Therapeutic effect of Yinhuapinggan granules mediated through the intestinal flora in mice infected with the H1N1 influenza virus.

Objective: In this study, we examined the therapeutic effects of Yinhuapinggan granules (YHPGs) in influenza-infected mice. We also examined how YHPGs affect the composition of the intestinal flora and associated metabolites. Methods: We used the nasal drip method to administer the influenza A virus (IAV) H1N1 to ICR mice. Following successful model construction, the mice were injected with 0.9% sterile saline and low (5.5 g/kg), medium (11 g/kg), and high (22 g/kg) doses of YHPGs. The pathological changes in the lungs and intestines were evaluated by gavage for 5 consecutive days. Detection of sIgA, IL-6, TNF-α, INF-γ, and TGF-ß cytokine levels in serum by enzyme-linked immunosorbent assay. Real-time fluorescence quantitative polymerase chain reaction and Western blot were used to measure the mRNA and protein expression of the tight junction proteins claudin-1, occludin, and zonula occludens-1 (ZO-1) in the colon. To assess the influence of YHPGs on the intestinal microbiota, feces were obtained from the mice for 16s rRNA sequencing, and short-chain fatty acids (SCFAs) were measured in the feces. Results: By reducing the production of pro-inflammatory cytokines and increasing the relative expression of claudin-1, occludin, and ZO-1 in colon tissues, YHPGs had a protective effect in tissues from the lungs and colon. When YHPGs were administered to mice with IAV infection, the relative abundance of Lactobacillus, Coprobacillus, Akkermansia, Prevotella, Oscillospira, and Ruminococcus increased, whereas the relative abundance of Desulfovibrio decreased. Conclusion: The therapeutic mechanism of YHPGs against IAV infection in mice may be underpinned by modulation of the structural composition of colonic bacteria and regulation of SCFA production.

Caracterización demográfica y clínica de pacientes críticos con neumonía por influenza A H1N1 / Demographic and clinical characterization of critically ill patients with influenza A H1N1 pneumonia

INTRODUCCIÓN. La epidemia de influenza y sus complicaciones profundizaron el estudio de las neumonías virales en cuidados intensivos. En nuestro país hay pocos datos sobre este tema. OBJETIVOS. Realizar una caracterización demográfica y clínica de pacientes críticos con neumonía por Influenza A H1N1 en un hospital de tercer nivel de complejidad. MATERIALES Y MÉTODOS. Estudio observacional, analítico, retrospectivo, con análisis univariante y multivariante. Población de 293 y muestra de 44 datos de historias clínicas electrónicas de pacientes diagnosticados con A H1N1 ingresados a la Unidad de cuidados intensivos del Hospital de Especialidades Carlos Andrade Marín en el período enero 2016 a diciembre de 2018. Como criterios de inclusión se consideró a todos los pacientes adultos mayores de 18 años que ingresaron a la UCI, con el diagnóstico de neumonía comunitaria grave con confirmación por reacción de cadena de polimerasa en tiempo real para influenza A H1N1 en hisopado nasal o aspirado traqueal. Se excluyó a pacientes embarazadas con diagnóstico de influenza A H1N1, pacientes con más de 48 horas de ingreso hospitalario previo a su ingreso a UCI, pacientes con datos insuficientes en los registros. Los datos se obtuvieron del sistema AS-400. El análisis estadístico se realizó en el programa Statistical Package for Social Sciences, versión 22. El nivel de significación fue una p<0.05. RESULTADOS. La prevalencia en pacientes críticos de neumonía por influenza A H1N1 durante 2016-2018 fue de 16,72%, la mediana de edad fue de 55 años, 25% masculinos, 34% obesos, 34% con hipertensión arterial. Escala "Acute Physiology and Chronic Health Evaluation II" 23,50, "Simplified Acute Physiologic Score III" 54, "Sepsis related Organ Failure Assessment" 11,50, Lactato deshidrogenasa 99,50, Procalcitonina 0,99; 9 días de ventilación mecánica invasiva, 10,50 días de estancia en la unidad. El 91% presentó shock séptico, 59% lesión renal aguda. El 89% tuvo Síndrome de Distrés Respiratorio del Adultos, 69% fue grave, 87% usó ventilación mecánica, 38,50% corticoides, 36% posición prona, Presión parcial de oxígeno/Fracción inspirada de oxígeno 74, volumen tidal/kilogramo de 7 mililitros, presión plateau de 27,50 centímetros de agua. La mortalidad general en la Unidad de Cuidados Intensivos fue de 38,63% y a los 28 días de 63,60%, en shock séptico fue 42,50% y en Síndrome de Distrés Respiratorio del Adultos del 41,02%. El análisis de regresión logística multivariable identificó como factores independientes asociados a mortalidad el incremento de Lactato deshidrogenasa (OR 2,69, 9% IC 1,090-6,642) y Procalcitonina (OR 2,51, IC 1,005-6,272). CONCLUSIONES. Las características, frecuencia y mortalidad de este grupo de pacientes críticos con neumonía por influenza A H1N1 son similares a lo reportado en la literatura mundial.

