Angiotensin-converting enzyme 2 (ACE2) in COVID-19 and other diseases.

The coronavirus SARS-CoV-2 was detected in isolates of pneumonia patients in January 2020. The virus cannot multiply extracellularly but requires access to the cells of a host organism. SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as a receptor, to which it docks with its spikes. ACE2 belongs to the renin angiotensin system (RAS), whose inhibitors have been used for years against high blood pressure. Renin is an endopeptidase that is predominantly formed in the juxtaglomerular apparatus of the kidney and cleaves the decapeptide angiotensin I (Ang I) from angiotensinogen. Through the angiotensin-converting enzyme (ACE), another 2 C-terminal amino acids are removed from Ang I, so that finally the active octapeptide angiotensin II (Ang II) is formed. The biological effect of Ang II via the angiotensin II receptor subtype 1 (AT1-R) consists of vasoconstriction, fibrosis, proliferation, inflammation, and thrombosis formation. ACE2 is a peptidase that is a homolog of ACE. ACE2 is predominantly expressed by pulmonary alveolar epithelial cells in humans and has been detected in arterial and venous endothelial cells. In contrast to the dicarboxy-peptidase ACE, ACE2 is a monocarboxypeptidase that cleaves only one amino acid from the C-terminal end of the peptides. ACE2 can hydrolyze the nonapeptide Ang-(1-9) from the decapeptide Ang I and the heptapeptide Ang-(1-7) from the octapeptide Ang II. Ang-(1-7) acts predominantly antagonistically (vasodilatory, anti-fibrotic, anti-proliferative, anti-inflammatory, anti-thrombogenetically) via the G protein-coupled Mas receptor to the AT1-R-mediated effects of Ang II. In the pathogenesis of COVID-19 infection, it is therefore assumed that there is an imbalance due to overstimulation of the AT1 receptor in conjunction with a weakening of the biological effects of the Mas receptor.Copyright © 2022 Dustri-Verlag Dr. K. Feistle.

Uncovering the interplay between hypertension and the inflammatory response for the patient affected by COVID-19 via mathematical modeling and computer-based analysis

We explore here the systems-based regulatory mechanisms that determine human blood pressure patterns. This in the context of the reported negative association between hypertension and COVID-19 disease. We are particularly interested in the key role that plays angiotensin converting enzyme 2 (ACE2), one of the first identified receptors that enable the entry of the SARS-CoV-2 virus into a cell. Taking into account the two main systems involved in the regulation of blood pressure, that is, the Renin-Angiotensin system and the Kallikrein-Kinin system, we follow a Bottom-Up systems biology modeling approach in order to built the discrete Boolean model of the gene regulatory network that underlies both the typical hypertensive phenotype and the hypotensive/normotensive phenotype. These phenotypes correspond to the dynamic attractors of the regulatory network modeled on the basis of publicly available experimental information. Our model recovers the observed phenotypes and shows the key role played by the inflammatory response in the emergence of hypertension. Source code go to the next url: https://github.com/cxro-cc/red_ras_kks © 2023, EasyChair. All rights reserved.

Alzheimer's disease and COVID-19.

In elderly patients with COVID-19 cognitive functions decline;it has been suggested that SARS-CoV-2 infection may lead to the development of Alzheimer's disease (AD) and other long-term neurological consequences. We review several parallels between AD and COVID-19 in terms of pathogenetic mechanisms and risk factors. Possible mechanisms through which COVID-19 can initiate AD are discussed. These include systemic inflammation, hyperactivation of the renin-angiotensin system, innate immune activation, oxidative stress, and direct viral damage. It has been shown that increased expression of angiotensin-renin receptors (ACE2) may be a risk factor for COVID-19 in patients with AD. When entering the central nervous system, the SARS-CoV-2 virus can directly activate glial cell-mediated immune responses, which in turn can lead to the accumulation of beta-amyloid and the subsequent onset or progression of current AD. The involvement of inflammatory biomarkers, including interleukins (IL): IL6, IL1, as well as galectin-3, as a link between COVID-19 and AD is discussed. The rationale for the use of memantine (akatinol memantine) in patients with COVID-19 in order to prevent the development of cognitive deficits is discussed. Memantine has been shown to have a positive effect on neuroinflammatory processes in the onset or exacerbation of cognitive deficits, in reducing cerebral vasospasm and endothelial dysfunction in viral infections. Memantine therapy may improve everyday activity and reduce the risk of severe SARS-CoV-2 infection.Copyright © 2022 Ima-Press Publishing House. All rights reserved.

