Avian flu: «for whom the bell tolls¼?

The family Orthomyxoviridae consists of 9 genera, including Alphainfluenza virus, which contains avian influenza viruses. In two subtypes H5 and H7 besides common low-virulent strains, a specific type of highly virulent avian virus have been described to cause more than 60% mortality among domestic birds. These variants of influenza virus are usually referred to as «avian influenza virus¼. The difference between high (HPAI) and low (LPAI) virulent influenza viruses is due to the structure of the arginine-containing proteolytic activation site in the hemagglutinin (HA) protein. The highly virulent avian influenza virus H5 was identified more than 100 years ago and during this time they cause outbreaks among wild and domestic birds on all continents and only a few local episodes of the disease in humans have been identified in XXI century. Currently, a sharp increase in the incidence of highly virulent virus of the H5N1 subtype (clade h2.3.4.4b) has been registered in birds on all continents, accompanied by the transmission of the virus to various species of mammals. The recorded global mortality rate among wild, domestic and agricultural birds from H5 subtype is approaching to the level of 1 billion cases. A dangerous epidemic factor is becoming more frequent outbreaks of avian influenza with high mortality among mammals, in particular seals and marine lions in North and South America, minks and fur-bearing animals in Spain and Finland, domestic and street cats in Poland. H5N1 avian influenza clade h2.3.4.4b strains isolated from mammals have genetic signatures of partial adaptation to the human body in the PB2, NP, HA, NA genes, which play a major role in regulating the aerosol transmission and the host range of the virus. The current situation poses a real threat of pre-adaptation of the virus in mammals as intermediate hosts, followed by the transition of the pre-adapted virus into the human population with catastrophic consequences.

Association between influenza vaccination and one-year all-cause and cardiovascular mortality risk: A self-controlled case series and matched case-control study.

Debates surrounding the efficacy of influenza vaccination for survival benefits persist, and there is a lack of data regarding its duration of protection. A self-controlled case series (SCCS) and a 1:4 matched case-control study were conducted using the National Health Interview Survey (NHIS) and public-use mortality data from 2005 to 2018 in the United States. The SCCS study identified participants who received influenza vaccination within 12 months before the survey and subsequently died within 1 year of postvaccination. The matched case-control study paired participants who died during the influenza season at the time of survey with four survivors. Among 1167 participants in the SCCS study, there was a 46% reduction in all-cause mortality and a 43% reduction in cardiovascular mortality within 29-196 days of postvaccination. The greatest protection was observed during days 29-56 (all-cause mortality: RI: 0.19; 95% CI: 0.12-0.29; cardiovascular mortality: RI: 0.28; 95% CI: 0.14-0.56). Among 626 cases and 2504 controls included in the matched case-control study, influenza vaccination was associated with a reduction in all-cause mortality (OR: 0.74, 95% CI: 0.60-0.92) and cardiovascular mortality (OR: 0.64, 95% CI: 0.44-0.93) during the influenza season. This study highlights the importance of influenza vaccination in reducing the risks of all-cause and cardiovascular mortality, with effects lasting for approximately 6 months.

The Hospital Burden of Flu in Italy: a retrospective study on administrative data from season 2014-2015 to 2018-2019.