INTRODUCTION. The influenza epidemic and its complications deepened the study of viral pneumonias in intensive care. In our country there is little data on this subject. OBJECTIVES. To perform a demographic and clinical characterization of critical patients with pneumonia due to pneumonia due to Influenza A H1N1 in a third level hospital. MATERIALS AND METHODS. Observational, analytical, retrospective study, with univariate and multivariate analysis. We compared the groups of dead patients and survivors. The significance level was p<0,05. RESULTS. The prevalence in critically ill patients of influenza A H1N1 pneumonia during 2016-2018 was 16,72%, 44 cases were collected, median age 55 years, 25% male, 34% obese, 34% with arterial hypertension. APACHE II 23,50, SAPS III 54, SOFA 11,50, LDH 99,50, PCT 0,99, 9 days of invasive mechanical ventilation, 10,50 days of unit stay. 91% presented septic shock, 59% with acute kidney injury 89% had ARDS, 69% were severe, 87% used mechanical ventilation, 38,50% corticosteroids, 36% prone position, PaO2/FiO2 74, tidal volume/kg of 7 ml, plateau pressure of 27,50 cmH2O. Overall mortality in the ICU was 38,63% and at 28 days was 63,60%, in septic shock it was 42,50% and in Adult Respiratory Distress Syndrome it was 42,50%. was 42,50% and 41,02% in Adult Respiratory Distress Syndrome. The ultivariate logistic regression analysis identified as independent factors associated with mortality, the increase in LDH (OR 2,69, 9% CI 1,090-6,642) and PCT (OR 2,51, CI 1,005-6,272). CONCLUSIONS. The characteristics, frequency and mortality of this group of critical patients with pneumonia due to influenza A H1N1 are similar to those reported in the world literature.

Comparison of clinical characteristics and outcomes between COVID-19 pneumonia and H1N1 influenza.

INTRODUCTION: The COVID-19 pandemic has been likened to the 2009 H1N1 influenza pandemic. We aim to study the similarities and differences between patients hospitalized with COVID-19 and H1N1 influenza in order to provide better care to patients, particularly during the co-circulation of Influenza A Subtype H1N1 and SARS-CoV-2. MATERIAL AND METHODS: A retrospective cohort study was conducted in order to compare clinical characteristics, complications, and outcomes of hospitalized patients with PCR-confirmed H1N1 influenza pneumonia and COVID-19 at a tertiary care center in Karachi, Pakistan. RESULTS: A total of 115 patients hospitalized with COVID-19 were compared with 55 patients with H1N1 Influenza A pneumonia. Median age was similar in both COVID-19 patients (54 years) and in patients with H1N1 influenza (59 years), but there was male predominance in COVID-19 patients (OR = 2.95; 95% CI: 1.12-7.79). Patients with COVID-19 pneumonia were 1.34 (95% CI: 1.14-1.62) times more likely to have a greater duration of illness prior to presentation compared to H1N1 influenza patients. COVID-19 patients were 4.59 times (95% CI: 1.32-15.94) more likely to be admitted to a general ward compared to H1N1 pneumonia patients. Moreover, patients with COVID-19 were 7.62 times (95% CI: 2.42-24.00) more likely to be treated with systemic steroids compared to patients with H1N1 pneumonia. The rate of nosocomial infections as well as mortality was similar in both H1N1 and COVID-19 pneumonia. CONCLUSION: Our study found a male predominance and longer duration of illness in hospitalized patients with COVID-19 compared to H1N1 influenza patients but no difference in outcomes with either infection.