ASSOCIATIONS OF POLYMORPHISMS OF THE ACE AND ACE2 GENES WITH CLINICAL MANIFESTATIONS AND CARDIOVASCULAR COMPLICATIONS OF THE CORONAVIRUS INFECTION

A problem of the novel coronavirus infection pandemic is the absence of specific biomarkers, the determination of which would make it possible to assess the likelihood of a severe disease course, development of complications, immediate and long-term consequences, and effective etiotropic (antiviral) therapy. The severity of the novel coronavirus infection depends on various factors such as the initial state of health, immune status, age, smoking status, concomitant cardiovascular diseases, and diabetes mellitus. However, a severe disease course is also observed in patients without the aforementioned risk factors. The development of the disease and its complications depends on sex and geographical identity. Angiotensin-converting enzyme 2 (ACE2), associated by gene-gene interaction with ACE, plays a main role in the pathogenesis of the penetration of severe acute respiratory syndrome-2 coronavirus into the cell. The main body of information on this problem is represented by systematic meta-analyses and results of single-center cohort studies, which offer insufficient information to unequivocally assert the associations of ACE and ACE2 gene polymorphisms with pathological changes in the circulatory system during and after a new coronavirus infection. Differences in the incidence of ACE and ACE2 alleles may explain the differences between susceptible populations and/or response to the severe coronavirus infection. The above studies were carried out on the effect of the coronavirus in the initial period of the pandemic. For a more complete molecular genetic picture of the influence of polymorphism, persons with different strains of the coronavirus must be considered. In addition, no data are available regarding the expressions of ACE and ACE2 genes in response to a coronavirus infection. Moreover, the identification of the polymorphic variants of the genes of the renin–angiotensin–aldosterone system and ACE2 associated with a high risk of developing and worsening cardiovascular diseases may be one of the promising areas for the early diagnosis and prevention of post-COVID-19 changes. Therefore, all scientific interest research is aimed at studying genetic factors, such as single nucleotide polymorphisms that affect susceptibility to infection, severity of the disease course, and development of circulatory system consequences. In general, polymorphic variants of ACE and ACE2 and their interaction will help us understand this problem and systematize knowledge for further research in this area. All rights reserved © Eco-Vector, 2022.

Role of Angiotensin II in Cardiovascular Diseases: Introducing Bisartans as a Novel Therapy for Coronavirus 2019.

Cardiovascular diseases (CVDs) are the main contributors to global morbidity and mortality. Major pathogenic phenotypes of CVDs include the development of endothelial dysfunction, oxidative stress, and hyper-inflammatory responses. These phenotypes have been found to overlap with the pathophysiological complications of coronavirus disease 2019 (COVID-19). CVDs have been identified as major risk factors for severe and fatal COVID-19 states. The renin-angiotensin system (RAS) is an important regulatory system in cardiovascular homeostasis. However, its dysregulation is observed in CVDs, where upregulation of angiotensin type 1 receptor (AT1R) signaling via angiotensin II (AngII) leads to the AngII-dependent pathogenic development of CVDs. Additionally, the interaction between the spike protein of severe acute respiratory syndrome coronavirus 2 with angiotensin-converting enzyme 2 leads to the downregulation of the latter, resulting in the dysregulation of the RAS. This dysregulation favors AngII/AT1R toxic signaling pathways, providing a mechanical link between cardiovascular pathology and COVID-19. Therefore, inhibiting AngII/AT1R signaling through angiotensin receptor blockers (ARBs) has been indicated as a promising therapeutic approach to the treatment of COVID-19. Herein, we review the role of AngII in CVDs and its upregulation in COVID-19. We also provide a future direction for the potential implication of a novel class of ARBs called bisartans, which are speculated to contain multifunctional targeting towards COVID-19.

Respiratory issues in patients with multiple sclerosis as a risk factor during SARS-CoV-2 infection: a potential role for exercise.

