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1.
Front Immunol ; 11: 552909, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013925

RESUMO

The 2019 novel coronavirus (SARS-CoV-2) pandemic has caused a global health emergency. The outbreak of this virus has raised a number of questions: What is SARS-CoV-2? How transmissible is SARS-CoV-2? How severely affected are patients infected with SARS-CoV-2? What are the risk factors for viral infection? What are the differences between this novel coronavirus and other coronaviruses? To answer these questions, we performed a comparative study of four pathogenic viruses that primarily attack the respiratory system and may cause death, namely, SARS-CoV-2, severe acute respiratory syndrome (SARS-CoV), Middle East respiratory syndrome (MERS-CoV), and influenza A viruses (H1N1 and H3N2 strains). This comparative study provides a critical evaluation of the origin, genomic features, transmission, and pathogenicity of these viruses. Because the coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 is ongoing, this evaluation may inform public health administrators and medical experts to aid in curbing the pandemic's progression.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/epidemiologia , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H3N2/genética , Influenza Humana/epidemiologia , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Pneumonia Viral/epidemiologia , Vírus da SARS/genética , Síndrome Respiratória Aguda Grave/epidemiologia , Animais , Betacoronavirus/patogenicidade , Aves/virologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Genoma Viral , Humanos , Vírus da Influenza A Subtipo H1N1/patogenicidade , Vírus da Influenza A Subtipo H3N2/patogenicidade , Influenza Aviária/epidemiologia , Influenza Aviária/transmissão , Influenza Aviária/virologia , Influenza Humana/transmissão , Influenza Humana/virologia , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Pandemias , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/transmissão , Síndrome Respiratória Aguda Grave/virologia , Virulência/imunologia
2.
Mem Inst Oswaldo Cruz ; 115: e200232, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32965332

RESUMO

Coronavirus disease 2019 (COVID-19) surveillance, in Brazil, initiated shortly after its description, in China. Our aim was to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and additional pathogens in samples from the initial phase of the outbreak in Brazil, from late February to late March. From 707 samples analysed, 29 (4.1%) were SARS-CoV-2 positive. Fever and cough were their most prevalent symptoms. Co-detection of rhinovirus was observed in 2 (6.9%) cases. Additional pathogens were identified in 66.1% of the SARS-CoV-2 negative cases, mainly rhinovirus and influenza A(H1N1)pdm09. Thus, we emphasise the importance of differential diagnosis in COVID-19 suspected cases.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Brasil/epidemiologia , China , Infecções por Coronavirus/epidemiologia , Diagnóstico Diferencial , Humanos , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Pandemias , Pneumonia Viral/epidemiologia , Rhinovirus/isolamento & purificação
4.
JMIR Public Health Surveill ; 6(3): e17242, 2020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32909955

RESUMO

BACKGROUND: A better understanding of the influenza epidemiology among primary care workers could guide future recommendations to prevent transmission in primary care practices. Therefore, we designed a pilot study to assess the feasibility of using a work-based online influenza surveillance system among primary care workers. Such an approach is of particular relevance in the context of the coronavirus disease (COVID-19) pandemic, as its findings could apply to other infectious diseases with similar mechanisms of transmission. OBJECTIVE: This study aims to determine the feasibility of using a work-based online influenza surveillance system for primary care workers in Switzerland. METHODS: Physicians and staff of one walk-in clinic and two selected primary care practices were enrolled in this observational prospective pilot study during the 2017-2018 influenza season. They were invited to record symptoms of influenza-like illness in a weekly online survey sent by email and to self-collect a nasopharyngeal swab in case any symptoms were recorded. Samples were tested by real-time polymerase chain reaction for influenza A, influenza B, and a panel of respiratory pathogens. RESULTS: Among 67 eligible staff members, 58% (n=39) consented to the study and 53% (n=36) provided data. From the time all participants were included, the weekly survey response rate stayed close to 100% until the end of the study. Of 79 symptomatic episodes (mean 2.2 episodes per participant), 10 episodes in 7 participants fitted the definition of an influenza-like illness case (attack rate: 7/36, 19%). One swab tested positive for influenza A H1N1 (attack rate: 3%, 95% CI 0%-18%). Swabbing was considered relatively easy. CONCLUSIONS: A work-based online influenza surveillance system is feasible for use among primary care workers. This promising methodology could be broadly used in future studies to improve the understanding of influenza epidemiology and other diseases such as COVID-19. This could prove to be highly useful in primary care settings and guide future recommendations to prevent transmission. A larger study will also help to assess asymptomatic infections.


