Uncounted Long COVID Patients Never Had Test Results Positive for the Virus

Many people in the United States appear to be suffering from a post-viral syndrome similar to Long COVID, even though they never actually received a positive test result for the SARS-CoV-2 virus. A new study documents that many of them appeared to have had undiagnosed COVID and argues that those patients – possibly millions -- should be eligible for the same care as other Americans who have been diagnosed with Long COVID. Here is more information.

CHICAGO – Could many more Americans be suffering from long COVID symptoms than previously suggested?

A new study in the journal Neurology Neuroimmunology & Neuroinflammation makes an argument that might be the case. It advises that millions of people in the United States who were exposed to SARS-CoV-2, the virus that causes COVID-19, could not get diagnosed due to testing limitations early in the pandemic.


Researchers from the Feinberg School of Medicine at Northwestern University and colleagues raise the possibility that many of those patients developed a post-viral syndrome with symptoms similar to those of long COVID.

“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,” explained study author Igor J. Koralnik, MD, of Northwestern Medicine Comprehensive COVID-19 Center in Chicago. “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.”

The study was small, involving only 29 people with post-viral syndrome. Their symptoms included problems with memory and thinking skills, headache and fatigue, but they never had received a positive COVID test result. Those participants were matched with 32 COVID-19 survivors of similar age who reported long COVID symptoms and had received positive test results at some point. Both groups were also compared to 18 people with none of those symptoms and no known exposure to COVID or positive test results.

Participants were tested for antibodies to two types of proteins that show an immune response that indicates a prior COVID infection—nucleocapsid protein and spike protein. Of the 29 participants with post-viral syndrome, 41% had immune responses consistent with prior exposure to COVID and similar to the long COVID group. In addition, three-quarters had responses against the nucleocapsid protein and one-half had responses against the spike protein. The researchers note that highlights “the importance of multitargeted COVID-19 immunologic evaluation and the limitations of commercially available diagnostic tests.”

The group with symptoms but no prior positive COVID-19 test also had similar symptoms to the long COVID group and similar results on tests of thinking skills.

“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,” Koralnik said. “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.”

The researchers concluded that those patients “deserve the same access to care and inclusion in research studies as patients with NP with confirmed COVID-19 diagnosis.”

They advise that, currently, “Because most post–COVID–19 clinics in the United States are only accepting patients with a prior positive SARS-CoV-2 test result,7 individuals experiencing postviral syndrome (PVS) identical to PASC are left without specialized care when exposure to SARS-CoV-2 is not confirmed. Furthermore, the same people are also excluded from participation in research studies on PASC.”