scholarly journals K18-hACE2 Mice for Studies of COVID-19 Treatments and Pathogenesis Including Anosmia

2020 ◽  
Author(s):  
Jian Zheng ◽  
Lok-Yin Roy Wong ◽  
Kun Li ◽  
Abhishek K. Verma ◽  
Miguel Ortiz ◽  
...  
Keyword(s):  
Severe Disease ◽  
Severe Pneumonia ◽  
Clinical Disease ◽  
Morbidity And Mortality ◽  
Therapeutic Interventions ◽  
Mild Disease ◽  
Common Presentation ◽  
Experimental Infections ◽  
The Brain ◽  
Substantial Morbidity

ABSTRACTThe ongoing COVID-19 pandemic is associated with substantial morbidity and mortality. While much has been learned in the first months of the pandemic, many features of COVID-19 pathogenesis remain to be determined. For example, anosmia is a common presentation and many patients with this finding show no or only minor respiratory signs. Studies in animals experimentally infected with SARS-CoV-2, the cause of COVID-19, provide opportunities to study aspects of the disease not easily investigated in human patients. COVID-19 severity ranges from asymptomatic to lethal. Most experimental infections provide insights into mild disease. Here, using K18-hACE2 mice that we originally developed for SARS studies, we show that infection with SARS-CoV-2 causes severe disease in the lung, and in some mice, the brain. Evidence of thrombosis and vasculitis was detected in mice with severe pneumonia. Further, we show that infusion of convalescent plasma (CP) from a recovered COVID-19 patient provided protection against lethal disease. Mice developed anosmia at early times after infection. Notably, while treatment with CP prevented significant clinical disease, it did not prevent anosmia. Thus K18-hACE2 mice provide a useful model for studying the pathological underpinnings of both mild and lethal COVID-19 and for assessing therapeutic interventions.

scholarly journals Endotrophin and C6Ma3, serological biomarkers of type VI collagen remodelling, reflect endoscopic and clinical disease activity in IBD

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Majken Lindholm ◽  
Line E. Godskesen ◽  
Tina Manon-Jensen ◽  
Jens Kjeldsen ◽  
Aleksander Krag ◽  
...  
Keyword(s):  
Severe Disease ◽  
Fecal Calprotectin ◽  
Clinical Disease ◽  
Inactive Disease ◽  
Type Vi Collagen ◽  
Mild Disease ◽  
C Terminus ◽  
Irritable Bowel ◽  
Serological Biomarkers ◽  
Active Disease

AbstractIn inflammatory bowel disease (IBD), the chronic inflammation deeply affects the intestinal extracellular matrix. The aim of this study was to investigate if remodeling of the intestinal basement membrane type VI collagen was associated with pathophysiological changes in Crohn’s disease (CD) and ulcerative colitis (UC). Serum from IBD patients (CD: n = 65; UC: n = 107; irritable bowel syndrome: n = 18; healthy subjects: n = 20) was investigated in this study. The serological biomarkers C6Ma3 (a matrix metalloproteinase (MMP) generated fragment of the type VI collagen α3 chain) and PRO-C6, also called endotrophin (the C-terminus of the released C5 domain of the type VI collagen α3 chain) were measured by ELISAs. Serum C6Ma3 was increased in CD patients with moderate to severe and mild endoscopically active disease compared to endoscopic remission (p = 0.002, p = 0.0048), respectively, and could distinguish endoscopically active disease from remission with an AUC of 1.0 (sensitivity: 100%, specificity: 100%) (p < 0.0001), which was superior to CRP. C6Ma3 was increased in CD patients with moderate to severe clinical disease compared to mild and remission (p = 0.04; p = 0.009). Serum PRO-C6, endotrophin, was increased in CD patients in clinically remission compared to mild disease (p = 0.04) and moderate to severe disease (p = 0.065). In UC, fecal calprotectin was the only marker that alone could distinguish both clinical and endoscopic active and inactive disease. Type VI collagen degradation of the α3 chain mediated by MMPs was increased in CD patients with endoscopically active disease, measured by the serological biomarker C6Ma3, which was able to distinguish endoscopically active from inactive CD.

scholarly journals Cytomegalovirus Infection and Inflammation in Developing Brain

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1078
Author(s):  
Fran Krstanović ◽  
William J. Britt ◽  
Stipan Jonjić ◽  
Ilija Brizić
Keyword(s):  
Cytomegalovirus Infection ◽  
Hcmv Infection ◽  
Severe Disease ◽  
Intraperitoneal Administration ◽  
Inflammatory Factors ◽  
Mcmv Infection ◽  
Newborn Mice ◽  
Organ Systems ◽  
Congenital Hcmv Infection ◽  
The Brain