Assuntos
Pessoal de Saúde , Influenza Humana/epidemiologia , Programas de Rastreamento/métodos , Sistemas On-Line , Vigilância da População/métodos , Atenção Primária à Saúde , Adulto , Betacoronavirus , Controle de Doenças Transmissíveis/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Estudos de Viabilidade , Feminino , Inquéritos Epidemiológicos , Humanos , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/diagnóstico , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Pandemias , Projetos Piloto , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Prevalência , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Suíça
5.
PLoS Med ; 17(9): e1003225, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32926731

RESUMO

BACKGROUND: Early studies of narcolepsy after AS03-adjuvanted pandemic A/H1N12009 vaccine (Pandemrix) could not define the duration of elevated risk post-vaccination nor the risk in children aged under 5 years who may not present until much older. METHODS/FINDINGS: Clinical information and sleep test results, extracted from hospital notes at 3 large pediatric sleep centers in England between September 2017 and June 2018 for narcolepsy cases aged 4-19 years with symptom onset since January 2009, were reviewed by an expert panel to confirm the diagnosis. Vaccination histories were independently obtained from general practitioners (GPs). The odds of vaccination in narcolepsy cases compared with the age-matched English population was calculated after adjustment for clinical conditions that were indications for vaccination. GP questionnaires were returned for 242 of the 244 children with confirmed narcolepsy. Of these 5 were under 5 years, 118 were 5-11 years, and 119 were 12-19 years old at diagnosis; 39 were vaccinated with Pandemrix before onset. The odds ratio (OR) for onset at any time after vaccination was 1.94 (95% confidence interval [CI] 1.30-2.89), The elevated risk period was restricted to onsets within 12 months of vaccination (OR 6.65 [3.44-12.85]) and was highest within the first 6 months. After one year, ORs were not significantly different from 1 up to 8 years after vaccination. The ORs were similar in under five-year-olds and older ages. The estimated attributable risk was 1 in 34,500 doses. Our study is limited by including cases from only 3 sleep centers, who may differ from cases diagnosed in nonparticipating centers, and by imprecision in defining the centers' catchment population. The potential for biased recall of onset shortly after vaccination in cases aware of the association cannot be excluded. CONCLUSIONS: In this study, we found that vaccine-attributable cases have onset of narcolepsy within 12 months of Pandemrix vaccination. The attributable risk is higher than previously estimated in England because of identification of vaccine-attributable cases with late diagnoses. Absence of a compensatory drop in risk 1-8 years after vaccination suggests that Pandemrix does not trigger onsets in those in whom narcolepsy would have occurred later.


Assuntos
Narcolepsia/etiologia , Polissorbatos/efeitos adversos , Esqualeno/efeitos adversos , Vacinação/efeitos adversos , alfa-Tocoferol/efeitos adversos , Adolescente , Criança , Pré-Escolar , Combinação de Medicamentos , Inglaterra/epidemiologia , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/efeitos adversos , Vacinas contra Influenza/uso terapêutico , Influenza Humana/epidemiologia , Masculino , Narcolepsia/epidemiologia , Narcolepsia/imunologia , Razão de Chances , Pandemias , Fatores de Risco , Inquéritos e Questionários
6.
Braz J Med Biol Res ; 53(10): e9183, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32901688

