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1.
Molecules ; 26(4)2021 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-33562349

RESUMO

As a member of the Orthomyxoviridae family of viruses, influenza viruses (IVs) are known causative agents of respiratory infection in vertebrates. They remain a major global threat responsible for the most virulent diseases and global pandemics in humans. The virulence of IVs and the consequential high morbidity and mortality of IV infections are primarily attributed to the high mutation rates in the IVs' genome coupled with the numerous genomic segments, which give rise to antiviral resistant and vaccine evading strains. Current therapeutic options include vaccines and small molecule inhibitors, which therapeutically target various catalytic processes in IVs. However, the periodic emergence of new IV strains necessitates the continuous development of novel anti-influenza therapeutic options. The crux of this review highlights the recent studies on the biology of influenza viruses, focusing on the structure, function, and mechanism of action of the M2 channel and neuraminidase as therapeutic targets. We further provide an update on the development of new M2 channel and neuraminidase inhibitors as an alternative to existing anti-influenza therapy. We conclude by highlighting therapeutic strategies that could be explored further towards the design of novel anti-influenza inhibitors with the ability to inhibit resistant strains.


Assuntos
Influenza Humana/tratamento farmacológico , Orthomyxoviridae/efeitos dos fármacos , Infecções Respiratórias/tratamento farmacológico , Proteínas da Matriz Viral/genética , Farmacorresistência Viral/efeitos dos fármacos , Inibidores Enzimáticos/uso terapêutico , Humanos , Influenza Humana/virologia , Neuraminidase/antagonistas & inibidores , Neuraminidase/genética , Orthomyxoviridae/genética , Infecções Respiratórias/patologia , Infecções Respiratórias/virologia , Proteínas da Matriz Viral/antagonistas & inibidores
2.
Viruses ; 13(1)2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33418959

RESUMO

Juvenile-onset recurrent respiratory papillomatosis (JoRRP) is driven by human papillomavirus (HPV) low-risk strains and is associated with significant morbidity. While previous studies of 2D cultures have shed light on disease pathogenesis and demonstrated the utility of personalized medicine approaches, monolayer cultures lack the 3D tissue architecture and physiology of stratified, sequentially differentiated mucosal epithelium important in RRP disease pathogenesis. Herein we describe the establishment of JoRRP-derived primary cell populations that retain HPV genomes and viral gene expression in culture. These were directly compared to cells from matched adjacent non-diseased tissue, given the known RRP patient-to-patient variability. JoRRP papilloma versus control cells displayed decreased growth at subconfluency, with a switch to increased growth after reaching confluency, suggesting relative resistance to cell-cell contact and/or differentiation. The same papilloma cells grown as 3D organotypic rafts harbored hyperproliferation as compared to controls, with increased numbers of proliferating basal cells and inappropriately replicating suprabasal cells, mimicking phenotypes in the patient biopsies from which they were derived. These complementary model systems provide novel opportunities to elucidate disease mechanisms at distinct stages in JoRRP progression and to identify diagnostic, prognostic and therapeutic factors to personalize patient management and treatment.


Assuntos
Alphapapillomavirus/genética , Alphapapillomavirus/isolamento & purificação , Células Epiteliais/virologia , Infecções por Papillomavirus/virologia , Infecções Respiratórias/patologia , Humanos , Técnicas de Cultura de Órgãos , Infecções por Papillomavirus/patologia , Fenótipo , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real , Infecções Respiratórias/virologia , Fatores de Risco
3.
Pediatr Infect Dis J ; 40(1): e36-e39, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33044434

RESUMO

The clinical presentation of human coronavirus (HCoV) infections in children varies strongly. We show that children with an HCoV-associated lower respiratory tract infection more frequently had respiratory syncytial virus codetected and higher abundance of Haemophilus influenzae/haemolyticus than asymptomatic HCoV carriers as well as children with a non-HCoV-associated lower respiratory tract infection. Viral and bacterial cooccurrence may drive symptomatology of HCoV-associated infections including coronavirus disease 2019.


