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1.
Influenza Other Respir Viruses ; 18(5): e13275, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38692663

RESUMO

BACKGROUND: Influenza, respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) are common respiratory viruses causing similar symptoms. Optimal tools to assess illness severity for these viruses have not been defined. Using the Hospitalized Acute Respiratory Tract Infection (HARTI) study data, we report symptom severity by clinician-rated clinical severity scores (CSS) in adults with influenza, RSV, or hMPV and correlations between CSS and patient-reported outcomes (PROs). METHODS: HARTI was a global epidemiologic study in adults hospitalized with acute respiratory tract infections. Patients were assessed at enrollment within 24 h of admission with CSS and twice during hospitalization with CSS, Respiratory Infection Intensity and Impact Questionnaire™ (RiiQ™), and EQ-5D-5L. Data were summarized descriptively, stratified by pathogen and baseline and hospitalization characteristics. Domain (general, upper respiratory, and lower respiratory) and sign/symptom subscores are presented for CSS; sign/symptom subscores are presented for RiiQ™ results. RESULTS: Data from 635 patients with influenza, 248 with RSV, and 107 with hMPV were included. At enrollment, total CSS and general and lower respiratory signs/symptoms (LRS) scores were higher for RSV and hMPV than influenza. Between-pathogen differences were greatest for LRS scores. Dyspnea, rales/rhonchi, wheezing, and shortness of breath scores trended higher for RSV and hMPV than influenza. RiiQ™ scores for cough, fatigue, and short of breath were strongly correlated with corresponding clinician-rated symptoms. CONCLUSIONS: These findings support the use of PROs (e.g., the RiiQ™) correlating with clinician assessments to gauge patient well-being and aid patient management by accurately assessing respiratory illness severity due to RSV, hMPV, or influenza.


Assuntos
Hospitalização , Influenza Humana , Metapneumovirus , Infecções por Paramyxoviridae , Infecções por Vírus Respiratório Sincicial , Infecções Respiratórias , Índice de Gravidade de Doença , Humanos , Metapneumovirus/isolamento & purificação , Masculino , Feminino , Infecções Respiratórias/virologia , Infecções Respiratórias/epidemiologia , Pessoa de Meia-Idade , Infecções por Vírus Respiratório Sincicial/virologia , Infecções por Vírus Respiratório Sincicial/complicações , Infecções por Vírus Respiratório Sincicial/epidemiologia , Influenza Humana/virologia , Influenza Humana/complicações , Influenza Humana/epidemiologia , Adulto , Infecções por Paramyxoviridae/virologia , Infecções por Paramyxoviridae/epidemiologia , Infecções por Paramyxoviridae/complicações , Idoso , Adulto Jovem , Vírus Sincicial Respiratório Humano/isolamento & purificação , Idoso de 80 Anos ou mais , Adolescente
2.
Influenza Other Respir Viruses ; 18(5): e13299, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38700006

RESUMO

INTRODUCTION: Traditional surveillance systems may underestimate the burden caused by respiratory syncytial virus (RSV). Capture-recapture methods provide alternatives for estimating the number of RSV-related hospitalizations in a population. METHODS: Capture-recapture methods were used to estimate the number of RSV-related hospitalizations in adults in Middle Tennessee from two independent hospitalization surveillance systems during consecutive respiratory seasons from 2016-2017 to 2019-2020. Data from the Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) and the Emerging Infections Program (EIP) were used. Annual RSV hospitalization rates were calculated using the capture-recapture estimates weighted by hospitals' market share divided by the corresponding census population. RESULTS: Using capture-recapture methods, the estimated overall adult hospitalization rates varied from 8.3 (95% CI: 5.9-15.4) RSV-related hospitalizations per 10,000 persons during the 2016-2017 season to 28.4 (95% CI: 18.2-59.0) hospitalizations per 10,000 persons in the 2019-2020 season. The proportion of hospitalizations that HAIVEN determined ranged from 8.7% to 36.7% of the total capture-recapture estimated hospitalization, whereas EIP detected 23.5% to 52.7% of the total capture-recapture estimated hospitalizations. CONCLUSION: Capture-recapture estimates showed that individual traditional surveillance systems underestimated the hospitalization burden in adults. Using capture-recapture allows for a more comprehensive estimate of RSV hospitalizations.


