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Elevated Biomarkers Associated with PASC Phenotype

Elevated biomarkers suggest that acute infection with COVID-19 may have led to damage in central nervous system (CNS) tissue and caused systemic inflammation, a new study has found.

Published online in June ahead of the September publication in Neurology, the study examined the link between plasma biomarkers and eight self-reported neurologic symptoms in people recovering from SARS-CoV-2. It included measurements of inflammation and an evaluation of neurologic injury biomarkers in people who did and did not have a specific post-acute sequelae of SARS-CoV-2 infection (PASC) phenotype.

Lead author Michael J. Peluso, MD, assistant professor at the School of Medicine at University of California, San Francisco, and colleagues said an “urgent need" exists to understand the pathophysiology behind post-acute conditions resulting from COVID-19 infection. Previous research has shown that structural changes have taken place in the brains of people following infection with COVID-19, and a high number of people who had the virus experienced continuing mental and physical health symptoms two to 12 months afterward.

Recent research also suggests “that immune activation might play a role in PASC," researchers said. “Although a spectrum of symptoms is reported among individuals experiencing PASC, neurologic symptoms are particularly common," they said. “Limited data are available on the biologic predictors and correlates of these symptoms."

Their study involved 121 people previously diagnosed with COVID-19. Researchers evaluated them both before and after 90 days following their initial illness, focusing on several biomarkers of neurologic injury: glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and soluble markers of inflammation. Inflammatory markers including interleukin (IL)-6, tumor necrosis factor-alpha and interferon (IFN)-γ-induced protein (IP)-10 have been linked with patients' ongoing symptoms and “may correlate with long-term neuropsychiatric manifestations of COVID-19," researchers said.

Researchers asked participants about whether they currently had any of 32 symptoms, including eight neurologic ones, that had appeared or worsened since the person became infected with COVID-19. They also obtained plasma samples from participants.

“We compared fold changes in marker values between those with and without CNS PASC symptoms using linear mixed-effects models and examined relationships between neurologic and immunologic markers using rank linear correlations," they explained.

Fifty-two participants reported having central nervous system (CNS) PASC symptoms more than 90 days after first experiencing COVID-19 symptoms. The most common symptoms were trouble concentrating (81 percent), headache (35 percent), and dizziness (35 percent). Researchers also checked participants for memory, vision, and balance issues.

“We selected these symptoms because they were believed to best reflect dysfunction of the CNS and most likely to associate with biologic processes that could be identified using the two primary biomarker outcomes," researchers said.

The participants who reported these symptoms had elevated levels of GFAP but not NfL in the first 90 days after developing COVID-19 symptoms. After those 90 days, however, neither of the levels were elevated.

“Although absolute levels of NfL did not differ, those who reported CNS PASC symptoms demonstrated a stronger downward trend over time in comparison with those who did not report CNS PASC symptoms," researchers said.

Participants who later reported CNS PASC also had higher levels of (IL)-6, monocyte chemoattractant protein 1, and TNFα in both early and late recovery.

“A better understanding of the relationships between these markers among individuals with neurologic manifestations of PASC could help in identifying therapies to prevent and/or manage this condition as the pandemic continues," researchers said

Link Up for More Information:

Peluso MJ, Sans HN, Forman CA, et al. Plasma markers of neurologic injury and inflammation in p​​eople with self-reported neurologic postacute sequelae of SARS=CoV-2 infection. Neurol Neuroimmunol Neuroinflamm 2022;9(5):e200003.​