Coronavirus disease-2019 (COVID-19) is associated with cytokine storm and is characterized by acute respiratory distress syndrome (ARDS) and pneumonia problems. The respiratory system is a place of inappropriate activation of the immune system in people with multiple sclerosis (MS), and this may cause damage to the lung and worsen both MS and infections.The concerns for patients with multiple sclerosis are because of an enhance risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The MS patients pose challenges in this pandemic situation, because of the regulatory defect of autoreactivity of the immune system and neurological and respiratory tract symptoms. In this review, we first indicate respiratory issues associated with both diseases. Then, the main mechanisms inducing lung damages and also impairing the respiratory muscles in individuals with both diseases is discussed. At the end, the leading role of physical exercise on mitigating respiratory issues inducing mechanisms is meticulously evaluated.

Molecular Mimicry of the Viral Spike in the SARS-CoV-2 Vaccine Possibly Triggers Transient Dysregulation of ACE2, Leading to Vascular and Coagulation Dysfunction Similar to SARS-CoV-2 Infection.

The benefits of SARS-CoV-2 spike mRNA vaccines are well known, including a significant decline in COVID-19 morbidity and a decrease in the mortality rate of SARS-CoV-2 infected persons. However, pharmacovigilance studies have revealed the existence of rare cases of cardiovascular complications after mass vaccination using such formulations. Cases of high blood pressure have also been reported but were rarely documented under perfectly controlled medical supervision. The press release of these warning signals triggered a huge debate over COVID-19 vaccines' safety. Thereby, our attention was quickly focused on issues involving the risk of myocarditis, acute coronary syndrome, hypertension and thrombosis. Rare cases of undesirable post-vaccine pathophysiological phenomena should question us, especially when they occur in young subjects. They are more likely to occur with inappropriate use of mRNA vaccine (e.g., at the time when the immune response is already very active during a low-noise infection in the process of healing), leading to angiotensin II (Ang II) induced inflammation triggering tissue damage. Such harmful effects observed after the COVID-19 vaccine evoke a possible molecular mimicry of the viral spike transiently dysregulating angiotensin converting enzyme 2 (ACE2) function. Although the benefit/risk ratio of SARS-CoV-2 spike mRNA vaccine is very favorable, it seems reasonable to suggest medical surveillance to patients with a history of cardiovascular diseases who receive the COVID-19 vaccine.

Nanoparticle approaches for the renin-angiotensin system

The renin-angiotensin system (RAS) is a hormonal cascade that contributes to several disorders: systemic hypertension, heart failure, kidney disease, and neurodegenerative disease. Activation of the RAS can promote inflammation and fibrosis. Drugs that target the RAS can be classified into 3 categories, AT1 receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, and renin inhibitors. The therapeutic efficacy of current RAS-inhibiting drugs is limited by poor penetration across the blood-brain barrier, low bioavailability, and to some extent, short half-lives. Nanoparticle-mediated drug delivery systems (DDSs) are possible emerging alternatives to overcome such limitations. Nanoparticles are ideally 1–100 nm in size and are considered efficient DDSs mainly due to their unique characteristics, including water dispersity, prolonged half-life in blood circulation, smaller size, and biocompatibility. Nano-scale DDSs can reduce the drug dosage frequency and acute toxicity of drugs while enhancing therapeutic success. Different types of nanoparticles, such as chitosan, polymeric, and nanofibers, have been examined in RAS-related studies, especially in hypertension, cardiovascular disease, and COVID-19. In this review article, we summarize the physical and chemical characteristics of each nanoparticle to elaborate on their potential use in RAS-related nano-drug delivery research and clinical application.

Alzheimer's disease and COVID-19

In elderly patients with COVID-19 cognitive functions decline;it has been suggested that SARS-CoV-2 infection may lead to the development of Alzheimer's disease (AD) and other long-term neurological consequences. We review several parallels between AD and COVID-19 in terms of pathogenetic mechanisms and risk factors. Possible mechanisms through which COVID-19 can initiate AD are discussed. These include systemic inflammation, hyperactivation of the renin-angiotensin system, innate immune activation, oxidative stress, and direct viral damage. It has been shown that increased expression of angiotensin-renin receptors (ACE2) may be a risk factor for COVID-19 in patients with AD. When entering the central nervous system, the SARS-CoV-2 virus can directly activate glial cell-mediated immune responses, which in turn can lead to the accumulation of beta-amyloid and the subsequent onset or progression of current AD. The involvement of inflammatory biomarkers, including interleukins (IL): IL6, IL1, as well as galectin-3, as a link between COVID-19 and AD is discussed. The rationale for the use of memantine (akatinol memantine) in patients with COVID-19 in order to prevent the development of cognitive deficits is discussed. Memantine has been shown to have a positive effect on neuroinflammatory processes in the onset or exacerbation of cognitive deficits, in reducing cerebral vasospasm and endothelial dysfunction in viral infections. Memantine therapy may improve everyday activity and reduce the risk of severe SARS-CoV-2 infection.Copyright © 2022 Ima-Press Publishing House. All rights reserved.