BACKGROUND: Every year in Italy, influenza affects about 4 million people. Almost 5% of them are hospitalised. During peak illness, enormous pressure is placed on healthcare and economic systems. This study aims to quantify the clinical and economic burden of severe influenza during 5 epidemic seasons (2014-2019) from administrative claims data. METHODS: Patients hospitalized with a diagnosis of influenza between October 2014, and April 2019, were analyzed. Clinical characteristics and administrative information were retrieved from health-related Administrative Databases (ADs) of 4 Italian Local Health Units (LHUs). The date of first admission was set as the Index Date (ID). A follow-up period of six months after ID was considered to account for complications and re-hospitalizations, while a lookback period (2 years before ID) was set to assess the prevalence of underlying comorbidities. RESULTS: Out of 2,333 patients with severe influenza, 44.1% were adults ≥ 65, and 25.6% young individuals aged 0-17. 46.8% had comorbidities (i.e., were at risk), mainly cardiovascular and metabolic diseases (45.3%), and chronic conditions (24.7%). The highest hospitalization rates were among the elderly (≥ 75) and the young individuals (0-17), and were 37.6 and 19.5/100,000 inhabitants/year, respectively. The average hospital stay was 8 days (IQR: 14 - 4). It was higher for older individuals (≥ 65 years, 11 days, [17 - 6]) and for those with comorbidities (9 days, [16 - 6]), p-value < 0.001. Similarly, mortality was higher in elderly and those at risk (p-value < 0.001). Respiratory complications occurred in 12.7% of patients, and cardiovascular disorders in 5.9%. Total influenza-related costs were €9.7 million with hospitalization accounting for 95% of them. 47.3% of hospitalization costs were associated with individuals ≥ 65 and 52.9% with patients at risk. The average hospitalisation cost per patient was € 4,007. CONCLUSIONS: This retrospective study showed that during the 2014-2019 influenza seasons in Italy, individuals of extreme ages and those with pre-existing medical conditions, were more likely to be hospitalized with severe influenza. Together with complications and ageing, they worsen patient's outcome and may lead to a prolonged hospitalization, thus increasing healthcare utilization and costs. Our data generate real-world evidence on the burden of influenza, useful to inform public health decision-making.

Effect of a Structured Multilevel Telehealth Service on Hospital Admissions and Mortality During COVID-19 in a Resource-Limited Region in Brazil: Retrospective Cohort Study.

BACKGROUND: The COVID-19 pandemic represented a great stimulus for the adoption of telehealth and many initiatives in this field have emerged worldwide. However, despite this massive growth, data addressing the effectiveness of telehealth with respect to clinical outcomes remain scarce. OBJECTIVE: The aim of this study was to evaluate the impact of the adoption of a structured multilevel telehealth service on hospital admissions during the acute illness course and the mortality of adult patients with flu syndrome in the context of the COVID-19 pandemic. METHODS: A retrospective cohort study was performed in two Brazilian cities where a public COVID-19 telehealth service (TeleCOVID-MG) was deployed. TeleCOVID-MG was a structured multilevel telehealth service, including (1) first response and risk stratification through a chatbot software or phone call center, (2) teleconsultations with nurses and medical doctors, and (3) a telemonitoring system. For this analysis, we included data of adult patients registered in the Flu Syndrome notification databases who were diagnosed with flu syndrome between June 1, 2020, and May 31, 2021. The exposed group comprised patients with flu syndrome who used TeleCOVID-MG at least once during the illness course and the control group comprised patients who did not use this telehealth service during the respiratory illness course. Sociodemographic characteristics, comorbidities, and clinical outcomes data were extracted from the Brazilian official databases for flu syndrome, Severe Acute Respiratory Syndrome (due to any respiratory virus), and mortality. Models for the clinical outcomes were estimated by logistic regression. RESULTS: The final study population comprised 82,182 adult patients with a valid registry in the Flu Syndrome notification system. When compared to patients who did not use the service (n=67,689, 82.4%), patients supported by TeleCOVID-MG (n=14,493, 17.6%) had a lower chance of hospitalization during the acute respiratory illness course, even after adjusting for sociodemographic characteristics and underlying medical conditions (odds ratio [OR] 0.82, 95% CI 0.71-0.94; P=.005). No difference in mortality was observed between groups (OR 0.99, 95% CI 0.86-1.12; P=.83). CONCLUSIONS: A telehealth service applied on a large scale in a limited-resource region to tackle COVID-19 was related to reduced hospitalizations without increasing the mortality rate. Quality health care using inexpensive and readily available telehealth and digital health tools may be delivered in areas with limited resources and should be considered as a potential and valuable health care strategy. The success of a telehealth initiative relies on a partnership between the involved stakeholders to define the roles and responsibilities; set an alignment between the different modalities and levels of health care; and address the usual drawbacks related to the implementation process, such as infrastructure and accessibility issues.