RESUMO

H1N1 virus-induced excessive inflammatory response contributes to severe disease and high mortality rates. There is currently no effective strategy against virus infection in lung. The present study evaluated the protective roles of a natural compound, lapiferin, in H1N1 virus-induced pulmonary inflammation in mice and in cultured human bronchial epithelial cells. Initially, Balb/C mice were grouped as Control, H1N1 infection (intranasally infected with 500 plaque-forming units of H1N1 virus), lapiferin (10 mg/kg), and H1N1+lapiferin (n=10/group). Lung histology, expression of inflammatory factors, and survival rates were assessed after 14 days of exposure. Administration of lapiferin significantly alleviated the virus-induced inflammatory infiltrate in lung tissues. Major pro-inflammatory cytokines, such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α, were decreased at both mRNA and protein levels by lapiferin administration in the lung homogenate. Lapiferin also reduced inflammatory cell numbers in bronchoalveolar fluid. Mechanistically, lapiferin suppressed the transcriptional activity and protein expression of NF-κB p65, causing inhibition on NF-κB signaling. Pre-incubation of human bronchial epithelial cells with an NF-κB signaling specific activator, ceruletide, significantly blunted lapiferin-mediated inhibition of pro-inflammatory cytokines secretion in an air-liquid-interface cell culture experiment. Activation of NF-κB signaling also blunted lapiferin-ameliorated inflammatory infiltrate in lungs. These results suggested that lapiferin was a potent natural compound that served as a therapeutic agent for virus infection in the lung.


Assuntos
Vírus da Influenza A Subtipo H1N1 , NF-kappa B/metabolismo , Pneumonia , Substâncias Protetoras/farmacologia , Sesquiterpenos/farmacologia , Animais , Citocinas , Humanos , Inflamação , Camundongos , Transdução de Sinais
7.
Cell Rep ; 32(6): 108016, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32755598

RESUMO

The influenza virus hemagglutinin (HA) and coronavirus spike (S) protein mediate virus entry. HA and S proteins are heavily glycosylated, making them potential targets for carbohydrate binding agents such as lectins. Here, we show that the lectin FRIL, isolated from hyacinth beans (Lablab purpureus), has anti-influenza and anti-SARS-CoV-2 activity. FRIL can neutralize 11 representative human and avian influenza strains at low nanomolar concentrations, and intranasal administration of FRIL is protective against lethal H1N1 infection in mice. FRIL binds preferentially to complex-type N-glycans and neutralizes viruses that possess complex-type N-glycans on their envelopes. As a homotetramer, FRIL is capable of aggregating influenza particles through multivalent binding and trapping influenza virions in cytoplasmic late endosomes, preventing their nuclear entry. Remarkably, FRIL also effectively neutralizes SARS-CoV-2, preventing viral protein production and cytopathic effect in host cells. These findings suggest a potential application of FRIL for the prevention and/or treatment of influenza and COVID-19.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Fabaceae/química , Infecções por Orthomyxoviridae/tratamento farmacológico , Lectinas de Plantas/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Células A549 , Administração Intranasal , Animais , Antivirais/administração & dosagem , Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Embrião de Galinha , Chlorocebus aethiops , Cães , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Células Madin Darby de Rim Canino , Camundongos , Camundongos Endogâmicos BALB C , Pandemias , Lectinas de Plantas/administração & dosagem , Lectinas de Plantas/farmacologia , Ligação Proteica , Células Vero , Proteínas do Envelope Viral/metabolismo
8.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(6): 597-601, 2020 Jun 06.
Artigo em Chinês | MEDLINE | ID: mdl-32842276

RESUMO

On March 11, 2020, WHO officially declared that COVID-19 had become Pandemic. As of March 31, the epidemic had affected more than 178 countries and regions, with more than 780 000 confirmed cases. The Pandemic Influenza Preparedness Framework for the sharing of influenza viruses and access to vaccines and other benefits (the 'PIP Framework' or 'Framework') is an international arrangement adopted by the World Health Organization in May 2011 to improve global pandemic influenza preparedness and response. Since the transmission route and transmission capacity of COVID-19 are similar to that of influenza A (H1N1) in 2009, which conforms to the basic elements of "human pandemic", and the epidemic scale has exceeded that of influenza A (H1N1), it is probable to incorporate COVID-19 epidemic response into PIPF, and at the same time to verify and improve PIPF in practice. It is recommended that WHO, other international organizations and relevant countries make full use of the PIPF system to respond to the epidemic and better coordinate national actions at the global level. At the same time, China should also make the planning and deploy of domestic epidemic prevention and control and international epidemic cooperation under the framework.