Assuntos
Coinfecção/microbiologia , Coinfecção/virologia , Infecções por Coronavirus/patologia , Infecções Respiratórias/patologia , Bactérias/classificação , Bactérias/isolamento & purificação , Pré-Escolar , Coinfecção/epidemiologia , Coinfecção/patologia , Coronavirus , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/microbiologia , Infecções por Coronavirus/virologia , Feminino , Haemophilus/classificação , Haemophilus/isolamento & purificação , Humanos , Lactente , Masculino , Países Baixos/epidemiologia , Vírus Sincicial Respiratório Humano/isolamento & purificação , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/microbiologia , Infecções Respiratórias/virologia , Estações do Ano , Índice de Gravidade de Doença
4.
Pediatr Infect Dis J ; 40(1): e12-e17, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33165274

RESUMO

BACKGROUND: Human coronaviruses (HCoVs) are a significant cause of acute respiratory illness (ARI) in children; however, the role of HCoVs in ARI among hospitalized children in the Middle East is not well defined. METHODS: Children under 2 years admitted with fever and/or respiratory symptoms were enrolled from 2010 to 2013 in Amman, Jordan. Nasal/throat swabs were collected and stored for testing. Demographic and clinical characteristics were collected through parent/guardian interviews and medical chart abstractions. Prior stored specimens were tested for HCoVs (HKU1, OC43, 229E and NL63) by qRT-PCR. RESULTS: Of the 3168 children enrolled, 6.7% were HCoVs-positive. Among HCoV-positive children, the median age was 3.8 (1.9-8.4) months, 59% were male, 14% were premature, 11% had underlying medical conditions and 76% had viral-codetection. The most common presenting symptoms were cough, fever, wheezing and shortness of breath. HCoVs were detected year-round, peaking in winter-spring months. Overall, 56%, 22%, 13% and 6% were OC43, NL63, HKU1 and 229E, respectively. There was no difference in disease severity between the species, except higher intensive care unit admission frequency in NL63-positive subjects. CONCLUSIONS: HCoVs were detected in around 7% of children enrolled in our study. Despite HCoV detection in children with ARI with highest peaks in respiratory seasons, the actual burden and pathogenic role of HCoVs in ARI merits further evaluation given the high frequency of viral codetection.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Coronavirus/isolamento & purificação , Doença Aguda , Coinfecção/epidemiologia , Coinfecção/patologia , Coinfecção/virologia , Coronavirus/classificação , Coronavirus/genética , Infecções por Coronavirus/patologia , Feminino , Hospitalização , Humanos , Lactente , Jordânia/epidemiologia , Masculino , Vigilância da População , Estudos Prospectivos , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/patologia , Infecções Respiratórias/virologia , Fatores de Risco , Estações do Ano , Vírus/classificação , Vírus/genética , Vírus/isolamento & purificação
5.
PLoS One ; 15(11): e0241262, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33137167

RESUMO

The coronavirus disease 2019 (COVID-19) has become a pandemic. Rapidly distinguishing COVID-19 from other respiratory infections is a challenge for first-line health care providers. This retrospective study was conducted at the Taipei Medical University Hospital, Taiwan. Patients who visited the outdoor epidemic prevention screening station for respiratory infection from February 19 to April 30, 2020, were evaluated for blood biomarkers to distinguish COVID-19 from other respiratory infections. Monocyte distribution width (MDW) ≥ 20 (odds ratio [OR]: 8.39, p = 0.0110, area under curve [AUC]: 0.703) and neutrophil-to-lymphocyte ratio (NLR) < 3.2 (OR: 4.23, p = 0.0494, AUC: 0.673) could independently distinguish COVID-19 from common upper respiratory tract infections (URIs). Combining MDW ≥ 20 and NLR < 3.2 was more efficient in identifying COVID-19 (AUC: 0.840). Moreover, MDW ≥ 20 and NLR > 5 effectively identified influenza infection (AUC: 0.7055). Thus, MDW and NLR can distinguish COVID-19 from influenza and URIs.


Assuntos
Infecções por Coronavirus/patologia , Influenza Humana/patologia , Linfócitos/citologia , Monócitos/citologia , Neutrófilos/citologia , Pneumonia Viral/patologia , Área Sob a Curva , Biomarcadores/metabolismo , Infecções por Coronavirus/imunologia , Feminino , Humanos , Influenza Humana/imunologia , Linfócitos/metabolismo , Masculino , Monócitos/metabolismo , Neutrófilos/metabolismo , Razão de Chances , Pandemias , Projetos Piloto , Pneumonia Viral/imunologia , Curva ROC , Infecções Respiratórias/imunologia , Infecções Respiratórias/patologia
6.
Diagn Microbiol Infect Dis ; 98(4): 115199, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32979617

RESUMO

COVID-19 positive (194) and negative (212) pneumonia patients were selected to analyze bacterial pathogens coinfection. Results showed that 50% of COVID-19 patients were coinfected or carried bacterial pathogens. Bordetella pertussis infection rate was significantly higher in positive patients. Consequently, preventions should be taken to control bacterial pathogens coinfection in COVID-19 patients.


