It’s been estimated that up to one third of people who survive acute SARS-CoV-2 infection will suffer a post-viral syndrome with lingering neurologic and other symptoms — now known as long COVID or neurological postacute sequelae of SARS-CoV-2 infection (Neuro-PASC).
However, new research suggests that may be an underestimate and that far more people may be suffering from long COVID without ever having tested positive for the virus. Researchers found a significant proportion of patients in their small study who had never tested positive for COVID-19 but who were having symptoms of long COVID nevertheless showed evidence of immune responses consistent with previous exposure.
“We estimate that millions of people got COVID in the US during the first year of the pandemic and then developed long COVID, yet they did not get a positive COVID diagnosis because of testing limitations,” Igor J. Koralnik, MD, of Northwestern Medicine Comprehensive COVID-19 Center in Chicago, Illinois, told Medscape Medical News.
He noted that many post-COVID-19 clinics in the US don’t accept people with long COVID symptoms who do not have a positive test result.
Patients with long COVID symptoms but without laboratory evidence of prior infection, “who have often been rejected and stigmatized, should feel vindicated by the results of our study,” Koralnik said.
“We think that those patients deserve the same clinical care as those with a positive test, as well as inclusion in research studies. This is what we are doing at Northwestern Medicine’s Comprehensive COVID[-19] Center,” Koralnik added.
The study was published online August 23 in the journal Neurology: Neuroimmunology & Neuroinflammation.
The researchers measured SARS-CoV-2-specific humoral and cell-mediated immune responses against nucleocapsid protein and spike proteins, which indicate a prior COVID-19 infection, in 29 patients with post-viral syndrome after suspected COVID-19, including neurologic symptoms such as cognitive impairment, headache, and fatigue, but who did not have a confirmed positive COVID-19 test.
They did the same in 32 age- and sex-matched COVID long haulers with confirmed Neuro-PASC and 18 healthy controls with none of the symptoms of long COVID and no known exposure to SARS-CoV-2 or positive test result.
They found that 12 of the 29 patients (41%) with post-viral syndrome (but no positive COVID-19 test) had detectable humoral and cellular immune responses consistent with prior exposure to SARS-CoV-2. Three-quarters harbored antinucleocapsid and 50% harbored antispike responses.
“Our data suggest that at least 4 million people with post-viral syndrome similar to long COVID may indeed have detectable immune responses to support a COVID diagnosis,” Koralnik said in a news release.
The 12 patients with post-viral syndrome but without a confirmed COVID-19 test had similar neurologic symptoms as those with confirmed Neuro-PASC.
However, lack of a confirmed COVID-19 diagnosis likely contributed to the 5-month delay in the median time from symptom onset to clinic visit, the researchers said. They were evaluated at a median of 10.7 months vs 5.4 months for Neuro-PASC patients.
Koralnik told Medscape Medical News the “most important take-home message” of the study is that patients with post-viral syndrome often present with similar clinical manifestations as confirmed patients with Neuro-PASC, suggesting that a positive result by commercially available SARS-CoV-2 diagnostic test should not be a prerequisite for accessing care.
Patients with post-viral syndrome may benefit from the same clinical care as confirmed patients with Neuro-PASC, and the absence of a positive SARS-CoV-2 test should not preclude or delay treatment, he added.
The study had no specific funding. The authors report no relevant financial relationships.
Neurol Neuroimmunol Neuroinflammation. Published online August 23, 2023. Full text.
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