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)

Association between plasma glycocalyx component levels and poor prognosis in severe influenza type A (H1N1).

Influenza A virus infection causes a series of diseases, but the factors associated with disease severity are not fully understood. Disruption of the endothelial glycocalyx contributes to acute lung injury in sepsis, but has not been well studied in H1N1 influenza. We aim to determine whether the plasma glycocalyx components levels are predictive of disease severity in H1N1 influenza. This prospective observational study included 53 patients with influenza A (H1N1) during the influenza season, and 30 healthy controls in our hospital. Patients were grouped by severity and survival. We collected clinical data and blood samples at admission. Inflammatory factors (tumor necrosis factor-α, interleukin-6, interleukin-10) and endothelial glycocalyx components (syndecan-1, hyaluronan, heparan sulfate) were measured. The plasma levels of syndecan-1, hyaluronan, and heparan sulfate were significantly higher in patients with severe influenza A (H1N1) than in mild cases. Syndecan-1 and hyaluronan were positively correlated with disease severity, which was indicated by the APACHE II and SOFA scores and lactate levels, and negatively correlated with albumin levels. At a cutoff point ≥ 173.9 ng/mL, syndecan-1 had a 81.3% sensitivity and 70.3% specificity for predicting of 28-day mortality. Kaplan-Meier analysis demonstrated a strong association between syndecan-1 levels and 28-day mortality (log-rank 11.04, P = 0.001). Elevated plasma levels of syndecan-1 has a potential role in systemic organ dysfunction and may be indicative of disease severity in patients with influenza A (H1N1).

Comparative outcomes between COVID-19 and influenza patients placed on veno-venous extracorporeal membrane oxygenation for severe ARDS.

BACKGROUND: ECMO is an established supportive adjunct for patients with severe, refractory ARDS from viral pneumonia. However, the exact role and timing of ECMO for COVID-19 patients remains unclear. METHODS: We conducted a retrospective comparison of the first 32 patients with COVID-19-associated ARDS to the last 28 patients with influenza-associated ARDS placed on V-V ECMO. We compared patient factors between the two cohorts and used survival analysis to compare the hazard of mortality over sixty days post-cannulation. RESULTS: COVID-19 patients were older (mean 47.8 vs. 41.2 years, p = 0.033), had more ventilator days before cannulation (mean 4.5 vs. 1.5 days, p < 0.001). Crude in-hospital mortality was significantly higher in the COVID-19 cohort at 65.6% (n = 21/32) versus 36.3% (n = 11/28, p = 0.041). The adjusted hazard ratio over sixty days for COVID-19 patients was 2.81 (95% CI 1.07, 7.35) after adjusting for age, race, ECMO-associated organ failure, and Charlson Comorbidity Index. CONCLUSION: ECMO has a role in severe ARDS associated with COVID-19 but providers should carefully weigh patient factors when utilizing this scarce resource in favor of influenza pneumonia.

Clinical outcomes of adults hospitalized for laboratory confirmed respiratory syncytial virus or influenza virus infection.

OBJECTIVES: Respiratory syncytial virus (RSV) can cause severe disease in adults, but far less is known than for influenza. The aim of our study was to compare the disease course of RSV infections with influenza infections among hospitalized adults. METHODS: We retrieved clinical data from an ongoing surveillance of adults hospitalized with RSV or influenza virus infection in two acute care hospitals in North-Eastern Switzerland during the winter seasons 2017/2018 and 2018/2019. Our main analysis compared the odds between RSV and influenza patients for admission to an intensive care unit (ICU) or in-hospital death within 7 days after admission. RESULTS: There were 548 patients, of whom 79 (14.4%) had an RSV and 469 (85.6%) an influenza virus infection. Both groups were similar with respect to age, sex, smoking status, nutritional state, and comorbidities. More RSV patients had an infiltrate on chest radiograph on admission (46.4% vs 29.9%, p = .007). The proportion of patients with RSV who died or were admitted to ICU within seven days after admission was 19.0% compared to 10.2% in influenza patients (p = .024). In multivariable analysis, a higher leukocyte count (adjusted OR 1.07, 95% CI 1.02-1.13, p = .013) and the presence of a pneumonic infiltrate (aOR 3.41, 95% CI 1.93-6.02) significantly increased the risk for experiencing the adverse primary outcome while the effect of the underlying viral pathogen became attenuated (aOR 1.18, 95% CI 0.58-2.41, p = .0.655). CONCLUSIONS: Our results suggest that RSV is responsible for clinical courses at least as severe as influenza in adults. This supports the need for better guidance on diagnostic strategies as well as on preventive and therapeutic measures for hospitalized adults with RSV infection.

