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

Abstract

OBJECTIVE:

Little is known about CSF profiles in patients with acute COVID-19 infection and neurological symptoms. Here, CSF was tested for SARS-CoV-2 RNA and inflammatory cytokines and chemokines and compared to controls and patients with known neurotropic pathogens.

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: Erica Normandin, Kathryn B Holroyd, Sarah I Collens, Bennett M Shaw, Katherine J Siddle, Gordon Adams, Melissa Rudy, Isaac H Solomon, Melis N Anahtar, Jacob E Lemieux, Bianca A Trombetta, Pia Kivisakk, Steven E Arnold, Otto Rapalino, Anne L Piantadosi, Pritha Sen, Eric S Rosenberg, John Branda, Pardis C Sabeti, Shibani S Mukerji
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 430 Pg. 120023 (Nov 15 2021) ISSN: 1878-5883 [Electronic] Netherlands
• PMID: 34678659 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Chemokines
• Cytokines
• RNA, Viral

Topics

• Blood-Brain Barrier
• COVID-19 (physiopathology)
• Case-Control Studies
• Chemokines
• Cytokines
• Humans
• Inflammation (virology)
• RNA, Viral (cerebrospinal fluid)
• SARS-CoV-2