Blood Pressure, Proteases and Inhibitors

Blood pressure is controlled through a complex network of interacting peptide systems, principally involving the angiotensin, natriuretic peptide, endothelin and apelin families. The most complex and thoroughly investigated is the renin-angiotensin system (RAS) in which selective and potent inhibitors of the key biosynthetic proteolytic enzymes, renin and angiotensin-converting enzyme (ACE), have proved to be valuable drugs for the effective treatment of hypertension and heart failure, as well as other cardiovascular and renal disorders. Some of the other proteases in these pathways, e.g.neprilysin and ACE2, are also being explored as potential drug targets. © 2023 Elsevier Inc. All rights reserved.

The des-Arg9-bradykinin/B1R axis: Hepatic damage in COVID-19.

Patients infected by the SARS-CoV-2 virus are commonly diagnosed with threatening liver conditions associated with drug-induced therapies and systemic viral action. RNA-Seq data from cells in bronchoalveolar lavage fluid from COVID-19 patients have pointed out dysregulation of kallikrein-kinin and renin-angiotensin systems as a possible mechanism that triggers multi-organ damage away from the leading site of virus infection. Therefore, we measured the plasma concentration of biologically active peptides from the kallikrein-kinin system, bradykinin and des-Arg9-bradykinin, and liver expression of its proinflammatory axis, bradykinin 1 receptor (B1R). We measured the plasma concentration of bradykinin and des-Arg9-bradykinin of 20 virologically confirmed COVID-19 patients using a liquid chromatography-tandem mass spectrometry-based methodology. The expression of B1R was evaluated by immunohistochemistry from post-mortem liver specimens of 27 COVID-19 individuals. We found a significantly higher blood level of des-Arg9-bradykinin and a lower bradykinin concentration in patients with COVID-19 compared to a healthy, uninfected control group. We also observed increased B1R expression levels in hepatic tissues of patients with COVID-19 under all hepatic injuries analyzed (liver congestion, portal vein dilation, steatosis, and ischemic necrosis). Our data indicate that des-Arg9-bradykinin/B1R is associated with the acute hepatic dysfunction induced by the SARS-CoV-2 virus infection in the pathogenesis of COVID-19.

ACE and ACE2 catalytic activity in the fecal content along the gut.

BACKGROUND: Angiotensin-converting enzyme (ACE) and ACE2 are two major enzymes of the renin-angiotensin-aldosterone system (RAAS), which control the formation/degradation of angiotensin (Ang) II and Ang1-7, regulating their opposite effects. We aimed at evaluating the catalytic activity of ACE and ACE2 in the intestinal content and corresponding intestinal tissue along the gut of Wistar Han rats. METHODS: Portions of the ileum, cecum, proximal colon, and distal colon, and the corresponding intestinal content were collected from Wistar Han rats. Enzyme activity was evaluated by fluorometric assays using different substrates: Hippuryl-His-Leu for ACE-C-domain, Z-Phe-His-Leu for ACE-N-domain, and Mca-APK(Dnp) for ACE2. ACE and ACE2 concentration was assessed by ELISA. Ratios concerning concentrations and activities were calculated to evaluate the balance of the RAAS. Statistical analysis was performed using Friedman test followed by Dunn's multiple comparisons test or Wilcoxon matched-pairs test whenever needed. KEY RESULTS: ACE and ACE2 are catalytically active in the intestinal content along the rat gut. The ACE N-domain shows higher activity than the C-domain both in the intestinal content and in the intestinal tissue. ACE and ACE2 are globally more active in the intestinal content than in the corresponding intestinal tissue. There was a distal-to-proximal prevalence of ACE2 over ACE in the intestinal tissue. CONCLUSIONS & INFERENCES: This work is the first to report the presence of catalytically active ACE and ACE2 in the rat intestinal content, supporting future research on the regulatory role of the intestinal RAAS on gut function and a putative link to the microbiome.

Circulating ACE2 level and zinc/albumin ratio as potential biomarkers for a precision medicine approach to COVID-19.

