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.
Keywords: COVID-19; Cerebrospinal fluid; Inflammation; Neurology; Sequencing.
【저자키워드】 COVID-19, Inflammation, NEUROLOGY, cerebrospinal fluid, sequencing., 【초록키워드】 HIV, Cytokines, IL-6, Sequencing, Infection, chemokines, chemokine, monocyte, NEUROLOGY, Protein, proinflammatory, RT-qPCR, White blood cell, pathogen, HIV-1, Patient, albumin, Control, IL-8, MCP-1, Pathogens, SARS-CoV-2 RNA, Inflammatory cytokines, Neurological symptoms, cerebrospinal fluid, proinflammatory cytokines, reverse transcription PCR, Quantitative, metagenomic sequencing, patients, Inflammatory cytokine, COVID-19 patients, Blood, CSF, IL-15, marker, West Nile Virus, Blood brain barrier, Atypical, COVID-19 patient, evidence of, Cryptococcus neoformans, Proinflammatory cytokine, profile, healthy control, two patients, acute COVID-19, cell count, inhibitory, neurotropic, Neurological symptom, pleocytosis, MIP-1β, performed, were infected, detectable, correlated, suppressed, subset, associations, consecutive patient, patients with COVID-19, was tested, with COVID-19, 【제목키워드】 CSF, Inflammatory response, SARS-CoV-2 nucleic acid, absence, hospitalized patient, Intrathecal,