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Cytomegalovirus (CMV) can cause recalcitrant recurrent keratouveitis and secondary glaucoma. We report a case of chronic recurrent anterior uveitis with secondary glaucoma presenting with acute visual loss and interface fluid 9 years after laser in situ keratomileusis. Based on clinical presentation, a viral aetiology was suspected. Aqueous tap was positive for CMV-DNA by real-time quantitative PCR of the aqueous humour. The patient was treated with systemic antivirals, topical corticosteroids and antiglaucoma medications. The interface fluid resorbed rapidly. The intraocular pressure (IOP) was controlled by trabeculectomy. There was no further corneal deterioration at 7-month follow-up and the IOP had also stabilised. We believe this is only the third reported case of CMV-related interface fluid syndrome. This case highlights the role of quantitative PCR analysis for establishing viral aetiology in recurrent unilateral hypertensive anterior uveitis and reports the unusual finding of interface fluid which resolved after starting systemic antiviral therapy.

A 27-year-old immunocompetent woman presented to our clinic with redness, mild pain and blurring of vision in her left eye (LE) for 3 weeks with no preceding history of injury or contact lens wear. At presentation, her visual acuity was 20/20 and 20/60 in the right eye and LE, respectively. Slit

Introduction and aim. COVID-19 is a viral infectious disease, which was first reported in patients with unusual pneumonia in December 2019. However, as the pandemic progressed, extrapulmonary manifestations including various neurologic complications have been started to be increasingly reported. In this retrospective study, we tried to search the neurological complications seen in our patients with positive rRT-PCR test for COVID-19 and examine the underlying associated risk factors. Material and methods. We have retrospectively analyzed the neuroimaging studies performed in our patients with positive rRT-PCR test for COVID-19 between April, 2020 and August, 2021. Both computed tomography (CT) scans and magnetic resonance imagings (MRI) of brain, head & neck region and the spine were retrospectively evaluated for the presence of any complications in patients with positive rRT-PCR test for COVID-19. Results. There were 147 patients having neuroradiological imaging studies performed for various neurological symptoms. Among these patients we detected 10 acute neurologicalcomplications.The most common was acute ischemic stroke in 5 patients and intracranial hemorrhage in 3 patients, two of which were intraventricular hemorrhage. The other complications included a preasumed cytotoxic lesion of corpus callosum in a 18 year old girl and lumbar spondylodiscitis complicated with psoas abcess in a 47 year-old man. Conclusion. In COVID-19 patients severe neurological complications can occur even as a presenting manifestation. Early cytotoxic endothelial injury can be the underlying cause in these patients and should be further studied in larger series in terms of what the susceptibility factors in these patients.

The global propagation of SARS-CoV-2 leads to an unprecedented public health emergency. Despite that the lungs are the primary organ targeted by COVID-19, systemic endothelial inflammation and dysfunction is observed particularly in patients with severe COVID-19, manifested by elevated endothelial injury markers, endotheliitis, and coagulopathy. Here, we review the clinical characteristics of COVID-19 associated endothelial dysfunction; and the likely pathological mechanisms underlying the disease including direct cell entry or indirect immune overreactions after SARS-CoV-2 infection. In addition, we discuss potential biomarkers that might indicate the disease severity, particularly related to the abnormal development of thrombosis that is a fatal vascular complication of severe COVID-19. Furthermore, we summarize clinical trials targeting the direct and indirect pathological pathways after SARS-CoV-2 infection to prevent or inhibit the virus induced endothelial disorders., Graphical abstract Unlabelled Image

The clinical outcomes of COVID-19 patients highlight a significant minority of subjects with very rapid lethal outcomes subsequent to the almost complete healing after coronavirus infections for most of the subjects involved. In addition, the reckless use of some drugs and therapeutic protocols that have not shown any efficacy in reducing mortality in those patients where the progression of the disease was unstoppable suggests a different interpretative model in the pathogenesis of severe cases. Starting from the clinical data already known for almost twenty years on the behavior of human SARS coronaviruses, it is possible to develop a new hypothesis. The reference points taken into consideration are: i) the comparison of the histological evidence of the autoptic material; ii) the poor pharmacological response in subjects with severe phenotypes of the pathology; iii) the common element of endotheliitis in a subgroup of the population characterized by harmful clinical outcomes during the evolution of the pathology. The tendency to develop widespread, massive endothelial lesions not responding to any drug therapy or other interventions necessarily plays a crucial role in the onset of the systemic and severe stage of the disease. The present perspective opens the door to a different therapeutic approach both to the full-blown phase of COVID-19 and to the preventive phase or the very first manifestations of the disease. It is imperative to pay more attention to the protection of the vascular endothelium in subjects who already have a predisposition to the development of a severe evolution of this ailment rather than to give a simple antiviral therapy together with symptomatic drugs.

