Septic cavernous sinus thrombosis in a patient with COVID-19.

The cavernous sinus is one of the dural venous sinuses which plays an important role in venous outflow from the brain and eye sockets and in the regulation of intracranial circulation. We report a case of septic cavernous sinus thrombosis in a female patient with COVID-19. The disease often results in alterations of blood rheology, thrombosis in different organs, and septic complications. This article aims to raise awareness of healthcare professionals about the characteristics of COVID-19 that might cause septic cavernous sinus thrombosis in patients with severe comorbidities. Laboratory testing revealed severe comorbidities, including diabetes mellitus and liver cirrhosis caused by hepatitis C. They manifested with an impaired protein production in the liver and coagulation disorders. Systemic effects of SARS-CoV-2 on the vascular endothelium aggravated preexisting coagulation disorders and led to hemorrhage into retrobulbar tissue and clinical signs of septic cavernous sinus thrombosis, including swelling of the eyelids, bilateral exophthalmos, and ophthalmoplegia, followed by necrosis of the facial skin.Copyright © 2022, Dynasty Publishing House. All rights reserved.

Septic cavernous sinus thrombosis in a patient with COVID-19.

The cavernous sinus is one of the dural venous sinuses which plays an important role in venous outflow from the brain and eye sockets and in the regulation of intracranial circulation. We report a case of septic cavernous sinus thrombosis in a female patient with COVID-19. The disease often results in alterations of blood rheology, thrombosis in different organs, and septic complications. This article aims to raise awareness of healthcare professionals about the characteristics of COVID-19 that might cause septic cavernous sinus thrombosis in patients with severe comorbidities. Laboratory testing revealed severe comorbidities, including diabetes mellitus and liver cirrhosis caused by hepatitis C. They manifested with an impaired protein production in the liver and coagulation disorders. Systemic effects of SARS-CoV-2 on the vascular endothelium aggravated preexisting coagulation disorders and led to hemorrhage into retrobulbar tissue and clinical signs of septic cavernous sinus thrombosis, including swelling of the eyelids, bilateral exophthalmos, and ophthalmoplegia, followed by necrosis of the facial skin.Copyright © 2022, Dynasty Publishing House. All rights reserved.

Viral enteritis in cattle: To well known viruses and beyond

Livestock products supply about 13 percent of energy and 28 percent of protein in diets consumed worldwide. Diarrhea is a leading cause of sickness and death of beef and dairy calves in their first month of life and also affecting adult cattle, resulting in large economic losses and a negative impact on animal welfare. Despite the usual multifactorial origin, viruses are generally involved, being among the most important causes of diarrhea. There are several viruses that have been confirmed as etiological agents (i.e., rotavirus and coronavirus), and some viruses that are not yet confirmed as etiological agents. This review summarizes the viruses that have been detected in the enteric tract of cattle and tries to deepen and gather knowledge about them.Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Clinical Evidence and Therapeutic Treatments at the Time of the Coronaviruses Responsible for SARS: A Perspective and Points of view with a Focus on Vascular Endothelium

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 pathogene-sis of severe cases. Starting from the clinical data already known for almost twenty years on the be-havior 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 patholo-gy;iii) the common element of endotheliitis in a subgroup of the population characterized by harm-ful 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 predis-position to the development of a severe evolution of this ailment rather than to give a simple antiviral therapy together with symptomatic drugs.Copyright © 2021 Bentham Science Publishers.

Protective effects of GHRH antagonists against hydrogen peroxide-induced lung endothelial barrier disruption.

