Document text
Principal Investigator: Prosper N Boyaka
Organization: OHIO STATE UNIVERSITY
Fiscal Year: 2024
Award: $658,785
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT 1 - ABSTRACT
The rapid development of SARS-CoV-2 vaccines has helped ease most of the restrictions in place during the
height of the pandemic to limit transmission of the virus. Unfortunately, the adaptive immunity (i.e., antibody and
T cell responses) induced by current vaccines declines rapidly, thus requiring frequent boosts. Most importantly,
current vaccines fail to optimally protect against emerging SARS-CoV-2 variants of concern (VOCs). The clinical
manifestations of SARS-CoV-2 infections are highly variable, and patients can be asymptomatic or exhibit
symptoms ranging from mild, moderate, or severe conditions that can lead to death. It is estimated that over
30% of SARS-CoV-2 infected people worldwide (~ 65 millions) have developed Post-Acute COVID Syndrome
(PACS), or Long COVID, characterized by pulmonary, mental health, neurological, hematological, diabetes,
gastrointestinal, kidney, musculoskeletal, and cardiovascular disorders. Prior infections do not eliminate risks of
PACS, and 10-12% of cases are after breakthrough SARS-CoV-2 infection in vaccinated individuals
Furthermore, reinfections were recently reported to increase the risks of death, hospitalization and PACS. Thus,
new therapeutic approaches are needed to prevent or better manage acute SARS-CoV-2 infections and PACS.
COVID-19 patients exhibit excessive inflammatory responses and the release of a large amount of pro-
inflammatory cytokines, or cytokine storm which directly correlate with lung injury, multiple organ failure, and an
unfavorable prognosis. We recently observed that human caspase-4 (CASP4), which is a homolog of mouse
CASP11, is significantly upregulated in nasal swabs and lungs of patients with severe SARS-CoV-2 disease.
Furthermore, we found that mice lacking CASP11 develop less severe disease after infection with SARS-CoV-2
and we reported that CASP11 mediates lung pathology, inflammation, and thrombosis during SARS-CoV-2
infection. This project aims to elucidate immune check points regulated by CASP11 during mild, severe COVID-
19 and PACS. We will also test whether targeting CASP11 alone of together with factors which regulate viral
replication during severe SARS-CoV-2 could improve/prevent pathologies and enhance/promote protective
adaptive immunity.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV vaccine><2019-nCoV variant><2019-nCoV variant forms><2019-nCoV variant strains><Affect><Alimentary Canal><Antibodies><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Bacterial Infections><Blood Coagulation Disorders><Blood Sample><Blood specimen><Body Tissues><Brain><Brain Nervous System><CASP11><CASP4><CASP4 gene><COVID infected patient><COVID patient><COVID positive patient><COVID-19><COVID-19 antibody><COVID-19 immunity><COVID-19 infected patient><COVID-19 infection><COVID-19 patient><COVID-19 positive patient><COVID-19 therapy><COVID-19 treatment><COVID-19 vaccine><COVID-19 variant><COVID-19 variant forms><COVID-19 variant strains><COVID-19 virus><COVID-19 virus infection><COVID19 infection><COVID19 patient><COVID19 positive patient><COVID19 virus><CV-19><Cardiovascular Diseases><Caspase><Caspase Gene><Cell Body><Cell Death><Cell Function><Cell Locomotion><Cell Migration><Cell Movement><Cell Physiology><Cell Process><Cell-Death Protease><Cells><Cellular Function><Cellular Migration><Cellular Motility><Cellular Physiology><Cellular Process><Cessation of life><Clinical><CoV-2><CoV2><Coagulation Disorder><Coagulopathy><Coronavirus Infectious Disease 2019><Cysteine Endopeptidases><Cysteine Protease><Cysteine Proteinases><Data><Death><Development><Diabetes Mellitus><Digestive Tract><Disease><Disease