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1.
J Med Virol ; 96(7): e29797, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38988215

RESUMO

Temperature and humidity are studied in the context of seasonal infections in temperate and tropical zones, but the relationship between viral trends and climate variables in temperate subtropical zones remains underexplored. Our retrospective study analyzes respiratory pathogen incidence and its correlation with climate data in a subtropical zone. Retrospective observational study at Moinhos de Vento Hospital, South Brazil, aiming to assess seasonal trends in respiratory pathogens, correlating them with climate data. The study included patients of all ages from various healthcare settings, with data collected between April 2022 and July 2023. Biological samples were analyzed for 24 pathogens using polymerase chain reaction and hybridization techniques; demographic variables were also collected. The data was analyzed descriptively and graphically. Spearman tests and Poisson regression were used as correlation tests. Tests were clustered according to all pathogens, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza viruses, rhinovirus, and respiratory syncytial virus (RSV). Between April 2022 and July 2023, 3329 tests showed a 71.6% positivity rate. Rhinovirus and RSV predominated, exhibiting seasonal patterns. Temperature was inversely correlated with the viruses, notably rhinovirus, but SARS-CoV-2 was positively correlated. Air humidity was positively correlated with all pathogens, RSV, rhinovirus, and atmospheric pressure with all pathogens and rhinovirus. Our results showed statistically significant correlations, with modest effect sizes. Our study did not evaluate causation effects. Despite the correlation between climate and respiratory pathogens, our work suggests additional factors influencing transmission dynamics. Our findings underscore the complex interplay between climate and respiratory infections in subtropical climates.


Assuntos
COVID-19 , Umidade , Estações do Ano , Temperatura , Humanos , Estudos Retrospectivos , COVID-19/epidemiologia , COVID-19/transmissão , COVID-19/virologia , Brasil/epidemiologia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Criança , Adolescente , Pré-Escolar , Idoso , Adulto Jovem , Lactente , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Clima , Infecções Respiratórias/virologia , Infecções Respiratórias/epidemiologia , Clima Tropical , Recém-Nascido , Rhinovirus/genética , Rhinovirus/isolamento & purificação , Incidência , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/virologia , Idoso de 80 Anos ou mais
2.
Nat Commun ; 15(1): 5766, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982052

RESUMO

Respiratory viruses are a major trigger of exacerbations in chronic obstructive pulmonary disease (COPD). Airway neutrophilia is a hallmark feature of stable and exacerbated COPD but roles played by neutrophil extracellular traps (NETS) in driving disease pathogenesis are unclear. Here, using human studies of experimentally-induced and naturally-occurring exacerbations we identify that rhinovirus infection induces airway NET formation which is amplified in COPD and correlates with magnitude of inflammation and clinical exacerbation severity. We show that inhibiting NETosis protects mice from immunopathology in a model of virus-exacerbated COPD. NETs drive inflammation during exacerbations through release of double stranded DNA (dsDNA) and administration of DNAse in mice has similar protective effects. Thus, NETosis, through release of dsDNA, has a functional role in the pathogenesis of COPD exacerbations. These studies open up the potential for therapeutic targeting of NETs or dsDNA as a strategy for treating virus-exacerbated COPD.


Assuntos
Armadilhas Extracelulares , Neutrófilos , Doença Pulmonar Obstrutiva Crônica , Rhinovirus , Armadilhas Extracelulares/imunologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/virologia , Doença Pulmonar Obstrutiva Crônica/patologia , Animais , Humanos , Rhinovirus/imunologia , Camundongos , Neutrófilos/imunologia , Masculino , Feminino , Infecções por Picornaviridae/imunologia , Infecções por Picornaviridae/virologia , Infecções por Picornaviridae/complicações , Camundongos Endogâmicos C57BL , DNA/imunologia , Modelos Animais de Doenças , Pessoa de Meia-Idade , Inflamação/imunologia , Inflamação/virologia , Idoso
3.
J Infect ; 89(2): 106218, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38950866

RESUMO

OBJECTIVES: Children are generally considered main drivers of transmission for respiratory viruses, but the emergence of SARS-CoV-2 challenged this paradigm. Human rhinovirus (RV) continued to co-circulate throughout the pandemic, allowing for direct comparison of age-specific infectivity and susceptibility within households between these viruses during a time of low SARS-CoV-2 population immunity. METHODS: Households with children were prospectively monitored for ≥23 weeks between August 2020 and July 2021. Upon onset of respiratory symptoms in a household, an outbreak study was initiated, including questionnaires and repeated nasal self-sampling in all household members. Swabs were tested by PCR. Age-stratified within-household secondary attack rates (SARs) were compared between SARS-CoV-2 and RV. RESULTS: A total of 307 households participated, including 582 children and 627 adults. Overall, SAR was lower for SARS-CoV-2 than for RV (aOR 0.55) and age distributions differed between both viruses (p < 0.001). Following household exposure, children were significantly less likely to become infected with SARS-CoV-2 compared to RV (aOR 0.16), whereas this was opposite in adults (aOR 1.71). CONCLUSION: In households, age-specific susceptibility to SARS-CoV-2 and RV differs and drives differences in household transmission between these pathogens. This highlights the importance of characterizing age-specific transmission risks, particularly for emerging infections, to guide appropriate infection control interventions.