Mortality in Patients Hospitalized for COVID-19 vs Influenza in Fall-Winter 2023-2024.

This cohort study evaluates the risk of death in patients hospitalized for COVID-19 or seasonal influenza following the emergence of the JN.1 variant in winter 2023.

Unveiling the role of preceding seasonal influenza in the development of bacteremic pneumococcal pneumonia in older adults before the COVID-19 pandemic in Japan.

OBJECTIVE: We aimed to investigate the impact of preceding seasonal influenza on the clinical characteristics of adult patients with invasive pneumococcal disease (IPD) in Japan. METHODS: Data for 1722 adult patients with IPD were analyzed before (2017-2019) and during the COVID-19 pandemic (2020-2022). RESULTS: The seasonal influenza epidemic disappeared soon after the emergence of the pandemic. Compared with that before the pandemic (66.7%), we observed a lower bacteremic pneumonia proportion in patients with IPD during the pandemic (55.6%). The clinical presentations of IPD cases significantly differed between those with and without preceding influenza. The proportion of bacteremic pneumonia was higher in IPD patients with preceding influenza than in those without in both younger (44.9% vs 84.2%) and older adults (65.5% vs 87.0%) before the pandemic. The case fatality rate was significantly higher in IPD patients with preceding influenza (28.3%) than in those without (15.3%) in older adults before the pandemic (P = 0.020). Male and aging are high risk factors for death in older patients with IPD who had preceding influenza. CONCLUSION: Our study reveals that preceding seasonal influenza plays a role in the development of bacteremic pneumococcal pneumonia, increasing the risk of death in older adults.

Population-based Influenza and Respiratory Syncytial Virus Hospitalizations and In-hospital Mortality Rates Among Mexican Children Less Than Five Years of Age.

BACKGROUND: Population-based information regarding the impact of respiratory syncytial virus (RSV) and influenza on hospital admissions and mortality is scant for many countries. METHODS: Prospective testing of RSV and influenza virus was undertaken in patients <5 years old admitted to hospital with acute respiratory infection (ARI) between July, 2014 and June, 2015, and mortality rates for children living in 3 municipalities in the state of San Luis Potosí were calculated. RESULTS: During the 12-month study period, 790 children living in these municipalities were admitted with ARI. RSV was detected in 245 (31%) and influenza in 47 (5.9%). History of preterm birth was recorded for 112 children on admission. For children <5 years old, ARI-, RSV- and influenza-associated admission rates were 23.2, 7.2 and 1.4 (per 1000 population), respectively. The corresponding admission rates per 1000 infants <1 year old were 78, 25.2 and 4.4. Preterm infant admission rates were 2 times higher than those of term infants. Six children died; RSV was detected in 4 (66.6%) of the deceased, while no deaths were associated with influenza. ARI and RSV in-hospital mortality rates for children <5 years were 0.18 and 0.12 per 1000 population. ARI and RSV mortality rates in preterm infants were 7 and 14 times higher than in term infants, respectively. CONCLUSIONS: RSV was associated with both high admission and in-hospital mortality rates in children <5 years old. Specific interventions, such as active or passive immunization, to prevent RSV infections are required to reduce ARI-associated infant mortality.

Impact of influenza vaccination history in the clinical course of older adults hospitalized with COVID-19.

BACKGROUND AND PURPOSE: Some studies have shown that influenza vaccination is associated with a lower risk of SARS-CoV-2 infection; in patients with COVID-19 infection, admission to intensive care is reduced, with less need for mechanical ventilation, shorter hospital stays, and reduced mortality. This study aimed to determine if a history of annual influenza vaccination impacts the clinical course of SARS-CoV-2 infection during hospitalization. METHODS: This was an observational, prospective, cohort study of patients older than 65 admitted to the COVID-19 unit from January to June 2021. The history of influenza vaccination over the last 5 years was assessed in each patient during hospitalization. We measured the length of hospital stay, the need for admission to the intensive care unit (ICU), the patient's oxygen requirements, complications during hospitalization, and outcome (medical discharge or death). Patients with a history of vaccination against SARS-CoV-2 were not included. RESULTS: We analyzed 125 patients, 50.4% (n=63) with history of influenza vaccination and 49.6% (n=62) without a history of influenza vaccination. In-hospital mortality was 44.8%, higher in the unvaccinated (54.8%) population (p=0.008). ICU admission was 27% higher in vaccinated (35%) patients (p=0.05). Patients without a history of influenza vaccination had a higher prevalence of cardiac (8% vs. 5%, p=0.04) and renal complications (29% vs. 13%, p=0.02). Patients with a history of vaccination had a greater need for invasive mechanical ventilation (25.4%, p=0.02). CONCLUSION: In this study, a history of influenza vaccination in older adults with SARS-CoV-2 infection was related to lower in-hospital mortality.

