RESUMEN

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.

Asunto(s)

COVID-19 , Genoma Viral , Gripe Humana , Filogenia , SARS-CoV-2 , Humanos , Brasil/epidemiología , COVID-19/epidemiología , COVID-19/virología , SARS-CoV-2/genética , SARS-CoV-2/clasificación , SARS-CoV-2/aislamiento & purificación , Gripe Humana/epidemiología , Gripe Humana/virología , Persona de Mediana Edad , Adulto , Femenino , Genoma Viral/genética , Masculino , Adulto Joven , Anciano , Adolescente , Brotes de Enfermedades , Secuenciación Completa del Genoma , Niño , Preescolar , Lactante , Coinfección/epidemiología , Coinfección/virología , Secuenciación de Nucleótidos de Alto Rendimiento , Anciano de 80 o más Años , Genómica

RESUMEN

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.

Asunto(s)

COVID-19 , Virus de la Influenza A , Virus de la Influenza B , Reacción en Cadena de la Polimerasa Multiplex , Ribonucleasa P , SARS-CoV-2 , Humanos , Ribonucleasa P/genética , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Virus de la Influenza A/aislamiento & purificación , Virus de la Influenza A/genética , Virus de la Influenza B/aislamiento & purificación , Virus de la Influenza B/genética , COVID-19/diagnóstico , COVID-19/virología , Reacción en Cadena de la Polimerasa Multiplex/métodos , Diagnóstico Diferencial , Gripe Humana/diagnóstico , Gripe Humana/virología , Sensibilidad y Especificidad , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Límite de Detección , ARN Viral/genética , ARN Viral/análisis

RESUMEN

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.

Asunto(s)

Evolución Molecular , Variación Genética , Subtipo H1N1 del Virus de la Influenza A , Subtipo H3N2 del Virus de la Influenza A , Infecciones por Orthomyxoviridae , Filogenia , Enfermedades de los Porcinos , Animales , Porcinos , Colombia/epidemiología , Infecciones por Orthomyxoviridae/virología , Infecciones por Orthomyxoviridae/veterinaria , Infecciones por Orthomyxoviridae/epidemiología , Enfermedades de los Porcinos/virología , Enfermedades de los Porcinos/epidemiología , Subtipo H3N2 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/clasificación , Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificación , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/clasificación , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Salud Única , Humanos , Virus de la Influenza A/genética , Virus de la Influenza A/clasificación , Virus de la Influenza A/aislamiento & purificación , Secuenciación Completa del Genoma , Genoma Viral , Monitoreo Epidemiológico , Virus Reordenados/genética , Virus Reordenados/clasificación , Virus Reordenados/aislamiento & purificación , Subtipo H1N2 del Virus de la Influenza A/genética , Subtipo H1N2 del Virus de la Influenza A/aislamiento & purificación , Subtipo H1N2 del Virus de la Influenza A/clasificación , Gripe Humana/virología , Gripe Humana/epidemiología

RESUMEN

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.

Asunto(s)

Anticuerpos Neutralizantes , Camélidos del Nuevo Mundo , Glicoproteínas Hemaglutininas del Virus de la Influenza , Subtipo H1N1 del Virus de la Influenza A , Infecciones por Orthomyxoviridae , Anticuerpos de Dominio Único , Animales , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Humanos , Subtipo H1N1 del Virus de la Influenza A/inmunología , Anticuerpos de Dominio Único/inmunología , Anticuerpos Neutralizantes/inmunología , Ratones , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/prevención & control , Infecciones por Orthomyxoviridae/virología , Camélidos del Nuevo Mundo/inmunología , Anticuerpos Antivirales/inmunología , Femenino , Gripe Humana/inmunología , Gripe Humana/prevención & control , Gripe Humana/virología , Epítopos/inmunología , Perros , Ratones Endogámicos BALB C

RESUMEN

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.

