Pathophysiology of thromboembolism in patients with COVID-19

Introduction and aim. A small number of critically ill patients with coronavirus disease (COVID-19) develop thromboembolism (arterial or venous), both micro- and macrovascular complications such as deep vein thrombosis, pulmonary embolism, and pulmonary arterial thrombosis. The objective of the study is to describe the pathophysiology of venous thromboembolism in patients with COVID-19. Material and methods. In this article a narrative review regarding pathophysiology of thromboembolism in patients with COVID-19. Analysis of the literature. The development of coagulopathy is a consequence of the intense inflammatory response associated with hypercoagulability, platelet activation, and endothelial dysfunction. The pathophysiology that relates pulmonary thromboembolism (PTE) with COVID-19 is associated with a hypercoagulable state. PTE is suspected in hospitalized patients presenting dyspnea, decreased oxygen requirement, hemodynamic instability, and dissociation between hemodynamic and respiratory changes. In COVID-19-associated coagulopathy, initially, patients present with elevated levels of fibrinogen and D-dimer, with minimal changes in prothrombin time and platelet count. The main risk factor for the development of pulmonary embolism is the increase in D-dimer that is associated with the development of PTE. The administration of iodine-based contrast agent to patients with COVID-19 would affect P-creatinine and renal function, where Ultrasound is viewed as cost-effective and highly portable, can be performed at the bedside. Conclusion. Acute respiratory distress syndrome severity in patients with COVID-19 can explain PTE as a consequence of an exaggerated immune response. © 2022 Publishing Office of the University of Rzeszow. All Rights Reserved.

Spontaneous pneumomediastinum, pneumothorax, pneumoperitoneum and soft tissue emphysema as complication in patients with COVID-19, series of cases.

Spontaneous pneumomediastinum, pneumothorax, pneumoperitoneum, and soft tissue emphysema have been recently described in several sources as possible complications in patients with severe COVID-19 and lung damage. This clinical case is dedicated to demonstrarte the development of these lesions in 3 male patients with comorbid conditions. The putative pathophysiological mechanism of these complications is air leakage due to extensive diffuse alveolar damage followed by rupture of the alveoli. All presented patients had a favorable outcome of the disease without lethal cases, their laboratory data and clinical dynamics were described. It should be noted that such conditions are not rare complications of COVID-19, and are observed mainly in male patients with severe form of the disease and the presence of comorbid conditions. Such complications are associated with long hospitalization and a severe prognosis. In some cases, with a mild course of the disease and positive dynamics in a decrease of the percentage of pulmonary lesions, the outcome is favorable, not requiring additional invasive interventions.Copyright © 2022 Medical Visualization. All rights reserved.

Spectrum of echocardiographic findings in patients with severe and critical COVID-19: a single center experience

Introduction: Information on the cardiac manifestations of coronavirus disease 2019 (COVID-19) is scarce. In this study we assessed the echocardiogram of consecutive patients with COVID-19 infection to assess the frequency of cardiac abnormalities. Materials and Methods: This retrospective descriptive study examined the echocardiographic study of 43 patients with severe and critical COVID-19 infection admitted at the ICU of Chitwan Medical College from May 16, 2021 to June 05, 2021. The study focused on left ventricle (LV) and right ventricle (RV) function. The results were then compared between severe and critical infections to examine if any differences exist between them. Results: The mean age of the study population was 54 years and predominately males. One-third were classified as critical COVID-19 while the remaining were severe COVID-19. Majority(83.7%) had a normal echocardiogram. Among the patients with abnormal reports, the distribution of echocardiographic pattern were biventricular dilation with biventricular dysfunction in two patients (4.6%), LV dialtion with LV dysfunction in two patients (4.6%) and isolated LV dysfunction (diastolic and systolic) in three patients (6.9%). None of the echocardiographic parameters were significantly different between the severe and the critical infection. Conclusion: COVID-19 in primarily a respiratory disease and the cardiac complications is largely attributed to the critical nature of the illness than the specific infection. Considering the risk of infection spread, routine echocardiography for all patients with COVID-19 infection is not advisable.

