Human Cardiac Pericytes are Susceptible to SARS-CoV-2 Infection.

Coronavirus disease 2019 (COVID-19) is associated with serious cardiovascular complications, with incompletely understood mechanism(s). Pericytes have key functions in supporting endothelial cells and maintaining vascular integrity. We demonstrate that human cardiac pericytes are permissive to SARS-CoV-2 infection in organotypic slice and primary cell cultures. Viral entry into pericytes is mediated by endosomal proteases, and infection leads to upregulation of inflammatory markers, vasoactive mediators, and NF-κB-dependent cell death. Furthermore, we present evidence of cardiac pericyte infection in COVID-19 myocarditis patients. These data demonstrate that human cardiac pericytes are susceptible to SARS-CoV-2 infection and suggest a role for pericyte infection in COVID-19.

Cardiovascular symptom phenotypes of post-acute sequelae of SARS-CoV-2.

BACKGROUND: Acute COVID-19 infection has been shown to have significant effects on the cardiovascular system. Post-acute sequelae of SARS-CoV-2 (PASC) are being identified in patients; however, the cardiovascular effects are yet to be well-defined. The Post-COVID Cardiology Clinic at Washington University evaluates and treats patients with ongoing cardiovascular PASC. OBJECTIVES: This investigation aims to describe the phenotypes of cardiovascular symptoms of PASC in patients presenting to the Post-COVID Cardiology Clinic, including their demographics, symptoms, and the clinical phenotypes observed. METHODS: This was a retrospective analysis of symptoms, clinical findings, and test results from the first 100 consecutive adult patients who presented to the Post-COVID Cardiology Clinic at Washington University in St. Louis, between September 2020 to May 2021 with cardiovascular symptoms following COVID-19 infection. RESULTS: The population (n = 100) had a mean age of 46.3 years and was 81% female. Most patients had mild acute illness, with only 23% of patients requiring hospitalization during acute COVID-19 infection. The most commonly reported PASC symptoms were chest pain (66%), palpitations (59%), and dyspnea on exertion (56%). Of those presenting with these symptoms, 74/98 patients (75.5%) were found to have a significant blood pressure elevation, considerable sinus tachycardia burden, reduced global longitudinal strain, increased indexed left-ventricular end-diastolic volume (LVEDVi) by echocardiogram, and/or cMRI findings consistent with possible active or healing myocarditis. CONCLUSIONS: Our findings highlight clinical phenotypes of the cardiovascular manifestations of PASC. Further studies are needed to evaluate the pathophysiology, treatment options and long-term outcomes for these patients.

Cardiovascular Tropism and Sequelae of SARS-CoV-2 Infection.

The extrapulmonary manifestation of coronavirus disease-19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), became apparent early in the ongoing pandemic. It is now recognized that cells of the cardiovascular system are targets of SARS-CoV-2 infection and associated disease pathogenesis. While some details are emerging, much remains to be understood pertaining to the mechanistic basis by which SARS-CoV-2 contributes to acute and chronic manifestations of COVID-19. This knowledge has the potential to improve clinical management for the growing populations of patients impacted by COVID-19. Here, we review the epidemiology and pathophysiology of cardiovascular sequelae of COVID-19 and outline proposed disease mechanisms, including direct SARS-CoV-2 infection of major cardiovascular cell types and pathogenic effects of non-infectious viral particles and elicited inflammatory mediators. Finally, we identify the major outstanding questions in cardiovascular COVID-19 research.

Cardiovascular Tropism and Sequelae of SARS-CoV-2 Infection

The extrapulmonary manifestation of coronavirus disease-19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), became apparent early in the ongoing pandemic. It is now recognized that cells of the cardiovascular system are targets of SARS-CoV-2 infection and associated disease pathogenesis. While some details are emerging, much remains to be understood pertaining to the mechanistic basis by which SARS-CoV-2 contributes to acute and chronic manifestations of COVID-19. This knowledge has the potential to improve clinical management for the growing populations of patients impacted by COVID-19. Here, we review the epidemiology and pathophysiology of cardiovascular sequelae of COVID-19 and outline proposed disease mechanisms, including direct SARS-CoV-2 infection of major cardiovascular cell types and pathogenic effects of non-infectious viral particles and elicited inflammatory mediators. Finally, we identify the major outstanding questions in cardiovascular COVID-19 research.

Cell specific peripheral immune responses predict survival in critical COVID-19 patients.

SARS-CoV-2 triggers a complex systemic immune response in circulating blood mononuclear cells. The relationship between immune cell activation of the peripheral compartment and survival in critical COVID-19 remains to be established. Here we use single-cell RNA sequencing and Cellular Indexing of Transcriptomes and Epitomes by sequence mapping to elucidate cell type specific transcriptional signatures that associate with and predict survival in critical COVID-19. Patients who survive infection display activation of antibody processing, early activation response, and cell cycle regulation pathways most prominent within B-, T-, and NK-cell subsets. We further leverage cell specific differential gene expression and machine learning to predict mortality using single cell transcriptomes. We identify interferon signaling and antigen presentation pathways within cDC2 cells, CD14 monocytes, and CD16 monocytes as predictors of mortality with 90% accuracy. Finally, we validate our findings in an independent transcriptomics dataset and provide a framework to elucidate mechanisms that promote survival in critically ill COVID-19 patients. Identifying prognostic indicators among critical COVID-19 patients holds tremendous value in risk stratification and clinical management.

SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis.

There is ongoing debate as to whether cardiac complications of coronavirus disease-2019 (COVID-19) result from myocardial viral infection or are secondary to systemic inflammation and/or thrombosis. We provide evidence that cardiomyocytes are infected in patients with COVID-19 myocarditis and are susceptible to severe acute respiratory syndrome coronavirus 2. We establish an engineered heart tissue model of COVID-19 myocardial pathology, define mechanisms of viral pathogenesis, and demonstrate that cardiomyocyte severe acute respiratory syndrome coronavirus 2 infection results in contractile deficits, cytokine production, sarcomere disassembly, and cell death. These findings implicate direct infection of cardiomyocytes in the pathogenesis of COVID-19 myocardial pathology and provides a model system to study this emerging disease.