Long-term outcomes for epidemic viral pneumonia survivors after discharge from the intensive care unit: a systematic review

ABSTRACT Objective To review the long-term outcomes (functional status and psychological sequelae) of survivors of critical illnesses due to epidemic viral pneumonia before the COVID-19 pandemic and to establish a benchmark for comparison of the COVID-19 long-term outcomes. Methods This systematic review of clinical studies reported the long-term outcomes in adults admitted to intensive care units who were diagnosed with viral epidemic pneumonia. An electronic search was performed using databases: MEDLINE®, Web of Science™, LILACS/IBECS, and EMBASE. Additionally, complementary searches were conducted on the reference lists of eligible studies. The quality of the studies was assessed using the Newcastle-Ottawa Scale. The results were grouped into tables and textual descriptions. Results The final analysis included 15 studies from a total of 243 studies. This review included 771 patients with Influenza A, Middle East Respiratory Syndrome, and Severe Acute Respiratory Syndrome. It analyzed the quality of life, functionality, lung function, mortality, rate of return to work, rehospitalization, and psychiatric symptoms. The follow-up periods ranged from 1 to 144 months. We found that the quality of life, functional capacity, and pulmonary function were below expected standards. Conclusion This review revealed great heterogeneity between studies attributed to different scales, follow-up time points, and methodologies. However, this systematic review identified negative long-term effects on patient outcomes. Given the possibility of future pandemics, it is essential to identify the long-term effects of viral pneumonia outbreaks. This review was not funded. Prospero database registration: (www.crd.york.ac.uk/prospero) under registration ID CRD42021190296.

Biological, social, and healthcare factors associated with death due to influenza A(H1N1) during the 2009 epidemic in Brazil

Background: In June 2009, the World Health Organization (WHO) raised the global alert level for the A(H1N1)pdm09 influenza pandemic and at that time sustained transmission in Brazil was established. It was urgent to carry out studies that evaluated possible risk factors for death from Influenza A(H1N1) to improve case management strategies to reduce the lethality of the disease. This study aimed to identify risk factors for death from Influenza A(H1N1), including the effectiveness of the vaccine against influenza A(H1N1) concerning mortality. Methods: A case-control of incident cases of influenza A(H1N1) reported in the Epidemiological Information Systems of the states of São Paulo, Paraná, Pará, Amazonas, and Rio Grande do Sul was conducted. Results: 305 participants were included, 70 of them cases and 235 controls, distributed as follows: Amazonas ­ 9 cases/10 controls, Pará ­ 22 cases/77 controls, São Paulo ­ 19 cases/49 controls, Paraná ­ 10 cases/54 controls, Rio Grande do Sul ­ 10 cases/45 controls. These participants had a mean age of 30 years, with 33 years among cases and 25 years among controls. There was a predominance of females both among cases and controls. Biological (age), pre-existing diseases (congestive heart failure, respiratory disease, and diabetes mellitus), and care factors (ICU admission) associated with death from Influenza A(H1N1) were identified. Conclusion: The risk factors identified in this investigation allowed subsidizing the elaboration of clinical conducts, but also indicate important aspects for facing "new" influenza epidemics that are likely to occur in our country.

Inference of age-dependent case-fatality ratios for seasonal influenza virus subtypes A(H3N2) and A(H1N1)pdm09 and B lineages using data from the Netherlands.

Background: Despite the known relatively high disease burden of influenza, data are lacking regarding a critical epidemiological indicator, the case-fatality ratio. Our objective was to infer age-group and influenza (sub)type specific values by combining modelled estimates of symptomatic incidence and influenza-attributable mortality. Methods: The setting was the Netherlands, 2011/2012 through 2019/2020 seasons. Sentinel surveillance data from general practitioners and laboratory testing were synthesised to supply age-group specific estimates of incidence of symptomatic infection, and ecological additive modelling was used to estimate influenza-attributable deaths. These were combined in an Bayesian inferential framework to estimate case-fatality ratios for influenza A(H3N2), A(H1N1)pdm09 and influenza B, per 5-year age-group. Results: Case-fatality estimates were highest for influenza A(H3N2) followed by influenza B and then A(H1N1)pdm09 and were highest for the 85+ years age-group, at 4.76% (95% credible interval [CrI]: 4.52-5.01%) for A(H3N2), followed by influenza B at 4.08% (95% CrI: 3.77-4.39%) and A(H1N1)pdm09 at 2.51% (95% CrI: 2.09-2.94%). For 55-59 through 85+ years, the case-fatality risk was estimated to double with every 3.7 years of age. Conclusions: These estimated case-fatality ratios, per influenza sub(type) and per age-group, constitute valuable information for public health decision-making, for assessing the retrospective and prospective value of preventative interventions such as vaccination and for health economic evaluations.