Human cytomegalovirus (HCMV) is a highly prevalent herpesvirus that can cause severe disease in immunocompromised individuals and immunologically immature fetuses and newborns. Most infected newborns are able to resolve the infection without developing sequelae. However, in severe cases, congenital HCMV infection can result in life-threatening pathologies and permanent damage of organ systems that possess a low regenerative capacity. Despite the severity of the problem, HCMV infection of the central nervous system (CNS) remains inadequately characterized to date. Cytomegaloviruses (CMVs) show strict species specificity, limiting the use of HCMV in experimental animals. Infection following intraperitoneal administration of mouse cytomegalovirus (MCMV) into newborn mice efficiently recapitulates many aspects of congenital HCMV infection in CNS. Upon entering the CNS, CMV targets all resident brain cells, consequently leading to the development of widespread histopathology and inflammation. Effector functions from both resident cells and infiltrating immune cells efficiently resolve acute MCMV infection in the CNS. However, host-mediated inflammatory factors can also mediate the development of immunopathologies during CMV infection of the brain. Here, we provide an overview of the cytomegalovirus infection in the brain, local immune response to infection, and mechanisms leading to CNS sequelae.

scholarly journals SAT0541 THE SEVERITY OF FMF MAY BE ASSOCIATED WITH CO-MORBIDITIES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1227.3-1228
Author(s):  
M. E. Tezcan ◽  
N. Şen ◽  
M. Yilmaz ◽  
Ö. Volkan ◽  
E. Tükel ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Scoring System ◽  
Disease Duration ◽  
Severe Disease ◽  
Smoking History ◽  
Disease Group ◽  
Severity Scoring ◽  
Mild Disease ◽  
Co Morbidity ◽  
Mediterranean Fever

Background:Familial Mediterranean fever (FMF) is an auto inflammatory disease with recurrent attacks of serositis. Frequent attacks and disease related sequels may be associated with co-morbidities in FMF patients.Objectives:One of the tools for evaluating the FMF severity is the international severity scoring system for FMF (ISSF)1. This score includes disease related sequels, acute phase measurements, attack features and exertional leg pain. Therefore, more severe disease may be link with subclinical inflammation, amyloidosis and frequent, prolonged and widespread attacks. All these components may augment the frequency of non-disease related co-morbidities.Methods:We enrolled 158 FMF patients who fulfilled modifiedTel-HashomerDiagnosisCriteria2. The patients dichotomized based upon disease severity (mild disease or severe disease). Patients with ISSF scores lower or equal to 2 were accepted to have mild disease. Then, we compared frequency of non-disease related co-morbidities between the groups. These co-morbidities arehypertension, hypothyroidism, hyperthyroidism cardiovascular diseases, coronary artery diseases, cerebrovascular diseases, chronic renal disease (non-FMF related), chronic obstructive pulmonary diseases, and diabetes mellitus. This study was approved by the Local Research Ethics Committee and carried out in compliance with the Helsinki Declaration. All the patients gave written informed consent. P-value lower than 0.05 was considered as statistically significant.Results:Demographic features, disease duration, smoking history and body mass index (BMI) were similar between the groups. Frequency of co-morbidity in severe disease group was statistically higher than mild disease group (p=0.02). Most frequent co-morbidity was hypertension in both groups.Table.Features of mild and severe FMF groupsMild (n=135)Severe (n=23)pGender (M/F)47/8811/120.23Age36.4±11.336.5±14.30.68Smoking (%)38 (28.1)5 (21.7)0.52BMI (kg/m2)24.3±9.224.0±8.90.34Disease duration (year)7.7±11.38.6±14.30.09Amyloidosis (%)2 (1.4)3 (13.0)0.02Exon 10 homozygote (%)35 (25.9)9 (39.1)0.19Colchicine dosage (mg/day)1.2±0.41.4±0.50.02ISSF scores0.7 ±0.73.4±0.5<0.001Co-morbidity (%)25 (18.5)9 (39.1)0.02Conclusion:In our FMF patient cohort, we found that severity of the disease may be associated with higher frequency of co-morbidities. Therefore, clinicians should be aware of the high possibility of co-morbidities in patients with more severe FMF and addressed these co-morbidities timely and properly.References:[1]Demirkaya E, et al. Development and initial validation of international severity scoring system for familial Mediterranean fever (ISSF). Ann Rheum Dis 2016;75:1051-6.[2]Berkun Y, et al. Diagnostic criteria of familial Mediterranean fever. Autoimmun Rev 2014;13:388-90.Acknowledgments:NoneDisclosure of Interests:None declared

