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Principal Investigator: Jason V Baker
Organization: UNIVERSITY OF MINNESOTA
Fiscal Year: 2024
Award: $671,068
Funding agency: National Heart Lung and Blood Institute
ABSTRACT
Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-
CoV-2) has become a widespread global pandemic. While the predominant clinical manifestation of severe
COVID-19 is respiratory failure, other organ complications such as cardiac injury are common. Cardiac injury
and cardiomyopathy are frequent cardiac manifestations during acute illness. Additionally, some survivors of
COVID-19 are experiencing cardiopulmonary symptoms months after the acute illness, referred to as Post-
Acute Sequelae of SARS-CoV-2 (PASC) or “Long COVID”. Given the frequency of cardiovascular injury during
COVID-19 and the persistence of symptoms for extended periods after the acute illness, there is an urgent
need for studies of the late effects of SARS-CoV-2 on the cardiovascular system. We aim to investigate the
central hypothesis that immune responses to severe COVID-19 cause acute inflammation and injury that result
in clinically relevant myocardial fibrosis and dysfunction over the long-term. Since August 2020, we have been
enrolling patients in a COVID-19 Immune Profiling (IP) Study, which includes a protocol to collect blood
specimens from patients with COVID-19 at admission, during hospitalization, 1-3 months, and 3-12 months
after recovery. We will co-enroll participants from this study and perform cardiac magnetic resonance imaging
(CMR) and additional functional cardiopulmonary assessments at 3-12 months and 2-3 years after recovery.
Our specific aims include, Aim 1) Identify innate immune profiles during severe COVID-19 that predict long-
term cardiac damage. We will focus innate immunity measures in blood specimens collected at admission and
early recovery, Aim 2) Establish whether adaptive immune responses contribute to cardiac injury after COVID-
19. We will quantify responses targeting SARS-CoV-2 as well as explore maladaptive responses targeting
cardiac proteins. Analysis of blood specimens will be supplemented with exploratory studies of cardiac tissue,
and Aim 3) Determine the long-term structural and functional cardiac abnormalities after severe COVID-19.
This includes characterization of cardiac fibrosis and dysfunction, cardiopulmonary dysfunction, and clinical
symptoms. Comparisons will be made with control participants who had influenza infection 1-2 years prior. Our
proposal responds to urgent need for science characterizing long-term cardiac complications following COVID-
19. Our collaborative team has extensive experience spanning cardiology, infectious disease, immunology,
and epidemiology, and will be led by a cardiologist with expertise in CMR and inflammatory cardiomyopathies,
and an infectious diseases specialist with expertise in cardiovascular complications in the context of chronic
viral infections. Successful completion of our work will help understand the long-term cardiovascular effects of
severe COVID-19 illness. This knowledge could, in turn, help enhance health, lengthen life, and reduce illness
and disability in COVID-19 survivors.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><ACE2><Acute><Admission><Admission activity><Adventitial Cell><Adverse Late Effects><Airway failure><Award><Biological Markers><Blood Neutrophil><Blood Polymorphonuclear Neutrophil><Blood Sample><Blood monocyte><Blood specimen><Body Tissues><CD4 Cells><CD4 Positive T Lymphocytes><CD4 T cells><CD4 helper T cell><CD4 lymphocyte><CD4+ T-Lymphocyte><CD4-Positive Lymphocytes><COVID infected patient><COVID patient><COVID positive patient><COVID survivors><COVID-19><COVID-19 infected patient><COVID-19 infection><COVID-19 infection survivors><COVID-19 patient><COVID-19 positive patient><COVID-19 survivors><COVID-19 virus><COVID-19 virus infection><COVID19 infection><COVID19 patient><COVID19 positive patient><COVID19 virus><CV-19><Cardiac><Cardiac Abnormalities><Cardiac Diseases><Cardiac Disorders><Cardiology><Cardiomyopathies><Cardiopulmonary><Cardiovascular><Cardiovascular Body System><Cardiovascular Organ System><Cardiovascular system><Cell Body><Cells><Chronic><Clinical><CoV-2><CoV2><Communicable Diseases><Coronavirus Infectious Disease 2019><Diffuse><Dysfunction><Endothelial Cells><Epidemic><Epidemiology><Fibroblasts><Fibrosis><Fibrosis in the heart><Fibrosis in the myocardium><Fibrosis within the heart><Fibrosis within the myocardium><Fibrotic myocardium><Frequencies><Functional disorder><Goals><Grippe><Health><Heart Abnormalities><Heart Diseases><Heart Injuries><Heart Vascular><Hospital Admission><Hospitalization><Immune><Immune Cell Activation><Immune response><Immunes><Immunochemical Immunologic><Immunofluorescence><Immunofluorescence Immunologic><Immunologic><Immunological><Immunological response><Immunologically><Immunologics><Immunology><In Vitro><Infection><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Inflammation><Inflammatory><Influenza><Injury><Innate Immunity><Intervention><Intervention Strategies><Knowledge><Late Effects><Life><Long COVID><Long COVID-19><Long coronavirus disease><Long coronavirus disease 2019><Low Prevalence><Lymphocytopenia><Lymphopenia><Macrophage><Magnetic Resonance><Marrow Neutrophil><Marrow monocyte><Measures><Mediating><Microcirculation><Mononuclear><Muscle Cells><Myocardial><Myocardial Diseases><Myocardial Disorder><Myocardial depression><Myocardial dysfunction><Myocardiopathies><Myocarditis><Myocytes><Mφ><Native Immunity><Natural Immunity><Neutrophilic Granulocyte><Neutrophilic Leukocyte><Non-Specific Immunity><Nonspecific Immunity><Organ><PASC><Participant><Pathology><Patients><Peptides><Pericapillary Cell><Pericytes><Perivascular Cell><Phenotype><Physiopathology><Polymorphonuclear Cell><Polymorphonuclear