The new coronavirus disease (COVID-19) is a viral respiratory infection accompanied by systemic endotheliitis. COVID-19 patients usually encounter changes related to hypercoagulability, hypofibrinolysis, and increased intravascular platelet aggregation. There is also a vascular wall thromboresistance decrease and impaired vasomotor function, which significantly increase the risk of thromboembolic complications. Currently, pathogenic aspects of the relationship between COVID-19 and vascular and inflammatory conditions of the optic nerve and retina are actively investigated. One of the triggers of impaired blood flow in ocular vessels may be a perfusion pressure decrease, observed in the acute period of the infectious process. This is related to both COVID-19 clinical course features and to resuscitation specificity as well. Secondary autoimmune inflammation is being considered as a mechanism of damage to the vascular wall in the post-infectious period. In this publication, possible pathogenic links of these diseases are considered for the first time in a specific context of the example of ischemic optic neuropathy associated with coronavirus infection.

The pandemic of the new coronavirus infection COVID-19 in 2020 has become the main health problem across the globe. A special characteristic of the SARSCoV-2 virus is tropism to the vascular endothelium with the development of endotheliitis, which entails a number of typical disorders of the blood coagulation system: coagulopathy with increased thrombin generation, D-dimer, decreased fibrinolysis and prolonged prothrombin time. The coagulation disorder in COVID-19 is called thromboinflammation. Hyperinflammation, increased blood levels of von Willebrand factor, coagulation factor VIII, neutrophil extracellular traps, platelet activation, microvesicles play a significant role in the pathogenesis of hypercoagulation in COVID-19. To date, it is known that cases of COVID-19 in children and adolescents constitute a small part of the total number of patients with diagnosed COVID-19, and disorders of the blood coagulation system are similar to those in adults. The degree of hypercoagulable syndrome and the risk of thrombosis depend on the severity of COVID-19. And for children they are most expressed with the development of a hyperinflammatory immune response, called multisystem inflammatory syndrome. At the same time, clinical studies of the pathogenesis of COVID-19 in adults and children and the search for optimal methods of therapy for thrombus inflammation, which underlies the pathogenesis of COVID-19, continue.

Capillary endothelial cells possess a specialized metabolism necessary to adapt to the unique alveolar-capillary environment. Here, we highlight how endothelial metabolism preserves the integrity of the pulmonary circulation by controlling vascular permeability, defending against oxidative stress, facilitating rapid migration and angiogenesis in response to injury, and regulating the epigenetic landscape of endothelial cells. Recent reports on single-cell RNA-sequencing reveal subpopulations of pulmonary capillary endothelial cells with distinctive reparative capacities, which potentially offer new insight into their metabolic signature. Lastly, we discuss broad implications of pulmonary vascular metabolism on acute respiratory distress syndrome, touching on emerging findings of endotheliitis in coronavirus disease 2019 (COVID-19) lungs.

Purpose Herpes simplex diffuse endotheliitis with accompanying feathery infiltration is difficult to diagnose due to corneal findings that are similar to fungal keratitis. This case series reports on the effectiveness of using real-time polymerase chain reaction (PCR) to diagnose herpes simplex diffuse endotheliitis that is similar in appearance to fungal keratitis. Methods After extracting corneal smear sample DNA, samples were then applied to two independent PCR assays, a qualitative multiplex 24-pathogen strip PCR assay, and a quantitative real-time PCR assay of herpes simplex virus type 1 (HSV-1). Results All 3 cases showed ciliary injection, feathery infiltration in the corneal stroma and hypopyon, which are corneal findings similar to that observed for fungal keratitis. Retrocorneal plaques, which showed clear boundaries between the corneal endothelial surfaces and retrocorneal plaques in anterior segment optical coherence tomography, were observed in 2 out of 3 cases. Corneal scraping was performed in all cases, followed by initiation of antifungal treatment. However, real-time PCR of the corneal scraping detected 6.0 × 106, 1.0 × 105 and 5.0 × 105 copies/μg glyceraldehyde 3-phosphate dehydrogenase (GAPDH) of HSV-1 DNA per each microgram of the samples. Fungi were not cultured in any of the cases. After switching the medication from antifungal to antiviral, the feathery corneal infiltration was cured with only mild scarring. Conclusions Real-time PCR was an effective tool in diagnosing HSV diffuse endotheliitis with feathery infiltration. Topical corticosteroids in conjunction with oral and topical antivirals were an effective treatment.

