Impact of acute TTE-evidenced cardiac dysfunction on in-hospital and outpatient mortality: A multicenter NYC COVID-19 registry study.

BACKGROUND: COVID-19 is associated with cardiac dysfunction. This study tested the relative prognostic role of left (LV), right and bi- (BiV) ventricular dysfunction on mortality in a large multicenter cohort of patients during and after acute COVID-19 hospitalization. METHODS/RESULTS: All hospitalized COVID-19 patients who underwent clinically indicated transthoracic echocardiography within 30 days of admission at four NYC hospitals between March 2020 and January 2021 were studied. Images were re-analyzed by a central core lab blinded to clinical data. Nine hundred patients were studied (28% Hispanic, 16% African-American), and LV, RV and BiV dysfunction were observed in 50%, 38% and 17%, respectively. Within the overall cohort, 194 patients had TTEs prior to COVID-19 diagnosis, among whom LV, RV, BiV dysfunction prevalence increased following acute infection (p<0.001). Cardiac dysfunction was linked to biomarker-evidenced myocardial injury, with higher prevalence of troponin elevation in patients with LV (14%), RV (16%) and BiV (21%) dysfunction compared to those with normal BiV function (8%, all p<0.05). During in- and out-patient follow-up, 290 patients died (32%), among whom 230 died in the hospital and 60 post-discharge. Unadjusted mortality risk was greatest among patients with BiV (41%), followed by RV (39%) and LV dysfunction (37%), compared to patients without dysfunction (27%, all p<0.01). In multivariable analysis, any RV dysfunction, but not LV dysfunction, was independently associated with increased mortality risk (p<0.01). CONCLUSIONS: LV, RV and BiV function declines during acute COVID-19 infection with each contributing to increased in- and out-patient mortality risk. RV dysfunction independently increases mortality risk.

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.

The Johns Hopkins University Center for Systems Science and Engineering COVID-19 Dashboard: data collection process, challenges faced, and lessons learned.

On Jan 22, 2020, a day after the USA reported its first COVID-19 case, the Johns Hopkins University Center for Systems Science and Engineering (JHU CSSE) launched the first global real-time coronavirus surveillance system: the JHU CSSE COVID-19 Dashboard. As of June 1, 2022, the dashboard has served the global audience for more than 30 consecutive months, totalling over 226 billion feature layer requests and 3·6 billion page views. The highest daily record was set on March 29, 2020, with more than 4·6 billion requests and over 69 million views. This Personal View reveals the fundamental technical details of the entire data system underlying the dashboard, including data collection, data fusion logic, data curation and sharing, anomaly detection, data corrections, and the human resources required to support such an effort. The Personal View also covers the challenges, ranging from data visualisation to reporting standardisation. The details presented here help develop a framework for future, large-scale public health-related data collection and reporting.

