Human Stem Cell Models of SARS-CoV-2 Infection in the Cardiovascular System.

The virus responsible for coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected over 190 million people to date, causing a global pandemic. SARS-CoV-2 relies on binding of its spike glycoprotein to angiotensin-converting enzyme 2 (ACE2) for infection. In addition to fever, cough, and shortness of breath, severe cases of SARS-CoV-2 infection may result in the rapid overproduction of pro-inflammatory cytokines. This overactive immune response is known as a cytokine storm, which leads to several serious clinical manifestations such as acute respiratory distress syndrome and myocardial injury. Cardiovascular disorders such as acute coronary syndrome (ACS) and heart failure not only enhance disease progression at the onset of infection, but also arise in hospitalized patients with COVID-19. Tissue-specific differentiated cells and organoids derived from human pluripotent stem cells (hPSCs) serve as an excellent model to address how SARS-CoV-2 damages the lungs and the heart. In this review, we summarize the molecular basis of SARS-CoV-2 infection and the current clinical perspectives of the bidirectional relationship between the cardiovascular system and viral progression. Furthermore, we also address the utility of hPSCs as a dynamic model for SARS-CoV-2 research and clinical translation.

Involvement of cardiovascular system as the critical point in coronavirus disease 2019 (COVID-19) prognosis and recovery.

The novel coronavirus disease 2019 (COVID-19) pandemic has already caused more than 300,000 deaths worldwide. Several studies have elucidated the central role of cardiovascular complications in the disease course. Herein, we provide a concise review of current knowledge regarding the involvement of cardiovascular system in the pathogenesis and prognosis of COVID-19. We summarize data from 21 studies involving in total more than 21,000 patients from Asia, Europe, and the USA indicating that severe disease is associated with the presence of myocardial injury, heart failure, and arrhythmias. Additionally, we present the clinical and laboratory differences between recovered and deceased patients highlighting the importance of cardiac manifestations. For the infected patients, underlying cardiovascular comorbidities and particularly existing cardiovascular disease seem to predispose to the development of cardiovascular complications, which are in turn associated with higher mortality rates. We provide mechanistic insights into the underlying mechanisms including direct myocardial damage by the virus and the consequences of the hyperinflammatory syndrome developed later in the disease course. Finally, we summarize current knowledge on therapeutic modalities and recommendations by scientific societies and experts regarding the cardiovascular management of patients with COVID-19.

Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues.

BACKGROUND: Since its discovery in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 2 180 000 people worldwide and has caused more than 150 000 deaths as of April 16, 2020. SARS-CoV-2, which is the virus causing coronavirus disease 2019 (COVID-19), uses the angiotensin-converting enzyme 2 (ACE2) as a cell receptor to invade human cells. Thus, ACE2 is the key to understanding the mechanism of SARS-CoV-2 infection. This study is to investigate the ACE2 expression in various human tissues in order to provide insights into the mechanism of SARS-CoV-2 infection. METHODS: We compared ACE2 expression levels across 31 normal human tissues between males and females and between younger (ages ≤ 49 years) and older (ages > 49 years) persons using two-sided Student's t test. We also investigated the correlations between ACE2 expression and immune signatures in various tissues using Pearson's correlation test. RESULTS: ACE2 expression levels were the highest in the small intestine, testis, kidneys, heart, thyroid, and adipose tissue, and were the lowest in the blood, spleen, bone marrow, brain, blood vessels, and muscle. ACE2 showed medium expression levels in the lungs, colon, liver, bladder, and adrenal gland. ACE2 was not differentially expressed between males and females or between younger and older persons in any tissue. In the skin, digestive system, brain, and blood vessels, ACE2 expression levels were positively associated with immune signatures in both males and females. In the thyroid and lungs, ACE2 expression levels were positively and negatively associated with immune signatures in males and females, respectively, and in the lungs they had a positive and a negative correlation in the older and younger groups, respectively. CONCLUSIONS: Our data indicate that SARS-CoV-2 may infect other tissues aside from the lungs and infect persons with different sexes, ages, and races equally. The different host immune responses to SARS-CoV-2 infection may partially explain why males and females, young and old persons infected with this virus have markedly distinct disease severity. This study provides new insights into the role of ACE2 in the SARS-CoV-2 pandemic.