Principal Investigator: Kevin Shah
Keywords: Covid-19 , biomarkers , heart failure Department: Cardiovascular Services
IRB Number: 00133899
Specialty: Cardiology
Sub Specialties: Heart Failure
Recruitment Status: Recruiting

Contact Information

Jeff  Gibbs
Jeffrey.Gibbs@hsc.utah.edu
801-587-4877

Brief Summary

The objectives of this study goal is to identify clinical risk factors which predict adverse cardiovascular (CV) events in patients admitted with COVID-19 infection. Our overarching hypothesis is that both primary myocardial injury and secondary inflammatory-mediated myocardial injury are involved in this process.

We will characterize the time course and degree of involvement at different phases and advance our ability to predict and manage the CV sequelae of the COVID-19 infection. We plan to prospectively collect blood specimens from COVID-19 infected patients upon hospital admission, weekly, and upon discharge. In collaboration with co-PI Dr Lazar-Molnar at ARUP Laboratory, peripheral blood mononuclear cells (PBMCs) and plasma samples will be preserved and used for biomarker studies. Major immune cell populations, including innate (monocytes) and adaptive (lymphocyte) subsets from cryopreserved PBMCs will be analyzed by mass cytometry for the expression of immune activation markers and intracellular cytokines. Mass cytometry is a robust multiplex platform that allows for the analysis of 35 cell surface and intracellular markers from the same sample, providing unparalleled ability for phenotypical and functional profiling of immune cells. Dr. Lazar-Molnar et al at ARUP have developed panels for analyzing major cellular subsets from peripheral blood (manuscript in preparation). Analysis will include quantification of T cell subsets (Th1, Th2, Th17); naïve, activated and memory subsets, and analyzing lymphocyte activation (CD69, CD25, HLA-DR) and exhaustion markers (PD-1). Intracellular cytokine analysis will include TNF- a, IFN- a, IL-2, IL-4, IL-6, IL-17 and cytotoxic T cell effector molecules granzyme B and perforin. Naïve and memory B cells, plasma cells, and NK cells will also be quantified. In addition, plasma cytokines including TNF-a, IL-1, IL-6, sIL-2R and IL-17 will be analyzed by multiplex Luminex assay. 

Cardiac bridging integrator 1 (cBIN1) is a membrane-scaffolding protein found in heart cells. cBIN1 organizes the microdomains at transverse tubules responsible for systolic and diastolic calcium transients. cBIN1 Score (CS) is a regulator of cardiac contractile and diastolic function and an emerging novel biomarker of heart cell health. Plasma concentrations of CS are increased in patients with cardiomyopathy  and correlate with allograft rejection in heart transplant recipients . Given the ability of CS to detect cardiomyocyte injury and remodeling, this novel biomarker could serve a complementary role in understanding the nature and time course of myocardial injury relative to the systemic inflammatory milieu of COVID-19 infection and provide insight into those at particular risk for cardiovascular complications.

Study aim #1: Identify clinical risk factors associated with adverse CV events in patients hospitalized with COVID-19 infection. The working hypothesis is that age, pre-existing CV comorbidities, serum cardiac troponin and serum natriuretic peptide levels will predict adverse CV events. We will use traditional regression models, as well as random forest and Bayesian network analyses to identify the associations.

Study aim #2: Identify the value of the novel biomarker CS and specific inflammatory mediators in predicting adverse CV events. The working hypothesis is that elevations of specific soluble inflammatory biomarkers and CS, as well as immune activation status of lymphocytes/monocyte subsets will be independently associated with adverse CV events and occur earlier than traditional markers of clinical decompensation.

Study aim #3  In subjects that give permission for long-term storage the remaining tissue will be banked. This is a registry (database) and tissue banking project; there are no investigational treatments, drugs or procedures associated with participation in the study.

Detailed Description

The purpose of this project is to collect blood samples from patients admitted with COVID-19. These samples will be tested for cardiac biomarkers (troponin, natriuretic peptides), a novel biomarker (cBIN1), and a panel of inflammatory biomarkers. In subjects that give permission for long-term storage the remaining tissue will be banked. This is a registry (database) and tissue banking project; there are no investigational treatments, drugs or procedures associated with participation in the study. The study procedures are collection of clinical data from the medical record and collection of blood (during a non-study related clinical phlebotomy). The patient data and information from the collected tissue samples has no bearing on medical decisions or medical care the patient receives at the time consent is given. This is a long-term project at the University of Utah Hospital; there is no limit to enrollment, we expect to enroll 50 patients per year at the University of Utah. All clinical data will be stored electronically on a password protected computer. Access to the data will be limited to co-investigators.The data that will be collected from the patients’ records will include the following:A.Demographics (Name, DOB, Race/ethnicity, medical record number, height, weight, BSA)B.Admission and discharge dateC.Discharge dispositionD.Past medical historyE.Medications prior to admissionF.ECGG.Cardiovascular events:a.Sustained ventricular arrhythmiab.Atrial fibrillationc.Heart block requiring temporary or permanent pacemakerd.Acute MIe.Percutaneous coronary interventionf.LVEF assessmentg.Coronary angiogramh.In-hospital shocki.New-onset heart failurej.Myocarditisk.Deep vein thrombosis (DVT)l.Pulmonary embolism (PE)m.Intracardiac thrombusn.New hemodialysis or CRRTo.Cardiac arrestH.LabsI.Inpatient medications

Inclusion Criteria

Inclusion

1. >18 years of age admitted to University of Utah with positive laboratory or clinical diagnosis of COVID-  19.

 

Exclusion Criteria

Exclusion Criteria:

Patients will be excluded from the study if any of the following conditions are present:

 

1. Neither patient nor patient representative understands spoken English.

2. Neither patient nor the patient’s personal representative is willing to give written consent for participation.

3. Unwilling to undergo serial phlebotomy