Why some people die while others recover is thought to depend in large part on the human immune response, which spirals out of control in severe disease. Over the past few months, researchers have developed a better understanding of this dysfunctional immune response. By comparing patients with varying degrees of disease severity, they’ve catalogued a number of dramatic changes across the human immune arsenal that are often apparent when patients first come into the hospital—from signaling cytokine proteins and first-responder cells of the innate immune system, to the B cells and T cells that confer pathogen-specific adaptive immunity.
The factors that trigger this immune dysregulation have so far remained elusive due to the complexity of the immune system, which consists of seemingly endless biological pathways that twist and turn and feed back on one another like a ball of spaghetti. But researchers—drawing on knowledge from other conditions such as sepsis, cancer, and autoimmune disease—are gradually building coherent theories of what puts patients en route to severe disease. Along the way, they’re also uncovering signals that clinicians could use to predict disease prognosis and identify potential new treatment avenues.
“We don’t have the clearest picture yet. Nor do we know why there’s variability in this immune response,” says Nuala Meyer, a critical care physician at the Hospital of the University of Pennsylvania who researches sepsis. While it’s well-established that underlying conditions increase the risk for developing severe COVID-19, “I definitely see patients with diabetes, obesity, and high lipids that did not become severe [cases],” she says. “I think we have a lot of work to do to understand precisely what accounts for this differential response.”
Read the story at The Scientist