MINNEAPOLIS — COVID-19 is a serious enough disease all on its own, but the emergence of “long COVID” has been a uniquely concerning aspect of the coronavirus pandemic. Defined as any lingering signs, symptoms, or conditions still present six weeks post-infection, long COVID can appear in a multitude of ways. These include general fatigue and respiratory, cardiovascular, or neurological symptoms. Now, new research suggests far more people than originally thought may be living with a form of long COVID.

Researchers at Northwestern University explain that when the COVID-19 pandemic first began in 2020, millions of Americans were exposed to SARS-CoV-2 (the virus that causes COVID-19) yet were unable to attain an official diagnosis due to testing limitations. As time passed, many of those not-officially-counted COVID-19 patients developed a post-viral syndrome with symptoms very similar to those of long COVID. This latest research, a small study focusing on the immune responses of that group of individuals, shows 41 percent had evidence of SARS-CoV-2 exposure.

“Since most long COVID clinics are only accepting patients with a positive test result, these people experiencing identical symptoms are left without specialized care and excluded from research studies on long COVID,” says study author Igor J. Koralnik, MD, of Northwestern Medicine Comprehensive COVID-19 Center in Chicago and a Fellow of the American Academy of Neurology, in a media release. “Our data suggest that millions of Americans with post-viral syndrome  may have been exposed to SARS-CoV-2 at the beginning of the pandemic, and they deserve the same access to care and inclusion in research studies as people with a confirmed COVID diagnosis.”

This project involved 29 people with post-viral syndrome, including neurologic symptoms like issues with memory and thinking skills, headache, and fatigue — yet did not have a positive COVID test result. Those participants were matched up with 32 people of similar ages diagnosed with long COVID and who tested positive for COVID-19 during their acute infection. Additionally, both cohorts were compared to 18 people with no known exposure to COVID-19 showing none of those symptoms.

Each person was tested for antibodies tied to two distinct types of proteins that show an immune response indicating a prior COVID infection: nucleocapsid protein and spike protein. Among the 29 people examined with post-viral syndrome, 12 (41%) showed immune responses consistent with prior exposure to COVID and similar to the long COVID cohort. Another three-quarters displayed responses against the nucleocapsid protein, while half had responses against the spike protein. That group also had similar symptoms in comparison to the long COVID group, as well as similar results on thinking skills tests.

“Unlike our clinic, about 70% of post-COVID clinics in the U.S. do not accept people with long COVID symptoms who do not have a positive test result for COVID,” Dr. Koralnik explains. “Our data suggest that at least four million people with post-viral syndrome similar to long COVID may indeed have detectable immune responses to support a COVID diagnosis. More research is needed to confirm our findings.”

It’s worth noting this research was limited by the small number of people examined with post-viral syndrome. Moreover, some participants may have tested positive for COVID-19 immune responses because their blood samples were collected closer to when their symptoms began than others.

The study is published in the journal Neurology.

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