RESUMO
TMPRSS2, a human transmembrane protease enzyme, plays a crucial role in the spread of certain viruses, including influenza and coronaviruses. This enzyme promotes viral infection by cleaving viral glycoproteins, which helps viruses like SARS-CoV-2 and influenza A enter cells more effectively. Genetic differences in TMPRSS2 may affect people's susceptibility to COVID-19, underscoring the need for studies that consider diverse populations. Beyond infectious diseases, TMPRSS2 has also been linked to some cancers, suggesting it could be a valuable target for drug development. This review provides a summary of TMPRSS2 inhibitors currently under study, with some already in clinical trials to test their effectiveness against viral infections. As we uncover more about TMPRSS2's role in pathogenesis, it could open new doors for therapies to combat future outbreaks.
Assuntos
Influenza Humana , SARS-CoV-2 , Serina Endopeptidases , Humanos , Serina Endopeptidases/metabolismo , Serina Endopeptidases/genética , SARS-CoV-2/patogenicidade , SARS-CoV-2/metabolismo , Influenza Humana/virologia , Influenza Humana/metabolismo , Influenza Humana/genética , COVID-19/virologia , COVID-19/metabolismo , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Vírus da Influenza A/patogenicidade , Vírus da Influenza A/genética , Vírus da Influenza A/fisiologiaRESUMO
AIM: Backyard production systems (BPS) represent an interface of contact between people, domestic and wild animals. Studies conducted in Chile during the last decade have provided extensive evidence of influenza A virus (IAV) circulation in backyard poultry and swine. The aim of this study was to investigate exposure practices of humans to animal-origin IAV within backyards. METHODS AND RESULTS: Backyard farmers and household members of a total of 101 BPS in the proximity of wetlands located throughout Chile were interviewed between 2021 and 2022. Data were collected on the nature of human-animal contacts through participation in productive activities conducted within backyards, which was used to estimate participants' exposure risk to animal-origin IAV. Additionally, RT-qPCR and serologic IAV active surveillance was carried out in backyard animals. Multilinear regression was used to identify factors associated with exposure risk. Overall, IAV prevalence was 10.1% (95% CI: 4.7%-15.5%) and seroprevalence was 43.5% (95% CI: 29.7%-54.2%), both at the BPS level. Of 180 interviewees, 86% reported participating regularly in poultry or swine exposure activities within the backyard. A greater participation of male participants was observed when evaluating swine exposure activities, while female participation was greater for some activities related to poultry handling. Handwashing was a very extended hygiene practice; however, the use of personal protective equipment was uncommon. Different factors related to participants, households and backyards were associated with an increased exposure risk of participants to animal-origin IAV: (i) older age, (ii) less years of education, (iii) no off-farm work, (iv) greater backyard production value and (v) greater household consumption of backyard products. CONCLUSION: These results indicate the circulation of IAV in BPS and the frequent human-animal contact at this interface, highlighting the need for awareness campaigns and educational programmes aimed at backyard farmers on prevention and biosecurity measures in the management of backyard animals.
Assuntos
Criação de Animais Domésticos , Vírus da Influenza A , Influenza Humana , Infecções por Orthomyxoviridae , Aves Domésticas , Doenças dos Suínos , Animais , Humanos , Suínos , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/virologia , Doenças dos Suínos/transmissão , Feminino , Masculino , Influenza Humana/prevenção & controle , Influenza Humana/epidemiologia , Influenza Humana/virologia , Influenza Humana/transmissão , Adulto , Pessoa de Meia-Idade , Infecções por Orthomyxoviridae/epidemiologia , Infecções por Orthomyxoviridae/veterinária , Infecções por Orthomyxoviridae/transmissão , Infecções por Orthomyxoviridae/virologia , Infecções por Orthomyxoviridae/prevenção & controle , Influenza Aviária/epidemiologia , Influenza Aviária/transmissão , Influenza Aviária/prevenção & controle , Zoonoses , Chile/epidemiologia , Doenças das Aves Domésticas/virologia , Doenças das Aves Domésticas/epidemiologia , Doenças das Aves Domésticas/transmissão , Estudos Soroepidemiológicos , Interação Humano-Animal , Fazendas , Fazendeiros/psicologiaRESUMO
Zoonotic infections (swine-human) caused by influenza A viruses (IAVs) have been reported and linked to close contact between these species. Here, we describe eight human IAV variant infections (6 mild and 2 severe cases, including 1 death) detected in Paraná, Brazil, during 2020-2023. Genomes recovered were closely related to Brazilian swIAVs of three major lineages (1 A.3.3.2/pdm09, 1B/human-like, and H3.1990.5), including three H1N1v, two H1N2v, two H3N2v and one H1v. Five H1v were closely related to pdm09 lineage, one H1v (H1N2v) grouped within 1B.2.3 clade, and the two H3v grouped within a clade composed exclusively of Brazilian H3 swIAV (clade H3.1990.5.1). Internal gene segments were closely related to H1N1pdm09 isolated from pigs. IAV variant rarely result in sustained transmission between people, however the potential to develop such ability is of concern and must not be underestimated. This study brings into focus the need for continuous influenza surveillance and timely risk assessment.
