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1.
Cell Death Dis ; 12(1): 53, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33414457

RESUMO

Interleukin-38 has recently been shown to have anti-inflammatory properties in lung inflammatory diseases. However, the effects of IL-38 in viral pneumonia remains unknown. In the present study, we demonstrate that circulating IL-38 concentrations together with IL-36α increased significantly in influenza and COVID-19 patients, and the level of IL-38 and IL-36α correlated negatively and positively with disease severity and inflammation, respectively. In the co-cultured human respiratory epithelial cells with macrophages to mimic lung microenvironment in vitro, IL-38 was able to alleviate inflammatory responses by inhibiting poly(I:C)-induced overproduction of pro-inflammatory cytokines and chemokines through intracellular STAT1, STAT3, p38 MAPK, ERK1/2, MEK, and NF-κB signaling pathways. Intriguingly, transcriptomic profiling revealed that IL-38 targeted genes were associated with the host innate immune response to virus. We also found that IL-38 counteracts the biological processes induced by IL-36α in the co-culture. Furthermore, the administration of recombinant IL-38 could mitigate poly I:C-induced lung injury, with reduced early accumulation of neutrophils and macrophages in bronchoalveolar lavage fluid, activation of lymphocytes, production of pro-inflammatory cytokines and chemokines and permeability of the alveolar-epithelial barrier. Taken together, our study indicates that IL-38 plays a crucial role in protection from exaggerated pulmonary inflammation during poly(I:C)-induced pneumonia, thereby providing the basis of a novel therapeutic target for respiratory viral infections.


Assuntos
/metabolismo , Imunidade Inata/efeitos dos fármacos , Influenza Humana/metabolismo , Interleucinas/farmacologia , Pneumonia/prevenção & controle , Poli I-C/toxicidade , Sistema Respiratório/imunologia , Animais , /virologia , Citocinas/metabolismo , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , Vírus da Influenza A/isolamento & purificação , Influenza Humana/imunologia , Influenza Humana/virologia , Interleucina-1/sangue , Interleucinas/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pneumonia/induzido quimicamente , Pneumonia/imunologia , Pneumonia/patologia , Sistema Respiratório/metabolismo , Sistema Respiratório/patologia , /isolamento & purificação
2.
Viruses ; 13(1)2021 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-33477379

RESUMO

Porcine deltacoronavirus (PDCoV) strain OH-FD22 infects poultry and shares high nucleotide identity with sparrow-origin deltacoronaviruses (SpDCoV) ISU73347 and HKU17 strains. We hypothesized that the spike (S) protein or receptor-binding domain (RBD) from these SpDCoVs would alter the host and tissue tropism of PDCoV. First, an infectious cDNA clone of PDCoV OH-FD22 strain (icPDCoV) was generated and used to construct chimeric icPDCoVs harboring the S protein of HKU17 (icPDCoV-SHKU17) or the RBD of ISU73347 (icPDCoV-RBDISU). To evaluate their pathogenesis, neonatal gnotobiotic pigs were inoculated orally/oronasally with the recombinant viruses or PDCoV OH-FD22. All pigs inoculated with icPDCoV or OH-FD22 developed severe diarrhea and shed viral RNA at moderate-high levels (7.62-10.56 log10 copies/mL) in feces, and low-moderate levels in nasal swabs (4.92-8.48 log10 copies/mL). No pigs in the icPDCoV-SHKU17 and icPDCoV-RBDISU groups showed clinical signs. Interestingly, low-moderate levels (5.07-7.06 log10 copies/mL) of nasal but not fecal viral RNA shedding were detected transiently at 1-4 days post-inoculation in 40% (2/5) of icPDCoV-SHKU17- and 50% (1/2) of icPDCoV-RBDISU-inoculated pigs. These results confirm that PDCoV infected both the upper respiratory and intestinal tracts of pigs. The chimeric viruses displayed an attenuated phenotype with the loss of tropism for the pig intestine. The SpDCoV S protein and RBD reduced viral replication in pigs, suggesting limited potential for cross-species spillover upon initial passage.