Assuntos
Infecções por Coronavirus/prevenção & controle , Epidemias/prevenção & controle , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Humanos , Influenza Humana/epidemiologia , Pneumonia Viral/epidemiologia
10.
MMWR Recomm Rep ; 69(8): 1-24, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32820746

RESUMO

This report updates the 2019-20 recommendations of the Advisory Committee on Immunization Practices (ACIP) regarding the use of seasonal influenza vaccines in the United States (MMWR Recomm Rep 2019;68[No. RR-3]). Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. For each recipient, a licensed and age-appropriate vaccine should be used. Inactivated influenza vaccines (IIVs), recombinant influenza vaccine (RIV4), and live attenuated influenza vaccine (LAIV4) are expected to be available. Most influenza vaccines available for the 2020-21 season will be quadrivalent, with the exception of MF59-adjuvanted IIV, which is expected to be available in both quadrivalent and trivalent formulations.Updates to the recommendations described in this report reflect discussions during public meetings of ACIP held on October 23, 2019; February 26, 2020; and June 24, 2020. Primary updates to this report include the following two items. First, the composition of 2020-21 U.S. influenza vaccines includes updates to the influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B/Victoria lineage components. Second, recent licensures of two new influenza vaccines, Fluzone High-Dose Quadrivalent and Fluad Quadrivalent, are discussed. Both new vaccines are licensed for persons aged ≥65 years. Additional changes include updated discussion of contraindications and precautions to influenza vaccination and the accompanying Table, updated discussion concerning use of LAIV4 in the setting of influenza antiviral medication use, and updated recommendations concerning vaccination of persons with egg allergy who receive either cell culture-based IIV4 (ccIIV4) or RIV4.The 2020-21 influenza season will coincide with the continued or recurrent circulation of SARS-CoV-2 (the novel coronavirus associated with coronavirus disease 2019 [COVID-19]). Influenza vaccination of persons aged ≥6 months to reduce prevalence of illness caused by influenza will reduce symptoms that might be confused with those of COVID-19. Prevention of and reduction in the severity of influenza illness and reduction of outpatient illnesses, hospitalizations, and intensive care unit admissions through influenza vaccination also could alleviate stress on the U.S. health care system. Guidance for vaccine planning during the pandemic is available at https://www.cdc.gov/vaccines/pandemic-guidance/index.html.This report focuses on recommendations for the use of vaccines for the prevention and control of seasonal influenza during the 2020-21 season in the United States. A brief summary of the recommendations and a link to the most recent Background Document containing additional information are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html. These recommendations apply to U.S.-licensed influenza vaccines used within Food and Drug Administration (FDA)-licensed indications. Updates and other information are available from CDC's influenza website (https://www.cdc.gov/flu). Vaccination and health care providers should check this site periodically for additional information.


Assuntos
Vacinas contra Influenza/uso terapêutico , Influenza Humana/prevenção & controle , Adolescente , Adulto , Comitês Consultivos , Idoso , Centers for Disease Control and Prevention, U.S. , Criança , Pré-Escolar , Feminino , Humanos , Esquemas de Imunização , Lactente , Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H3N2 , Vírus da Influenza B , Vacinas contra Influenza/efeitos adversos , Influenza Humana/epidemiologia , Masculino , Pessoa de Meia-Idade , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Estações do Ano , Estados Unidos/epidemiologia , Vacinas Atenuadas/uso terapêutico , Adulto Jovem
11.
Vaccine ; 38(41): 6374-6380, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32798142

