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1.
Eur J Clin Microbiol Infect Dis ; 43(1): 87-93, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37966626

RESUMO

Early, accurate, and bulk detection of respiratory pathogens is essential for patient management and infection control. STARlet-All-in-One System (AIOS) (Seegene) is a new, fully automated, sample-to-result, molecular diagnostic platform. This study describes the first evaluation of STARlet-AIOS, by testing the Allplex™ SARS-CoV-2 (AS) and Allplex™ SARS-CoV-2/FluA/FluB/RSV combination (AC) assays in comparison to the SARS-CoV-2 assays used at our institute. Over a 3-week period, all naso-/oropharyngeal specimens tested for SARS-CoV-2 using either GeneXpert, Panther, or in-house developed test (LDT) were tested on the AIOS using the AS or AC assays. In addition, retrospective cohorts of specimens containing SARS-CoV-2, influenza virus A, influenza virus B, and RSV were tested. Discrepant results were re-tested with another assay used in this study. Hands-on time (HOT) and turn-around time (TAT) of the different systems were monitored and compared. A total of 738 specimens were tested on the AIOS using the AS assay. In addition, 210 specimens were tested using the AC assay. Overall agreement for SARS-CoV-2 detection was established as 98.5% and 95.2% for the AS and AC assay, respectively. Retrospective testing revealed high agreements for all targets, except for influenza virus A (agreement of 87.5%). HOT of the system was comparable to the HOT of GeneXpert and Panther and TAT comparable to Panther and LDT. The AIOS proved to be a robust sample-to-result system with low HOT and moderate TAT. This study showed reliable detection of SARS-CoV-2, influenza virus B, and RSV, whereas detection of influenza virus A using the AC assay appeared to be suboptimal.


Assuntos
Alphainfluenzavirus , Betainfluenzavirus , COVID-19 , Vírus da Influenza A , Influenza Humana , Humanos , SARS-CoV-2/genética , Estudos Retrospectivos , Vírus da Influenza A/genética , Nasofaringe , Sensibilidade e Especificidade , COVID-19/diagnóstico , Vírus da Influenza B/genética , Influenza Humana/diagnóstico , Técnicas de Diagnóstico Molecular
2.
Science ; 379(6632): 586-591, 2023 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-36758070

RESUMO

Orthomyxo- and bunyaviruses steal the 5' cap portion of host RNAs to prime their own transcription in a process called "cap snatching." We report that RNA modification of the cap portion by host 2'-O-ribose methyltransferase 1 (MTr1) is essential for the initiation of influenza A and B virus replication, but not for other cap-snatching viruses. We identified with in silico compound screening and functional analysis a derivative of a natural product from Streptomyces, called trifluoromethyl-tubercidin (TFMT), that inhibits MTr1 through interaction at its S-adenosyl-l-methionine binding pocket to restrict influenza virus replication. Mechanistically, TFMT impairs the association of host cap RNAs with the viral polymerase basic protein 2 subunit in human lung explants and in vivo in mice. TFMT acts synergistically with approved anti-influenza drugs.


Assuntos
Alphainfluenzavirus , Antivirais , Betainfluenzavirus , Produtos Biológicos , Inibidores Enzimáticos , Metiltransferases , Capuzes de RNA , Tubercidina , Replicação Viral , Animais , Humanos , Camundongos , Capuzes de RNA/metabolismo , RNA Mensageiro/metabolismo , RNA Viral/biossíntese , Replicação Viral/efeitos dos fármacos , Alphainfluenzavirus/efeitos dos fármacos , Betainfluenzavirus/efeitos dos fármacos , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Antivirais/química , Antivirais/farmacologia , Tubercidina/análogos & derivados , Tubercidina/farmacologia , Metiltransferases/antagonistas & inibidores , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Streptomyces/química , Simulação por Computador , Células A549
3.
Phys Chem Chem Phys ; 24(41): 25391-25402, 2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36239696

RESUMO

Here, we have carried out a proof-of-concept molecular dynamics (MD) simulation with adaptive tempering in a membrane mimetic environment to study the folding of single-pass membrane peptides. We tested the influenza A M2 viroporin, influenza B M2 viroporin, and protein E from coronaviruses MERS-Cov-2 and SARS-CoV-2 peptides with known experimental secondary structures in membrane bilayers. The two influenza-derived peptides are significantly different in the peptide sequence and secondary structure and more polar than the two coronavirus-derived peptides. Through a total of more than 50 µs of simulation time that could be accomplished in trifluoroethanol (TFE), as a membrane model, we characterized comparatively the folding behavior, helical stability, and helical propensity of these transmembrane peptides that match perfectly their experimental secondary structures, and we identified common motifs that reflect their quaternary organization and known (or not) biochemical function. We showed that BM2 is organized into two structurally distinct parts: a significantly more stable N-terminal half, and a fast-converting C-terminal half that continuously folds and unfolds between α-helical structures and non-canonical structures, which are mostly turns. In AM2, both the N-terminal half and C-terminal half are very flexible. In contrast, the two coronavirus-derived transmembrane peptides are much more stable and fast helix-formers when compared with the influenza ones. In particular, the SARS-derived peptide E appears to be the fastest and most stable helix-former of all the four viral peptides studied, with a helical structure that persists almost without disruption for the whole of its 10 µs simulation. By comparing the results with experimental observations, we benchmarked TFE in studying the conformation of membrane and hydrophobic peptides. This work provided accurate results suggesting a methodology to run long MD simulations and predict structural properties of biologically important membrane peptides.