SINGLE CELL MULTIOMIC PROFILING OF DISRUPTED REGULATORY NETWORKS IN COVID19 ASSOCIATED MULTISYSTEM INFLAMMATORY SYNDROME IN CHILDREN

BackgroundChildren infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) usually present minimal symptoms or are asymptomatic. Nevertheless, a subset of children 2-6 weeks after the initial SARS-CoV-2 infection develops a postinfectious SARS-CoV-2-related multisystem inflammatory syndrome in (MIS-C). Recently, transient expansion of TRBV11-2 T cell clonotypes in MIS-C was associated with signatures of inflammation and T cell activation, however, the underlying pathophysiology of MIS-C is not fully understood [1].ObjectivesThe purpose of our project is to characterize the complexity of cell populations and capture cellular heterogeneity to uncover the regulatory networks and interactions that are disrupted during MIS-C flare with simultaneous profiling of gene expression and open chromatin regions from the same nuclei.MethodsSamples of peripheral blood mononuclear cells from patients with MIS-C diagnosed at the University Children's Hospital, University Medical Center Ljubljana, were collected during the initial presentation before any treatment and at 6-12 months in remission. The primary aim is to identify which regulatory networks are driving inflammation in MIS-C flare, for which we are performing single cell Multiome ATAC + Gene Expression Sequencing. To enable simultaneous profiling of epigenomic landscape and gene expression from the same nuclei, we are using Chromium Next GEM Single Cell Multiome ATAC + Gene Expression kit from 10X Genomics.ResultsWe included 32 patients with MIS-C from whom we collected paired blood samples during the initial presentation before treatment and at 6-12 months in remission. In single cell multiomic experiment we included 10 patients with paired samples, with the most viable cell count prior cryopreservation. All samples that are included into multiomic single cell analysis have 75% - 99% viability prior cryopreservation. In the protocol the key is to remove remaining granulocytes causing high mitochondrial RNA burden and extensively optimize the dilution factor of lysis buffer and the length of cell lysis step in order to get intact nuclei with no significant blebbing. Afterward, the single cell ATAC libraries as well as single-cell gene expression libraries are constructed and sequenced. Data are undergoing pairwise analysis to compare the cell population heterogeneity, expression profile and open chromatin landscape in the time of the initial presentation of MIS-C and in the remission, with Cell ranger software as well as with R package scREG [2], and custom scripting. In the second step we will inspect if the resulting altered transcriptomic signature from single-cell experiment is present on larger cohort. In that regard, we will perform bulk transcriptomic profiling on all paired collected samples during the initial presentation of MIS-C before treatment and at 6-12 months in remission.ConclusionThe results of this project are expected to enlighten the underlying pathophysiology of MIS-C flare and thus support clinical decision on more targeted treatment. The identified disrupted networks during MIS-C flare could lead the way to establish an early diagnosis and improve long-term outcome, including prevention of myocardial and neuropsychological impairment. Moreover, a better understanding of the disrupted regulatory networks that are driving inflammation in MIS-C, could lead to new insights into diseases with similar clinical presentations as is Kawasaki Disease.References[1]Sacco, K., Castagnoli, R., Vakkilainen, S. et al. Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19. Nat Med 28, 1050–1062 (2022).[2]Duren, Z., Chang, F., Naqing, F. et al. Regulatory analysis of single cell multiome gene expression and chromatin accessibility data with scREG. Genome Biol 23, 114 (2022).AcknowledgementsThis research was supported by Slovenian research agency grant J3-3061 and Interreg ITA-SLO project Cattedra.Disclosure of InterestsNone Declared.

An Echocardiographic Insight Into Post-COVID-19 Symptoms.

INTRODUCTION AND OBJECTIVES: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has frequent acute cardiovascular manifestations, but long-term sequelae are yet to be described. Our main objective is to describe the echocardiographic findings of patients with a previous SARS-CoV-2 infection. METHODS: A single-center prospective study was conducted. Patients who tested positive for SARS-CoV-2 were selected and submitted to a transthoracic echocardiogram six months after infection. A complete echocardiographic assessment was performed, including tissue Doppler, E/E' ratio, and ventricular longitudinal strain. Patients were divided into two subgroups according to their need for admission to the ICU. RESULTS: A total of 88 patients were enrolled. The mean values and respective standard deviations of the echocardiographic parameters were as follows: left ventricular ejection fraction 60.8 ± 5.9%; left ventricular longitudinal strain 17.9 ± 3.6%; tricuspid annular plane systolic excursion 22.1 ± 3.6 mm; a longitudinal strain of the free wall of the right ventricle 19.0 ± 6.0%. We found no statistically significant differences between subgroups. CONCLUSIONS: At the six-month follow-up, we found no significant impact of past SARS-CoV-2 infection on the heart using echocardiography parameters.

