Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 9 de 9
Filter
1.
Biomed Pharmacother ; 148: 112753, 2022 04.
Article in English | MEDLINE | ID: covidwho-1707727

ABSTRACT

COVID-19 is a lethal disease caused by the pandemic SARS-CoV-2, which continues to be a public health threat. COVID-19 is principally a respiratory disease and is often associated with sputum retention and cytokine storm, for which there are limited therapeutic options. In this regard, we evaluated the use of BromAc®, a combination of Bromelain and Acetylcysteine (NAC). Both drugs present mucolytic effect and have been studied to treat COVID-19. Therefore, we sought to examine the mucolytic and anti-inflammatory effect of BromAc® in tracheal aspirate samples from critically ill COVID-19 patients requiring mechanical ventilation. METHOD: Tracheal aspirate samples from COVID-19 patients were collected following next of kin consent and mucolysis, rheometry and cytokine analysis using Luminex kit was performed. RESULTS: BromAc® displayed a robust mucolytic effect in a dose dependent manner on COVID-19 sputum ex vivo. BromAc® showed anti-inflammatory activity, reducing the action of cytokine storm, chemokines including MIP-1alpha, CXCL8, MIP-1b, MCP-1 and IP-10, and regulatory cytokines IL-5, IL-10, IL-13 IL-1Ra and total reduction for IL-9 compared to NAC alone and control. BromAc® acted on IL-6, demonstrating a reduction in G-CSF and VEGF-D at concentrations of 125 and 250 µg. CONCLUSION: These results indicate robust mucolytic and anti-inflammatory effect of BromAc® ex vivo in tracheal aspirates from critically ill COVID-19 patients, indicating its potential to be further assessed as pharmacological treatment for COVID-19.


Subject(s)
Acetylcysteine/pharmacology , Bromelains/pharmacology , COVID-19/pathology , Chemokines/drug effects , Cytokines/drug effects , Sputum/cytology , Acetylcysteine/administration & dosage , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/pharmacology , Bromelains/administration & dosage , Cytokine Release Syndrome/pathology , Dose-Response Relationship, Drug , Down-Regulation , Drug Combinations , Expectorants/pharmacology , Female , Humans , Inflammation Mediators/metabolism , Male , Middle Aged , Respiration, Artificial , Rheology , SARS-CoV-2 , Trachea/pathology , Young Adult
2.
Vet Res ; 52(1): 121, 2021 Sep 16.
Article in English | MEDLINE | ID: covidwho-1414142

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is causing a global crisis. It is still unresolved. Although many therapies and vaccines are being studied, they are still in their infancy. As this pandemic continues, rapid and accurate research for the development of therapies and vaccines is needed. Therefore, it is necessary to understand characteristics of diseases caused by SARS-CoV-2 through animal models. Syrian hamsters are known to be susceptible to SARS-CoV-2. They were intranasally inoculated with SARS-CoV-2. At 2, 4, 8, 12, and 16 days post-infection (dpi), these hamsters were euthanized, and tissues were collected for ultrastructural and microstructural examinations. Microscopic lesions were prominent in the upper and lower respiratory tracts from 2 and 4 dpi groups, respectively. The respiratory epithelium in the trachea, bronchiole, and alveolar showed pathological changes. Inflammatory cells including neutrophils, lymphocytes, macrophages, and eosinophils were infiltrated in/around tracheal lamina propria, pulmonary vessels, alveoli, and bronchiole. In pulmonary lesions, alveolar wall was thickened with infiltrated inflammatory cells, mainly neutrophils and macrophages. In the trachea, epithelial damages started from 2 dpi and recovered from 8 dpi, consistent with microscopic results, High levels of SARS-CoV-2 nucleoprotein were detected at 2 dpi and 4 dpi. In the lung, lesions were most severe at 8 dpi. Meanwhile, high levels of SARS-CoV-2 were detected at 4 dpi. Electron microscopic examinations revealed cellular changes in the trachea epithelium and alveolar epithelium such as vacuolation, sparse micro-organelle, and poor cellular margin. In the trachea epithelium, the number of cytoplasmic organelles was diminished, and small vesicles were prominent from 2 dpi. Some of these electron-lucent vesicles were filled with virion particles. From 8 dpi, the trachea epithelium started to recover. Because of shrunken nucleus and swollen cytoplasm, the N/C ratio of type 2 pneumocyte decreased at 8 and 12 dpi. From 8 dpi, lamellar bodies on type 2 pneumocyte cytoplasm were increasingly observed. Their number then decreased from 16 dpi. However, there was no significant change in type 1 pneumocyte. Viral vesicles were only observed in the cytoplasm of type 2 pneumocyte. In conclusion, ultra- and micro-structural changes presented in this study may provide useful information for SARS-CoV-2 studies in various fields.