Assuntos
COVID-19 , Influenza Humana , Humanos , Betainfluenzavirus , Coronavírus da Síndrome Respiratória do Oriente Médio , Simulação de Dinâmica Molecular , Peptídeos/química , Dobramento de Proteína , Estrutura Secundária de Proteína , SARS-CoV-2 , Solventes , Trifluoretanol/química , Proteínas Viroporinas
4.
Sci Rep ; 12(1): 310, 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013354

RESUMO

Influenza virus is a persistent threat to human health; indeed, the deadliest modern pandemic was in 1918 when an H1N1 virus killed an estimated 50 million people globally. The intent of this work is to better understand influenza from an RNA-centric perspective to provide local, structural motifs with likely significance to the influenza infectious cycle for therapeutic targeting. To accomplish this, we analyzed over four hundred thousand RNA sequences spanning three major clades: influenza A, B and C. We scanned influenza segments for local secondary structure, identified/modeled motifs of likely functionality, and coupled the results to an analysis of evolutionary conservation. We discovered 185 significant regions of predicted ordered stability, yet evidence of sequence covariation was limited to 7 motifs, where 3-found in influenza C-had higher than expected amounts of sequence covariation.


Assuntos
Betainfluenzavirus/genética , Gammainfluenzavirus/genética , Vírus da Influenza A/genética , Estabilidade de RNA , RNA Viral/ultraestrutura , Antivirais/farmacologia , Vírus da Influenza A/efeitos dos fármacos , Betainfluenzavirus/efeitos dos fármacos , Gammainfluenzavirus/efeitos dos fármacos , Modelos Moleculares , Conformação de Ácido Nucleico , Motivos de Nucleotídeos , RNA Viral/efeitos dos fármacos , RNA Viral/genética , Análise de Sequência de RNA , Relação Estrutura-Atividade
5.
Aging (Albany NY) ; 13(23): 24931-24942, 2021 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-34897035

RESUMO

Since the Coronavirus 19 (COVID-19) pandemic, several SARS-CoV-2 variants of concern (SARS-CoV-2 VOC) have been reported. The B.1.1.7 variant has been associated with increased mortality and transmission risk. Furthermore, cluster and possible co-infection cases could occur in the next influenza season or COVID-19 pandemic wave, warranting efficient diagnosis and treatment decision making. Here, we aimed to detect SARS-CoV-2 and other common respiratory viruses using multiplex RT-PCR developed on the LabTurbo AIO 48 open system. We performed a multicenter study to evaluate the performance and analytical sensitivity of the LabTurbo AIO 48 system for SARS-CoV-2, influenza A/B, and respiratory syncytial virus (RSV) using 652 nasopharyngeal swab clinical samples from patients. The LabTurbo AIO 48 system demonstrated a sensitivity of 9.4 copies/per PCR for N2 of SARS-CoV-2; 24 copies/per PCR for M of influenza A and B; and 24 copies/per PCR for N of RSV. The assay presented consistent performance in the multicenter study. The multiplex RT-PCR applied on the LabTurbo AIO 48 open platform provided highly sensitive, robust, and accurate results and enabled high-throughput detection of B.1.1.7, influenza A/B, and RSV with short turnaround times. Therefore, this automated molecular diagnostic assay could enable streamlined testing if COVID-19 becomes a seasonal disease.


Assuntos
Teste de Ácido Nucleico para COVID-19/métodos , COVID-19/diagnóstico , Influenza Humana/diagnóstico , Reação em Cadeia da Polimerase Multiplex/métodos , Infecções por Vírus Respiratório Sincicial/diagnóstico , Adulto , Idoso , COVID-19/virologia , Feminino , Humanos , Vírus da Influenza A/genética , Vírus da Influenza A/isolamento & purificação , Influenza Humana/virologia , Betainfluenzavirus/genética , Betainfluenzavirus/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sinciciais Respiratórios/genética , Vírus Sinciciais Respiratórios/isolamento & purificação , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Sensibilidade e Especificidade , Adulto Jovem
6.
Front Immunol ; 12: 786617, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868073

RESUMO

Neuraminidase of influenza A and B viruses plays a critical role in the virus life cycle and is an important target of the host immune system. Here, we highlight the current understanding of influenza neuraminidase structure, function, antigenicity, immunogenicity, and immune protective potential. Neuraminidase inhibiting antibodies have been recognized as correlates of protection against disease caused by natural or experimental influenza A virus infection in humans. In the past years, we have witnessed an increasing interest in the use of influenza neuraminidase to improve the protective potential of currently used influenza vaccines. A number of well-characterized influenza neuraminidase-specific monoclonal antibodies have been described recently, most of which can protect in experimental challenge models by inhibiting the neuraminidase activity or by Fc receptor-dependent mechanisms. The relative instability of the neuraminidase poses a challenge for protein-based antigen design. We critically review the different solutions that have been proposed to solve this problem, ranging from the inclusion of stabilizing heterologous tetramerizing zippers to the introduction of inter-protomer stabilizing mutations. Computationally engineered neuraminidase antigens have been generated that offer broad, within subtype protection in animal challenge models. We also provide an overview of modern vaccine technology platforms that are compatible with the induction of robust neuraminidase-specific immune responses. In the near future, we will likely see the implementation of influenza vaccines that confront the influenza virus with a double punch: targeting both the hemagglutinin and the neuraminidase.