Assuntos
COVID-19 , Características da Família , Rhinovirus , SARS-CoV-2 , Humanos , COVID-19/transmissão , COVID-19/epidemiologia , Rhinovirus/isolamento & purificação , Adulto , Criança , Feminino , Masculino , SARS-CoV-2/isolamento & purificação , Pré-Escolar , Adolescente , Pessoa de Meia-Idade , Adulto Jovem , Lactente , Estudos Prospectivos , Infecções por Picornaviridae/transmissão , Infecções por Picornaviridae/epidemiologia , Fatores Etários , Idoso , Pandemias
4.
Environ Microbiol Rep ; 16(4): e13303, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38982659

RESUMO

The development of effective methods for the surveillance of seasonal respiratory viruses is required for the timely management of outbreaks. We aimed to survey Influenza-A, Influenza-B, RSV-A, Rhinovirus and SARS-CoV-2 surveillance in a tertiary hospital and a campus over 5 months. The effectiveness of air screening as an early warning system for respiratory viruses was evaluated in correlation with respiratory tract panel test results. The overall viral positivity was higher on the campus than in the hospital (55.0% vs. 38.0%). Influenza A was the most prevalent pathogen in both locations. There were two influenza peaks (42nd and 49th weeks) in the hospital air, and a delayed peak was detected on campus in the 1st-week of January. Panel tests indicated a high rate of Influenza A in late December. RSV-A-positivity was higher on the campus than the hospital (21.6% vs. 7.4%). Moreover, we detected two RSV-A peaks in the campus air (48th and 51st weeks) but only one peak in the hospital and panel tests (week 49). Although rhinovirus was the most common pathogen in panel tests, rhinovirus positivity was low in air samples. The air screening for Influenza-B and SARS-Cov-2 revealed comparable positivity rates with panel tests. Air screening can be integrated into surveillance programs to support infection control programs for potential epidemics of respiratory virus infections except for rhinoviruses.


Assuntos
COVID-19 , Rhinovirus , SARS-CoV-2 , Humanos , Rhinovirus/isolamento & purificação , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/genética , COVID-19/epidemiologia , COVID-19/diagnóstico , COVID-19/virologia , Aerossóis/análise , Infecções Respiratórias/virologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/diagnóstico , Microbiologia do Ar , Influenza Humana/epidemiologia , Influenza Humana/virologia , Poluição do Ar em Ambientes Fechados/análise , Vírus da Influenza A/isolamento & purificação , Estações do Ano , Epidemias , Monitoramento Ambiental/métodos , Vírus da Influenza B/isolamento & purificação , Vírus/isolamento & purificação , Vírus/classificação , Vírus/genética
5.
Pediatr Allergy Immunol ; 35(7): e14197, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39016335

RESUMO

BACKGROUND: Viral wheezing is an important risk factor for asthma, which comprises several respiratory phenotypes. We sought to understand if the etiology of early-life wheezing illnesses relates to childhood respiratory and asthma phenotypes. METHODS: Data were collected prospectively on 429 children in the Urban Environment and Childhood Asthma (URECA) birth cohort study through age 10 years. We identified wheezing illnesses and the corresponding viral etiology (PCR testing of nasal mucus) during the first 3 years of life. Six phenotypes of respiratory health were identified at 10 years of age based on trajectories of wheezing, allergic sensitization, and lung function. We compared the etiology of early wheezing illnesses to these wheezing respiratory phenotypes and the development of asthma. RESULTS: In the first 3 years of life, at least one virus was detected in 324 (67%) of the 483 wheezing episodes documented in the study cohort. Using hierarchical partitioning we found that non-viral wheezing episodes accounted for the greatest variance in asthma diagnosed at both 7 and 10 years of age (8.0% and 5.8% respectively). Rhinovirus wheezing illnesses explained the most variance in respiratory phenotype outcome followed by non-viral wheezing episodes (4.9% and 3.9% respectively) at 10 years of age. CONCLUSION AND RELEVANCE: Within this high-risk urban-residing cohort in early life, non-viral wheezing episodes were frequently identified and associated with asthma development. Though rhinovirus wheezing illnesses had the greatest association with phenotype outcome, the specific etiology of wheezing episodes in early life provided limited information about subsequent wheezing phenotypes.


Assuntos
Asma , Fenótipo , Sons Respiratórios , População Urbana , Humanos , Asma/epidemiologia , Asma/virologia , Lactente , Feminino , Masculino , Pré-Escolar , Criança , Estudos Prospectivos , Rhinovirus , Fatores de Risco , Estudos de Coortes , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Infecções por Picornaviridae/epidemiologia , Infecções por Picornaviridae/complicações , Recém-Nascido
6.
Nat Commun ; 15(1): 5112, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879641

RESUMO

Virus infectivity is traditionally determined by endpoint titration in cell cultures, and requires complex processing steps and human annotation. Here we developed an artificial intelligence (AI)-powered automated framework for ready detection of virus-induced cytopathic effect (DVICE). DVICE uses the convolutional neural network EfficientNet-B0 and transmitted light microscopy images of infected cell cultures, including coronavirus, influenza virus, rhinovirus, herpes simplex virus, vaccinia virus, and adenovirus. DVICE robustly measures virus-induced cytopathic effects (CPE), as shown by class activation mapping. Leave-one-out cross-validation in different cell types demonstrates high accuracy for different viruses, including SARS-CoV-2 in human saliva. Strikingly, DVICE exhibits virus class specificity, as shown with adenovirus, herpesvirus, rhinovirus, vaccinia virus, and SARS-CoV-2. In sum, DVICE provides unbiased infectivity scores of infectious agents causing CPE, and can be adapted to laboratory diagnostics, drug screening, serum neutralization or clinical samples.


