Abstract Details

Title Cognitive Symptoms After Mild SARS-CoV-2 Infection Associate with Higher Levels of CSF Immune Activation and Immunovascular Markers

Topic Behavioral and Cognitive Neurology

Presentation(s) N6 - Neuroscience in the Clinic: Neurological Implications of Long-haul COVID Infection (2:35 PM-2:45 PM)

Poster/Presentation
Number 002

Objective

To measure cerebrospinal fluid (CSF) immune activation and immunovascular markers in individuals with cognitive post-acute sequelae of SARS-CoV-2 infection (PASC) who had mild COVID-19.

Background

Cognitive PASC is a condition without identified biological correlates, although we reported a high rate of CSF abnormalities on clinically-available tests (77%). Theorized mechanisms include immune dysfunction.

Design/Methods

We enrolled participants in recovery from documented SARS-CoV-2 infection not requiring hospitalization who endorsed new, persistent cognitive symptoms (cognitive PASC, n=23) or no cognitive symptoms (controls, n=10) on structured neurocognitive interview. Participants underwent neurological examination and neuropsychological testing. Optional lumbar puncture and CSF analysis of immune activation and immunovascular markers were performed in 54% (n=13 cognitive PASC, n=5 controls).

Results

CSF was collected a median of 10.2 months after first COVID symptom without group differences in timing or demographics. Cognitive PASC participants had higher median levels of CSF acute phase reactants C-reactive protein (0.007 vs. 0.000 mg/L, p=0.004) and serum amyloid A (0.001 vs 0.000 mg/L, p=0.001) compared to controls, with trends in higher CSF immune activation markers interferon-gamma-inducible protein (IP-10; p=0.059), interleukin (IL)-8 (p=0.059), and immunovascular markers vascular endothelial growth factor-C (VEGF-C, p=0.095) and VEGFR-1 (the soluble receptor for VEGFs, p=0.059). Analyzing by time of cognitive symptom onset, acute onset cognitive PASC (n=7) associated with higher levels of CSF VEGF-C compared to delayed onset cognitive PASC (1+ months after first COVID symptom; n=5; 173 vs. 99 pg/mL p=0.048) and controls (79 pg/mL, p=0.048). Acute onset cognitive PASC had higher CSF levels of IP-10 (p=0.030), IL-8 (p=0.048), pIacental growth factor (p=0.030), and intercellular adhesion molecule-1 (p=0.045) compared to controls.

Conclusions

We found higher levels of CSF immune activation and immunovascular markers in cognitive PASC cases compared to controls; some markers showed specificity for acute onset cognitive PASC. These findings imply intrathecal immune activation and endothelial activation/dysfunction may contribute to cognitive PASC.

Authors/Disclosures
Joanna Hellmuth, MD PRESENTER	Dr. Hellmuth has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for McAngus Goudelock & Courie law firm.
	No disclosure on file
	No disclosure on file
Breton Asken	Breton Asken has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Samuel Pleasure, MD, PhD (UCSF)	Dr. Pleasure has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JAMA Neurology. The institution of Dr. Pleasure has received research support from NINDS, NIMH, NIDA, National MS Society, Brain Research Foundation, John Merck Fund, Whitehall Foundation, Lupus Research Association, Juvenile Diabetes Research Foundation.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Bruce L. Miller, MD, FAAN (University of California, San Francisco)	Dr. Miller has nothing to disclose.
Fanny M. Elahi, MD, PhD	Dr. Elahi has nothing to disclose.
Melanie Stephens, PhD	Dr. Stephens has nothing to disclose.

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