Pericytes may facilitate SARS-CoV-2 entry into the nervous system

Objective: Although the neurological and olfactory symptoms of coronavirus disease 2019 have been identified, the neurotropic properties of the causative virus, severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2), remain unknown. We sought to identify the susceptible cell types and potential routes of SARS-CoV-2 entry into the central nervous system, olfactory system, and respiratory system. Method(s): We collected single-cell RNA data from normal brain and nasal epithelium specimens, along with bronchial, tracheal, and lung specimens in public datasets. The susceptible cell types that express SARS-CoV-2 entry genes were identified using single-cell RNA sequencing and the expression of the key genes at protein levels was verified by immunohistochemistry. We compared the coexpression patterns of the entry receptor angiotensin-converting enzyme 2 (ACE2) and the spike protein priming enzyme transmembrane serine protease (TMPRSS)/cathepsin L among the specimens. Result(s): The SARS-CoV-2 entry receptor ACE2 and the spike protein priming enzyme TMPRSS/cathepsin L were coexpressed by pericytes in brain tissue;this coexpression was confirmed by immunohistochemistry. In the nasal epithelium, ciliated cells and sustentacular cells exhibited strong coexpression of ACE2 and TMPRSS. Neurons and glia in the brain and nasal epithelium did not exhibit coexpression of ACE2 and TMPRSS. However, coexpression was present in ciliated cells, vascular smooth muscle cells, and fibroblasts in tracheal tissue;ciliated cells and goblet cells in bronchial tissue;and alveolar epithelium type 1 cells, AT2 cells, and ciliated cells in lung tissue. Conclusion(s): Neurological symptoms in patients with coronavirus disease 2019 could be associated with SARS-CoV-2 invasion across the blood-brain barrier via pericytes. Additionally, SARS-CoV-2-induced olfactory disorders could be the result of localized cell damage in the nasal epithelium.Copyright © Wolters Kluwer Health, Inc. All rights reserved.

Hepatotoxicity From Marijuana Gummies

Introduction: We report a case of drug-induced liver injury (DILI) induced by cannabis gummies containing Corydalis Rhizome. Case Description/Methods: A 37-year-old female presented to her primary care clinic with recurrent fevers, night sweats, and myalgias for 7 weeks accompanied by eye redness, brain fog, headache, nausea, and abdominal pain. She denied rashes, tick-bites, cough, dyspnea, chest pain, joint swelling, or genitourinary symptoms. Past medical history was notable for IBS, migraines, and anxiety. She reported edible marijuana use four times a week, rare alcohol use, and denied tobacco use. She denied a family history of liver disease. Physical exam was notable for tachycardia to 110 and scleral injection with the remainder of vitals and exam unremarkable. Initial labs were notable for AST 61, ALT 44 and CRP of 12. CBC, BMP, urinalysis, ESR, blood cultures, blood smear for parasite screen, tests for Lyme disease, Babesia, Tularemia, Anaplasma, Ehrlichia, Rickettsia, EBV, HIV, RPR, ANA, CMV, parvovirus B19, and chest x-ray were all negative. The patient was referred to infectious disease with further testing for West Nile, Leptospira, lymphocytic choriomeningitis virus, and COVID-19 returning negative. Repeat LFTs showed worsening transaminitis with ALT 979 and AST 712, alkaline phosphatase 88, total bilirubin 0.7, and albumin 4.9. Hepatitis workup including hepatitis A, B, and C, HSV, EBV, VZV serologies, AMA, ASMA, antiLKM Ab, acetaminophen level, INR, iron panel, CPK, TSH, and abdominal ultrasound were all normal. It was later discovered that her marijuana gummies contained Corydalis rhizome extract known to be hepatotoxic. Cessation of this drug was strongly advised. She was discharged with hepatology follow-up and underwent a liver biopsy showing patchy periportal and lobular inflammation with extension across the limiting plate, hepatocyte injury and apoptosis, and increased lipofuscin for age compatible with mild to moderate hepatitis. She had complete recovery after cessation of Corydalis-containing gummies. (Figure) Discussion: Our patient consumed '1906 Midnight', an American cannabis brand containing Corydalis rhizopus 100 mg, advertised to improve sleep, pain, and have a liver protective effect. A Korean systematic review on herbal-induced liver injury reported that Corydalis was the 3rd most frequent causative herb, with 36 cases. Although there are several personal accounts on social networking sites and other websites, there are no American-based publications reported on DILI from Corydalis. (Table Presented).