Assuntos
Hospitalização , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Humanos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Hospitalização/estatística & dados numéricos , Adulto , Vírus Sincicial Respiratório Humano/isolamento & purificação , Pessoa de Meia-Idade , Tennessee/epidemiologia , Adulto Jovem , Idoso , Masculino , Feminino , Adolescente , Estações do Ano , Efeitos Psicossociais da Doença
3.
Hum Genomics ; 18(1): 48, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769549

RESUMO

BACKGROUND: After the occurrence of the COVID-19 pandemic, detection of other disseminated respiratory viruses using highly sensitive molecular methods was declared essential for monitoring the spread of health-threatening viruses in communities. The development of multiplex molecular assays are essential for the simultaneous detection of such viruses even at low concentrations. In the present study, a highly sensitive and specific multiplex one-step droplet digital PCR (RT-ddPCR) assay was developed for the simultaneous detection and absolute quantification of influenza A (IAV), influenza B (IBV), respiratory syncytial virus (RSV), and beta-2-microglobulin transcript as an endogenous internal control (IC B2M). RESULTS: The assay was first evaluated for analytical sensitivity and specificity, linearity, reproducibility, and recovery rates with excellent performance characteristics and then applied to 37 wastewater samples previously evaluated with commercially available and in-house quantitative real-time reverse transcription PCR (RT-qPCR) assays. IAV was detected in 16/37 (43%), IBV in 19/37 (51%), and RSV in 10/37 (27%) of the wastewater samples. Direct comparison of the developed assay with real-time RT-qPCR assays showed statistically significant high agreement in the detection of IAV (kappa Cohen's correlation coefficient: 0.834, p = 0.001) and RSV (kappa: 0.773, p = 0.001) viruses between the two assays, while the results for the detection of IBV (kappa: 0.355, p = 0.27) showed good agreement without statistical significance. CONCLUSIONS: Overall, the developed one-step multiplex ddPCR assay is cost-effective, highly sensitive and specific, and can simultaneously detect three common respiratory viruses in the complex matrix of wastewater samples even at low concentrations. Due to its high sensitivity and resistance to PCR inhibitors, the developed assay could be further used as an early warning system for wastewater monitoring.


Assuntos
Vírus da Influenza A , Vírus da Influenza B , Reação em Cadeia da Polimerase Multiplex , Águas Residuárias , Águas Residuárias/virologia , Vírus da Influenza A/genética , Vírus da Influenza A/isolamento & purificação , Humanos , Vírus da Influenza B/genética , Vírus da Influenza B/isolamento & purificação , Reação em Cadeia da Polimerase Multiplex/métodos , Sensibilidade e Especificidade , Vírus Sinciciais Respiratórios/genética , Vírus Sinciciais Respiratórios/isolamento & purificação , Reprodutibilidade dos Testes , Influenza Humana/diagnóstico , Influenza Humana/virologia , Influenza Humana/genética , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real/métodos , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação
5.
Influenza Other Respir Viruses ; 18(5): e13303, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38757258

RESUMO

BACKGROUND: Data available for RSV and influenza infections among children < 2 years in Mongolia are limited. We present data from four districts of Ulaanbaatar from April 2015 to June 2021. METHODS: This study was nested in an enhanced surveillance project evaluating pneumococcal conjugate vaccine (PCV13) impact on the incidence of hospitalized lower respiratory tract infections (LRTIs). Our study was restricted to children aged < 2 years with arterial O2 saturation < 93% and children with radiological pneumonia. Nasopharyngeal (NP) swabs collected at admission were tested for RSV and influenza using qRT-PCR. NP swabs of all patients with radiological pneumonia and of a subset of randomly selected NP swabs were tested for S. pneumoniae (S.p.) by qPCR and for serotypes by culture and DNA microarray. RESULTS: Among 5705 patients, 2113 (37.0%) and 386 (6.8%) had RSV and influenza infections, respectively. Children aged 2-6 months had a higher percentage of very severe RSV infection compared to those older than 6 months (42.2% versus 31.4%, p-value Fisher's exact = 0.001). S.p. carriage was detected in 1073/2281 (47.0%) patients. Among S.p. carriage cases, 363/1073 (33.8%) had S.p. and RSV codetection, and 82/1073 (7.6%) had S.p. and influenza codetection. S.p. codetection with RSV/influenza was not associated with more severe LRTIs, compared to only RSV/influenza cases. CONCLUSION: In Mongolia, RSV is an important pathogen causing more severe LRTI in children under 6 months of age. Codetection of RSV or influenza virus and S.p. was not associated with increased severity.