The Immunosuppressive Roles of PD-L1 during Influenza A Virus Infection.

The clinical benefits of targeting programmed death-ligand 1 (PD-L1) in various cancers represent a strategy for the treatment of immunosuppressive diseases. Here, it was demonstrated that the expression levels of PD-L1 in cells were greatly upregulated in response to H1N1 influenza A virus (IAV) infection. Overexpression of PD-L1 promoted viral replication and downregulated type-I and type-III interferons and interferon-stimulated genes. Moreover, the association between PD-L1 and Src homology region-2, containing protein tyrosine phosphatase (SHP2), during IAV/H1N1 infection was analyzed by employing the SHP2 inhibitor (SHP099), siSHP2, and pNL-SHP2. The results showed that the expressions of PD-L1 mRNA and protein were decreased under SHP099 or siSHP2 treatment, whereas the cells overexpressing SHP2 exhibited the opposite effects. Additionally, the effects of PD-L1 on the expression of p-ERK and p-SHP2 were investigated in PD-L1-overexpressed cells following WSN or PR8 infection, determining that the PD-L1 overexpression led to the decreased expression of p-SHP2 and p-ERK induced by WSN or PR8 infection. Taken together, these data reveal that PD-L1 could play an important role in immunosuppression during IAV/H1N1 infection; thus, it may serve as a promising therapeutic target for development of novel anti-IAV drugs.

Acute necrotising encephalopathy: A rare complication providing a clue for the outbreak of H1N1 among medical students in Kanpur, India.

Kanpur, India, recently witnessed an outbreak of undifferentiated febrile illness among medical students. Several students developed high-grade fever with altered sensorium within 2-3 days after the index case. Surprisingly, this outbreak coincided with the death of several pigs in the vicinity. Acute necrotising encephalitis, although rare, was noted in some patients. When correlated with each other, all of these incidents were suggestive of an outbreak of H1N1.

Modulation of Immune Responses Against HA1 Influenza Vaccine Candidate by B-lymphocyte Stimulator Cytokine in Mice.

Utilizing subunit vaccines is one of the strategies to address influenza infection. Recent innovations have focused on high doses of vaccine antigens and immune enhancers or adjuvant to induce more robust and long-lasting immune responses. Here, an effect of the B cell-activating factor receptor (BAFF-R) to increase the magnitude and durability of immune responses of the recombinant HA1 (rHA1) protein against the H1N1 influenza virus was studied. The HA1 protein and the effector domain of BAFF-R were expressed in the pET-28a (+) vector. Eight-week-old BALB/c mice were equally grouped into five groups (n=20). The 15 and 25 µg/µL of rHA1 were mixed with 2 µg/µL of rBAFF-R and injected three times for vaccinated groups. Three control groups were received normal saline and two concentrations of rHA1. The ability of rBAFF-R in eliciting HA-specific antibody response and stimulating T lymphocyte proliferation to induce the cell-mediated immunity was assayed. Induction of protection was evaluated following the challenge with PR8 strain. Analysis of immune responses showed that the co-administration of rBAFF-R with rHA1 boosted HI responses to the antigen in mice, whilst it was not able to promote the T cell proliferation responses against influenza. Compared to rHA1alone, the rBAFF-R/rHA1 generated efficient protection for the animals. There were no significant differences in eliciting the immune responses in mice immunized with the lower dose of rHA1 than that with the higher dose. The data indicate the rBAFF-R can enhance the primary and memory immune responses to protect against influenza infection.

Anti-bacterial and anti-viral effects of Fengreqing oral liquid () in vitro and in vivo.

OBJECTIVE: To investigate the anti-bacterial and anti-viral effects of Fengreqing oral liquid (, FRQ) in vitro and in vivo. METHODS: The minimum inhibitory concentrations of Fengreqing Oral Liquid against six gram-positive bacteria (Staphylococcus aureus, Streptococcus mutans, Peptostreptococcus anaerobius, Hemolytic streptococcus, Streptococcus pneumoniae, Klebsiella pneumoniae), seven gram-negative bacteria (Escherichia coli, Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Haemophilus influenzae, Helicobacter pylori, Pseudomonas aeruginosa, Gardnerella vaginalis) and Candida albicans were detected by the paper disc diffusion method. The inhibition rate of A/PuertoRico/8/34(H1N1) (PR8) influenza virus in different concentrations of Fengreqing oral solution was detected by chicken embryo method. CCK8 method was used to detect the half-cell infection of RSV, VSV and CVB3. The effect of FRQ on the survival curve of mice was detected by using co-infection model of Streptococcus pneumoniae and influenza virus. RESULTS: In vitro, FRQ can inhibit Actinobacillus actinomycetemcomitans, Helicobacter pylori, Gardnerella vaginalis, Staphylococcus aureus, Streptococcus mutans and Streptococcus pneumoniae and has an antiviral effect on the envelope virus H1N1. In vivo, Fengreqing oral solution had therapeutic effect on influenza-Streptococcus pneumoniae co-infection in mice, significantly improving the survival rate of mice. The medium dose and low dose FRQ significantly prolonged the survival time of mice. CONCLUSION: FRQ has good anti-bacterial and anti-viral effectsin vivo and in vitro.