Assuntos
Vírus da Influenza A , Influenza Humana , Infecções por Orthomyxoviridae , Filogenia , Brasil/epidemiologia , Animais , Humanos , Influenza Humana/transmissão , Influenza Humana/virologia , Influenza Humana/epidemiologia , Suínos , Vírus da Influenza A/genética , Vírus da Influenza A/classificação , Vírus da Influenza A/isolamento & purificação , Infecções por Orthomyxoviridae/transmissão , Infecções por Orthomyxoviridae/virologia , Infecções por Orthomyxoviridae/epidemiologia , Feminino , Masculino , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza A Subtipo H1N1/classificação , Zoonoses/transmissão , Zoonoses/virologia , Zoonoses/epidemiologia , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Pessoa de Meia-Idade , Adulto , Genoma Viral/genética , Zoonoses Virais/transmissão , Zoonoses Virais/epidemiologia , Zoonoses Virais/virologia , Doenças dos Suínos/virologia , Doenças dos Suínos/transmissão , Doenças dos Suínos/epidemiologia , Adulto Jovem , Criança , AdolescenteRESUMO
The emergence of highly pathogenic avian influenza (HPAI) A H5N1 virus in dairy cattle marks a troubling new chapter in the ongoing battle against zoonotic diseases. Since its initial detection in 1955, the H5N1 virus has primarily been associated with poultry, posing significant threats to both animal and human health. However, recent outbreaks in U.S. dairy herds across nine states have revealed an alarming expansion of the virus, with over 190 herds affected as of September 2024. This unprecedented spread in cattle has sparked intense concern among scientists and health officials, especially with reports indicating that up to 20% of dairy products may contain traces of the virus. The implications of the H5N1 virus establishing itself in cattle populations are profound. This potential endemic presence could transform dairy farms into reservoirs of the virus, facilitating its evolution and increasing the risk of human transmission. Mutations enhancing viral replication in mammals have already been identified, including the notorious PB2 E627K mutation linked to increased virulence. Moreover, the detection of the virus in the central nervous system of infected animals, including cats, underscores the broad tissue tropism and severe pathogenic potential of the H5N1 virus. Current containment efforts include stringent biosecurity measures and financial incentives for enhanced testing and personal protective equipment (PPE) for farmers. Yet, gaps in testing infrastructure and the resurgence of raw milk consumption pose significant challenges. The U.S. Department of Agriculture (USDA) and the Centers for Disease Control and Prevention (CDC) emphasize the critical need for comprehensive testing and pasteurization to mitigate the risk of human infection. As the scientific community races to adapt existing antiviral treatments and develop effective vaccines, the concept of a One Health approach becomes increasingly vital. This holistic strategy calls for coordinated actions across human, animal, and environmental health sectors to preemptively tackle emerging zoonotic threats. Strengthening surveillance, fostering international cooperation, and investing in research are essential steps to prevent the H5N1 virus from igniting the next global health crisis. The current avian influenza outbreak serves as a stark reminder of the delicate balance between human activities and viral evolution. Our collective ability to respond effectively and proactively will determine whether we can avert the perfect storm brewing on the horizon.
Assuntos
Virus da Influenza A Subtipo H5N1 , Influenza Humana , Pandemias , Animais , Bovinos , Humanos , Virus da Influenza A Subtipo H5N1/patogenicidade , Virus da Influenza A Subtipo H5N1/genética , Influenza Aviária/epidemiologia , Influenza Aviária/virologia , Influenza Aviária/transmissão , Influenza Aviária/prevenção & controle , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Influenza Humana/virologia , Influenza Humana/transmissão , Pandemias/prevenção & controle , Pandemias/veterinária , Estados Unidos/epidemiologia , Zoonoses/epidemiologia , Zoonoses/prevenção & controle , Zoonoses/transmissão , Zoonoses/virologiaRESUMO
Influenza circulation was significantly affected in 2020-21 by the COVID-19 pandemic. During this time, few influenza cases were recorded. However, in the summer of 2021-22, an increase in atypical influenza cases was observed, leading to the resurgence of influenza in the southernmost state of Brazil, Rio Grande do Sul (RS). The present study aimed to identify the circulation of FLUAV, FLUBV and SARS-CoV-2 and characterize the influenza genomes in respiratory samples using high-throughput sequencing technology (HTS). Respiratory samples (n = 694) from patients in RS were selected between July 2021 and August 2022. The samples were typed using reverse transcriptase real-time PCR (RT-qPCR) and showed 32% (223/694) of the samples to be positive for SARS-CoV-2, 7% for FLUAV (H3) (49/694). FLUBV was not detected. RT-qPCR data also resulted in FLUAV and SARS-CoV-2 co-infections in 1.7% (4/223) of samples tested. Whole genome sequencing of FLUAV produced 15 complete genomes of the H3N2 subtype, phylogenetically classified in the 3C.2a1b.2a.2a.3 subclade and revealing the dominance of viruses in the southern region of Brazil. Mutation analysis identified 72 amino acid substitutions in all genes, highlighting ongoing genetic evolution with potential implications for vaccine effectiveness, viral fitness, and pathogenicity. This study underscores limitations in current surveillance systems, advocating for comprehensive data inclusion to enhance understanding of influenza epidemiology in southern Brazil. These findings contribute valuable insights to inform more effective public health responses and underscore the critical need for continuous genomic surveillance.