PURPOSE: Growth hormone-releasing hormone (GHRH) is a hypothalamic hormone, which regulates growth hormone release from the anterior pituitary gland. GHRH antagonists (GHRHAnt) are anticancer agents, which also exert robust anti-inflammatory activities in malignancies. GHRHAnt exhibit anti-oxidative and anti-inflammatory effects in vascular endothelial cells, indicating their potential use against disorders related to barrier dysfunction (e.g. sepsis). Herein, we aim to investigate the effects of GHRHAnt against lung endothelial hyperpermeability. METHODS: The in vitro effects of GHRHAnt in H2O2-induced endothelial barrier dysfunction were investigated in bovine pulmonary artery endothelial cells (BPAEC). Electric cell-substrate impedance sensing (ECIS) was utilized to measure transendothelial resistance, an indicator of barrier function. RESULTS: Our results demonstrate that GHRHAnt protect against H2O2-induced endothelial barrier disruption via P53 and cofilin modulation. Both proteins are crucial modulators of vascular integrity. Moreover, GHRHAnt prevent H2O2 - induced decrease in transendothelial resistance. CONCLUSIONS: GHRHAnt represent a promising therapeutic intervention towards diseases related to lung endothelial hyperpermeability, such as acute respiratory distress syndrome - related or not to COVID-19 - and sepsis. Targeted medicine for those potentially lethal disorders does not exist.

NEUTROPHIL AND MONOCYTE EXTRACELLULAR TRAPS IN THE DIAGNOSIS OF POST-COVID SYNDROME

Post-COVID syndrome (long covid, post COVID-19 condition) is characterized by cognitive and mental disorders, chest and joint pain, impaired sense of smell and taste, as well as by gastrointestinal and cardiac disorders. The diagnosis of post-COVID syndrome is based mainly on the patients' complaints. To date, no optimal diagnostic method has been proposed. The study was aimed to compare the informative value of the indicators obtained during conventional assessment of patients with post-COVID syndrome and the blood levels of neutrophil (NETs) and monocyte (METs) extracellular traps. The study involved neutropils and monocytes collected from 21 patients with post-COVID syndrome aged 18-59. Fluorescence microscopy and the SYBR Green (Evrogen) fluorescent dye for double-stranded DNA were used for enumeration and imaging of extracellular traps. Clinical and laboratory indicators make it impossible to identify the changes specific for post-COVID syndrome. At the same time, post-COVID syndrome is characterized by inflammation in the vascular endothelium. The filamentous forms of NETs found in blood are a laboratory feature of such aseptic inflammation. The filamentous forms of NETs have been detected only in those patients who have a history of mild to severe СOVID-19, while the filamentous forms of METs have been found in patients having a history of severe infection. The findings show that the detection of the filamentous forms of NETs and METs in blood is the most informative diagnostic feature of post-COVID syndrome.

SARS Cov-2 infection in a pregnant patient with Fabry's disease type I

Aqui va el texto que falta: Fabry's disease (EF) [OMIM 301500] is a lysosomal deposit disease, linked to an X chromosome, caused by the deficiency of the α-galactosidase enzyme (α gal), which generates the progressive accumulation of globotriaosylceramide (GB3)(2) mainly in vascular endothelium, producing endotheliopathy with important systemic manifestations(3). The factors for critical disease by SARSCov-2, identified in the general population, overlap with symptoms seen in adult patients with EF. Objective: Report the case of a patient with EF type I who presented infection by the SARSCov-2 virus during the third pregnancy quarter. Results: Pregnancy evolved at term without complications;the resolution was segmental cesarean section due to dilatation dystocia, obtaining a single male product in good general conditions, without exacerbation of the symptoms of the EF;The bimonthly trend scheme was maintained with home infusion Agalsidase B. Conclusion: Pregnancy can evolve without complications in patients with EF;that enzymatic replacement therapy is safe during it, and despite the vulnerability of EF patients, SARS COV-2 infection can evolve in a benign way.

The influence of rhinovirus infections and SARS-CoV-2 on the release of factors related to angiogenesis and blood coagulation in the respiratory tract

Angiogenesis is a process of forming new vessels form existing ones. There are known numerous of pro-angiogenic and anti-angiogenic factors and the proportion between their expression determines the enhancement or inhibition of angiogenesis. Coagulation cascade is physiologically activated as a result of trauma or tissue disruption, but pathological prothrombotic processes are also caused by inflamma-tion. It is postulated that viral infections exert a post-thrombotic effect and may increase angiogenesis. This article summarizes reports on the influence of respiratory viruses on angiogenesis and coagulation using the example of HRV and SARS-CoV-2.