Comparison of two pandemics: H1N1 and SARS-CoV-2

SUMMARY OBJECTIVE: We aimed to compare the clinical, epidemiological, and prognostic features of the H1N1 pandemic in 2009 and the severe acute respiratory syndrome coronavirus 2 pandemic in 2020. METHODS: This retrospective study involved subjects from seven centers that were admitted and found to be positive for H1N1 or COVID-19 real-time polymerase chain reaction test. RESULTS: A total of 143 patients with H1N1 and 309 patients with COVID-19 were involved in the study. H1N1 patients were younger than COVID-19 ones. While 58.7% of H1N1 patients were female, 57.9% of COVID-19 patients were male. Complaints of fever, cough, sputum, sore throat, myalgia, weakness, headache, and shortness of breath in H1N1 patients were statistically higher than in COVID-19 ones. The duration of symptoms until H1N1 patients were admitted to the hospital was shorter than that for COVID-19 patients. Leukopenia was more common in COVID-19 patients. C-reactive protein levels were higher in COVID-19 patients, while lactate dehydrogenase levels were higher in H1N1 ones. The mortality rate was also higher in H1N1 cases. CONCLUSIONS: The severe acute respiratory syndrome coronavirus 2 pandemic is a major public health problem that continues to affect the world with its high rate of contagion. In addition, no vaccines or a specific drug for the benefit of millions of people have been found yet. The H1N1 pandemic is an epidemic that affected the whole world about ten years ago and was prevented by the development of vaccines at a short period. Experience in the H1N1 pandemic may be the guide to prevent the COVID-19 pandemic from a worse end.

Respiratory Viral Infections in Sickle Cell Anemia: Special Emphasis on H1N1 Co-infection.

OBJECTIVES: Patients with sickle cell anemia (SCA) are immunocompromised and at an increased risk of developing infections. Our aim was to establish the clinical, laboratory, and radiological manifestations of respiratory viral infections in SCA at Sultan Qaboos University Hospital (SQUH), Oman and assess its impact on disease morbidity and mortality, with special emphasis on H1N1. METHODS: We undertook a retrospective study in SCA patients with respiratory viral infections following up at the hematology department at SQUH. We collected demographic data and clinical, radiological, and laboratory parameters. RESULTS: In 84 SCA patients with 109 admission episodes for vaso-occlusive crisis (VOC), molecular diagnostic techniques confirmed 125 respiratory viral infections. Rhinovirus was the most prevalent infection (35.8%), whereas H1N1 virus infection was seen only in 10.1%. Laboratory investigations revealed a significant fall in mean hemoglobin levels, mean white blood cell, and platelet counts from baseline, whereas there was a significant rise in the mean lymphocyte and retic count, serum lactate dehydrogenase, and C-reactive protein levels during infective episodes (p < 0.050, Wilcoxon signed rank test). One-third (32.1%) of the VOC episodes progressed to acute chest syndrome (ACS), but in the H1N1 cohort, only two episodes of ACS was seen (18.2%). CONCLUSIONS: Rhinovirus was the commonest respiratory virus infections in SCA patients, whereas parainfluenza 3 was associated with a significant adverse outcome. H1N1 was associated with a mild course. ACS was seen in approximately one-third of this group of patients.

Reduning plus ribavirin display synergistic activity against severe pneumonia induced by H1N1 influenza A virus in mice.