Coronavirus disease 2019 (COVID-19) predisposes patients to thrombotic and thromboembolic events, owing to excessive inflammation, endothelial cell activation and injury, platelet activation and hypercoagulability. Patients with COVID-19 have a prothrombotic or thrombophilic state, with elevations in the levels of several biomarkers of thrombosis, which are associated with disease severity and prognosis. Although some biomarkers of COVID-19-associated coagulopathy, including high levels of fibrinogen and d-dimer, were recognized early during the pandemic, many new biomarkers of thrombotic risk in COVID-19 have emerged. In this Consensus Statement, we delineate the thrombotic signature of COVID-19 and present the latest biomarkers and platforms to assess the risk of thrombosis in these patients, including markers of platelet activation, platelet aggregation, endothelial cell activation or injury, coagulation and fibrinolysis as well as biomarkers of the newly recognized post-vaccine thrombosis with thrombocytopenia syndrome. We then make consensus recommendations for the clinical use of these biomarkers to inform prognosis, assess disease acuity, and predict thrombotic risk and in-hospital mortality. A thorough understanding of these biomarkers might aid risk stratification and prognostication, guide interventions and provide a platform for future research., In this Consensus Statement, the authors delineate the thrombotic signature of COVID-19 and present the latest biomarkers and platforms to assess thrombotic risk in these patients. Consensus recommendations are made about the clinical use of these biomarkers to inform prognosis, assess disease acuity, and predict thrombosis and in-hospital mortality.

This article, being based on the analysis of literature and the author’s own materials, outlines the features of the lesion of the central nervous system in a new coronavirus infection. The main idea is that despite the primary damage to the respiratory tract, SARS-CoV-2 can be attributed to a number of signs as neurotropic viruses, which is ultimately realized by the transport of the pathogen COVID-19 from the place of primary localization — the respiratory tract to the human brain. The virus is capable of hitting all possible pathways of being transferred through tissues and within a short time appears in the brain, interacting with ACE2 receptors and co-receptors, which are expressed in almost all brain cells, neurons, astrocytes, oligodendrocytes, microgliocytes, which carry out the main functional tasks of the brain. The clinical part is devoted to radiation diagnosis of lesions of the nervous system caused by the SARS-CoV-2 coronavirus. Analysis of the literature has made it possible to identify radiation variants of CNS lesions in COVID-19, illustrating the main clinical manifestations of the disease. There are several main clinical and morphological variants of CNS damage in COVID-19 1: acute ischemic stroke, acute encephalopathy, due to massive diffuse damage to the endothelium against the background of vasculitis / endotheliitis, occurring both with and without signs of cerebral artery thrombosis, hemorrhages, primarily of the type of small petechiae, polyetiologic in nature (endothelial damage, acute hypoxia, microembolism). In addition, hemorrhages can be a consequence of venous infarction against the background of sinus thrombosis. Radiological methods can diagnose multi-step lesions of the supra- and subtentorial white matter, vasculitis, in particular Susak’s syndrome, posterior reversible leukoencephalopathy — PRES, leukoencephalopathy, delayed post-hypoxic leukoencephalopathy, Miller–Fischer’s polyneuropathy (Guillain-Barre syndrome), syndrome.

Background Although the lung is seen as the main target organ affected by SARS-CoV-2, other organs are also damaged. Aim We aimed to determine the extrapulmonary findings of autopsies performed on cases with positive results with postmortem polymerase chain reaction test. Methods Pathological changes in extrapulmonary organs were examined with light microscopy. Results Heart, liver, spleen, kidney, pancreas, and central nervous system samples of these cases were evaluated. About 80% of the cases were men, and 20% were women. In the examination of heart, 28 of the cases had scar, 14 had acute myocardial infarction, 6 had acute and previous myocardial infarction findings, 2 had myocarditis, and 4 had interstitial mononuclear inflammatory cell infiltration. In the examination of the liver, portal inflammation was observed in 84 of the cases, steatosis in 54, centrilobular necrosis in 9, and capillary endotheliitis in the portal area in 7 of them. In the evaluation of the kidney, 37 cases had chronic pyelonephritis, 36 had tubular damage, 15 had tubulointerstitial necrosis, 16 had subcapsular microhemorrhage, 10 had capillary endothelitis, and 9 had a microvascular fibrin trombosis in their glomerular capillaries. In the central nervous system, 8 cases had infarction and liquefaction, 56 had perivascular petechial hemorrhage, 54 had acute hypoxic ischemic change, 3 had parenchymal microhemorrhage, and 52 had capillary endotheliitis. Conclusion Autopsies play an important role in systematically examining the damage caused by the virus in all organs in order to elucidate the pathogenesis of SARS-CoV-2 infection and contribute to the clinical management of infected patients.