The effect of Bacillus Calmette-Guerin vaccine sonicates on coronavirus 229E infection of human pulmonary endothelium and development of the inflammatory response

It is postulated that vaccination against tuberculosis with Bacillus Cal-mette-Gue'rin (BCG) vaccine may translate into lower incidence of respiratory tract infections by modulating the release of pro-inflammatory cytokines by innate immune cells. This modulation may be due to epigenetic changes in these cells resulting in an increase in the production of pro-inflammatory cytokines such as IL-1 beta, IL-6 or TNF-alpha. It is not known whether the pulmonary vascular endothelium equip-ped with molecular pattern recognition receptors (PRRs) and with en-try receptors for human coronaviruses can be infected by them, or whether BCG vaccination may modulate its susceptibility to infection with these viruses. This study analyzes the effect of the HCoV 229E human coronavirus on human pulmonary vascular endothelium. Mo-reover, the influence of BCG sonicates on susceptibility to HCoV 229E endothelial infection and the generation of antiviral and inflammatory responses was assessed.

Alterations in heparan sulfate proteoglycan synthesis and sulfation and the impact on vascular endothelial function.

The glycocalyx attached to the apical surface of vascular endothelial cells is a rich network of proteoglycans, glycosaminoglycans, and glycoproteins with instrumental roles in vascular homeostasis. Given their molecular complexity and ability to interact with the intra- and extracellular environment, heparan sulfate proteoglycans uniquely contribute to the glycocalyx's role in regulating endothelial permeability, mechanosignaling, and ligand recognition by cognate cell surface receptors. Much attention has recently been devoted to the enzymatic shedding of heparan sulfate proteoglycans from the endothelial glycocalyx and its impact on vascular function. However, other molecular modifications to heparan sulfate proteoglycans are possible and may have equal or complementary clinical significance. In this narrative review, we focus on putative mechanisms driving non-proteolytic changes in heparan sulfate proteoglycan expression and alterations in the sulfation of heparan sulfate side chains within the endothelial glycocalyx. We then discuss how these specific changes to the endothelial glycocalyx impact endothelial cell function and highlight therapeutic strategies to target or potentially reverse these pathologic changes.

Clinical, morphological and molecular biological examination of the myocardium in COVID-19 patients

The presence of coronavirus-associated myocarditis remains controversial despite elevations in cardiac troponin and natriuretic peptide in many patients. Aim. To assess the morphological changes in the myocardium of patients who died due to coronavirus disease 2019 (COVID-19) and compare them with the intravital level of cardiac biomarkers. Material and methods. A total of 420 hospital charts and 77 autopsies of those who died from COVID-19 were analyzed. In 15 of 77 cases (19%) with histologically suspected myocarditis, an immunohistochemical examination of the myocardium with antibodies to CD3, CD45, CD8, CD68, CD34, Ang1, VWF, VEGF, HLA-DR, MHC1, C1q, VP1 of enteroviruses was performed, and in 8 patients with immunohistochemically confirmed myocarditis (10%) — polymerase chain reaction for SARS-CoV-2. Results. Hemorrhage, intramural thrombosis, necrosis of non-coronary origin, myocardial infarction and lymphocytic myocarditis were detected in 43%, 10%, 17%, 19% and 10% of cases, respectively, without coronavirus N and E gene sequences in the myocardium. Dysplasia, hyperplasia and hypertrophy of the vascular endothelium, expression of Ang1, VWF, VEGF, MHC1, C1q, VP1 of enteroviruses were determined in 100, 100, 87, 100, 75 and 62% of cases of myocarditis, respectively. There were no significant correlations between inflammatory biomarkers and myo-carditis. Conclusion. The main morphological manifestation of COVID-19 in the myo-cardium is the so-called endotheliitis with dysplasia and endothelial activation, leading to hemorrhages, intramural thrombosis and necrosis. There is no con-vincing evidence of a direct involvement of coronavirus in myocarditis induction.