OBJECTIVE: To investigate synergistic effect of Reduning (RDN) injection plus ribavirin against severe pneumonia induced by H1N1 influenza A virus in mice. METHODS: We established a mouse model of severe pneumonia induced by influenza A virus by infecting Balb/c mice with CA07 virus. We randomly assigned the infected mice into four groups, and treated them with normal saline (NS group), RDN (injection, 86.6 mg/kg), ribavirin (injection, 66.6 mg/kg) or double Ribavirin plus RDN group, the same dosage as used in the single treatments) for 5 d. Lung index and lung pathology were recorded or calculated in terms of the curative effective. Cytokines, NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome related protein including caspase-associated recruitment domain (CARD) domain Apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC), caspase-1 and NOD-like receptor family, pyrin domain containing 3 (NLRP3), and reactive oxygen species were simultaneously investigated. RESULTS: RDN plus ribavirin treatment, not RDN or ribavirin alone, provided a significant survival benefit to the influenza A virus-infected mice. The combination treatment protected the mice against severe influenza infection by attenuating the severe lung injury. The combined treatment also reduced the viral titers in mouse lungs and lung index, downregulated their immunocytokine levels, including IL-1ß and IL-18, and down regulated the NLRP3, especially the transcription and translation of caspase-1. Meanwhile NS group had significantly higher reactive oxygen species (ROS) expression which could was dramatically reduced by the treatment of RDN plus ribavirin. CONCLUSION: Our study showed that RDN combined with ribavirin could protect the mice, and reduce the lung immunopathologic damage caused by severe influenza pneumonia. The mechanism could be that it reduced ROS produce and inhibited NLRP3 inflammasome activation so that mainly lower the downstream inflammatory cytokines IL-1ß and IL-18.

In silico analysis and molecular characterization of Influenza A (H1N1) pdm09 virus circulating and causing major outbreaks in central India, 2009-2019.

BACKGROUND AND OBJECTIVES: Influenza A/H1N1pdm09 causes respiratory illness and remains a concern for public health. Since its first emergence in 2009, the virus has been continuously circulating in the form of its genetic variants. Influenza A/H1N1pdm09 surveillance is essential for uncovering emerging variants of epidemiologic and vaccine efficacy. The present study attempts in silico analysis and molecular characterization of Influenza A (H1N1) pdm09 virus circulating and causing major outbreaks in central India during 2009-2019. MATERIALS AND METHODS: We have investigated the antigenic drift analysis of 96 isolates' hemagglutinin (HA) gene sequences (59 central Indian and 37 local Indian and 28 global reference HA gene sequences) of Influenza A/H1N1pdm09 viruses from 2009 to 2019. The study includes mutational (Multiple sequence Alignment), phylogenetic (Maximum Likelihood Method), and statistical analysis (Covariance and correlation) of HA sequences submitted in NCBI, IRD and GISAID from central India. RESULTS: Phylogenetic analysis indicated maximum clustering of central Indian HA gene sequences in genogroup 6B. Analysis of amino acid sequence alignment revealed changes in receptor binding site (RBS). The frequency of S220T amino acid substitution was found to be high followed by S202T, K300E A273T, K180Q. The Karl Pearson correlation coefficient (r) and covariance between the number of mutations and the death toll was found +0.246 and +100.3 respectively. CONCLUSION: The study identifies the continuous genetic variations in the HA gene sequences of circulating Influenza A/H1N1pdm09 in central India from the year 2009 to 2019. Further suggesting importance of monitoring the gradual evolution of the virus with regards to an increase in virulence, pathogenicity and vaccine efficacy timely.

H1N1: perfil clínico-epidemiológico de pacientes atendidos em um hospital / H1N1: clinical and epidemiological profile of patients treated in a hospital

Objetivo: Avaliar casos de suspeita de gripe H1N1, bem como comparar aspectos epidemiológicos e clínicos dos pacientes com gripe H1N1 confirmada em relação àqueles não confirmados; analisar os critérios de gravidade clínica com relação à confirmação (ou não) da gripe H1N1 e seu desfecho (mortalidade); e criar um banco de dados para fins de comparação com a literatura nacional e mundial. Métodos: Estudo retrospectivo de coorte transversal realizado no período sazonal (outono e inverno) no ano de 2016. Foram analisados os prontuários, acessíveis e completos, de pacientes com suspeita clínica de H1N1, além daqueles com resultados definidos na sorologia. A partir dos dados coletados, foi elaborada tabela de análise epidemiológica, com informações clínicas, laboratoriais e sorológicas. Resultados: Destacam-se a média das faixas etárias mais acometidas de 48 anos, além dos sintomas mais comuns que foram dispneia, tosse e mialgia; as comorbidades foram hipertensão arterial sistêmica, cardiopatias, diabetes e doença pulmonar obstrutiva crônica. Conclusão: Este trabalho contribuiu com a caracterização do perfil epidemiológico regional e auxiliou na definição de indicadores de diagnóstico e gravidade, além de agregar à literatura conteúdos de caráter relevante. Este estudo está registrado como CAAE 58664016.2.0000.5515 na Plataforma Brasil. (AU)