Beyond the sine wave: unveiling climate-driven baseline mortality cycles.

The relationship between temperature and mortality is well-established, with higher mortality rates occurring in moderate climates during winter. Studies on COVID-19 and influenza-related excess deaths often assume a sine-like wave pattern for baseline mortality. This study aims to assess the accuracy of this approximation in capturing the observed mortality pattern and explore its linkage with climate. Weekly mortality data from European regions (2000-2019) were modeled using the seasonal-trend decomposition procedure based on Loess. Cycles were grouped into clusters, and underlying trends were extracted using principal component analysis. Generalized linear models assuming a sine-like pattern were used to test predictive value. Cluster analysis divided the regional cycles approximately into continental and temperate climate regions, further subdivided into oceanic and Mediterranean. While the continental region exhibited a sine-like mortality pattern, it displayed modest deviations that compounded further south. The period of elevated winter mortality became shorter but more intense, while decreased summer mortality became more pronounced yet delayed. This study improves weekly estimations of excess mortality models by providing enhanced baselines. The deviation from the sine-like approximation mirrors the idealized outbreak pattern from epidemiological models with sharper surges and more gradual declines. The results point to winter infections, impacted by acquired immunity and weather conditions, as the primary drivers of fluctuations in mortality. In warmer regions, there is an apparent shift toward a lower number of overall infections within a compressed time span.

Boletim epidemiológico de vírus respiratórios (RS): semana epidemiológica (SE) 34 de 2023 / Epidemiological bulletin of respiratory viruses (RS): epidemiological week (SE) 34 of 2023

Com a declaração do fim das emergências de saúde pública de importância Nacional (abril/2022) e Internacional (maio/2023) e o ressurgimentos dos outros vírus respiratórios, o Boletim de COVID-19 foi expandido e passa avaliar de forma integrada os agentes virais de importância à saúde pública. Utilizado o modelo de Vigilância Sentinela para monitoramento da circulação de vírus respiratórios de interesse à saúde pública nas Síndromes Gripais(SG). O objetivo desta estratégia é detectar novos agentes virais e/ou novas linhagens para oportunamente desencadear medidas de controle necessárias e reduzir a carga da doença na sociedade. (AU)

Boletim Epidemiológico de Vírus Respiratórios (RS): semana epidemiológica (SE) 30 de 2023 / Epidemiological bulletin of respiratory viruses (RS): epidemiological week (SE) 30 of 2023

Com a declaração do fim das emergências de saúde pública de importância Nacional (abril/2022) e Internacional (maio/2023) e o ressurgimentos dos outros vírus respiratórios, o Boletim de COVID-19 foi expandido e passa avaliar de forma integrada os agentes virais de importância à saúde pública. Utilizado o modelo de Vigilância Sentinela para monitoramento da circulação de vírus respiratórios de interesse à saúde pública nas Síndromes Gripais(SG). O objetivo desta estratégia é detectar novos agentes virais e/ou novas linhagens para oportunamente desencadear medidas de controle necessárias e reduzir a carga da doença na sociedade. (AU)

Severe forms of influenza infections admitted in intensive care units: Analysis of mortality factors.