Highly mutable influenza is successfully countered based on individual susceptibility and similar precision-like medicine approach should be effective against SARS-COV-2. Among predictive markers to bring precision medicine to COVID-19, circulating ACE2 has potential features being upregulated in both severe COVID-19 and predisposing comorbidities. Spike SARS-CoVs were shown to induce ADAM17-mediated shedding of enzymatic active ACE2, thus accounting for its increased activity that has also been suggested to induce positive feedback loops leading to COVID-19-like manifestations. For this reason, pre-existing ACE2 activity and inhibition of ACE2/ADAM17 zinc-metalloproteases through zinc chelating agents have been proposed to predict COVID-19 outcome before infection and to protect from COVID-19, respectively. Since most diagnostic laboratories are not equipped for enzymatic activity determination, other potential predictive markers of disease progression exploitable by diagnostic laboratories were explored. Concentrations of circulating albumin, zinc, ACE2 protein and its activity were investigated in healthy, diabetic (COVID-19-susceptible) and SARS-CoV-2-negative COVID-19 individuals. ACE2 both protein levels and activity significantly increased in COVID-19 and diabetic patients. Abnormal high levels of ACE2 characterised a subgroup (16-19%) of diabetics, while COVID-19 patients were characterised by significantly higher zinc/albumin ratios, pointing to a relative increase of albumin-unbound zinc species, such as free zinc ones. Data on circulating ACE2 levels are in line with the hypothesis that they can drive susceptibility to COVID-19 and elevated zinc/albumin ratios support the therapeutic use of zinc chelating inhibitors of ACE2/ADAM17 zinc-metalloproteases in a targeted therapy for COVID-19.

Research progress of angiotensin-converting enzyme-2 in septic acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is a common clinical syndrome in intensive care unit. Sepsis is a clinical syndrome, which is with life-threatening organ function damage caused by infection. As an important part of local microcirculation, the structure of alveolar-capillary membrane is easily damaged in the course of sepsis. So sepsis is the most prime and important inducing factor of ARDS, and it has higher mortality and fatality. As an important constitution of renin-angiotensin system (RAS), angiotensin-converting enzyme-2 (ACE-2) has the function of protecting endothelium and regulating the expression of inflammatory factors, so it has received additional attention in recent years. Through the intervention of ACE-2, ARDS and the severity of COVID- 19 can be affected to a certain extent, so the role of ACE-2 in septic ARDS is worth discussing. This paper summarizes the biological characteristics and main mechanism of ACE-2, discusses the possible role of ACE-2 in septic ARDS, and finally explores the significance of ACE-2 in the evaluation and treatment of septic ARDS, in order to provide reference and inspiration for clinical treatment of sepsis-related ARDS.

Ras and Sars-Cov-2 Interaction: Short Review of the Latest Evidence

Coronavirus SARS-CoV-2 is responsible for the coronavirus disease (COVID-19) cause of the recent global pandemic, which is causing thousands of deaths worldwide and represents a health challenge with few precedents in human history. The angiotensin 2 conversion enzyme (ACE-2) has been identified as the receptor that facilitates access to SARSCoV-2 in cells;evidence shows that its concentration varies during the various stages of viral infection. Therapeutic agents modifying the renin-angiotensin system (RAS) may be able to modulate the concentration of ACE-2 and the various components of the system. In this article we examine the latest evidence on the association between the use of RAS modifying agents and coronavirus 2019 (COVID-19) disease caused by SARS-CoV-2. Our investigation and critical literature research does not suggest discontinuation of ACEIs/ARBs treatment in clinical practice as there is a lack of robust evidence. However, we recommend further well-structured epidemiological studies investigating this sensitive issue that may provide important new suggestions for implementing guidelines.Copyright © Vitiello A., Ferrara F., 2023.