Assuntos
Influenza Humana , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Humanos , Mongólia/epidemiologia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Lactente , Influenza Humana/epidemiologia , Influenza Humana/virologia , Feminino , Masculino , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/isolamento & purificação , Pré-Escolar , Nasofaringe/virologia , Recém-Nascido , Incidência , Hospitalização/estatística & dados numéricos , Streptococcus pneumoniae/isolamento & purificação , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/classificação , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia
6.
BMC Pediatr ; 24(1): 334, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750503

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of acute lower respiratory tract infections, particularly in infants and young children during winter. We aimed to study the demographics and clinical characteristics of RSV infections and age-related patterns. METHODS: This retrospective study evaluated pediatric respiratory syncytial virus (RSV) infections conducted in Jordan from September 2021 to March 2022. Patients under the age of five who had viral polymerase chain reaction results showing RSV infection from nasopharyngeal aspiration were included. In addition, demographic information, medical history, and clinical data were gathered. These included comorbidities, outcomes, length of stay, ICU hospitalization, use of antibiotics, and oxygen supplementation. RESULTS: A total of 199 patients were included. Most patients were males (56.8%) and less than one year (43.7%). Children aged between 1 and 2 years presented with more shortness of breath (90.1%) than infants and children more than two years (66.7% and 87%, respectively) (p < 0.001). Older children (> 2 years) were significantly more likely to use antibiotics and have ICU admission than younger children ≤ 2 years (p = 0.045 and 0.018, respectively). There was no relationship between age groups, recurrent hospitalization, previous RSV infection, oxygen therapy, coinfection, and hospitalization duration. The respiratory rate was higher among patients with co-infection (p = 0.031). CONCLUSION: The current study provides information on the demographics and clinical characteristics of RSV infections. These findings contribute to a nuanced understanding of RSV infections in the specified population, emphasizing age-specific variations and clinical implications for better management strategies.


Assuntos
Infecções por Vírus Respiratório Sincicial , Centros de Atenção Terciária , Humanos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/terapia , Masculino , Feminino , Estudos Retrospectivos , Lactente , Pré-Escolar , Jordânia/epidemiologia , Hospitalização/estatística & dados numéricos , Fatores Etários , Tempo de Internação/estatística & dados numéricos , Vírus Sincicial Respiratório Humano/isolamento & purificação , Antibacterianos/uso terapêutico
7.
Influenza Other Respir Viruses ; 18(5): e13298, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38751165

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV) is a substantial cause of infant morbidity and mortality due to seasonal peaks of bronchiolitis across the United States. Clinical and viral surveillance plays a pivotal role in helping hospital systems prepare for expected surges in RSV bronchiolitis. Existing surveillance efforts have shown a geographic pattern of RSV positivity across the United States, with cases typically starting in the southeast and spreading north and west. Public health measures implemented due to the COVID-19 pandemic disrupted viral transmission across the nation and altered the expected seasonality of RSV. The impact of these changes on the geographic progression of infant RSV bronchiolitis across the United States has not been described. METHODS: Here, we used clinical and viral surveillance data from four health care systems located in different regions of the United States to describe the geographic progression of infant RSV bronchiolitis across the country from 2015 to 2023. RESULTS: Prior to widespread circulation of SARS-CoV-2, infant RSV bronchiolitis followed an established geographic pattern associated with seasonal epidemics originating in Florida and spreading north (North Carolina and New York) and later westward (Nevada). Although public health and social measures implemented during the COVID-19 pandemic disrupted the seasonality of RSV disease, infant RSV bronchiolitis epidemics progressed across the nation in a pattern identical to the prepandemic era. CONCLUSIONS: Our findings highlight the importance of ongoing clinical and viral surveillance to optimally track the onset of RSV epidemics and allow health care systems to prepare for expected RSV bronchiolitis surges.