The COVID-19 pandemic has caused serious health and social concerns worldwide. Although the primary target of SARS-CoV-2 is the respiratory tract, SARS-CoV-2 infection also causes extrapulmonary symptoms. Previous articles have reported ischemic colitis in COVID-19 patients; however, information regarding its clinical manifestations and pathophysiology is limited. In this case report, we present two cases of ischemic enterocolitis in COVID-19 patients and review past case reports. Our literature review has shown that computed tomography rather than endoscopy was used for the diagnosis, and any region of the intestine was affected. Because the elevation of the D-dimer, which suggested a hypercoagulable state, was reported in most cases, we assumed that thrombosis at any level in the artery and vein was involved in the pathophysiology of COVID-19–associated enterocolitis. SARS-CoV-2–induced endotheliitis can cause both coarctation of the vessels and thrombosis; therefore, both patterns of ischemic colitis, occlusive and nonocclusive, may be involved in COVID-19–associated enterocolitis.

BACKGROUND: Both arterial and venous thrombotic events of the extremities occur in coronavirus disease 2019 (COVID-19) infection, but the etiology of these events remains unclear. This study sought to evaluate pathology specimens of COVID-19-positive patients postamputation, who were found to have Rutherford 3 acute limb ischemia requiring amputation. METHODS: A retrospective review was performed of all vascular surgery emergency room and inpatient consultations in patients who presented to the Mount Sinai Health System from March 26, 2020, to May 10, 2020. Pathology specimens were examined using hematoxylin and eosin stain. The specimens were assessed for the following: inflammatory cells associated with endothelium/apoptotic bodies, mononuclear cells, small vessel congestion, and lymphocytic endotheliitis. Of the specimens evaluated, 2 patients with a known history of peripheral vascular disease were excluded. RESULTS: Inflammatory cells associated with endothelium/apoptotic bodies were seen in all 4 patients and in 4 of 5 specimens. Mononuclear cells were found in 2 of 4 patients. Small vessel congestion was seen in all patients. Lymphocytic endotheliitis was seen in 1 of 4 patients. CONCLUSIONS: This study shows endotheliitis in amputation specimens of four patients with COVID-19 disease and Rutherford Class 3 acute limb ischemia. The findings in these patients is more likely an infectious angiitis because of COVID-19.

OBJECTIVE: To describe the clinical findings, multimodal corneal imaging features and treatment in canine patients diagnosed with endotheliitis. ANIMALS STUDIED: Four canine patients met inclusion criteria for bilateral corneal disease with endothelial inflammation and secondary corneal edema that responded to topical anti-inflammatory treatment. METHODS: The patients selected underwent a complete ophthalmic examination with emphasis on the cornea including ultrasound pachymetry (USP), Fourier-domain optical coherence tomography (FD-OCT), in vivo confocal microscopy (IVCM), and digital slit lamp photography. RESULTS: All patients in this study demonstrated thickened corneas due to edema with USP and FD-OCT. With IVCM, mild to severe polymegathism and pleomorphism of corneal endothelial cells, reduced endothelial cell density (ECD), hyperreflective keratic precipitates (KPs) and extracellular debris as well as hyporeflective pseudoguttata were observed. With FD-OCT, hyperreflective KPs were commonly observed on the inferior cornea. Clinical examination and advanced imaging results were consistent with a diagnosis of endotheliitis. All patients initially responded to topical anti-inflammatory treatment and required continued therapy. All patients received topical anti-inflammatory treatment and two patients received topical netarsudil, a rho-associated coiled-coil kinase (ROCK) inhibitor. CONCLUSION: Endotheliitis should be considered for canine patients with bilateral edema that is most severe in the inferior cornea. Careful inspection of Descemet’s membrane-endothelial complex should be performed for KPs or inflammatory debris. Chronic administration of topical anti-inflammatories may be necessary to prevent flare-ups of endotheliitis.

