Autoantibodies Block Interferons in 10% of Severe COVID-19 Cases

At least 10% of patients with life-threatening coronavirus diseases 2019 (COVID-19) pneumonia have antibodies that attack their own interferons, according to a new study by a team of international investigators.

The study, published in Science, found that 101 out of 987 patients with severe COVID-19 pneumonia had IgG autoantibodies that neutralize the ability of type 1 interferons to block SARS-CoV-2 infection.

“This was a huge surprise, much unexpected,” corresponding author Paul Bastard, affiliated with Inserm, University of Paris Imagine Institute and St. Giles Laboratory of Human Genetics of Infectious Diseases at The Rockefeller University, told Contagion®. “Very surprising how it mimics genetic inborn errors of immunity. Extremely surprising too that individuals with complete genetic defects in key interferon genes (as described in Zhang Q and al., Science, 2020) were adult patients who had not suffered previously from severe viral infections.”

In a separate study, the team detailed genetic variants contributing to life-threatening COVID-19 pneumonia. Loss-of-function variants at 13 human loci known to govern TLR3- and IRF7-dependent type 1 interferon immunity to influenza virus were examined. Genetic defects leading to impaired production or response to type 1 interferons were reported in 23 patients (3.5%).

The twin studies come from lab of Jean-Laurent Casanova, MD, PhD, head of the St. Giles Laboratory of Human Genetics of Infectious Diseases at the Rockefeller University, and the COVID Human Genetic Effort, a international collaboration aiming to determine how human genetics determine severe COVID-19.

The antibody study included 987 patients with critical COVID-19, 663 asymptomatic or pauci-symptomatic patients with COVID-19, and 1227 healthy controls. Autoantibodies were found in none of the patients with asymptomatic or mild COVID-19 and in only 4 of the healthy participants. Based on this, the estimated prevalence of these autoantibodies in the general population is 0.33%.

The study also could help explain why men have been more adversely affected by COVID-19 than women, finding that 95 of the 101 patients with the autoantibodies were men.

The neutralizing autoantibodies are believed to have been present before SARS-CoV-2 infection and caused the severity of the disease. They were identified in 2 patients before infection and 3 patients with APS-1, a serious but rare immune diseased marked by a high concentration of antibodies against interferons, had life-threatening COVID-19.

“It would be important to implement routine testing for auto-antibodies in all patients infected with COVID-19 to be able to implement adequate treatments and preventive measures. And perform genetic testing in the patients with unexplained severe COVID-19,” Bastard said.

Treatment could include early injected or nebulized IFN-β because autoantibodies that work against that type of interferon are rare among those affected, while treatment with IFN-α is unlikely to be affective, the study said.

Early intervention might be key. Once patients are hospitalized, it might be too late for treatment to show benefits. The World Health Organization Solidarity Trial recently released results indicating that interferon-beta therapy didn’t lower mortality nor the need for ventilation among more than 2,000 people who received the drug.