Assuntos
Bronquiolite , COVID-19 , Infecções por Vírus Respiratório Sincicial , Humanos , COVID-19/epidemiologia , COVID-19/transmissão , Estados Unidos/epidemiologia , Lactente , Infecções por Vírus Respiratório Sincicial/epidemiologia , Bronquiolite/epidemiologia , Bronquiolite/virologia , Vírus Sincicial Respiratório Humano/isolamento & purificação , Estações do Ano , SARS-CoV-2 , Recém-Nascido , Feminino , Masculino
8.
Arch Virol ; 169(5): 106, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38644429

RESUMO

In this study, conducted at the National Institute of Health, Islamabad, during an outbreak of human respiratory syncytial virus (hRSV) from December 2022 to January 2023, the first whole-genome sequences of hRSV isolates from Islamabad, Pakistan, were determined. Out of 10 positive samples, five were sequenced, revealing the presence of two genotypes: RSV-A (GA2.3.5, ON1 strain) and RSV-B (GB5.0.5.a, BA-10 strain). A rare non-synonymous substitution (E232G) in G the protein and N276S in the F protein were found in RSV-A. In RSV-B, the unique mutations K191R, Q209R, and I206M were found in the F protein. These mutations could potentially influence vaccine efficacy and viral pathogenicity. This research underscores the importance of genomic surveillance for understanding RSV diversity and guiding public health responses in Pakistan.


Assuntos
Surtos de Doenças , Genoma Viral , Genótipo , Filogenia , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Paquistão/epidemiologia , Humanos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/classificação , Vírus Sincicial Respiratório Humano/isolamento & purificação , Genoma Viral/genética , Mutação , Sequenciamento Completo do Genoma , Genômica , Feminino , Lactente , Masculino , Proteínas Virais de Fusão/genética , Pré-Escolar
9.
J Infect ; 88(5): 106154, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38583722

RESUMO

OBJECTIVES: We aimed to study whether the percentwise age distribution of RSV cases changes over time during annual epidemics. METHODS: We used surveillance data (2008-2019) from the Netherlands, Lyon (France), Portugal, Singapore, Ecuador, South Africa, and New Zealand. In each country, every season was divided into "epidemic quarters", i.e. periods corresponding to each quartile of RSV cases. Multinomial logistic regression models were fitted to evaluate whether the likelihood of RSV cases being aged <1 or ≥5 years (vs. 1 to <5) changed over time within a season. RESULTS: In all countries, RSV cases were significantly more likely to be aged <1 year in the 4th vs. 1st epidemic quarter; the relative risk ratio [RRR] ranged between 1.35 and 2.56. Likewise, RSV cases were significantly more likely to be aged ≥5 years in the 4th vs. 1st epidemic quarter (except in Singapore); the RRR ranged from 1.75 to 6.70. The results did not change when stratifying by level of care or moving the lower cut-off to 6 months. CONCLUSIONS: The age profile of RSV cases shifts within a season, with infants and adolescents, adults, and the elderly constituting a higher proportion of cases in the later phases of annual epidemics. These findings may have implications for RSV prevention policies with newly approved vaccines.


Assuntos
Epidemias , Infecções por Vírus Respiratório Sincicial , Estações do Ano , Humanos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Lactente , Adolescente , Pré-Escolar , Criança , Adulto , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Masculino , Feminino , Recém-Nascido , Distribuição por Idade , Vírus Sincicial Respiratório Humano/isolamento & purificação , Fatores Etários , Idoso de 80 Anos ou mais , Nova Zelândia/epidemiologia , Singapura/epidemiologia
10.
Viruses ; 16(4)2024 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-38675883

RESUMO

This study aims to analyze the epidemiological and pathogenic characteristics of an outbreak primarily caused by respiratory syncytial virus (RSV), human rhinovirus (HRV), and human metapneumovirus (HMPV) in a kindergarten and primary school. The outbreak was investigated by field epidemiological investigation, and the common respiratory pathogens were screened by RT-PCR detection technology. The attack rate of this outbreak was 63.95% (110/172). Main symptoms included cough (85.45%), sore throat (60.91%), and sneezing (60.00%). Multifactorial logistic regression analysis revealed that continuous handwashing and mouth and nose covering when sneezing were protective factors. All 15 collected throat swab specimens tested positive for viruses, with HMPV as the predominant pathogen (80.00%), followed by HRV (53.33%), and two cases of positive respiratory syncytial virus (13.33%). Among them, six samples showed coinfections of HMPV and HRV, and one had coinfections of HMPV and RSV, resulting in a coinfection rate of 46.67%. Genetic sequencing indicated that the HMPV genotype in this outbreak was A2c, and the HRV genotype was type A, resulting in a coinfection outbreak of HMPV, HRV, and RSV in schools and kindergartens, suggesting that multi-pathogen surveillance of respiratory tract infections should be strengthened.