Assuntos
Inteligência Artificial , Efeito Citopatogênico Viral , Microscopia , SARS-CoV-2 , Humanos , SARS-CoV-2/patogenicidade , SARS-CoV-2/fisiologia , Microscopia/métodos , COVID-19/virologia , Redes Neurais de Computação , Animais , Vaccinia virus/fisiologia , Vaccinia virus/patogenicidade , Saliva/virologia , Chlorocebus aethiops , Células Vero , Rhinovirus/patogenicidade , Rhinovirus/fisiologia , Linhagem Celular
7.
Viruses ; 16(6)2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38932217

RESUMO

Wheezing children infected with rhinovirus (RV) have a markedly increased risk of subsequently developing recurrencies and asthma. No previous studies have assessed the association between cytokine response and the severity of acute illness in the first wheezing episode in children infected with RV. Forty-seven children treated both as inpatients and as outpatients infected with RV only, aged 3-23 months, with severe first wheezing episodes were recruited. During acute illness, peripheral blood mononuclear cells (PBMCs) were isolated and stimulated with anti-CD3/anti-CD28 in vitro. A multiplex ELISA was used to quantitatively identify 56 different cytokines. The mean age of the children was 17 months, 74% were males, 79% were hospitalized, and 33% were sensitized. In adjusted analyses, the inpatient group was characterized by decreased expressions of interferon gamma (IFN-γ), interleukin 10 (IL-10), macrophage inflammatory protein 1 alpha (MIP-1α), RANTES (CCL5), and tumor necrosis factor-alpha (TNF-α) and an increased expression of ENA-78 (CXCL5) compared to the outpatient group. The cytokine response profiles from the PBMCs were different between the inpatient and outpatient groups. Our results support that firmly controlled interplay between pro-inflammatory and anti-inflammatory responses are required during acute viral infection to absolve the initial infection leading, to less severe illness.


Assuntos
Citocinas , Leucócitos Mononucleares , Infecções por Picornaviridae , Sons Respiratórios , Rhinovirus , Humanos , Masculino , Rhinovirus/imunologia , Feminino , Citocinas/metabolismo , Lactente , Sons Respiratórios/etiologia , Infecções por Picornaviridae/imunologia , Infecções por Picornaviridae/virologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/virologia , Índice de Gravidade de Doença
8.
Viruses ; 16(6)2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38932250

RESUMO

This study aimed to determine the incidence and etiological, seasonal, and genetic characteristics of respiratory viral coinfections involving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Between October 2020 and January 2024, nasopharyngeal samples were collected from 2277 SARS-CoV-2-positive patients. Two multiplex approaches were used to detect and sequence SARS-CoV-2, influenza A/B viruses, and other seasonal respiratory viruses: multiplex real-time polymerase chain reaction (PCR) and multiplex next-generation sequencing. Coinfections of SARS-CoV-2 with other respiratory viruses were detected in 164 (7.2%) patients. The most common co-infecting virus was respiratory syncytial virus (RSV) (38 cases, 1.7%), followed by bocavirus (BoV) (1.2%) and rhinovirus (RV) (1.1%). Patients ≤ 16 years of age had the highest rate (15%) of mixed infections. Whole-genome sequencing produced 19 complete genomes of seasonal respiratory viral co-pathogens, which were subjected to phylogenetic and amino acid analyses. The detected influenza viruses were classified into the genetic groups 6B.1A.5a.2a and 6B.1A.5a.2a.1 for A(H1N1)pdm09, 3C.2a1b.2a.2a.1 and 3C.2a.2b for A(H3N2), and V1A.3a.2 for the B/Victoria lineage. The RSV-B sequences belonged to the genetic group GB5.0.5a, with HAdV-C belonging to type 1, BoV to genotype VP1, and PIV3 to lineage 1a(i). Multiple amino acid substitutions were identified, including at the antibody-binding sites. This study provides insights into respiratory viral coinfections involving SARS-CoV-2 and reinforces the importance of genetic characterization of co-pathogens in the development of therapeutic and preventive strategies.