Thromboprophylaxis and anticoagulation in COVID-19.

The immunological reaction that facilitates the cytokine storm in the infection by the new coronavirus facilitates the appearance of microvascular, endothelial and direct cellular damage, which leads to a prothrombotic state and events of thromboembolism to different apparatus and systems as a complication. Therefore, the need to provide adequate prophylactic therapy or anticoagulant management in time and adequate dosage to these patients, as well as an individualized coagulation and hemostasis study. This document is intended to summarize in a practical way the evidence published to date and provide a broader view of the pathophysiological phenomena that occur in this hyperinflammatory state that has taught us a lot since its arrival.Copyright © 2022 Comunicaciones Cientificas Mexicanas S.A. de C.V.. All rights reserved.

Could COVID-19 be a Causative Factor for Hyperglycaemia and Cause Diabetes Mellitus.

Since the outbreak of the COVID-19 pandemic, it has been suspected that its causative agent, the SARS-CoV-2 coronavirus, may cause transient or permanent hyperglycemia. This fact has resulted in a new focus of research interest related to the study of potential mechanisms leading to damage of pancreatic insulin-producing cells, as well as the possible impact of the virus on insulin sensitivity, which may manifest as metabolic disturbances in patients with COVID-19 and cause diabetes mellitus. Evidence from the literature suggests that Corona viruses can damage pancreatic (beta-cells by direct or indirect mechanisms and cause changes in insulin secretion and sensitivity. To what extent all these changes are valid claims that SARS-CoV-2 can trigger diabetes mellitus is still not fully proven.Copyright © 2022 Medical Information Center. All rights reserved.

Clinical, Biochemical, and ATR-FTIR Spectroscopic Parameters Associated with Death or Survival in Patients with Severe COVID-19

The wide range of symptoms of the coronavirus disease 2019 (COVID-19) makes it challenging to predict the disease evolution using a single parameter. Therefore, to describe the pathophysiological response to SARS-CoV-2 infection in hospitalized patients with severe COVID-19, we compared according to survival or death, the sociodemographic and clinical characteristics, the biochemical and immunological attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectra from saliva samples and their correlation with chemometric findings. Herein, we demonstrate that ATR-FTIR spectroscopy allows the description of the events related to cell damage, such as lipids biogenesis and the secondary structure of proteins associated with lactate dehydrogenase and albumin levels. Moreover, humoral (IgM) and cellular (IFN-gamma, TNF-alpha, IL-10, and IL-6) responses were also increased in patients who died from COVID-19. Copyright © 2023 Adriana Martinez-Cuazitl et al.

Covid-19 and Cytokine Storm

Introduction: Covid-19 is associated with elevated proinflammatory cytokines that are associated with increased severity and mortality. There is controversy about the true role of cytokine storm (CS) in the pathophysiology of COVID-19. Method(s): Prospective, observational, longitudinal study of 91 hospitalized patients with different severity. It included Viral phase(1-9 days from clinical onset), early inflammatory (10-16 days), and late (>17 days). Clinical data, immune cell counts, proinflammatory cytokine levels (TNF-alpha,IL-1beta,IL-8,IL-6,INF-gamma,IL-17A andG-CSF), serum inflammatory markers (CRP,PCT,D-dimer,ferritin) and tissue damage markers (LDH and cfDNA) were included. Result(s): TNF- alpha, IL-8,IL-6 and G-CSF, were elevated in the most severe patients. IL-6, IL-8 and G-CSF were already elevated in the first admission sample in those who died. Only IL-6 remained elevated in all 3 phases of the disease in deceased patients. IL-1beta, INF-gamma and IL-17A were not related to severity. We found increased levels of cytokines from the viral phase to the early inflammatory phase, significant in moderate Covid-19, but stable in severe and decreasing in critically ill patients. Only IL-6 showed increasing levels in the evolution of critically ill patients. IL-6 correlated with the tissue damage markers studied and with length of stay, especially in critical patients (r=0.598). Conclusion(s): Only IL-6, TNF-alpha,IL-8 and G-CSF were associated with severity. IL-6 was the cytokine that best expressed hyperactivation of the innate immune response and cellular damage in critically ill. There was no significant and sustained increase in cytokines in late inflammation, as would be expected in major CS.