Assuntos
Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Neuraminidase/imunologia , Proteínas Virais/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Deriva e Deslocamento Antigênicos , Antígenos Virais/imunologia , Antígenos Virais/ultraestrutura , Domínio Catalítico/genética , Domínio Catalítico/imunologia , Proteção Cruzada , Evolução Molecular , Humanos , Imunogenicidade da Vacina , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/genética , Influenza Humana/imunologia , Influenza Humana/virologia , Alphainfluenzavirus/enzimologia , Alphainfluenzavirus/genética , Alphainfluenzavirus/imunologia , Betainfluenzavirus/enzimologia , Betainfluenzavirus/genética , Betainfluenzavirus/imunologia , Mutação , Nanopartículas , Neuraminidase/administração & dosagem , Neuraminidase/genética , Neuraminidase/ultraestrutura , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/ultraestrutura , Proteínas Virais/administração & dosagem , Proteínas Virais/genética , Proteínas Virais/ultraestrutura
8.
Viruses ; 13(6)2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-34070388

RESUMO

Influenza viruses continue to be a major public health threat due to the possible emergence of more virulent influenza virus strains resulting from dynamic changes in virus adaptability, consequent of functional mutations and antigenic drift in surface proteins, especially hemagglutinin (HA) and neuraminidase (NA). In this study, we describe the genetic and evolutionary characteristics of H1N1, H3N2, and influenza B strains detected in severe cases of seasonal influenza in Thailand from 2018 to 2019. We genetically characterized seven A/H1N1 isolates, seven A/H3N2 isolates, and six influenza B isolates. Five of the seven A/H1N1 viruses were found to belong to clade 6B.1 and were antigenically similar to A/Switzerland/3330/2017 (H1N1), whereas two isolates belonged to clade 6B.1A1 and clustered with A/Brisbane/02/2018 (H1N1). Interestingly, we observed additional mutations at antigenic sites (S91R, S181T, T202I) as well as a unique mutation at a receptor binding site (S200P). Three-dimensional (3D) protein structure analysis of hemagglutinin protein reveals that this unique mutation may lead to the altered binding of the HA protein to a sialic acid receptor. A/H3N2 isolates were found to belong to clade 3C.2a2 and 3C.2a1b, clustering with A/Switzerland/8060/2017 (H3N2) and A/South Australia/34/2019 (H3N2), respectively. Amino acid sequence analysis revealed 10 mutations at antigenic sites including T144A/I, T151K, Q213R, S214P, T176K, D69N, Q277R, N137K, N187K, and E78K/G. All influenza B isolates in this study belong to the Victoria lineage. Five out of six isolates belong to clade 1A3-DEL, which relate closely to B/Washington/02/2009, with one isolate lacking the three amino acid deletion on the HA segment at position K162, N163, and D164. In comparison to the B/Colorado/06/2017, which is the representative of influenza B Victoria lineage vaccine strain, these substitutions include G129D, G133R, K136E, and V180R for HA protein. Importantly, the susceptibility to oseltamivir of influenza B isolates, but not A/H1N1 and A/H3N2 isolates, were reduced as assessed by the phenotypic assay. This study demonstrates the importance of monitoring genetic variation in influenza viruses regarding how acquired mutations could be associated with an improved adaptability for efficient transmission.


Assuntos
Betainfluenzavirus , Hospitalização , Vírus da Influenza A , Influenza Humana/epidemiologia , Influenza Humana/virologia , Adolescente , Adulto , Idoso , Antígenos Virais/química , Antígenos Virais/imunologia , Antivirais/farmacologia , Antivirais/uso terapêutico , Comorbidade , Feminino , História do Século XXI , Humanos , Vírus da Influenza A/classificação , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza A/genética , Influenza Humana/tratamento farmacológico , Influenza Humana/história , Betainfluenzavirus/classificação , Betainfluenzavirus/efeitos dos fármacos , Betainfluenzavirus/genética , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Neuraminidase/química , Neuraminidase/imunologia , Neuraminidase/metabolismo , Filogenia , Estações do Ano , Tailândia/epidemiologia , Proteínas Virais/química , Proteínas Virais/imunologia , Proteínas Virais/metabolismo , Adulto Jovem
9.
Medicine (Baltimore) ; 100(18): e25799, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33950979