Asunto(s)

Antivirales , Farmacorresistencia Viral , Virus de la Influenza B , Gripe Humana , Neuraminidasa , Oseltamivir , Zanamivir , Farmacorresistencia Viral/genética , Antivirales/farmacología , México/epidemiología , Humanos , Virus de la Influenza B/efectos de los fármacos , Virus de la Influenza B/genética , Gripe Humana/virología , Gripe Humana/tratamiento farmacológico , Gripe Humana/epidemiología , Oseltamivir/farmacología , Zanamivir/farmacología , Neuraminidasa/genética , Neuraminidasa/antagonistas & inhibidores , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Mutación , Subtipo H3N2 del Virus de la Influenza A/efectos de los fármacos , Subtipo H3N2 del Virus de la Influenza A/genética , Adulto , Virus de la Influenza A/efectos de los fármacos , Virus de la Influenza A/genética , Adolescente , Niño , Sustitución de Aminoácidos , Adulto Joven , Persona de Mediana Edad , Femenino , Preescolar , Genotipo , Masculino , Anciano , Pruebas de Sensibilidad Microbiana , Proteínas Virales/genética

RESUMEN

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.

Asunto(s)

COVID-19 , Virus de la Influenza A , Virus de la Influenza B , Gripe Humana , SARS-CoV-2 , Estaciones del Año , Humanos , Brasil/epidemiología , Gripe Humana/epidemiología , Gripe Humana/virología , Virus de la Influenza B/genética , Virus de la Influenza B/aislamiento & purificación , COVID-19/epidemiología , COVID-19/virología , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Virus de la Influenza A/aislamiento & purificación , Virus de la Influenza A/genética , Virus de la Influenza A/clasificación

RESUMEN

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.

Asunto(s)

Biomarcadores , Gripe Humana , Mucina 5AC , Índice de Severidad de la Enfermedad , Humanos , Gripe Humana/diagnóstico , Gripe Humana/virología , Masculino , Femenino , Biomarcadores/sangre , Mucina 5AC/metabolismo , Estudios Prospectivos , Preescolar , Lactante , Niño , Factores de Riesgo , Hospitalización , Adolescente , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/diagnóstico

RESUMEN

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.

Asunto(s)

COVID-19 , Mortalidad Hospitalaria , Hospitalización , SARS-CoV-2 , Humanos , COVID-19/mortalidad , COVID-19/epidemiología , Brasil/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Hospitalización/estadística & datos numéricos , Anciano , Adulto , Estudios de Cohortes , Estaciones del Año , Factores de Riesgo , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/mortalidad , Comorbilidad , Anciano de 80 o más Años , Adulto Joven , Gripe Humana/epidemiología , Gripe Humana/mortalidad , Gripe Humana/virología

RESUMEN

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.

Asunto(s)

Hurones , Subtipo H5N1 del Virus de la Influenza A , Gripe Humana , Infecciones por Orthomyxoviridae , Animales , Hurones/virología , Humanos , Chile , Gripe Humana/virología , Gripe Humana/transmisión , Infecciones por Orthomyxoviridae/virología , Infecciones por Orthomyxoviridae/transmisión , Infecciones por Orthomyxoviridae/veterinaria , Subtipo H5N1 del Virus de la Influenza A/genética , Subtipo H5N1 del Virus de la Influenza A/patogenicidad , Subtipo H5N1 del Virus de la Influenza A/aislamiento & purificación , Subtipo H5N1 del Virus de la Influenza A/clasificación , Subtipo H5N1 del Virus de la Influenza A/fisiología , Virus Reordenados/genética , Virus Reordenados/aislamiento & purificación , Virus Reordenados/patogenicidad , Virus Reordenados/clasificación , Filogenia , Gripe Aviar/virología , Gripe Aviar/transmisión

RESUMEN

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.

Asunto(s)

Gripe Humana , Microbiota , Síndrome de Dificultad Respiratoria , Sistema Respiratorio , Humanos , Gripe Humana/genética , Gripe Humana/microbiología , Gripe Humana/virología , Microbiota/genética , Nariz , Sistema Respiratorio/microbiología , ARN Ribosómico 16S/genética

RESUMEN

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.

