Sex specific immune response to SARS-CoV-2 leads to chronic neurologic symptoms

项目总结 到目前为止，美国已有超过1600万人感染了严重急性呼吸综合征 冠状病毒2型病毒(SARS-CoV-2)，导致2019年冠状病毒病(新冠肺炎)。而浩瀚的 大多数人将在急性疾病中幸存下来，许多人面临在急性疾病后出现长期症状的风险。 生病了。据报道，COVID患者出现了包括脑炎、中风和癫痫在内的急性神经系统症状。 19例患者。越来越多地，即使没有急性神经疾病的幸存者也报告了神经精神疾病 症状(NPS)在他们患病几个月后。本病的发病率及影响其发展的因素。 术语NPS未知。SARS-CoV-2感染触发一种称为细胞因子的全身性促炎反应 风暴‘，其特征是不受控制地释放促炎分子。其后果是 对大脑的全身性炎症失控以及与新冠肺炎后长期NPS的联系尚不清楚。 新冠肺炎测试结果中的性别差异越来越明显。男性的结果会更差 急性新冠肺炎感染，住院率和死亡率更高，这是全球都能看到的影响。性 免疫功能的差异 文学 急性 炎症性 流通中 免疫 反应是急性病程差异的基础，正如在两者中所看到的那样 在我们的初步数据中。我们发现男性对人类的先天免疫反应 新冠肺炎感染，循环中中性粒细胞和单核细胞增加，血清中 脑损伤的细胞因子和标志物(神经元特异性烯醇化酶)。相比之下，女性拥有更多 与男性相比，T和B细胞对急性感染的反应是一种抗原特异性的特征 有趣的是，我们的初步数据表明，女性可能不成比例 受感染的慢性影响，包括较高的NPS发生率。为了研究NPS的机制， 我们建议进行一项纵向的前瞻性研究，以评估急性和慢性炎症对 脑损伤的标志物，以及新冠肺炎感染后长达2年的NPS。为了实现这一目标，我们 将利用我们潜在的临床生物库和长期的新冠肺炎后续诊所。到目前为止，已经有400多个 来自三家不同医院的新冠肺炎住院患者参加了一项前瞻性研究 生物库和休斯顿现在正处于另一次激增的边缘。确定有发展风险的患者 新冠肺炎感染的慢性后果，并发现导致 核动力源将对提高数以百万计新冠肺炎幸存者的健康至关重要。

PROJECT SUMMARY To date over 16 million people in the US have been infected with the severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19). While the vast majority will survive the acute illness, many are at risk for experiencing long-term symptoms after the acute illness. Acute neurologic symptoms including encephalitis, strokes and seizures have been reported in COVID- 19 patients. Increasingly, even survivors without acute neurologic conditions have reported neuropsychiatric symptoms (NPS) months after their illness. The incidence and factors that influence the development of long- term NPS is unknown. SARS-CoV-2 infection triggers a systemic pro-inflammatory response termed `cytokine storm', characterized by an uncontrolled release of pro-inflammatory molecules. The consequences of uncontrolled systemic inflammation on the brain and the link to long-term NPS after COVID-19 is unknown. Sex differences in the outcome from COVID-19 are increasingly evident. Men have worse outcomes with acute COVID-19 infection, with higher hospitalization rates and mortality, an effect seen globally. Sex differences in the immune literature acute inflammatory circulating immune responses underlie the differences i n the acute disease course, as seen both in t he and in our preliminary data. We have found that men have a more robust innate immune response to COVID-19 infection, with increased circulating neutrophils and monocytes and higher serum levels of cytokines and markers of brain injury (neuron specific enolase). In contrast, women have more T and B cells in response to acute infection compared to men, hallmarks of an antigen-specific response.Interestingly, our preliminary data suggest that women however, may be disproportionally affected by the chronic effects of infection, including higher rates of NPS. To examine the mechanism of NPS, we propose a longitudinal, prospective study to assess the impact of acute and chronic inflammation on markers of brain injury, and long-term NPS for up to 2 years after COVID-19 infection. To accomplish this, we will leverage our prospective clinical biorepository and long-term COVID-19 follow-up clinic. To date, over 400 hospitalized COVID-19 patients from three different hospitals have been enrolled into a prospective biorepository and Houston is now at the verge of another surge. Identifying patients at risk for developing chronic consequences of COVID-19 infection, and discovering potential underlying mechanisms leading to NPS will be critical to the enhance the health of millions of COVID-19 survivors.