Does airborne pollen influence COVID-19 outbreak?

The fast spread of SARS-CoV-2 presented a worldwide challenge to public health, economy, and educational system, affecting wellbeing of human society. With high transmission rates, there are increasing evidences of COVID-19 spread via bioaerosols from an infected person. The current review was conducted to examine airborne pollen impact on COVID-19 transmission and to identify the major gaps for post-pandemic research. The study used all key terms to identify revenant literature and observation were collated for the current research. Based on existing literature, there is a potential association between pollen bioaerosols and COVID-19. There are few studies focusing the impact of airborne pollen on SARS-CoV-2, which could be useful to advance future research. Allergic rhinitis and asthma patients were found to have pre-modified immune activation, which could help to provide protection against COVID-19. However, does airborne pollen acts as a potent carrier for SARS-CoV-2 transport, dispersal and its proliferation still require multidisciplinary research. Further, a clear conclusion cannot be drawn due to limited evidence and hence more research is needed to show how pollen bioaerosols could affect virus survivals. The small but growing literature review focuses on searching for every possible answer to provide additional security layers to overcome near future corona-like infectious diseases.

Single center analysis of patients with H1N1 vaccine-related narcolepsy and sporadic narcolepsy presenting over the same time period.

STUDY OBJECTIVES: We aimed to describe the clinical features of narcolepsy in patients referred to our sleep center between 2009 and 2016, and to compare these features across age groups and between sporadic vs AS03-adjuvanted H1N1 influenza vaccine-related patients. METHODS: This is a retrospective, consecutive study of adult and pediatric narcolepsy patients in the Republic of Ireland. All participants underwent structured assessments, including polysomnography and the Multiple Sleep Latency Test. Brain magnetic resonance imaging, hypocretin levels, and human leukocyte antigen typing were also carried out on the majority of patients. Patients were compared across age groups as well as etiology. RESULTS: The conditions of 40 (74%) patients were vaccine-related. The median age was 13.5 years and time from symptom onset to diagnosis was 112 weeks. Median time from vaccination to symptom onset was 26 weeks. In children, hypnogogic hallucinations and sleep paralysis were less frequent than in adults (17% vs 67%, P = .018 and 0% vs 75%, P < .0005). Sleep latency determined by the Multiple Sleep Latency Test was shorter in children than adults (median 1.75 vs 4 minutes, P = .011). Patients with vaccine-related and sporadic narcolepsies had typical clinical presentations. Vaccine-related patients had longer polysomnography latency (median 10.5 vs 5 minutes, P = .043), longer stage N2 sleep (209.6 ± 44.6 vs 182.3 ± 34.2 minutes, P = .042), and a trend toward longer total sleep times (P = .09). No differences were noted in relation to Multiple Sleep Latency Test, hypocretin, human leukocyte antigen typing, and magnetic resonance imaging. CONCLUSIONS: Results show that vaccine-related patients greatly outnumbered sporadic patients during the study period and suggest that sporadic and vaccine-related narcolepsy are clinically similar entities.

Nitric oxide and viral infection: Recent developments in antiviral therapies and platforms.

Nitric oxide (NO) is a gasotransmitter of great significance to developing the innate immune response to many bacterial and viral infections, while also modulating vascular physiology. The generation of NO from the upregulation of endogenous nitric oxide synthases serves as an efficacious method for inhibiting viral replication in host defense and warrants investigation for the development of antiviral therapeutics. With increased incidence of global pandemics concerning several respiratory-based viral infections, it is necessary to develop broad therapeutic platforms for inhibiting viral replication and enabling more efficient host clearance, as well as to fabricate new materials for deterring viral transmission from medical devices. Recent developments in creating stabilized NO donor compounds and their incorporation into macromolecular scaffolds and polymeric substrates has created a new paradigm for developing NO-based therapeutics for long-term NO release in applications for bactericidal and blood-contacting surfaces. Despite this abundance of research, there has been little consideration of NO-releasing scaffolds and substrates for reducing passive transmission of viral infections or for treating several respiratory viral infections. The aim of this review is to highlight the recent advances in developing gaseous NO, NO prodrugs, and NO donor compounds for antiviral therapies; discuss the limitations of NO as an antiviral agent; and outline future prospects for guiding materials design of a next generation of NO-releasing antiviral platforms.