Asunto(s)

Evolución Biológica , Variación Genética , Genoma Viral , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/genética , Gripe Humana/epidemiología , Pandemias/estadística & datos numéricos , Chile/epidemiología , Genotipo , Humanos , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/virología , Filogenia , Estaciones del Año

RESUMEN

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.

Asunto(s)

Conocimientos, Actitudes y Práctica en Salud , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/prevención & control , Aceptación de la Atención de Salud , Mujeres Embarazadas/psicología , Cobertura de Vacunación/estadística & datos numéricos , Vacunación/psicología , Adulto , Anciano , Niño , Comunicación , Femenino , Humanos , Gripe Humana/epidemiología , Gripe Humana/virología , Masculino , Persona de Mediana Edad , Madres/psicología , Orthomyxoviridae , Embarazo , Factores de Riesgo , América del Sur/epidemiología , Población Urbana

RESUMEN

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

Asunto(s)

Infecciones por Adenovirus Humanos/epidemiología , Coinfección/epidemiología , Gripe Humana/epidemiología , Infecciones por Paramyxoviridae/epidemiología , Infecciones por Virus Sincitial Respiratorio/epidemiología , Adenoviridae/aislamiento & purificación , Infecciones por Adenovirus Humanos/diagnóstico , Infecciones por Adenovirus Humanos/virología , Brasil/epidemiología , Preescolar , Coinfección/diagnóstico , Coinfección/virología , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Incidencia , Lactante , Recién Nacido , Gripe Humana/diagnóstico , Gripe Humana/virología , Alphainfluenzavirus/aislamiento & purificación , Betainfluenzavirus/aislamiento & purificación , Masculino , Metapneumovirus/aislamiento & purificación , Infecciones por Paramyxoviridae/diagnóstico , Infecciones por Paramyxoviridae/virología , Infecciones por Virus Sincitial Respiratorio/diagnóstico , Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitiales Respiratorios/aislamiento & purificación , Respirovirus/aislamiento & purificación , Estudios Retrospectivos , Índice de Severidad de la Enfermedad

RESUMEN

BACKGROUND: Respiratory Syncytial Virus (RSV) is the main cause of pediatric morbidity and mortality. The complex evolution of RSV creates a need for worldwide surveillance, which may assist in the understanding of multiple viral aspects. OBJECTIVES: This study aimed to investigate RSV features under the Brazilian Influenza Surveillance Program, evaluating the role of viral load and genetic diversity in disease severity and the influence of climatic factors in viral seasonality. METHODOLOGY: We have investigated the prevalence of RSV in children up to 3 years of age with severe acute respiratory infection (SARI) in the state of Espirito Santo (ES), Brazil, from 2016 to 2018. RT-qPCR allowed for viral detection and viral load quantification, to evaluate association with clinical features and mapping of local viral seasonality. Gene G sequencing and phylogenetic reconstruction demonstrated local genetic diversity. RESULTS: Of 632 evaluated cases, 56% were caused by RSV, with both subtypes A and B co-circulating throughout the years. A discrete inverse association between average temperature and viral circulation was observed. No correlation between viral load and disease severity was observed, but children infected with RSV-A presented a higher clinical severity score (CSS), stayed longer in the hospital, and required intensive care, and ventilatory support more frequently than those infected by RSV-B. Regarding RSV diversity, some local genetic groups were observed within the main genotypes circulation RSV-A ON1 and RSV-B BA, with strains showing modifications in the G gene amino acid chain. CONCLUSION: Local RSV studies using the Brazilian Influenza Surveillance Program are relevant as they can bring useful information to the global RSV surveillance. Understanding seasonality, virulence, and genetic diversity can aid in the development and suitability of antiviral drugs, vaccines, and assist in the administration of prophylactic strategies.

