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Aims Since December 2019, the novel coronavirus SARS-CoV-2 has spread rapidly throughout China and keeps the world in suspense. Cardiovascular complications with myocarditis and embolism due to COVID-19 have been reported. SARS-CoV-2 genome detection in the heart muscle has not been demonstrated so far, and the underlying pathophysiological mechanisms remain to be investigated. Methods and results Endomyocardial biopsies (EMBs) of 104 patients (mean age: 57.90 ± 16.37 years; left ventricular ejection fraction: 33.7 ± 14.6%, sex: n = 79 male/25 female) with suspected myocarditis or unexplained heart failure were analysed. EMB analysis included histology, immunohistochemistry, and detection of SARS-CoV-2 genomes by real-time reverse transcription polymerase chain reaction in the IKDT Berlin, Germany. Among 104 EMBs investigated, five were confirmed with SARS-CoV-2 infected by reverse real-time transcriptase polymerase chain reaction. We describe patients of different history of symptoms and time duration. Additionally, we investigated histopathological changes in myocardial tissue showing that the inflammatory process in EMBs seemed to permeate vascular wall leading to small arterial obliteration and damage. Conclusions This is the first report that established the evidence of SARS-CoV-2 genomes detection in EMBs. In these patients, myocardial injury ischaemia may play a role, which could explain the ubiquitous troponin increases. EMB-based identification of the cause of myocardial injury may contribute to explain the different evolution of complicated SARS-CoV-2infection and to design future specific and personalized treatment strategies.

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Asymmetric dimethylarginine is an endogenous inhibitor of mobilization, differentiation, and function of EPCs. This contributes to the cardiovascular risk in patients with high ADMA levels and may explain low numbers and function of EPCs in patients with coronary artery disease.

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BackgroundNo evidence-based therapy exists for non-arteritic central retinal artery occlusion (NA-CRAO). Retinal ischemic tolerance is low; irreversible damage occurs within four hours of experimental NA-CRAO. In previous randomized trials evaluating intra-arterial or intravenous thrombolysis (IVT) in NA-CRAO, only one patient was treated this early. In December 2013, the Departments of Neurology & Stroke and Ophthalmology at University Hospital Tuebingen, Germany, decided to treat patients using IVT within 4.5 hours of NA-CRAO, the therapeutic window established for ischemic stroke.Materials and methodsConsecutive NA-CRAO patients with severe visual loss received IVT after exclusion of intracranial hemorrhage. Follow-up was conducted at day 5 (d5) and day 30 (d30). Visual outcomes were compared to the conservative standard treatment (CST) arm of the EAGLE-trial.ResultsUntil August 2016, 20 patients received IVT within 4.5 hours after NA-CRAO with a median onset-to-treatment time of 210 minutes (IQR 120–240). Visual acuity improved from baseline mean logarithm of the minimum angle of resolution 2.46±0.33 (SD) (light perception) to 1.52±1.09 (Snellen equivalent: 6/200) at d5 (p = 0.002) and 1.60±1.08 (Snellen equivalent: 6/240) at d30. Compared to the EAGLE CST-arm, functional recovery to reading ability occurred more frequently after IVT: 6/20 (30%) versus 1/39 (3%) at d5 (p = 0.005) and at d30 5/20 (25%) versus 2/37 (5%) (p = 0.045). Two patients experienced serious adverse events (one angioedema and one bleeding from an abdominal aortic aneurysm) but recovered without sequelae.ConclusionsIVT within 4.5 hours after symptom onset may represent an effective treatment of NA-CRAO. Randomized trials are warranted to evaluate efficacy and safety of early IVT in acute NA-CRAO.