Selection and validation of optimal endogenous reference genes for analysis of quantitative PCR in four tissues pathologically associated with Kidney-yang deficiency syndrome following influenza A infection.

Kidney-yang deficiency syndrome (KYDS) infected with the influenza virus is a suitable model to imitate a population at high-risk to influenza infection with a high rate of morbidity and mortality. However, the specific molecular mechanisms underlying this disease remain unclear. A stable reference gene is essential as an internal control for molecular biology research of this condition. Reverse-transcription-quantitative PCR (RT-qPCR) is considered an extremely sensitive technique used for absolute and relative quantification of target genes transcript levels. To accurately estimate the relative expression of genes in cells from mice with KYDS in response to infection with influenza A virus subtype H1N1 (A/H1N1) virus using RT-qPCR, it is necessary to identify suitable reference genes. In the present study, analysis of 10 reference genes (Act-ß, ß2m, GAPDH, Gusß, Tubα, Grcc10, Eif4h, Rnf187, Nedd8 and Ywhae) was performed across a set of 4 tissue types: Lung; heart; liver; and kidney. KYDS mice were inoculated with A/H1N1 virus or a mock control. For analysis, geNorm, BestKeeper, NormFinder, and Bio-Rad Maestro™ statistical programs were used for the estimation of the stability of the reference genes. The results were authenticated through extended experimental settings using a group of 10 samples, parallel to 3 additional innate immune system-associated genes of the host, TLR3, TLR7 and RIG-I, which were also analyzed using the same algorithms. From the 4 algorithms, taking into account the joint analyses of the ranking order outputs, the 2 genes Ywhae and Nedd8 were identified to be the most stable for mice with KYDS following infection with A/H1N1 virus. In contrast, the least stable genes in all 4 tissues were GAPDH and ß2m. These results may affect the choice of reference genes in future studies that use RT-qPCR analysis of target genes in experimental conditions, such as mice with KYDS infected with influenza A virus.

Hospital biosecurity capacitation: Analysis and recommendations for the prevention and control of COVID-19.

The outbreak of the coronavirus disease 2019 (COVID-19) in December 2019 highlighted several concerns regarding hospital biosafety capacitation in the People's Republic of China, although the epidemic is now under control. This study examined the primary problems related to hospital biosecurity, including the absence of a hospital emergency system, inadequate management and control of nosocomial infection, limited hospital laboratory capacity, and poor hospital admission capacity. Accordingly, this study puts forward the following countermeasures and suggestions for hospitals to deal with future biosecurity events, such as a major epidemic: first, biosecurity management systems and emergency response mechanisms in hospitals need to be set up; second, the investment and guarantee mechanisms for hospital biosecurity construction should be improved; third, the capacity building of biosecurity incident management requires special attention in general hospitals; and finally, comprehensive plans need to be developed for the integrated construction of medical treatment and prevention facilities through disease-control systems.

In silico modification of oseltamivir as neuraminidase inhibitor of influenza A virus subtype H1N1.

This research focused on the modification of the functional groups of oseltamivir as neuraminidase inhibitor against influenza A virus subtype H1N1. Interactions of three of the best ligands were evaluated in the hydrated state using molecular dynamics simulation at two different temperatures. The docking result showed that AD3BF2D ligand (N-[(1S,6R)-5-amino-5-{[(2R,3S,4S)-3,4-dihydroxy-4-(hydroxymethyl) tetrahydrofuran-2-yl]oxy}-4-formylcyclohex-3-en-1-yl]acetamide-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate) had better binding energy values than standard oseltamivir. AD3BF2D had several interactions, including hydrogen bonds, with the residues in the catalytic site of neuraminidase as identified by molecular dynamics simulation. The results showed that AD3BF2D ligand can be used as a good candidate for neuraminidase inhibitor to cope with influenza A virus subtype H1N1.