Assuntos
Coinfecção/epidemiologia , Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , Infecções por Pseudomonas/epidemiologia , Coqueluche/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Bordetella pertussis/isolamento & purificação , Criança , Pré-Escolar , Coinfecção/microbiologia , Coinfecção/patologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Pandemias , Pseudomonas aeruginosa/isolamento & purificação , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/microbiologia , Infecções Respiratórias/patologia , Adulto Jovem
7.
Pediatr Infect Dis J ; 39(10): e291-e296, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32773657

RESUMO

BACKGROUND: Human coronaviruses (HCoVs) cause respiratory tract infections during childhood manifesting as common colds, bronchiolitis, croup and pneumonia. In temperate geographies, HCoV activity peaks between December and March. The epidemiology and manifestations of HCoV infections have not been previously reported from Ecuador. METHODS: Children <5 years who presented with ≥2 symptoms consistent with an acute respiratory tract infection were eligible for enrollment. After obtaining informed consent, demographic data and details regarding the acute illness were recorded. Secretions collected with a nasopharyngeal swab underwent diagnostic testing using multiplex polymerase chain reaction. RESULTS: A total of 850 subjects were enrolled. A total of 677 (80%) tested positive for at least 1 pathogen, including 49 (7.2%) who tested positive for ≥1 HCoV type. HCoV-NL63 was the most frequent type detected (39%), followed by HCoV-OC43 (27%), 229E (22%) and HKU1 (12%). Nearly all subjects who tested positive for HCoV had nasal congestion or secretions (47/49; 96%). The most frequent syndromic diagnosis was common cold (41%), followed by bronchiolitis (27%). We found no association between the infecting HCoV type and subject's syndromic diagnosis (P > 0.05) or anatomic location of infection (upper vs. lower respiratory tract; P > 0.05). The 2018-2019 peak HCoV activity occurred from October to November; the 2019-2020 peak occurred from January to February. CONCLUSIONS: HCoVs were detected in ~7% of outpatient Ecuadorean children <5 years of age with symptoms of acute respiratory tract infection. The most frequently detected HCoV types, and the period of peak HCoV activity differed for the 2018-2019 and 2019-2020 seasons.


Assuntos
Infecções por Coronavirus/virologia , Coronavirus/isolamento & purificação , Infecções Respiratórias/virologia , Doença Aguda , Assistência Ambulatorial/estatística & dados numéricos , Pré-Escolar , Coronavirus/classificação , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/patologia , Equador/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Nasofaringe/virologia , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/patologia , Estações do Ano
8.
Emerg Microbes Infect ; 9(1): 1958-1964, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32815458

RESUMO

Objectives Severe or critical COVID-19 is associated with intensive care unit admission, increased secondary infection rate, and would lead to significant worsened prognosis. Risks and characteristics relating to secondary infections in severe COVID-19 have not been described. Methods Severe and critical COVID-19 patients from Shanghai were included. We collected lower respiratory, urine, catheters, and blood samples according to clinical necessity and culture and mNGS were performed. Clinical and laboratory data were archived. Results We found 57.89% (22/38) patients developed secondary infections. The patient receiving invasive mechanical ventilation or in critical state has a higher chance of secondary infections (P<0.0001). The most common infections were respiratory, blood-stream and urinary infections, and in respiratory infections, the most detected pathogens were gram-negative bacteria (26, 50.00%), following by gram-positive bacteria (14, 26.92%), virus (6, 11.54%), fungi (4, 7.69%), and others (2, 3.85%). Respiratory Infection rate post high flow, tracheal intubation, and tracheotomy were 12.90% (4/31), 30.43% (7/23), and 92.31% (12/13) respectively. Secondary infections would lead to lower discharge rate and higher mortality rate. Conclusion Our study originally illustrated secondary infection proportion in severe and critical COVID-19 patients. Culture accompanied with metagenomics sequencing increased pathogen diagnostic rate. Secondary infections risks increased after receiving invasive respiratory ventilations and intravascular devices, and would lead to a lower discharge rate and a higher mortality rate.