Review of the Literature on Ramadan Fasting and Health in 2022

Objectives The literature on health and disease during Ramadan fasting (RF) is widely spread in many journals making it not readily accessible to those interested in the subject. Here, we provide an overview of the research on the interplay of RF with various aspects of well-being published in 2022.Materials and Methods A narrative, nonsystematic review of the international literature from a single major medical online database, PubMed, in one calendar year (2022) was conducted. The search term "Ramadan fasting" was used to retrieve the appropriate records. The relevant literature with substantial data-based content was presented in a concise thematic account, excluding those concerned with diabetes.Results Themes that emerged from the review included the pathophysiology of metabolic changes during RF, nutritional aspects including body composition and energy metabolism, cardiovascular disease and risk factors, renal function and structure, endocrinology (mainly thyroid), neurological disorders, mental health, pregnancy and fetal life, and infections (including COVID). Some miscellaneous clinical themes were identified, such as patients' and professional perspectives.Conclusions In 2022, the medical interest in RF was again widely spread across specialties. Cardiovascular disease and risk factors attract the most interest in terms of original articles and professional guidelines. We hope with this review to present a concise summary of the scholarly work on the subject in this year.

Options for the course of COVID-19

Introduction. Currently it is well-recognized that tissue markers allow to classify the process of different infectious diseases and help to identify patients' to subclasses and endotypes for clarifying the prognosis and therapy effectiveness. Objective. To detect different COVID-19 course types according to pathophysiological mechanisms, and evaluate clinical, lab and instrumental features of each clinical course. Material and methods. 108 first COVID-19 patients were admitted at special hospital based on Bakoulev National Medical Research Center for Cardiovascular Surgery. The average age of patients was 57.4 +/- 2.3 years, 54.6% of women, the degree of lung damage was 36.2 +/- 2.3%. All patients were identified with C-reactive protein (CRP) and D-dimer. Results. The patients were divided in 4 groups depending on the degree of main pathophysiological process of system inflammatory response (SIR) and hypercoagulation: with inflammatory (1group) (n = 22), coagulation (2 group) (n = 8), inflammatory-coagulation (3 group) (n = 71) and affectless (4 group) (n = 7) types of disease progression. All the 4 groups of the discharged patients were equal in pulmonic parenchymatous tissue damage degree. The level of lactate dehydrogenase (LDH) was significantly higher in patients of group 3 (334.2 +/- 20.6 U/L) compared with LDH in groups 1, 2 and 4 (respectively 264.2 +/- 21.5, 231 +/- 14.2, 206.3 +/- 32.2 U/L, p < 0.01), which indicates more severe damage to the pulmonary parenchyma. In groups 1 and 3, the level of lymphocytes was lower than in groups 2 and 4. In terms of the D-dimer level, the 3rd and 2nd groups did not differ (1537.4 +/- 126.7 and 1682.5 +/- 394.2, respectively, p > 0.05), but its level was significantly higher in the 3rd group compared with the 1st and 4th (359 +/- 32.9 and 309.3 +/- 50.8, p < 0.01). Over the course of staying in hospital the features of each type of disease progression kept preserved. Conclusions. It is possible to accentuate 4 possible development scenario of the COVID-19: the inflammatory one (with SVR manifestation without hypercoagulation), the hypercoagulation one (without SVR activation), the inflammatory-coagulation (active SVR together with hypercoagulation) and affectless type (without SVR and hypercoagulation). The most prevalent type of COVID-19 disease progression is inflammatory-coagulation scenario which is manifested at 65% of patients.Copyright © Creative Cardiology 2021.

Audiovestibular and vaccination complications of COVID-19

Objectives: Since its first appearance in Wuhan December 2019, SARS-CoV2 virus received great attention due to its severe symptoms and high spread causing COVID-19 disease which spread all over the world like a pandemic. The causative virus is capable of human-to-human transmission via droplet and direct contact suggesting that upper respiratory tract is the main site to virus manifestations. There is a great diversity in its clinical picture, although the severe respiratory and neurological symptoms are commonly present;however, other symptoms are present. Although otological manifestations are reported in many COVID-19 patients even in asymptomatic cases, they did not receive much attention compared with other critical manifestations. In this article, we paid our attention specifically to the otological manifestations of COVID-19 and their relevance either to the virus infection, treatment, or vaccination through literature review. Conclusion(s): COVID-19 disease has a deleterious effect on the inner ear. This effect is not only due to SARS-Cov-2 infection, but it could be also due to the ototoxic drugs used for treatment. The COVID-19 vaccinations are found to be implicated in the otological symptoms in some cases.Copyright © 2022, The Author(s).