The Role of Angiotensin 1‐7 in Isolated Human Arterioles with SARS‐CoV‐2

Introduction The vascular endothelium plays a crucial role to regulate vascular tone. Recently, our laboratory reported severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection significantly reduced endothelial‐dependent vasodilation months after exposed to SARS‐CoV‐2 in human microvessels. SARS‐CoV‐2 enters host cells through angiotensin‐converting enzyme (ACE)2 as a cell surface receptor. Downregulation of ACE2 protein expression by the virus leads to imbalance between angiotensin (ANG) II and ANG 1‐7, causing vasoconstriction, inflammation and increase oxidative stress. With this background, we intend to test our new hypothesis that administration of ANG 1‐7 will improve vasodilation in human arterioles from previously SARS‐CoV‐2 positive subjects. Methods Fresh human tissues were obtained as de‐identified surgical discarded specimens. Control subjects (n=9) were SARS‐CoV‐2 negative and without known virus exposure. We had 11 previously SARS‐CoV‐2 positive subjects or post‐COVID. For all post‐COVID patients, a negative COVID test was obtained prior to collection of surgical specimens. We isolated arterioles (100‐200 µm) and cannulated onto glass micropipettes under 60 mmHg and examined for diameter changes to the endothelial‐dependent vasodilator acetylcholine (ACh;10−9 to 10−5 M) using videomicroscopy. Flow‐mediated dilation (FMD) was recorded at steady‐state during varying intraluminal pressure gradients (5‐100 cm H2O). All post‐COVID vessels were incubated in a culture media at 37°C for 12–15 hours with or without 1 nM of ANG 1‐7. Results Dilation to ACh and FMD in arterioles from post‐COVID was significantly reduced (ACh max. dilation at 10−5 M: 74±6% vs. 93±4% in control, n=7‐9, P<0.001;FMD max. dilation at 100 cm H2O: 49±3% vs. 86±2% in control, n=6‐11, P<0.001) while overnight incubation of 1 nM ANG 1‐7 significantly improved the dilation (ACh max. dilation at 10−5 M: 74±6% in post‐COVID vs. 88±5% in post‐COVID + AND 1‐7, n=11, P<0.001;FMD max. dilation at 100 cm H2O: 49±3% in post‐COVID vs. 76±3% in post‐COVID + ANG 1‐7, n=11, P<0.001). Conclusion Administration of ANG 1‐7 significantly improved vasodilation in isolated arterioles from post‐COVID subjects.

Pulmonary fibrosis 4 months after COVID-19 is associated with severity of illness and blood leucocyte telomere length.

The risk factors for development of fibrotic-like radiographic abnormalities after severe COVID-19 are incompletely described and the extent to which CT findings correlate with symptoms and physical function after hospitalisation remains unclear. At 4 months after hospitalisation, fibrotic-like patterns were more common in those who underwent mechanical ventilation (72%) than in those who did not (20%). We demonstrate that severity of initial illness, duration of mechanical ventilation, lactate dehydrogenase on admission and leucocyte telomere length are independent risk factors for fibrotic-like radiographic abnormalities. These fibrotic-like changes correlate with lung function, cough and measures of frailty, but not with dyspnoea.

Corilagin prevents SARS-CoV-2 infection by targeting RBD-ACE2 binding.

BACKGROUND: The outbreak of coronavirus (SARS-CoV-2) disease caused more than 100,000,000 people get infected and over 2,200,000 people being killed worldwide. However, the current developed vaccines or drugs may be not effective in preventing the pandemic of COVID-19 due to the mutations of coronavirus and the severe side effects of the newly developed vaccines. Chinese herbal medicines and their active components play important antiviral activities. Corilagin exhibited antiviral effect on human immunodeficiency virus (HIV), hepatitis C virus (HCV) and Epstein-Barr virus (EBV). However, whether it blocks the interaction between SARS-CoV-2 RBD and hACE2 has not been elucidated. PURPOSE: To characterize an active compound, corilagin derived from Phyllanthus urinaria as potential SARS-CoV-2 entry inhibitors for its possible preventive application in daily anti-virus hygienic products. METHODS: Computational docking coupled with bio-layer interferometry, BLI were adopted to screen more than 1800 natural compounds for the identification of SARS-CoV-2 spike-RBD inhibitors. Corilagin was confirmed to have a strong binding affinity with SARS-CoV-2-RBD or human ACE2 (hACE2) protein by the BLI, ELISA and immunocytochemistry (ICC) assay. Furthermore, the inhibitory effect of viral infection of corilagin was assessed by in vitro pseudovirus system. Finally, the toxicity of corilagin was examined by using MTT assay and maximal tolerated dose (MTD) studies in C57BL/6 mice. RESULTS: Corilagin preferentially binds to a pocket that contains residues Cys 336 to Phe 374 of spike-RBD with a relatively low binding energy of -9.4 kcal/mol. BLI assay further confirmed that corilagin exhibits a relatively strong binding affinity to SARS-CoV-2-RBD and hACE2 protein. In addition, corilagin dose-dependently blocks SARS-CoV-2-RBD binding and abolishes the infectious property of RBD-pseudotyped lentivirus in hACE2 overexpressing HEK293 cells, which mimicked the entry of SARS-CoV-2 virus in human host cells. Finally, in vivo studies revealed that up to 300 mg/kg/day of corilagin was safe in C57BL/6 mice. Our findings suggest that corilagin could be a safe and potential antiviral agent against the COVID-19 acting through the blockade of the fusion of SARS-CoV-2 spike-RBD to hACE2 receptors. CONCLUSION: Corilagin could be considered as a safe and environmental friendly anti-SARS-CoV-2 agent for its potential preventive application in daily anti-virus hygienic products.