Assuntos
COVID-19 , Coinfecção , Filogenia , SARS-CoV-2 , Humanos , Coinfecção/virologia , Coinfecção/epidemiologia , SARS-CoV-2/genética , SARS-CoV-2/classificação , SARS-CoV-2/isolamento & purificação , COVID-19/virologia , COVID-19/epidemiologia , Pessoa de Meia-Idade , Adulto , Feminino , Masculino , Adolescente , Pré-Escolar , Criança , Idoso , Adulto Jovem , Lactente , Infecções Respiratórias/virologia , Infecções Respiratórias/epidemiologia , Rhinovirus/genética , Rhinovirus/classificação , Rhinovirus/isolamento & purificação , Vírus da Influenza A/genética , Vírus da Influenza A/classificação , Vírus da Influenza A/isolamento & purificação , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/isolamento & purificação , Vírus Sincicial Respiratório Humano/classificação , Nasofaringe/virologia , Sequenciamento Completo do Genoma , China/epidemiologia , Estações do Ano , Idoso de 80 Anos ou mais , Genoma Viral , Vírus da Influenza B/genética , Vírus da Influenza B/isolamento & purificação , Vírus da Influenza B/classificação
9.
J Med Virol ; 96(6): e29755, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38922896

RESUMO

Throughout the COVID-19 pandemic, rhinovirus (RV) remained notable persistence, maintaining its presence while other seasonal respiratory viruses were largely suppressed by pandemic restrictions during national lockdowns. This research explores the epidemiological dynamics of RV infections among pediatric populations on Hainan Island, China, specifically focusing on the impact before and after the zero-COVID policy was lifted. From January 2021 to December 2023, 19 680 samples were collected from pediatric patients hospitalized with acute lower respiratory tract infections (ARTIs) at the Hainan Maternal and Child Health Hospital. The infection of RV was detected by tNGS. RV species and subtypes were identified in 32 RV-positive samples representing diverse time points by analyzing the VP4/VP2 partial regions. Among the 19 680 pediatric inpatients with ARTIs analyzed, 21.55% were found to be positive for RV infection, with notable peaks observed in April 2021 and November 2022. A gradual annual decline in RV infections was observed, alongside a seasonal pattern of higher prevalence during the colder months. The highest proportion of RV infections was observed in the 0-1-year age group. Phylogenetic analysis on 32 samples indicated a trend from RV-A to RV-C in 2022. This observation suggests potential evolving dynamics within the RV species although further studies are needed due to the limited sample size. The research emphasizes the necessity for ongoing surveillance and targeted management, particularly for populations highly susceptible to severe illnesses caused by RV infections.


Assuntos
COVID-19 , Variação Genética , Filogenia , Infecções por Picornaviridae , Infecções Respiratórias , Rhinovirus , Humanos , Rhinovirus/genética , Rhinovirus/classificação , Rhinovirus/isolamento & purificação , China/epidemiologia , Lactente , Pré-Escolar , Infecções por Picornaviridae/epidemiologia , Infecções por Picornaviridae/virologia , Criança , Feminino , Masculino , COVID-19/epidemiologia , COVID-19/virologia , Infecções Respiratórias/virologia , Infecções Respiratórias/epidemiologia , Recém-Nascido , Estações do Ano , Adolescente , Prevalência , Criança Hospitalizada/estatística & dados numéricos , SARS-CoV-2/genética , Hospitalização/estatística & dados numéricos
10.
New Microbiol ; 47(1): 60-67, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38700885

RESUMO

Acute respiratory tract infection (ARTI) is common in all age groups, especially in children and the elderly. About 85% of children who present with bronchiolitis are infected with respiratory syncytial virus (RSV); however, nearly one-third are coinfected with another respiratory virus, such as human rhinovirus (HRV). Therefore, it is necessary to explore the immune response to coinfection to better understand the molecular and cellular pathways involving virus-virus interactions that might be modulated by innate immunity and additional host cell response mechanisms. This study aims to investigate the host innate immune response against RSV-HRV coinfection compared with monoinfection. Human primary bronchial/tracheal epithelial cells (HPECs) were infected with RSV, HRV, or coinfected with both viruses, and the infected cells were collected at 48 and 72 hours. Gene expression profiles of IL-6, CCL5, TNF-α, IFN-ß, IFN-λ1, CXCL10, IL-10, IL-13, IRF3, and IRF7 were investigated using real-time quantitative PCR, which revealed that RSV-infected cells exhibited increased expression of IL-10, whereas HRV infection increased the expression of CXCL10, IL-10, and CCL5. IFN-λ1 and CXCL10 expression was significantly different between the coinfection and monoinfection groups. In conclusion, our study revealed that two important cytokines, IFN-λ1 and CXCL10, exhibited increased expression during coinfection.


Assuntos
Brônquios , Quimiocina CXCL10 , Coinfecção , Células Epiteliais , Interferon lambda , Interferons , Interleucinas , Infecções por Picornaviridae , Infecções por Vírus Respiratório Sincicial , Rhinovirus , Humanos , Rhinovirus/fisiologia , Coinfecção/virologia , Quimiocina CXCL10/genética , Quimiocina CXCL10/metabolismo , Células Epiteliais/virologia , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/virologia , Brônquios/virologia , Brônquios/citologia , Infecções por Picornaviridae/virologia , Infecções por Picornaviridae/imunologia , Interferons/genética , Interferons/metabolismo , Vírus Sincicial Respiratório Humano/fisiologia , Vírus Sincicial Respiratório Humano/genética , Células Cultivadas , Vírus Sinciciais Respiratórios/fisiologia
11.
Microbiol Spectr ; 12(7): e0385323, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38780281