Assuntos
Coinfecção , Surtos de Doenças , Metapneumovirus , Epidemiologia Molecular , Infecções por Vírus Respiratório Sincicial , Infecções Respiratórias , Humanos , China/epidemiologia , Coinfecção/epidemiologia , Coinfecção/virologia , Masculino , Pré-Escolar , Feminino , Criança , Infecções Respiratórias/virologia , Infecções Respiratórias/epidemiologia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/virologia , Metapneumovirus/genética , Metapneumovirus/isolamento & purificação , Genótipo , Rhinovirus/genética , Rhinovirus/isolamento & purificação , Rhinovirus/classificação , Filogenia , Infecções por Paramyxoviridae/epidemiologia , Infecções por Paramyxoviridae/virologia , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/isolamento & purificação , Instituições Acadêmicas
11.
J Clin Virol ; 172: 105674, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38643722

RESUMO

BACKGROUND: Rapid and accurate detection of viral respiratory infections is important for infection control measures. This study compares the analytical and clinical performance of the Xpert® Xpress CoV-2/Flu/RSV plus test ("Xpert", Cepheid) and the STANDARD™ M10 Flu/RSV/SARS-CoV-2 test ("M10", SD Biosensor). Both tests are quadruplex RT-PCR assays for rapid diagnosis of SARS-CoV-2, influenza A/B and RSV. STUDY DESIGN: Analytical sensitivities were determined by limit of detection for SARS-CoV-2, influenza A, influenza B and RSV, respectively. Additionally, the clinical performance of the Xpert and the M10 tests was evaluated against standard-of-care RT-PCR by testing of 492 clinical specimens. RESULTS: The analytical sensitivities for Xpert versus M10 test was 10, 50, 50 and 300 versus 300, 200, 800 and 1500 copies/mL for SARS-CoV-2, influenza A, influenza B and RSV, respectively. Clinical sensitivity for the Xpert test was superior across all four pathogens compared to the M10 test. Xpert showed clinical sensitivity of 100 % in all Ct-ranges for all four pathogens whereas M10 showed clinical sensitivity of 100 % in the 25-30 Ct-range, 84-100 % in the 30-35 Ct-range and 47-67 % in the >35 Ct-range across the four pathogens. Translating into real-life clinical sensitivity, the Xpert would detect 100 % of all four pathogens, whereas M10 would detect 92.1, 92.4, 84.8 and 94.7 % for SARS-CoV-2, influenza A, influenza B and RSV. CONCLUSION: This study demonstrates improved analytical and clinical performance of Xpert Xpress CoV-2/Flu/RSV plus compared to STANDARD M10 Flu/RSV/SARS-CoV-2, which is important for ensuring accuracy of diagnosis at all stages of a respiratory infection.


Assuntos
COVID-19 , Vírus da Influenza A , Vírus da Influenza B , Influenza Humana , Infecções por Vírus Respiratório Sincicial , SARS-CoV-2 , Sensibilidade e Especificidade , Humanos , COVID-19/diagnóstico , COVID-19/virologia , Influenza Humana/diagnóstico , Influenza Humana/virologia , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Vírus da Influenza B/isolamento & purificação , Vírus da Influenza B/genética , Vírus da Influenza A/isolamento & purificação , Vírus da Influenza A/genética , Infecções por Vírus Respiratório Sincicial/diagnóstico , Infecções por Vírus Respiratório Sincicial/virologia , Testes Imediatos , Teste de Ácido Nucleico para COVID-19/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/isolamento & purificação
13.
Clin Infect Dis ; 78(5): 1352-1359, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38366649

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory illnesses in children. RSV can be broadly categorized into 2 major subtypes: A and B. RSV subtypes have been known to cocirculate with variability in different regions of the world. Clinical associations with viral subtype have been studied among children with conflicting findings such that no conclusive relationships between RSV subtype and severity have been established. METHODS: During 2016-2020, children aged <5 years were enrolled in prospective surveillance in the emergency department or inpatient settings at 7 US pediatric medical centers. Surveillance data collection included parent/guardian interviews, chart reviews, and collection of midturbinate nasal plus/minus throat swabs for RSV (RSV-A, RSV-B, and untyped) using reverse transcription polymerase chain reaction. RESULTS: Among 6398 RSV-positive children aged <5 years, 3424 (54%) had subtype RSV-A infections, 2602 (41%) had subtype RSV-B infections, and 272 (5%) were not typed, inconclusive, or mixed infections. In both adjusted and unadjusted analyses, RSV-A-positive children were more likely to be hospitalized, as well as when restricted to <1 year. By season, RSV-A and RSV-B cocirculated in varying levels, with 1 subtype dominating proportionally. CONCLUSIONS: Findings indicate that RSV-A and RSV-B may only be marginally clinically distinguishable, but both subtypes are associated with medically attended illness in children aged <5 years. Furthermore, circulation of RSV subtypes varies substantially each year, seasonally and geographically. With introduction of new RSV prevention products, this highlights the importance of continued monitoring of RSV-A and RSV-B subtypes.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Estações do Ano , Humanos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/virologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Lactente , Pré-Escolar , Estados Unidos/epidemiologia , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/classificação , Vírus Sincicial Respiratório Humano/isolamento & purificação , Masculino , Feminino , Estudos Prospectivos , Hospitalização/estatística & dados numéricos , Recém-Nascido , Vacinas contra Vírus Sincicial Respiratório/administração & dosagem
16.
N Engl J Med ; 386(7): 655-666, 2022 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-35172056