Assuntos
COVID-19 , Genoma Viral , Influenza Humana , Filogenia , SARS-CoV-2 , Humanos , Brasil/epidemiologia , COVID-19/epidemiologia , COVID-19/virologia , SARS-CoV-2/genética , SARS-CoV-2/classificação , SARS-CoV-2/isolamento & purificação , Influenza Humana/epidemiologia , Influenza Humana/virologia , Pessoa de Meia-Idade , Adulto , Feminino , Genoma Viral/genética , Masculino , Adulto Jovem , Idoso , Adolescente , Surtos de Doenças , Sequenciamento Completo do Genoma , Criança , Pré-Escolar , Lactente , Coinfecção/epidemiologia , Coinfecção/virologia , Sequenciamento de Nucleotídeos em Larga Escala , Idoso de 80 Anos ou mais , GenômicaRESUMO
BACKGROUND: We examined the added value of serologic testing for estimating influenza virus infection incidence based on illness surveillance with molecular testing versus periodic serologic testing. METHODS: Pregnant persons unvaccinated against influenza at <28 weeks gestation were enrolled before the 2017 and 2018 influenza seasons in Peru and Thailand. Blood specimens were collected at enrollment and ≤14 days postpartum for testing by hemagglutination inhibition assay for antibodies against influenza reference viruses. Seroconversion was defined as a ≥4-fold rise in antibody titers from enrollment to postpartum with the second specimen's titer of ≥40. Throughout pregnancy, participants responded to twice weekly surveillance contacts asking about influenza vaccination and influenza-like symptoms (ILS). A mid-turbinate swab was collected with each ILS episode for influenza real-time reverse transcription polymerase chain reaction (rRT-PCR). RESULTS: Of 1,466 participants without evidence of influenza vaccination during pregnancy, 296 (20.2%) had evidence of influenza virus infections. Fifteen (5.1%) were detected by rRT-PCR only, 250 (84.4%) by serologic testing only, and 31 (10.5%) by both methods. CONCLUSIONS: Influenza virus infections during pregnancy occurred in 20% of cohort participants; >80% were not detected by a broad illness case definition coupled with rRT-PCR.
Assuntos
Anticorpos Antivirais , Influenza Humana , Complicações Infecciosas na Gravidez , Testes Sorológicos , Humanos , Feminino , Gravidez , Influenza Humana/epidemiologia , Influenza Humana/diagnóstico , Influenza Humana/virologia , Adulto , Incidência , Tailândia/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/diagnóstico , Anticorpos Antivirais/sangue , Peru/epidemiologia , Adulto Jovem , Testes Sorológicos/métodos , Testes de Inibição da Hemaglutinação , Vacinas contra Influenza/imunologia , AdolescenteRESUMO
INTRODUCTION: Lower respiratory tract infections (LRTI) remain a significant global cause of mortality and disability. Viruses constitute a substantial proportion of LRTI cases, with their pandemic potential posing a latent threat. After the SARS-CoV-2 pandemic, the resurgence of other respiratory viruses, including Influenza and Respiratory Syncytial Virus responsible for LRTI has been observed especially in susceptible populations. AREAS COVERED: This review details the inflammatory mechanisms associated with three primary respiratory viruses: SARS-CoV-2, Influenza, and Respiratory Syncytial Virus (RSV). The focus will be on elucidating the activation of inflammatory pathways, understanding cellular contributions to inflammation, exploring the role of interferon and induced cell death in the response to these pathogens and detailing viral evasion mechanisms. Furthermore, the distinctive characteristics of each virus will be explained. EXPERT OPINION: The study of viral pneumonia, notably concerning SARS-CoV-2, Influenza, and RSV, offers critical insights into infectious and inflammatory mechanisms with wide-ranging implications. Addressing current limitations, such as diagnostic accuracy and understanding host-virus interactions, requires collaborative efforts and investment in technology. Future research holds promise for uncovering novel therapeutic targets, exploring host microbiome roles, and addressing long-term sequelae. Integrating advances in molecular biology and technology will shape the evolving landscape of viral pneumonia research, potentially enhancing global public health outcomes.