Asunto(s)

Epidemiología Molecular/métodos , ARN Viral/genética , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitial Respiratorio Humano/aislamiento & purificación , Brasil/epidemiología , Monitoreo Epidemiológico , Femenino , Genotipo , Humanos , Lactante , Virus de la Influenza A/aislamiento & purificación , Virus de la Influenza A/patogenicidad , Gripe Humana/epidemiología , Gripe Humana/patología , Gripe Humana/virología , Masculino , Filogenia , Infecciones por Virus Sincitial Respiratorio/patología , Virus Sincitial Respiratorio Humano/genética , Virus Sincitial Respiratorio Humano/patogenicidad , Estaciones del Año , Carga Viral/métodos , Virulencia

RESUMEN

The differentiation between influenza and coronavirus disease 2019 (COVID-19) could constitute a diagnostic challenge during the ongoing winter owing to their clinical similitude. Thus, novel biomarkers are required to enable making this distinction. Here, we evaluated whether the surfactant protein D (SP-D), a collectin produced at the alveolar epithelium with known immune properties, was useful to differentiate pandemic influenza A(H1N1) from COVID-19 in critically ill patients. Our results revealed high serum SP-D levels in patients with severe pandemic influenza but not those with COVID-19. This finding was validated in a separate cohort of mechanically ventilated patients with COVID-19 who also showed low plasma SP-D levels. However, plasma SP-D levels did not distinguish seasonal influenza from COVID-19 in mild-to-moderate disease. Finally, we found that high serum SP-D levels were associated with death and renal failure among severe pandemic influenza cases. Thus, our studies have identified SP-D as a unique biomarker expressed during severe pandemic influenza but not COVID-19.

Asunto(s)

COVID-19/genética , Expresión Génica , Interacciones Huésped-Patógeno/genética , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/genética , Proteína D Asociada a Surfactante Pulmonar/genética , SARS-CoV-2 , Adulto , Anciano , Biomarcadores , COVID-19/sangre , COVID-19/diagnóstico , COVID-19/virología , Coinfección , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Gripe Humana/diagnóstico , Gripe Humana/virología , Masculino , Persona de Mediana Edad , Pronóstico , Proteína D Asociada a Surfactante Pulmonar/sangre , Índice de Severidad de la Enfermedad , Evaluación de Síntomas , Adulto Joven

RESUMEN

OBJECTIVE: We aimed to evaluate the clinical and epidemiological behavior of influenza type A versus type B and analyze if there was any correlation or differences between the characteristics of both groups. METHODS: An observational, retrospective, descriptive, and population-based study based of children who were hospitalized at the only national pediatric hospital of Costa Rica from January 1, 2010 to December 31, 2018 and had a confirmed influenza virus infection. RESULTS: 336 patients were analyzed. Mean age was 35,6 ± 36,7 months (3,0 ± 3,1 years). The only significant variables at 25% in relation to influenza type A or B virus were: sex, month of diagnosis, fever, vomiting, cough, use of antibiotics and admission to the PICU. The hospitalization rate at our hospital increased between the months of October to December, with a higher percentage of cases in November and December, which reveals that the "real peak" in our population begins between 3 to 4 months after the end of the vaccination campaign. Patients with influenza A virus had a 2.5 times greater risk of being admitted to the PICU. Mortality rate was 0.6% and 0% among influenza A and B children, respectively. CONCLUSIONS: Variables in which a causality was found with type A or B virus were: admission to the PICU, month of diagnosis, and cough. However, influenza B clinical behavior continues to be unpredictable.