The Vascular Endothelium and Coagulation: Homeostasis, Disease, and Treatment, with a Focus on the Von Willebrand Factor and Factors VIII and V.

The vascular endothelium has several important functions, including hemostasis. The homeostasis of hemostasis is based on a fine balance between procoagulant and anticoagulant proteins and between fibrinolytic and antifibrinolytic ones. Coagulopathies are characterized by a mutation-induced alteration of the function of certain coagulation factors or by a disturbed balance between the mechanisms responsible for regulating coagulation. Homeostatic therapies consist in replacement and nonreplacement treatments or in the administration of antifibrinolytic agents. Rebalancing products reestablish hemostasis by inhibiting natural anticoagulant pathways. These agents include monoclonal antibodies, such as concizumab and marstacimab, which target the tissue factor pathway inhibitor; interfering RNA therapies, such as fitusiran, which targets antithrombin III; and protease inhibitors, such as serpinPC, which targets active protein C. In cases of thrombophilia (deficiency of protein C, protein S, or factor V Leiden), treatment may consist in direct oral anticoagulants, replacement therapy (plasma or recombinant ADAMTS13) in cases of a congenital deficiency of ADAMTS13, or immunomodulators (prednisone) if the thrombophilia is autoimmune. Monoclonal-antibody-based anti-vWF immunotherapy (caplacizumab) is used in the context of severe thrombophilia, regardless of the cause of the disorder. In cases of disseminated intravascular coagulation, the treatment of choice consists in administration of antifibrinolytics, all-trans-retinoic acid, and recombinant soluble human thrombomodulin.

SPONTANEOUS CECAL PERFORATION IN COVID-19 - AN UNCOMMON MANIFESTATION

BACKGROUND: Gastrointestinal (GI) manifestations are the most frequently reported extrapulmonary symptoms of COVID-19 infection with a prevalence of 10%-50%. Most common ones are nausea, vomiting, diarrhea and abdominal pain. GI perforation especially spontaneous colonic perforations are rare in the disease course. METHODS: We report the case of a patient with COVID-19 infection, who developed cecal perforation while recovering from COVID pneumonia, necessitating emergent surgical treatment, and the current literature was reviewed. CASE PRESENTATION: 65-year-old male presented to the hospital with shortness of breath, myalgias and fever. He was admitted to ICU secondary to acute hypoxemic respiratory failure due to COVID 19 pneumonia. He was treated with steroids, tocilizumab and remdesivir. On day-11, he developed severe abdominal pain with worsening leukocytosis. His CXR showed air under diaphragm and abdominal CT showed large pneumoperitoneum, suggestive of a perforated viscus. He underwent emergent laparotomy and was found to have non-obstructive cecal perforation. A colonic de-tension and right colectomy with ileotransverse anastomosis was performed and he was successfully discharged later. The tissue pathology showed distended colon, active colitis, transmural granulocytic inflammation, micro-abscesses, and ulceration suggestive of bowel perforation. DISCUSSIONS: ACE2 protein, a cell receptor for SARS-CoV-2, has been found in glandular cells of gastrointestinal epithelia. Direct viral infection, small vessel thrombosis, or nonocclusive mesenteric ischemia are some possible explanations for the spectrum of bowel findings. SARS-CoV-2 can have direct inflammatory effect on vascular endothelium too. Use of steroids, tocilizumab and systemic coagulopathy seen in severe COVID-19 infection also contributes to these manifestations. In our patient, an acute over-distension of colon, without mechanical distal obstruction, in the setting of COVID-19 infection & tocilizumab led to cecal perforation. Our literature review confirmed only 33 case-reports or series of bowel perforation (either as presenting symptom or during hospital course) in the setting of COVID-19 infection have been reported, with combined 28.5% mortality rate and 5 studies not reporting the outcome. Considering the worldwide incidence of this pandemic, it is a rare complication. CONCLUSIONS: GI perforation is a rare but dangerous complication of COVID19. Treatment with interleukin- 6 inhibitors or steroids is often associated in most cases. As we are gaining more knowledge about clinical spectrum of this novel disease, we are learning more about its possible rare expression, associations, and complications. Our case underlines the need to be vigilant for severe GI symptoms in setting of COVID-19 infection to enrich our understanding of this pandemic and as a result improve patients' outcome. (Figure Presented)

Characteristic patterns of SARS-CoV-2 on chest CT suggests a hematologic pathway for viral entry into the lung.