To assess prevalence, clinical manifestations, required keratoplasties, follow-up, and outcome in patients with Herpes Simplex Virus Keratitis (HSK) attending a University Tertiary Referral Center.Retrospective (12 years), descriptive, observational study.A total of 817 eyes with clinical diagnosis of HSK from 779 patients were classified by the type of presentation. We gathered data on the visual acuity, refraction, IOP, and required surgical procedures.Stromal involvement including scars represented the most common diagnosis in our department and the main indication of penetrating keratoplasty (PKP). Epithelial keratitis (16%) presented with the best visual acuity at the first visit. Necrotizing keratitis represented 17% of the patients, 78% of whom required PKP; this group also had the worst visual acuity at first examination and was the main indication for emergency PKP. Among all eyes, 288 (35%) required PKP. A total of 230 (28%) PKPs were elective procedures and 58 (7%) PKPs were performed as emergency procedures. Two patients with quiet endothelial decompensations after recurrent HSV endotheliitis were treated with DMEK and had good visual outcomes without HSV recurrence at last follow-up.HSK is a prevalent disease with severe consequences when not treated appropriately and on time. Even when making an accurate diagnosis, the disease can be extremely aggressive, with all the implications it brings to the patients and health system. Elective PKP had better outcomes in terms of visual acuity and clear graft percentage compared to emergency PKP.Beurteilung der Prävalenz, der klinischen Manifestationen, der erforderlichen Keratoplastiken, der Nachsorge und der Ergebnisse bei Patienten mit Herpes-simplex-Virus-Keratitis (HSK), die ein tertiäres universitäres Referenzzentrum besuchen.Retrospektive (12 Jahre), deskriptive Beobachtungsstudie.Insgesamt wurden 817 Augen mit der klinischen Diagnose HSK von 779 Patienten nach der Art der Präsentation klassifiziert. Wir sammelten Daten zur Sehschärfe, Refraktion, IOD und den erforderlichen chirurgischen Eingriffen.Die stromale Beteiligung einschließlich Narben stellte die häufigste Diagnose in unserer Abteilung und die Hauptindikation für eine perforierende Keratoplastik (PKP) dar. Patienten mit epithelialer Keratitis (16%) stellten sich beim ersten Besuch mit der besten Sehschärfe vor. Die nekrotisierende Keratitis machte 17% der Patienten aus, von denen 78% eine PKP benötigten; diese Gruppe hatte auch die schlechteste Sehschärfe bei der Erstuntersuchung und war die Hauptindikation für eine PKP à chaud. Von allen Augen benötigten 288 (35%) eine PKP. Insgesamt 230 (28%) PKPs waren elektive Eingriffe und 58 (7%) PKPs wurden à chaud durchgeführt. Zwei Patienten mit ruhigen endothelialen Dekompensationen nach rezidivierender HSV-Endotheliitis wurden mit DMEK behandelt und hatten bei der letzten Nachbeobachtung einen guten Visus ohne HSV-Rezidiv.HSK ist eine weitverbreitete Erkrankung mit schwerwiegenden Folgen, wenn sie nicht angemessen und rechtzeitig behandelt wird. Selbst wenn die richtige Diagnose gestellt wird, kann die Krankheit extrem aggressiv sein, mit all ihren Auswirkungen auf die Patienten und das Gesundheitssystem. Die elektive PKP hatte im Vergleich zur PKP à chaud bessere Ergebnisse in Bezug auf die Sehschärfe und das Transplantatüberleben.

Myocarditis has been reported as a possible clinical presentation or complication in patients with coronavirus disease (COVID)-19 due to SARS-CoV-2. Despite the alarm that this possibility generated among physicians, there is paucity of information about mechanisms, prevalence, prognosis, diagnosis and therapy of myocarditis in the context of COVID-19. This brief review has the goal to revise and summarize current knowledge on myocarditis in COVID-19 patients and underline problems especially related to diagnosis and treatment.

Coronavirus Disease 2019 (COVID-19), caused by the novel Severe Acute Respiratory Syndrome-associated Coronavirus 2 (SARS-CoV-2), has become a global threat to public health. COVID-19 is more pathogenic and infectious than the prior 2002 pandemic caused by SARS-CoV-1. The pathogenesis of certain disease manifestations in COVID-19 such as diffuse alveolar damage (DAD) are thought to be similar to SARS-CoV-1. However, the exact pathogenesis of COVID-19 related deaths remains poorly understood. The aim of this article was to systematically summarize the rapidly emerging literature regarding COVID-19 autopsies. A meta-analysis was also conducted based on data accrued from preprint and published articles on COVID-19 (n=241 patients) and the results compared with postmortem findings associated with SARS-CoV-1 deaths (n=91 patients). Both autopsy groups included mostly adults of median age 70 years with COVID-19 and 50 years with SARS-CoV-1. Overall, prevalence of DAD was more common in SARS-CoV-1 (100.0%) than COVID-19 (80.9%) autopsies (P=0.001). Extrapulmonary findings among both groups were not statistically significant except for hepatic necrosis (P