RESUMO

The rapid spread of the Coronavirus pandemic and its significant health and social impact urges the search for effective and readily available solutions to mitigate the damages. Thus, evaluating the effectiveness of existing vaccines like Bacillus Calmette-Guérin (BCG) has attracted attention. The aim of this review was evidence synthesis on the effect of BCG vaccine in preventing severe infectious respiratory disease including COVD-19, but not tuberculosis. We considered studies conducted on human participants of any study design from any country setting that were published in Enlgish. We did a systematic literature search in MEDLINE, Scopus and Google scholar databases and a free search on Google. The identified studies were appraised and relevant data were extracted using Joanna Briggs Institute tools. The extracted findings were synthesized with tables and narrative summary. Nine studies met the inclusion criteria. The findings indicated that BCG vaccine has a strong protective effect against both upper and lower acute respiratory tract infections. For instance in countries with universal BCG vaccination policy, the incidence of COVID-19 was lower compared to the counterparts. Addtionally, BCG vaccine was found to protect against infections like lethal influenza A virus, pandemic influenza (H1N1), and other acute respiratory tract infections. BCG improved the human body's immune response involving antigen-specific T cells and memory cells. It also induced adaptive functional reprogramming of mononuclear phagocytes that induce protective effects against different respiratory infections other than tuberculosis. In countries with universal BCG vaccination, the incidence and death from acute respiratory viral infection including COVID - 19 is significantly low. However, there is an urgent need for further evidence from well-designed studies to understand the possible role of BCG vaccination over time and across age groups, its possible benefits in special populations such as health workers and cost-savings related to a policy of universal BCG vaccination.


Assuntos
Vacina BCG/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Mycobacterium bovis/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Anticorpos Antivirais/imunologia , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Humana/prevenção & controle , Tuberculose Pulmonar/prevenção & controle , Vacinação
14.
Artigo em Inglês | MEDLINE | ID: mdl-32784978

RESUMO

This study investigated the impact of COVID-19 on the insurance industry by studying the case of Ghana from March to June 2020. With a parallel comparison to previous pandemics such as SARS-CoV, H1N1 and MERS, we developed outlines for simulating the impact of the pandemic on the insurance industry. The study used qualitative and quantitative interviews to estimate the impact of the pandemic. Presently, the trend is an economic recession with decreasing profits but increasing claims. Due to the cancellation of travels, events and other economic losses, the Ghanaian insurance industry witnessed a loss currently estimated at GH Ȼ112 million. Our comparison and forecast predicts a normalization of economic indicators from January 2021. In the meantime, while the pandemic persists, insurers should adapt to working from remote locations, train and equip staff to work under social distancing regulations, enhance cybersecurity protocols and simplify claims/premium processing using e-payment channels. It will require the collaboration of the Ghana Ministry of Health, Banking Sector, Police Department, Customs Excise and Preventive Service, other relevant Ministries and the international community to bring the pandemic to a stop.


Assuntos
Infecções por Coronavirus/epidemiologia , Seguradoras/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Betacoronavirus , Recessão Econômica , Gana/epidemiologia , Humanos , Vírus da Influenza A Subtipo H1N1 , Seguradoras/economia , Coronavírus da Síndrome Respiratória do Oriente Médio , Pandemias
15.
BMC Med ; 18(1): 265, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32825816

RESUMO

BACKGROUND: New emerging infections have no known treatment. Assessing potential drugs for safety and efficacy enables clinicians to make evidence-based treatment decisions and contributes to overall outbreak control. However, it is difficult to launch clinical trials in the unpredictable environment of an outbreak. We conducted a bibliometric systematic review for the 2009 influenza pandemic to determine the speed and quality of evidence generation for treatments. This informs approaches to high-quality evidence generation in this and future pandemics. METHODS: We searched PubMed for all clinical data (including clinical trial, observational and case series) describing treatment for patients with influenza A(H1N1)pdm09 and ClinicalTrials.gov for research that aimed to enrol patients with the disease. RESULTS: Thirty-three thousand eight hundred sixty-nine treatment courses for patients hospitalised with A(H1N1)pdm09 were detailed in 160 publications. Most were retrospective observational studies or case series. Five hundred ninety-two patients received treatment (or placebo) as participants in a registered interventional clinical trial with results publicly available. None of these registered trial results was available during the timeframe of the pandemic, and the median date of publication was 213 days after the Public Health Emergency of International Concern ended. CONCLUSION: Patients were frequently treated for pandemic influenza with drugs not registered for this indication, but rarely under circumstances of high-quality data capture. The result was a reliance on use under compassionate circumstances, resulting in continued uncertainty regarding the potential benefits and harms of anti-viral treatment. Rapid scaling of clinical trials is critical for generating a quality evidence base during pandemics.


