ABSTRACT
INTRODUCTION: Pandemic A/H1N1/2009 influenza causes severe lower respiratory complications in rare cases. The association between host immune responses and clinical outcome in severe cases is unknown. METHODS: We utilized gene expression, cytokine profiles and generation of antibody responses following hospitalization in 19 critically ill patients with primary pandemic A/H1N1/2009 influenza pneumonia for identifying host immune responses associated with clinical outcome. Ingenuity pathway analysis 8.5 (IPA) (Ingenuity Systems, Redwood City, CA) was used to select, annotate and visualize genes by function and pathway (gene ontology). IPA analysis identified those canonical pathways differentially expressed (P < 0.05) between comparison groups. Hierarchical clustering of those genes differentially expressed between groups by IPA analysis was performed using BRB-Array Tools v.3.8.1. RESULTS: The majority of patients were characterized by the presence of comorbidities and the absence of immunosuppressive conditions. pH1N1 specific antibody production was observed around day 9 from disease onset and defined an early period of innate immune response and a late period of adaptive immune response to the virus. The most severe patients (n = 12) showed persistence of viral secretion. Seven of the most severe patients died. During the late phase, the most severe patient group had impaired expression of a number of genes participating in adaptive immune responses when compared to less severe patients. These genes were involved in antigen presentation, B-cell development, T-helper cell differentiation, CD28, granzyme B signaling, apoptosis and protein ubiquitination. Patients with the poorest outcomes were characterized by proinflammatory hypercytokinemia, along with elevated levels of immunosuppressory cytokines (interleukin (IL)-10 and IL-1ra) in serum. CONCLUSIONS: Our findings suggest an impaired development of adaptive immunity in the most severe cases of pandemic influenza, leading to an unremitting cycle of viral replication and innate cytokine-chemokine release. Interruption of this deleterious cycle may improve disease outcome.
Subject(s)
Adaptive Immunity/genetics , Influenza A Virus, H1N1 Subtype/immunology , Influenza, Human/genetics , Influenza, Human/immunology , Pandemics , Severity of Illness Index , Adaptive Immunity/immunology , Adult , Down-Regulation/genetics , Down-Regulation/immunology , Female , Gene Expression Profiling/methods , Humans , Influenza A Virus, H1N1 Subtype/genetics , Influenza, Human/epidemiology , Male , Middle AgedSubject(s)
Drug Interactions , Drug Prescriptions/standards , Family Practice , Female , Humans , MaleABSTRACT
INTRODUCCIÓN: Desde el descubrimiento del virus SARSCoV-2 la técnica de reacción en cadena de la polimerasa (RT-PCR) se ha convertido en el método fundamental para el diagnóstico de la enfermedad en su fase aguda. El objetivo es describir la serie basada en la demanda de determinaciones de RT-PCR recibidas en un Servicio de Microbiología en un hospital de tercer nivel de referencia durante tres meses desde el inicio de la epidemia por SARS-CoV-2. MATERIAL Y MÉTODOS: Se realizó un análisis retrospectivo del total de las RT-PCR solicitadas en el servicio de microbiología analizado desde el 25 de febrero de 2020 al 26 de mayo de 2020 (90 días). Se agruparon por semanas epidemiológicas y servicio peticionario. Se realizó un análisis descriptivo por edad, género y número de solicitudes por paciente. Se consideró significativo un nivel de confianza del 95% (p < 0.05). RESULTADOS: Se recibieron un total de 27.106 de solicitudes que correspondían a 22.037 pacientes. Edad mediana 53,7 (RIC 40,9-71,7) años, mujeres: 61,3%. Proporción de pacientes con alguna RT-PCR positiva: 14%. Del total de peticiones de RT-PCR fueron positivas 3.710. La rentabilidad máxima fue la semana epidemiológica 13, con un 39,0%. El servicio peticionario que más RT-PCR ha solicitado de forma global ha sido atención primaria con 15.953 solicitudes. Pacientes con 3 o más RT-PCR: 565, de ellos, 19 pacientes presentaron un resultado positivo tras haber sido negativos. CONCLUSIONES: Las solicitudes han ido aumentando en función de la evolución de la epidemia. La RT-PCR posee un elevado rendimiento diagnóstico en las fases de mayor contagiosidad y/o transmisibilidad del virus
INTRODUCTION: Since the discovery of the SARS-CoV-2 virus, the polymerase chain reaction technique (RT-PCR) has become the fundamental method for diagnosing the disease in its acute phase. The objective is to describe the demand-based series of RT-PCR determinations received at a Microbiology Service at a third-level reference hospital for a health area for three months spanning from the onset of the epidemic by SARS-CoV-2. METHODS: A retrospective analysis of the total of the RT-PCR requested in the Microbiology Service analyzed from 02/25/2020 to 05/26/2020 (90 days) has been carried out. They have been grouped by epidemiological weeks and by the petitioner service. A descriptive analysis was carried out by age, gender and number of requests for each patient. In the tests carried out, a confidence level of 95% (p <0.05) was considered significant. RESULTS: A total of 27,106 requests was received corresponding to 22,037 patients. Median age 53.7 (RIC 40.9-71.7) years, women: 61.3%. Proportion of patients with any positive RT-PCR: 14%. Of the total requests for RT-PCR, positive 3,710. Week 13 had the highest diagnosis performance (39.0%). The primary care has been the service thar has made the most requests (15,953). Patients with 3 or more RT-PCR: 565, of them, 19 patients had a positive result after previously having a negative one. CONCLUSIONS: Requests have been increasing depending on the evolution of the epidemic. The RT-PCR has a high diagnostic performance in the phases of highest contagiousness and / or transmissibility of the virus
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Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Young Adult , Adult , Middle Aged , Aged , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Pandemics , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Antibodies, Viral/blood , Betacoronavirus/immunology , Immunoglobulin G/blood , Immunoglobulin M/blood , Point-of-Care Testing , Risk Factors , Seroepidemiologic Studies , Spain/epidemiology , PrevalenceABSTRACT
Diagnostic methods based upon exclusive detection of haemagglutinin do not detect sequence variation in other gene segments of the Influenza A virus. A complementary approach is described based upon high-resolution melting curve analysis of the neuraminidase gene, an approach with the potential ability to detect small changes in the neuraminidase sequence without the need for specific probes.
Subject(s)
Influenza A Virus, H1N1 Subtype/isolation & purification , Influenza, Human/diagnosis , Neuraminidase/genetics , Reverse Transcriptase Polymerase Chain Reaction/methods , Transition Temperature , Viral Proteins/genetics , Virology/methods , Electrophoresis, Agar Gel/methods , Humans , Influenza A Virus, H1N1 Subtype/genetics , Sensitivity and SpecificityABSTRACT
No disponible
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Humans , Thromboembolism/prevention & control , Fibrinolytic Agents/therapeutic use , Thrombolytic Therapy/standards , Safety ManagementABSTRACT
No disponible
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Humans , Drug Prescriptions/standards , Electronic Prescribing/standards , Safety ManagementABSTRACT
No disponible
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Humans , Digoxin/toxicity , Heart Failure/drug therapy , Renal Insufficiency/chemically induced , Atrial Fibrillation/drug therapy , /drug therapyABSTRACT
No disponible
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Humans , Drug Interactions , Safety Management/methods , Drug Prescriptions/standards , /prevention & control , Risk FactorsABSTRACT
No disponible