Now researchers think prior exposure to another coronavirus—one that causes a common cold—may play a role in some patients.

In the new study by Harvard University–affiliated scientists, published Sept. 26 to Yale University–affiliated preprint server medRxiv, authors tested the blood of 43 patients who had arthritis or a similar condition before the pandemic.

Such patients who later developed long COVID showed evidence of an underwhelming antibody response to COVID—and of an overwhelming antibody response to OC43, one of several circulating coronaviruses that cause common colds.

The patients were likely infected with the cold at some point in their lives before they were infected with COVID, the authors theorize. When their bodies’ immune systems were exposed to the coronavirus SARS-CoV-2, which causes COVID, they responded with OC43 antibodies that, while similar, were less than ideal, leading to chronic inflammation and other long COVID symptoms.

Dr. Eric Topol, a professor of molecular medicine at Scripps Research and founder and director of the Scripps Research Translational Institute, said the new findings come in a “very interesting report that adds to the possible underpinnings of long COVID.”

Researchers have looked at prior infection with Epstein-Barr virus, a form of herpes that can cause mono, and other viruses as potentially contributing to the development of long COVID, Topol tweeted Sept. 26. But the new study is the first to look at the role a common cold might play.

There are thought to be multiple categories of long COVID with, perhaps, different triggers for each, aside from COVID. While prior infection with this common cold may play a role in arthritis patients with long COVID, it may or may not play a role in other categories of patients, the authors wrote.

But for arthritis patients in particular, the discovery could serve as a way to identify long COVID and potentially develop a treatment for it, they added.

Nearly 20% of American adults who’ve had COVID—an estimated 50 million Americans—report having long COVID symptoms after their infection resolves, according to data collected by the U.S. Census Bureau this summer.

Long COVID is roughly defined as symptoms that persist or appear long after the initial COVID infection is gone, but a consensus definition has not yet been broadly accepted.

Many experts contend that long COVID is best defined as a chronic-fatigue-syndrome-like condition that develops after COVID illness, similar to other post-viral syndromes like those that can occur after infection with herpes, Lyme disease, and even Ebola. Other post-COVID complications, like organ damage and post-intensive-care syndrome, should not be defined as long COVID, they say.

Coronaviruses, named for their crown-like appearance under a microscope, were discovered in the 1960s. Four types, including OC43, commonly circulate among humans, usually causing colds. Three additional coronaviruses involve more serious symptoms: MERS (Middle Eastern respiratory syndrome), which caused an epidemic in 2012; SARS (severe acute respiratory syndrome), which caused an epidemic in the early 2000s; and COVID.