Patients with influenza admitted to a tertiary-care hospital in Riyadh between 2018 and 2022: characteristics, outcomes and factors associated with ICU admission and mortality.

BACKGROUND: Influenza is a common cause of hospital admissions globally with regional variations in epidemiology and clinical profile. We evaluated the characteristics and outcomes of patients with influenza admitted to a tertiary-care center in Riyadh, Saudi Arabia. METHODS: This was a retrospective cohort of adult patients admitted with polymerase chain reaction-confirmed influenza to King Abdulaziz Medical City-Riyadh between January 1, 2018, and May 31, 2022. We compared patients who required intensive care unit (ICU) admission to those who did not and performed multivariable logistic regression to assess the predictors of ICU admission and hospital mortality. RESULTS: During the study period, 675 adult patients were hospitalized with influenza (median age 68.0 years, females 53.8%, hypertension 59.9%, diabetes 55.1%, and chronic respiratory disease 31.1%). Most admissions (83.0%) were in the colder months (October to March) in Riyadh with inter-seasonal cases even in the summertime (June to August). Influenza A was responsible for 79.0% of cases, with H3N2 and H1N1 subtypes commonly circulating in the study period. Respiratory viral coinfection occurred in 12 patients (1.8%) and bacterial coinfection in 42 patients (17.4%). 151 patients (22.4%) required ICU admission, of which 62.3% received vasopressors and 48.0% mechanical ventilation. Risk factors for ICU admission were younger age, hypertension, bilateral lung infiltrates on chest X-ray, and Pneumonia Severity Index. The overall hospital mortality was 7.4% (22.5% for ICU patients, p < 0.0001). Mortality was 45.0% in patients with bacterial coinfection, 30.9% in those requiring vasopressors, and 29.2% in those who received mechanical ventilation. Female sex (odds ratio [OR], 2.096; 95% confidence interval [CI] 1.070, 4.104), ischemic heart disease (OR, 3.053; 95% CI 1.457, 6.394), immunosuppressed state (OR, 7.102; 95% CI 1.803, 27.975), Pneumonia Severity Index (OR, 1.029; 95% CI, 1.017, 1.041), leukocyte count and serum lactate level (OR, 1.394; 95% CI, 1.163, 1.671) were independently associated with hospital mortality. CONCLUSIONS: Influenza followed a seasonal pattern in Saudi Arabia, with H3N2 and H1N1 being the predominant circulating strains during the study period. ICU admission was required for > 20%. Female sex, high Pneumonia Severity Index, ischemic heart disease, and immunosuppressed state were associated with increased mortality.

Trends in Hospitalisations for Vaccine Preventable Respiratory Infections Following Emergency Department Presentations in New South Wales, Australia, 2012-2022.

BACKGROUND: Vaccine-preventable respiratory infections impact on healthcare systems globally. Despite availability of vaccines, fluctuations in vaccination rates, pathogen virulence and community transmission dynamics mean that these respiratory infections continue to pose substantial public health risks. To understand trends in vaccine-preventable respiratory infections, we analysed linked data from emergency department (ED), hospitalisations and deaths in New South Wales, Australia, from 2012 to 2022. METHODS: ED presentations with respiratory infection like illness were linked to hospitalisation and death records. Age-standardised rates of ED presentations, proportions subsequently hospitalised for acute respiratory infection (ARI) and specific vaccine-preventable disease diagnoses and 28-day mortality rates were estimated by year and age. RESULTS: From 2012 to 2022, there were 3,127,090 ARI-like ED presentations. Age-standardised rates increased until 2020, declined in 2021 and rebounded in 2022. Across all years, of these ARI-like ED presentations, 16.6% were hospitalised for acute respiratory infections, including pneumonia (7.9%), influenza (1.1%), RSV disease (1.3%), COVID-19 (0.8%) and pneumococcal disease (0.3%). Proportions hospitalised were highest in those aged 65+ years, except for RSV, which was highest in children aged 0-4 years. The highest 28-day mortality post-ARI-like ED presentation was observed with COVID-19 in adults aged 65+ years at 13.1%. CONCLUSIONS: This study highlights the continuing burden of vaccine-preventable respiratory infections on an Australian healthcare system. These data can be used to monitor the effectiveness of vaccination programmes and other public health interventions. Future efforts should focus on enhancing surveillance and data linkage to improve precision and guide targeted public health strategies.

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

OBJECTIVE: 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 the 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 not only 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.

Associations Between Severe Influenza-Complicated Thromboembolism Events, Intensive Care Unit Stays and Mortality, and Associated Risk Factors: A Retrospective Cohort Study.