A Case Series of SARS-CoV-2 RT-PCR-Positive Hospitalized Infants 60 Days of Age or Younger From 2 New York City Pediatric Emergency Departments

2021 ◽  
Vol 60 (4-5) ◽  
pp. 247-251
Author(s):  
Ameer Hassoun ◽  
Nessy Dahan ◽  
Christopher Kelly
Keyword(s):  
New York ◽  
Case Reports ◽  
Severe Disease ◽  
Case Series ◽  
Pediatric Emergency ◽  
Rt Pcr ◽  
Vulnerable Group ◽  
Mild Disease ◽  
Young Infants ◽  
Novel Coronavirus

The emergence of novel coronavirus disease-2019 poses an unprecedented challenge to pediatricians. While the majority of children experience mild disease, initial case reports on young infants are conflicting. We present a case series of 8 hospitalized infants 60 days of age or younger with coronavirus disease-2019. A quarter of these patients had coinfections (viral or bacterial). None of these infants had severe disease. Continued vigilance in testing this vulnerable group of infants is warranted.

scholarly journals Analysis of clinical characteristics of severe pertussis in infants and children: a retrospective study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Caiying Wang ◽  
Huimin Zhang ◽  
Yanlan Zhang ◽  
Lin Xu ◽  
Min Miao ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Clinical Characteristics ◽  
Severe Disease ◽  
Severe Pneumonia ◽  
Infants And Children ◽  
Critically Ill Children ◽  
Young Infants ◽  
Incidence And Mortality ◽  
Increasing Trend ◽  
Medical University

Abstract Background The incidence of pertussis shows an increasing trend in recent years, but some clinicians often lack sufficient understanding of the clinical characteristics and risk factors for severe pertussis, and more effective measures should be taken to reduce the incidence and mortality of pertussis in young infants Methods A retrospective study was conducted, and 184 infants and children with pertussis who had been hospitalized in the Department of Pediatrics of Beijing Ditan Hospital affiliated with Capital Medical University from January 2016 to December 2017 were included. Clinical data of the patients were collected and the clinical characteristics were statistically analyzed Results Among the 184 patients, 41.85% were infants < 3 months of age, and 65.22% of the total patients were not vaccinated against pertussis. There were 22 critically ill children, among whom 4 died, and compared with mild cases, they had a higher proportion of children younger than 3 months of age and infants not vaccinated against pertussis (63.64% vs. 38.89% and 100% vs. 60.49%, respectively); a higher proportion of children with severe pneumonia (100% vs. 0%); higher leukocyte count(× 109/L , 35.80 ± 20.53 vs 19.41 ± 8.59); and a higher proportion of children with severe hyperleukocytosis (18.18% vs. 0%, respectively) (P<0.05) Conclusions 1. Infants aged <3 months not vaccinated for pertussis appear more likely to become infected and have more severe disease. 2. Severe pneumonia and hyperleukocytosis are the main mechanisms underlying severe pertussis.

scholarly journals SARS-CoV-2-Laden Respiratory Aerosol Deposition in the Lung Alveolar-Interstitial Region Is a Potential Risk Factor for Severe Disease: A Modeling Study

2021 ◽  
Vol 11 (5) ◽  
pp. 431
Author(s):  
Sabine Hofer ◽  
Norbert Hofstätter ◽  
Albert Duschl ◽  
Martin Himly
Keyword(s):  
Risk Factor ◽  
Particle Deposition ◽  
Early Stage ◽  
Severe Disease ◽  
Ambient Air ◽  
Aerosol Deposition ◽  
Pulmonary Involvement ◽  
Mild Disease ◽  
Disease Initiation

COVID-19, predominantly a mild disease, is associated with more severe clinical manifestation upon pulmonary involvement. Virion-laden aerosols and droplets target different anatomical sites for deposition. Compared to droplets, aerosols more readily advance into the peripheral lung. We performed in silico modeling to confirm the secondary pulmonary lobules as the primary site of disease initiation. By taking different anatomical aerosol origins into consideration and reflecting aerosols from exhalation maneuvers breathing and vocalization, the physicochemical properties of generated respiratory aerosol particles were defined upon conversion to droplet nuclei by evaporation at ambient air. To provide detailed, spatially-resolved information on particle deposition in the thoracic region of the lung, a top-down refinement approach was employed. Our study presents evidence for hot spots of aerosol deposition in lung generations beyond the terminal bronchiole, with a maximum in the secondary pulmonary lobules and a high preference to the lower lobes of both lungs. In vivo, initial chest CT anomalies, the ground glass opacities, resulting from partial alveolar filling and interstitial thickening in the secondary pulmonary lobules, are likewise localized in these lung generations, with the highest frequency in both lower lobes and in the early stage of disease. Hence, our results suggest a disease initiation right there upon inhalation of virion-laden respiratory aerosols, linking the aerosol transmission route to pathogenesis associated with higher disease burden and identifying aerosol transmission as a new independent risk factor for developing a pulmonary phase with a severe outcome.