Influenza co-infection associated with severity and mortality in COVID-19 patients.

BACKGROUND: In COVID-19 patients, undetected co-infections may have severe clinical implications associated with increased hospitalization, varied treatment approaches and mortality. Therefore, we investigated the implications of viral and bacterial co-infection in COVID-19 clinical outcomes. METHODS: Nasopharyngeal samples were obtained from 48 COVID-19 patients (29% ICU and 71% non-ICU) and screened for the presence of 24 respiratory pathogens using six multiplex PCR panels. RESULTS: We found evidence of co-infection in 34 COVID-19 patients (71%). Influenza A H1N1 (n = 17), Chlamydia pneumoniae (n = 13) and human adenovirus (n = 10) were the most commonly detected pathogens. Viral co-infection was associated with increased ICU admission (r = 0.1) and higher mortality (OR 1.78, CI = 0.38-8.28) compared to bacterial co-infections (OR 0.44, CI = 0.08-2.45). Two thirds of COVID-19 critically ill patients who died, had a co-infection; and Influenza A H1N1 was the only pathogen for which a direct relationship with mortality was seen (r = 0.2). CONCLUSIONS: Our study highlights the importance of screening for co-infecting viruses in COVID-19 patients, that could be the leading cause of disease severity and death. Given the high prevalence of Influenza co-infection in our study, increased coverage of flu vaccination is encouraged to mitigate the transmission of influenza virus during the on-going COVID-19 pandemic and reduce the risk of severe outcome and mortality.

Disease-Specific Excess Mortality During the COVID-19 Pandemic: An Analysis of Weekly US Death Data for 2020.

Objectives. To examine the disease-specific excess deaths during the COVID-19 pandemic in the United States. Methods. We used weekly death data from the National Center for Health Statistics to analyze the trajectories of excess deaths from specific diseases in the United States during the COVID-19 pandemic, at the national level and in 4 states, from the first to 52nd week of 2020. We used the average weekly number of deaths in the previous 6 years (2014-2019) as baseline. Results. Compared with the same week at baseline, the trajectory of number of excess deaths from cardiovascular disease (CVD) was highly parallel to the trajectory of the number of excess deaths related to COVID-19. The number of excess deaths from diabetes mellitus, influenza and respiratory diseases, and malignant neoplasms remained relatively stable over time. Conclusions. The parallel trajectory of excess mortality from CVD and COVID-19 over time reflects the fact that essential health services for noncommunicable diseases were reduced or disrupted during the COVID-19 pandemic, and the severer the pandemic, the heavier the impact.

Modelo estadístico para estimar el impacto histórico de la influenza sobre la mortalidad en Cuba / Statistical model to estimate the historical impact of influenza on mortality in Cuba

