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

对 SARS-CoV-2 的性别特异性免疫反应导致慢性神经系统症状

• 批准号: 10669769
• 负责人: Fudong Liu
• 金额: $ 69.08万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10669769
• 关键词: 2019-nCoV; Acute; Acute Brain Injuries; Acute Disease; Affect; Age; Antigens; Anxiety; B-Lymphocytes; Blood; Brain; Brain Injuries; COVID-19; COVID-19 impact; COVID-19 patient; COVID-19 survivors; Cardiology; Cells; Chronic; Clinic; Clinical; Control Groups; Data; Development; Disease; Disease Progression; Drowsiness; Encephalitis; Endothelium; Enrollment; Event; Fatigue; Flow Cytometry; Functional disorder; Health; Hospitalization; Hospitals; Immune; Immune response; Incidence; Infection; Inflammation; Inflammatory; Inflammatory Response; Injury; Innate Immune Response; Internal Medicine; Investigation; Length of Stay; Leukocytes; Link; Literature; Long COVID; Longitudinal Studies; Measures; Mechanical ventilation; Mental Depression; Modeling; Neurologic; Neurologic Symptoms; Neurological outcome; Neuron-Specific Enolase; Neuronal Injury; Outcome; Pain; Pathway interactions; Patients; Peripheral; Persons; Population; Post-Traumatic Stress Disorders; Prevalence; Public Health; Reaction; Reporting; Research; Risk; SARS-CoV-2 infection; Sampling; Seizures; Serum; Serum Markers; Sex Differences; Stroke; Survivors; Symptoms; T-Lymphocyte; Time; Virus; Woman; acute infection; biobank; bioinformatics tool; cognitive function; coronavirus disease; cytokine; cytokine release syndrome; experience; follow-up; functional status; hospitalization rates; immune activation; inflammatory marker; long-term sequelae; longitudinal, prospective study; men; monocyte; mortality; mortality risk; neuropsychiatric symptom; neutrophil; pandemic disease; post SARS-CoV-2 infection; predictive modeling; prospective; response; sex; systemic inflammatory response; vaccine access

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.

项目摘要 迄今为止，美国已有超过1600万人感染了严重的急性呼吸综合症 冠状病毒2病毒（SARS-COV-2），导致冠状病毒疾病2019（Covid-19）。而广大 多数将在急性疾病中幸存下来，许多人有急性后出现长期症状的风险 疾病。急性神经系统症状包括脑炎，中风和癫痫发作 19位患者。甚至没有急性神经系统疾病的幸存者也报道了神经精神病学 症状（NPS）在患病后几个月。影响长期发展的发生率和因素 NP术语未知。 SARS-COV-2感染触发了一种被称为细胞因子的全身性促炎反应 风暴”，其特征是促炎分子的不受控制。后果 尚不清楚大脑上的不受控制的全身炎症，以及与19 Covid-19之后的长期NP的联系是未知的。 Covid-19的结果差异越来越明显。男人的结果更糟 急性共同COVID-19感染，住院率和死亡率较高，这一影响在全球范围内。性别 免疫的差异 文学 急性 炎症 循环 免疫 在急性疾病过程中的差异是基于急性疾病的差异的基础 在我们的初步数据中。我们发现男人对 共vid-19感染，循环中性粒细胞和单核细胞增加，血清水平较高 脑损伤的细胞因子和标记（神经元特异性烯醇酶）。相反，女性有更多 与男性相比，T和B细胞响应急性感染，抗原特异性的标志 响应。令人讨厌的是，我们的初步数据表明女性可能不成比例 受感染的慢性作用的影响，包括较高的NP。要检查NP的机制， 我们提出了一项纵向的前瞻性研究，以评估急性和慢性炎症对 脑损伤的标记和长期NP在19次感染后长达2年。为此，我们 将利用我们的前瞻性临床生物疗法和长期Covid-19的随访诊所。迄今为止，超过400 来自三家不同医院的住院Covid-19患者已入学 Biorepository和Houston现在正处于另一场激增的边缘。确定有发展风险的患者 COVID-19感染的慢性后果，并发现潜在的潜在机制导致 NP对于增强数百万COVID-19幸存者的健康至关重要。

项目成果

Brain injury, endothelial injury and inflammatory markers are elevated and express sex-specific alterations after COVID-19.

• DOI: 10.1186/s12974-021-02323-8
• 发表时间: 2021-11-27
• 期刊: Journal of neuroinflammation
• 影响因子: 9.3
• 作者: Savarraj J;Park ES;Colpo GD;Hinds SN;Morales D;Ahnstedt H;Paz AS;Assing A;Liu F;Juneja S;Kim E;Cho SM;Gusdon AM;Dash P;McCullough LD;Choi HA
• 通讯作者: Choi HA

Upregulation of PD-L1 by SARS-CoV-2 promotes immune evasion.

• DOI: 10.1002/jmv.28478
• 发表时间: 2023-02
• 期刊: JOURNAL OF MEDICAL VIROLOGY
• 影响因子: 12.7
• 作者: Huang, Hsiang-Chi;Wang, Shih-Han;Fang, Guo-Chen;Chou, Wen-Cheng;Liao, Chun-Che;Sun, Cheng-Pu;Jan, Jia-Tsrong;Ma, Hsiu-Hua;Ko, Hui-Ying;Ko, Yi-An;Chiang, Ming-Tsai;Liang, Jian-Jong;Kuo, Chun-Tse;Lee, Te-An;Morales-Scheihing, Diego;Shen, Chen-Yang;Chen, Shih-Yu;McCullough, Louise D.;Cui, Lu;Wernig, Gerlinde;Tao, Mi-Hua;Lin, Yi-Ling;Chang, Yao-Ming;Wang, Shu-Ping;Lai, Yun-Ju;Li, Chia-Wei
• 通讯作者: Li, Chia-Wei

Pain and Other Neurological Symptoms Are Present at 3 Months After Hospitalization in COVID-19 Patients.

• DOI: 10.3389/fpain.2021.737961
• 发表时间: 2021
• 期刊: Frontiers in pain research (Lausanne, Switzerland)
• 作者: Savarraj JPJ;Burkett AB;Hinds SN;Paz AS;Assing A;Juneja S;Colpo GD;Torres LF;Cho SM;Gusdon AM;McCullough LD;Choi HA
• 通讯作者: Choi HA

Sex differences in global metabolomic profiles of COVID-19 patients.

• DOI: 10.1038/s41419-022-04861-2
• 发表时间: 2022-05-14
• 期刊: CELL DEATH & DISEASE
• 影响因子: 9
• 作者: Escarcega, Rocio Diaz;Honarpisheh, Pedram;Colpo, Gabriela Delevati;Ahnstedt, Hilda W.;Couture, Lucy;Juneja, Shivanki;Torres, Glenda;Ortiz, Guadalupe J.;Sollome, James;Tabor, Natalie;Ganesh, Bhanu P.;Choi, H. Alex;Liu, Fudong;McCullough, Louise D.;Tsvetkov, Andrey S.
• 通讯作者: Tsvetkov, Andrey S.