Subject(s)
COVID-19/pathology , Respiratory System/pathology , SARS-CoV-2/pathogenicity , Animals , Cricetinae , Immunohistochemistry/veterinary , Male , Mesocricetus , Pilot Projects , RNA, Viral/chemistry , RNA, Viral/isolation & purification , Real-Time Polymerase Chain Reaction/veterinary , Respiratory System/chemistry , Respiratory System/ultrastructure , Respiratory System/virology , Time Factors , Trachea/pathology , Trachea/ultrastructure , Trachea/virology , Weight Loss
3.
Cell Res ; 31(8): 836-846, 2021 08.
Article in English | MEDLINE | ID: covidwho-1275907

ABSTRACT

Severe COVID-19 disease caused by SARS-CoV-2 is frequently accompanied by dysfunction of the lungs and extrapulmonary organs. However, the organotropism of SARS-CoV-2 and the port of virus entry for systemic dissemination remain largely unknown. We profiled 26 COVID-19 autopsy cases from four cohorts in Wuhan, China, and determined the systemic distribution of SARS-CoV-2. SARS-CoV-2 was detected in the lungs and multiple extrapulmonary organs of critically ill COVID-19 patients up to 67 days after symptom onset. Based on organotropism and pathological features of the patients, COVID-19 was divided into viral intrapulmonary and systemic subtypes. In patients with systemic viral distribution, SARS-CoV-2 was detected in monocytes, macrophages, and vascular endothelia at blood-air barrier, blood-testis barrier, and filtration barrier. Critically ill patients with long disease duration showed decreased pulmonary cell proliferation, reduced viral RNA, and marked fibrosis in the lungs. Permanent SARS-CoV-2 presence and tissue injuries in the lungs and extrapulmonary organs suggest direct viral invasion as a mechanism of pathogenicity in critically ill patients. SARS-CoV-2 may hijack monocytes, macrophages, and vascular endothelia at physiological barriers as the ports of entry for systemic dissemination. Our study thus delineates systemic pathological features of SARS-CoV-2 infection, which sheds light on the development of novel COVID-19 treatment.


Subject(s)
COVID-19/pathology , Lung/virology , SARS-CoV-2/isolation & purification , Aged , Aged, 80 and over , Autopsy , COVID-19/virology , China , Cohort Studies , Critical Illness , Female , Fibrosis , Hospitalization , Humans , Kidney/pathology , Kidney/virology , Leukocytes, Mononuclear/pathology , Leukocytes, Mononuclear/virology , Lung/pathology , Male , Middle Aged , RNA, Viral/metabolism , SARS-CoV-2/genetics , Spleen/pathology , Spleen/virology , Trachea/pathology , Trachea/virology
4.
Gastroenterology ; 160(5): 1647-1661, 2021 04.
Article in English | MEDLINE | ID: covidwho-1065985

ABSTRACT

BACKGROUND & AIMS: Gastrointestinal (GI) manifestations have been increasingly reported in patients with coronavirus disease 2019 (COVID-19). However, the roles of the GI tract in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not fully understood. We investigated how the GI tract is involved in SARS-CoV-2 infection to elucidate the pathogenesis of COVID-19. METHODS: Our previously established nonhuman primate (NHP) model of COVID-19 was modified in this study to test our hypothesis. Rhesus monkeys were infected with an intragastric or intranasal challenge with SARS-CoV-2. Clinical signs were recorded after infection. Viral genomic RNA was quantified by quantitative reverse transcription polymerase chain reaction. Host responses to SARS-CoV-2 infection were evaluated by examining inflammatory cytokines, macrophages, histopathology, and mucin barrier integrity. RESULTS: Intranasal inoculation with SARS-CoV-2 led to infections and pathologic changes not only in respiratory tissues but also in digestive tissues. Expectedly, intragastric inoculation with SARS-CoV-2 resulted in the productive infection of digestive tissues and inflammation in both the lung and digestive tissues. Inflammatory cytokines were induced by both types of inoculation with SARS-CoV-2, consistent with the increased expression of CD68. Immunohistochemistry and Alcian blue/periodic acid-Schiff staining showed decreased Ki67, increased cleaved caspase 3, and decreased numbers of mucin-containing goblet cells, suggesting that the inflammation induced by these 2 types of inoculation with SARS-CoV-2 impaired the GI barrier and caused severe infections. CONCLUSIONS: Both intranasal and intragastric inoculation with SARS-CoV-2 caused pneumonia and GI dysfunction in our rhesus monkey model. Inflammatory cytokines are possible connections for the pathogenesis of SARS-CoV-2 between the respiratory and digestive systems.