COVID 19 Induced Hyperglycaemic Complications

Background: COVID 19 has two-way interaction with Type II Diabetes Mellitus. First, patient with DM are more prone for developing severe COVID 19. Second, moderate to severe COVID 19 can present with new onset DM or may lead to hyperglycaemia and hyperglycaemic complications in Type II DM patients. In this report we present 4 cases of COVID 19 associated Hyperglycaemic Complication (3 with Diabetic Ketoacidosis and 1 with Hyperglycaemic hyperosmolar state). Method(s): Case Series of patients admitted to Thumbay Hospital, Ajman. Result(s): We report 4 cases of COVID 19 patients who presented to us with hyperglycaemic complications. There of them had features of Diabetic Ketoacidosis and one had Hyperglycaemic hyperosmolar state. All were treated with IV Insulin infusion and IV Fluids. COVID 19 infection was managed as per MOH protocol. All patients recovered well and were discharged in stable condition. Discussion(s): COVID 19 is associated with new onset DM or may lead to hyperglycaemic complications in patients with Type II DM. There are three pathophysiological processes which may be responsible for this finding. One, SARS-CoV-2 virus is known to enter the body through angiotensin-converting enzyme (ACE) II receptors in the pulmonary pneumocytes leading to infection and inflammation. Similar ACE-II receptors are also expressed in key metabolic organs and tissues, including pancreatic beta cells, adipose tissue, the small intestine, and the kidneys. Direct infection of pancreatic beta-cells with SARS-CoV-2 virus with beta-cell cell injury is likely the underlying mechanism for development of new onset diabetes and hyperglycaemia in existing diabetic patients. Such direct beta cell infection can cause hyperglycaemic complications in asymptomatic or mild COVID 19 as well. Two, moderate to severe COVID 19 is associated with hyperinflammatory immune response leading to marked rise in inflammatory mediators such as C-reactive protein and ferritin. Such hyperinflammatory response can also lead to hyperglyacemia in patients with diabetes mellitus. Three, corticosteroids are mainstay treatment of patients with moderate to severe COVID 19 and would definitely contribute to worsening of hyperglycaemia in these patients. Our patients presented to us with hyperglycaemic complications before initiation of any treatment. It is likely that such a situation would be due to direct infection and destruction of beta cells with SARS-CoV-2 virus infection. Conclusion(s): Type II Diabetes Mellitus patients are high risk of developing hyperglycaemic complications due to COVID 19. This can lead to increased morbidity and mortality. Patients with Type II DM should seek medical attention even if they have mild to asymptomatic COVID 19 to monitor for hyperglycaemic complication which can develop irrespective of severity of stage of illness.

COVID-19 and pancreatitis: A review of the potential association

Originally thought to be a respiratory pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), has been shown to cause a dizzying array of symptoms, including all major organ systems of the human body. As time elapsed, new strains of the virus have emerged, validating concerns about genetic mutation. No single treatment has proven beneficial in treating the consequences, and the world has been left at the mercy of this deadly pathogen. It has been proven that COVID-19 can cause strokes, myocardial infarcts, mesenteric infarcts, acute limb ischemia, and a wide array of other symptomatology. This review aimed to evaluate whether there exists an association between COVID-19 and pancreatitis. Forty publications (34 case reports and 4 case series) were included in the review. In total, 44 cases of acute pancreatitis (38 cases of acute edematous pancreatitis and 6 cases of necrotizing pancreatitis) in COVID-19 patients without any predisposing factors have been published since January 2020. Fortunately, only 4 (9.1%) of these patients were reported to have died. Although the exact mechanism by which COVID-19 causes pancreatitis is still unclear, studies so far have reported it as a multifactorial phenomenon. COVID-19 associated pancreatic injury is thought to involve direct cellular damage via local replication of SARS-CoV-2 within pancreatic cells, as they express angiotensin-converting enzyme 2 receptors even more strongly than lung cells. Our review concludes that acute pancreatitis should be kept in the differential list of all COVID-19 patients with gastrointestinal manifestations, especially in patients with acute abdomen.Copyright © 2023, Society of Gastrointestinal Intervention.

Research progress on the mechanism of multiple organ dysfunction in patients with COVID-19.