Introducción: La influenza tiene elevado impacto en la mortalidad humana y en Cuba la categoría influenza y neumonía ocupa el cuarto lugar entre sus causales generales. En los países templados, con marcada estacionalidad, esto se capta con modelos estadísticos, tarea que se dificulta en el trópico y pendiente en Cuba por la ausencia de igual definición estacional. Objetivo: Estimar el impacto histórico de la influenza tipo A y B y los subtipos A(H3N2) y A(H1N1) sobre la mortalidad mediante el ajuste de un modelo de regresión a las condiciones estacionales específicas de Cuba. Métodos: Se ejecutó un estudio longitudinal y retrospectivo. En un primer paso se ajustaron dos modelos de Poisson con la mortalidad influenza y neumonía total y las personas ≥ 65 años de edad como variables respuestas en los cinco meses de mayor positividad en influenza, desde la temporada 1987-1988 hasta la 2004-2005 y los positivos en tipo A y en tipo B como explicatorias. En otro par de modelos se estimó el impacto del A(H3N2) y el A(H1N1), considerando como respuesta los fallecidos atribuidos previamente al tipo A. Resultados: Se atribuyeron a la influenza 7803 fallecidos entre todas las edades y 6152 entre las personas ≥ 65 años de edad, con un 56,3 por ciento asociados al A(H3N2), el 17,6 por ciento al A(H1N1) y el 26,1 por ciento al tipo B. Conclusiones. Se logró estimar el impacto de la influenza sobre la mortalidad mediante el ajuste para Cuba de un modelo estadístico que permitió demostrar la asociación de la circulación de estos virus con la mortalidad en el país, lo que ratifica la necesidad de reforzar la vigilancia, el control y la vacunación contra esta infección viral. Se demuestra la posibilidad de ajustar estos modelos de regresión a otros virus respiratorios y a la actual pandemia por la COVID-19, en las condiciones estacionales de Cuba(AU)

Introduction: Influenza has a high impact on human mortality and in Cuba influenza and pneumonia rank fourth among its general causes. In temperate climate countries, with marked seasonality, this is captured by statistical models, a task that is difficult in the tropics and pending in Cuba due to the absence of the same seasonal definition. Objective: Estimate the historical impact of influenza type A and B and subtypes A(H3N2) and A(H1N1) on mortality, by adjusting a regression model to the specific seasonal conditions of Cuba. Methods: A longitudinal and retrospective study was performed. In a first step, two Poisson models were adjusted with influenza and total pneumonia mortality and people ≥ 65 years old as response variables in the five months with the highest positivity to influenza in the period 1987-1988 to 2004-2005, and the positive ones to type A and type B as explanatory variables. In another pair of models was estimated the impact of A(H3N2) and A(H1N1), considering as a response the deaths previously attributed to type A. Results: 7 803 deaths among all ages and 6 152 among 65-year-olds were attributed to influenza, with 56.3 percent associated to A(H3N2), 17.6 percent to A(H1N1) and 26.1 percent to type B. Conclusions: It was possible to estimate the impact of influenza on mortality by adjusting for Cuba a statistical model that demonstrated the association of the circulation of these viruses with the mortality in the country, which confirms the need to strengthen surveillance, control and vaccination against this viral infection. The possibility of adjusting in the seasonal conditions of Cuba these regression models to other respiratory viruses and the current pandemic by COVID-19 is demonstrated(AU)

Fine Particulate Matter Air Pollution and Mortality Risk Among US Cancer Patients and Survivors.

Background: Exposure to fine particulate matter (PM2.5) air pollution has been linked to increased risk of mortality, especially cardiopulmonary and lung cancer mortality. It is unknown if cancer patients and survivors are especially vulnerable to PM2.5 air pollution exposure. This study evaluates PM2.5 exposure and risk for cancer and cardiopulmonary mortality in cohorts of US cancer patients and survivors. Methods: A primary cohort of 5 591 168 of cancer patients and a 5-year survivor cohort of 2 318 068 was constructed using Surveillance, Epidemiology, and End Results Program data from 2000 to 2016, linked with county-level estimates of long-term average concentrations of PM2.5. Cox proportional hazards models were used to estimate PM2.5-mortality hazard ratios controlling for age-sex-race combinations and individual and county-level covariables. Results: Of those who died, 26% died of noncancer causes, mostly from cardiopulmonary disease. Minimal PM2.5-mortality associations were observed for all-cause mortality (hazard ratio [HR] = 1.01, 95% confidence interval [CI] = 1.00 to 1.03) per 10 µg/m3 increase in PM2.5. Substantial adverse PM2.5-mortality associations were observed for cardiovascular (HR = 1.32, 95% CI = 1.26 to 1.39), chronic obstructive pulmonary disease (HR = 1.10, 95% CI = 1.01 to 1.20), influenza and pneumonia (HR = 1.55, 95% CI = 1.33 to 1.80), and cardiopulmonary mortality combined (HR = 1.25, 95% CI = 1.21 to 1.30). PM2.5-cardiopulmonary mortality hazard ratio was higher for cancer patients who received chemotherapy or radiation treatments. Conclusions: Air pollution is adversely associated with cardiopulmonary mortality for cancer patients and survivors, especially those who received chemotherapy or radiation treatment. Given ubiquitous and involuntary air pollution exposures and large numbers of cancer patients and survivors, these results are of substantial clinical and public health importance.