The coronavirus infection, COVID-19, caused by SARS-CoV-2 is associated not only with a wide range of respiratory syndromes, but also with a pronounced destructive effect on the blood vessels of the whole body. Age and concomitant pathology predispose to a more severe course of the disease. Endothelial damage, widespread vasculitis and thrombosis can be distinguished as general nonspecific pathomorphological changes developing in blood vessels under the influence of SARS-CoV-2. For the blood vessels of the lungs, in addition to alteration of the endothelium and thrombosis, angiogenesis of the cleaving (invagination) type was typical. The general mechanism of alteration of blood vessels and the development of vasculopathy is the direct cytopathic effect of the virus on endotheliocytes and immune-mediated damage to the endothelium, manifested by the development of endotheliitis, destruction of intercellular contacts of endothelial cells, their swelling and separation from the basement membrane, accompanied by endo- and perivascular inflammation. Molecular biological mechanisms of virus invasion involve various ways of its penetration into the cell and various forms of development of the inflammatory response with the participation of innate and acquired immunity reactions.

We present results from clinical, radiologic, gas exchange, lung mechanics, and fibre-optic bronchoscopy-guided transbronchial biopsies in a case of acute respiratory failure due to SARS-CoV-2 (Covid-19). This report highlights the pulmonary, immunological, and inflammatory changes found during acute diffuse alveolar damage and the later organizing phase. An early diffuse alveolar damage pattern with predominant epithelial involvement with active recruitment of T cells and monocytes was observed followed by a late organizing pattern with pneumocyte hyperplasia, inflammatory infiltration, prominent endotheliitis, and secondary germinal centers. The patient’s deterioration paralleling the late immuno-pathological findings based the decision to administer intravenous corticosteroids, resulting in clinical, gasometric, and radiologic improvement. We believe that real-time clinicopathological correlation, along with the description of the immunological processes at play, will contribute to the full clinical picture of Covid-19 and might lead to a more rational approach in the precise timing of anti-inflammatory, anti-cytokine, or steroid therapies. Supplementary Information The online version contains supplementary material available at 10.1007/s00428-020-02975-6.

Rationale: Pulmonary vascular endotheliitis, perivascular inflammation, and immune activation are observed in COVID-19 patients. While the initial SARS-CoV-2 infection mainly infects lung epithelial cells, whether it also infects endothelial cells (ECs) and to what extent SARS-CoV-2-mediated pulmonary vascular endotheliitis is associated with immune activation remain to be determined. Methods: To address these questions, we studied SARS-CoV-2-infected K18-hACE2 (K18) mice, a severe COVID-19 mouse model, as well as lung samples from SARS-CoV-2-infected nonhuman primates (NHP) and patient deceased from COVID-19. We used immunostaining, RNAscope, and electron microscopy to analyze the organs collected from animals and patient. We conducted bulk and single cell (sc) RNA-seq analyses, and cytokine profiling of lungs or serum of the severe COVID-19 mice. Results: We show that SARS-CoV-2-infected K18 mice develop severe COVID-19, including progressive body weight loss and fatality at 7 days, severe lung interstitial inflammation, edema, hemorrhage, perivascular inflammation, systemic lymphocytopenia, and eosinopenia. Body weight loss in K18 mice correlated with the severity of pneumonia, but not with brain infection. We also observed endothelial activation and dysfunction in pulmonary vessels evidenced by the up-regulation of VCAM1 and ICAM1 and the downregulation of VE-cadherin. We detected SARS-CoV-2 in capillary ECs, activation and adhesion of platelets and immune cells to the vascular wall of the alveolar septa, and increased complement deposition in the lungs, in both COVID-19-murine and NHP models. We also revealed that pathways of coagulation, complement, K-ras signaling, and genes of ICAM1 and VCAM1 related to EC dysfunction and injury were upregulated, and were associated with massive immune activation in the lung and circulation. Conclusion: Together, our results indicate that SARS-CoV-2 causes endotheliitis via both infection and infection-mediated immune activation, which may contribute to the pathogenesis of severe COVID-19 disease.