RESUMO

ABSTRACT: To investigate the epidemiology and factors associated with the severity of viral acute lower respiratory infection (ALRI) in children hospitalized in Manaus, Amazonas, in 2017 to 2018.Retrospective cohort study of children hospitalized at the Hospital and Emergency Room Delphina Rinaldi Abdel Aziz, in Manaus, from April 01, 2017 to August 31, 2018, with a clinical diagnosis of ALRI and nasopharyngeal aspirates positive for at least 1 respiratory virus.One hundred forty-six children aged 0.2 to 66 months (median 7 months) were included. Patients were divided into 2 groups according to the disease severity classified by an adapted Walsh et al score: moderate disease, score 0-4, n = 66 (45.2%) and severe disease, score 5-7, n = 80 (54.8%). A greater number of viral ALRI cases were observed in the rainiest months. Respiratory syncytial virus was the most prevalent (n = 103, 70.3%), followed by metapneumovirus (n = 24, 16.4%), influenza virus (n = 17, 11.6%), parainfluenza virus (n = 11, 7.5%), and adenovirus (n = 4, 2.7%). Co-detections of 2 to 3 viruses were found in 12 (8.2%) patients. The presence of viral coinfection was an independent risk factor for disease severity (adjusted relative risk [RR] 1.53; 95% CI 1.10-2.14). Twelve patients (8.2%) died, all with severe disease. Risk factors for death were shock (adjusted RR 10.09; 95% CI 2.31-43.90) and need for vasoactive drugs (adjusted RR 10.63; 95% CI 2.44-46.31).There was a higher incidence of viral ALRI in Manaus in the rainy season. Respiratory syncytial virus was the most prevalent virus. The presence of viral coinfection was an independent risk factor for disease severity.


Assuntos
Infecções por Adenovirus Humanos/epidemiologia , Coinfecção/epidemiologia , Influenza Humana/epidemiologia , Infecções por Paramyxoviridae/epidemiologia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Adenoviridae/isolamento & purificação , Infecções por Adenovirus Humanos/diagnóstico , Infecções por Adenovirus Humanos/virologia , Brasil/epidemiologia , Pré-Escolar , Coinfecção/diagnóstico , Coinfecção/virologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Lactente , Recém-Nascido , Influenza Humana/diagnóstico , Influenza Humana/virologia , Alphainfluenzavirus/isolamento & purificação , Betainfluenzavirus/isolamento & purificação , Masculino , Metapneumovirus/isolamento & purificação , Infecções por Paramyxoviridae/diagnóstico , Infecções por Paramyxoviridae/virologia , Infecções por Vírus Respiratório Sincicial/diagnóstico , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sinciciais Respiratórios/isolamento & purificação , Respirovirus/isolamento & purificação , Estudos Retrospectivos , Índice de Gravidade de Doença
10.
Food Chem ; 334: 127508, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32711265

RESUMO

Quercetin, a potential polyphenolic which possesses several biological effects. The influenza virus polymerase basic 2 (PB2) subunit of RNA polymerase responsible for replication, degree of virus conservation and active target site for designing specific antivirals. The quercetin derivatives downloaded from PubChem were screened using PyRX software configured with Vina Wizard, targeted on cap-binding site of the PB2 of influenza viral RNA polymerase. Among the PubChem library (total 97,585,747 compounds), 410 quercetin derivatives were screened using molecular docking (affinity: <-9.0 kcal) for their drug-likeness and in vitro cytopathic effect by Sulforhodamine B (SRB) assay. Among all quercetin derivatives, quercetin 3'-glucuronide (Q3G) showed strongest binding affinity towards cap-binding site of the PB2 subunit with -9.6 kcal of binding affinity and 0.00054 mM of Ki value, while quercetin 3'-glucuronide (Q7G) was presented highest anti-influenza activity with 2.10 ± 0.05 of IC50 on influenza A/PR/8/34 virus and non-cytotoxic effect as CC50 > 100 µg/mL.


Assuntos
Antivirais/farmacologia , Vírus da Influenza A/efeitos dos fármacos , Quercetina/análogos & derivados , Animais , Antivirais/química , Antivirais/metabolismo , Sítios de Ligação , Sobrevivência Celular/efeitos dos fármacos , RNA Polimerases Dirigidas por DNA/química , RNA Polimerases Dirigidas por DNA/metabolismo , Cães , Humanos , Vírus da Influenza A/enzimologia , Betainfluenzavirus/efeitos dos fármacos , Células Madin Darby de Rim Canino , Simulação de Acoplamento Molecular , Estrutura Terciária de Proteína , Subunidades Proteicas/química , Subunidades Proteicas/metabolismo , Quercetina/química , Quercetina/metabolismo , Quercetina/farmacologia , Termodinâmica
11.
J Clin Microbiol ; 59(3)2021 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-33298612

RESUMO

During the ongoing coronavirus disease 2019 (COVID-19) outbreak, robust detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key element for clinical management and to interrupt transmission chains. We organized an external quality assessment (EQA) of molecular detection of SARS-CoV-2 for European expert laboratories. An EQA panel composed of 12 samples, containing either SARS-CoV-2 at different concentrations to evaluate sensitivity or other respiratory viruses to evaluate specificity of SARS-CoV-2 testing, was distributed to 68 laboratories in 35 countries. Specificity samples included seasonal human coronaviruses hCoV-229E, hCoV-NL63, and hCoV-OC43, as well as Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV, and human influenza viruses A and B. Sensitivity results differed among laboratories, particularly for low-concentration SARS-CoV-2 samples. Results indicated that performance was mostly independent of the selection of specific extraction or PCR methods.