The pathogen of COVID-19 is 2019-nCoV, which belongs to the beta coronavirus. Angiotensin-converting enzyme 2 (ACE2) is the receptor of 2019-nCoV as the same of SARS-CoV. Most of the severe patients were the elderly with underlying diseases, which may be related to the decrease in the number of naive T cells. In addition to pulmonary symptoms, COVID-19 can also cause multiple organ dysfunction and even multiple organ failure (liver, nervous system, heart, kidney, etc.). Pathogenic mechanisms such as direct virus invasion, cytokine storm, endothelial cells damage, and down-regulation of ACE2 may play important roles in the severity of the disease.Copyright © 2021 Chinese Medical Association

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.

Elevated plasma levels of CXCL16 in severe COVID19 patients

Genome-wide association studies have recently identified 3p21.31, with lead variant pointing to the CXCR6 gene, as the strongest thus far reported susceptibility risk locus for severe manifestation of COVID-19. In order the determine its role, we measured plasma levels of Chemokine (CXC motif) ligand 16 (CXCL16) in the plasma of COVID-19 hospitalized patients. CXCL16 interacts with CXCR6 promoting chemotaxis or cell adhesion. The CXCR6/CXCL16 axis mediates homing of T cells to the lungs in disease and hyper-expression is associated with localized cellular injury. To characterize the CXCR6/CXCL16 axis in the pathogenesis of severe COVID-19, plasma concentrations of CXCL16 collected at baseline from 115 hospitalized COVID-19 patients participating in ODYSSEY COVID-19 clinical trial were assessed together with a set of controls. We report elevated levels of CXCL16 in a cohort of COVID-19 hospitalized patients. Specifically, we report significant elevation of CXCL16 plasma levels in association with severity of COVID-19 (as defined by WHO scale) (P-value<0.02). We replicate this finding in an independent replication set CALYPSO (P-value<0.0012). We also observe a highly significant effect on mortality (P-value<0.0004) in association with higher CXCL16 plasma levels. We are further characterizing the expression of CXCR6 in in CD8+ T cells. Our current study is the largest thus far study reporting CXCL16 levels in COVID-19 hospitalized patients (with whole-genome sequencing data available). Latest results support the significant role of the CXCR6/CXCL16 axis in the immunopathogenesis of severe COVID-19 and warrants further studies to understand which patients would benefit most from targeted treatments.

New Onset Diabetes Mellitus in Post Covid Patients - an Observational Study

Background and Aims: The novel coronavirus,binds to angiotensin- converting enzyme 2 (ACE2) receptors, which are expressed in key metabolic organs and tissues, including pancreatic beta cells, adipose tissue, small intestine and kidneys. COVID-19 is attributed to the cytokine storm, followed by pancreatic cell damage.Thus, it is plausible that SARS-CoV-2 may cause pleiotropic alterations of glucose metabolism that could complicate the pathophysiology of pre-existing diabetes or lead to new onset Diabetes Mellitus.Thus, the study aims to analyze the development of new onset diabetes in post covid patients Methods: Serum glucose level of 500 patients, between the age of 18 to 50 who were previously normoglycemic and recovered from COVID-19 was measured and incidence of new onset diabetes mellitus was obtained. Result(s): Out of 500previously normoglycemic COVID-19 patients selected for the study, 97 patients (19.4%) developed new onset diabetes mellitus after recovering from COVID-19 disease. Conclusion(s): The results of this study show that a significant amount of people developed new onset type 2 diabetes mellitus after having recovered from COVID-19. Blood glucose control is important not only for prediabetics affected with COVID but also for those affected with no previous status of diabetes mellitus. The results of this paper could be useful in screening and diagnosis of new onset diabetes mellitus at an early stage can be beneficial to avoid further worsening of the patient's health.

Brief Research Report: Serum clara cell 16 kDa protein levels are increased in patients hospitalized for severe SARS-CoV-2 or sepsis infection.

