Molecular Mechanisms of SARS-CoV-2 Infection and Therapeutic Targets

Document text

Principal Investigator: Helen Chun-Hui Su
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2024
Award: $144,905
Funding agency: National Institute of Allergy and Infectious Diseases

The single-stranded RNA virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has proven to be easily transmissible in humans. Infected individuals present with a range of COVID-19 disease-associated characteristics: on the low end of the spectrum patients are asymptomatic or display mild symptoms and on the high end of the spectrum patients require intensive medical treatment and may die of respiratory failure. Many factors can contribute to the course of the disease, one of the most important being the host's ability to mount an appropriate immune response. Before last year, few details were known about the immunological response to SARS-CoV-2. We are interested in investigating disease susceptibility of the host based on genetic defects and discovering possible targets for drug development.

NIAID spearheaded a COVID consortium database with over 20,000 samples collected largely from international sites and a small percentage from domestic sites. Many other NIAID and other NIH PI's joined our group, with each researcher providing their unique expertise so that we were able to collectively elucidate innate and adaptive immune response to COVID-19 infection. The overall goal was to identify immunological and virological correlates and predictors of clinical outcomes. The MDISS has contributed to this consortium through its organizational efforts including annotation, standardization, and entry of clinical data associated with the collected patient samples. This work has facilitated sharing of these valuable samples across multiple ongoing collaborative studies.

The most recent project to come out of this database (FY 2024) analyzed the breadth and magnitude of T-cell responses in patients with COVID-19 and in individuals with inborn errors of immunity who had received COVID-19 mRNA vaccine. Elderly individuals were found to have impaired capacity to develop broad and sustained T-cell responses after SARS-CoV-2 infection. COVID-19 mRNA vaccines were effective in inducing T-cell responses in patients with IEIs, but further work is needed to confirm these findings in ethnic groups other than white and individuals with other IEIs.

Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><Airway failure><COVID crisis><COVID epidemic><COVID infected patient><COVID pandemic><COVID patient><COVID positive patient><COVID-19><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 infected patient><COVID-19 infection><COVID-19 pandemic><COVID-19 patient><COVID-19 period><COVID-19 positive patient><COVID-19 predisposition><COVID-19 public health crisis><COVID-19 susceptibility><COVID-19 virus><COVID-19 virus infection><COVID-19 vulnerability><COVID-19 years><COVID19 infection><COVID19 patient><COVID19 positive patient><COVID19 virus><CV-19><Cell Body><Cell Death><Cells><Characteristics><Clinical Data><CoV-2><CoV2><Coronavirus Infectious Disease 2019><Coronavirus disease 2019 predisposition><Coronavirus disease 2019 susceptibility><Coronavirus disease 2019 vulnerability><Data Bases><Databases><Diathesis><Disease><Disease susceptibility><Disorder><Drug Targeting><Elderly><Ethnic Group><Ethnic People><Ethnic Population><Ethnic individual><Ethnicity People><Ethnicity Population><Genetic Alteration><Genetic Change><Genetic defect><Goals><Human><Immune response><Immunochemical Immunologic><Immunologic><Immunological><Immunological response><Immunologically><Immunologics><Individual><Infection><Innate Immune Response><International><Investigators><Medical><Modern Man><Molecular><Mutation><NIAID><NIH><National Institute of Allergy and Infectious Disease><National Institutes of Health><Pathogenicity><Patients><Population><Predisposed to COVID-19><Predisposed to SARS-CoV-2><Predisposed to Severe acute respiratory syndrome coronavirus 2><Primary Immunodeficiency><Public Health><RNA Viruses><RNA vaccine><RNA-based vaccine><Research Personnel><Researchers><Respiratory Failure><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 infected patient><SARS-CoV-2 infection><SARS-CoV-2 pandemic><SARS-CoV-2 patient><SARS-CoV-2 positive patient><SARS-CoV-2 predisposition><SARS-CoV-2 susceptibility><SARS-CoV-2 vulnerability><SARS-CoV2><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Sampling><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome coronavirus 2 predisposition><Severe acute respiratory syndrome coronavirus 2 susceptibility><Severe acute respiratory syndrome coronavirus 2 vulnerability><Severe acute respiratory syndrome related corona virus 2><Site><Standardization><Symptoms><T cell response><Therapeutic><United States National Institutes of Health><Viral Pathogenesis><Virus><Work><Wuhan coronavirus><adaptive immune response><advanced age><after COVID-19 infection><after SARS-CoV-2 infection><after SARS-CoV2 infection><after infection by SARS-CoV-2><after severe acute respiratory distress syndrome CoV-2 infection><congenital immune deficiency><congenital immunodeficiency><coronavirus disease 2019><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 infected patient><coronavirus disease 2019 infection><coronavirus disease 2019 pandemic><coronavirus disease 2019 patient><coronavirus disease 2019 positive patient><coronavirus disease 2019 public health crisis><coronavirus disease 2019 virus><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease infected patient><coronavirus disease pandemic><coronavirus disease patient><coronavirus disease positive patient><coronavirus disease-19><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><coronavirus disease-19 patient><coronavirus disease-19 virus><coronavirus infectious disease-19><coronavirus patient><data base><drug development><ethnic subgroup><ethnicity group><following COVID-19 infection><following SARS-CoV-2 infection><following SARS-CoV2 infection><following infection by SARS-CoV-2><following severe acute respiratory distress syndrome CoV-2 infection><genetic immune defect><genetic immune deficiency><genetic immunodeficiency><genome mutation><geriatric><hCoV19><host response><immune system response><immunoresponse><impaired capacity><inborn errors in immunity><inborn errors of immunity><inborn immunodeficiency><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><inherited immune defect><inherited immune deficiency><inherited immunodeficiency><interest><liability to disease><mRNA vaccine><mRNA-based vaccine><nCoV2><necrocytosis><new drug target><new druggable target><new pharmacotherapy target><new therapeutic target><new therapy target><novel drug target><novel druggable target><novel pharmacotherapy target><novel therapeutic target><novel therapy target><patient infected with COVID><patient infected with COVID-19><patient infected with SARS-CoV-2><patient infected with coronavirus disease><patient infected with coronavirus disease 2019><patient infected with severe acute respiratory syndrome coronavirus 2><patient with COVID><patient with COVID-19><patient with COVID19><patient with SARS-CoV-2><patient with coronavirus disease><patient with coronavirus disease 2019><patient with severe acute respiratory distress syndrome coronavirus 2><post SARS-CoV-2 infection><predict clinical outcome><predisposed to Coronavirus disease 2019><prevent><preventing><previous COVID-19 infection><previous SARS-CoV-2 infection><previous SARS-CoV2 infection><previous severe acute respiratory distress syndrome CoV-2 infection><primary immune defect><primary immune deficiency><prior COVID-19 infection><prior SARS-CoV-2 infection><prior SARS-CoV2 infection><prior severe acute respiratory distress syndrome CoV-2 infection><senior citizen><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><severe acute respiratory syndrome coronavirus 2 infected patient><severe acute respiratory syndrome coronavirus 2 patient><severe acute respiratory syndrome coronavirus 2 positive patient><susceptible to COVID-19><susceptible to Coronavirus disease 2019><susceptible to SARS-CoV-2><susceptible to Severe acute respiratory syndrome coronavirus 2><therapeutic target><virus pathogenesis><vulnerable to COVID-19><vulnerable to Coronavirus disease 2019><vulnerable to SARS-CoV-2><vulnerable to Severe acute respiratory syndrome coronavirus 2>