The Extent of Aspergillosis in Critically Ill Patients With Severe Influenza Pneumonia: A Multicenter Cohort Study.

OBJECTIVES: To determine the frequency and prognosis of invasive pulmonary aspergillosis in critically ill patients with severe influenza pneumonia. DESIGN: Retrospective multicenter cohort study. SETTING: Five French ICUs. PATIENTS: Patients with influenza admitted to ICU between 2009 and 2018. MEASUREMENTS AND MAIN RESULTS: Of the 524 patients admitted for severe influenza diagnosed with a positive airway reverse-transcriptase polymerase chain reaction test, 450 (86%) required mechanical ventilation. A lower respiratory tract sample yielded with Aspergillus (Asp+) in 28 patients (5.3%). Ten patients (1.9%) were diagnosed with putative or proven invasive pulmonary aspergillosis, based on the validated AspICU algorithm. A multivariate model was built to identify independent risk factors for Aspergillus-positive pulmonary culture. Factors independently associated with Aspergillus-positive culture were liver cirrhosis (odds ratio = 6.7 [2.1-19.4]; p < 0.01), hematologic malignancy (odds ratio = 3.3 [1.2-8.5]; p = 0.02), Influenza A(H1N1)pdm09 subtype (odds ratio = 3.9 [1.6-9.1]; p < 0.01), and vasopressor requirement (odds ratio = 4.1 [1.6-12.7]; p < 0.01). In-hospital mortality of Asp+ patients was 36% versus 21% in patients without Aspergillus-positive pulmonary culture (p = 0.09). CONCLUSIONS: In this large retrospective multicenter cohort of critically ill patients, putative invasive pulmonary aspergillosis according to AspICU algorithm was a relatively rare complication of influenza. Patients at higher risk of Aspergillus pulmonary colonization included those with liver cirrhosis, hematologic malignancy, H1N1pdm09 influenza A virus, and requiring vasopressors. Our results provide additional data on the controversial association between severe influenza and invasive pulmonary aspergillosis. Reaching a consensual definition of invasive pulmonary aspergillosis becomes mandatory and confers further prospective research.

Gender differences and influenza-associated mortality in hospitalized influenza A patients during the 2018/19 season.

BACKGROUND: In this study we analyzed gender differences in the clinical presentation of patients with molecular confirmed influenza A. Additionally, we tried to identify predictors of influenza-associated mortality. MATERIALS/METHODS: In this prospective observational multi-center-study we included all influenza-positive patients ≥ 18 years who were hospitalized and treated on flu-isolation-wards in three hospitals in Vienna during the 2018/19 influenza season. Diagnoses were made via Cobas® Liat® POCT. RESULTS: 490 Patients (48.8% female) tested positive for influenza A. Female patients were older (median age 76 years vs. 70 years, p < 0.001). Male patients had a higher rate of chronic liver disease in history (8.8% vs. 2.9%, p = 0.006), myositis (11.7% vs. 3.1%, p < 0.001) and ICU admissions (9.6% vs. 4.6%, p = 0.03). The in-hospital mortality rate was 4.3% and increased to 9.5% during the 90-day follow-up period. Female patients > 75 years had a significantly higher in-hospital mortality rate than ≤ 75-year-old females (9.2% vs. 1.7%, p = 0.019). This effect was not observed in male patients (5.4% vs. 1.9%, p = ns). Age > 75 years (OR 5.49, 95% CI 1.10-27.43), acute heart failure (OR 3.56, 95% CI 1.03-12.05) and ICU admission (OR 6.1, 95% CI 0.98-37.91) were predictors for in-hospital mortality for female patients, while any malignancy (OR 9.4, 95% CI 1.90-46.54) and ICU admission (OR 7.05, 95% CI 1.44-34.55) were predictors in male patients. CONCLUSIONS: Gender is associated with differences in clinical presentation and complications of influenza A virus infection. Women with acute heart failure or aged > 75 years have an increased risk of influenza associated in-hospital mortality, while ICU admission and any malignancy are predictors for male patients. Mortality rates in patients > 75 years are 5-10 times higher compared to their non-hospitalized influenza-negative Austrian counterparts.

