Lack of evidence of ACE2 expression and replicative infection by SARS-CoV-2 in human endothelial cells (preprint)

A striking feature of severe COVID-19 is thrombosis in large as well as small vessels of multiple organs. This has led to the assumption that SARS-CoV-2 virus directly infects and damages the vascular endothelium. However, endothelial expression of ACE2, the cellular receptor for SARS-CoV-2, has not been convincingly demonstrated. Interrogating human bulk and single-cell transcriptomic data, we found ACE2 expression in endothelial cells to be extremely low or absent in vivo and not upregulated by exposure to inflammatory agents in vitro. Also, the endothelial chromatin landscape at the ACE2 locus showed presence of repressive and absence of activation marks, suggesting that the gene is inactive in endothelial cells. Finally, we failed to achieve infection and replication of SARS-CoV-2 in cultured human endothelial cells, which were permissive to productive infection by coronavirus 229E that uses CD13 as the receptor. Our data suggest that SARS-Cov-2 is unlikely to infect endothelial cells directly; these findings are consistent with a scenario where endothelial injury is indirectly caused by the infection of neighbouring epithelial cells and/or due to systemic effects mediated by immune cells, platelets, complement activation, and/or proinflammatory cytokines.

Clinical Characteristics on Admission Predict In-Hospital Fatal Outcome in Patients Aged ≥75 Years with novel coronavirus disease (COVID-19): A Retrospective Cohort Study (preprint)

Background: ： Novel coronavirus disease（COVID-19）has become a worldwide pandemic and precise fatality data by age group are needed urgently. This study to delineate the clinical characteristics and outcome of COVID-19 patients aged ≥75 years and identify the risk factors of in-hospital death. Methods: ： A total of 141 consecutive patients aged ≥75 years who were admitted to the hospital between 12 th and 19 th February 2020. In-hospital death, clinical characteristics and laboratory findings on admission were obtained from medical records. The final follow-up observation was 31 st March 2020. Results: ： The median age was 81 years (84 female, 59.6%). Thirty-eight (27%) patients were classified as severe or critical cases. 18 (12.8%) patients had died in hospital and the remaining 123 were discharged. Patients who died were more likely to present with fever (38.9% vs. 7.3%); low percutaneous oxygen saturation(SpO 2 ) (55.6% vs. 7.3%); reduced lymphocytes (72.2% vs. 35.8%) and platelets (27.8% vs. 4.1%); and increased D-dimer (94.4% vs. 42.3%), creatinine (50.0% vs. 22.0%), lactic dehydrogenase (LDH) (77.8% vs. 30.1%), high sensitivity troponin I (hs-TnI) (72.2% vs. 14.6%), and N-terminal pro-brain natriuretic peptide (NT-proBNP) (72.2% vs. 6.5%; all P<0.05) than patients who recovered. Male sex (odds ratio [OR]=13.1, 95% confidence interval[CI] 1.1 to 160.1, P=0.044), body temperature >37.3°C (OR=80.5, 95% CI 4.6 to 1407.6, P=0.003), SpO 2 ≤90% (OR=70.1, 95% CI 4.6 to 1060.4, P=0.002), and NT-proBNP>1800ng/L (OR=273.5, 95% CI 14.7 to 5104.8, P<0.0001) were independent risk factors of in-hospital death. Conclusions: ： In-hospital fatality among COVID-19 patients can be estimated by sex and on-admission measurements of body temperature, SpO 2 , and NT-proBNP.

Pericyte-specific vascular expression of SARS-CoV-2 receptor ACE2 - implications for microvascular inflammation and hypercoagulopathy in COVID-19 patients (preprint)

Accumulating clinical observations implicate vascular inflammation as an underlying cause of coagulopathy in severely ill COVID-19 patients and it was recently suggested that SARS-CoV-2 virus particles infect endothelial cells. Here, we show that endothelial cells do not express angiotensin-converting enzyme-2 (ACE2), the SARS-CoV-2 receptor. Instead, pericytes and microvascular smooth muscle cells express ACE2 in an organotypic manner. Pericyte deficiency leads to increased endothelial expression and release of Von Willebrand factor and intravascular platelet and fibrin aggregation, suggesting that pericytes limit endothelial pro-thrombotic responses. That pericytes and not endothelial cells express ACE2 may provide important clues to the pathology of COVID-19, as pericytes are normally shielded behind an endothelial barrier and may get infected only when this barrier is compromised by COVID-19 risk factors.

Myocardial injury is associated with in-hospital mortality of confirmed or suspected COVID-19 in Wuhan, China: A single center retrospective cohort study (preprint)

[Background] Since December 2019, a cluster of coronavirus disease 2019 (COVID-19) occurred in Wuhan, Hubei Province, China and spread rapidly from China to other countries. In-hospital mortality are high in severe cases and cardiac injury characterized by elevated cardiac troponin are common among them. The mechanism of cardiac injury and the relationship between cardiac injury and in-hospital mortality remained unclear. Studies focused on cardiac injury in COVID-19 patients are scarce. [Objectives] To investigate the association between cardiac injury and in-hospital mortality of patients with confirmed or suspected COVID-19. [Methods] Demographic, clinical, treatment, and laboratory data of consecutive confirmed or suspected COVID-19 patients admitted in Wuhan No.1 Hospital from 25th December, 2019 to 15th February, 2020 were extracted from electronic medical records and were retrospectively reviewed and analyzed. Univariate and multivariate Cox regression analysis were used to explore the risk factors associated with in-hospital death. [Results] A total of 110 patients with confirmed (n=80) or suspected (n=30) COVID-19 were screened and 48 patients (female 31.3%, mean age 70.58{+/-}13.38 year old) among them with high-sensitivity cardiac troponin I (hs-cTnI) test within 48 hours after admission were included, of whom 17 (17/48, 35.4%) died in hospital while 31 (31/48, 64.6%) were discharged or transferred to other hospital. High-sensitivity cardiac troponin I was levated in 13 (13/48, 27.1%) patents. Multivariate Cox regression analysis showed pulse oximetry of oxygen saturation (SpO2) on admission (HR 0.704, 95% CI 0.546-0.909, per 1% decrease, p=0.007), elevated hs-cTnI (HR 10.902, 95% 1.279-92.927, p=0.029) and elevated d-dimer (HR 1.103, 95%CI 1.034-1.176, per 1mg/L increase, p=0.003) on admission were independently associated with in-hospital mortality. [Conclusions] Cardiac injury defined by hs-cTnI elevation and elevated d-dimer on admission were risk factors for in-hospital death, while higher SpO2 could be seen as a protective factor, which could help clinicians to identify patients with adverse outcome at the early stage of COVID-19.