RESUMO

Allergic rhinitis (AR) is a global health challenge that particularly affects the quality of life of children. Human rhinovirus (HRV) infection usually causes common cold in the upper respiratory tract (URT) and can also affect airway allergy development, such as asthma exacerbation, but its relationship with AR is poorly understood. The study aimed to gain insight into the characteristics of HRV that is prevalent in AR children and its role in AR severity. A total of 362 children with symptomatic AR were enrolled from southwestern China during 2022-2023, and nasal lavage samples were collected for HRV molecular characterization and cytokine measurement. HRV was detected in 40% of the AR children, with peak detection in autumn. The positive rate was not correlated with whether the subjects were under allergen-specific immunotherapy (AIT). Among the detected HRVs, 42% were species A, 36% were species B, and 22% were species C, involving 21 A genotypes, 6 B genotypes, and 7 C genotypes. HRV positivity was significantly associated with symptom severity (visual analog scale [VAS] score) and elevated levels of local nasal IgE, interleukin-25 (IL-25), IL-4, and CXCL13 in AR children who did not receive antiallergic treatment. All three species of HRV strains (A1B, A21, B27, B70, and C17) had been isolated and were able to infect respiratory epithelial tissue in vitro. Complete genome sequencing showed that the antigenic epitopes of the isolated HRVs had certain variations. Our work reveals the etiological characteristics of URT-HRV in AR children and suggests a role of HRV infection in the pathogenesis of childhood AR. IMPORTANCE: Our study revealed high human rhinovirus (HRV) detection rate in children with allergic rhinitis (AR), and HRV infection (A, B, or C species) is positively associated with the symptom severity in AR children. Elevated nasal IgE, interleukin-25 (IL-25), IL-4, and CXCL13 levels suggest a potential pathogenic mechanism by which HRV infection induces nasal type 2 immune/inflammation responses and local IgE production in AR patients. In addition, etiological analysis found that the main prevalent HRV species in AR children are A and B (~80%), which is different from acute respiratory infection and asthma exacerbation, where species A and C are dominant. The data reveal the distinct species prevalence characteristics of HRV infection in AR. Finally, we isolated all three species of HRV strains from nasal cavity of AR children with varying degrees of antigenic epitope mutations and in vitro infectivity, highlighting the importance of strengthening monitoring and intervention for respiratory HRV infection in AR children.


Assuntos
Infecções por Picornaviridae , Rinite Alérgica , Rhinovirus , Humanos , Rhinovirus/genética , Rhinovirus/imunologia , Rhinovirus/isolamento & purificação , Rhinovirus/classificação , Criança , Masculino , Feminino , Infecções por Picornaviridae/virologia , Infecções por Picornaviridae/imunologia , Infecções por Picornaviridae/epidemiologia , Pré-Escolar , China/epidemiologia , Rinite Alérgica/virologia , Rinite Alérgica/imunologia , Imunoglobulina E/imunologia , Imunoglobulina E/sangue , Índice de Gravidade de Doença , Citocinas/metabolismo , Citocinas/imunologia , Genótipo , Infecções Respiratórias/virologia , Infecções Respiratórias/imunologia , Adolescente , Filogenia , Resfriado Comum/virologia , Resfriado Comum/imunologia , Resfriado Comum/epidemiologia
12.
Sci Rep ; 14(1): 10431, 2024 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714841

RESUMO

Reverse zoonotic respiratory diseases threaten great apes across Sub-Saharan Africa. Studies of wild chimpanzees have identified the causative agents of most respiratory disease outbreaks as "common cold" paediatric human pathogens, but reverse zoonotic transmission pathways have remained unclear. Between May 2019 and August 2021, we conducted a prospective cohort study of 234 children aged 3-11 years in communities bordering Kibale National Park, Uganda, and 30 adults who were forest workers and regularly entered the park. We collected 2047 respiratory symptoms surveys to quantify clinical severity and simultaneously collected 1989 nasopharyngeal swabs approximately monthly for multiplex viral diagnostics. Throughout the course of the study, we also collected 445 faecal samples from 55 wild chimpanzees living nearby in Kibale in social groups that have experienced repeated, and sometimes lethal, epidemics of human-origin respiratory viral disease. We characterized respiratory pathogens in each cohort and examined statistical associations between PCR positivity for detected pathogens and potential risk factors. Children exhibited high incidence rates of respiratory infections, whereas incidence rates in adults were far lower. COVID-19 lockdown in 2020-2021 significantly decreased respiratory disease incidence in both people and chimpanzees. Human respiratory infections peaked in June and September, corresponding to when children returned to school. Rhinovirus, which caused a 2013 outbreak that killed 10% of chimpanzees in a Kibale community, was the most prevalent human pathogen throughout the study and the only pathogen present at each monthly sampling, even during COVID-19 lockdown. Rhinovirus was also most likely to be carried asymptomatically by adults. Although we did not detect human respiratory pathogens in the chimpanzees during the cohort study, we detected human metapneumovirus in two chimpanzees from a February 2023 outbreak that were genetically similar to viruses detected in study participants in 2019. Our data suggest that respiratory pathogens circulate in children and that adults become asymptomatically infected during high-transmission times of year. These asymptomatic adults may then unknowingly carry the pathogens into forest and infect chimpanzees. This conclusion, in turn, implies that intervention strategies based on respiratory symptoms in adults are unlikely to be effective for reducing reverse zoonotic transmission of respiratory viruses to chimpanzees.