IMPORTANCECurrent recommendations are to avoid tissue for corneal transplant from donors with coronavirus disease 2019 or those who were recently exposed to COVID-19 owing to the lack of knowledge about the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in corneal tissues. Evidence of SARS-CoV-2 in corneal tissue would seem to have clinical relevance for corneal transplant.OBJECTIVES To investigate the presence of viral SARS-CoV-2 RNA in corneal discs of deceased patients with confirmed COVID-19 and assess viral genomic and subgenomic RNA load, possible infectivity, and histologic abnormalities. DESIGN, SETTING, AND PARTICIPANTSA case series was conducted of 11 deceased patients with COVID-19 who underwent autopsy between March 20 and May 14, 2020. Eleven corneal discs (1 corneal disc per patient) were harvested for molecular detection of viral genomic and subgenomic RNA, virus isolation, and immunohistochemistry. The SARS-CoV-2 RNA loads were compared with RNA loads in the conjunctival and throat swab samples and aqueous humor, vitreous humor, and blood samples. MAIN OUTCOMES AND MEASURES Evidence of SARS-CoV-2 RNA in human corneas.RESULTS This study comprised 11 patients (6 women [55%]; mean [SD] age, 68.5 [18.8] years). In 6 of 11 eyes (55%), SARS-CoV-2 genomic RNA was detected in the cornea; subgenomic RNA was present in 4 of these 6 eyes (67%). Infectivity or the presence of viral structural proteins could not be confirmed in any eye. However, patients whose corneal disc was positive for SARS-CoV-2 RNA also had positive results for SARS-CoV-2 RNA in 4 of 6 conjunctival swab samples, 1 of 3 aqueous humor samples, 3 of 5 vitreous humor samples, and 4 of 5 blood samples. Overall, conjunctival swab samples had positive results for SARS-CoV-2 RNA in 5 of 11 cases. Postmortem SARS-CoV-2 viremia was detected in 5 of 9 patients.CONCLUSIONS AND RELEVANCE Viral genomic and subgenomic RNA of SARS-CoV-2 was detected in the cornea of patients with COVID-19 viremia. The risk of COVID-19 infection via corneal transplant is low even in donors with SARS-CoV-2 viremia, but further research is necessary to assess the rate of SARS-CoV-2 transmission via corneal transplant.

Key Words: endothelial progenitor cells Ⅲ nitrates Ⅲ nitric oxide Ⅲ reactive oxygen species Ⅲ atherosclerosis Ⅲ free radicals N itrate compounds have been used in the treatment of myocardial ischemia for more than a hundred years. Their common mechanism is the release of nitric oxide (NO), but the majority of nitrates, such as nitroglycerine (NTG) or isosorbide-5-dinitrate (ISDN), additionally stimulate production of reactive oxygen species (ROS). [1][2][3][4][5] This may counteract the beneficial effects of NO on the endothelium. 6 Indeed, NTG treatment was shown to reduce NO bioavailability 1 as a result of increased superoxide anion (O 2 Ϫ ) and peroxynitrite production. 7,8 Clinically, prolonged NTG therapy leads to the development of endothelial dysfunction and nitrate tolerance. 2,9 Therefore, the use of long-acting nitrates with less development of tolerance has become routine in chronic treatment of cardiac ischemia. However, even long-acting nitrates, such as ISDN, may increase ROS production in endothelial cells, smooth muscle cells, and platelets (reviewed by Schwemmer and Bassenge 10 ). In contrast, treatment with pentaerythritol tetranitrate (PETN) was not associated with increased ROS production in patients. 2 PETN treatment did also not stimulate endothelial ROS formation, and displayed antiatherosclerotic effects. 11-13 Indeed, PETN, but not ISDN, prevented plaque formation and endothelial dysfunction in animal models of atherosclerosis. 11,14 Bone marrow-derived endothelial progenitor cells (EPCs) circulate in the blood and contribute to the formation of new blood vessels and homeostasis of the vasculature. 15,16 NO is a major regulator of EPC mobilization, differentiation, and function. [17][18][19][20] Although nitrates are potent NO releasing substances, the effects of long-acting nitrates on circulating levels and function of EPCs have not been determined so far. We therefore compared the effects of ISDN and PETN (or its major metabolite pentaerythrityl trinitrate [PETriN]) on EPC number and function in healthy rats and rats after myocardial infarction. Additional in vitro studies were performed with human EPCs to identify potential underlying events leading to the different effects of both nitrates.