Assuntos
Teste para COVID-19/normas , COVID-19/diagnóstico , Coronavirus Humano 229E , Coronavirus Humano NL63 , Coronavirus Humano OC43 , Humanos , Alphainfluenzavirus , Betainfluenzavirus , Laboratórios , Coronavírus da Síndrome Respiratória do Oriente Médio , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave , SARS-CoV-2 , Sensibilidade e Especificidade
12.
J Exp Med ; 218(3)2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33326020

RESUMO

CD4+ follicular regulatory T (Tfr) cells control B cell responses through the modulation of follicular helper T (Tfh) cells and germinal center development while suppressing autoreactivity; however, their role in the regulation of productive germinal center B cell responses and humoral memory is incompletely defined. We show that Tfr cells promote antigen-specific germinal center B cell responses upon influenza virus infection. Following viral challenge, we found that Tfr cells are necessary for robust generation of virus-specific, long-lived plasma cells, antibody production against both hemagglutinin (HA) and neuraminidase (NA), the two major influenza virus glycoproteins, and appropriate regulation of the BCR repertoire. To further investigate the functional relevance of Tfr cells during viral challenge, we used a sequential immunization model with repeated exposure of antigenically partially conserved strains of influenza viruses, revealing that Tfr cells promote recall antibody responses against the conserved HA stalk region. Thus, Tfr cells promote antigen-specific B cell responses and are essential for the development of long-term humoral memory.


Assuntos
Linfócitos B/imunologia , Betainfluenzavirus/imunologia , Antígenos CD4/metabolismo , Imunidade , Linfócitos T Reguladores/imunologia , Animais , Formação de Anticorpos/imunologia , Antígenos/metabolismo , Modelos Animais de Doenças , Epitopos/imunologia , Fatores de Transcrição Forkhead/metabolismo , Centro Germinativo/imunologia , Humanos , Memória Imunológica , Influenza Humana/imunologia , Influenza Humana/virologia , Integrases/metabolismo , Camundongos Endogâmicos C57BL , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Receptores de Antígenos de Linfócitos B/metabolismo , Especificidade da Espécie , Vacinação
13.
Lancet Respir Med ; 9(4): 419-429, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33285143

RESUMO

BACKGROUND: Diagnosis of influenza in patients admitted to hospital is delayed due to long turnaround times with laboratory testing, leading to inappropriate and late antiviral treatment and isolation facility use. Molecular point-of-care tests (mPOCTs) are highly accurate, easy to use, and generate results in less than 1 h, but high-quality evidence for their effect on management and clinical outcomes is needed. The aim of this study was to assess the clinical impact of an mPOCT on influenza detection, antiviral use, infection control measures, and clinical outcomes in adults admitted to hospital with acute respiratory illness. METHODS: In this multicentre, pragmatic, open-label, randomised controlled trial (FluPOC), we recruited adults admitted to hospital with acute respiratory illness during influenza seasons from two hospitals in Hampshire, UK. Eligible patients were aged 18 years and older, with acute respiratory illness of 10 days or fewer duration before admission to hospital, who were recruited within 16 h of admission to hospital. Participants were randomly assigned (1:1), using random permuted blocks of varying sizes (4, 6 and 8), to receive mPOCT for influenza or routine clinical care (control group). The primary outcome was the proportion of patients infected with influenza who were treated appropriately with antivirals (neuraminidase inhibitors) within 5 days of admission. Safety was assessed in all patients. Secondary outcomes included time to antivirals, isolation facility use, and clinical outcomes. This study is registered with the ISRCTN registry, ISRCTN17197293, and is now complete. FINDINGS: Between Dec 12, 2017, and May 3, 2019, over two influenza seasons, 613 patients were enrolled, of whom 307 were assigned to the mPOCT group and 306 to the control group, and all were analysed. Median age was 62 years (IQR 45-75) and 332 (54%) of 612 participants with data were female. 100 (33%) of 307 patients in the mPOCT group and 102 (33%) of 306 in the control group had influenza. 100 (100%) of 100 patients with influenza were diagnosed in the mPOCT group and 60 (59%) of 102 were diagnosed though routine clinical care in the control group (relative risk 1·7, 95% CI 1·7-1·7; p<0·0001). 99 (99%) of 100 patients with influenza in the mPOCT group were given antiviral treatment within 5 days of admission versus 63 (62%) 102 in the control group (relative risk 1·6, 95% CI 1·4-1·9; p<0·0001). Median time to antivirals was 1·0 h (IQR 0·0 to 2·0) in the mPOCT group versus 6·0 h (0·0 to 12·0) in the control group (difference of 5·0 h [95% CI 0·0-6·0; p=0·0039]). 70 (70%) of 100 patients with influenza in the mPOCT group were isolated to single-room accommodation versus 39 (38%) of 102 in the control group (relative risk 1·8 [95% CI 1·4-2·4; p<0·0001]). 19 adverse events occurred among patients with influenza in the mPOCT group compared with 34 events in the control group. No patients with influenza died in the mPOCT group and two (2%) died in the control group (p=0·16). INTERPRETATION: Routine mPOCT for influenza was associated with improved influenza detection and improvements in appropriate and timely antiviral and isolation facility use. Routine mPOCT should replace laboratory-based diagnostics for acute admissions to hospital during the influenza season. FUNDING: National Institute for Health Research.