Assuntos
COVID-19 , Inflamação , Influenza Humana , Infecções por Vírus Respiratório Sincicial , SARS-CoV-2 , Humanos , Inflamação/imunologia , COVID-19/imunologia , SARS-CoV-2/imunologia , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/virologia , Influenza Humana/imunologia , Influenza Humana/virologia , Influenza Humana/epidemiologia , Infecções Respiratórias/virologia , Infecções Respiratórias/imunologia , AnimaisRESUMO
The multiplex molecular diagnostic assays described for severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), influenza A (IAV) and B (IBV) viruses have been mainly based on real-time reaction, which limits their access to many laboratories or diagnostic institutions. To contribute to available strategies and expand access to differential diagnosis, we describe an end-point multiplex RT-PCR targeting SARS-CoV-2, IAV and IBV with simultaneous endogenous control amplification. Initially, we looked for well-established primers sets for SARS-CoV-2, IAV, IBV and RNAse P whose amplicons could be distinguished on agarose gel. The multiplex assay was then standardized by optimizing the reaction mix and cycle conditions. The limit of detection (LoD) was determined using titrated viruses (for SARS-CoV-2 and IAV) and by dilution from a pool of IBV-positive samples. The diagnostic performance of the multiplex was evaluated by testing samples with different RNAse P and viral loads, previously identified as positive or negative for the target viruses. The amplicons of IAV (146 bp), SARS-CoV-2 (113 bp), IBV (103 bp) and RNAse P (65 bp) were adequately distinguished in our multiplex. The LoD for SARS-CoV-2, IAV and IBV was 0.02 TCID50/ml, 0.07 TCID50/ml and 10-3 from a pool of positive samples, respectively. All samples positive for SARS-CoV-2 (n=70, Ct 17.2-36.9), IAV (n=53, Ct 14-34.9) and IBV (n=12, Ct 23.9-31.9) remained positive in our multiplex assay. RNAse P from negative samples (n=40, Ct 25.2-30.2) was also amplified in the multiplex. Overall, our assay is a timely and alternative tool for detecting SARS-CoV-2 and influenza viruses in laboratories with limited access to supplies/equipment.
Assuntos
COVID-19 , Vírus da Influenza A , Vírus da Influenza B , Reação em Cadeia da Polimerase Multiplex , Ribonuclease P , SARS-CoV-2 , Humanos , Ribonuclease P/genética , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Vírus da Influenza A/isolamento & purificação , Vírus da Influenza A/genética , Vírus da Influenza B/isolamento & purificação , Vírus da Influenza B/genética , COVID-19/diagnóstico , COVID-19/virologia , Reação em Cadeia da Polimerase Multiplex/métodos , Diagnóstico Diferencial , Influenza Humana/diagnóstico , Influenza Humana/virologia , Sensibilidade e Especificidade , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Limite de Detecção , RNA Viral/genética , RNA Viral/análiseRESUMO
Influenza A viruses (IAV) impose significant respiratory disease burdens in both swine and humans worldwide, with frequent human-to-swine transmission driving viral evolution in pigs and highlighting the risk at the animal-human interface. Therefore, a comprehensive One Health approach (interconnection among human, animal, and environmental health) is needed for IAV prevention, control, and response. Animal influenza genomic surveillance remains limited in many Latin American countries, including Colombia. To address this gap, we genetically characterized 170 swine specimens from Colombia (2011-2017). Whole genome sequencing revealed a predominance of pandemic-like H1N1 lineage, with a minority belonging to H3N2 and H1N2 human seasonal-like lineage and H1N1 early classical swine lineages. Significantly, we have identified reassortant and recombinant viruses (H3N2, H1N1) not previously reported in Colombia. This suggests a broad genotypic viral diversity, likely resulting from reassortment between classical endemic viruses and new introductions established in Colombia's swine population (e.g. the 2009 H1N1 pandemic). Our study highlights the importance of a One Health approach in disease control, particularly in an ecosystem where humans are a main source of IAV to swine populations, and emphasizes the need for continued surveillance and enhanced biosecurity measures. The co-circulation of multiple subtypes in regions with high swine density facilitates viral exchange, underscoring the importance of monitoring viral evolution to inform vaccine selection and public health policies locally and globally.