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV) infection causes substantial morbidity and mortality among infants, older adults, and immunocompromised adults. EDP-938, a nonfusion replication inhibitor of RSV, acts by modulating the viral nucleoprotein. METHODS: In a two-part, phase 2a, randomized, double-blind, placebo-controlled challenge trial, we assigned participants who had been inoculated with RSV-A Memphis 37b to receive EDP-938 or placebo. Different doses of EDP-938 were assessed. Nasal-wash samples were obtained from day 2 until day 12 for assessments. Clinical symptoms were assessed by the participants, and pharmacokinetic profiles were obtained. The primary end point was the area under the curve (AUC) for the RSV viral load, as measured by reverse-transcriptase-quantitative polymerase-chain-reaction assay. The key secondary end point was the AUC for the total symptom score. RESULTS: In part 1 of the trial, 115 participants were assigned to receive EDP-938 (600 mg once daily [600-mg once-daily group] or 300 mg twice daily after a 500-mg loading dose [300-mg twice-daily group]) or placebo. In part 2, a total of 63 participants were assigned to receive EDP-938 (300 mg once daily after a 600-mg loading dose [300-mg once-daily group] or 200 mg twice daily after a 400-mg loading dose [200-mg twice-daily group]) or placebo. In part 1, the AUC for the mean viral load (hours × log10 copies per milliliter) was 204.0 in the 600-mg once-daily group, 217.7 in the 300-mg twice-daily group, and 790.2 in the placebo group. The AUC for the mean total symptom score (hours × score, with higher values indicating greater severity) was 124.5 in the 600-mg once-daily group, 181.8 in the 300-mg twice-daily group, and 478.8 in the placebo group. The results in part 2 followed a pattern similar to that in part 1: the AUC for the mean viral load was 173.9 in the 300-mg once-daily group, 196.2 in the 200-mg twice-daily group, and 879.0 in the placebo group, and the AUC for the mean total symptom score was 99.3, 89.6, and 432.2, respectively. In both parts, mucus production was more than 70% lower in each EDP-938 group than in the placebo group. The four EDP-938 regimens had a safety profile similar to that of placebo. Across all dosing regimens, the EDP-938 median time to maximum concentration ranged from 4 to 5 hours, and the geometric mean half-life ranged from 13.7 to 14.5 hours. CONCLUSIONS: All EDP-938 regimens were superior to placebo with regard to lowering of the viral load, total symptom scores, and mucus weight without apparent safety concerns. (ClinicalTrials.gov number, NCT03691623.).


Assuntos
Antivirais , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Adulto , Feminino , Humanos , Masculino , Administração Oral , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Antivirais/farmacologia , Área Sob a Curva , Relação Dose-Resposta a Droga , Método Duplo-Cego , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/virologia , Vacinas contra Vírus Sincicial Respiratório , Vírus Sincicial Respiratório Humano/efeitos dos fármacos , Vírus Sincicial Respiratório Humano/isolamento & purificação , Carga Viral/efeitos dos fármacos
17.
Microbiol Spectr ; 9(3): e0093721, 2021 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-34878317

