was a small number of patients, so we can’t say that it helped anybody. It didn’t hurt anyone.”

The bottom line, she says, is “we have to know what we’re using, and we have to know more about how the body’s immune response will receive this, and how it will work.”