Asunto(s)

Virus de la Influenza A/aislamiento & purificación , Virus de la Influenza B/aislamiento & purificación , Gripe Humana/epidemiología , Niño , Preescolar , Costa Rica/epidemiología , Femenino , Hospitalización/estadística & datos numéricos , Hospitales Pediátricos/estadística & datos numéricos , Humanos , Lactante , Recién Nacido , Vacunas contra la Influenza/uso terapéutico , Gripe Humana/mortalidad , Gripe Humana/prevención & control , Gripe Humana/virología , Unidades de Cuidado Intensivo Pediátrico/estadística & datos numéricos , Masculino , Estudios Retrospectivos

RESUMEN

Influenza A virus (IAV) is the most common infectious agent in humans, and infects approximately 10-20% of the world's population, resulting in 3-5 million hospitalizations per year. A scientific literature search was performed using the PubMed database and the Medical Subject Headings (MeSH) "Influenza A H1N1" and "Genetic susceptibility". Due to the amount of information and evidence about genetic susceptibility generated from the studies carried out in the last influenza A H1N1 pandemic, studies published between January 2009 to May 2020 were considered; 119 papers were found. Several pathways are involved in the host defense against IAV infection (innate immune response, pro-inflammatory cytokines, chemokines, complement activation, and HLA molecules participating in viral antigen presentation). On the other hand, single nucleotide polymorphisms (SNPs) are a type of variation involving the change of a single base pair that can mean that encoded proteins do not carry out their functions properly, allowing higher viral replication and abnormal host response to infection, such as a cytokine storm. Some of the most studied SNPs associated with IAV infection genetic susceptibility are located in the FCGR2A, C1QBP, CD55, and RPAIN genes, affecting host immune responses through abnormal complement activation. Also, SNPs in IFITM3 (which participates in endosomes and lysosomes fusion) represent some of the most critical polymorphisms associated with IAV infection, suggesting an ineffective virus clearance. Regarding inflammatory response genes, single nucleotide variants in IL1B, TNF, LTA IL17A, IL8, IL6, IRAK2, PIK3CG, and HLA complex are associated with altered phenotype in pro-inflammatory molecules, participating in IAV infection and the severest form of the disease.

Asunto(s)

Predisposición Genética a la Enfermedad , Subtipo H1N1 del Virus de la Influenza A/fisiología , Gripe Humana/genética , Animales , Humanos , Inmunidad Innata , Subtipo H1N1 del Virus de la Influenza A/genética , Gripe Humana/inmunología , Gripe Humana/virología , Replicación Viral

RESUMEN

In March 2013 it was reported by the World Health Organization (WHO) the first cases of human infections with avian influenza virus A (H7N9). From 2013 to December 2019, 1568 cases have been reported with 616 deaths. H7N9 infection has been associated with high morbidity and mortality rates, and vaccination is currently the most effective way to prevent infections and consequently flu-related severe illness. Developing and producing vaccines against pandemic influenza viruses is the main strategy for a response to a possible pandemic. This study aims to present the production of three industrial lots under current Good Manufacturing Practices (cGMP) of the active antigen used to produce the pandemic influenza vaccine candidate against A(H7N9). These batches were characterized and evaluated for quality standards and tested for immunogenicity in mice. The average yield was 173.50 ± 7.88 µg/mL of hemagglutinin and all the preparations met all the required specifications. The formulated H7N9 vaccine is poorly immunogenic and needs to be adjuvanted with an oil in water emulsion adjuvant (IB160) to achieve a best immune response, in a prime and in a boost scheme. These data are important for initial production planning and preparedness in the case of a H7N9 pandemic.

Asunto(s)

Subtipo H7N9 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/biosíntesis , Gripe Humana/prevención & control , Pandemias/prevención & control , Animales , Antígenos Virales/biosíntesis , Antígenos Virales/inmunología , Composición de Medicamentos/métodos , Composición de Medicamentos/estadística & datos numéricos , Industria Farmacéutica/normas , Femenino , Humanos , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/aislamiento & purificación , Gripe Humana/inmunología , Gripe Humana/virología , Ratones , Ratones Endogámicos BALB C , Vacunas de Productos Inactivados/biosíntesis , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/aislamiento & purificación