RESUMO

Rapid antigen tests may enhance the diagnostic yield of respiratory syncytial virus (RSV) infections, but studies have shown low sensitivity in adults. We evaluated the novel ImmuView RSV test in adult patients with influenza-like symptoms who were prospectively enrolled at three emergency departments in two Swedish hospitals during two influenza seasons, 2017 to 2018 and 2018 to 2019. The ImmuView RSV test was performed on nasopharyngeal swabs and results were compared to those of the BinaxNOW RSV test. In the first season, tests were performed on frozen samples, while unfrozen samples were used in the second season. For comparison, tests were also performed on selected samples from children. Of 333 included adult patients, the sensitivity of ImmuView and BinaxNOW was 27% for both tests and specificities were 98% and 100%, respectively. The interassay agreement was good (κ = 0.61). There was no significant difference in test performance between frozen and unfrozen samples. In samples from children, the sensitivities of ImmuView and BinaxNOW were 67% and 70%, respectively. In conclusion, the ImmuView RSV test showed low sensitivity and high specificity for identifying RSV in adult patients with influenza-like symptoms, comparable with the BinaxNOW RSV test. Rapid RSV testing is of limited value for diagnosing RSV infection in adults. IMPORTANCE By timely RSV diagnosis among patients with influenza-like symptoms, especially when influenza diagnostics turn negative, it is possible to prevent unnecessary antibiotic usage as well as reduce diagnostic testing, nosocomial transmission, and hospital stay. Previous rapid RSV tests have demonstrated poor sensitivity in adults, and we could demonstrate that the novel ImmuView RSV test similarly showed limited value for diagnosing RSV infection in adult patients. However, in contrast to many other studies, we investigated patient characteristics in cases with false-positive tests and we compared the performance between unfrozen and frozen samples. Thus, our results are important, as they generate new knowledge about rapid antigen tests.


Assuntos
Antígenos Virais/análise , Testes Diagnósticos de Rotina/métodos , Infecções por Vírus Respiratório Sincicial/diagnóstico , Vírus Sincicial Respiratório Humano/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Reações Falso-Positivas , Feminino , Humanos , Influenza Humana/diagnóstico , Masculino , Pessoa de Meia-Idade , Testes Imediatos , Estudos Prospectivos , Vírus Sincicial Respiratório Humano/imunologia , Sensibilidade e Especificidade , Adulto Jovem
18.
J Korean Med Sci ; 36(48): e328, 2021 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-34904407

RESUMO

BACKGROUND: In the coronavirus disease 2019 (COVID-19) pandemic era, the simultaneous detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza virus (Flu), and respiratory syncytial virus (RSV) is important in the rapid differential diagnosis in patients with respiratory symptoms. Three multiplex real-time reverse transcription polymerase chain reaction (rRT-PCR) assays have been recently developed commercially in Korea: PowerChek™ SARS-CoV-2, Influenza A&B Multiplex Real-time PCR Kit (PowerChek; KogeneBiotech); STANDARD™ M Flu/SARS-CoV-2 Real-time Detection Kit (STANDARD M; SD BioSensor); and Allplex™ SARS-CoV-2/FluA/FluB/RSV Assay (Allplex; Seegene). We evaluated the analytical and clinical performances of these kits. METHODS: A limit of detection tests were performed and cross-reactivity analysis was executed using clinical respiratory samples. Ninety-seven SARS-CoV-2-positive, 201 SARS-CoV-2-negative, 71 influenza A-positive, 50 influenza B-positive, 78 RSV-positive, and 207 other respiratory virus-positive nasopharyngeal swabs were tested using the three assays. The AdvanSure™ respiratory viruses rRT-PCR assay (AdvanSure; LG Life Sciences) was used as a comparator assay for RSV. RESULTS: Except in influenza B, in SARS-CoV-2 and influenza A, there were no significant differences in detecting specific genes of the viruses among the three assays. All three kits did not cross-react with common respiratory viruses. All three kits had greater than 92% positive percent agreement and negative percent agreement and ≥ 0.95 kappa value in the detection of SARS-CoV-2 and flu A/B. Allplex detected RSV more sensitively than AdvanSure. CONCLUSION: The overall performance of three multiplex rRT-PCR assays for the concurrent detection of SARS-CoV-2, influenza A/B, and RSV was comparable. These kits will promote prompt differential diagnosis of COVID-19, influenza, and RSV infection in the COVID-19 pandemic era.