Many SARS-CoV-2 studies have supported the theory that the Type II alveolar epithelial cells (AEC-2) are the primary portal of entry of the virus into the lung following its brief nasal occupation. However, the theory of inhalational transmission of the virus from the ciliated and goblet nasal cells to the lung parenchyma is not supported by the imaging findings on chest computerized tomography (CT), leading the authors to consider an alternative pathway from the nose to the lung parenchyma that could explain the peripheral, basilar predominant pattern of early disease. Imaging supports that the pulmonary capillaries may be an important vehicle for transmission of the virus and/or associated inflammatory mediators to the lung epithelium.

PATHOLOGICAL CHANGES IN THE KIDNEYS IN PATIENTS WITH ACUTE RENAL INJURY DUE TO CORONAVIRUS INFECTION

INTRODUCTION AND OBJECTIVE: Acute kidney injury (AKI) in coronavirus infection (COVID-19) caused by the SARS-CoV-2 virus is much more common than previously thought and is associated with severe disease and high mortality. Despite the fact that the respiratory and immune systems are the main targets of the COVID- 19 virus, AKI is also observed, identified by the occurrence of proteinuria or hematuria, an increase in serum urea and creatinine levels. The aim of the study is to assess the pathomorphological changes in the kidneys in 100 cases of autopsy of patients with COVID-19 using light microscopy and immunohistochemical diagnostic methods in order to clarify the possible mechanism of AKI. METHODS: The study was carried out using samples obtained from 100 patients, the time interval of the onset of the disease corresponded to the 4th wave of the peak of the incidence in Russia (from June 2021). The age of patients varied from 37 to 94 years 72 (s =12.5), men - 34, women - 66. Patients with chronic kidney disease, diabetes mellitus and cancer were not included in the analysis. The cause of death in all cases was acute respiratory failure, histologically defined as diffuse alveolar injury. AKI in accordance with the KDIGO criteria was detected in 34 patients. RESULTS: On light microscopy, diffuse massive damage to the proximal tubules with loss of the brush border, degeneration of vacuoles was detected in 46 patients, massive necrosis of the tubules in 11 patients. In 65 patients, an extremely pronounced congestion of paretic dilated vessels with widespread paravasal hemorrhages was revealed. Paravasal lymphoid infiltration of the vascular endothelium was detected in 27 patients. Severe sludge syndrome in small and medium-sized vessels in 46 patients. In almost all cases, hemosiderin granules and hyaline casts were found. The quantitative and qualitative composition of tissue macrophages corresponded to the population data, without visible correlations with the disease. CONCLUSIONS: According to the study, the factors contributing to AKI include systemic hypoxia, abnormal coagulation, increased catabolism due to fever, drug-related rhabdomyolysis or hyperventilation with increased serum degradation products. Thus, our research provides evidence for AKI during the progression of COVID-10. These results contribute to a better understanding of the course and progression of SARS-CoV-2 virus infection.

Interrelationships between polymorphonuclear leukocytes (PMNs) - neutrophils, blood coagulation system and vascular endothelium during Covid-19 infection

Background. Polymorphonuclear leukocytes (PMNs-neutrophils) influence the processes of inflammation and immunity, participating in phagocytosis, cytoplasmic degranulation, NETosis, generation of reactive oxygen species (ROS), receptor-mediated communications with other cells and systems, innate and adaptive immunity, blood coagulation-and circulatory systems, etc. Neutrophils during development of Covid-19 disease. The participation of neutrophils during development, treatment and management of COVID-19 infection is evaluated and largely discussed in the scientific medical literature. The elevated neutrophil-to-lymphocyte ratio (NLR) and dynamic lowering of some routine blood parameters seem to be critical markers of severe COVID-19. Thus, dysregulation of immune system-with special participation of complement, leads to hyperproduction of cytokines and chemokines („cytokine storm”). The resulting pro-adhesive and prothrombotic effects stimulate further adhesion of leukocytes and platelets to the vascular endothelium, causing macro-and microvascular thromboses, capillary plugging and impaired microvascular flow. © 2022, Bulgarska Akademiya na Naukite. All rights reserved.