Treatment of coronavirus disease 2019: Timing determines prognosis

The global epidemic of coronavirus disease 2019 (COVID-19) is still growing. The response to this emerging disease should be considered with the context of its clinical characteristics and pathophysiological mechanisms. Although available therapeutic options are still very limited, current experience has suggested that the choice of clinical strategies should be based upon the disease stage and immune functions of the patients. The present article reviews the clinical characteristics of COVID-19 and current evidence of various treatment approaches. Combined with first-line experience, we summarize the current clinical strategies for COVID-19 management based on disease progress and staging.Copyright © 2021, Peking Union Medical College Hospital. All rights reserved.

Essential Multiorgan Pathophysiology of COVID-19

Typical manifestations of coronavirus disease-2019 (COVID-19) include mild-to-moderate "flu-like” symptoms, although more severe manifestations have been reported. The pathophysiology of COVID-19 is complex, and its clinical spectrum might not be limited to local pneumonia, but rather may represent a multisystem illness with potential for severe acute respiratory distress syndrome (ARDS) and multiorgan impairment. In this context, the aim of the present handbook is to provide an overview of possible multisystemic manifestations and therapeutic strategies, in order to guide the clinician to deal with COVID-19 critical illness and to prevent potential systemic consequences. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Progress in the research of COVID-19 effects on Alzheimer's disease

Coronavirus disease 2019 (COVID-19) is a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). More than one-third of patients with COVID-19 experience neurological symptoms, including confusion, headaches, and decreased/disordered taste. Alzheimer's disease (AD) is a slowly progressive neurodegenerative disease and the most common type of dementia. Alzheimer's disease patients are at high risk and susceptible to infection with COVID-19, which may cause severe illness and even death. There appears to be an interaction between AD and COVID-19, and on the one hand, patients with COVID-19 seem to be more likely to develop AD. AD patients, on the other hand, may be more susceptible to severe COVID-19. Therefore, understanding the common link between COVID-19 and AD may help to develop treatment strategies. Risk factors common to AD and COVID-19 are aging, ApoE T4 allele, beta-amyloid (Abeta) deposition, angiotensin-converting enzyme (ACE), neuroinflammation, oxidative stress. Here, this article focuses on the relationship between COVID-19 and AD, explores common risk factors and potential pathogenesis, and provides help for early prevention, treatment and recovery.

Does previous anti-thrombotic use affect the course of coronavirus disease-2019?

Introduction: Proinflammatory cytokines, produced as an immune response in severe acute respiratory syndrome-coronavirus 2 infection, activate the coagulation cascade as well. In this study, we investigated the difference in the clinical course of patients who had been already using anti-thrombotic therapy before coronavirus disease-2019 (COVID-19) for any reason compared to the group who had not. Methods: In this retrospective, multicenter study;patients who were hospitalized between March 11 and July 1, 2020 were divided into two main groups as who had been on anti-thrombotic therapy for any indication use previously at the time of admission or who had not been on anti-thrombotic therapy at the time of admission, and their selected clinical parameters were compared. Results: After analyzing the study population of 124 patients with a homogeneous distribution in terms of age and gender, the comparison of anti-thrombotic users and non-users showed no significant difference in hospitalization. There was a statistically significant decrease in mechanical ventilation apply rate, intensive care unit duration and mortality rate between the group using anti-thrombotic compared to the group not using it (p<0.05). Conclusion: It has already been shown that COVID-19 patients are more prone to thromboembolic events as it activates the coagulation cascade with the cytokine storm it creates and thus the mortality of COVID-19 infection increases significantly. Parallel to this fact the results of our study demonstrated that using anti-thrombotic therapy for any reason may affect the bad prognosis of the disease positively.

Restrospective study of hemogram profile in effusive feline infectious peritonitis

Feline Infectious Peritonitis (FIP) is highly mortality disease in cats. The reliable and fast diagnosis is crucial to the best prognosis. The aim of this study to evaluate the hemogram profile in cats infected with effusive FIP. Twenty cats had been diagnosed effusive FIP at Animal Clinic Department of Internal Medicine, Faculty Veterinary Medicine, Universitas Gadjah Mada were used in the study. The diagnosis were based on clinical examination, ultrasound, x-ray, rivalta test, and rapid test. The hemogram profile were analyzed include routine hematology and serum biochemistry. Hemogram profile in effusive FIP showed the decreased hematocrit, hyperproteinemia, and leukocytosis with an average 22.9+or-7.4%;9.0+or-2.2 g/dL;22425+or-4116 cells/mm3 respectively. Erythrocyte, hemoglobin and fibrinogen levels were still in the normal range. The results of differential leukocytes revealed that 90% cats had neutrophilia and 75% lymphopenia with an average 20066+or-3337 cells/mm3 and 1861+or-1818 cells/mm3 respectively. The blood chemistry profile showed 60% of cats experienced increase in SGPT and SGOT with an average 138.4+or-72.3 IU/L and 101+or-60.5 IU/L respectively. Hyperglobulinemia was found in 90% samples with an average 6.7+or-0.8 g/dL. All cats have a low albumin:globulin ratio with an average 0.3+or-0.1. The hemogram profile of effusive FIP were: leukocytosis, neutrophilia, lymphopenia, hyperglobulinemia, and decreased albumin-globulin ratio..

