Study identifies immune pathways activated in severe COVID-19 infection

Scientists work in a lab.

After analyzing publicly available data from blood and lung tissue samples from patients with severe COVID-19 infection, a team of 30 scientists took these findings back to the lab to study immune pathways that can become hyperextended. They observed, surprisingly, that interferon signaling initiated by the JAK1/2-STAT1 pathway activated complement genes and pathways within virus-infected cells that line the lungs, which created a cascading proinflammatory immune response. After confirming genes and other pathways involved in this detrimental immune feedback loop, the researchers used computer and lab models to test how targeted treatments could interrupt this process. Their goal is to advance research that helps patients with severe lung infections recover faster.

“This is a timely study, with exciting new insights into the unexpected local activity of an ancient arm of our immune system, complement. It also shows how principal investigators across academia and the clinical community can quickly and successfully collaborate to understand and respond to human disease,” said Claudia Kemper, Ph.D., chief of the complement and inflammation research section in the division of intramural research at the National Heart, Lung, and Blood Institute (NHLBI).

The study published in Science Immunology and was supported by several NIH institutes, including NHLBI, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, and the National Cancer Institute.