Assuntos
Antivirais/uso terapêutico , Controle de Infecções/organização & administração , Influenza Humana/diagnóstico , Técnicas de Diagnóstico Molecular/instrumentação , Testes Imediatos/organização & administração , Idoso , Feminino , Humanos , Controle de Infecções/estatística & dados numéricos , Influenza Humana/tratamento farmacológico , Influenza Humana/epidemiologia , Influenza Humana/virologia , Alphainfluenzavirus/genética , Alphainfluenzavirus/isolamento & purificação , Betainfluenzavirus/genética , Betainfluenzavirus/isolamento & purificação , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular/métodos , Admissão do Paciente , Reação em Cadeia da Polimerase , RNA Viral/isolamento & purificação , Fatores de Tempo , Tempo para o Tratamento/estatística & dados numéricos , Resultado do Tratamento
14.
BMC Infect Dis ; 20(1): 913, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33261559

RESUMO

BACKGROUND: Influenza B is often perceived as a less severe strain of influenza. The epidemiology and clinical outcomes of influenza B have been less thoroughly investigated in hospitalised patients. The aims of this study were to describe clinical differences and outcomes between influenza A and B patients admitted over a period of 4 years. METHODS: We retrospectively collected data of all laboratory confirmed influenza patients ≥18 years at two tertiary hospitals in South Australia. Patients were confirmed as influenza positive if they had a positive polymerase-chain-reaction (PCR) test of a respiratory specimen. Complications during hospitalisation along with inpatient mortality were compared between influenza A and B. In addition, 30 day mortality and readmissions were compared. Logistic regression model compared outcomes after adjustment for age, Charlson index, sex and creatinine levels. RESULTS: Between January 2016-March 2020, 1846 patients, mean age 66.5 years, were hospitalised for influenza. Of whom, 1630 (88.3%) had influenza A and 216 (11.7%) influenza B. Influenza B patients were significantly younger than influenza A. Influenza A patients were more likely be smokers with a history of chronic obstructive pulmonary disease (COPD) and ischaemic heart disease (IHD) than influenza B. Complications, including pneumonia and acute coronary syndrome (ACS) were similar between two groups, however, septic shock was more common in patients with influenza B. Adjusted analyses showed similar median length of hospital stay (LOS), in hospital mortality, 30-day mortality and readmissions between the two groups. CONCLUSIONS: Influenza B is less prevalent and occurs mostly in younger hospitalised patients than influenza A. Both strains contribute equally to hospitalisation burden and complications. TRIAL REGISTRATION: Australia and New Zealand Clinical Trial Registry (ANZCR) no ACTRN12618000451202 date of registration 28/03/2018.


Assuntos
Betainfluenzavirus/genética , Vírus da Influenza A/genética , Influenza Humana/epidemiologia , Influenza Humana/mortalidade , Síndrome Coronariana Aguda/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Feminino , Mortalidade Hospitalar , Humanos , Influenza Humana/complicações , Influenza Humana/virologia , Tempo de Internação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente , Pneumonia/etiologia , Reação em Cadeia da Polimerase , Prevalência , Estudos Retrospectivos
15.
Rev Med Suisse ; 16(705): 1598-1604, 2020 Sep 09.
Artigo em Francês | MEDLINE | ID: mdl-32914590

RESUMO

Influenza A and B infections are marred with variable morbidity and, in some cases, develop into severe or even fatal respiratory, circulatory and neurologic complications. Respiratory complications are most common and involve primary-Influenza pneumonia and pneumonia from bacterial or fungal superinfections. Nonrespiratory complications can affect several organs/systems, namely the heart (myocarditis, type 1 and 2 myocardial infarction) and the nervous system (stroke, encephalitis, Guillain-Barré Syndrome). This article provides an overview of the basic pathophysiological aspects of Influenza virus infection, reviews the main severe respiratory and nonrespiratory complications and discusses the different treatments with their respective indications, contraindications and limitations.


L'infection par les virus de la grippe de types A et B (influenza A et B) est grevée d'une morbidité variable, pouvant évoluer en diverses complications respiratoires, circulatoires et neurologiques sévères, voire fatales. Les complications pulmonaires sont les plus fréquentes et l'on distingue parmi elles les pneumonies dues au virus de celles par surinfection bactérienne ou fongique. Les complications extrapulmonaires, plus rares, peuvent toucher divers organes, dont le cœur (myocardite, infarctus du myocarde de types 1 et 2) et le système nerveux (AVC, encéphalite, syndrome de Guillain-Barré). Cet article aborde les aspects physiopatho logiques de base de la grippe, passe en revue les principales complications sévères pulmonaires et extrapulmonaires, et discute les indications, contre-indications et limites des différents traitements disponibles.