Assuntos
Infecções por Coronavirus/patologia , Intestinos/patologia , Sistema Respiratório/patologia , Glicoproteína da Espícula de Coronavírus/genética , Tropismo Viral/genética , Motivos de Aminoácidos , Animais , Doenças das Aves/virologia , Linhagem Celular , Intestinos/virologia , Proteínas Recombinantes/genética , Sistema Respiratório/virologia , Pardais , Suínos , Doenças dos Suínos/virologia , Virulência/genética
3.
PLoS One ; 15(12): e0243735, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33315873

RESUMO

INTRODUCTION: Wheezing is a major problem in children, and respiratory viruses are often believed to be the causative agent. While molecular detection tools enable identification of respiratory viruses in wheezing children, it remains unclear if and how these viruses are associated with wheezing. The objective of this systematic review is to clarify the prevalence of different respiratory viruses in children with wheezing. METHODS: We performed an electronic in Pubmed and Global Index Medicus on 01 July 2019 and manual search. We performed search of studies that have detected common respiratory viruses in children ≤18 years with wheezing. We included only studies using polymerase chain reaction (PCR) assays. Study data were extracted and the quality of articles assessed. We conducted sensitivity, subgroup, publication bias, and heterogeneity analyses using a random effects model. RESULTS: The systematic review included 33 studies. Rhinovirus, with a prevalence of 35.6% (95% CI 24.6-47.3, I2 98.4%), and respiratory syncytial virus, at 31.0% (95% CI 19.9-43.3, I2 96.4%), were the most common viruses detected. The prevalence of other respiratory viruses was as follows: human bocavirus 8.1% (95% CI 5.3-11.3, I2 84.6%), human adenovirus 7.7% (95% CI 2.6-15.0, I2 91.0%), influenza virus6.5% (95% CI 2.2-12.6, I2 92.4%), human metapneumovirus5.8% (95% CI 3.4-8.8, I2 89.0%), enterovirus 4.3% (95% CI 0.1-12.9, I2 96.2%), human parainfluenza virus 3.8% (95% CI 1.5-6.9, I2 79.1%), and human coronavirus 2.2% (95% CI 0.6-4.4, I2 79.4%). CONCLUSIONS: Our results suggest that rhinovirus and respiratory syncytial virus may contribute to the etiology of wheezing in children. While the clinical implications of molecular detection of respiratory viruses remains an interesting question, this study helps to illuminate the potential of role respiratory viruses in pediatric wheezing. REVIEW REGISTRATION: PROSPERO, CRD42018115128.


Assuntos
Sons Respiratórios/etiologia , Sons Respiratórios/genética , Infecções Respiratórias/diagnóstico , Bocavirus/genética , Bocavirus/isolamento & purificação , Bocavirus/patogenicidade , Criança , Pré-Escolar , Coronavirus/isolamento & purificação , Coronavirus/patogenicidade , Humanos , Orthomyxoviridae/genética , Orthomyxoviridae/isolamento & purificação , Orthomyxoviridae/patogenicidade , Vírus da Parainfluenza 1 Humana/genética , Vírus da Parainfluenza 1 Humana/isolamento & purificação , Vírus da Parainfluenza 1 Humana/patogenicidade , Reação em Cadeia da Polimerase , Sons Respiratórios/fisiopatologia , Sistema Respiratório/patologia , Sistema Respiratório/virologia , Infecções Respiratórias/genética , Infecções Respiratórias/virologia
4.
Nat Commun ; 11(1): 5453, 2020 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-33116139

RESUMO

The coronavirus SARS-CoV-2 is the causative agent of the ongoing severe acute respiratory disease pandemic COVID-19. Tissue and cellular tropism is one key to understanding the pathogenesis of SARS-CoV-2. We investigate the expression and subcellular localization of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), within the upper (nasal) and lower (pulmonary) respiratory tracts of human donors using a diverse panel of banked tissues. Here, we report our discovery that the ACE2 receptor protein robustly localizes within the motile cilia of airway epithelial cells, which likely represents the initial or early subcellular site of SARS-CoV-2 viral entry during host respiratory transmission. We further determine whether ciliary ACE2 expression in the upper airway is influenced by patient demographics, clinical characteristics, comorbidities, or medication use, and show the first mechanistic evidence that the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) does not increase susceptibility to SARS-CoV-2 infection through enhancing the expression of ciliary ACE2 receptor. These findings are crucial to our understanding of the transmission of SARS-CoV-2 for prevention and control of this virulent pathogen.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Infecções por Coronavirus/patologia , Expressão Gênica/efeitos dos fármacos , Peptidil Dipeptidase A/genética , Pneumonia Viral/patologia , Sistema Respiratório/patologia , Fatores Etários , Cílios/metabolismo , Infecções por Coronavirus/virologia , Células Endoteliais , Células Caliciformes/metabolismo , Humanos , Pulmão/patologia , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/virologia , Sistema Respiratório/metabolismo , Sistema Respiratório/virologia , Fatores Sexuais , Sinusite/metabolismo , Fumar
5.
Endocrine ; 70(3): 454-460, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32870469

