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Many long COVID sufferers never even tested positive for the virus

In the early days of the COVID-19 pandemic, the true reach of the virus remained obscured as countless Americans who were exposed to SARS-CoV-2 went undiagnosed due to the shortage of testing infrastructure. 

A considerable number of these individuals subsequently developed a post-viral syndrome exhibiting symptoms closely mirroring those of long COVID. 

A widespread issue

A new study from the Northwestern Medicine Comprehensive COVID-19 Center in Chicago has now shed light on the magnitude of this issue, suggesting that the prevalence of long COVID might be significantly more widespread than previously believed.

Long COVID, as defined by health experts, comprises symptoms that linger for more than six weeks after the onset of the virus. 

While our understanding of this condition is still evolving, it is increasingly being acknowledged as a post-infection syndrome with substantial health repercussions.

Focus of the study

In this recent investigation led by Dr. Igor J. Koralnik, a research fellow with the American Academy of Neurology, a group of 29 individuals displaying post-viral symptoms were examined.

These individuals were experiencing neurological manifestations such as memory lapses, cognitive impairments, fatigue, and headaches, but had never formally tested positive for COVID-19.

How the study was conducted

The subjects were compared to a cohort of 32 individuals of comparable age brackets who had confirmed cases of long COVID. An additional comparison was drawn with 18 individuals without any trace of these symptoms or any known exposure.

The pivotal aspect of the research involved testing participants for antibodies against two protein markers – the nucleocapsid protein and the spike protein. These markers are pivotal indicators of an immune response triggered by a previous COVID infection. 

What the researchers discovered 

The results were eye-opening: 41 percent (12 out of the 29 people with post-viral syndrome) demonstrated immune responses aligned with a prior COVID brush, mirroring the immune profile of the long COVID group. 

Furthermore, three-quarters exhibited responses against the nucleocapsid protein, while half reacted to the spike protein.

“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,” said Dr. Koralnik.

“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.”

More research is needed 

Dr. Koralnik pointed out a troubling trend: “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,” said Dr. Koralnik. 

“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.”

Study limitations 

The study had some limitations, primarily due to the small size of the post-viral syndrome group. Also, some participants could have shown positive immune responses if their blood samples were obtained sooner after the onset of symptoms.

As the science continues to advance, it’s pivotal for the medical community and policymakers to recognize potential long COVID patients which are often overlooked. 

The study is published in the journal Neuroimmunology & Neuroinflammation.


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