Assuntos
Alphainfluenzavirus/patogenicidade , Betainfluenzavirus/patogenicidade , Cardiopatias/virologia , Influenza Humana/fisiopatologia , Influenza Humana/virologia , Doenças do Sistema Nervoso/virologia , Cardiopatias/fisiopatologia , Humanos , Doenças do Sistema Nervoso/fisiopatologia
16.
Eur Rev Med Pharmacol Sci ; 24(17): 9196-9201, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32965014

RESUMO

OBJECTIVE: The aim of this study is to find the distributions of pathogens in 164 suspected COVID-19 patients from the outpatient clinic of Shenjing Hospital of China Medical University from 24th January, 2020, to 29th February of 2020. PATIENTS AND METHODS: 164 COVID-19 suspected patients were from the Shengjing Hospital of China Medical University. Oropharyngeal swab specimens were acquired by respiratory doctors under standardized conditions. Specific nucleic acids of SARS-CoV-2, influenza A and B, respiratory syncytial virus A and B, adenovirus, parainfluenza virus, along with pneumonic mycoplasma were detected by real-time fluorescence PCR. Symptomatic, epidemiologic, laboratory and radiological data of the patients were obtained from the electronic medical record system of our hospital. RESULTS: Among the 164 patients, 3 were positive for SARS-CoV-2, 15 were positive for other respiratory viruses and 16 were positive for pneumonic mycoplasma. Of the positive patients above, 1 patient was co-infected with SARS-CoV-2 and adenovirus, and 1 was co-infected with influenza B and pneumonic mycoplasma. The 3 SARS-CoV-2 infected patients were clinically diagnosed as COVID-19 because they meet the diagnostic criteria listed in "Chinese Clinical Guidance for COVID-19 Pneumonia diagnosis and treatment", including epidemic history, symptom and pathogenic detection, as well as abnormalities of the laboratory and radiological data. However, the clinical characteristics of COVID-19 patients were non-specific compared to those of the patients infected with other respiratory viruses. CONCLUSIONS: The endemic common respiratory pathogens are more prevalent than SARS-CoV-2 in the SARS-CoV-2 non-epidemic areas of this research. Detection of the pathogen is the unique means for definite COVID-19 diagnosis.


Assuntos
Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , Adenoviridae/genética , Adenoviridae/isolamento & purificação , Betacoronavirus/genética , Betacoronavirus/isolamento & purificação , COVID-19 , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Humanos , Vírus da Influenza A/genética , Vírus da Influenza A/isolamento & purificação , Betainfluenzavirus/genética , Betainfluenzavirus/isolamento & purificação , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , RNA Viral/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , SARS-CoV-2 , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X
17.
PLoS One ; 15(8): e0237214, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764788

RESUMO

INTRODUCTION: Every winter, emergency departments (EDs) face overcrowding with patients presenting influenza-like symptoms, and organisational issues such as single room assignment and droplet precautions to avoid hospital-acquired influenza. Our main objective was to assess the impact of PCR results and patient's severity on single room assignment. METHODS: All patients admitted to Bichat-Claude Bernard Hospital through the ED and tested for influenza by PCR (GenXpert, Cepheid) or (FilmArray, BioMérieux) on a nasopharyngeal swab were retrospectively included during three influenza seasons (2015-2018. RESULTS: Of 1,330 included patients, 278 (20.9%) had a positive PCR for influenza. The median time to obtain a PCR result was 19 hours, and 238 (18.3%) patients were assigned a single room. Among patients with positive and negative influenza PCR, 22.3% and 16.7% were assigned a single room (p = 0.03). The multivariable analysis was performed on the two first epidemic periods, excluding the third epidemic because of the concomitant use of influenza immune-chromatic test. Only level 1 of the Emergency severity index (ESI) (aOR, 1.9; 95% CI, 1.3-2.8; p < 0.01) was associated with single-room assignment. PCR result was not statistically associated with the decision of single room assignment (aOR, 1.4; 95%CI, 1.0-1.4; p = 0.07). CONCLUSION: A PCR positive for influenza was not significantly associated with single-room assignment. Less than one quarter of influenza patients were adequately assigned a single room, likely due to the long turnaround time of PCR result and other conflicting indications for single room-assignment. Accelerating biological diagnosis could improve single-room assignment.


Assuntos
Betainfluenzavirus/isolamento & purificação , Serviço Hospitalar de Emergência/organização & administração , Vírus da Influenza A/isolamento & purificação , Influenza Humana/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Testes Diagnósticos de Rotina , Feminino , Humanos , Vírus da Influenza A/genética , Influenza Humana/epidemiologia , Betainfluenzavirus/genética , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Estudos Retrospectivos
18.
Medicine (Baltimore) ; 99(32): e21469, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769879

RESUMO

Influenza is an acute respiratory infectious disease that poses a threat to public health. We assessed the association between atmospheric visibility and influenza and influenza-like illness (ILI) in Wuxi city, China.Daily meteorological data, ILI activity, and influenza virus infection rates were collected between 31 December 2012 and 31 December 2017. A distributed lag non-linear model (DLNM) was used to analyze the exposure-lag-response of ILI and influenza activity and daily average visibility.A total of 12,800 cases were detected; 1046 cases (8.17%) were of Flu-A and 527 (4.12%) were of Flu-B infection. Our analysis suggested a non-linear relationship between atmospheric visibility and influenza: U-shaped for ILI, and L-shaped for Flu-A and Flu-B. Comparing low visibility (2.5 km) to ILI cases, the risk appeared between day 1 and day 2. For Flu-A, the risk appeared between days 5 and 9, whereas for Flu-B, the risk effect was much stronger and had a longer reaction delay, staying above zero until day 9. The protective effects of high visibility (14 km) on ILI and Flu-B occurred the same day or one day later. However, we found no association between high visibility and Flu-A.In conclusion, our study contributes novel evidence for the effects of atmospheric visibility on influenza. These findings are important for the development of influenza surveillance and early warning systems in Wuxi city.