RESUMO

PURPOSE: The length of time a critically ill coronavirus disease 2019 (COVID-19) patient remains infectious and should therefore be isolated remains unknown. This prospective study was undertaken in critically ill patients to evaluate the reliability of single negative real-time polymerase chain reaction (RT-PCR) in lower tracheal aspirates (LTA) in predicting a second negative test and to analyze clinical factors potentially influencing the viral shedding. METHODS: From April 9, 2020 onwards, intubated COVID-19 patients treated in the intensive care unit were systematically evaluated for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by RT-PCR of nasopharyngeal swabs and LTA. The time to negativity was defined as the time between the onset of symptoms and the viral clearance in LTA. In order to identify risk factors for prolonged viral shedding, we used univariate and multivariate Cox proportional hazards models. RESULTS: Forty-eight intubated SARS-CoV-2 patients were enrolled. Overall, we observed that the association of the first negative RT-PCR with a second negative result was 96.7%. Median viral shedding was 25 (IQR: 21.5-28) days since symptoms' onset. In the univariate Cox model analysis, type 2 diabetes mellitus was associated with a prolonged viral RNA shedding (hazard ratio [HR]: 0.41, 95% CI: 0.06-3.11, p = 0.04). In the multivariate Cox model analysis, type 2 diabetes was associated with a prolonged viral RNA shedding (HR: 0.31, 95% CI: 0.11-0.89, p = 0.029). CONCLUSION: Intubated patients with type 2 diabetes mellitus may have prolonged SARS-CoV-2 shedding. In critically ill COVID-19 patients, one negative LTA should be sufficient to assess and exclude infectivity.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/virologia , Estado Terminal , Diabetes Mellitus Tipo 2/virologia , Pneumonia Viral/virologia , Sistema Respiratório/virologia , Eliminação de Partículas Virais , Idoso , Betacoronavirus/genética , Técnicas de Laboratório Clínico/métodos , Técnicas de Laboratório Clínico/normas , Comorbidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Progressão da Doença , Feminino , Humanos , Unidades de Terapia Intensiva , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Sistema Respiratório/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/normas , Fatores de Risco , Manejo de Espécimes/métodos , Manejo de Espécimes/normas , Suíça/epidemiologia , Fatores de Tempo
6.
EBioMedicine ; 60: 102976, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32971472

RESUMO

BACKGROUND: Zoonotically transmitted coronaviruses are responsible for three disease outbreaks since 2002, including the current COVID-19 pandemic, caused by SARS-CoV-2. Its efficient transmission and range of disease severity raise questions regarding the contributions of virus-receptor interactions. ACE2 is a host ectopeptidase and the receptor for SARS-CoV-2. Numerous reports describe ACE2 mRNA abundance and tissue distribution; however, mRNA abundance is not always representative of protein levels. Currently, there is limited data evaluating ACE2 protein and its correlation with other SARS-CoV-2 susceptibility factors. MATERIALS AND METHODS: We systematically examined the human upper and lower respiratory tract using single-cell RNA sequencing and immunohistochemistry to determine receptor expression and evaluated its association with risk factors for severe COVID-19. FINDINGS: Our results reveal that ACE2 protein is highest within regions of the sinonasal cavity and pulmonary alveoli, sites of presumptive viral transmission and severe disease development, respectively. In the lung parenchyma, ACE2 protein was found on the apical surface of a small subset of alveolar type II cells and colocalized with TMPRSS2, a cofactor for SARS-CoV2 entry. ACE2 protein was not increased by pulmonary risk factors for severe COVID-19. Additionally, ACE2 protein was not reduced in children, a demographic with a lower incidence of severe COVID-19. INTERPRETATION: These results offer new insights into ACE2 protein localization in the human respiratory tract and its relationship with susceptibility factors to COVID-19.