Comparison of the clinical characteristics and outcomes of hospitalized adult COVID-19 and influenza patients - a prospective observational study.

BACKGROUND: We compared the clinical characteristics, findings, and outcomes of hospitalized patients with coronavirus disease 2019 (COVID-19) or influenza to detect relevant differences. METHODS: From December 2019 to April 2020, we recruited all eligible hospitalized adults with respiratory infection to a prospective observational study at a tertiary care hospital in Finland. Influenza and SARS-CoV-2 infections were confirmed by RT-PCR. Follow-up lasted for 3 months from admission. RESULTS: We included 61 patients, of whom 28 were COVID-19 and 33 influenza patients with median ages of 53 and 56 years. Majority of both COVID-19 and influenza patients were men (61% vs. 67%) and had at least one comorbidity (68% vs. 85%). Pulmonary diseases and current smoking were less common among COVID-19 than influenza patients (5 [18%] vs. 15 [45%], p=.03 and 1 [4%] vs. 10 [30%], p=.008). In chest X-ray at admission, ground-glass opacities (GGOs) and consolidations were more frequent among COVID-19 than influenza patients (19 [68%] and 7 [21%], p<.001). Severe disease and intensive care unit (ICU) admission occurred more often among COVID-19 than influenza patients (26 [93%] vs. 19 [58%], p=.003 and 8 [29%] vs. 2 [6%], p=.034). COVID-19 patients were hospitalized longer than influenza patients (six days [IQR 4-21] vs. 3 [2-4], p<.001). CONCLUSIONS: Bilateral GGOs and consolidations in chest X-ray may help to differentiate COVID-19 from influenza. Hospitalized COVID-19 patients had more severe disease, required longer hospitalization and were admitted to ICU more often than influenza patients, which has important implications for public health policies.

Outcome of Patients Admitted to Intensive Care Units due to Influenza-Related Severe Acute Respiratory Illness in 2017-2018 Flu Season: A Multicenter Study from Turkey.

BACKGROUND: Influenza can cause severe acute respiratory illness (SARI), which occurs as local outbreaks or seasonal epidemics with high intensive care unit (ICU) admission and mortality rates. Mortality is mainly due to SARI. OBJECTIVE: The aim of this study was to evaluate the outcome of patients admitted to ICU due to influenza-related SARI in 2017-2018 flu season in Turkey. METHODS: A retrospective multicenter study was conducted in 13 ICUs with a total of 216 beds from 6 cities in Turkey. All adult patients (over 18 years) admitted to the ICUs in 2017-2018 flu season (between September 1, 2017, and April 30, 2018) because of SARI and with a positive nasopharyngeal swab for influenza were included in the study. RESULTS: A total of 123 cases were included in the study. The mean age of patients was 64.5 ± 17.5 years, and 66 (53.7%) patients were older than 65 years. The ICU mortality was 33.9%, and hospital mortality was 35.6%. Invasive mechanical ventilation (IMV), acute kidney injury (AKI), hematologic malignancy, and >65 years of age were the factors affecting mortality in influenza. CONCLUSION: SARI due to influenza carries a high mortality rate, and IMV, AKI, presence of hematologic malignancy, and older age are independent risk factors for mortality.

Environmental Cadmium and Mortality from Influenza and Pneumonia in U.S. Adults.