Assuntos
Evolução Molecular , Variação Genética , Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H3N2 , Infecções por Orthomyxoviridae , Filogenia , Doenças dos Suínos , Animais , Suínos , Colômbia/epidemiologia , Infecções por Orthomyxoviridae/virologia , Infecções por Orthomyxoviridae/veterinária , Infecções por Orthomyxoviridae/epidemiologia , Doenças dos Suínos/virologia , Doenças dos Suínos/epidemiologia , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/classificação , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Saúde Única , Humanos , Vírus da Influenza A/genética , Vírus da Influenza A/classificação , Vírus da Influenza A/isolamento & purificação , Sequenciamento Completo do Genoma , Genoma Viral , Monitoramento Epidemiológico , Vírus Reordenados/genética , Vírus Reordenados/classificação , Vírus Reordenados/isolamento & purificação , Vírus da Influenza A Subtipo H1N2/genética , Vírus da Influenza A Subtipo H1N2/isolamento & purificação , Vírus da Influenza A Subtipo H1N2/classificação , Influenza Humana/virologia , Influenza Humana/epidemiologiaRESUMO
Influenza viruses constitute a major threat to human health globally. The viral surface glycoprotein hemagglutinin (HA) is the immunodominant antigen, contains the site for binding to the cellular receptor (RBS), and it is the major target of neutralizing antibody responses post-infection. We developed llama-derived single chain antibody fragments (VHHs) specific for type A influenza virus. Four VHHs were identified and further characterized. VHH D81 bound residues in the proximity of the C-terminal region of HA1 of H1 and H5 subtypes, and showed weak neutralizing activity, whereas VHH B33 bound residues in the proximity of the N-terminal region of the HA's stem domain (HA2) of H1, H5, and H9 subtypes, and showed no neutralizing activity. Of most relevance, VHHs E13 and G41 recognized highly conserved conformational epitopes on the H1 HA's globular domain (HA1) and showed high virus neutralizing activity (ranging between 0.94 to 0.01µM), when tested against several human H1N1 isolates. Additionally, E13 displayed abrogated virus replication of a panel of H1N1 strains spanning over 80 years of antigenic drift and isolated from human, avian, and swine origin. Interestingly, E13 conferred protection in vivo at a dose as low as 0.05 mg/kg. Mice treated with E13 intranasally resulted in undetectable virus challenge loads in the lungs at day 4 post-challenge. The transfer of sterilizing pan-H1 immunity, by a dose in the range of micrograms given intranasally, is of major significance for a monomeric VHH and supports the further development of E13 as an immunotherapeutic agent for the mitigation of influenza infections.
Assuntos
Anticorpos Neutralizantes , Camelídeos Americanos , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Vírus da Influenza A Subtipo H1N1 , Infecções por Orthomyxoviridae , Anticorpos de Domínio Único , Animais , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Anticorpos de Domínio Único/imunologia , Anticorpos Neutralizantes/imunologia , Camundongos , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/virologia , Camelídeos Americanos/imunologia , Anticorpos Antivirais/imunologia , Feminino , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Influenza Humana/virologia , Epitopos/imunologia , Cães , Camundongos Endogâmicos BALB CRESUMO
BACKGROUND: The outbreak of the COVID-19 pandemic has had a profound impact on the circulation of seasonal respiratory viruses. This study aimed to compare the outcomes of SARS-CoV-2 and seasonal viruses in adults hospitalized with severe acute respiratory infection during the COVID-19 pandemic. METHODS: This population-based cohort study included patients aged >18 years hospitalized for severe acute respiratory infection in Brazil between February 2020 and February 2023. The primary outcome was in-hospital mortality. A competing risk analysis was used to account for competing events. RESULTS: In total, 2 159 171 patients were included in the study. SARS-CoV-2 was the predominant virus (98.7%). Among patients testing positive, the cumulative incidence of in-hospital mortality was 33.1% for SARS-CoV-2, 31.5% for adenovirus, 21.0% for respiratory syncytial virus, 18.7% for influenza, and 18.6% for other viruses. SARS-CoV-2 accounted for 99.3% of the deaths. Older age, male sex, comorbidities, hospitalization in the northern region, and oxygen saturation <95% were the common risk factors for death among all viruses. CONCLUSIONS: In this large cohort study, individuals infected with SARS-CoV-2 or adenovirus had the highest risk of mortality. Irrespective of the virus type, older age, male sex, comorbidities, hospitalization in vulnerable regions, and low oxygen saturation were associated with an increased risk of fatality.
Assuntos
COVID-19 , Mortalidade Hospitalar , Hospitalização , SARS-CoV-2 , Humanos , COVID-19/mortalidade , COVID-19/epidemiologia , Brasil/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Hospitalização/estatística & dados numéricos , Idoso , Adulto , Estudos de Coortes , Estações do Ano , Fatores de Risco , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Infecções Respiratórias/mortalidade , Comorbidade , Idoso de 80 Anos ou mais , Adulto Jovem , Influenza Humana/epidemiologia , Influenza Humana/mortalidade , Influenza Humana/virologiaRESUMO
Until 2022, the COVID-19 pandemic caused by the SARS-CoV-2, had profoundly impacted the world. Consequently, Brazil, including the state of Goiás, was also significantly affected. Furthermore, in the second half of 2022, the state of Goiás experienced an unusual rise in influenza cases, despite it being an off-season period for influenza viruses in this region. As SARS-CoV-2 and Influenza infection have similar clinical manifestations, surveillance strategies are crucial for public health. Understanding how SARS-CoV-2 and Influenza viruses co-circulate is important for surveillance and monitoring of these patterns of respiratory infections. In this context, this investigation monitored Influenza A and B cases from symptomatic individuals diagnosed as negative for COVID-19. Between September 2022 and May 2023, among the 779 samples tested, 126 (16.2%) were positive for Influenza A, whereas 93 samples (11.9%) were positive for Influenza B. In this period, the peak Influenza infection cases did not coincide with the peak of SARS-CoV-2 infections, suggesting a seasonal shift in viral circulation patterns.