Objective: To evaluate cases of suspected H1N1 flu, as well as to compare epidemiological and clinical aspects of patients with confirmed H1N1 influenza to those who were not confirmed; to analyze the criteria of clinical severity regarding the confirmation (or not) of H1N1 influenza, and its outcome (mortality); and to create a database to be compared with the national and world literature. Methods: This is a cross-sectional retrospective cohort study, carried out in the seasonal period ( fall/winter) of 2016. Accessible and complete medical records of patients with clinical suspicion of H1N1 were analyzed along with those with defined serology results. Based on the collected data, a table of epidemiological analysis was elaborated with clinical, laboratory and serological information. Results: The mean age of the most affected age groups was 48 years; the most common symptoms were dyspnea, cough and myalgia; and the comorbidities were systemic arterial hypertension, cardiopathies, diabetes, and chronic obstructive pulmonary disease. Conclusion: This work contributed to the characterization of the regional epidemiological profile, and helped in the definition of indicators of diagnosis and severity, besides adding relevant content to the literature. This study is registered as CAAE 58664016.2.0000.5515 at Plataforma Brasil. (AU)

Uso da ventilação não invasiva na SDRA e pneumonia secundária a H1N1: revisão sistemática / Use of non-invasive ventilation in ARDS and secondary pneumonia H1N1: systematic review

INTRODUÇÃO: A influenza A é uma infecção respiratória aguda, associada a epidemias e pandemias, sendo um vírus de comportamento sazonal. O uso precoce da ventilação não invasiva tem se mostrado um tratamento de primeira linha em pacientes com síndrome do desconforto respiratório e pneumonia secundaria a influenza A H1N1, resultando em menores taxas de mortalidade. OBJETIVO: Investigar através de revisão sistemática o uso da ventilação não invasiva em pacientes diagnosticados com Influenza A H1N1, secundário a pneumonia e a síndrome do desconforto respiratório agudo. MATERIAIS E MÉTODOS: Foram realizadas buscas nas bases de dados do Periódicos Capes, Science Direct, SciELO, e Pubmed, selecionandose os estudos desenvolvidos nos últimos 10 anos, não sendo imposta restrição de idiomas para a pesquisa. A qualidade metodológica dos estudos foi apontada utilizando a escala de PEDro. RESULTADOS: 16 estudos preencheram o critério de elegibilidade e foram incluídos neste estudo segundo escore de PEDro. Nove estudos mostraram que o uso da ventilação não invasiva foi eficiente em pacientes de média e baixa hipoxemia, diminuindo a taxa de intubação orotraqueal e doenças associadas, menor permanência hospitalar e menores taxas de mortalidade. CONCLUSÃO: O uso da VNI em pacientes com Síndrome do Desconforto Respiratório Agudo e pneumonia secundária ao vírus influenza A H1N1 mostrou-se relevante na reversão da hipoxemia moderada e leve. Critérios, parâmetros e protocolos bem estabelecidos, torna-se muito útil, juntamente com profissionais experientes e preparados, visando assim uma menor taxa de intubação orotraqueal e doenças associadas, e consequentemente uma menor permanência hospitalar e menores taxas de mortalidade.

INTRODUCTION: Influenza A is an acute respiratory infection, associated with epidemics and pandemics, being a virus with seasonal behavior. Early use of noninvasive ventilation has been shown to be first-line treatment in patients with respiratory distress syndrome and influenza A H1N1 secondary pneumonia, resulting in lower mortality rates. OBJECTIVE: To investigate through a systematic review the use of noninvasive ventilation in patients diagnosed with influenza A H1N1, secondary to pneumonia and acute respiratory distress syndrome. MATERIALS AND METHODS: Searches were carried out in the Capes, Science Direct, SciELO, and Pubmed journals, selecting the studies developed in the last 10 years, with no language restriction for the research. The methodological quality of the studies was indicated using the PEDro scale. RESULTS: 16 studies met the eligibility criteria and were included in this study according to PEDro score. Where 9 studies showed that the use of noninvasive ventilation was efficient in patients with medium and low hypoxemia, decreasing the rate of orotracheal intubation and associated diseases, shorter hospital stay and lower mortality rates. CONCLUSION: The use of NIV in patients with Acute Respiratory Distress Syndrome and influenza A H1N1 secondary pneumonia has been shown to be relevant for reversing moderate and mild hypoxemia. Well-established criteria, parameters and protocols become very useful, along with experienced and prepared professionals, thus aiming at a lower rate of orotracheal intubation and associated diseases, and consequently a shorter hospital stay and lower mortality rates.

[Clinical analysis of seven cases of H1N1 influenza-associated encephalopathy in children].