Subject(s)
COVID-19/transmission , Gastroenteritis/pathology , Gastrointestinal Tract/pathology , Lung/pathology , Animals , Bronchi/metabolism , Bronchi/pathology , COVID-19/immunology , COVID-19/metabolism , COVID-19/pathology , COVID-19 Nucleic Acid Testing , Caspase 3/metabolism , Cytokines/immunology , Disease Models, Animal , Gastric Mucosa , Gastroenteritis/metabolism , Gastroenteritis/virology , Gastrointestinal Tract/immunology , Gastrointestinal Tract/metabolism , Goblet Cells/pathology , Intestine, Small/metabolism , Intestine, Small/pathology , Ki-67 Antigen/metabolism , Lung/diagnostic imaging , Lung/immunology , Lung/metabolism , Macaca mulatta , Nasal Mucosa , RNA, Viral/isolation & purification , Random Allocation , Rectum/metabolism , Rectum/pathology , SARS-CoV-2 , Trachea/metabolism , Trachea/pathology
5.
Lancet ; 396(10247): 320-332, 2020 08 01.
Article in English | MEDLINE | ID: covidwho-981695

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic, with increasing deaths worldwide. To date, documentation of the histopathological features in fatal cases of the disease caused by SARS-CoV-2 (COVID-19) has been scarce due to sparse autopsy performance and incomplete organ sampling. We aimed to provide a clinicopathological report of severe COVID-19 cases by documenting histopathological changes and evidence of SARS-CoV-2 tissue tropism. METHODS: In this case series, patients with a positive antemortem or post-mortem SARS-CoV-2 result were considered eligible for enrolment. Post-mortem examinations were done on 14 people who died with COVID-19 at the King County Medical Examiner's Office (Seattle, WA, USA) and Snohomish County Medical Examiner's Office (Everett, WA, USA) in negative-pressure isolation suites during February and March, 2020. Clinical and laboratory data were reviewed. Tissue examination was done by light microscopy, immunohistochemistry, electron microscopy, and quantitative RT-PCR. FINDINGS: The median age of our cohort was 73·5 years (range 42-84; IQR 67·5-77·25). All patients had clinically significant comorbidities, the most common being hypertension, chronic kidney disease, obstructive sleep apnoea, and metabolic disease including diabetes and obesity. The major pulmonary finding was diffuse alveolar damage in the acute or organising phases, with five patients showing focal pulmonary microthrombi. Coronavirus-like particles were detected in the respiratory system, kidney, and gastrointestinal tract. Lymphocytic myocarditis was observed in one patient with viral RNA detected in the tissue. INTERPRETATION: The primary pathology observed in our cohort was diffuse alveolar damage, with virus located in the pneumocytes and tracheal epithelium. Microthrombi, where observed, were scarce and endotheliitis was not identified. Although other non-pulmonary organs showed susceptibility to infection, their contribution to the pathogenesis of SARS-CoV-2 infection requires further examination. FUNDING: None.


Subject(s)
Coronavirus Infections/pathology , Pneumonia, Viral/pathology , Adult , Aged , Aged, 80 and over , Alveolar Epithelial Cells/pathology , Alveolar Epithelial Cells/ultrastructure , Alveolar Epithelial Cells/virology , Autopsy , Betacoronavirus , COVID-19 , Coronavirus Infections/epidemiology , Female , Gastrointestinal Tract/pathology , Gastrointestinal Tract/ultrastructure , Gastrointestinal Tract/virology , Heart/virology , Humans , Kidney/pathology , Kidney/ultrastructure , Kidney/virology , Liver/pathology , Liver/ultrastructure , Liver/virology , Male , Middle Aged , Myocardium/pathology , Myocardium/ultrastructure , Pandemics , Pneumonia, Viral/epidemiology , Pulmonary Alveoli/pathology , Pulmonary Alveoli/ultrastructure , Respiratory Mucosa/pathology , Respiratory Mucosa/ultrastructure , Respiratory Mucosa/virology , SARS-CoV-2 , Spleen/pathology , Spleen/ultrastructure , Spleen/virology , Thrombosis/pathology , Trachea/pathology , Trachea/ultrastructure , Trachea/virology , Washington/epidemiology
6.
Avian Pathol ; 49(3): 243-250, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-828848

ABSTRACT

This paper describes the characterization of a new infectious bronchitis virus (IBV) strain D181, that rapidly evolved from a low-level incidental finding in 2017 to become the second most isolated IBV strain in Dutch layers and breeders in 2018, as well as being found in samples from Germany and Belgium. Based on the sequence of the S gene and the results of cross-neutralization tests, D181 can be considered as a new serotype and the second lineage within genotype II (GII-2). The experimental infection of SPF hens confirmed the ability of D181 to cause a drop in egg production, and immunohistochemistry showed presence of the virus in the trachea, lung and conjunctiva at 5 days post inoculation and in the caecal tonsils at 5 and 8 days post inoculation. In silico analysis of several widely used PCR primers indicated that primer sets adapted for GII might be needed to detect D181, as many general S1 primers might miss it.


