Inflammatory leptomeningeal cytokines mediate COVID-19 neurologic symptoms in cancer patients

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

SARS-CoV-2 infection induces a wide spectrum of neurologic dysfunction that emerges weeks after the acute respiratory infection. To better understand this pathology, we prospectively analyzed of a cohort of cancer patients with neurologic manifestations of COVID-19, including a targeted proteomics analysis of the cerebrospinal fluid. We find that cancer patients with neurologic sequelae of COVID-19 harbor leptomeningeal inflammatory cytokines in the absence of viral neuroinvasion. The majority of these inflammatory mediators are driven by type II interferon and are known to induce neuronal injury in other disease states. In these patients, levels of matrix metalloproteinase-10 within the spinal fluid correlate with the degree of neurologic dysfunction. Furthermore, this neuroinflammatory process persists weeks after convalescence from acute respiratory infection. These prolonged neurologic sequelae following systemic cytokine release syndrome lead to long-term neurocognitive dysfunction. Our findings suggest a role for anti-inflammatory treatment(s) in the management of neurologic complications of COVID-19 infection.