Assuntos
Células Epiteliais Alveolares/metabolismo , Peptidil Dipeptidase A/genética , Análise de Sequência de RNA/métodos , Adulto , Idoso , Células Epiteliais Alveolares/patologia , Betacoronavirus/isolamento & purificação , Betacoronavirus/fisiologia , Criança , Pré-Escolar , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/patologia , Pneumonia Viral/virologia , RNA Mensageiro/metabolismo , Sistema Respiratório/metabolismo , Sistema Respiratório/patologia , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo , Análise de Célula Única , Adulto Jovem
7.
Future Microbiol ; 15: 1287-1305, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32851877

RESUMO

Aim: Despite the similarities in the pathogenesis of the beta coronaviruses, the precise infective mechanisms of SARS-CoV-2 remain unclear. Objective: In this review, we aim to focus on the proposed theories behind the pathogenesis of SARS-CoV-2 and highlight the clinical complications related to COVID-19. Methods: We conducted a literature search in Pubmed, Scopus and Google Scholar for the relevant articles regarding clinical complications and pathogenesis of COVID-19. Results: Related articles were included and discussed. Conclusion: Respiratory system and the lungs are the most commonly involved sites of COVID-19 infection. Cardiovascular, liver, kidneys, gastrointestinal and central nervous systems are involved with different frequencies and degrees of severity.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , Sistema Cardiovascular/patologia , Sistema Cardiovascular/virologia , Sistema Nervoso Central/patologia , Sistema Nervoso Central/virologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/transmissão , Citocinas/sangue , Trato Gastrointestinal/patologia , Trato Gastrointestinal/virologia , Humanos , Rim/patologia , Rim/virologia , Fígado/patologia , Fígado/virologia , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/transmissão , Sistema Respiratório/patologia , Sistema Respiratório/virologia
8.
Nat Commun ; 11(1): 4207, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32826924

RESUMO

The rapid spread of coronavirus SARS-CoV-2 greatly threatens global public health but no prophylactic vaccine is available. Here, we report the generation of a replication-incompetent recombinant serotype 5 adenovirus, Ad5-S-nb2, carrying a codon-optimized gene encoding Spike protein (S). In mice and rhesus macaques, intramuscular injection with Ad5-S-nb2 elicits systemic S-specific antibody and cell-mediated immune (CMI) responses. Intranasal inoculation elicits both systemic and pulmonary antibody responses but weaker CMI response. At 30 days after a single vaccination with Ad5-S-nb2 either intramuscularly or intranasally, macaques are protected against SARS-CoV-2 challenge. A subsequent challenge reveals that macaques vaccinated with a 10-fold lower vaccine dosage (1 × 1010 viral particles) are also protected, demonstrating the effectiveness of Ad5-S-nb2 and the possibility of offering more vaccine dosages within a shorter timeframe. Thus, Ad5-S-nb2 is a promising candidate vaccine and warrants further clinical evaluation.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/administração & dosagem , Adenoviridae/genética , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Infecções por Coronavirus/imunologia , Relação Dose-Resposta Imunológica , Feminino , Células HEK293 , Humanos , Imunidade Celular , Macaca mulatta , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pneumonia Viral/imunologia , Sistema Respiratório/patologia , Sistema Respiratório/virologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Sintéticas/administração & dosagem
9.
Nat Commun ; 11(1): 3910, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32764693

RESUMO

SARS-CoV-2, a ß-coronavirus, has rapidly spread across the world, highlighting its high transmissibility, but the underlying morphogenesis and pathogenesis remain poorly understood. Here, we characterize the replication dynamics, cell tropism and morphogenesis of SARS-CoV-2 in organotypic human airway epithelial (HAE) cultures. SARS-CoV-2 replicates efficiently and infects both ciliated and secretory cells in HAE cultures. In comparison, HCoV-NL63 replicates to lower titers and is only detected in ciliated cells. SARS-CoV-2 shows a similar morphogenetic process as other coronaviruses but causes plaque-like cytopathic effects in HAE cultures. Cell fusion, apoptosis, destruction of epithelium integrity, cilium shrinking and beaded changes are observed in the plaque regions. Taken together, our results provide important insights into SARS-CoV-2 cell tropism, replication and morphogenesis.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/virologia , Células Epiteliais/virologia , Morfogênese/fisiologia , Pneumonia Viral/virologia , Sistema Respiratório/virologia , Betacoronavirus/patogenicidade , Linhagem Celular , Células Cultivadas , Efeito Citopatogênico Viral , Células Epiteliais/patologia , Humanos , Pandemias , Sistema Respiratório/patologia , Tropismo , Replicação Viral
10.
Cell ; 182(2): 429-446.e14, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32526206