BACKGROUND: Environmental cadmium exposure is widespread. In humans, cadmium is poorly excreted, triggers pulmonary inflammation, reduces pulmonary function, and enhances lung injury by respiratory syncytial virus. OBJECTIVES: We examined the association of cadmium burden with mortality related to influenza or pneumonia. METHODS: This prospective analysis of the National Health and Nutrition Examination Survey (NHANES) included 7,173 and 8,678 participants ≥45 years of age enrolled in NHANES-III and NHANES 1999-2006, respectively. Associations were evaluated between cadmium and mortality from influenza or pneumonia during a median follow-up of 17.3 y (NHANES-III, based on creatinine-corrected urine cadmium) and 11.4 y (NHANES 1999-2006, based on blood cadmium). Survey-weighted Cox proportional hazard models were used to compute hazard ratios (HRs) comparing the mortality of individuals at the 80th vs. the 20th percentile of cadmium concentrations. RESULTS: In NHANES-III, after adjustment for sex, race/ethnicity, education, body mass index, serum cholesterol, hypertension, and NHANES phase (or cycle), the HR comparing influenza or pneumonia mortality among participants with creatinine-corrected urinary cadmium in the 80th vs. 20th percentile was 1.15 (95% CI: 1.05, 1.26; p=0.002) in the population as a whole and 1.27 (95% CI: 1.12, 1.43; p=0.002) among never smokers. In NHANES 1999-2006, adjusted HRs for the 80th vs. 20th percentile of blood cadmium were 1.14 (95% CI: 0.96, 1.36; p=0.15) for the overall population and 1.71 (95% CI: 0.95, 3.09; p=0.07) in never smokers. DISCUSSION: Among middle-aged and older adults in the United States, higher cadmium burdens are associated with higher mortality from influenza or pneumonia. This raises the possibility that cadmium may worsen outcomes from COVID-19 infections. https://doi.org/10.1289/EHP7598.

Mortality rates and causes of death in Swedish Myasthenia Gravis patients.

Myasthenia Gravis (MG) is an autoimmune disease with several comorbidities, however information on MG mortality remains sparse. We conducted a nationwide register-based study on mortality rates and causes of death among Swedish MG patients. Data was acquired from four Swedish National Board of Health and Welfare registers. A total of 4559 MG patients (2522 women, 55.3%) being alive entering the year 2006, were identified. 1121 patients (562 women, 50.1%) died during 2006-2016. Age- and gender-standardized mortality rate was 1.51 (95% CI 0.40) per 100 patients and did not differ from the Swedish general population. Time from MG diagnosis to death was 8.9 ±â€¯6.8 years. The most common ultimate cause of death was cancer (19.5%), followed by ischemic heart disease (13.3%) and MG (11.3%). When MG was stated as the ultimate cause of death, there was a strikingly higher likelihood of having influenza/pneumonia as a contributing cause of death (OR 2.5, p<0.0001). In conclusion, although we could not confirm a higher mortality rate in Swedish MG patients compared to the general population, and despite modern advancements in treatment, we observed that MG itself was stated as the third most common ultimate cause of death in Swedish MG patients.

Iron status is linked to disease severity after avian influenza virus H7N9 infection.

BACKGROUND AND OBJECTIVES: The high mortality rate of H7N9 strain of avian influenza virus (AIV) infected patients has been a major clinical concern. Iron overload increases the susceptibility of host for several kinds of microbial infection. However, the study on patients' iron and ferritin status associated with clinical outcome of AIVH7N9 virus infection is poorly understood, and in order to explain the linkage we carried out this study. METHODS AND STUDY DESIGN: We retrospectively collected serum from 46 patients infected with H7N9 virus from the hospital in Hangzhou city, Zhejiang province of China in 2013. We measured the level of serum iron and ferritin by Enzyme-Linked Immunosorbent Assay (ELISA). The correlation analysis of iron and ferritin with disease severity was done by SPSS 16.0 and MedCalc Software. RESULTS: After H7N9 infection, there is a reduction in iron level and an increase in ferritin, hepcidin and C-reactive protein (CRP) level in patient's serum compared to those of the control (p<0.001), and there's little correlation between procalcitonin (PCT) level and H7N9 infection. At week 1 and week 2 post-infection, serum iron level is much lower and ferritin level is much higher in the patients who died later than those in the patients who survived. The sensitivity, specificity, and Area Under the Curve (AUC) of the assay was calculated with MedCalc software and they were 85.5%, 65.9% and 0.803 for iron and 84.9%, 80.7% and 0.900 for ferritin, 95.2%, 51.1% and 0.684 for PCT and 100%, 94.6% and 0.988 for CRP, respectively. CONCLUSIONS: Our study found that low serum iron and high serum ferritin levels are correlated with the disease severity of H7N9-infected patients and can predict fatal outcomes.