Subject(s)
Chickens , Coronavirus Infections/veterinary , Infectious bronchitis virus/genetics , Poultry Diseases/virology , Serogroup , Animals , Cilia/pathology , Cilia/virology , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Europe/epidemiology , Genotype , Phylogeny , Poultry Diseases/epidemiology , Trachea/pathology , Trachea/virology
7.
Avian Pathol ; 49(1): 21-28, 2020 Feb.
Article in English | MEDLINE | ID: covidwho-822641

ABSTRACT

Since the emergence of low pathogenic avian influenza (LPAI) H9N2 viruses in Morocco in 2016, severe respiratory problems have been encountered in the field. Infectious bronchitis virus (IBV) is often detected together with H9N2, suggesting disease exacerbation in cases of co-infections. This hypothesis was therefore tested and confirmed in laboratory conditions using specific-pathogen-free chickens. Most common field vaccine programmes were then tested to compare their efficacies against these two co-infecting agents. IBV γCoV/chicken/Morocco/I38/2014 (Mor-IT02) and LPAI virus A/chicken/Morocco/SF1/2016 (Mor-H9N2) were thus inoculated to commercial chickens. We showed that vaccination with two heterologous IBV vaccines (H120 at day one and 4/91 at day 14 of age) reduced the severity of clinical signs as well as macroscopic lesions after simultaneous experimental challenge. In addition, LPAI H9N2 vaccination was more efficient at day 7 than at day 1 in limiting disease post simultaneous challenge.RESEARCH HIGHLIGHTS Simultaneous challenge with IBV and AIV H9N2 induced higher pathogenicity in SPF birds than inoculation with IBV or AIV H9N2 alone.Recommended vaccination programme in commercial broilers to counter Mor-IT02 IBV and LPAIV H9N2 simultaneous infections: IB live vaccine H120 (d1), AIV H9N2 inactivated vaccine (d7), IB live vaccine 4-91 (d14).


Subject(s)
Chickens , Coinfection/veterinary , Coronavirus Infections/veterinary , Infectious bronchitis virus , Influenza A Virus, H9N2 Subtype , Influenza in Birds/virology , Animals , Antibodies, Viral/blood , Chick Embryo , Coinfection/prevention & control , Coinfection/virology , Coronavirus Infections/prevention & control , Coronavirus Infections/virology , Influenza in Birds/prevention & control , Lung/pathology , Morocco , Oropharynx/virology , Pilot Projects , Poultry Diseases/prevention & control , Poultry Diseases/virology , RNA, Viral/chemistry , RNA, Viral/isolation & purification , Real-Time Polymerase Chain Reaction/veterinary , Specific Pathogen-Free Organisms , Trachea/pathology , Vaccination/veterinary , Vaccines, Attenuated , Viral Vaccines , Virus Shedding
9.
Heart Lung ; 49(6): 855-857, 2020.
Article in English | MEDLINE | ID: covidwho-276571

ABSTRACT

A 51-year-old man known to be affected by Mounier-Kuhn syndrome (MKS). presented to Accident & Emergecy (A&E) with fever, dyspnea and deterioration of his chronic coughs. Increased diameters of his trachea (39 mm), right (30 mm) and left (26 mm) main bronchi were revealed by chest computerized tomography (CT) scan. CT scan showed also ground-glass opacities (GGO) and bronchiectasis in the mid and lower zones of both lungs. COIVD-19 infection was eventually confirmed by RT-PCR. A severe form of COVID-19 could occur even in the early stages of the disease in presence of underlying co-morbidities including MKS, which increases the susceptibility to more recurrent and severe respiratory infections.


Subject(s)
Coronavirus Infections/complications , Pneumonia, Viral/complications , Respiratory Distress Syndrome/virology , Tracheobronchomegaly/complications , COVID-19 , Dyspnea/etiology , Humans , Lung/physiopathology , Male , Middle Aged , Pandemics , Tomography, X-Ray Computed , Trachea/pathology
SELECTION OF CITATIONS
SEARCH DETAIL