Background: Clara cell 16 kDa protein (CC16) is a secretory protein primarily expressed in epithelial cells in the lungs. Previous studies show that CC16 exerts anti-inflammatory and immune-modulatory properties in both acute and chronic pulmonary diseases. However, despite the evidence of CC16's high biomarker potential, evaluation of its role in infectious diseases is yet very limited. Methods: Serum CC16 concentrations were measured by ELISA and assessed in two different types of severe infections. Using a case-control study design, patients treated for either severe SARS-CoV-2 or severe non-pulmonary sepsis infection were compared to age- and sex-matched healthy human subjects. Results: Serum CC16 was significantly increased in both types of infection (SARS-CoV-2: 96.22 ± 129.01 ng/ml vs. healthy controls: 14.05 ± 7.48 ng/ml, p = 0.022; sepsis: 35.37 ± 28.10 ng/ml vs. healthy controls: 15.25 ± 7.51 ng/ml, p = 0.032) but there were no distinct differences between infections with and without pulmonary focus (p = 0.089). Furthermore, CC16 serum levels were positively correlated to disease duration and inversely to the platelet count in severe SARS-CoV-2 infection. Conclusions: Increased CC16 serum levels in both SARS-CoV-2 and sepsis reinforce the high potential as a biomarker for epithelial cell damage and bronchoalveolar-blood barrier leakage in pulmonary as well as non-pulmonary infectious diseases.

Hyperglycemia and Insulin Utilization in the Setting of Multisystem Inflammatory Syndrome in Children

Objectives Multisystem Inflammatory Syndrome in Children (MIS-C), a hyperinflammatory illness that occurs 4-6 weeks after acute infection with SARS-CoV-2, has been associated with hyperglycemia. The aim of this study was to investigate the onset, duration and severity of hyperglycemia as well as its management in MIS-C. Methods A retrospective analysis of four previously healthy patients with no prior diagnosis of diabetes mellitus was conducted on patients who developed hyperglycemia requiring insulin administration during hospitalization with MIS-C. Results All four patients were admitted to the pediatric intensive care unit for multisystem organ dysfunction in the setting of MIS-C. Patient A was a 14-year-old Hispanic male admitted for pneumonia, cardiogenic shock and encephalopathy. Patient B was a 14-year old African American (AA) female admitted for acute renal failure and shock. Patient C was a 15-year-old AA male admitted for respiratory failure and cardiogenic shock. Patient D was a 16-year-old AA male admitted for cardiogenic shock. All patients tested positive for SARS-CoV-2 IgG confirming past infection. Two patients were normal weight and the other two were obese. They developed hyperglycemia within 1-3 days of staring IV glucocorticoids, requiring a maximum of 0.5-1.5 units/kg/day of subcutaneous basal bolus insulin. Hemoglobin A1c (HbA1c) prior to starting insulin had a median of 6.7% with a range of 5.3-6.9%. All severe symptoms of MIS-C and hyperglycemia in the patients reported here ultimately resolved. One patient stopped insulin prior to cessation of steroids and two patients stopped 2-5 months after cessation. One patient was lost to follow up but their insulin prescription for home treatment was never filled. Conclusions Children with MIS-C may experience transient hyperglycemia requiring insulin, which may be caused by a combination of factors. These include insulin resistance due to increased counterregulatory hormones in the setting of critical illness. There was likely pancreatic s-cell damage by SARS-CoV-2 infection preceding the development of MIS-C as evidenced by elevated HbA1c during hospitalization. Treatment for MIS-C includes glucocorticoids, which can further induce insulin resistance. Future studies are needed to determine long-term effects of SARSCoV- 2 infection and MIS-C on the glycemic outcomes in this population.

Study of D-Dimer and Serum Ferritin Levels as Prognostic Biomarkers in Covid-19 Patients

Objective: Coronavirus disease 2019 (COVID-19) is primarily a respiratory illness causing thrombotic disorders. Pro-inflammatory cytokines are one of the responsible causes of cytokine storm syndrome in patients with COVID-19. Coagulopathy and inflammation are associated with COVID-19 severity. The coronavirus spike protein facilitates the entry of the virus into the target cells causing coagulopathy and inflammation.Other infections include direct viral toxicity, endothelial cell damage, inflammation, and deregulation of the immune response and renin-angiotensinaldosterone system. The study aims to estimate levels of D-Dimer and Serum Ferritin in symptomatic and asymptomatic COVID-19 patients and its comparison with healthy controls. Method(s): The study includes 30 healthy control and 30 symptomatic and 30 asymptomatic COVID-19 patients of both sexes. Analysis of serum ferritin was done on a fully automated immunology analyzer-SIEMENS based on the principle of chemiluminescence. D-dimer was estimated on mLab which is cartridge-based. Result(s): We observed that the levels of D-Dimer and Serum Ferritin significantly increased in symptomatic COVID-19 patients as compared to asymptomatic COVID-19 positive patients and healthy non-COVID-19 controls. Conclusion(s): The elevated serum ferritin and D-dimer were associated with a poor outcome and poor prognosis and could predict the worsening of COVID-19 patients. The significant increase showed that D-Dimer and serum ferritin accurately predicts patients developing severe COVID- infection. Copyright © 2022 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Clinical/biochemical characteristics and related outcomes in people with new-onset diabetes and COVID-19: experience from a single centre