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.

Respiratory disorders and their association with clinical outcomes in COVID-19: a narrative review of current literature.

BACKGROUND AND OBJECTIVE: The coronavirus disease 2019, also known as COVID-19, has caused significant worldwide morbidity and mortality. Given the direct effect of severe acute respiratory syndrome virus-2 (SARS-CoV-2) on the respiratory system, it is important that clinicians who manage chronic respiratory conditions are familiar with the pathophysiology and impact of COVID-19 on pre-existing respiratory disease. METHODS: Literature review relating to COVID-19 and respiratory disorders from PubMed and Google Scholar was conducted, with aim to encompass all publications relating to the most commonly encountered respiratory diseases in clinical practice, namely chronic obstructive lung disease (COPD), asthma, interstitial lung disease (ILD), obstructive sleep apnea (OSA), as well as obesity given it's known effect on both gas exchange and mechanistic aspects of respiration. The publications were analyzed for relevance to clinical implications and pathophysiologic mechanisms. Additional manual literature review was conducted based on citations from large review articles and society guidelines/statement papers. KEY CONTENT AND FINDINGS: Certain respiratory disorders such as COPD, ILD, OSA, and obesity carry higher burden of morbidity and mortality associated with COVID-19. Surprisingly, and in contrast to previously studied viral epidemics, asthma does not carry increased associated risk of contracting the virus or worse clinical outcomes. CONCLUSIONS: A thorough understanding of the mechanisms responsible for control of breathing and the effect of COVID-19 on pulmonary pathophysiology will allow clinicians who manage chronic respiratory disease to effectively predict associated clinical outcomes as well as improve management strategies.

Immune and Hereditary Thrombotic Thrombocytopenic Purpura: Can ADAMTS13 Deficiency Alone Explain the Different Clinical Phenotypes?

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy caused by a hereditary or immune-mediated deficiency of the enzyme ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). TTPs are caused by the following pathophysiological mechanisms: (1) the presence of inhibitory autoantibodies against ADAMTS13; and (2) hereditary mutations of the ADAMTS13 gene, which is present on chromosome 9. In both syndromes, TTP results from a severe deficiency of ADAMTS13, which is responsible for the impaired proteolytic processing of high-molecular-weight von Willebrand factor (HMW-VWF) multimers, which avidly interact with platelets and subendothelial collagen and promote tissue and multiorgan ischemia. Although the acute presentation of the occurring symptoms in acquired and hereditary TTPs is similar (microangiopathic hemolytic anemia, thrombocytopenia, and variable ischemic end-organ injury), their intensity, incidence, and precipitating factors are different, although, in both forms, a severe ADAMTS13 deficiency characterizes their physiopathology. This review is aimed at exploring the possible factors responsible for the different clinical and pathological features occurring in hereditary and immune-mediated TTPs.

A Clinical Update on Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) traditionally refers to abnormal glucose tolerance with onset or first recognition during pregnancy. GDM has long been associated with obstetric and neonatal complications primarily relating to higher infant birthweight and is increasingly recognized as a risk factor for future maternal and offspring cardiometabolic disease. The prevalence of GDM continues to rise internationally due to epidemiological factors including the increase in background rates of obesity in women of reproductive age and rising maternal age and the implementation of the revised International Association of the Diabetes and Pregnancy Study Groups' criteria and diagnostic procedures for GDM. The current lack of international consensus for the diagnosis of GDM reflects its complex historical evolution and pragmatic antenatal resource considerations given GDM is now 1 of the most common complications of pregnancy. Regardless, the contemporary clinical approach to GDM should be informed not only by its short-term complications but also by its longer term prognosis. Recent data demonstrate the effect of early in utero exposure to maternal hyperglycemia, with evidence for fetal overgrowth present prior to the traditional diagnosis of GDM from 24 weeks' gestation, as well as the durable adverse impact of maternal hyperglycemia on child and adolescent metabolism. The major contribution of GDM to the global epidemic of intergenerational cardiometabolic disease highlights the importance of identifying GDM as an early risk factor for type 2 diabetes and cardiovascular disease, broadening the prevailing clinical approach to address longer term maternal and offspring complications following a diagnosis of GDM.