RESUMO

The mode of acquisition and causes for the variable clinical spectrum of coronavirus disease 2019 (COVID-19) remain unknown. We utilized a reverse genetics system to generate a GFP reporter virus to explore severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis and a luciferase reporter virus to demonstrate sera collected from SARS and COVID-19 patients exhibited limited cross-CoV neutralization. High-sensitivity RNA in situ mapping revealed the highest angiotensin-converting enzyme 2 (ACE2) expression in the nose with decreasing expression throughout the lower respiratory tract, paralleled by a striking gradient of SARS-CoV-2 infection in proximal (high) versus distal (low) pulmonary epithelial cultures. COVID-19 autopsied lung studies identified focal disease and, congruent with culture data, SARS-CoV-2-infected ciliated and type 2 pneumocyte cells in airway and alveolar regions, respectively. These findings highlight the nasal susceptibility to SARS-CoV-2 with likely subsequent aspiration-mediated virus seeding to the lung in SARS-CoV-2 pathogenesis. These reagents provide a foundation for investigations into virus-host interactions in protective immunity, host susceptibility, and virus pathogenesis.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Sistema Respiratório/virologia , Genética Reversa/métodos , Idoso , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Linhagem Celular , Células Cultivadas , Chlorocebus aethiops , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Fibrose Cística/patologia , DNA Recombinante , Feminino , Furina/metabolismo , Humanos , Imunização Passiva , Pulmão/metabolismo , Pulmão/patologia , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Mucosa Nasal/virologia , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/imunologia , Sistema Respiratório/patologia , Serina Endopeptidases/metabolismo , Células Vero , Virulência , Replicação Viral
11.
Nat Biotechnol ; 38(8): 970-979, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32591762

RESUMO

To investigate the immune response and mechanisms associated with severe coronavirus disease 2019 (COVID-19), we performed single-cell RNA sequencing on nasopharyngeal and bronchial samples from 19 clinically well-characterized patients with moderate or critical disease and from five healthy controls. We identified airway epithelial cell types and states vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In patients with COVID-19, epithelial cells showed an average three-fold increase in expression of the SARS-CoV-2 entry receptor ACE2, which correlated with interferon signals by immune cells. Compared to moderate cases, critical cases exhibited stronger interactions between epithelial and immune cells, as indicated by ligand-receptor expression profiles, and activated immune cells, including inflammatory macrophages expressing CCL2, CCL3, CCL20, CXCL1, CXCL3, CXCL10, IL8, IL1B and TNF. The transcriptional differences in critical cases compared to moderate cases likely contribute to clinical observations of heightened inflammatory tissue damage, lung injury and respiratory failure. Our data suggest that pharmacologic inhibition of the CCR1 and/or CCR5 pathways might suppress immune hyperactivation in critical COVID-19.


Assuntos
Infecções por Coronavirus/patologia , Infecções por Coronavirus/fisiopatologia , Pneumonia Viral/patologia , Pneumonia Viral/fisiopatologia , Sistema Respiratório/patologia , Análise de Célula Única , Transcriptoma , Adulto , Idoso , Líquido da Lavagem Broncoalveolar/virologia , Comunicação Celular , Diferenciação Celular , Infecções por Coronavirus/virologia , Células Epiteliais/patologia , Células Epiteliais/virologia , Feminino , Humanos , Sistema Imunitário/patologia , Inflamação/imunologia , Inflamação/patologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , Pandemias , Peptidil Dipeptidase A/genética , Pneumonia Viral/virologia , Sistema Respiratório/imunologia , Sistema Respiratório/virologia , Índice de Gravidade de Doença
12.
Ann Agric Environ Med ; 27(2): 194-200, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32588592

RESUMO

INTRODUCTION: Pesticides are widely employed in agriculture, and the food industry is forced to combat the pests and diseases they cause. Respiratory pathology is related to occupational exposure to pesticides. Impairment of pulmonary function was observed among people professionally exposed to pesticides. Because of the marked use of pesticides in agriculture during the last 20 years, there has been a significant increase in respiratory problems within the population, not only among people who come in direct contact with them, but even in the case of manipulators. OBJECTIVE: The aim is a review of the literature of the past 10 years on the correlation between occupational exposure to pesticides and respiratory pathology. MATERIAL AND METHODS: Electronic search in 'Pub Med' and 'Web of Science' was performed in September 2019 to find papers regarding the above-investigated aspects. Abstracts and full-text articles containing the targeted subject were included. Reviews and studies about the influence of pesticides on other pathologies than respiratory were excluded. After applying the inclusion and exclusion criteria, eligible full-text articles were identified. CONCLUSIONS: Exposure to pesticides is highly correlated with respiratory pathologies (asthma, COPD, lung cancer). Contact with these substances can occur at any time in the production, transport, preparation or application of the treatments. Numerous studies documented the association between exposure to pesticides, and therefore the increased incidence of respiratory, cardiovascular and renal diseases, as well as the aging phenomenon.