Assuntos
Alphainfluenzavirus , Betainfluenzavirus , Influenza Humana/epidemiologia , Conceitos Meteorológicos , China , Humanos , Influenza Humana/diagnóstico , Dinâmica não Linear , Estações do Ano
19.
BMC Infect Dis ; 20(1): 465, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32615985

RESUMO

BACKGROUND: Since 2011, the Global Influenza Hospital Surveillance Network (GIHSN) has used active surveillance to prospectively collect epidemiological and virological data on patients hospitalized with influenza virus infection. Here, we describe influenza virus strain circulation in the GIHSN participant countries during 2017-2018 season and examine factors associated with complicated hospitalization among patients admitted with laboratory-confirmed influenza illness. METHODS: The study enrolled patients who were hospitalized in a GIHSN hospital in the previous 48 h with acute respiratory symptoms and who had symptoms consistent with influenza within the 7 days before admission. Enrolled patients were tested by reverse transcription-polymerase chain reaction to confirm influenza virus infection. "Complicated hospitalization" was defined as a need for mechanical ventilation, admission to an intensive care unit, or in-hospital death. In each of four age strata (< 15, 15-< 50, 50-< 65, and ≥ 65 years), factors associated with complicated hospitalization in influenza-positive patients were identified by mixed effects logistic regression and those associated with length of hospital stay using a linear mixed-effects regression model. RESULTS: The study included 12,803 hospitalized patients at 14 coordinating sites in 13 countries, of which 4306 (34%) tested positive for influenza. Influenza viruses B/Yamagata, A/H3N2, and A/H1N1pdm09 strains dominated and cocirculated, although the dominant strains varied between sites. Complicated hospitalization occurred in 10.6% of influenza-positive patients. Factors associated with complicated hospitalization in influenza-positive patients included chronic obstructive pulmonary disease (15-< 50 years and ≥ 65 years), diabetes (15-< 50 years), male sex (50-< 65 years), hospitalization during the last 12 months (50-< 65 years), and current smoking (≥65 years). Chronic obstructive pulmonary disease (50-< 65 years), other chronic conditions (15-< 50 years), influenza A (50-< 65 years), and hospitalization during the last 12 months (< 15 years) were associated with a longer hospital stay. The proportion of patients with complicated influenza did not differ between influenza A and B. CONCLUSIONS: Complicated hospitalizations occurred in over 10% of patients hospitalized with influenza virus infection. Factors commonly associated with complicated or longer hospitalization differed by age group but commonly included chronic obstructive pulmonary disease, diabetes, and hospitalization during the last 12 months.


Assuntos
Betainfluenzavirus/genética , Hospitalização , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H3N2/genética , Influenza Humana/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Mortalidade Hospitalar , Humanos , Lactente , Influenza Humana/mortalidade , Influenza Humana/virologia , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Respiração Artificial , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , Adulto Jovem
20.
Influenza Other Respir Viruses ; 14(5): 515-523, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32614504

RESUMO

BACKGROUND: We used data from the Sentinel Enhanced Dengue Surveillance System (SEDSS) to describe influenza trends in southern Puerto Rico during 2012-2018 and compare them to trends in the United States. METHODS: Patients with fever onset ≤ 7 days presenting were enrolled. Nasal/oropharyngeal swabs were tested for influenza A and B viruses by PCR. Virologic data were obtained from the US World Health Organization (WHO) Collaborating Laboratories System and the National Respiratory and Enteric Virus Surveillance System (NREVSS). We compared influenza A and B infections identified from SEDSS and WHO/NREVSS laboratories reported by US Department of Health and Human Services (HHS) region using time series decomposition methods, and analysed coherence of climate and influenza trends by region. RESULTS: Among 23,124 participants, 9% were positive for influenza A and 5% for influenza B. Influenza A and B viruses were identified year-round, with no clear seasonal patterns from 2012 to 2015 and peaks in December-January in 2016-2017 and 2017-2018 seasons. Influenza seasons in HHS regions were relatively synchronized in recent years with the seasons in Puerto Rico. We observed high coherence between absolute humidity and influenza A and B virus in HHS regions. In Puerto Rico, coherence was much lower in the early years but increased to similar levels to HHS regions by 2017-2018. CONCLUSIONS: Influenza seasons in Puerto Rico have recently become synchronized with seasons in US HHS regions. Current US recommendations are for everyone 6 months and older to receive influenza vaccination by the end of October seem appropriate for Puerto Rico.


Assuntos
Influenza Humana/epidemiologia , Clima Tropical , Feminino , Febre/epidemiologia , Febre/virologia , Humanos , Vírus da Influenza A/isolamento & purificação , Influenza Humana/virologia , Betainfluenzavirus/isolamento & purificação , Masculino , Vigilância da População , Porto Rico/epidemiologia , Estações do Ano , Estados Unidos/epidemiologia
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