Background: The severe forms of influenza infection requiring intensive care unit (ICU) admission remain a medical challenge due to its high mortality. New H1N1 strains were hypothesized to increase mortality. The studies below represent a large series focusing on ICU-admitted influenza patients over the last decade with an emphasis on factors related to death. Methods: A retrospective study of patients admitted in ICU for influenza infection over the 2010-2019 period in Réunion Island (a French overseas territory) was conducted. Demographic data, underlying conditions, and therapeutic management were recorded. A univariate analysis was performed to assess factors related to ICU mortality. Results: Three hundred and fifty adult patients were analyzed. Overall mortality was 25.1%. Factors related to higher mortality were found to be patient age >65, cancer history, need for intubation, early intubation within 48 h after admission, invasive mechanical ventilation (MV), acute respiratory distress syndrome (ARDS), vaso-support drugs, extracorporal oxygenation by membrane (ECMO), dialysis, bacterial coinfection, leucopenia, anemia, and thrombopenia. History of asthma and oseltamivir therapy were correlated with a lower mortality. H1N1 did not impact mortality. Conclusion: Patient's underlying conditions influence hospital admission and secondary ICU admission but were not found to impact ICU mortality except in patients age >65, history of cancer, and bacterial coinfections. Pulmonary involvement was often present, required MV, and often evolved toward ARDS. ICU mortality was strongly related to ARDS severity. We recommend rapid ICU admission of patients with influenza-related pneumonia, management of bacterial coinfection, and early administration of oseltamivir.

A Pathology-based Case Series of Influenza- and COVID-19-associated Pulmonary Aspergillosis: The Proof Is in the Tissue.

Rationale: Invasive pulmonary aspergillosis has emerged as a frequent coinfection in severe coronavirus disease (COVID-19), similarly to influenza, yet the clinical invasiveness is more debated. Objectives: We investigated the invasive nature of pulmonary aspergillosis in histology specimens of influenza and COVID-19 ICU fatalities in a tertiary care center. Methods: In this monocentric, descriptive, retrospective case series, we included adult ICU patients with PCR-proven influenza/COVID-19 respiratory failure who underwent postmortem examination and/or tracheobronchial biopsy during ICU admission from September 2009 until June 2021. Diagnosis of probable/proven viral-associated pulmonary aspergillosis (VAPA) was made based on the Intensive Care Medicine influenza-associated pulmonary aspergillosis and the European Confederation of Medical Mycology (ECMM) and the International Society for Human and Animal Mycology (ISHAM) COVID-19-associated pulmonary aspergillosis consensus criteria. All respiratory tissues were independently reviewed by two experienced pathologists. Measurements and Main Results: In the 44 patients of the autopsy-verified cohort, 6 proven influenza-associated and 6 proven COVID-19-associated pulmonary aspergillosis diagnoses were identified. Fungal disease was identified as a missed diagnosis upon autopsy in 8% of proven cases (n = 1/12), yet it was most frequently found as confirmation of a probable antemortem diagnosis (n = 11/21, 52%) despite receiving antifungal treatment. Bronchoalveolar lavage galactomannan testing showed the highest sensitivity for VAPA diagnosis. Among both viral entities, an impeded fungal growth was the predominant histologic pattern of pulmonary aspergillosis. Fungal tracheobronchitis was histologically indistinguishable in influenza (n = 3) and COVID-19 (n = 3) cases, yet macroscopically more extensive at bronchoscopy in influenza setting. Conclusions: A proven invasive pulmonary aspergillosis diagnosis was found regularly and with a similar histological pattern in influenza and in COVID-19 ICU case fatalities. Our findings highlight an important need for VAPA awareness, with an emphasis on mycological bronchoscopic work-up.