Assuntos
COVID-19/diagnóstico , Influenza Humana/diagnóstico , Reação em Cadeia da Polimerase Multiplex/métodos , Nasofaringe/virologia , RNA Viral/análise , Infecções por Vírus Respiratório Sincicial/diagnóstico , COVID-19/virologia , Reações Cruzadas , Humanos , Vírus da Influenza A/genética , Vírus da Influenza A/isolamento & purificação , Vírus da Influenza B/genética , Vírus da Influenza B/isolamento & purificação , Influenza Humana/virologia , Limite de Detecção , Proteínas do Nucleocapsídeo/genética , Poliproteínas/genética , RNA Viral/metabolismo , Kit de Reagentes para Diagnóstico , República da Coreia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/isolamento & purificação , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Proteínas da Matriz Viral/genética , Proteínas Virais/genética
19.
Sci Rep ; 11(1): 24442, 2021 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-34952911

RESUMO

Therapeutic interventions targeting viral infections remain a significant challenge for both the medical and scientific communities. While specific antiviral agents have shown success as therapeutics, viral resistance inevitably develops, making many of these approaches ineffective. This inescapable obstacle warrants alternative approaches, such as the targeting of host cellular factors. Respiratory syncytial virus (RSV), the major respiratory pathogen of infants and children worldwide, causes respiratory tract infection ranging from mild upper respiratory tract symptoms to severe life-threatening lower respiratory tract disease. Despite the fact that the molecular biology of the virus, which was originally discovered in 1956, is well described, there is no vaccine or effective antiviral treatment against RSV infection. Here, we demonstrate that targeting host factors, specifically, mTOR signaling, reduces RSV protein production and generation of infectious progeny virus. Further, we show that this approach can be generalizable as inhibition of mTOR kinases reduces coronavirus gene expression, mRNA transcription and protein production. Overall, defining virus replication-dependent host functions may be an effective means to combat viral infections, particularly in the absence of antiviral drugs.


Assuntos
Coronavirus/metabolismo , Vírus Sincicial Respiratório Humano/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteínas Virais/metabolismo , Células A549 , Coronavirus/efeitos dos fármacos , Coronavirus/genética , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Humanos , Biossíntese de Proteínas/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Proteína Companheira de mTOR Insensível à Rapamicina/antagonistas & inibidores , Proteína Companheira de mTOR Insensível à Rapamicina/genética , Proteína Companheira de mTOR Insensível à Rapamicina/metabolismo , Proteína Regulatória Associada a mTOR/antagonistas & inibidores , Proteína Regulatória Associada a mTOR/genética , Proteína Regulatória Associada a mTOR/metabolismo , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/patologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/efeitos dos fármacos , Vírus Sincicial Respiratório Humano/isolamento & purificação , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/genética , Proteínas Virais/genética
20.
Med Microbiol Immunol ; 210(5-6): 277-282, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34604931

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has forced the implementation of unprecedented public health measures strategies which might also have a significant impact on the spreading of other viral pathogens such as influenza and Respiratory Syncytial Virus (RSV) . The present study compares the incidences of the most relevant respiratory viruses before and during the SARS-CoV-2 pandemic in emergency room patients. We analyzed the results of in total 14,946 polymerase chain reaction point-of-care tests (POCT-PCR) for Influenza A, Influenza B, RSV and SARS-CoV-2 in an adult and a pediatric emergency room between December 1, 2018 and March 31, 2021. Despite a fivefold increase in the number of tests performed, the positivity rate for Influenza A dropped from 19.32% (165 positives of 854 tests in 2018/19), 14.57% (149 positives of 1023 in 2019-20) to 0% (0 positives of 4915 tests) in 2020/21. In analogy, the positivity rate for Influenza B and RSV dropped from 0.35 to 1.47%, respectively, 10.65-21.08% to 0% for both in 2020/21. The positivity rate for SARS-CoV2 reached 9.74% (110 of 1129 tests performed) during the so-called second wave in December 2020. Compared to the two previous years, seasonal influenza and RSV incidence was eliminated during the COVID-19 pandemic. Corona-related measures and human behavior patterns could lead to a significant decline or even complete suppression of other respiratory viruses such as influenza and RSV.


Assuntos
COVID-19/epidemiologia , Influenza Humana/diagnóstico , Testes Imediatos/estatística & dados numéricos , Infecções por Vírus Respiratório Sincicial/diagnóstico , COVID-19/virologia , Hospitais/estatística & dados numéricos , Humanos , Incidência , Influenza Humana/epidemiologia , Influenza Humana/virologia , Orthomyxoviridae/genética , Orthomyxoviridae/isolamento & purificação , Orthomyxoviridae/fisiologia , Pandemias , Reação em Cadeia da Polimerase , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/isolamento & purificação , Vírus Sincicial Respiratório Humano/fisiologia , Estudos Retrospectivos
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