Abstract Details

Title Intrathecal inflammatory responses in the absence of SARS-CoV-2 nucleic acid in the CSF of COVID-19 hospitalized patients

Topic Infectious Disease

Presentation(s) S18 - COVID-19: From Bedside and Beyond (1:36 PM-1:48 PM)

Poster/Presentation
Number 004

Background Neurologic symptoms have been described in 30-60% of hospitalized patients with Coronavirus Disease 2019 (COVID-19). However, little is known about CSF profiles in these patients.

Objective Evaluate SARS-CoV-2 RNA and inflammatory cytokines and chemokines in the CSF of patients with acute COVID-19 and neurologic symptoms, and to compare these to controls and patients with known neurotropic pathogens.

Design/Methods

CSF from twenty-seven consecutive patients with COVID-19 and neurological symptoms was assayed for SARS-CoV-2 RNA using quantitative reverse transcription PCR (RT-qPCR) and unbiased metagenomic sequencing. Assays for blood brain barrier (BBB) breakdown (CSF:serum albumin ratio (Q-Alb)), and proinflammatory cytokines and chemokines (IL-6, IL-8, IL-15, IL-16, monocyte chemoattractant protein -1 (MCP-1) and monocyte inhibitory protein – 1β (MIP-1β)) were performed in 23 patients and compared to CSF from patients with HIV-1 (16 virally suppressed, 5 unsuppressed), West Nile virus (WNV) (n=4) and 16 healthy controls (HC).

Results

Median CSF cell count for COVID-19 patients was 1 white blood cell/μL; two patients were infected with a second pathogen (Neisseria, Cryptococcus neoformans). No CSF samples had detectable SARS-CoV-2 RNA by either detection method. In patients with COVID-19 only, CSF IL-6, IL-8, IL-15, and MIP-1β levels were higher than HC and suppressed HIV (corrected-p < 0.05). MCP-1 and MIP-1β levels were higher, while IL-6, IL-8, IL-15 were similar in COVID-19 compared to WNV patients. Q-Alb correlated with all proinflammatory markers, with IL-6, IL-8, and MIP-1β (r≥0.6, p<0.01) demonstrating the strongest associations.

Conclusions

Lack of SARS-CoV-2 RNA in CSF is consistent with pre-existing literature. Evidence of intrathecal proinflammatory markers in a subset of COVID-19 patients with BBB breakdown despite minimal CSF pleocytosis is atypical for neurotropic pathogens.

Authors/Disclosures
Kathryn Holroyd, MD PRESENTER	The institution of Dr. Holroyd has received research support from NINDS.
Erica Normandin (Broad Institute)	Erica Normandin has received research support from Howard Hughes Medical Institute. Erica Normandin has received research support from Broad Institute.
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Pia Kivisakk Webb, MD, PhD	Dr. Kivisakk Webb has nothing to disclose.
Steven E. Arnold, MD (Massachusetts General Hospital)	Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EIP Pharma. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sage Therapeutics. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cortexyme. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Boyle Shaughnessy Law. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Wolf Greenfield. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Advisory Board Member with Bob's Last Marathon.
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Shibani S. Mukerji, MD, PhD (Massachusetts General Hospital)	Dr. Mukerji has stock in Gilead Science. The institution of Dr. Mukerji has received research support from NIH. The institution of Dr. Mukerji has received research support from Massachusetts General Hospital.