Objective: To investigate the clinical manifestations, diagnosis, and treatment of H1N1 influenza A-associated encephalopathy (IAE) in children. Methods: The clinical manifestations, laboratory tests, cranial magnetic resonance imaging (MRI), electroencephalography (EEG) examinations and treatments of seven children with H1N1 IAE hospitalized in Guangzhou Women and Children's Medical Center from December 2018 to January 2019 were retrospectively analyzed. Results: Five of the seven children with H1N1 IAE were female. The age at admission was 4 years and 5 months (range 7 months-9 years). Neurological symptoms occurred simultaneously or early (0-3 days) after the flu-like symptom appeared. The main clinical manifestations of neurological symptoms were seizures (repeated seizures in five cases and status convulsion in two cases, including one case of unexpected fever and repeated seizures in a nine-year old girl) accompanied with altered consciousness (drowsiness in five cases and coma in two cases). Cranial MRI in three cases displayed multifocal lesions, mainly in the bilateral thalamus, brainstem and cerebellar hemisphere. MRI also showed reversible splenial lesion in the corpus callusumin in three cases. EEG tracings were characterized by diffuse slow wave activity in four cases, and status epilepticus was monitored in one case. All the 7 cases were treated with oral oseltamivir. Three cases were treated with pulsed methylprednisolone and intravenous immunoglobulin. One case was treated with intravenous immunoglobulin alone and all the patients received oral oseltamivir. All the patients survived, with three patients had minor neurological sequelae at discharge. Conclusions: The main clinical manifestations of H1N1 IAE are seizures and altered consciousness. Cranial MRI combined with EEG is helpful for early diagnosis. Intravenous immunoglobulin and (or) methylprednisolone should be considered for severe cases.

Interesting post-mortem findings in a H1N1 influenza-positive pneumonia patient.

Reports of histopathological findings in a patient infected with H1N1 influenza virus are limited in the literature, although many deaths have occurred because of this viral infection. In an otherwise healthy individual with no underlying co-morbid conditions, this virus passes off as a very mild disease. However, it can be fatal in the presence of underlying risk factors. Here, we present the autopsy findings of a patient who died of H1N1 infection, but who was apparently healthy with no predisposing ailments. The autopsy revealed chronic kidney disease and caseating granulomatous lymphadenitis in addition to the known classical diffuse alveolar damage picture seen in this condition. These underlying co-morbidities may provide greater insight and a better understanding of this infection.

Initial chest X-ray findings in pediatric patients diagnosed with H1N1 virus infection.

OBJECTIVE: To evaluate chest X-ray findings in pediatric patients diagnosed with influenza A (H1N1) virus infection. MATERIALS AND METHODS: We retrospectively reviewed chest X-ray findings in 17 cases of pulmonary infection with the H1N1 virus (in 7 males and 10 females) examined between 2012 and 2016. The mean age of the patients was 14 months (range, 2-89 months). The diagnosis was established on the basis of clinical and radiographic criteria, and the virus was detected by polymerase chain reaction. The radiographic findings were categorized by type/pattern of opacity and by lung zone. The patients were divided into two groups: those not requiring ventilatory support; and those requiring ventilatory support or evolving to death. RESULTS: The abnormality most often seen on chest X-rays was that of peribronchovascular opacities, the majority of which affected less than 25% of the lung, the involvement being bilateral and asymmetric. The lung zone most frequently involved was the middle third, with central and peripheral distribution, without pleural effusion. There was a statistically significant difference between the groups in terms of the symmetry of pulmonary involvement, asymmetric findings predominating in the group that required ventilatory support (p = 0.029). CONCLUSION: In pediatric patients with H1N1 virus infection, the main alterations on the initial chest X-rays are peribronchovascular opacities, nonspecific alveolar opacities, and consolidations. Although the definitive diagnosis of H1N1 virus infection cannot be made on the basis of imaging characteristics alone, using a combination of clinical and radiographic findings can substantially improve the diagnostic accuracy.

OBJETIVO: Avaliar os achados na radiografia de tórax de pacientes com diagnóstico de infecção pelo vírus influenza. MATERIAIS E MÉTODOS: Revisamos, retrospectivamente, os achados na radiografia de tórax de 17 casos de infecção pulmonar pelo vírus influenza (7 do sexo masculino e 10 do sexo feminino; idade média de 14 meses, variação de 2 a 89 meses). Os pacientes foram examinados entre 2012 e 2016 e o diagnóstico foi estabelecido por critérios clinicorradiológicos e detecção do vírus por reação em cadeia de polimerase. Os achados radiológicos foram caracterizados por tipo e padrão de opacidade e distribuição por zonas pulmonares. A população estudada foi dividida em dois grupos: sem suporte ventilatório e com suporte ventilatório e/ou óbito. RESULTADOS: A anormalidade encontrada com maior frequência na radiografia de tórax foram as marcas peribroncovasculares, a maioria delas com extensão menor de 25% do pulmão, envolvimento bilateral e assimétrico. A região mais frequentemente envolvida foi o terço médio, com distribuição central e periférica e ausência de derrame pleural. Houve diferença estatisticamente significante na simetria do envolvimento pulmonar, entre os grupos, havendo preponderância de achado assimétrico (p = 0,029) no grupo que necessitou de suporte ventilatório. CONCLUSÃO: Pacientes pediátricos com infecção pelo H1N1 apresentam como alterações principais na radiografia do tórax inicial marcas peribroncovasculares, opacidades alveolares inespecíficas e consolidações. Embora o diagnóstico definitivo não possa ser feito com base em imagens características isoladas, uma combinação dos achados clínicos e radiográficos pode melhorar substancialmente a acurácia do diagnóstico nessa doença.

