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
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Cancer Cell. 2021 Feb 8;39(2):276-283.e3. doi: 10.1016/j.ccell.2021.01.007. Epub 2021 Jan 16.
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.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染会引发广泛的神经功能障碍，这些障碍在急性呼吸道感染数周后出现。为了更好地理解这种病理情况，我们对一组出现新型冠状病毒肺炎（COVID-19）神经症状的癌症患者进行了前瞻性分析，包括对脑脊液进行靶向蛋白质组学分析。我们发现，患有COVID-19神经后遗症的癌症患者在没有病毒神经侵袭的情况下，软脑膜存在炎性细胞因子。这些炎性介质大多由II型干扰素驱动，并且已知在其他疾病状态下会诱导神经元损伤。在这些患者中，脑脊液中基质金属蛋白酶-10的水平与神经功能障碍的程度相关。此外，这种神经炎症过程在急性呼吸道感染康复数周后仍持续存在。全身性细胞因子释放综合征后的这些长期神经后遗症会导致长期神经认知功能障碍。我们的研究结果表明抗炎治疗在COVID-19感染神经并发症的管理中具有作用。