Assuntos
Exposição Ocupacional/efeitos adversos , Praguicidas/efeitos adversos , Sistema Respiratório/patologia , Humanos
13.
Mod Pathol ; 33(11): 2104-2114, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32561849

RESUMO

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has led to a global public health crisis. In elderly individuals and those with comorbidities, COVID-19 is associated with high mortality, frequently caused by acute respiratory distress syndrome. We examine in situ expression of SARS-CoV-2 in airways and lung obtained at autopsy of individuals with confirmed COVID-19 infection. Seven autopsy cases (male, N = 5; female, N = 2) with reverse transcriptase-polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infection and a median age of 66 years (range, 50-77 years) were evaluated using a rabbit polyclonal antibody against SARS Nucleocapsid protein in correlation with clinical parameters. The median time from symptom onset to death was 9 days (range, 6-31 days), from hospitalization 7 days (range, 1-21 days), from positive RT-PCR 7 days (range, 0-18 days), and from intensive care unit admission defining onset of respiratory failure 3 days (range, 1-18 days). Chest imaging identified diffuse airspace disease in all patients corresponding to acute and (N = 5) or organizing (N = 2) diffuse alveolar damage (DAD) on histologic examination. Among five patients with acute-phase DAD (≤7 days from onset of respiratory failure), SARS-CoV-2 was detected in pulmonary pneumocytes and ciliated airway cells (N = 5), and in upper airway epithelium (N = 2). In two patients with organizing DAD (>14 days from onset of respiratory failure), no virus was detected in lungs or airways. No endothelial cell infection was observed. The findings suggest that SARS-CoV-2 infection of epithelial cells in lungs and airways of patients with COVID-19 who developed respiratory failure can be detected during the acute phase of lung injury and is absent in the organizing phase.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Síndrome Respiratória Aguda Grave/patologia , Síndrome Respiratória Aguda Grave/virologia , Idoso , Autopsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Sistema Respiratório/patologia , Sistema Respiratório/virologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa
14.
Presse Med ; 49(2): 103909, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32563946

RESUMO

Interstitial lung disease (ILD) in children (chILD) is a heterogeneous group of rare respiratory disorders that are mostly chronic and associated with high morbidity and mortality. The pathogenesis of the various chILD is complex and the diseases share common features of inflammatory and fibrotic changes of the lung parenchyma that impair gas exchanges. The etiologies of chILD are numerous. In this review, we chose to classify them as ILD related to exposure/environment insults, ILD related to systemic and immunological diseases, ILD related to primary lung parenchyma dysfunctions and ILD specific to infancy. A growing part of the etiologic spectrum of chILD is being attributed to molecular defects. Currently, the main genetic mutations associated with chILD are identified in the surfactant genes SFTPA1, SFTPA2, SFTPB, SFTPC, ABCA3 and NKX2-1. Other genetic contributors include mutations in MARS, CSF2RA and CSF2RB in pulmonary alveolar proteinosis, and mutations in TMEM173 and COPA in specific auto-inflammatory forms of chILD. However, only few genotype-phenotype correlations could be identified so far. Herein, information is provided about the clinical presentation and the diagnosis approach of chILD. Despite improvements in patient management, the therapeutic strategies are still relying mostly on corticosteroids although specific therapies are emerging. Larger longitudinal cohorts of patients are being gathered through ongoing international collaborations to improve disease knowledge and targeted therapies. Thus, it is expected that children with ILD will be able to reach the adulthood transition in a better condition.


Assuntos
Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/etiologia , Fatores Etários , Criança , Doença Crônica , Doenças do Tecido Conjuntivo/complicações , Doenças do Tecido Conjuntivo/diagnóstico , Exposição Ambiental/efeitos adversos , Interação Gene-Ambiente , Genótipo , Humanos , Doenças do Sistema Imunitário/complicações , Lactente , Recém-Nascido , Doenças Pulmonares Intersticiais/classificação , Doenças Pulmonares Intersticiais/tratamento farmacológico , Fenótipo , Proteinose Alveolar Pulmonar/genética , Transtornos Respiratórios/complicações , Sistema Respiratório/patologia , Esteroides/uso terapêutico
15.
Cell Host Microbe ; 27(6): 883-890.e2, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32407669