Simultaneous circulation of COVID-19 and flu in Italy: Potential combined effects on the risk of death?

Based on data updated to 20 May 2020, the total recorded number of patients who died due to COVID-19-related reasons in Italy was 31,851. Demographic and clinical characteristics of patients who have died (including the number of comorbidities) are extremely relevant, especially to define those with a higher risk of mortality. Health authorities recommend influenza (flu) vaccinations in a number of categories at risk of serious medical complications, including: people aged ≥65 years, or patients with diabetes, cardiovascular diseases, chronic obstructive pulmonary disease (COPD), renal failure, cancer, immunodeficiencies, chronic hepatopathies, and chronic inflammatory bowel diseases. The seasonal flu peak certainly preceded that of the pandemic; however, it would seem clear that the two viruses have been simultaneously circulating in Italy for a while. Hence, after the peak of seasonal flu, influenza-like illness-related (ILI) deaths started to grow again. While some of the excess mortality reported in the ILI group may be attributable to COVID-19, a question arises: do we have to consider this observation as a result of a random sequence of events or a potential relationship between the two viruses play a role? A cooperation mechanism intended at establishing an absolute advantage over the host could also be assumed; this system often takes place to boost the reproductive probabilities. A characterization of those who died due to virus-related reasons can be performed by cross-linking data (stored in different warehouses) from the same geographical area and developing electronic health records. It would be of great relevance to identify people at very high risk of mortality as a result of an overlapping or combination of risk factors that were separately reported in patients who died from COVID-19 or influenza. A description of the subgroup of people at higher risk of mortality will be crucial for prioritizing and implementing future public health prevention and treatment programs.

Influenza Vaccination Is Associated With Reduced Cardiovascular Mortality in Adults With Diabetes: A Nationwide Cohort Study.

OBJECTIVE: Recent influenza infection is associated with an increased risk of atherothrombotic events, including acute myocardial infarction (AMI) and stroke. Little is known about the association between influenza vaccination and cardiovascular outcomes in patients with diabetes. RESEARCH DESIGN AND METHODS: We used nationwide register data to identify patients with diabetes in Denmark during nine consecutive influenza seasons in the period 2007-2016. Diabetes was defined as use of glucose-lowering medication. Patients who were not 18-100 years old or had ischemic heart disease, heart failure, chronic obstructive lung disease, cancer, or cerebrovascular disease were excluded. Patient exposure to influenza vaccination was assessed before each influenza season. We considered the outcomes of death from all causes, death from cardiovascular causes, and death from AMI or stroke. For each season, patients were monitored from December 1 until April 1 the next year. RESULTS: A total of 241,551 patients were monitored for a median of four seasons (interquartile range two to eight seasons) for a total follow-up of 425,318 person-years. The vaccine coverage during study seasons ranged from 24% to 36%. During follow-up, 8,207 patients died of all causes (3.4%), 4,127 patients died of cardiovascular causes (1.7%), and 1,439 patients died of AMI/stroke (0.6%). After adjustment for confounders, vaccination was significantly associated with reduced risks of all-cause death (hazard ratio [HR] 0.83, P < 0.001), cardiovascular death (HR 0.84, P < 0.001), and death from AMI or stroke (HR 0.85, P = 0.028) and a reduced risk of being admitted to hospital with acute complications associated with diabetes (diabetic ketoacidosis, hypoglycemia, or coma) (HR 0.89, P = 0.006). CONCLUSIONS: In patients with diabetes, influenza vaccination was associated with a reduced risk of all-cause death, cardiovascular death, and death from AMI or stroke. Influenza vaccination may improve outcome in patients with diabetes.