Background & Aims: Liver injury due to coronavirus disease 2019 (COVID-19) is being increasingly recognized. Abnormal liver chemistry tests of varying severities occur in a majority of patients. However, there is a dearth of accompanying liver histologic studies in these patients. Methods: The current report details the clinical courses of 2 patients having severe COVID-19 hepatitis. Liver biopsies were analyzed under light microscopy, portions of liver tissue were hybridized with a target probe to the severe acute respiratory syndrome coronavirus-2 S gene, and small sections from formalin-fixed paraffin-embedded liver tissue were processed for electron microscopy. Results: The liver histology of both cases showed a mixed inflammatory infiltrate with prominent bile duct damage, endotheliitis, and many apoptotic bodies. In situ hybridization and electron microscopy suggest the intrahepatic presence of severe acute respiratory syndrome coronavirus-2, the findings of which may indicate the possibility of direct cell injury. Conclusions: On the basis of the abundant apoptosis and severe cholangiocyte injury, these histopathologic changes suggest a direct cytopathic injury. Furthermore, some of the histopathologic changes may resemble acute cellular rejection occurring after liver transplantation. These 2 cases demonstrate that severe COVID-19 hepatitis can occur even in the absence of significant involvement of other organs.

Background Cytomegalovirus (CMV) can manifest as corneal endotheliitis in immunocompetent individuals. Early diagnosis is prudent to prevent endothelial cell loss, which could ultimately lead to corneal decompensation. CMV DNA was first detected in an eye with corneal endotheliitis in 2006; since then, clinical evidence from numerous case reports and case series have accumulated. Main text In this narrative review, we identified several drugs, including ganciclovir, valganciclovir, and their combination in oral, intravenous, intravitreal, and topical forms in different concentrations, together with the judicious use of topical steroids, have reported variable success. There has yet to be any prospective comparative study evaluating the efficacy and safety of these assorted forms of treatment; clinical evidence is based on case reports and case series. CMV endotheliitis presenting with corneal edema can masquerade as other corneal diseases and thus poses a great challenge especially in post-keratoplasty eyes. Heightened awareness is needed before and after keratoplasty to start prompt prophylaxis and treatment. Conclusion There is no consensus on the management of CMV endotheliitis. Further studies are much needed to elucidate the optimal treatment modality, regime, and duration in the treatment and prophylaxis of CMV endotheliitis.

Сonsidering the influence of the SARS-CoV-2 virus on the pulmonary vascular system, manifested by the development of endotheliitis, vasculitis, thrombosis and coagulopathies, one of the leading directions of radiological examination may be the study of microcirculation by SPECT. Purpose. To assess changes in the microvasculature of the lungs of patients who have undergone COVID infection at different times from the onset of the disease. Material and methods. SPECT data were analyzed in 170 patients with previous coronavirus infection from May 2020 to June 2021 of varying severity. The results of SPECT, MSCT, FVD and coagulation hemostasis (D-dimer, fibrinogen) were compared. Results. All patients were found to have changes in microcirculation in the lungs in the postcoid period. The severity of microcirculation disorders had a significant dependence (p

Purpose To report two cases of herpes simplex virus keratitis reactivation following Pfizer-BioNTech COVID-19 (BNT162b2) mRNA vaccination. Methods Two patients (one male, age 42 years, and one female, age 29 years) who are known to have herpetic keratitis presented to our emergency room in a time frame between 4 days and 4 weeks of receiving the vaccine. One patient presented with necrotizing stromal keratitis; the other presented with endotheliitis and epithelial keratitis. PCR for herpes simplex virus (HSV) was obtained from the two patients, and all cases received systemic acyclovir. Results PCR for HSV came positive in both cases. Patients responded well to the provided treatment. Conclusion Ocular herpetic infection may be activated by COVID-19 (BNT162b2) mRNA vaccine. Treating physician should be alert to such associations, and patients should be followed closely. No direct causality has been proven, but further reporting and investigating similar conditions is recommended.

