Health study suggests that brain inflammation may not be responsible for persistent cognitive symptoms in patients with long COVID.
Researchers from the Yale School of Medicine found little evidence of abnormal cytokines in cerebrospinal fluid (CSF) or blood-brain barrier dysfunction in people with neurologic long COVID symptoms such as brain fog. This poses the challenge that interventions targeting brain inflammation may not help individuals with post-COVID conditions.
“Our results indicate that neuroinflammation and blood-brain barrier dysfunction are unlikely to be drivers of neuropsychiatric symptoms after COVID-19, and that interventions aimed at quieting brain inflammation likely won’t help people with post-COVID conditions,” said lead researcher Shelli Farhadian, MD, PhD.
In addition, the study found that elevated CSF cytokines in people with brain infections and other neuroinflammatory diseases were not present in patients with long COVID cognitive symptoms. Furthermore, researchers were unable to pinpoint the exact cause for the persistence of symptoms years after having COVID.
Neuroinflammation, coagulopathy, neuronal injury, and potential viral infection in the central nervous system are among the proposed mechanisms behind long COVID neurologic and psychiatric symptoms.
While the study is an important step in understanding the complexities of post-acute sequelae of SARS-CoV-2 infection (PASC), experts note that more sophisticated research tools may be required to unravel the underlying mechanisms.
The small case-control study at Yale analyzed cerebrospinal fluid and blood samples from 37 individuals with long COVID symptoms and 22 asymptomatic participants. Despite differences in demographics and health behaviors, the study did not find significant immune abnormalities between the two groups.
The lack of immune abnormalities in the study is consistent with similar findings from a smaller Swedish study that demonstrated consistent absence of cerebrospinal fluid (CSF) abnormalities in people with neurocognitive long COVID.
While the results offer insight into the neurology of long COVID, several limitations were acknowledged, including the small sample size and potential biases due to demographic differences in the control group.
This research was supported by grants from the NIH and the Merck Investigator Studies Program.
A co-author reported receiving grants from the National Institute of Mental Health during the conduct of the study. No other disclosures were reported.
JAMA Network Open
Source Reference: Farhadian SF, et al “Self-reported neuropsychiatric post-COVID-19 condition and CSF markers of neuroinflammation” JAMA Netw Open 2023; DOI: 10.1001/jamanetworkopen.2023.42741.