RESUMEN

Influenza B virus (IBV) causes respiratory tract infections with mild, moderate, or life-threatening symptoms. This study describes the epidemiology of IBV infection in Rio Grande do Sul (RS), Brazil, over 17 years. Nasopharyngeal samples were collected from outpatients presenting acute respiratory illness (ARI) between 2003 and 2019, and from inpatients with severe acute respiratory infection (SARI) from 2009 to 2019. IBV was detected by immunofluorescence assay or quantitative real-time polymerase chain reaction; demographic and clinical data were analyzed. In total, 48,656 cases of respiratory infection were analyzed, of which 20.45% were ARI, and 79.46% were SARI. Respiratory viruses accounted for 22.59% and 37.47% of the cases of ARI and SARI, respectively. Considering respiratory viral infections, 17.10% of ARI and 3.06% of SARI were associated with IBV. IBV circulated year-round in RS, with an increase in autumn and winter, peaking in July (p = .005). IBV infection showed an association with age, and most outpatients positive for IBV were between 10 and 49 years old, whereas IBV infection in SARI affected mainly individuals ≤ 1 year or ≥ 60 years old. No significant association was found between sex and IBV infection. Coryza, sore throat, and myalgia were associated with ARI (p < .001). Moreover, 3.18% of the deaths associated with respiratory virus infection were positive for IBV; notably, cardiopathy (p < .001), metabolic disease (p < .001), and smoking (p = .003) were associated to fatality in IBV infection. IBV is an important cause of severe respiratory infections, and the fatality risk is high in individuals with cardiopathy and metabolic diseases.

Asunto(s)

Monitoreo Epidemiológico , Virus de la Influenza B/patogenicidad , Gripe Humana/epidemiología , Nasofaringe/virología , Infecciones del Sistema Respiratorio/virología , Adolescente , Adulto , Brasil/epidemiología , Niño , Preescolar , Femenino , Humanos , Lactante , Gripe Humana/complicaciones , Gripe Humana/diagnóstico , Gripe Humana/virología , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios/estadística & datos numéricos , Infecciones del Sistema Respiratorio/diagnóstico , Estaciones del Año , Índice de Severidad de la Enfermedad , Adulto Joven

RESUMEN

Influenza is one of the most relevant respiratory viruses to human health causing annual epidemics, and recurrent pandemics. Influenza disease is principally associated with inappropriate activation of the immune response. Chemokine receptor 5 (CCR5) and its cognate chemokines CCL3, CCL4 and CCL5 are rapidly induced upon influenza infection, contributing to leukocyte recruitment into the airways and a consequent effective antiviral response. Here we discuss the existing evidence for CCR5 role in the host immune responses to influenza virus. Complete absence of CCR5 in mice revealed the receptor's role in coping with influenza via the recruitment of early memory CD8+ T cells, B cell activation and later recruitment of activated CD4+ T cells. Moreover, CCR5 contributes to inflammatory resolution by enhancing alveolar macrophages survival and reprogramming macrophages to pro-resolving phenotypes. In contrast, CCR5 activation is associated with excessive recruitment of neutrophils, inflammatory monocytes, and NK cells in models of severe influenza pneumonia. The available data suggests that, while CCL5 can play a protective role in influenza infection, CCL3 may contribute to an overwhelming inflammatory process that can harm the lung tissue. In humans, the gene encoding CCR5 might contain a 32-base pair deletion, resulting in a truncated protein. While discordant data in literature regarding this CCR5 mutation and influenza severity, the association of CCR5delta32 and HIV resistance fostered the development of different CCR5 inhibitors, now being tested in lung inflammation therapy. The potential use of CCR5 inhibitors to modulate the inflammatory response in severe human influenza infections is to be addressed.

Asunto(s)

Interacciones Huésped-Patógeno , Virus de la Influenza A , Gripe Humana/metabolismo , Gripe Humana/virología , Receptores CCR5/metabolismo , Animales , Biomarcadores , Susceptibilidad a Enfermedades , Interacciones Huésped-Patógeno/genética , Interacciones Huésped-Patógeno/inmunología , Humanos , Virus de la Influenza A/inmunología , Gripe Humana/inmunología , Gripe Humana/terapia , Mutación , Fenotipo , Receptores CCR5/genética , Índice de Severidad de la Enfermedad