Assuntos
Antivirais/uso terapêutico , Ensaios de Uso Compassivo , Prescrição Inadequada/prevenção & controle , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/tratamento farmacológico , Uso Off-Label , Betacoronavirus , Bibliometria , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Análise Custo-Benefício , Saúde Global , Humanos , Influenza Humana/epidemiologia , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Projetos de Pesquisa , Resultado do Tratamento
16.
BMC Bioinformatics ; 21(1): 370, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32842958

RESUMO

BACKGROUND: Deciphering the relationship between clinical responses and gene expression profiles may shed light on the mechanisms underlying diseases. Most existing literature has focused on exploring such relationship from cross-sectional gene expression data. It is likely that the dynamic nature of time-series gene expression data is more informative in predicting clinical response and revealing the physiological process of disease development. However, it remains challenging to extract useful dynamic information from time-series gene expression data. RESULTS: We propose a statistical framework built on considering co-expression network changes across time from time series gene expression data. It first detects change point for co-expression networks and then employs a Bayesian multiple kernel learning method to predict exposure response. There are two main novelties in our method: the use of change point detection to characterize the co-expression network dynamics, and the use of kernel function to measure the similarity between subjects. Our algorithm allows exposure response prediction using dynamic network information across a collection of informative gene sets. Through parameter estimations, our model has clear biological interpretations. The performance of our method on the simulated data under different scenarios demonstrates that the proposed algorithm has better explanatory power and classification accuracy than commonly used machine learning algorithms. The application of our method to time series gene expression profiles measured in peripheral blood from a group of subjects with respiratory viral exposure shows that our method can predict exposure response at early stage (within 24 h) and the informative gene sets are enriched for pathways related to respiratory and influenza virus infection. CONCLUSIONS: The biological hypothesis in this paper is that the dynamic changes of the biological system are related to the clinical response. Our results suggest that when the relationship between the clinical response and a single gene or a gene set is not significant, we may benefit from studying the relationships among genes in gene sets that may lead to novel biological insights.


Assuntos
Algoritmos , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Vírus/patogenicidade , Área Sob a Curva , Teorema de Bayes , Humanos , Vírus da Influenza A Subtipo H1N1/patogenicidade , Curva ROC , Interface Usuário-Computador
17.
Immunity ; 53(3): 685-696.e3, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32783921

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic poses a current world-wide public health threat. However, little is known about its hallmarks compared to other infectious diseases. Here, we report the single-cell transcriptional landscape of longitudinally collected peripheral blood mononuclear cells (PBMCs) in both COVID-19- and influenza A virus (IAV)-infected patients. We observed increase of plasma cells in both COVID-19 and IAV patients and XIAP associated factor 1 (XAF1)-, tumor necrosis factor (TNF)-, and FAS-induced T cell apoptosis in COVID-19 patients. Further analyses revealed distinct signaling pathways activated in COVID-19 (STAT1 and IRF3) versus IAV (STAT3 and NFκB) patients and substantial differences in the expression of key factors. These factors include relatively increase of interleukin (IL)6R and IL6ST expression in COVID-19 patients but similarly increased IL-6 concentrations compared to IAV patients, supporting the clinical observations of increased proinflammatory cytokines in COVID-19 patients. Thus, we provide the landscape of PBMCs and unveil distinct immune response pathways in COVID-19 and IAV patients.