RESUMO

The outbreaks of 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV-2 infection have posed a severe threat to global public health. It is unclear how the human immune system responds to this infection. Here, we used metatranscriptomic sequencing to profile immune signatures in the bronchoalveolar lavage fluid of eight COVID-19 cases. The expression of proinflammatory genes, especially chemokines, was markedly elevated in COVID-19 cases compared to community-acquired pneumonia patients and healthy controls, suggesting that SARS-CoV-2 infection causes hypercytokinemia. Compared to SARS-CoV, which is thought to induce inadequate interferon (IFN) responses, SARS-CoV-2 robustly triggered expression of numerous IFN-stimulated genes (ISGs). These ISGs exhibit immunopathogenic potential, with overrepresentation of genes involved in inflammation. The transcriptome data was also used to estimate immune cell populations, revealing increases in activated dendritic cells and neutrophils. Collectively, these host responses to SARS-CoV-2 infection could further our understanding of disease pathogenesis and point toward antiviral strategies.


Assuntos
Líquido da Lavagem Broncoalveolar/imunologia , Infecções por Coronavirus/imunologia , Imunidade Inata , Pneumonia Viral/imunologia , Sistema Respiratório/imunologia , Líquido da Lavagem Broncoalveolar/citologia , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina , Citocinas/análise , Interações Hospedeiro-Patógeno , Humanos , Interferons/metabolismo , Pandemias , Pneumonia Viral/patologia , Sistema Respiratório/patologia
16.
Eur J Clin Invest ; 50(7): e13259, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32353898

RESUMO

BACKGROUND: The clinical features of COVID-19 pneumonia range from a mild illness to patients with a very severe illness with acute hypoxemic respiratory failure requiring ventilation and Intensive Care Unit admission. AIMS: To provide a brief overview of the existing evidence for such differences in host response and outcome, and generate hypotheses for divergent patterns and avenues for future research, by highlighting similarities and differences in histopathological appearance between COVID-19 and influenza as well as previous coronavirus outbreaks, and by discussing predisposition through genetics and underlying disease. MATERIALS AND METHOD: We assessed the available early literature for histopathological patterns of COVID-19 pneumonia and underlying risk factors. RESULT: The histopathological spectrum of COVID-19 pneumonia includes variable patterns of epithelial damage, vascular complications, fibrosis and inflammation. Risk factors for a fatal disease include older age, respiratory disease, diabetes mellitus, obesity and hypertension. DISCUSSION: While some risk factors and their potential role in COVID-19 pneumonia are increasingly recognized, little is known about the mechanisms behind episodes of sudden deterioration or the infrequent idiosyncratic clinical demise in otherwise healthy and young subjects. CONCLUSION: The answer to many of the remaining questions regarding COVID-19 pneumonia pathogenesis may in time be provided by genotyping as well careful clinical, serological, radiological and histopathological phenotyping.


Assuntos
Infecções por Coronavirus/patologia , Edema/patologia , Inflamação/patologia , Pneumonia Viral/patologia , Mucosa Respiratória/patologia , Trombose/patologia , Fatores Etários , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Diabetes Mellitus/epidemiologia , Fibrose , Predisposição Genética para Doença , Antígenos HLA/genética , Humanos , Hipertensão/epidemiologia , Inflamação/imunologia , Influenza Humana/patologia , Obesidade/epidemiologia , Pandemias , Peptidil Dipeptidase A/genética , Pneumonia Viral/epidemiologia , Pneumonia Viral/genética , Pneumonia Viral/imunologia , Polimorfismo Genético , Mucosa Respiratória/imunologia , Sistema Respiratório/patologia , Fatores de Risco , Serina Endopeptidases/genética , Síndrome Respiratória Aguda Grave/patologia
17.
PLoS One ; 15(5): e0233854, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32470006

RESUMO

Alpha-toxin (Hla) is a major virulence factor of Staphylococcus aureus (S. aureus) and plays an important role in S. aureus-induced pneumonia. It binds as a monomer to the cell surface of eukaryotic host cells and forms heptameric transmembrane pores. Sensitivities toward the toxin of various types of potential host cells have been shown to vary substantially, and the reasons for these differences are unclear. We used three human model airway epithelial cell lines (16HBE14o-, S9, A549) to correlate cell sensitivity (measured as rate of paracellular gap formation in the cell layers) with Hla monomer binding, presence of the potential Hla receptors ADAM10 or α5ß1 integrin, presence of the toxin-stabilizing factor caveolin-1 as well as plasma membrane lipid composition (phosphatidylserine/choline, sphingomyelin). The abundance of ADAM10 correlated best with gap formation or cell sensitivities, respectively, when the three cell types were compared. Caveolin-1 or α5ß1 integrin did not correlate with toxin sensitivity. The relative abundance of sphingomyelin in plasma membranes may also be used as a proxi for cellular sensitivity against alpha-toxin as sphingomyelin abundances correlated well with the intensities of alpha-toxin mediated gap formation in the cell layers.