Assuntos
Resfriado Comum , Pan troglodytes , Animais , Humanos , Criança , Feminino , Masculino , Pré-Escolar , Resfriado Comum/epidemiologia , Resfriado Comum/virologia , Adulto , Uganda/epidemiologia , Estudos Prospectivos , Zoonoses/epidemiologia , Zoonoses/virologia , COVID-19/epidemiologia , COVID-19/virologia , COVID-19/transmissão , Doenças dos Símios Antropoides/epidemiologia , Doenças dos Símios Antropoides/virologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Infecções Respiratórias/veterinária , Rhinovirus/isolamento & purificação , Rhinovirus/genética , SARS-CoV-2/isolamento & purificação , Incidência
13.
Curr Top Med Chem ; 24(15): 1343-1358, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38698747

RESUMO

BACKGROUND: Human rhinovirus 3C protease (HRV-3Cpro) plays a crucial role in viral proliferation, establishing it as a prime target for antiviral therapy. However, research on identifying HRV-3Cpro inhibitors is still limited. OBJECTIVE: This study had two primary objectives: first, to validate the efficacy of an end-point colorimetric assay, previously developed by our team, for identifying potential inhibitors of HRV-3Cpro; and second, to discover phytochemicals in medicinal plants that inhibit the enzyme's activity. METHODS: Rupintrivir, a well-known inhibitor of HRV-3Cpro, was used to validate the colorimetric assay. Following this, we conducted a two-step in silico screening of 2532 phytochemicals, which led to the identification of eight active compounds: apigenin, carnosol, chlorogenic acid, kaempferol, luteolin, quercetin, rosmarinic acid, and rutin. We subsequently evaluated these candidates in vitro. To further investigate the inhibitory potential of the most promising candidates, namely, carnosol and rosmarinic acid, molecular docking studies were performed to analyze their binding interactions with HRV-3Cpro. RESULTS: The colorimetric assay we previously developed is effective in identifying compounds that selectively inhibit HRV-3Cpro. Carnosol and rosmarinic acid emerged as potent inhibitors, inhibiting HRV-3Cpro activity in vitro by over 55%. Our analysis indicated that carnosol and rosmarinic acid exert their inhibitory effects through a competitive mechanism. Molecular docking confirmed their competitive binding to the enzyme's active site. CONCLUSION: Carnosol and rosmarinic acid warrant additional investigation for their potential in the development of common cold treatment. By highlighting these compounds as effective HRV-3Cpro inhibitors, our study presents a promising approach for discovering phytochemical inhibitors against proteases from similar pathogens.


Assuntos
Proteases Virais 3C , Antivirais , Resfriado Comum , Simulação de Acoplamento Molecular , Compostos Fitoquímicos , Rhinovirus , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Proteases Virais 3C/antagonistas & inibidores , Rhinovirus/enzimologia , Rhinovirus/efeitos dos fármacos , Humanos , Antivirais/farmacologia , Antivirais/química , Resfriado Comum/tratamento farmacológico , Resfriado Comum/virologia , Proteínas Virais/antagonistas & inibidores , Proteínas Virais/metabolismo , Estrutura Molecular , Relação Estrutura-Atividade , Inibidores de Proteases/farmacologia , Inibidores de Proteases/química
15.
Viruses ; 16(5)2024 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-38793579

RESUMO

Acute respiratory infections are a major global burden in resource-limited countries, including countries in Africa. Although COVID-19 has been well studied since the pandemic emerged in Gabon, Central Africa, less attention has been paid to other respiratory viral diseases, and very little data are available. Herein, we provide the first data on the genetic diversity and detection of 18 major respiratory viruses in Gabon during the COVID-19 pandemic. Of 582 nasopharyngeal swab specimens collected from March 2020 to July 2021, which were SARS-CoV-2 negative, 156 were positive (26%) for the following viruses: enterovirus (20.3%), human rhinovirus (HRV) (4.6%), human coronavirus OC43 (1.2%), human adenovirus (0.9%), human metapneumovirus (hMPV) (0.5%), influenza A virus (IAV) (0.3%), and human parainfluenza viruses (0.5%). To determine the genetic diversity and transmission route of the viruses, phylogenetic analyses were performed using genome sequences of the detected viruses. The IAV strain detected in this study was genetically similar to strains isolated in the USA, whereas the hMPV strain belonging to the A2b subtype formed a cluster with Kenyan strains. This study provides the first complete genomic sequences of HRV, IAV, and hMPV detected in Gabon, and provides insight into the circulation of respiratory viruses in the country.