Automated measurement of coagulation and fibrinolytic activation markers: Outcomes in coronavirus disease 2019 (COVID-19) patients.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) is characterized by marked hypoxaemia and lung oedema, often accompanied by disordered blood coagulation and fibrinolytic systems, endothelial damage and intravascular fibrin deposition. PATIENTS/METHODS: We present a retrospective observational study of 104 patients admitted to hospital with COVID-19. Plasma samples were collected within 72 h of admission. In addition to routine coagulation and haematology testing, soluble thrombomodulin (sTM), thrombin-antithrombin (TAT), tissue plasminogen activator-plasminogen activator inhibitor 1 complex (tPAI-C) and plasmin-α2 antiplasmin complex (PIC) were performed by automated chemiluminescent enzyme immunoassays. RESULTS: Significantly higher levels of D-dimer, TAT, sTM and tPAI-C were observed in non-survivors compared to survivors. To confirm which parameters were independent risk factors for mortality, multiple logistic regression was performed on D-dimer, TAT. sTM, tPAI-C and PIC data. Only increasing sTM was significantly associated with mortality, with an odds ratio of 1.065 for each 1.0 TU/mL increment (95% CI 1.025-1.115). CONCLUSIONS: Of the haemostatic variables measured, sTM, which can be rapidly assayed, is the best independent predictor of mortality in patients hospitalized with COVID-19, and this suggests that endothelial dysfunction plays an important role in disease progression.

Anti-COVID-19 potential of Azadirachta indica (Neem) leaf extract.

COVID-19 is caused by infection with the "severe acute respiratory syndrome coronavirus-2″ (i.e., SARS-CoV-2). This is an enveloped virus having a positive sense, single-stranded RNA genome; like the two earlier viruses SARS-CoV and the Middle East respiratory syndrome (MERS) virus. COVID-19 is unique in that, in the severe case, it has the propensity to affect multiple organs, leading to multiple organ distress syndrome (MODS), and causing high morbidity and mortality in the extreme case. In addition, comorbidities like age, cardiovascular disease, diabetes and its complications, obesity, are risk factors for severe COVID-19. It turns out that a most plausible, simple, single explanation for this propensity for MODS is the pivotal involvement of the vascular endothelium (VE). This is a consequence of the fact that the VE seamlessly connects all the entire vascular bed in the body, thus linking all the target organs (heart, lungs, kidney, liver, brain) and systems. Infection with SARS-CoV-2 leads to hyper-inflammation yielding uncontrolled production of a mixture of cytokines, chemokines, reactive oxygen species, nitric oxide, oxidative stress, acute phase proteins (e.g., C-reactive protein), and other pro-inflammatory substances. In the extreme case, a cytokine storm is created. Displacement of the virus bound to the VE, and/or inhibition of binding of the virus, would constitute an effective strategy for preventing COVID-19. In this regard, the acetone-water extract of the leaf of the Neem (Azadirachta indica) plant has been known to prevent the adherence of malaria parasitized red blood cells (pRBCs) to VE; prevent cytoadherence of cancer cells in metastasis; and prevent HIV from invading target T lymphocytes. We therefore hypothesize that this Neem leaf acetone-water extract will prevent the binding of SARS-CoV-2 to the VE, and therefore be an effective therapeutic formulation against COVID-19. It is therefore advocated herein that this extract be investigated through rigorous clinical trials for this purpose. It has the advantages of being (i) readily available, and renewable in favor of the populations positioned to benefit from it; (ii) simple to prepare; and (iii) devoid of any detectable toxicity.