[Clinical characteristics of pediatric patients treated for influenza A (H1N1). The 2009 pandemic in Mexico]. / Características de los pacientes pediátricos atendidos por influenza A H1N1. La pandemia de 2009 en México.

BACKGROUND: Pandemic influenza A (H1N1) virus was first reported in April 2009. The aim of this study is to describe the clinical course of patients with influenza-like illness treated in a tertiary care pediatric hospital. METHODS: Cross-sectional analytical study, encompassing the period from April 2009 to March 2010. Clinical and demographic information was obtained from clinical records. Data analysis was carried out using descriptive statistics, using a univariate analysis with the chi-square test, the exact Fisher test, and the Mann-Whitney U test for quantitative variables. RESULTS: 240 patients were included, out of which 53.9 % were female; median age was 5 years. Sixty four cases (26.6 %) were confirmed, 38 % had and underlying condition, and 10 % had received the influenza vaccine. One hundred and sixteen patients (48 %) were hospitalized. With regard to mortality, 10 out of 64 confirmed cases died, 3 of the 86 of the disregarded cases, and 2 of 90 without a confirmatory test died (p < 0.05). The patients who died started antiviral treatment on day 7; conversely, those who survived started the treatment on day 4 (p < 0.05). CONCLUSIONS: Lethality was higher in patients with confirmed infection. Antiviral treatment within the first 48 hours was observed to be essential for patients with risk for the development of complications.

INTRODUCCIÓN: en abril de 2009 se informó por primera vez del virus pandémico de la influenza A H1N1. El objetivo del presente estudio es describir el curso clínico de los pacientes atendidos con enfermedad tipo influenza en un hospital pediátrico de tercer nivel. MÉTODOS: estudio transversal analítico que comprendió el periodo de abril de 2009 a marzo de 2010. La información clínica y demográfica se obtuvo de los expedientes clínicos. El análisis de los datos se llevó a cabo mediante estadística descriptiva e inferencial, para lo cual se aplicó análisis univariado mediante chi cuadrada, prueba exacta de Fisher y U de Mann-Whitney para las variables cuantitativas. RESULTADOS: se incluyeron 240 pacientes, 53.9 % del sexo femenino; la mediana de la edad fue de cinco años. Se confirmaron 64 casos (26.6 %), 38 % tenía enfermedad subyacente y 10 % había sido vacunado contra el virus de la influenza. Fueron hospitalizados 116 pacientes (48 %). Respecto a la mortalidad, 10 casos fallecieron de los 64 confirmados, tres de los 86 casos descartados y dos de los 90 que carecían de prueba confirmatoria (p < 0.05). Los pacientes que fallecieron iniciaron tratamiento antiviral el séptimo día; por su parte, los que no fallecieron iniciaron el tratamiento en el cuarto día (p < 0.05). CONCLUSIONES: la letalidad fue mayor en los pacientes con infección confirmada. Se observó que el tratamiento antiviral en las primeras 48 horas es esencial para los pacientes con riesgo para desarrollar complicaciones.

Estudio comparativo entre una prueba rápida y RT-PCR tiempo real en el diagnóstico de influenza AH1N1 2009 / Comparative study of a rapid testing with real time RT-PCR for diagnosis of influenza AH1N1 2009

OBJETIVO: Comparar la prueba QuickVue Influenza A+B empleando como estándar la RT-PCR tiempo real para influenza AH1N1 2009. MATERIAL Y MÉTODOS: Estudio retrospectivo-comparativo de 135 muestras de vías respiratorias de individuos sintomáticos para influenza procesadas de mayo 2009 a octubre 2010.Las pruebas citadas se realizaron simultáneamente. Se utilizó el software Confidence Interval Analysis 2000. RESULTADOS: Sensibilidad 62.96; especificidad 94.44; valor predictivo negativo 62.9; valor predictivo positivo 94.44; razón de probabilidad positiva 11.33 y razón de probabilidad negativa 0.39. Se calcularon intervalos de confianza a 95. DISCUSIÓN: Los valores obtenidos concuerdan con otros estudios donde la sensibilidad fluctúa de 50 a 70 y especificidad entre 90 y 95 por ciento. La prueba QuickVue Influenza A+B es rápida, simple y de menor costo que el RT-PCR tiempo real, útil para identificar el tipo de virus en brotes de influenza de una población determinada.