Assuntos
COVID-19 , Vírus da Influenza A , Vírus da Influenza B , Influenza Humana , SARS-CoV-2 , Estações do Ano , Humanos , Brasil/epidemiologia , Influenza Humana/epidemiologia , Influenza Humana/virologia , Vírus da Influenza B/genética , Vírus da Influenza B/isolamento & purificação , COVID-19/epidemiologia , COVID-19/virologia , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Vírus da Influenza A/isolamento & purificação , Vírus da Influenza A/genética , Vírus da Influenza A/classificaçãoRESUMO
Numerous factors can increase the risk of severe influenza; however, a majority of severe cases occur in previously healthy children. Identification of high-risk children is important for targeted preventive interventions and prompt treatment. The aim of this study was to evaluate MUC5AC as a biomarker for influenza disease severity in children. For this, a prospective cohort study was conducted in 2019. Children hospitalized with acute respiratory infection (ARI) with confirmed positive influenza infection were enrolled. Influenza cases were identified by reverse transcriptase-polymerase chain reaction. Life-threatening disease (LTD) was defined by the need for intensive care and ventilatory support. MUC5AC, epidemiologic, and clinical risk factors were assessed. Three hundred and forty-two patients were hospitalized with ARI, of which 49 (14%) had confirmed influenza infection and 6 (12%) of them developed LTD. MUC5AC levels were higher in those patients with mild disease compared to cases with poorer outcomes. Our results show that the severity of influenza infection in children is significantly associated with low levels of MUC5AC. These findings suggest its potential as a suitable biomarker for predicting disease severity.
Assuntos
Biomarcadores , Influenza Humana , Mucina-5AC , Índice de Gravidade de Doença , Humanos , Influenza Humana/diagnóstico , Influenza Humana/virologia , Masculino , Feminino , Biomarcadores/sangue , Mucina-5AC/metabolismo , Estudos Prospectivos , Pré-Escolar , Lactente , Criança , Fatores de Risco , Hospitalização , Adolescente , Infecções Respiratórias/virologia , Infecções Respiratórias/diagnósticoRESUMO
The most widely used class of antivirals available for Influenza treatment are the neuraminidase inhibitors (NAI) Oseltamivir and Zanamivir. However, amino acid (AA) substitutions in the neuraminidase may cause reduced inhibition or high antiviral resistance. In Mexico, the current state of knowledge about NAI susceptibility is scarce, in this study we report the results of 14 years of Influenza surveillance by phenotypic and genotypic methods. A total of 255 isolates were assessed with the NAI assay, including Influenza A(H1N1)pdm09, A(H3N2) and Influenza B (IBV). Furthermore, 827 sequences contained in the GISAID platform were analyzed in search of relevant mutations.Overall, five isolates showed highly reduced inhibition or reduced inhibition to Oseltamivir, and two showed reduced inhibition to Zanamivir in the NAI assays. Additionally, five A(H1N1)pdm09 sequences from the GISAID possessed AA substitutions associated to reduced inhibition to Oseltamivir and none to Zanamivir. Oseltamivir resistant A(H1N1)pdm09 harbored the H275Y mutation. No genetic mutations were identified in Influenza A(H3N2) and IBV. Overall, these results show that in Mexico the rate of NAI resistance is low (0.6%), but it is essential to continue the Influenza surveillance in order to understand the drug susceptibility of circulating strains.
