COVID-19: Role of naïve T cells, Age associated T cell senescence, and Dysfunctional Immune regulation in host response to SARS-CoV-2

COVID-19：幼稚 T 细胞、年龄相关 T 细胞衰老和免疫调节功能失调在宿主对 SARS-CoV-2 反应中的作用

• 批准号: 10356083
• 负责人: Donald D Anthony
• 金额: --
• 依托单位: LOUIS STOKES CLEVELAND VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2023-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10356083
• 关键词: 2019-nCoV; Age; Antibodies; Antibody Response; Antigens; Automobile Driving; B-Lymphocytes; Benign; Biological Assay; CD4 Positive T Lymphocytes; COVID-19; COVID-19 morbidity; COVID-19 pandemic; COVID-19 severity; COVID-19 vaccine; Cell Aging; Cell Count; Cells; Clinical; Cryopreservation; Defect; Development; Disease; Disease Outbreaks; Effectiveness; Elderly; Enrollment; Enzyme-Linked Immunosorbent Assay; FOXP3 gene; Flow Cytometry; Frequencies; Functional disorder; Funding; Goals; Heterogeneity; Human; Hypertension; IL2RA gene; Immune; Immune response; Immunity; Impairment; Individual; Infection; Inflammation Mediators; Inflammatory; Influenza; Interleukin-6; Knowledge; Lymphopenia; Medical center; Memory; Morbidity - disease rate; Outcome; Output; Participant; Peptides; Phenotype; Plasma; Play; Protocols documentation; RNA Viruses; Regulatory T-Lymphocyte; Role; SARS-CoV-2 exposure; SARS-CoV-2 infection; Sample Size; Sampling; Severe Acute Respiratory Syndrome; Site; T cell response; T memory cell; T-Lymphocyte; TNF gene; Th1 Cells; Thymus Gland; Time; Vaccine Design; Vaccines; Virus; Virus Diseases; aged; cell age; cohort; comorbidity; coronavirus disease; enzyme linked immunospot assay; exhaust; experience; immunological status; immunoregulation; immunosenescence; improved; inflammatory marker; influenza virus vaccine; mortality; pandemic disease; pandemic influenza; pathogenic virus; patient oriented; patient population; prevent; prospective; research study; respiratory; response; senescence; severe COVID-19; vaccine efficacy; vaccine immunogenicity

The global pandemic of SARS-CoV-2 presents the unfortunate combination of a highly contagious and highly morbid RNA virus pathogen that is responsible for a world-wide outcome not seen since the 1917-1918 flu pandemic. This highlights the urgent need for a vaccine that prevents or mitigates disease. Understanding the natural host immune response to SARS-CoV-2 as it relates to clinical outcome is at the center of our current needed perspective as we embark on preparing for the very likely, less than ideal effectiveness on initial round vaccine. Understanding host immune response features that precede and participate in determining this heterogeneity in clinical outcome is needed to guide us forward to an improved second round vaccine. T cell lymphopenia may be one factor that correlates with severe COVID-19 morbidity. Certainly, both T cell and B cell immunity are required for a successful long term response to most all viruses. Additionally, we and others have described a number of features of host T cell immunity altered in older aged individuals with and without viral infection, including lymphopenia, naïve T cell numerical and functional defects, T cell senescence and deranged immune regulation. We will examine the hypothesis that: In the elderly, higher levels of IL-6 and sTNFR2, and lower frequencies of naïve T cells preclude initial adequate T cell responses to COVID-19 infection and are also associated with lower antibody levels to prior Influenza vaccine. Senescent and exhausted T cells and dysfunction in Tregs impair development of Th1 memory responses to SARS-CoV-2 and predict morbid COVID-19 outcome. We will Determine whether older age, IL-6, sTNFR2, or lower naïve CD4 T cell number/function prior to COVID-19 exposure is associated with host T and B cell response to prior influenza vaccine and/or impaired development of effective host Th1 cell response to SARS- Cov-2 and severity of clinical COVID-19 outcomes; and Determine whether older age and exhausted, senescent or aberrant Treg cell phenotype present before or after COVID-19 exposure is associated with lower SARS-CoV-2 Th1 memory response and/or host T cell and antibody response to prior influenza vaccine.

SARS-CoV-2的全球大流行呈现出高度传染性和高度传染性的不幸结合

项目成果

Rheumatoid arthritis and older age are associated with lower humoral and cellular immune response to primary series COVID-19 mRNA vaccine.

类风湿性关节炎和老年与初级系列 COVID-19 mRNA 疫苗的体液和细胞免疫反应较低有关。

• DOI: 10.1016/j.vaccine.2023.08.033
• 发表时间: 2023
• 期刊: Vaccine
• 影响因子: 5.5
• 作者: Dudley,HollyM;O'Mara,Megan;Auma,Ann;Gong,Jenny;Ross,Yael;Gurevich,Natalie;Carbone,Sarah;Reihs,Alex;Nguyen,Ynez;McComsey,GraceA;Cao,Yi;Balazs,AlejandroB;Gordesky,Larraine;Payne,Michael;Singer,Nora;Kostadinova,Lenche;Wilso
• 通讯作者: Wilso

COVID-19 vaccination experience in patients with rheumatoid arthritis treated at a single VA medical center.

• DOI: 10.1016/j.jvacx.2023.100295
• 发表时间: 2023-08
• 期刊: VACCINE: X
• 影响因子: 3.8
• 作者: Doumeth, Sarah Abi;Gong, Jenny;Silversteyn, Laura;O'Mara, Megan;Singh, Shivali;Anthony, Donald;Mattar, Maya
• 通讯作者: Mattar, Maya

Dr. Kostadinova et al reply.

Kostadinova 博士等人回复。

• DOI: 10.3899/jrheum.2023-0485
• 发表时间: 2023
• 期刊: The Journal of rheumatology
• 作者: Kostadinova,Lenche;Lange,Alyssa;Damjanovska,Sofi;Gad,Ibtissam;Syed,Sameena;Siddiqui,Husna;Yousif,Patrick;Kowal,CorinneM;Shive,Carey;Burant,Christopher;Singer,Nora;Bej,Taissa;Al-Kindi,Sadeer;Wilson,Brigid;Mattar,Maya;Zidar,D
• 通讯作者: Zidar,D