Boletim Epidemiológico de Vírus Respiratórios (RS): semana epidemiológica (SE) 25 de 2023 / Epidemiological bulletin of respiratory viruses (RS): epidemiological week (SE) 25 of 2023

Com a declaração do fim das emergências de saúde pública de importância Nacional (abril/2022) e Internacional (maio/2023) e o ressurgimentos dos outros vírus respiratórios, o Boletim de COVID-19 foi expandido e passa avaliar de forma integrada os agentes virais de importância à saúde pública. Utilizado o modelo de Vigilância Sentinela para monitoramento da circulação de vírus respiratórios de interesse à saúde pública nas Síndromes Gripais(SG). O objetivo desta estratégia é detectar novos agentes virais e/ou novas linhagens para oportunamente desencadear medidas de controle necessárias e reduzir a carga da doença na sociedade. (AU)

Boletim Epidemiológico de Vírus Respiratórios (RS): semana epidemiológica (SE) 23 de 2023 / Epidemiological bulletin of respiratory viruses (RS): epidemiological week (SE) 23 of 2023

Com a declaração do fim das emergências de saúde pública de importância Nacional (abril/2022) e Internacional (maio/2023) e o ressurgimentos dos outros vírus respiratórios, o Boletim de COVID-19 foi expandido e passa avaliar de forma integrada os agentes virais de importância à saúde pública. Utilizado o modelo de Vigilância Sentinela para monitoramento da circulação de vírus respiratórios de interesse à saúde pública nas Síndromes Gripais(SG). O objetivo desta estratégia é detectar novos agentes virais e/ou novas linhagens para oportunamente desencadear medidas de controle necessárias e reduzir a carga da doença na sociedade. (AU)

Boletim Epidemiológico de Vírus Respiratórios (RS): semana epidemiológica (SE) 21 de 2023 / Epidemiological bulletin of respiratory viruses (RS): epidemiological week (SE) 21 of 2023

Com a declaração do fim das emergências de saúde pública de importância Nacional (abril/2022) e Internacional (maio/2023) e o ressurgimentos dos outros vírus respiratórios, o Boletim de COVID-19 foi expandido e passa avaliar de forma integrada os agentes virais de importância à saúde pública. Utilizado o modelo de Vigilância Sentinela para monitoramento da circulação de vírus respiratórios de interesse à saúde pública nas Síndromes Gripais(SG). O objetivo desta estratégia é detectar novos agentes virais e/ou novas linhagens para oportunamente desencadear medidas de controle necessárias e reduzir a carga da doença na sociedade. (AU)

Boletim Epidemiológico de Vírus Respiratórios (RS): semana epidemiológica (SE) 18 de 2023 / Epidemiological bulletin of respiratory viruses (RS): epidemiological week (SE) 18 of 2023

Com a declaração do fim das emergências de saúde pública de importância Nacional (abril/2022) e Internacional (maio/2023) e o ressurgimentos dos outros vírus respiratórios, o Boletim de COVID-19 foi expandido e passa avaliar de forma integrada os agentes virais de importância à saúde pública. Utilizado o modelo de Vigilância Sentinela para monitoramento da circulação de vírus respiratórios de interesse à saúde pública nas Síndromes Gripais(SG). O objetivo desta estratégia é detectar novos agentes virais e/ou novas linhagens para oportunamente desencadear medidas de controle necessárias e reduzir a carga da doença na sociedade. (AU)

Risk of Death in Patients Hospitalized for COVID-19 vs Seasonal Influenza in Fall-Winter 2022-2023.

This study uses data from the US Department of Veterans Affairs to assess whether SARS-CoV-2 remains associated with higher risk of death compared with seasonal influenza in fall-winter 2022-2023.

Boletim Epidemiológico de Vírus Respiratórios (RS): semana epidemiológica (SE) 16 de 2023 / Epidemiological bulletin of respiratory viruses (RS): epidemiological week (SE) 16 of 2023

Com a declaração do fim das emergências de saúde pública de importância Nacional (abril/2022) e Internacional (maio/2023) e o ressurgimentos dos outros vírus respiratórios, o Boletim de COVID-19 foi expandido e passa avaliar de forma integrada os agentes virais de importância à saúde pública. Utilizado o modelo de Vigilância Sentinela para monitoramento da circulação de vírus respiratórios de interesse à saúde pública nas Síndromes Gripais(SG). O objetivo desta estratégia é detectar novos agentes virais e/ou novas linhagens para oportunamente desencadear medidas de controle necessárias e reduzir a carga da doença na sociedade. (AU)