Initial chest X-ray findings in pediatric patients diagnosed with H1N1 virus infection / Achados iniciais na radiografia de tórax em uma população pediátrica com diagnóstico de infecção viral por H1N1

Abstract Objective: To evaluate chest X-ray findings in pediatric patients diagnosed with influenza A (H1N1) virus infection. Materials and Methods: We retrospectively reviewed chest X-ray findings in 17 cases of pulmonary infection with the H1N1 virus (in 7 males and 10 females) examined between 2012 and 2016. The mean age of the patients was 14 months (range, 2-89 months). The diagnosis was established on the basis of clinical and radiographic criteria, and the virus was detected by polymerase chain reaction. The radiographic findings were categorized by type/pattern of opacity and by lung zone. The patients were divided into two groups: those not requiring ventilatory support; and those requiring ventilatory support or evolving to death. Results: The abnormality most often seen on chest X-rays was that of peribronchovascular opacities, the majority of which affected less than 25% of the lung, the involvement being bilateral and asymmetric. The lung zone most frequently involved was the middle third, with central and peripheral distribution, without pleural effusion. There was a statistically significant difference between the groups in terms of the symmetry of pulmonary involvement, asymmetric findings predominating in the group that required ventilatory support (p = 0.029). Conclusion: In pediatric patients with H1N1 virus infection, the main alterations on the initial chest X-rays are peribronchovascular opacities, nonspecific alveolar opacities, and consolidations. Although the definitive diagnosis of H1N1 virus infection cannot be made on the basis of imaging characteristics alone, using a combination of clinical and radiographic findings can substantially improve the diagnostic accuracy.

Resumo Objetivo: Avaliar os achados na radiografia de tórax de pacientes com diagnóstico de infecção pelo vírus influenza. Materiais e Métodos: Revisamos, retrospectivamente, os achados na radiografia de tórax de 17 casos de infecção pulmonar pelo vírus influenza (7 do sexo masculino e 10 do sexo feminino; idade média de 14 meses, variação de 2 a 89 meses). Os pacientes foram examinados entre 2012 e 2016 e o diagnóstico foi estabelecido por critérios clinicorradiológicos e detecção do vírus por reação em cadeia de polimerase. Os achados radiológicos foram caracterizados por tipo e padrão de opacidade e distribuição por zonas pulmonares. A população estudada foi dividida em dois grupos: sem suporte ventilatório e com suporte ventilatório e/ou óbito. Resultados: A anormalidade encontrada com maior frequência na radiografia de tórax foram as marcas peribroncovasculares, a maioria delas com extensão menor de 25% do pulmão, envolvimento bilateral e assimétrico. A região mais frequentemente envolvida foi o terço médio, com distribuição central e periférica e ausência de derrame pleural. Houve diferença estatisticamente significante na simetria do envolvimento pulmonar, entre os grupos, havendo preponderância de achado assimétrico (p = 0,029) no grupo que necessitou de suporte ventilatório. Conclusão: Pacientes pediátricos com infecção pelo H1N1 apresentam como alterações principais na radiografia do tórax inicial marcas peribroncovasculares, opacidades alveolares inespecíficas e consolidações. Embora o diagnóstico definitivo não possa ser feito com base em imagens características isoladas, uma combinação dos achados clínicos e radiográficos pode melhorar substancialmente a acurácia do diagnóstico nessa doença.

Interesting post-mortem findings in a H1N1 influenza-positive pneumonia patient

Reports of histopathological findings in a patient infected with H1N1 influenza virus are limited in the literature, although many deaths have occurred because of this viral infection. In an otherwise healthy individual with no underlying co-morbid conditions, this virus passes off as a very mild disease. However, it can be fatal in the presence of underlying risk factors. Here, we present the autopsy findings of a patient who died of H1N1 infection, but who was apparently healthy with no predisposing ailments. The autopsy revealed chronic kidney disease and caseating granulomatous lymphadenitis in addition to the known classical diffuse alveolar damage picture seen in this condition. These underlying co-morbidities may provide greater insight and a better understanding of this infection.