Assuntos
Bacteriemia/patologia , Infecções Bacterianas/patologia , Infecções por Coronavirus/patologia , Fungemia/patologia , Micoses/patologia , Infecções Oportunistas/patologia , Pneumonia Viral/patologia , Infecções Respiratórias/patologia , Infecções Urinárias/patologia , Idoso , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Bacteriemia/virologia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/mortalidade , Infecções Bacterianas/virologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/microbiologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Estado Terminal , Feminino , Fungemia/microbiologia , Fungemia/mortalidade , Fungemia/virologia , Fungos/patogenicidade , Bactérias Gram-Negativas/patogenicidade , Bactérias Gram-Positivas/patogenicidade , Humanos , Unidades de Terapia Intensiva , Pulmão/microbiologia , Pulmão/patologia , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , Micoses/microbiologia , Micoses/mortalidade , Micoses/virologia , Infecções Oportunistas/microbiologia , Infecções Oportunistas/mortalidade , Infecções Oportunistas/virologia , Pandemias , Pneumonia Viral/microbiologia , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Respiração Artificial/efeitos adversos , Infecções Respiratórias/microbiologia , Infecções Respiratórias/mortalidade , Infecções Respiratórias/virologia , Estudos Retrospectivos , Risco , Índice de Gravidade de Doença , Análise de Sobrevida , Infecções Urinárias/microbiologia , Infecções Urinárias/mortalidade , Infecções Urinárias/virologia
9.
Medicine (Baltimore) ; 99(30): e21320, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791725

RESUMO

BACKGROUND: Assessing the effectiveness and safety of traditional Chinese medicine (TCM) for symptoms of upper respiratory tract of coronavirus disease 2019 is the main purpose of this systematic review protocol. METHODS: The following electronic databases will be searched from inception to Sep 2020: the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Web of Science, TCM, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database (VIP database), and Wan-Fang Database. Search dates: from inception dates to June 2020. Language: English. Publication period: from inception dates to June 2020. The primary outcome is the time and rate of appearance of main symptoms (including coughing, pharyngalgia, and nasal obstruction). The secondary outcome is the length of hospital stay. Two independent reviewers will conduct the study selection, data extraction and assessment. RevMan V.5.3 will be used for the assessment of risk of bias and data synthesis. RESULTS: The results will provide a high-quality synthesis of current evidence for researchers in this subject area. CONCLUSION: The conclusion of our study will provide an evidence to judge whether TCM is effective and safe for the patients with symptoms of upper respiratory tract of coronavirus disease 2019. ETHICS AND DISSEMINATION: This protocol will not evaluate individual patient information or affect patient rights and therefore does not require ethical approval. Results from this review will be disseminated through peer-reviewed journals and conference reports. PROSPERO REGISTRATION NUMBER: CRD42020187422.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Medicina Tradicional Chinesa/métodos , Pneumonia Viral/terapia , Infecções Respiratórias/terapia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Humanos , Metanálise como Assunto , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Sistema Respiratório/virologia , Infecções Respiratórias/patologia , Infecções Respiratórias/virologia , Revisões Sistemáticas como Assunto , Resultado do Tratamento
10.
Allergol Immunopathol (Madr) ; 48(5): 500-506, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32771236

RESUMO

The reasons for the relative resistance of children to certain infections such as that caused by coronavirus SARS-CoV2 are not yet fully clear. Deciphering these differences can provide important information about the pathogenesis of the disease. Regarding the SARS-CoV2 virus, children are at the same risk of infection as the general population of all ages, with the most serious cases being found in infants. However, it has been reported that the disease is much less frequent than in adults and that most cases are benign or moderate (even with high viral loads), provided there are no other risk factors or underlying diseases. It is not clear why they have lower morbidity and virtually no mortality. A series of findings, relationships and behavioral patterns between the infectious agent and the child host may account for the lower incidence and a greatly attenuated clinical presentation of the disease in children.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/patologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/patologia , Adulto , Fatores Etários , Portador Sadio/transmissão , Portador Sadio/virologia , Criança , Coinfecção/epidemiologia , Coinfecção/imunologia , Coinfecção/patologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/transmissão , Humanos , Sistema Imunitário , Estilo de Vida , Melatonina/imunologia , Melatonina/metabolismo , Pandemias , Peptidil Dipeptidase A/imunologia , Peptidil Dipeptidase A/metabolismo , Vacinas Pneumocócicas/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/transmissão , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/imunologia , Infecções Respiratórias/patologia
11.
Vet Parasitol ; 285: 109215, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32862125