Assuntos
Infecções por Coronavirus/imunologia , Citocinas/imunologia , Influenza Humana/imunologia , Leucócitos Mononucleares/imunologia , Pneumonia Viral/imunologia , Transdução de Sinais/imunologia , Betacoronavirus/imunologia , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Pandemias
18.
Zhonghua Er Ke Za Zhi ; 58(8): 635-639, 2020 Aug 02.
Artigo em Chinês | MEDLINE | ID: mdl-32842383

RESUMO

Objective: To investigate the spectrum of pathogenic agents in pediatric patients with acute respiratory infections (ARI) during the outbreak of coronavirus infectious diseases 2019 (COVID-19). Methods: Three groups of children were enrolled into the prospective study during January 20 to February 20, 2020 from Capital Institute of Pediatrics, including children in the exposed group with ARI and epidemiological history associated with COVID-19 from whom both pharyngeal and nasopharyngeal swabs were collected, children in the ARI group without COVID-19 associated epidemiological history and children in the screening group for hospital admission, with neither COVID-19 associated epidemiological history nor ARI. Only nasopharyngeal swabs were collected in the ARI group and screening group. Each group is expected to include at least 30 cases. All specimens were tested for 2019-nCoV nucleic acid by two diagnostic kits from different manufacturers. All nasopharyngeal swabs were tested for multiple respiratory pathogens, whilst the results from the ARI group were compared with that in the correspondence periods of 2019 and 2018 used by t or χ(2) test. Results: A total of 244 children were enrolled into three groups, including 139 males and 105 females, the age was (5±4) years. The test of 2019-nCoV nucleic acid were negative in all children, and high positive rates of pathogens were detected in exposed (69.4%, 25/36) and ARI (55.3%, 73/132) groups, with the highest positive rate for mycoplasma pneumoniae (MP) (19.4%, 7/36 and 17.4%, 23/132, respectively), followed by human metapneumovirus (hMPV) (16.7%, 6/36 and 9.8%, 13/132, respectively). The positive rate (11.8%, 9/76) of pathogens in the screening group was low. In the same period of 2019, the positive rate of pathogens was 83.7% (77/92), with the highest rates for respiratory syncytial virus (RSV) A (29.3%, 27/92), followed by influenza virus (Flu) A (H1N1) (19.6%, 18/92) and adenovirus (ADV) (14.1%, 13/92), which showed significant difference with the positive rates of the three viruses in 2020 (RSV A: χ(2)=27.346, P<0.01; FluA (H1N1): χ(2)=28.083, P<0.01; ADV: χ(2)=7.848, P=0.005) . In 2018, the positive rate of pathogens was 61.0% (50/82), with the highest rate for human bocavirus (HBoV) (13.4%, 11/82) and followed by ADV (11.0%, 9/82), and significant difference was shown in the positive rate of HBoV with that in 2020 (χ(2)=6.776, P=0.009). Conclusions: The infection rate of 2019-nCoV is low among children in Beijing with no family clustering or no close contact, even with epidemiological history. The spectrum of pathogens of ARI in children during the research period is quite different from that in the previous years when the viral infections were dominant. MP is the highest positively detected one among the main pathogens during the outbreak of COVID-19 in Beijing where there is no main outbreak area.


Assuntos
Surtos de Doenças , Metapneumovirus/isolamento & purificação , Mycoplasma pneumoniae/isolamento & purificação , Infecções por Paramyxoviridae/diagnóstico , Infecções Respiratórias/diagnóstico , Pequim/epidemiologia , Betacoronavirus , Criança , Pré-Escolar , Coronavirus , Infecções por Coronavirus , Feminino , Humanos , Lactente , Vírus da Influenza A Subtipo H1N1 , Masculino , Metapneumovirus/patogenicidade , Mycoplasma pneumoniae/patogenicidade , Pandemias , Infecções por Paramyxoviridae/epidemiologia , Pediatria , Pneumonia por Mycoplasma/diagnóstico , Pneumonia por Mycoplasma/epidemiologia , Pneumonia Viral , Estudos Prospectivos , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/microbiologia , Infecções Respiratórias/virologia
19.
PLoS One ; 15(8): e0237218, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32760143