Aims: It is known that there is a bidirectional relationship between diabetes mellitus (DM) and coronavirus disease (COVID-19). It has been described that those patients infected with SARS-CoV-2 could develop severe metabolic decompensation of pre-existing or new-onset DM, although diabetogenic effect of SARS-CoV-2 has still not been well consolidated. In fact, the coexistence of SARS-CoV-2 infection and new-onset DM is an infrequent situation. Method(s): We describe the clinical and analytical characteristics of 19 patients admitted to a Spanish tertiary hospital - all 19 having COVID-19 infection and new-onset DM. Result(s): 12/19 patients (63.2%) were female;the mean age at diagnosis of DM was 54 (39-65) years. The most frequent ethnic group was Caucasian (n=9), followed by Latin-American (n=7);7/19 (36.8%) previously met criteria for prediabetes due to altered basal glycaemia or HbA1c. The mean BMI at diagnosis was 32.26kg/m2 (27.62-35.18kg/m2). Eighteen of 19 patients (94.7%) showed bilateral bronchopneumonia. The mean blood glucose of the first blood was 17.5mmol/L (11.1-21.1mmol/L), and the mean HbA1c was 88mmol/mol (60-115mmol/mol). C-peptide was requested in eight patients and it was within normal range in 87.5% (n=7) and below the inferior threshold in one case. Autoantibodies were requested in 26.3% (five patients), being negative in 4/5 (80%) and positive in 1/5 (20%). Regarding the type of diabetes diagnosed, 18 were type 2 DM and only one case was diagnosed with type 1 DM. Seventeen had simple hyperglycaemia and two suffered a diabetic ketoacidosis. The mean HbA1c at 8.0 months (5.0-12.0 months) follow-up was 42mmol/mol (40-49mmol/mol). Conclusion(s): The majority of those described had type 2 DM that appears to have been unmasked by the COVID-19 infection, since they had high HbA1c and several risk factors for diabetes development, such as obesity and prediabetes. Most of them had their pancreatic reserve preserved, and this may suggest insulin resistance as the aetiology rather than direct beta-cell damage. A good evolution of diabetes after hospital discharge was observed in the patients followed up at our centre. Copyright © 2022 John Wiley & Sons. Copyright © 2022 John Wiley & Sons, Ltd.

COVID-19- associated hemostasis alterations and outcomes in acute ischemic stroke patients treated with intravenous thrombolysis

Background: Coronavirus disease-2019 (COVID-19) increases the risk of acute ischemic stroke (AIS). Hemostasis alterations and outcomes of reperfusion therapy (thrombolysis or thrombectomy) in COVID-19- positive AIS patients are not well studied, as yet. (Figure Presented) Aims: We aimed to test hemostasis alterations in COVID-19- positive AIS patients receiving intravenous (i.v.) thrombolysis as compared to non-infected AIS patients and to correlate results with therapy outcomes and safety. Method(s): In this prospective observational study, 110 AIS patients receiving i.v. thrombolysis (recombinant tissue plasminogen activator) with/without thrombectomy were enrolled (April 2020-December 2021). Blood samples were taken on admission (within 4.5h of symptom onset), at 1h and 24h post-event. SARS-CoV- 2 RT-PCR test performed on admission confirmed acute infection in 9 cases (COVID-19+ group). Anti-SARS- CoV- 2 antibody test proved convalescence and/or vaccination in 48 patients (post-COVID/ post-vaccination group). Markers of inflammation (CRP, ferritin, IL-6), D-dimer, fibrinogen, von Willebrand factor (VWF) antigen, factor VIII (FVIII) and factor XIII (FXIII) activity, clot-lysis assay, thrombin generation, ROTEM and angiotensin convertase enzyme (ACE)1, ACE2 activities were analyzed. Stroke severity was determined by NIHSS. Therapy-associated intracerebral hemorrhage was classified according to ECASSII criteria. Short-and long-term outcomes were defined at 7 days and 3 months post-event according to the change in NIHSS and the modified Rankin Scale, respectively. Result(s): Stroke severity was significantly greater in the COVID-19+ group. VWF antigen levels were markedly elevated in the COVID-19+ group as compared to non-infected and post-COVID/ post-vaccination groups (323 +/- 72% vs. 248 +/- 75% and 222 +/- 80%, respectively, p = 0.006). FVIII levels were parallel to VWF levels and showed significant elevation in the COVID-19+ group. Short-term outcomes of therapy and the occurrence of hemorrhagic transformation did not differ between groups. Conclusion(s): Elevated FVIII and VWF levels in COVID-19- associated AIS seem to be linked to endothelial cell injury and are associated with more severe stroke. Efficacy of thrombolysis in COVID-19+ AIS patients was similar to non-infected patients in this cohort.

