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

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Abstract

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.

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Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Fei Zhou, Ting Yu, Ronghui Du … (2020)

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

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SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

Markus Hoffmann, Hannah Kleine-Weber, Simon Schroeder … (2020)

Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.

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Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China

Shaobo Shi, Mu Qin, Bo Shen … (2020)

Coronavirus disease 2019 (COVID-19) has resulted in considerable morbidity and mortality worldwide since December 2019. However, information on cardiac injury in patients affected by COVID-19 is limited.

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Author and article information

Journal

Journal ID (nlm-ta): JACC Basic Transl Sci

Journal ID (iso-abbrev): JACC Basic Transl Sci

Title: JACC: Basic to Translational Science

Publisher: The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

ISSN (Electronic): 2452-302X

Publication date PMC-release: 26 February 2021

Publication date (Electronic): 26 February 2021

Affiliations

[a ]Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA

[b ]Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA

[c ]Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri, USA

[d ]Washington University Center for Cellular Imaging, Washington University School of Medicine, St. Louis, Missouri, USA

[e ]Department of Pathology & Laboratory Medicine, University of Wisconsin Hospital and Clinics, Madison, Wisconsin, USA

[f ]Department of Medicine, Baylor College of Medicine, Houston, Texas, USA

[g ]Department of Pathology, Baylor College of Medicine, Houston, Texas, USA

[h ]Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA

[i ]Valleywise Health/Creighton University, Phoenix, Arizona, USA

[j ]Departments of Neuroscience, Cell Biology & Physiology, and Biomedical Engineering, Washington University School of Medicine, St. Louis, Missouri, USA

[k ]Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA

[l ]Departments of Cardiology, Genetics and Genome Sciences, UConn Health, Farmington, Connecticut, USA

[m ]The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA

[n ]Department of Internal Medicine III, University Hospital Heidelberg, University of Heidelberg, Heidelberg, Germany

[o ]Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA

[p ]Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri, USA

Author notes

[∗ ] Address for correspondence: Dr. Lavine, Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Campus Box 8086, St. Louis, Missouri 63110, USA.

[∗]

Drs. Bailey and L. Greenberg, and Mr. Dmytrenko contributed equally to this work and are joint first authors.

[†]

Drs. Lin, Diamond, M. J. Greenberg, and Lavine contributed equally to this work and are joint senior authors.

Article

Publisher Item ID: S2452-302X(21)00012-7

DOI: 10.1016/j.jacbts.2021.01.002

PMC ID: 7909907

PubMed ID: 33681537

SO-VID: ddb888bf-89ac-4763-b7d6-8d22c68c6d6e

License:

Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

History

Date received : 3 December 2020

Date revision received : 5 January 2021

Date accepted : 5 January 2021

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

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Most cited references 40

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China

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Cited by 75

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