Fatores associados ao óbito dos casos graves de influenza A(H1N1)pdm09 / Factors associated with death of severe cases of influenza A(H1N1)pdm09

Resumo Introdução A primeira pandemia de influenza do século XXI ocorreu em 2009, causada pelo novo subtipo de vírus da gripe, o vírus influenza A(H1N1)pdm09. Objetivo Analisar os fatores associados ao óbito por Síndrome Respiratória Aguda Grave (SRAG) por influenza A(H1N1)pdm09 em residentes do município do Rio de Janeiro. Método Análise de dados secundários, incluindo 1.191 casos confirmados para influenza A(H1N1) com critério clínico para SRAG, residentes no município do Rio de Janeiro, em 2009. Análise estatística descritiva e regressão logística para estudo dos fatores associados ao óbito. Resultados 60,3% ocorreram em mulheres, sendo 185 gestantes; 48,1% em menores de 20 anos; 35,7% tinham comorbidades; 91,4% foram hospitalizados; 7,4% foram a óbito. Observou-se maior chance de óbito associada à baixa escolaridade, à presença de comorbidade, ao padrão radiológico de infiltrado intersticial, consolidação ou misto, à confirmação laboratorial e ao estado vacinal contra gripe ignorado. Conclusão Indivíduos com baixa escolaridade, com pelo menos uma comorbidade e com comprometimento pulmonar com um padrão radiológico com infiltrado intersticial, consolidação ou misto tiveram maior chance de evolução a óbito. O melhor conhecimento desse perfil permite um planejamento mais eficiente da assistência à saúde dos pacientes.

Abstract Introduction the first influenza pandemic of the 21st century occurred in 2009, caused by the new subtype of influenza virus, influenza A (H1N1) pdm09. Objective to analyze the factors associated with death due to Severe Acute Respiratory Infection (SARI) caused by influenza A (H1N1) pdm09 in residents of the city of Rio de Janeiro. Method Analysis of secondary data, including 1,191 confirmed cases of influenza A (H1N1) pdm09 with clinical criteria for SARI, residents of the city of Rio de Janeiro, in 2009. Descriptive statistical analysis and logistic regression for the study of factors associated with death. Results 60.3% occurred in women, with 185 pregnant women; 48.1% in children under 20 years old; 35.7% had comorbidities; 91.4% were hospitalized, and 7.4% died. There was a higher chance of death associated with low educational level, presence of comorbidity, radiological pattern of interstitial infiltrate, consolidation or mixed; laboratory confirmation; vaccination status ignored. Conclusion individuals with low educational level who had at least one comorbidity and had pulmonary involvement with a radiological pattern with interstitial infiltrate, consolidation or mixed had a higher chance of dying. Knowledge of this profile allows for more efficient planning of health care.

Clinical analysis of seven cases of H1N1 influenza-associated encephalopathy in children / 中华儿科杂志

Objective@#To investigate the clinical manifestations, diagnosis, and treatment of H1N1 influenza A-associated encephalopathy (IAE) in children.@*Methods@#The clinical manifestations, laboratory tests, cranial magnetic resonance imaging (MRI), electroencephalography (EEG) examinations and treatments of seven children with H1N1 IAE hospitalized in Guangzhou Women and Children′s Medical Center from December 2018 to January 2019 were retrospectively analyzed.@*Results@#Five of the seven children with H1N1 IAE were female. The age at admission was 4 years and 5 months (range 7 months-9 years). Neurological symptoms occurred simultaneously or early (0-3 days) after the flu-like symptom appeared. The main clinical manifestations of neurological symptoms were seizures (repeated seizures in five cases and status convulsion in two cases, including one case of unexpected fever and repeated seizures in a nine-year old girl) accompanied with altered consciousness (drowsiness in five cases and coma in two cases). Cranial MRI in three cases displayed multifocal lesions, mainly in the bilateral thalamus, brainstem and cerebellar hemisphere. MRI also showed reversible splenial lesion in the corpus callusumin in three cases. EEG tracings were characterized by diffuse slow wave activity in four cases, and status epilepticus was monitored in one case. All the 7 cases were treated with oral oseltamivir. Three cases were treated with pulsed methylprednisolone and intravenous immunoglobulin. One case was treated with intravenous immunoglobulin alone and all the patients received oral oseltamivir. All the patients survived, with three patients had minor neurological sequelae at discharge.@*Conclusions@#The main clinical manifestations of H1N1 IAE are seizures and altered consciousness. Cranial MRI combined with EEG is helpful for early diagnosis. Intravenous immunoglobulin and (or) methylprednisolone should be considered for severe cases.