OBJECTIVE: Compare QuickVue Influenza A+B test with real-time RT-PCR for the diagnosis of influenza AH1N1 2009. MATERIAL AND METHODS: Retrospective-comparative study of 135 respiratory specimens from individuals with symptoms of influenza processed from May 2009 to October 2010.The above mentioned tests were performed simultaneously. For statistic analysisthe softwareof Confidence IntervalAnalysis 2000 was used. RESULTS: The parameters obtained were: sensitivity 62.96; specificity 94.44; negative predictive value 62.9; positive predictive value 94.44; positive likelihood ratio 11.33; negative likelihood ratio 0.39. Confidence intervals to 95,were calculated to all of the above data. DISCUSSION: The test QuickVue InfluenzaA+B is a rapid,simple test,with lower cost than real-time RT-PCR useful for identifying the type of virus outbreaks of influenza in a given population.It correlates well with more specific test and similar reports.

Perfil dos pacientes internados no Hospital São José do Avaí com suspeita de gripe A H1N1 / Profile of patients admitted at São José do Avaí Hospital suspected Influenza A H1N1

JUSTIFICATIVA E OBJETIVOS: A gripe A H1N1 tão logo que surgiu, tornou-se uma pandemia, afetando diversos países e gerando preocupações, tanto por levar a um número elevado de internações hospitalares, não somente no Brasil, mas em todo o mundo, por estar vinculada a complicações. Oobjetivo deste estudo foi avaliar o perfil dos primeiros pacientes com suspeita de gripe A H1N1 e a sua evolução clínica.MÉTODO: Participaram deste estudo 101 pacientes internados no período de 5 de agosto a 23 de novembro de 2009,avaliados através de dados secundários dos prontuários do Hospital São José do Avaí (HSJA) e dados do Setor de Epidemiologia do Posto de Saúde Raul Travassos (Secretaria Municipal de Saúde de Itaperuna, RJ).RESULTADOS: Dos 101 pacientes avaliados, 59,4% eram dos exo feminino e 40,6% do sexo masculino. A faixa etária varioude zero a 82 anos com predomínio de menores de 20 anos(34,7%). Foi coletado material para confirmação diagnóstica de 15 pacientes, com um total de 11 resultados positivos e 4 negativos. Desses 15 pacientes, 11 necessitaram de ventilação mecânica e 8 evoluíram para óbito. Todos os pacientes confirmados com gripe A que evoluíram para óbito, apresentavam comorbidades prévias. CONCLUSÃO: A avaliação inicial atenta dos pacientes com suspeita de gripe A é de suma importância para o diagnóstico clínico da doença, a fim de que através do tratamento adequado e precoce possa reduzir a ocorrência de complicações,formas graves e óbitos, obtendo melhor prognóstico.

BACKGROUND AND OBJECTIVES: As soon as Influenza A H1N1 emerged, it became a pandemic, affecting many countries, raising concern both for causing a high number of hospital admissions, not only in Brazil but all over the world, and for being linked to complications. The aim of this study was to evaluate the profile of the first patients suspected influenza A H1N1 and the clinical outcome.METHOD: In this study, a cohort of 101 patients was hospitalized from August 5 to November 23, 2009, assessed through secondary data from medical records at HSJA and data from the Epidemiology Section of Raul Travassos Health Post (Municipal Health Itaperuna, RJ).RESULTS: Of 101 patients, 59.4% were female and 40.6% male. Their ages ranged from 0 to 82 years with a prevalence of less than 20 years old (34.7%). Material was obtained to confirm the diagnosis of 15 patients, with a total of 11 positive and 4 negative. Of these 15 patients, 11 required mechanical ventilation and 8 died. All patients with confirmed influenza A who died, had comorbidities. CONCLUSION: The initial alert evaluation of patients suspectedof having influenza A is of great importance for theclinical diagnosis of the disease, so that by early and adequate treatment, the occurrence of complications and death can be reduced, obtaining a better prognosis.