Impact of lower body mass index on risk of all-cause mortality and infection-related death in Japanese chronic kidney disease patients.

BACKGROUND: Several studies have reported that lower body mass index (BMI) is associated with high mortality in patients with chronic kidney disease (CKD). Rate of infection-related death in CKD patients is increasing. However, the relationship between BMI and infection-related death is unclear. METHODS: Overall, 2648 CKD outpatients (estimated glomerular filtration rate < 60 mL/min and/or presenting with proteinuria) under the care of nephrologists were prospectively followed for 5 years. Patients were stratified by quartile of BMI levels. Data on all-cause mortality before progression to end-stage kidney disease (ESKD) and the cause of death were collected. RESULTS: The median follow-up time was 3.9 years (interquartile range, 1.7-5.0); 114 patients died and 308 started renal replacement therapy. The leading causes of death were as follows; cardiovascular (41%), infection-related (21%), and malignancy-related (18%). Advanced age and lower BMI were the significant risk factors for all-cause mortality before progression to ESKD. Advanced age was statistically associated with respective causes of death, while lower BMI was associated with infection-related death only. CKD stage had no significant impact on all-cause or individual mortality. CONCLUSIONS: Low BMI was associated with significant risk of all-cause mortality and infection-related death, which may indicate the novel clinical target to improve CKD outcomes.

Complicated hospitalization due to influenza: results from the Global Hospital Influenza Network for the 2017-2018 season.

BACKGROUND: Since 2011, the Global Influenza Hospital Surveillance Network (GIHSN) has used active surveillance to prospectively collect epidemiological and virological data on patients hospitalized with influenza virus infection. Here, we describe influenza virus strain circulation in the GIHSN participant countries during 2017-2018 season and examine factors associated with complicated hospitalization among patients admitted with laboratory-confirmed influenza illness. METHODS: The study enrolled patients who were hospitalized in a GIHSN hospital in the previous 48 h with acute respiratory symptoms and who had symptoms consistent with influenza within the 7 days before admission. Enrolled patients were tested by reverse transcription-polymerase chain reaction to confirm influenza virus infection. "Complicated hospitalization" was defined as a need for mechanical ventilation, admission to an intensive care unit, or in-hospital death. In each of four age strata (< 15, 15-< 50, 50-< 65, and ≥ 65 years), factors associated with complicated hospitalization in influenza-positive patients were identified by mixed effects logistic regression and those associated with length of hospital stay using a linear mixed-effects regression model. RESULTS: The study included 12,803 hospitalized patients at 14 coordinating sites in 13 countries, of which 4306 (34%) tested positive for influenza. Influenza viruses B/Yamagata, A/H3N2, and A/H1N1pdm09 strains dominated and cocirculated, although the dominant strains varied between sites. Complicated hospitalization occurred in 10.6% of influenza-positive patients. Factors associated with complicated hospitalization in influenza-positive patients included chronic obstructive pulmonary disease (15-< 50 years and ≥ 65 years), diabetes (15-< 50 years), male sex (50-< 65 years), hospitalization during the last 12 months (50-< 65 years), and current smoking (≥65 years). Chronic obstructive pulmonary disease (50-< 65 years), other chronic conditions (15-< 50 years), influenza A (50-< 65 years), and hospitalization during the last 12 months (< 15 years) were associated with a longer hospital stay. The proportion of patients with complicated influenza did not differ between influenza A and B. CONCLUSIONS: Complicated hospitalizations occurred in over 10% of patients hospitalized with influenza virus infection. Factors commonly associated with complicated or longer hospitalization differed by age group but commonly included chronic obstructive pulmonary disease, diabetes, and hospitalization during the last 12 months.