Human iPSC-Derived Cardiomyocytes are Susceptible to SARS-CoV-2 Infection

Abstract

words):Coronavirus disease 2019 is a viral pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is predominantly defined by respiratory symptoms, but cardiac complications including arrhythmias, heart failure, and viral myocarditis are also prevalent. Although the systemic ischemic and inflammatory responses caused by COVID-19 can detrimentally affect cardiac function, the direct impact of SARS-CoV-2 infection on human cardiomyocytes is not well-understood. We used human induced pluripotent stem cellderived cardiomyocytes (hiPSC-CMs) as a model system to examine the mechanisms of cardiomyocyte-specific infection by SARS-CoV-2. Microscopy and immunofluorescence demonstrated that SARS-CoV-2 can enter and replicate within hiPSC-CMs, localizing at perinuclear locations within the cytoplasm. Viral cytopathic effect induced hiPSC-CM apoptosis and cessation of beating after 72 hours of infection. These studies show that SARS-CoV-2 can infect hiPSC-CMs in vitro, establishing a model for elucidating the mechanisms of infection and potentially a cardiac-specific antiviral drug screening platform.was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.

COVID-19 update: Covid-19-associated coagulopathy

“…2). It is important to consider that apoptosis may not require host cell viral entry, but rather binding to the cell surface and subsequent apoptotic pathway signaling [23].…”

“…In critically ill patients, The available clinical and pathological evidence, coupled with strong and mature data that supports a relationship between CFRNA, polyphosphate and factor XI activation, raises a logical scientific premise that requires investigation. From [23] with permission thrombocytopenia correlates with multi-organ failure and death, and a decline in platelet count, even in the absence of overt thrombocytopenia, portends a worse outcome [33]. As mentioned previously, a unique feature of Covid-19 infection is the presence of extramedullary megakaryocytes that actively produce platelets.…”

SARS-CoV-2 induces double-stranded RNA-mediated innate immune responses in respiratory epithelial derived cells and cardiomyocytes

“…Furthermore, while it is well understood that SARS-CoV-2 enters the human body through the upper respiratory tract, it is unclear which cell types of the upper and lower respiratory system contribute to sustained infection and resulting disease in the airways and elsewhere. We have performed SARS-CoV-2 infections of primary nasal epithelial cells, induced pluripotent stem cell (iPSC)-derived alveolar type 2 cells (iAT2), and iPSC-derived cardiomyocytes (iCM), which together represent the host tissues likely affected by clinical SARS-CoV-2 infection (Hou et al, 2020;Sharma et al, 2020). We assessed viral replication in these cell types as well as the degree of ensuing dsRNA-sensing responses.…”

Cardiac Troponin I Associated with Poor Prognosis and Death Risk in 726 Severe and Critical COVID-19 Patients: A Retrospective Cohort Study

“…Given that only 10.8% of serious patients in this study had a heartrelated disease, and elevated hs-cTnI levels as shown in patients with severe and critical COVID-19 are more likely to be attributed to the primary myocardial injury caused by SARS-CoV-2. A newly research has also shown that SARS-CoV-2 can infect heart cells in petri dishes of laboratory, suggesting that the heart cells in COVID-19 patients may be directly infected by the virus, resulting in heart muscle damage and heart-related complications [27]. Previous studies have reported an increased risk of death in COVID-19…”