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[Preprint]. 2020 Sep 18:2020.09.15.20195511. [Version 1] doi: 10.1101/2020.09.15.20195511

Inflammatory leptomeningeal cytokines mediate delayed COVID-19 encephalopathy

Jan Remsik, Jessica A Wilcox, N Esther Babady, Tracy McMillen, Behroze A Vachha, Neil A Halpern, Vikram Dhawan, Marc Rosenblum, Christine A Iacobuzio-Donahue, Edward K Avila, Bianca Santomasso, Adrienne Boire
PMCID: PMC7523144  PMID: 32995805

Abstract

SARS-CoV-2 infection induces a wide spectrum of neurologic dysfunction. Here we show that a particularly vulnerable population with neurologic manifestations of COVID-19 harbor an influx of inflammatory cytokines within the cerebrospinal fluid in the absence of viral neuro-invasion. The majority of these inflammatory mediators are driven by type 2 interferon and are known to induce neuronal injury in other disease models. Levels of matrix metalloproteinase-10 within the spinal fluid correlate with the degree of neurologic dysfunction. Furthermore, this neuroinflammatory process persists weeks following convalescence from the acute respiratory infection. These prolonged neurologic sequelae following a systemic cytokine release syndrome lead to long-term neurocognitive dysfunction with a wide range of phenotypes.

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