Cohort and biomarkers for COVID-19 severity, natural history, and reinfection

COVID-19 严重程度、自然病程和再感染的队列和生物标志物

• 批准号: 10689118
• 负责人: MARTIN J BLASER
• 金额: $ 78.5万
• 依托单位: RUTGERS BIOMEDICAL AND HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-17 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10689118
• 关键词: 2019-nCoV; Address; Affect; Antibodies; Antibody Response; Autoimmunity; Biological; Biological Markers; Biological Specimen Banks; Blood Coagulation Factor; COVID-19; COVID-19 impact; COVID-19 pandemic; COVID-19 patient; COVID-19 severity; Cardiac; Cells; Characteristics; Clinical; Clinical Data; Communities; Convalescence; Data Collection; Diagnosis; Diagnostic Trial; Disease; Employee; Enzymes; Epidemiology; Ethnic Origin; Evolution; Functional disorder; Future; Health; Health Personnel; Hospitals; Human; Immune; Immune response; Immunity; Immunologic Markers; Immunologic Stimulation; Immunologics; Individual; Infection; Inflammatory; Light; Lung; Maintenance; Modeling; Monitor; Natural History; Oral; Organ; Outcome; Participant; Persons; Phase; Phenotype; Physiological; Population; Positioning Attribute; Predisposition; Research; SARS-CoV-2 antibody; SARS-CoV-2 infection; SARS-CoV-2 transmission; Sampling; Serum Markers; Severe Acute Respiratory Syndrome; Severities; Severity of illness; Slice; Surveys; Symptoms; Testing; Time; Vaccinated; Vaccination; Vaccinee; Vaccines; Variant; Viral; Virus; acute infection; asymptomatic COVID-19; biological heterogeneity; cohort; cytokine; data integration; data repository; early detection biomarkers; experience; follow-up; high risk; immunological status; infection rate; innovation; insight; long-term sequelae; multidisciplinary; pandemic disease; peripheral blood; post SARS-CoV-2 infection; pulmonary function; screening program; specific biomarkers; symptomatic COVID-19; transcriptome; treatment trial; vaccine response; vaccine trial; virome

Summary As the COVID-19 pandemic continues, there is an urgent need to better understand the illness and host responses. In spring 2020, we established two cohorts of U.S. healthcare workers (HCW), a particularly hard- hit frontline community, to understand the characteristics of the illness and to identify predictors of poor outcomes, as well as of long-term sequelae. With the current study phase ending, extending follow-up activities in these well-characterized cohorts is critical to monitor the evolution of the infection and its sequelae in a rapidly evolving situation, which now includes vaccination and emergence of virus variants. In this time- sensitive proposal, we extend the follow-up period for an additional 3 years, allowing us to answer important epidemiological and mechanistic questions about infection, symptoms, long-term outcomes, and protective immunity. In Aim 1, we will define biomarkers of SARS- CoV-2 symptom onset and severity, capitalizing on serial biospecimens collected from cohort subjects prior to and during early stages of infection. We will test the hypothesis that symptom onset and severity correspond to baseline differences in pre-existing factors, including oral virome characteristics and peripheral blood transcriptome. We also will test whether, among SARS-CoV-2+ individuals, progression of illness severity can be predicted by analysis of early biomarkers at the time of diagnosis, including inflammatory biomarkers, immune cell populations, and organ-specific biomarkers of dysfunction, such as cardiac enzymes and coagulation factors. In Aim 2, we will examine long- term sequelae of asymptomatic and symptomatic COVID-19 infections. We will assess evidence of sustained physiological dysregulation up to 3 years following SARS-CoV-2 infections of varying severity (including asymptomatic), focusing on longitudinal biomarkers and pulmonary function. We will examine whether some infected individuals have persistent abnormalities in immunologic, virologic, and end-organ biomarkers and pulmonary function, compared to pre-infection biomarker and uninfected comparison subjects. We also will assess whether persistent abnormalities in biomarkers are associated with prolonged convalescence and reduced pulmonary function. In Aim 3, we will identify serum markers persisting after acute infection that may confer protective immunity. Using sera from SARS-CoV-2+ individuals, we will characterize the spectrum and functions of anti-SARS-CoV-2 antibodies and their relation to immune protection in the cohort as well as in an innovative ex vivo lung slice model. We will specifically examine variation in magnitude, duration, function, and spectrum of antibody responses in relation to severity of initial clinical infection. We will test the hypothesis that anti-SARS-CoV-2 antibody concentrations and protective functions are associated with lower rates of subsequent re-infection in cohort participants, as affected by vaccination status. The biospecimens (currently >40,000) from these cohorts will be available for collaborative studies.

总结