Assuntos
Toxinas Bacterianas/metabolismo , Toxinas Bacterianas/toxicidade , Membrana Celular/metabolismo , Células Epiteliais/metabolismo , Proteínas Hemolisinas/metabolismo , Proteínas Hemolisinas/toxicidade , Interações Hospedeiro-Patógeno , Sistema Respiratório/patologia , Células A549 , Caveolina 1/metabolismo , Membrana Celular/efeitos dos fármacos , Tamanho Celular , Células Epiteliais/efeitos dos fármacos , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Modelos Biológicos , Fosfolipídeos/metabolismo , Ligação Proteica , Receptores de Superfície Celular/metabolismo
18.
PLoS One ; 15(5): e0228606, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32392246

RESUMO

Bordetella pertussis, the causative agent of whopping cough, produces an adenylate cyclase toxin (CyaA) that plays a key role in the host colonization by targeting innate immune cells which express CD11b/CD18, the cellular receptor of CyaA. CyaA is also able to invade non-phagocytic cells, via a unique entry pathway consisting in a direct translocation of its catalytic domain across the cytoplasmic membrane of the cells. Within the cells, CyaA is activated by calmodulin to produce high levels of cyclic adenosine monophosphate (cAMP) and alter cellular physiology. In this study, we explored the effects of CyaA toxin on the cellular and molecular structure remodeling of A549 alveolar epithelial cells. Using classical imaging techniques, biochemical and functional tests, as well as advanced cell mechanics method, we quantify the structural and functional consequences of the massive increase of intracellular cyclic AMP induced by the toxin: cell shape rounding associated to adhesion weakening process, actin structure remodeling for the cortical and dense components, increase in cytoskeleton stiffness, and inhibition of migration and repair. We also show that, at low concentrations (0.5 nM), CyaA could significantly impair the migration and wound healing capacities of the intoxicated alveolar epithelial cells. As such concentrations might be reached locally during B. pertussis infection, our results suggest that the CyaA, beyond its major role in disabling innate immune cells, might also contribute to the local alteration of the epithelial barrier of the respiratory tract, a hallmark of pertussis.


Assuntos
Toxina Adenilato Ciclase/genética , Bordetella pertussis/enzimologia , Imunidade Inata/genética , Coqueluche/genética , Toxina Adenilato Ciclase/metabolismo , Bordetella pertussis/patogenicidade , Calmodulina/metabolismo , Membrana Celular/metabolismo , AMP Cíclico/genética , Células Epiteliais/microbiologia , Humanos , Sistema Respiratório/metabolismo , Sistema Respiratório/microbiologia , Sistema Respiratório/patologia , Coqueluche/microbiologia , Coqueluche/patologia
20.
Forensic Sci Med Pathol ; 16(3): 471-476, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32399755

RESUMO

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a coronavirus responsible for COVID-19 (coronavirus disease 2019) which resulted in a cluster of cases of pneumonia that originated in China around 31 December 2019 and has subsequently spread across the globe. Currently, COVID-19 represents a health emergency worldwide, leading, in severe cases, to pneumonia, severe acute respiratory syndrome, multiorgan dysfunction or failure, and death. In the context of limited scientific knowledge and evidence of SARS-CoV-2 infection, guidance is becoming increasingly necessary for pathologists who have to perform postmortem investigations on COVID-19 cases. The aim of the present report is to share a procedure applicable to cases of COVID-19-related death, particularly in cases of death without medical intervention and in the absence of an ascertained SARS-CoV-2 infection and/or COVID-19 diagnosis, therefore providing support for diagnostic activity in the present COVID-19 pandemic. For this purpose, a standard operating procedure for correct swab collection, autopsy investigation and tissue sampling is provided.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Ciências Forenses/normas , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Sistema Respiratório/virologia , Manejo de Espécimes/normas , Virologia/normas , Autopsia , Causas de Morte , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Interações entre Hospedeiro e Microrganismos , Humanos , Itália , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Valor Preditivo dos Testes , Sistema Respiratório/patologia
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