Assuntos
COVID-19 , Variação Genética , Filogenia , Infecções Respiratórias , Humanos , Gabão/epidemiologia , COVID-19/epidemiologia , COVID-19/virologia , Infecções Respiratórias/virologia , Infecções Respiratórias/epidemiologia , SARS-CoV-2/genética , SARS-CoV-2/classificação , SARS-CoV-2/isolamento & purificação , Masculino , Adulto , Feminino , Criança , Pessoa de Meia-Idade , Adolescente , Pré-Escolar , Adulto Jovem , Rhinovirus/genética , Rhinovirus/isolamento & purificação , Rhinovirus/classificação , Vírus/genética , Vírus/classificação , Vírus/isolamento & purificação , Metapneumovirus/genética , Metapneumovirus/isolamento & purificação , Metapneumovirus/classificação , Genoma Viral , Nasofaringe/virologia , Lactente , Idoso , Pandemias , Vírus da Influenza A/genética , Vírus da Influenza A/isolamento & purificação , Vírus da Influenza A/classificação
16.
Front Cell Infect Microbiol ; 14: 1380855, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38803572

RESUMO

Introduction: Acute respiratory infections (ARI) are the most common infections in the general population and are mainly caused by respiratory viruses. Detecting several viruses in a respiratory sample is common. To better understand these viral codetections and potential interferences, we tested for the presence of viruses and developed quantitative PCR (Polymerase Chain Reaction) for the viruses most prevalent in coinfections: human rhinovirus (HRV) and respiratory syncytial virus (RSV), and quantified their viral loads according to coinfections and health status, age, cellular abundance and other variables. Materials and methods: Samples from two different cohorts were analyzed: one included hospitalized infants under 12 months of age with acute bronchiolitis (n=719) and the other primary care patients of all ages with symptoms of ARI (n=685). We performed Multiplex PCR on nasopharyngeal swabs, and quantitative PCR on samples positive for HRV or/and RSV to determine viral loads (VL). Cellular abundance (CA) was also estimated by qPCR targeting the GAPDH gene. Genotyping was performed either directly from first-line molecular panel or by PCR and sequencing for HRV. Results: The risks of viral codetection were 4.1 (IC95[1.8; 10.0]) and 93.9 1 (IC95[48.7; 190.7]) higher in infants hospitalized for bronchiolitis than in infants in primary care for RSV and HRV respectively (p<0.001). CA was higher in samples positive for multiple viruses than in mono-infected or negative samples (p<0.001), and higher in samples positive for RSV (p<0.001) and HRV (p<0.001) than in negative samples. We found a positive correlation between CA and VL for both RSV and HRV. HRV VL was higher in children than in the elderly (p<0.05), but not RSV VL. HRV VL was higher when detected alone than in samples coinfected with RSV-A and with RSV-B. There was a significant increase of RSV-A VL when codetecting with HRV (p=0.001) and when co-detecting with RSV-B+HRV versus RSV-A+ RSV-B (p=0.02). Conclusions: Many parameters influence the natural history of respiratory viral infections, and quantifying respiratory viral loads can help disentangle their contributions to viral outcome.


Assuntos
Coinfecção , Infecções Respiratórias , Rhinovirus , Carga Viral , Humanos , Coinfecção/virologia , Lactente , Infecções Respiratórias/virologia , Feminino , Pré-Escolar , Masculino , Rhinovirus/isolamento & purificação , Rhinovirus/genética , Criança , Nível de Saúde , Adulto , Infecções por Vírus Respiratório Sincicial/virologia , Adolescente , Pessoa de Meia-Idade , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/isolamento & purificação , Nasofaringe/virologia , Recém-Nascido , Adulto Jovem , Idoso , Reação em Cadeia da Polimerase em Tempo Real , Doença Aguda , Genótipo , Reação em Cadeia da Polimerase Multiplex , Idoso de 80 Anos ou mais
17.
Proc Natl Acad Sci U S A ; 121(21): e2402540121, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38758698

RESUMO

All respiratory viruses establish primary infections in the nasal epithelium, where efficient innate immune induction may prevent dissemination to the lower airway and thus minimize pathogenesis. Human coronaviruses (HCoVs) cause a range of pathologies, but the host and viral determinants of disease during common cold versus lethal HCoV infections are poorly understood. We model the initial site of infection using primary nasal epithelial cells cultured at an air-liquid interface (ALI). HCoV-229E, HCoV-NL63, and human rhinovirus-16 are common cold-associated viruses that exhibit unique features in this model: early induction of antiviral interferon (IFN) signaling, IFN-mediated viral clearance, and preferential replication at nasal airway temperature (33 °C) which confers muted host IFN responses. In contrast, lethal SARS-CoV-2 and MERS-CoV encode antagonist proteins that prevent IFN-mediated clearance in nasal cultures. Our study identifies features shared among common cold-associated viruses, highlighting nasal innate immune responses as predictive of infection outcomes and nasally directed IFNs as potential therapeutics.


Assuntos
Resfriado Comum , Imunidade Inata , Interferons , Mucosa Nasal , SARS-CoV-2 , Transdução de Sinais , Humanos , Mucosa Nasal/virologia , Mucosa Nasal/imunologia , Mucosa Nasal/metabolismo , Interferons/metabolismo , Interferons/imunologia , Resfriado Comum/imunologia , Resfriado Comum/virologia , Transdução de Sinais/imunologia , SARS-CoV-2/imunologia , Replicação Viral , Rhinovirus/imunologia , Coronavirus Humano 229E/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Células Epiteliais/virologia , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Coronavirus Humano NL63/imunologia
18.
J Gen Virol ; 105(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38717926