scholarly journals Hepatic steatosis: a risk factor for increased COVID-19 prevalence and severity—a computed tomography study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Asmaa Ali ◽  
Mona Hasan ◽  
Shaimaa Hamed ◽  
Amir Elhamy
Keyword(s):  
Hepatic Steatosis ◽  
Severe Disease ◽  
Severe Pneumonia ◽  
Liver Disorder ◽  
Control Group ◽  
Case Group ◽  
World Population ◽  
Positive Class ◽  
The Mean ◽  
And Control

Abstract Background Around 25% of the world population was affected by the metabolic-related fatty liver disorder. Hepatic steatosis is frequently observed in conjunction with hypertension, obesity comorbidities, and diabetes. We evaluate the hepatic steatosis frequency found in chest CT exams of COVID-19-positive cases compared to non-infected controls and evaluate the related increased prevalence and severity of COVID. Results Our research includes 355 subjects, 158 with positive PCR for COVID-19 (case group) and 197 with negative PCR and negative CT chest (control group). The mean age in the positive group was 50.6 ± 16 years, and in the control, it was 41.3 ± 16 years (p < 0.001). Our study consists of 321 men (90.5%) and 34 women (9.5%). The number of males in both cases and control groups was greater. In the case group, 93% men vs. 6.9% women, while in controls, 88.3% men vs.11.6% women, p < 0.001. CT revealed normal results in 55.5% of individuals (i.e., CORADs 1) and abnormal findings in 45.5% of participants (i.e., CORADs 2–5). In abnormal scan, CO-RADs 2 was 13.92%, while CO-RADs 3–4 were 20.89% of cases. CO-RADs 5 comprised 65.19% of all cases. Approximately 42.6% of cases had severe disease (CT score ≥ 20), all of them were CO-RADs 5. The PCR-positive class had a greater prevalence of hepatic steatosis than controls (28.5% vs.12.2%, p < 0.001). CO-RADs 2 represented 11.1%, CO-RADs 3–4 represented 15.6%, and CO-RADs 5 represented 73.3% in the hepatic steatosis cases. The mean hepatic attenuation value in the case group was 46.79 ± 12.68 and in the control group 53.34 ± 10.28 (p < 0.001). When comparing patients with a higher severity score (CT score ≥ 20) to those with non-severe pneumonia, it was discovered that hepatic steatosis is more prevalent (73.2% vs. 26.8%). Conclusions Steatosis was shown to be substantially more prevalent in COVID-19-positive individuals. There is a relation among metabolic syndrome, steatosis of the liver, and obesity, as well as the COVID-19 severity.

scholarly journals Outpatient Management of COVID-19 Disease: A Holistic Patient-Centered Proposal Based on the Greek Experience

2021 ◽  
Vol 11 (8) ◽  
pp. 709
Author(s):  
Adamantia Liapikou ◽  
Eleni Tzortzaki ◽  
Georgios Hillas ◽  
Miltiadis Markatos ◽  
Ilias C. Papanikolaou ◽  
...  
Keyword(s):  
Preventive Measures ◽  
Severe Disease ◽  
Hospital Setting ◽  
Guidance Document ◽  
Outpatient Management ◽  
Patient Centered ◽  
Mild Disease ◽  
Novel Coronavirus ◽  
Second Wave ◽  
Close Contacts

Novel coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide pandemic and affected more than 227 countries or territories, resulting in more than 179 million cases with over 3.890.00 deaths, as of June 25, 2021. The Hellenic Thoracic Society (HTS) during the second wave of COVID-19 pandemic released a guidance document for the management of patients with COVID-19 in the community and in hospital setting. In this review, with guidance the HTS document, we are discussing the outpatient management of COVID-19 patients, including the preventive measures, the patients’ isolation and quarantine criteria of close contacts, the severity and risk stratification, including the decisions for advanced hospitalization, and the disease management at home in patients with mild disease and after hospital discharge for those with more severe disease.

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