Prolonged Endothelial Dysfunction in Human Arterioles with SARS-CoV-2

The vascular endothelium plays a crucial role to regulate vascular tone. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is known to cause vascular endothelial dysfunction. However, the long-term effects of SARS-CoV-2 in resistance vessels remains unknown. This study is designed to test whether endothelium-dependent vasodilation in human arterioles remains impaired after clearance of SARS-CoV-2 virus. Fresh human adipose tissues were obtained as discarded surgical specimens from control subjects (n=15, no SARS-CoV-2 exposure, 46.7±4 years) and previously SARS-CoV-2 positive subjects (PSPSs: n=8, 35.8±3.8 years). Among PSPSs, the time between positive and negative SARS-CoV-2 test results was ≤3 months (n=6) or 8 months (n=2). Isolated arterioles (100-200 µm) were cannulated under 60 mmHg and examined for diameter changes to acetylcholine (ACh;10?9 to 10?5 M) and sodium nitroprusside (SNP: 10?9 to 10?4 M) using videomicroscopy. Flow-mediated dilation (FMD) was recorded at steady-state during graded increases in intraluminal pressure gradients (5-100 cm H2O). Dilation to ACh and FMD in arterioles from PSPSs was significantly reduced (ACh max. dilation at 10?5 M: 60±6% vs. 92.8±3.9% in control, n=7-8, P<0.001;FMD max. dilation at 100 cm H2O: 39.9±5.7% vs. 85.8±1.8% in control, n=6-8, P<0.001, Fig.1) while endothelial-independent dilation in response to SNP was not different between groups (max. dilation at 10-4 M: 86.6±2.7% vs. 92.3±2.1% in control, n=5). To compare time-dependent effects of previous SARS-CoV-2 infection, we compared max. dilator capacity vs. time after exposure (Fig. 2). At ≤3 months post exposure, FMD was significantly impaired (% max. dilation: 26.7±7.4, n=5) whereas at 8 months endothelial function began to normalize (% max. dilation: 41.8±17.6, n=2). In conclusion, we observed significantly reduced endothelial-dependent dilation months after exposed to SARS-CoV-2. Our data suggests SARS-CoV-2 may cause long-term endothelial dysfunction in human arterioles.

Harnessing nitric oxide for preventing, limiting and treating the severe pulmonary consequences of COVID-19.

The ongoing outbreak of COVID-19 has quickly become a daunting challenge to global health. In the absence of targeted therapy and a reported 5.5% case fatality rate in the United States, treatments preventing rapid cardiopulmonary failure are urgently needed. Clinical features, pathology and homology to better understood pathogens suggest that uncontrolled inflammation and a cytokine storm likely drive COVID-19's unrelenting disease process. Interventions that are protective against acute lung injury and ARDS can play a critical role for patients and health systems during this pandemic. Nitric oxide is an antimicrobial and anti-inflammatory molecule with key roles in pulmonary vascular function in the context of viral infections and other pulmonary disease states. This article reviews the rationale for exogenous nitric oxide use for the pathogenesis of COVID-19 and highlights its potential for contributing to better clinical outcomes and alleviating the rapidly rising strain on healthcare capacity.