RESUMO

Feline lungworms such as Aerulostrongylus abstrusus and Troglostrongylus brevior are snail-borne pathogens causing respiratory disease in domestic cats. Paratenic hosts such as rodents and reptiles have also been implicated in the epidemiology of these parasites. Although A. abstrusus has been recognized for a long time as the most prevalent lungworm among cats worldwide, T. brevior is of major concern in kittens. Bearing in mind that disease due to T. brevior occurs mainly in pediatric patients younger than 6 months of age, the diagnosis of this parasite in two kittens presenting severe respiratory disease from the garden of one of the authors inspired us to investigate the potential routes of transmission for T. brevior in domestic cats. Of the three queens (A, B and C) that delivered kittens (n = 8), only cat A was positive for T. brevior, presenting her two kittens severe respiratory clinical signs, which lead to the exitus in one of them, 18 days of age. In addition, three kittens, the offspring of queen B, turned to be positive at the coprological examination after suckling from queen A, whereas those from queen C (that suckled only on their own mother) remained negative. A series of coprological, histological and molecular tests were conducted to confirm the presence of T. brevior in the patients as well as in the other cats cohabiting the same garden. Adult nematodes were retrieved from the trachea and bronchi of the dead kitten (kitten 1A), and larvae at the histology of the lung and liver parenchyma associated with bronco pneumonitis and lymphocytic pericholangitis, respectively. Cornu aspersum (n = 60), Eobania vermiculata (n = 30) snails (intermediate hosts) as well as lizards and rats (potential paratenic hosts) were collected from the same garden and processed through tissue digestion and molecular detection. Troglostrongylus brevior larvae were recovered through tissue digestion from two C. aspersum (3.33 %) and it was confirmed by PCR-sequencing approach, which also detected T. brevior DNA in the liver and lungs of one rat and in the coelomatic cavity of one gecko lizard. During the COVID-19 lockdown, when scientists spent more time at home, we grasp the opportunity to decipher T. brevior biology and ecology starting in a small ecological niche, such as the garden of our house. Data herein presented led us to suggest: i) the transmammary transmission of T. brevior in domestic cats; ii) the role of intermediate and paratenic hosts (including reptiles) in the epidemiology of the infection which they transmit; as well as iii) the importance of observational parasitology in studying any event that certainly occurs in small ecological niches, as it could be in our home gardens.


Assuntos
Doenças do Gato/parasitologia , Doenças do Gato/transmissão , Transmissão Vertical de Doença Infecciosa/veterinária , Infecções Respiratórias/veterinária , Infecções por Strongylida/veterinária , Estrongilídios , Animais , Gatos , Feminino , Masculino , Infecções Respiratórias/parasitologia , Infecções Respiratórias/patologia , Infecções Respiratórias/transmissão , Infecções por Strongylida/parasitologia , Infecções por Strongylida/transmissão
12.
PLoS One ; 15(7): e0236806, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32730318

RESUMO

Adenotonsillectomy is a common paediatric surgery for treating obstructed breathing or recurrent inflammation; however, the long-term health consequences on the developing immune system are unknown. This study investigated the potential association between adenotonsillectomy and the development of asthma and upper respiratory infections (URI). This propensity score-matched retrospective cohort study utilized data from the National Sample Cohort 2002-2013. In the asthma cohort, we used a Cox-proportional hazards model to analyze the hazard ratio (HR) of adenotonsillectomy for asthma events. In the URI cohort, equivalence testing of postoperative visits for URI was performed. The margin of equivalence of the difference was set at -0.5-0.5. Asthma incidence was 66.97/1000 person-years in children who underwent adenotonsillectomy and 30.43/1000 person-years in those who did not. Adjusted asthma HRs were 2.25 (95% confidence interval, 1.96-2.57) in the adenotonsillectomy vs. non-adenotonsillectomy groups. In a subgroup analysis, children aged 5-9 years living in metropolitan areas showed a higher incidence of subsequent asthma than those of other ages and areas. However, any significant difference between the groups in terms of URI events in the 1-11-year postoperative period was not identified. Adenotonsillectomy in children is associated with an increased incidence of asthma, with no significant impact on postoperative visits for URI.


