Investigating Antidepressants’ Surprising Effect on COVID Deaths
Researchers are still puzzling over what this drug does at the molecular level to help COVID patients November 12, 2021
Researchers reported last month that an inexpensive, widely available pill substantially reduced hospitalizations and deaths in a large study of individuals with mild COVID symptoms who were at high risk for complications. It is the only existing oral medication with promising peer-reviewed data from multiple randomized COVID trials—and it is already used by millions of people worldwide. The drug is fluvoxamine, and it is approved in the U.S. for treating obsessive-compulsive disorder and depression. So how did this antidepressant end up in a trial for treating COVID?
“Drugs don’t know what their original indicated purpose was, they just do what they do, and they don’t usually do only one thing,” says Angela Reiersen, a child psychiatrist at Washington University in St. Louis (WashU). Along with her WashU psychiatry colleague Eric Lenze, Reiersen conducted a smaller randomized trial last year that suggested fluvoxamine could keep newly infected COVID patients from deteriorating.
Fluvoxamine is best understood for its impact on serotonin—a chemical messenger linked to mood and anxiety disorders. But the drug has other molecular targets. One is a protein called the sigma-1 receptor, which regulates the release of inflammatory molecules, including several that escalate in people with severe COVID. In a 2019 study, University of Virginia scientists chemically induced sepsis, a life-threatening infection complication, in mice. They observed that animals lacking the sigma-1 receptor developed severe inflammation, and many died. Yet in normal mice, a shot of fluvoxamine quieted the immunity overdrive and helped the animals survive.
That study caught Reiersen’s attention: the same overdrive immune response seen in those mice was a central feature observed in children who had come under her care because they had a rare genetic disorder—Wolfram syndrome—that led to psychiatric symptoms. When the pandemic hit and reports emerged that some people with COVID worsen because their inflammatory response goes haywire, Reiersen recalled the mouse study and wondered if fluvoxamine could also keep immune responses from spiraling out of control in these individuals.