Assuntos
Antivirais , Farmacorresistência Viral , Vírus da Influenza B , Influenza Humana , Neuraminidase , Oseltamivir , Zanamivir , Farmacorresistência Viral/genética , Antivirais/farmacologia , México/epidemiologia , Humanos , Vírus da Influenza B/efeitos dos fármacos , Vírus da Influenza B/genética , Influenza Humana/virologia , Influenza Humana/tratamento farmacológico , Influenza Humana/epidemiologia , Oseltamivir/farmacologia , Zanamivir/farmacologia , Neuraminidase/genética , Neuraminidase/antagonistas & inibidores , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Mutação , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Vírus da Influenza A Subtipo H3N2/genética , Adulto , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza A/genética , Adolescente , Criança , Substituição de Aminoácidos , Adulto Jovem , Pessoa de Meia-Idade , Feminino , Pré-Escolar , Genótipo , Masculino , Idoso , Testes de Sensibilidade Microbiana , Proteínas Virais/genéticaRESUMO
Clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) viruses have caused large outbreaks within avian populations on five continents, with concurrent spillover into a variety of mammalian species. Mutations associated with mammalian adaptation have been sporadically identified in avian isolates, and more frequently among mammalian isolates following infection. Reports of human infection with A(H5N1) viruses following contact with infected wildlife have been reported on multiple continents, highlighting the need for pandemic risk assessment of these viruses. In this study, the pathogenicity and transmissibility of A/Chile/25945/2023 HPAI A(H5N1) virus, a novel reassortant with four gene segments (PB1, PB2, NP, MP) from North American lineage, isolated from a severe human case in Chile, was evaluated in vitro and using the ferret model. This virus possessed a high capacity to cause fatal disease, characterized by high morbidity and extrapulmonary spread in virus-inoculated ferrets. The virus was capable of transmission to naïve contacts in a direct contact setting, with contact animals similarly exhibiting severe disease, but did not exhibit productive transmission in respiratory droplet or fomite transmission models. Our results indicate that the virus would need to acquire an airborne transmissible phenotype in mammals to potentially cause a pandemic. Nonetheless, this work warrants continuous monitoring of mammalian adaptations in avian viruses, especially in strains isolated from humans, to aid pandemic preparedness efforts.
Assuntos
Furões , Virus da Influenza A Subtipo H5N1 , Influenza Humana , Infecções por Orthomyxoviridae , Animais , Furões/virologia , Humanos , Chile , Influenza Humana/virologia , Influenza Humana/transmissão , Infecções por Orthomyxoviridae/virologia , Infecções por Orthomyxoviridae/transmissão , Infecções por Orthomyxoviridae/veterinária , Virus da Influenza A Subtipo H5N1/genética , Virus da Influenza A Subtipo H5N1/patogenicidade , Virus da Influenza A Subtipo H5N1/isolamento & purificação , Virus da Influenza A Subtipo H5N1/classificação , Virus da Influenza A Subtipo H5N1/fisiologia , Vírus Reordenados/genética , Vírus Reordenados/isolamento & purificação , Vírus Reordenados/patogenicidade , Vírus Reordenados/classificação , Filogenia , Influenza Aviária/virologia , Influenza Aviária/transmissãoRESUMO
The coronavirus disease 2019 (COVID-19) pandemic profoundly disrupted the epidemiology of respiratory viruses, driven primarily by widespread non-pharmaceutical interventions (NPIs) such as social distancing and masking. This eight-year retrospective study examines the seasonal patterns and incidence of influenza virus, respiratory syncytial virus (RSV), and other respiratory viruses across pre-pandemic, pandemic, and post-pandemic phases in Jalisco, Mexico. Weekly case counts were analyzed using an interrupted time series (ITS) model, segmenting the timeline into these three distinct phases. Significant reductions in respiratory virus circulation were observed during the pandemic, followed by atypical resurgences as NPIs were relaxed. Influenza displayed alternating subtype dominance, with influenza A H3 prevailing in 2022, influenza B surging in 2023, and influenza A H1N1 increasing thereafter, reflecting potential immunity gaps. RSV activity was marked by earlier onset and higher intensity post-pandemic. Other viruses, including human rhinovirus/enterovirus (HRV/HEV) and parainfluenza virus (HPIV), showed altered dynamics, with some failing to return to pre-pandemic seasonality. These findings underscore the need for adaptive surveillance systems and vaccination strategies to address evolving viral patterns. Future research should investigate the long-term public health implications, focusing on vaccination, clinical outcomes, and healthcare preparedness.
Assuntos
COVID-19 , Influenza Humana , Infecções por Vírus Respiratório Sincicial , Estações do Ano , Humanos , México/epidemiologia , Estudos Retrospectivos , COVID-19/epidemiologia , COVID-19/virologia , COVID-19/prevenção & controle , Influenza Humana/epidemiologia , Influenza Humana/virologia , Influenza Humana/prevenção & controle , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/virologia , SARS-CoV-2/imunologia , Vírus Sincicial Respiratório Humano , Pandemias , Incidência , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Vírus da Influenza A Subtipo H1N1RESUMO
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in young children. During the COVID-19 pandemic, a significant change in the epidemiology of RSV and other viruses occurred worldwide, leading to a reduction in the circulation of these infectious agents. After the pandemic, the resurgence of seasonal respiratory viruses occurred, but some features of these infections contrast to those registered prior to the pandemic. In the present work, we studied 390 children <5 years old admitted to the hospital to determine the contribution of RSV, SARS-CoV-2, human metapneumovirus (hMPV), and influenza viruses to acute respiratory infections during the 2023-2024 winter season in Mexico. RSV was the most frequently detected virus (n = 160, 41%), followed by SARS-CoV-2 (n = 69, 17.7%), hMPV (n = 68, 17.4%), and influenza A or B (n = 40, 10.26%). Fourteen patients required admission to the intensive care unit, including six (42.8%) with RSV infection. Four children died (1%). At least one of the four viruses was detected in all deceased patients: SARS-CoV-2 in one; SARS-CoV-2 and hMPV in two; and RSV, influenza A, and SARS-CoV-2 in one. The high impact of RSV and other respiratory viruses indicates the need to implement specific preventive programs to reduce the morbidity and mortality associated with them.