Assuntos
Adenoidectomia/efeitos adversos , Asma/epidemiologia , Infecções Respiratórias/epidemiologia , Tonsilectomia/efeitos adversos , Adolescente , Asma/etiologia , Asma/patologia , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , República da Coreia/epidemiologia , Infecções Respiratórias/etiologia , Infecções Respiratórias/patologia , Estudos Retrospectivos , Fatores de Risco
13.
Curr Protoc Stem Cell Biol ; 54(1): e118, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32640120

RESUMO

The normal development of the pulmonary system is critical to transitioning from placental-dependent fetal life to alveolar-dependent newborn life. Human lung development and disease have been difficult to study due to the lack of an in vitro model system containing cells from the large airways and distal alveolus. This article describes a system that allows human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) to differentiate and form three-dimensional (3D) structures that emulate the development, cytoarchitecture, and function of the lung ("organoids"), containing epithelial and mesenchymal cell populations, and including the production of surfactant and presence of ciliated cells. The organoids can also be invested with mesoderm derivatives, differentiated from the same human pluripotent stem cells, such as alveolar macrophages and vasculature. Such lung organoids may be used to study the impact of environmental modifiers and perturbagens (toxins, microbial or viral pathogens, alterations in microbiome) or the efficacy and safety of drugs, biologics, and gene transfer. © 2020 Wiley Periodicals LLC. Basic Protocol: hESC/hiPSC dissection, definitive endoderm formation, and lung progenitor cell induction.


Assuntos
Infecções por Coronavirus/patologia , Pulmão/citologia , Organoides/citologia , Pneumonia Viral/patologia , Infecções Respiratórias/patologia , Betacoronavirus , Técnicas de Cultura de Células , Diferenciação Celular , Infecções por Coronavirus/terapia , Endoderma/citologia , Células-Tronco Embrionárias Humanas/citologia , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Pulmão/crescimento & desenvolvimento , Pulmão/fisiologia , Modelos Biológicos , Pandemias , Modelagem Computacional Específica para o Paciente , Pneumonia Viral/terapia , Infecções Respiratórias/terapia , Imagem com Lapso de Tempo
14.
J Clin Microbiol ; 58(8)2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32522830

RESUMO

Discovery of bats with severe acute respiratory syndrome (SARS)-related coronaviruses (CoVs) raised the specter of potential future outbreaks of zoonotic SARS-CoV-like disease in humans, which largely went unheeded. Nevertheless, the novel SARS-CoV-2 of bat ancestral origin emerged to infect humans in Wuhan, China, in late 2019 and then became a global pandemic. Less than 5 months after its emergence, millions of people worldwide have been infected asymptomatically or symptomatically and at least 360,000 have died. Coronavirus disease 2019 (COVID-19) in severely affected patients includes atypical pneumonia characterized by a dry cough, persistent fever, and progressive dyspnea and hypoxia, sometimes accompanied by diarrhea and often followed by multiple organ failure, especially of the respiratory and cardiovascular systems. In this minireview, we focus on two endemic respiratory CoV infections of livestock: bovine coronavirus (BCoV) and porcine respiratory coronavirus (PRCV). Both animal respiratory CoVs share some common features with SARS-CoV and SARS-CoV-2. BCoV has a broad host range including wild ruminants and a zoonotic potential. BCoV also has a dual tropism for the respiratory and gastrointestinal tracts. These aspects, their interspecies transmission, and certain factors that impact disease severity in cattle parallel related facets of SARS-CoV or SARS-CoV-2 in humans. PRCV has a tissue tropism for the upper and lower respiratory tracts and a cellular tropism for type 1 and 2 pneumocytes in lung but is generally a mild infection unless complicated by other exacerbating factors, such as bacterial or viral coinfections and immunosuppression (corticosteroids).


Assuntos
Betacoronavirus/crescimento & desenvolvimento , Doenças dos Bovinos/fisiopatologia , Infecções por Coronavirus/veterinária , Coronavirus Bovino/crescimento & desenvolvimento , Pneumonia Viral/fisiopatologia , Infecções Respiratórias/veterinária , Doenças dos Suínos/fisiopatologia , Animais , Betacoronavirus/patogenicidade , Bovinos , Doenças dos Bovinos/patologia , Doenças dos Bovinos/virologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/fisiopatologia , Coronavirus Bovino/patogenicidade , Especificidade de Hospedeiro , Humanos , Pandemias , Pneumonia Viral/patologia , Coronavirus Respiratório Porcino/crescimento & desenvolvimento , Coronavirus Respiratório Porcino/patogenicidade , Infecções Respiratórias/patologia , Infecções Respiratórias/fisiopatologia , Suínos , Doenças dos Suínos/patologia , Doenças dos Suínos/virologia , Tropismo Viral
15.
Influenza Other Respir Viruses ; 14(6): 739-746, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32567818