RESUMO

Background. Respiratory tract infections are among the most important causes of mortality and morbidity in children worldwide. The COVID-19 pandemic has affected the distribution of seasonal respiratory viruses as in all areas of life. In this study, we have aimed to evaluate the changes in the rates of seasonal respiratory viruses with the onset of the pandemic.Methods. This study included patients who were admitted to the Pediatrics Clinic of Eskisehir Osmangazi University Faculty of Medicine Hospital between December 2018 and February 2022 with respiratory tract infections and in whom pathogens were detected from nasopharyngeal swab samples analysed by multiplex PCR method.Results. A total of 833 respiratory tract pathogens were detected in 684 cases consisting of male (55.3 %), and female (44.7 %), patients with a total mean age of 42 months. Single pathogen was revealed in 550, and multiple pathogens in 134 cases. Intensive care was needed in 14 % of the cases. Most frequently influenza A/B, rhinovirus and respiratory syncytial virus (RSV) were detected during the pre-pandemic period, while rhinovirus, RSV, and adenovirus were observed during the lockdown period. In the post-lockdown period, the incidence rates of rhinovirus, RSV, human bocavirus (HboV) (12 %), influenza virus infections increased, and patients with RSV and bocavirus infections required intensive care hospitalization.Conclusion. It is thought that the COVID-9 pandemic lockdown measures may have an impact on the distribution of seasonal respiratory viruses, especially RSV and influenza. Current, prospective and large case series regarding the mechanism of action and dynamics are needed.


Assuntos
COVID-19 , Infecções Respiratórias , SARS-CoV-2 , Estações do Ano , Humanos , Feminino , Masculino , COVID-19/epidemiologia , COVID-19/virologia , Pré-Escolar , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Lactente , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Criança , Rhinovirus/isolamento & purificação , Rhinovirus/genética , Nasofaringe/virologia , Adolescente , Influenza Humana/epidemiologia , Influenza Humana/virologia , Pandemias , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/virologia
19.
J Med Virol ; 96(4): e29582, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38590253

RESUMO

To understand the prevalence of rhinovirus (RV) among acute respiratory infection (ARI) patients, 10-year ARI surveillance in multiple provinces of China were conducted during 2012-2021. Of 15 645 ARI patients, 1180 (7.54%) were confirmed to have RV infection and 820 (69.49%) were children under 5 years of age. RV typing was performed on the 527 VP1 gene sequences, and species A, B, and C accounted for 73.24%, 4.93%, and 21.82%, respectively. Although no significant difference in the proportions of age groups or disease severity was found between RV species, RV-C was more frequently detected in children under 5 years of age, RV-A was more frequently detected in elderly individuals (≥60), and the proportions of pneumonia in RV-A and RV-C patients were higher than those in RV-B patients. The epidemic peak of RV-A was earlier than that of RV-C. A total of 57 types of RV-A, 13 types of RV-B, and 35 types of RV-C were identified in RV-infected patients, and two uncertain RV types were also detected. The findings showed a few differences in epidemiological and clinical features between RV species in ARI patients, and RV-A and RV-C were more prevalent than RV-B.


Assuntos
Infecções por Enterovirus , Infecções por Picornaviridae , Infecções Respiratórias , Criança , Humanos , Lactente , Pré-Escolar , Idoso , Rhinovirus/genética , Prevalência , Infecções por Picornaviridae/epidemiologia , Infecções Respiratórias/epidemiologia , China/epidemiologia , Variação Genética
20.
BMC Pediatr ; 24(1): 231, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561704

RESUMO

BACKGROUND: Effects of non-pharmaceutical interventions during the pandemic were mainly studied for severe outcomes. Among children, most of the burden of respiratory infections is related to infections which are not medically attended. The perspective on infections in the community setting is necessary to understand the effects of the pandemic on non-pharmaceutical interventions. METHODS: In the unique prospective LoewenKIDS cohort study, we compared the true monthly incidence of self-reported acute respiratory infections (ARI) in about 350 participants (aged 3-4 years old) between October 2019 to March 2020 (pre-pandemic period) and October 2020 to March 2021 (pandemic period). Parents reported children's symptoms using a diary. Parents were asked to take a nasal swab of their child during all respiratory symptoms. We analysed 718 swabs using Multiplex PCR for 25 common respiratory viruses and bacteria. RESULTS: During the pre-pandemic period, on average 44.6% (95% CI: 39.5-49.8%) of children acquired at least one ARI per month compared to 19.9% (95% CI: 11.1-28.7%) during the pandemic period (Incidence Rate Ratio = 0.47; 95% CI: 0.41-0.54). The detection of influenza virus decreased absolute by 96%, respiratory syncytial virus by 65%, metapneumovirus by 95%, parainfluenza virus by 100%, human enterovirus by 96% and human bocavirus by 70% when comparing the pre-pandemic to the pandemic period. However, rhinoviruses were nearly unaffected by NPI. Co-detection (detection of more than one virus in a single symptomatic swab) was common in the pre-pandemic period (222 of 390 samples with viral detection; 56.9%) and substantially less common during the pandemic period (46 of 216 samples; 21.3%). CONCLUSION: Non-pharmaceutical interventions strongly reduced the incidence of all respiratory infections in preschool children but did not affect rhinovirus.


Assuntos
COVID-19 , Metapneumovirus , Infecções Respiratórias , Humanos , Pré-Escolar , Lactente , Estudos de Coortes , Estudos Prospectivos , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/prevenção & controle , Rhinovirus
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