Outcome><Disorder><Encephalon><Endothelium><Ensure><Environment><Exhibits><Future><GI Tract><Gastrointestinal Diseases><Gastrointestinal Tract><Gastrointestinal tract structure><Generations><Goals><Height><Hematology><Hospital Admission><Hospitalization><Human><ICE and CED3 Homolog 2><ICE-like protease><ICH-2><IgA><Immune><Immune Cell Activation><Immune response><Immune system><Immunes><Immunity><Immunoglobulin A><Immunological response><Impairment><Infection><Infectious Agent><Inflammasome><Inflammation><Inflammatory><Inflammatory Response><Innate Immune Response><KO mice><Kidney Diseases><Knock-out Mice><Knockout Mice><Long COVID><Long COVID-19><Long coronavirus disease><Long coronavirus disease 2019><Lung><Lung Parenchyma><Lung Respiratory System><Lung Tissue><Lung damage><Lymphatic Tissue><Lymphoid Tissue><MOF syndrome><Measures><Mediating><Mental Health><Mental Hygiene><Mice><Mice Mammals><Modern Man><Molecular><Mouse Homolog of Caspase 11><Mucosa><Mucosal Immunity><Mucosal Tissue><Mucous Membrane><Multiple Organ Dysfunction Syndrome><Multiple Organ Failure><Murine><Mus><Musculoskeletal Diseases><Nasopharynx><Nature><Nephropathy><Neurologic><Neurological><Non-Polyadenylated RNA><Null Mouse><Organ><Pathology><Pathway interactions><Patients><Persons><Play><Production><Prognosis><Psychological Health><Pulmonary Pathology><RNA><RNA Gene Products><RNA Seq><RNA sequencing><RNAseq><Relaxation><Renal Disease><Reporting><Rhinopharynx><Ribonucleic Acid><Risk><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 antibody><SARS-CoV-2 immunity><SARS-CoV-2 infected patient><SARS-CoV-2 infection><SARS-CoV-2 patient><SARS-CoV-2 positive patient><SARS-CoV-2 therapy><SARS-CoV-2 treatment><SARS-CoV-2 vaccine><SARS-CoV-2 variant><SARS-CoV-2 variant forms><SARS-CoV-2 variant strains><SARS-CoV2><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 vaccine><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Sepsis><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 vaccine><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 immunity><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 vaccine><Severe acute respiratory syndrome related corona virus 2><Severities><Severity of illness><Shapes><Site><Structure of parenchyma of lung><Subcellular Process><Symptoms><Syndrome><T cell response><T-Cells><T-Lymphocyte><Testing><Thrombosis><Tissues><Transferase><Transferase Gene><Transmission><Travel><Vaccinee><Vaccines><Viral><Viral Burden><Viral Load><Viral Load result><Virus><Virus Replication><Wuhan coronavirus><acute COVID-19><acute SARS-CoV-2 infection><acute phase of COVID-19><acute phase of SARS-CoV-2 infection><adaptive immune response><adaptive immunity><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><alimentary tract><antibody against COVID-19><antibody against SARS-CoV-2><antibody against coronavirus disease 2019><antibody against severe acute respiratory syndrome coronavirus 2><antibody to COVID-19><antibody to SARS-CoV-2><antibody to coronavirus disease 2019><antibody to severe acute respiratory syndrome coronavirus 2><bacteria infection><bacterial disease><bleeding disorder><blood infection><bloodstream infection><cardiovascular disorder><cell motility><chronic COVID><chronic COVID-19><chronic novel coronavirus disease 2019><clotting disorder><coronavirus disease 2019><coronavirus disease 2019 antibody><coronavirus disease 2019 immunity><coronavirus disease 2019 infected patient><coronavirus disease 2019 infection><coronavirus disease 2019 patient><coronavirus disease 2019 positive patient><coronavirus disease 2019 therapy><coronavirus disease 2019 treatment><coronavirus disease 2019 vaccine><coronavirus disease 2019 variant><coronavirus disease 2019 variant forms><coronavirus disease 2019 variant strains><coronavirus disease 2019 virus><coronavirus disease infected 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