Assuntos
COVID-19 , Hospitalização , Metapneumovirus , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , SARS-CoV-2 , Estações do Ano , Humanos , México/epidemiologia , Lactente , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/virologia , Feminino , Masculino , Pré-Escolar , Vírus Sincicial Respiratório Humano/isolamento & purificação , COVID-19/epidemiologia , COVID-19/mortalidade , COVID-19/virologia , Hospitalização/estatística & dados numéricos , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Metapneumovirus/isolamento & purificação , Influenza Humana/epidemiologia , Influenza Humana/virologia , Recém-NascidoRESUMO
Several factors are associated with the severity of the respiratory disease caused by the influenza virus. Although viral factors are one of the most studied, in recent years the role of the microbiota and co-infections in severe and fatal outcomes has been recognized. However, most of the work has focused on the microbiota of the upper respiratory tract (URT), hindering potential insights from the lower respiratory tract (LRT) that may help to understand the role of the microbiota in Influenza disease. In this work, we characterized the microbiota of the LRT of patients with Influenza A using 16S rRNA sequencing. We tested if patients with different outcomes (deceased/recovered) and use of antibiotics differ in their microbial community composition. We found important differences in the diversity and composition of the microbiota between deceased and recovered patients. In particular, we detected a high abundance of opportunistic pathogens such as Granulicatella, in patients either deceased or with antibiotic treatment. Also, we found antibiotic treatment correlated with lower diversity of microbial communities and with lower probability of survival in Influenza A patients. Altogether, the loss of microbial diversity could generate a disequilibrium in the community, potentially compromising the immune response increasing viral infectivity, promoting the growth of potentially pathogenic bacteria that, together with altered biochemical parameters, can be leading to severe forms of the disease. Overall, the present study gives one of the first characterizations of the diversity and composition of microbial communities in the LRT of Influenza patients and its relationship with clinical variables and disease severity.
Assuntos
Influenza Humana , Microbiota , Síndrome do Desconforto Respiratório , Sistema Respiratório , Humanos , Influenza Humana/genética , Influenza Humana/microbiologia , Influenza Humana/virologia , Microbiota/genética , Nariz , Sistema Respiratório/microbiologia , RNA Ribossômico 16S/genéticaRESUMO
Understanding the diversity and circulation dynamics of seasonal influenza viruses is key to public health decision-making. The limited genetic information of pre-pandemic seasonal IAVs in Chile has made it difficult to accurately reconstruct the phylogenetic relationships of these viruses within the country. The objective of this study was to determine the genetic diversity of pre-pandemic human seasonal IAVs in Chile. We sequenced the complete genome of 42 historic IAV obtained between 1996 and 2007. The phylogeny was determined using HA sequences and complemented using other segments. Time-scale phylogenetic analyses revealed that the diversity of pre-pandemic human seasonal IAVs in Chile was influenced by continuous introductions of new A/H1N1 and A/H3N2 lineages and constant viral exchange between Chile and other countries every year. These results provide important knowledge about genetic diversity and evolutionary patterns of pre-pandemic human seasonal IAVs in Chile, which can help design optimal surveillance systems and prevention strategies. However, future studies with current sequences should be conducted.
Assuntos
Evolução Biológica , Variação Genética , Genoma Viral , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H3N2/genética , Influenza Humana/epidemiologia , Pandemias/estatística & dados numéricos , Chile/epidemiologia , Genótipo , Humanos , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Influenza Humana/virologia , Filogenia , Estações do AnoRESUMO
Influenza vaccination coverage in countries of Latin America is low among priority risk groups, ranging from 5 to 75% among older people. This paper aims to describe and analyze the determinants of influenza vaccination hesitancy through the lens of the 3C model of confidence, complacency and convenience among middle-class, urban risk group populations in Brazil, Chile, Paraguay, Peru, Uruguay, countries in South America with contrasting vaccination coverage. Focus groups were conducted among four risk groups: pregnant women, mothers of children aged <6 years, adults with risk factors, and adults aged ≥60 years in samples of urban residents. Adults with risk factors expressed the most detailed perceptions about confidence in the vaccine. A wide range of perceptions regarding complacency were expressed across risk groups and countries, with pregnant women and mothers showing greater concerns while convenience had a narrower and generally more positive range of perceptions. Participants from Chile and Paraguay expressed the most contrasts regarding confidence and complacency. Information and communication strategies need to be tailored for risk groups while confidence and complacency should be addressed in synergy.