Hiv and Chronic Comorbidities: Medication Adherence and Clinical Endpoint Covariation

Background: Evidence suggests negative monthly medication adherence trends during the COVID-19 era for patients with HIV (PWH) and multiple chronic conditions. However, it is unknown whether observed trends are associated with changes in outcomes of HIV care before and during the COVID-19 era. Method(s): Adult PWH with type 2 diabetes, hypertension, and/or hypercholesterolemia were identified in a US mid-Atlantic integrated health system. Multivariable population-averaged panel general estimating equations were used to assess the relationship between medication adherence [i.e., accepted dichotomous thresholds for optimal proportion of days covered (PDC)] for four medication groups: antiretrovirals [ART], diabetes medications [DMs], renin-angiotensin antagonists [RASMs], and statins [SMs] and their related clinical endpoints [i.e., viral load (VL;copies/mL), HbA1c, systolic and diastolic blood pressure (SBP, DBP;mmHg), and total cholesterol (TC;mg/dl)] during a 37-month longitudinal observation period [9/2018-9/2021]. Covariates included demographics, number of medication groups, COVID-19 era (starting 3/1/2020), and a COVID-19/PDC interaction term. Result(s): The cohort [n=543] was predominantly 51-64y [59.30%], Black [73.11%], male [69.24%], and privately insured [65.38%]. All patients were prescribed ART with 75.32% co-prescribed SMs;followed by RASMs [42.73%];and DMs [25.60%]. ART PDC>=0.9 was associated with decreased odds of VL>=200 copies/mL [aOR=0.77, 95% CI: 0.63-0.94]. For DMs, RASMs and SMS, PDC>=0.8 was not associated with the clinical endpoints of HbA1c>=7.0% [aOR=0.99, 95% CI: 0.94-1.04], SBP>=130 mmHg [aOR=1.03;95% CI: 0.93-1.14], DBP>=80 mmHg [aOR=1.05, 95% CI: 0.94-1.16] or TC>=200 mg/dl [aOR=1.00, 95% CI: 0.96-1.04], respectively. The COVID-19 era [3/2020 to 9/2021] was associated with increased odds of SBP>=130 [aOR=1.22, 95% CI: 1.01-1.48], but not for DBP>=80 mmHg [aOR=1.05, 95% CI: 0.85-1.28], VL>=200 copies/ mL [aOR=1.01, 95% CI: 0.67-1.52], HbA1c>=7.0% [aOR=0.99, 95% CI: 0.88-1.11], and TC>=200 mg/dl [aOR=0.95, 95% CI: 0.86-1.04]. No interactions between COVID-19 era and PDC on clinical endpoints were observed. Conclusion(s): ART adherence was associated with viral suppression in PWH, but there were no observed associations between DM, RASM, and SM adherence and their respective clinical endpoints. With the exception of a direct relationship between the COVID-19 start date and SBP, the COVID-19 era was not associated with variations in VL, HbA1c, DBP, and TC clinical endpoints.

Alzheimer's disease and COVID-19.

In elderly patients with COVID-19 cognitive functions decline;it has been suggested that SARS-CoV-2 infection may lead to the development of Alzheimer's disease (AD) and other long-term neurological consequences. We review several parallels between AD and COVID-19 in terms of pathogenetic mechanisms and risk factors. Possible mechanisms through which COVID-19 can initiate AD are discussed. These include systemic inflammation, hyperactivation of the renin-angiotensin system, innate immune activation, oxidative stress, and direct viral damage. It has been shown that increased expression of angiotensin-renin receptors (ACE2) may be a risk factor for COVID-19 in patients with AD. When entering the central nervous system, the SARS-CoV-2 virus can directly activate glial cell-mediated immune responses, which in turn can lead to the accumulation of beta-amyloid and the subsequent onset or progression of current AD. The involvement of inflammatory biomarkers, including interleukins (IL): IL6, IL1, as well as galectin-3, as a link between COVID-19 and AD is discussed. The rationale for the use of memantine (akatinol memantine) in patients with COVID-19 in order to prevent the development of cognitive deficits is discussed. Memantine has been shown to have a positive effect on neuroinflammatory processes in the onset or exacerbation of cognitive deficits, in reducing cerebral vasospasm and endothelial dysfunction in viral infections. Memantine therapy may improve everyday activity and reduce the risk of severe SARS-CoV-2 infection.Copyright © 2022 Ima-Press Publishing House. All rights reserved.