The TLR-NF-kB axis contributes to the monocytic inflammatory response against a virulent strain of Lichtheimia corymbifera, a causative agent of invasive mucormycosis.

Invasive mucormycosis (IM) is a life-threatening infection caused by the fungal order Mucorales, its diagnosis is often delayed, and mortality rates range from 40-80% due to its rapid progression. Individuals suffering from hematological malignancies, diabetes mellitus, organ transplantations, and most recently COVID-19 are particularly susceptible to infection by Mucorales. Given the increase in the occurrence of these diseases, mucormycosis has emerged as one of the most common fungal infections in the last years. However, little is known about the host immune response to Mucorales. Therefore, we characterized the interaction among L. corymbifera-one of the most common causative agents of IM-and human monocytes, which are specialized phagocytes that play an instrumental role in the modulation of the inflammatory response against several pathogenic fungi. This study covered four relevant aspects of the host-pathogen interaction: i) The recognition of L. corymbifera by human monocytes. ii) The intracellular fate of L. corymbifera. iii) The inflammatory response by human monocytes against the most common causative agents of mucormycosis. iv) The main activated Pattern-Recognition Receptors (PRRs) inflammatory signaling cascades in response to L. corymbifera. Here, we demonstrate that L. corymbifera exhibits resistance to intracellular killing over 24 hours, does not germinate, and inflicts minimal damage to the host cell. Nonetheless, viable fungal spores of L. corymbifera induced early production of the pro-inflammatory cytokine IL-1ß, and late release of TNF-α and IL-6 by human monocytes. Moreover, we revealed that IL-1ß production predominantly depends on Toll-like receptors (TLRs) priming, especially via TLR4, while TNF-α is secreted via C-type lectin receptors (CTLs), and IL-6 is produced by synergistic activation of TLRs and CTLs. All these signaling pathways lead to the activation of NF-kB, a transcription factor that not only regulates the inflammatory response but also the apoptotic fate of monocytes during infection with L. corymbifera. Collectively, our findings provide new insights into the host-pathogen interactions, which may serve for future therapies to enhance the host inflammatory response to L. corymbifera.

Effect Of Covid-19 Infection On Qtc Prolongation

Background Objective: What is the association between COVID-19 infection and QTc changes? Coronavirus SARS-COV2 uses angiotensin-converting enzyme receptors 2 (ACE2) on host cells to enter into human cells. These receptors are expressed on the heart cells among other major cells. This is one of the most accepted theories for direct cardiac cell injury of COVID-19disease and associated cardiorespiratory manifestations. COVID-19 infection leads to unstable myocardial cell membranes, by causing hypoxia, myocarditis, myocardial ischemia, and abnormal host immune response. This is the main reason behind Arrhythmia and EKG changes during COVID19 infection. But the specific effect on QTc has not been studied well so far, so our research try to study this connection. Method(s): This is an observational retrospective hospital chart review involving 320 adult participants diagnosed with COVID-19 infection at our facility. After applying the exclusion criteria, 130 participants remained, who were distributed into two groups. One group with long QTc and one group with normal QTc. Data was collected and demographics were recorded using Excel and SPSS, then compared using a student's t-test for independent groups. The quantitative data are summarized by the mean and standard deviation (SD). Statistical significance was taken as P <0.05. Result(s): A total of 63 participants (48.4% of total 130 participants) met the criteria for long QTc, and a total of 67 participants(51.5%) had normal QTc (P < 0.001). There was no statistically significant mortality outcome (0.8% vs. 3.8%, P = 0.21). Conclusion(s): Our study showed 48.4% participants having an increase in QTc during COVID-19 infection, (20% of 320 total admissions). This observation is very important to help healthcare providers to gaina better understanding of this disease.