RESUMO

Influenza is an infectious respiratory illness caused by influenza viruses. Despite yearly updates, the efficacy of influenza vaccines is significantly curtailed by the virus antigenic drift and antigenic shift. These constant changes to the influenza virus make-up also challenge the development of a universal flu vaccine, which requires conserved antigenic regions shared by influenza viruses of different subtypes. We propose that it is possible to bypass these challenges by the development of an influenza vaccine based on conserved proteins delivered in an adjuvanted nanoparticle system. In this study, we generated influenza nanoparticle constructs using trimethyl chitosan nanoparticles (TMC nPs) as the carrier of recombinant influenza hemagglutinin subunit 2 (HA2) and nucleoprotein (NP). The purified HA2 and NP recombinant proteins were encapsulated into TMC nPs to form HA2-TMC nPs and NP-TMC nPs, respectively. Primary human intranasal epithelium cells (HNEpCs) were used as an in vitro model to measure immunity responses. HA2-TMC nPs, NP-TMC nPs, and HA2-NP-TMC nPs (influenza nanoparticle constructs) showed no toxicity in HNEpCs. The loading efficiency of HA2 and NP into the TMC nPs was 97.9% and 98.5%, respectively. HA2-TMC nPs and NP-TMC nPs more efficiently delivered HA2 and NP proteins to HNEpCs than soluble HA2 and NP proteins alone. The induction of various cytokines and chemokines was more evident in influenza nanoparticle construct-treated HNEpCs than in soluble protein-treated HNEpCs. In addition, soluble factors secreted by influenza nanoparticle construct-treated HNEpCs significantly induced MoDCs maturation markers (CD80, CD83, CD86 and HLA-DR), as compared to soluble factors secreted by protein-treated HNEpCs. HNEpCs treated with the influenza nanoparticle constructs significantly reduced influenza virus replication in an in vitro challenge assay. The results indicate that TMC nPs can be used as influenza vaccine adjuvants and carriers capable of delivering HA2 and NP proteins to HNEpCs.


Assuntos
Adjuvantes Imunológicos/farmacologia , Quitosana/farmacologia , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/farmacologia , Influenza Humana/prevenção & controle , Adjuvantes Imunológicos/administração & dosagem , Animais , Linhagem Celular , Células Cultivadas , Quitosana/administração & dosagem , Cães , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/farmacologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/administração & dosagem , Glicoproteínas de Hemaglutininação de Vírus da Influenza/farmacologia , Humanos , Vacinas contra Influenza/administração & dosagem , Influenza Humana/imunologia , Células Madin Darby de Rim Canino , Nanopartículas/administração & dosagem , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Proteínas de Ligação a RNA/administração & dosagem , Proteínas de Ligação a RNA/farmacologia , Proteínas do Core Viral/administração & dosagem , Proteínas do Core Viral/farmacologia
20.
PLoS Pathog ; 16(8): e1008716, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32780760

RESUMO

Pandemic influenza A virus (IAV) remains a significant threat to global health. Preparedness relies primarily upon a single class of neuraminidase (NA) targeted antivirals, against which resistance is steadily growing. The M2 proton channel is an alternative clinically proven antiviral target, yet a near-ubiquitous S31N polymorphism in M2 evokes resistance to licensed adamantane drugs. Hence, inhibitors capable of targeting N31 containing M2 (M2-N31) are highly desirable. Rational in silico design and in vitro screens delineated compounds favouring either lumenal or peripheral M2 binding, yielding effective M2-N31 inhibitors in both cases. Hits included adamantanes as well as novel compounds, with some showing low micromolar potency versus pandemic "swine" H1N1 influenza (Eng195) in culture. Interestingly, a published adamantane-based M2-N31 inhibitor rapidly selected a resistant V27A polymorphism (M2-A27/N31), whereas this was not the case for non-adamantane compounds. Nevertheless, combinations of adamantanes and novel compounds achieved synergistic antiviral effects, and the latter synergised with the neuraminidase inhibitor (NAi), Zanamivir. Thus, site-directed drug combinations show potential to rejuvenate M2 as an antiviral target whilst reducing the risk of drug resistance.


Assuntos
Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Influenza Humana/virologia , Rimantadina/farmacologia , Proteínas da Matriz Viral/antagonistas & inibidores , Zanamivir/farmacologia , Antivirais/farmacologia , Farmacorresistência Viral , Sinergismo Farmacológico , Quimioterapia Combinada , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/metabolismo , Influenza Humana/tratamento farmacológico , Proteínas da Matriz Viral/genética , Proteínas da Matriz Viral/metabolismo
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