PURPOSE The purpose of this study was to report a case of microsporidial endotheliitis masquerading as graft rejection after deep anterior lamellar keratoplasty (DALK). METHODS A 36-year-old man visited the clinic with complaints of blurred vision, redness, pain, watering, and whitish appearance of the black portion of his left eye. On evaluation, there was diffuse stromal edema with epithelial defect and hypopyon. Microbial keratitis resolved with macular grade scar. He underwent DALK. After 3 years, he presented with complaints of sudden diminution of vision in the same eye for 10 days. His unaided visual acuity was counting finger 1 meter. The clinical findings were circumcorneal congestion, diffuse graft edema, Descemet membrane folds, and diffuse keratic precipitates. A presumptive diagnosis of left eye graft rejection was made. Topical steroids were administered. There was significant improvement within a week. However, at 1 month, there was an increase in graft edema after the steroids were tapered. At this point, a diagnosis of endotheliitis of viral origin was made. He was then administered oral antivirals and steroids. There were 2 such waxing and waning episodes of graft edema before the graft failed. Patient underwent penetrating keratoplasty with cataract extraction with intraocular lens implantation. RESULTS The previous donor and host Descemet endothelium complex was sent for histopathology and polymerase chain reaction. Both histology and polymerase chain reaction were positive for microsporidia. CONCLUSIONS Microsporidial endotheliitis may present as graft rejection. There should be a suspicion of microsporidial infection in cases of features mimicking as endothelial rejection after DALK.

The aim of this article is to explain the clinical benefits of the growing knowledge about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition to the lungs, SARS-CoV‑2 can invade multiple cell types in other organs, such as the kidneys and replicate there. Important damaging pathways of the virus, such as vascular endotheliitis, thrombotic events and systemic cytokine release are still incompletely understood. Coronavirus disease 2019 (COVID-19) is a systemic disease that necessitates intensive medical care and in particular, internal medicine involvement and represents a major challenge for all disciplines of internal medicine. Among these, nephrology in particular is involved in the fight against COVID-19 in a variety of ways: urine investigations can provide indications of multiple organ involvement, endotheliitis, microthrombi and microcirculation damage, etc. Experience with low serum albumin levels and antithrombin III activity in nephrotic patients helps to point out the decreasing effects of loop diuretics and heparin to other specialist disciplines. Nephrological knowledge of the complications of hypoalbuminemia and "resistance" to diuretics must lead to an early implementation of renal replacement procedures in order to be able to prevent mechanical ventilation in COVID-19 intensive care patients with increased extracellular lung fluid. The kidneys can be used as a seismograph for severe courses of COVID-19 and nephrological knowledge can be brought to use to optimize the intensive medical care for critically ill patients. Both together have the potential to considerably reduce morbidity and mortality further.

Coronavirus disease 2019 (COVID-19) is a viral illness caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There is worldwide emerging evidence of multisystem involvement including different neurological manifestations in COVID-19 patients. As a result, healthcare systems worldwide are not only experiencing diagnostic but also therapeutic and prognostic challenges with COVID-19-related complications. Cerebral microbleeds and leukoencephalopathy have been described in COVID-19 patients; although the mechanism remains unknown, possibilities include endotheliitis with thrombotic microangiopathy, excessive inflammation, prolonged respiratory failure, and hypoxemia. We describe here the clinical, radiological, and laboratory findings as well as the 90-day outcome of a 72-year-old gentleman who presented with severe SARS-CoV-2 infection, leading to diffuse cerebral microhemorrhages and ischemic infarct causing severe morbidity. He was tested positive for COVID-19 confirmed by reverse transcriptase polymerase chain reaction.

The review describes pathogenesis of the disease caused by the new SARS-CoV-2 virus. It infects the human cells by linking angiotensin-converting enzyme-2 (ACE2) and a number of other receptors. The virus imbalances the renin-angiotensin system, results to vasoconstriction and acts like pro-inflammatory agent. ACE2 is exposed on the alveolar epithelium cell surface. It is the main gates for virus entering and damaging of the respiratory system resulted in an acute respiratory distress syndrome. The injuring of the pulmonary vessel endothelium is the most important part of the COVID-19 pathogenesis. ACE2 of the endothelial and smooth muscle cell surface upon the SARS-CoV-2 infection facilitates the injury of cardiovascular system. The development of endotheliitis induced by «cytokine storm» leads to the main signs of the disease and the multiple disorder of the microcirculation. The investigation of that condition has a prognostic value and determines the treatment especially in critically ill patients. Systemic endothelial dysfunction upon the COVID-19 largely triggers the hemostasis disorders. High activity of platelets adhesion and aggregation, blood coagulation in died COVID-19 patients, disorder of fibrinolysis system functional activity could be induced by the endothelium activation. The unchanged anticoagulation blood activity in the COVID-19 patients distinguishes them from the patients with disseminated intravascular coagulation. Monitoring of the hemostasis system in COVID-19 is important for the disease severity assess and its prognosis, for justin-time correction of detected deviations.