RESUMO

BACKGROUND: Acute respiratory illnesses are a leading cause of global morbidity and mortality in children. Coinfection with multiple respiratory viruses is common. Although the effects of each virus have been studied individually, the impacts of coinfection on disease severity are less understood. METHODS: A secondary analysis was performed of a maternal influenza vaccine trial conducted between 2011 and 2014 in Nepal. Prospective weekly household-based active surveillance of infants was conducted from birth to 180 days of age. Mid-nasal swabs were collected and tested for respiratory syncytial virus (RSV), rhinovirus, influenza, human metapneumovirus (HMPV), coronavirus, parainfluenza (HPIV), and bocavirus by RT-PCR. Coinfection was defined as the presence of two or more respiratory viruses detected as part of the same illness episode. RESULTS: Of 1730 infants with a respiratory illness, 327 (19%) had at least two respiratory viruses detected in their primary illness episode. Of 113 infants with influenza, 23 (20%) had coinfection. Of 214 infants with RSV, 87 (41%) had coinfection. The cohort of infants with coinfection had increased occurrence of fever lasting ≥ 4 days (OR 1.4, 95% CI: 1.1, 2.0), and so did the subset of coinfected infants with influenza (OR 5.8, 95% CI: 1.8, 18.7). Coinfection was not associated with seeking further care (OR 1.1, 95% CI: 0.8, 1.5) or pneumonia (OR 1.2, 95% CI: 0.96, 1.6). CONCLUSION: A high proportion of infants had multiple viruses detected. Coinfection was associated with greater odds of fever lasting for four or more days, but not with increased illness severity by other measures.


Assuntos
Coinfecção/epidemiologia , Coinfecção/virologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Coinfecção/patologia , Febre/epidemiologia , Febre/patologia , Febre/virologia , Humanos , Lactente , Recém-Nascido , Nepal/epidemiologia , Razão de Chances , Estudos Prospectivos , Infecções Respiratórias/patologia , População Rural , Viroses/epidemiologia , Viroses/patologia , Viroses/virologia , Vírus/classificação , Vírus/isolamento & purificação
16.
Am J Pathol ; 190(10): 2095-2110, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32598882

RESUMO

Inhalational anthrax, a disease caused by inhaling Bacillus anthracis spores, leads to respiratory distress, vascular leakage, high-level bacteremia, and often death within days. Anthrax lethal toxin and edema toxin, which are composed of protective antigen (PA) plus either lethal factor (LF) or edema factor (EF), respectively, play an important yet incompletely defined role in the pulmonary pathophysiology. To better understand their contribution, we examined the structural integrity of the alveolar-capillary barrier in archival formalin-fixed lungs of cynomolgus monkeys challenged with the fully virulent B. anthracis Ames wild-type strain or the isogenic toxin-deficient mutants ΔEF, ΔLF, and ΔPA. Pulmonary spore challenge with the wild-type strain caused high mortality, intra-alveolar hemorrhages, extensive alveolar septal sequestration of bacteria and neutrophils, diffuse destabilization of epithelial and endothelial junctions, increased markers of coagulation and complement activation (including tissue factor and C5a), and multifocal intra-alveolar fibrin deposition. ΔEF challenge was lethal and showed similar alveolar-capillary alterations; however, intra-alveolar hemorrhages, bacterial deposition, and markers of coagulation or complement were absent or markedly lower. In contrast, ΔLF or ΔPA challenges were nonlethal and showed no signs of alveolar bacterial deposition or alveolar-capillary changes. These findings provide evidence that lethal toxin plays a determinative role in bacterial dissemination and alveolar-capillary barrier dysfunction, and edema toxin may significantly exacerbate pulmonary pathologies in a systemic infection.