Successful matched unrelated donor hematopoietic stem cell transplantation for infantile Wolman disease

Introduction: Wolman disease is a rare genetic disorder with an autosomal recessive inheritance. A mutation in the LIPA gene causes lysosomal acid lipase (LAL) deficiency results in lipid storage and adrenal insufficiency. Death in early infancy is due to liver failure. Patients and methods: We describe the clinical course of a three-month-old infant diagnosed with Wolman disease. A rapid mutational analysis confirmed a LIPA gene defect. Results: He underwent matched unrelated donor peripheral blood stem cell hematopoietic stem cell transplantation (HSCT) at 3 months of age, with a treosulfan-based conditioning, which resulted in engraftment with donor-derived hematopoietic cells. He required supportive care for sinusoidal obstruction syndrome and mucositis. He was administered low dose prednisolone for grade I skin graft versus host disease, and a complete donor chimerism was documented on several occasions. At one year post HSCT, his growth and development were optimal, and there was no hepatosplenomegaly. He is maintained on glucocorticoid and mineralocorticoid supplements for primary hypoaldosteronism. Conclusion: The case emphasizes the timely diagnosis and the potential for successful treatment of Wolman disease by HSCT. © 2022 Pediatric Hematology Oncology Chapter of Indian Academy of Pediatrics

Cardiovascular risk among patients recovered from COVID-19 in the short and medium term: what does the current evidence conclude?.

Cardiovascular risk and diseases among patients recovered from COVID-19 is a recent field of study in the world medical literature and is also of vital importance because a large number of patients develop complications once the acute phase of the disease is over. The broad spectrum of myocardial injury in cardiovascular diseases can range from the asymptomatic elevation of cardiac troponin levels to the development of fulminant myocarditis and/or circulatory shock, which can leave significant sequelae. Despite the fact that there is no clear strategy to treat cardiac events that occur during COVID-19 infection and taking into account that treatment is mainly aimed at relieving patients' symptoms as they arise, the objective of this work was to find out and collect current evidence on this subject, so that readers can be offered a reference guide in Spanish that contributes to the development of their health profession. The methodology used was a literature search in databases including Medline, Scopus and ScienceDirect within a time window between 2019 and 2022. The main results revealed that the molecular and pathophysiological mechanisms involved in post-COVID-19 syndrome include the renin-angiotensin-aldosterone system since SARS-CoV-2 tropism is linked to angiotensin-converting enzyme 2. This causes an alteration of the neurohumoral response of the cardiovascular, renal and digestive systems, generating deficits in the signaling pathways and causing direct damage to the heart, lungs and other organs. Post-COVID-19 syndrome, in general, is defined as the occurrence or persistence of symptoms three or four weeks after the acute phase of the disease. This could then be considered as a time window of risk and strict follow-up to assess in a personalized way the risk among the different groups of patients, especially those with a past history of cardiovascular disease. The main results revealed disorders such as heart failure, arrhythmias, pericarditis and myocarditis, which require early detection and occur days or even weeks after the acute phase of COVID-19.Copyright © La revista. Publicado por la Universidad de San Martin de Porres, Peru.

Pain in Covid-19 and Features of Pathogenetic Molecular Mechanisms

Although it has been almost three years since the World Health Organization (WHO) declared a pandemic, COVID-19 is still an unsolved problem, thereby attracting great scientific interest. The disease has a heterogeneous clinical picture with multiple manifestations from different organs and systems. Currently, COVID-19 is perceived as a polysyndromic inflammatory disease involving not only the respiratory system, but also the musculoskeletal system, the cardiovascular system, the skin, the excretory and the nervous system, and is accompanied by a number of hematological, gastrohepatoenterological and endocrine disorders. Various pain phenomena also appear in the clinical presentation of the disease, often as a single manifestation or in combination with symptoms from different organs and systems. The pathogenesis of pain is complex and there is still no consensus on the exact driving mechanisms. Several different signaling pathways play an important role in the generation of pain impulses and perception. They are different for different types of pain. At this stage, the role of angiotensin-converting enzyme 2 (ACE), the renin-angiotensin system (RAC), angiotensin 2 receptors (AT2R), direct neuronal invasion of the virus, the involvement of pro-inflammatory cytokines, hypoxia, the involvement of macrophages, is discussed. as well as the role of overactivity of the immune system, causing the so-called "cytokine storm". Pain is the result of complex biochemical processes influenced to varying degrees by biological, physiological and social factors. Our knowledge at this stage remains scarce and is the subject of many studies on the key pathogenic mechanisms. Therefore, the purpose of this review is to describe the known mechanisms for the occurrence and persistence of pain in patients with COVID-19, as well as to classify the pain phenomena and present its most common localizations. The diagnosis and treatment of COVID-19 and associated pain should be carried out by a multidisciplinary team of specialists, given the heterogeneous clinical presentation of the disease.Copyright © 2023 Medical Information Center. All rights reserved.