Variation in immune systems predicts patients with severe COVID-19

Editor's Note

Differing immune system responses of patients with COVID-19 can predict who will experience moderate and severe outcomes of the disease, this study by Yale researchers finds.

Of 113 patients analyzed, all shared common COVID-19 immune system activity early in the course of the disease. Patients with moderate symptoms had diminishing immune system responses and viral load over time. Those who developed severe cases showed no decrease in viral load or immune system reaction, and many of the immune signals in these patients accelerated.

Other early indicators that predicted which patients were at greatest risk of developing severe forms of the disease included:

• the presence of alpha interferon, a cytokine mobilized to combat viral pathogens such as the flu virus. However, COVID-19 patients with high levels of alpha interferon fared worse than those with low levels.
• activation of the inflammasome, a complex of proteins that detects pathogens and triggers an inflammatory response to infection. Inflammasome activation was linked to poor outcomes and death in several COVID-19 patients.
• those who responded better to the infection tended to express high levels of growth factors, a type of cytokine that repairs tissue damage to the linings of blood vessels and lungs.

Drugs that target specific causes of inflammation identified in the study could help treat patients at risk of developing severe cases of COVID-19, the researchers say.