Leukocytes><Polymorphonuclear Neutrophils><Post Acute Sequelae of COVID19><Post Acute Sequelae of SARS-CoV-2><Post Acute Sequelae of SARS-CoV2><Post Acute Sequelae of severe acute respiratory syndrome coronavirus 2><Post-Acute Sequelae of SARS-CoV-2 Infection><Proteins><Protocol><Protocols documentation><Receptor Protein><Recovery><Reporting><Research><Research Specimen><Respiratory Disease><Respiratory Failure><Respiratory System Disease><Respiratory System Disorder><Rouget Cells><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 infected patient><SARS-CoV-2 infection><SARS-CoV-2 patient><SARS-CoV-2 positive patient><SARS-CoV-2 survivors><SARS-CoV2><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Science><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-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 infection><Severe acute respiratory syndrome related corona virus 2><Specialist><Specimen><Survivors><Symptoms><T cell response><T-Cells><T-Lymphocyte><T4 Cells><T4 Lymphocytes><Testing><Tissues><Troponin><Viral><Viral Diseases><Virus Diseases><Work><Wound Repair><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><adverse sequelae of COVID><adverse sequelae of COVID-19><adverse sequelae of coronavirus disease><adverse sequelae of coronavirus disease 2019><airway injury><angiotensin converting enzyme 2><angiotensin converting enzyme II><bio-markers><biologic marker><biomarker><cardiac MRI><cardiac damage><cardiac dysfunction><cardiac fibrosis><cardiac inflammation><cardiac injury><cardiac magnetic resonance imaging><cardiovascular effects><cardiovascular injury><chronic COVID><chronic COVID-19><chronic COVID-19 sequelae><chronic novel coronavirus disease 2019><chronic symptom><circulatory system><clinical relevance><clinically relevant><cohort><coronary fibrosis><coronavirus disease 2019><coronavirus disease 2019 infected patient><coronavirus disease 2019 infection><coronavirus disease 2019 patient><coronavirus disease 2019 positive patient><coronavirus disease 2019 virus><coronavirus disease infected patient><coronavirus disease patient><coronavirus disease positive patient><coronavirus disease-19><coronavirus disease-19 patient><coronavirus disease-19 virus><coronavirus infectious disease-19><coronavirus patient><cytokine><disability><epidemiologic><epidemiological><experience><fibrotic heart><flu infection><flu virus infection><hCoV19><heart damage><heart disorder><heart dysfunction><heart fibrosis><host response><immune activation><immune system response><immunoresponse><impaired airway><improved><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with flu><infected with flu virus><infected with influenza><infected with influenza virus><infected with severe acute respiratory syndrome coronavirus 2><influenza infection><influenza virus infection><injured airway><injuries><injury to the myocardium><interventional strategy><life-threatening COVID><life-threatening COVID-19><life-threatening SARS-CoV-2><life-threatening coronavirus disease><life-threatening coronavirus disease 2019><life-threatening severe acute respiratory syndrome coronavirus 2><long haul COVID><long haul COVID-19><long haul coronavirus disease><long haul coronavirus disease 2019><long haul sequelae of COVID-19><long haul sequelae of coronavirus disease 2019><long-hauler COVID><long-hauler COVID-19><long-hauler coronavirus disease 2019><long-hauler syndrome><long-term COVID><long-term COVID-19><long-term coronavirus disease><long-term coronavirus disease 2019><long-term sequelae of COVID-19><long-term sequelae of SARS-CoV-2><long-term sequelae of coronavirus disease 2019><long-term sequelae of severe acute respiratory syndrome coronavirus 2><longterm COVID><longterm COVID-19><longterm coronavirus disease><longterm coronavirus disease 2019><lung failure><monocyte><myocardial fibrosis><myocardial injury><myocardium disease><myocardium disorder><nCoV2><neutrophil><novel><pandemic><pandemic disease><participant enrollment><particle><pathophysiology><patient enrollment><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><persistent COVID-19><persistent symptom><post COVID syndrome><post COVID-19 sequelae><post COVID-19 syndrome><post acute COVID syndrome><post acute COVID-19><post acute COVID-19 syndrome><post acute SARS-CoV-2><post acute coronavirus disease 2019><post acute coronavirus disease 2019 syndrome><post acute coronavirus disease syndrome><post acute sequelae following COVID-19><post acute severe acute respiratory syndrome coronavirus 2><post coronavirus disease 2019 syndrome><post coronavirus disease syndrome><post-acute phases of COVID-19><post-acute sequelae following SARS-CoV-2 infection><post-acute sequelae of COVID-19><post-acute sequelae of acute COVID infection><post-acute sequelae of coronavirus disease 2019><prolonged COVID-19 symptoms><pulmonary failure><receptor><respiratory injury><respiratory tract injury><response><risk stratification><serious COVID><serious COVID-19><serious SARS-CoV-2><serious coronavirus disease><serious coronavirus disease 2019><serious severe acute respiratory syndrome coronavirus 2><severe COVID><severe COVID-19><severe COVID19><severe SARS-CoV-2><severe acute respiratory syndrome coronavirus 2 infected patient><severe acute respiratory syndrome coronavirus 2 patient><severe acute respiratory syndrome coronavirus 2 positive patient><severe coronavirus disease><severe coronavirus disease 19><severe coronavirus disease 2019><severe severe acute respiratory syndrome coronavirus 2><spatial relationship><stratify risk><study population><survive COVID-19><survive SARS-CoV-2><systemic inflammation><systemic inflammatory response><thromboembolic complications><thrombosis complications><thrombotic complications><thymus derived lymphocyte><viral infection><virus infection><virus-induced disease><wound healing><wound recovery><wound resolution>