Assuntos
Antraz/patologia , Bacillus anthracis/patogenicidade , Bacteriemia/patologia , Pulmão/patologia , Infecções Respiratórias/patologia , Animais , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/farmacologia , Toxinas Bacterianas/farmacologia , Pulmão/efeitos dos fármacos , Macaca fascicularis/imunologia , Neutrófilos/imunologia , Esporos Bacterianos/imunologia , Esporos Bacterianos/patogenicidade , Virulência/imunologia
17.
J Immunol ; 205(2): 313-320, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32493812

RESUMO

Aging impairs immunity to promote diseases, especially respiratory viral infections. The current COVID-19 pandemic, resulting from SARS-CoV-2, induces acute pneumonia, a phenotype that is alarmingly increased with aging. In this article, we review findings of how aging alters immunity to respiratory viral infections to identify age-impacted pathways common to several viral pathogens, permitting us to speculate about potential mechanisms of age-enhanced mortality to COVID-19. Aging generally leads to exaggerated innate immunity, particularly in the form of elevated neutrophil accumulation across murine and large animal studies of influenza infection. COVID-19 patients who succumb exhibit a 2-fold increase in neutrophilia, suggesting that exaggerated innate immunity contributes to age-enhanced mortality to SARS-CoV-2 infection. Further investigation in relevant experimental models will elucidate the mechanisms by which aging impacts respiratory viral infections, including SARS-CoV-2. Such investigation could identify therapies to reduce the suffering of the population at large, but especially among older people, infected with respiratory viruses.


Assuntos
Envelhecimento/patologia , Betacoronavirus/fisiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Infecções Respiratórias/virologia , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/virologia , Citocinas/imunologia , Humanos , Influenza Humana/imunologia , Influenza Humana/patologia , Pandemias , Infecções Respiratórias/patologia , Vírus da SARS/fisiologia
18.
Jpn J Infect Dis ; 73(5): 377-380, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32475878

RESUMO

Coronavirus disease 2019 (COVID-19) is a severe infectious disease of the respiratory tract caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2, and has a high mortality rate. The disease emerged from Wuhan, China, in late 2019, and spread to Japan, including Hokkaido, in January 2020. In February 2020, 3 children were diagnosed with COVID-19 in Furano, Hokkaido, Japan. During this period, influenza and human metapneumovirus infections were prevalent among children in the Furano region. Two of the 3 patients experienced co-infection with other respiratory viruses, including influenza virus A or human metapneumovirus. To the authors' knowledge, the cases described in the present report were the first pediatric patients with COVID-19 in Japan. In children with COVID-19, the possibility of co-infection with other respiratory pathogens should be considered.


Assuntos
Coinfecção/diagnóstico , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Infecções Respiratórias/diagnóstico , Betacoronavirus/isolamento & purificação , Criança , Pré-Escolar , Coinfecção/patologia , Coinfecção/virologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Humanos , Japão/epidemiologia , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Infecções Respiratórias/patologia , Infecções Respiratórias/virologia
19.
Virulence ; 11(1): 486-488, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32434416

RESUMO

Lack of an appropriate animal model to study severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent responsible for COVID-19 pandemic disease, represents a significant hurdle in the process of understanding disease biology and evaluating therapeutic and preventive candidates. It is time for public health agencies to revisit regulation on transplantation of human pluripotent stem cells for the possibility of the development of a humanized mice model with a humanized lung.


Assuntos
Infecções por Coronavirus/patologia , Modelos Animais de Doenças , Células-Tronco Pluripotentes/transplante , Pneumonia Viral/patologia , Infecções Respiratórias/patologia , Transplante Heterólogo/legislação & jurisprudência , Animais , Humanos , Camundongos , Pandemias , Pesquisa/legislação & jurisprudência , Pesquisa/normas , Pesquisa/tendências , Transplante Heterólogo/tendências
20.
Nat Med ; 26(5): 676-680, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32371934

RESUMO

We identified seasonal human coronaviruses, influenza viruses and rhinoviruses in exhaled breath and coughs of children and adults with acute respiratory illness. Surgical face masks significantly reduced detection of influenza virus RNA in respiratory droplets and coronavirus RNA in aerosols, with a trend toward reduced detection of coronavirus RNA in respiratory droplets. Our results indicate that surgical face masks could prevent transmission of human coronaviruses and influenza viruses from symptomatic individuals.


Assuntos
Infecções por Coronavirus/transmissão , Máscaras/virologia , Pneumonia Viral/transmissão , Infecções Respiratórias/transmissão , Aerossóis/isolamento & purificação , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Expiração/fisiologia , Humanos , Orthomyxoviridae/isolamento & purificação , Orthomyxoviridae/patogenicidade , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/virologia , RNA Viral/isolamento & purificação , Infecções Respiratórias/patologia , Infecções Respiratórias/virologia , Eliminação de Partículas Virais
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