The association between influenza infection and thromboembolism (TE) events, including cardiovascular events, cerebrovascular events, pulmonary embolism, and deep vein thrombosis, is supported by compelling evidence. However, there is a disparity in the risk factors that impact the outcomes of severe influenza-complicated TE in intensive care unit (ICU) patients. The objective of this study was to evaluate the outcomes of severe influenza-complicated TE in ICU patients and identify any associated risk factors. METHODS: A retrospective cohort study was conducted, recruiting consecutive patients with TE events admitted to the ICU between December 2015 through December 2018 at our institution in Taiwan. The study included a group of 108 patients with severe influenza and a control group of 192 patients with severe community-acquired pneumonia. Associations between complicated TE, length of ICU stay, and 90-day mortality were evaluated using logistic regression analysis, and risk factors were identified using univariate and multivariate generalized linear regression analyses. RESULTS: TE event prevalence was significantly higher in ICU patients with severe influenza than in ICU patients with severe CAP (21.3% vs. 5.7%, respectively; p < 0.05). Patients with severe influenza who developed TE experienced a significant increase in the ratio of mechanical ventilation use, length of mechanical ventilation use, ICU stay, and 90-day mortality when compared to patients without TE (all p < 0.05). The comparison of severe CAP patients with and without TE revealed no significant differences (p > 0.05). The development of thromboembolic events in patients with severe influenza or severe noninfluenza CAP is linked to influenza infection and hypertension (p < 0.05). Furthermore, complicated TE and the severity of the APACHE II score are risk factors for 90-day mortality in ICU patients with severe influenza (p < 0.05). CONCLUSIONS: Patients with severe influenza and complicated TE are more likely to have an extended ICU stay and 90-day mortality than patients with severe CAP. The risk is significantly higher for patients with a higher APACHE II score. The results of this study may aid in defining better strategies for early recognition and prevention of severe influenza-complicated TE.

Impact of the COVID-19 Pandemic on Influenza Hospital Admissions and Deaths in Wales: Descriptive National Time Series Analysis.

Background: The COVID-19 pandemic and the ensuing implementation of control measures caused widespread societal disruption. These disruptions may also have affected community transmission and seasonal circulation patterns of endemic respiratory viruses. Objective: We aimed to investigate the impact of COVID-19-related disruption on influenza-related emergency hospital admissions and deaths in Wales in the first 2 years of the pandemic. Methods: A descriptive analysis of influenza activity was conducted using anonymized pathology, hospitalization, and mortality data from the Secure Anonymised Information Linkage Databank in Wales. The annual incidence of emergency hospitalizations and deaths with influenza-specific diagnosis codes between January 1, 2015, and December 31, 2021, was estimated. Case definitions of emergency hospitalization and death required laboratory confirmation with a polymerase chain reaction test. Trends of admissions and deaths were analyzed monthly and yearly. We conducted 2 sensitivity analyses by extending case definitions to include acute respiratory illnesses with a positive influenza test and by limiting admissions to those with influenza as the primary diagnosis. We also examined yearly influenza testing trends to understand changes in testing behavior during the pandemic. Results: We studied a population of 3,235,883 Welsh residents in 2020 with a median age of 42.5 (IQR 22.9-61.0) years. Influenza testing in Wales increased notably in the last 2 months of 2020, and particularly in 2021 to 39,720 per 100,000 people, compared to the prepandemic levels (1343 in 2019). The percentage of influenza admissions matched to an influenza polymerase chain reaction test increased from 74.8% (1890/2526) in 2019 to 85.2% (98/115) in 2021. However, admissions with a positive test per 100,000 population decreased from 17.0 in 2019 to 2.7 and 0.6 in 2020 and 2021, respectively. Similarly, deaths due to influenza with a positive influenza test per 100,000 population decreased from 0.4 in 2019 to 0.0 in 2020 and 2021. Sensitivity analyses showed similar patterns of decreasing influenza admissions and deaths in the first 2 years of the COVID-19 pandemic. Conclusions: Nonpharmaceutical interventions to control COVID-19 were associated with a substantial reduction in the transmission of the influenza virus, with associated substantial reductions in hospital cases and deaths observed. Beyond the pandemic context, consideration should be given to the role of nonpharmaceutical community-driven interventions to reduce the burden of influenza.

Outcomes of COVID-19 and Influenza in Cerebral Palsy Patients Hospitalized in the United States: Comparative Study of a Nationwide Database.

Patients with cerebral palsy (CP) are particularly vulnerable to respiratory infections, yet comparative outcomes between COVID-19 and influenza in this population remain underexplored. Using the National Inpatient Sample from 2020-2021, we performed a retrospective analysis of hospital data for adults with CP diagnosed with either COVID-19 or influenza. The study aimed to compare the outcomes of these infections to provide insights into their impact on this vulnerable population. We assessed in-hospital mortality, complications, length of stay (LOS), hospitalization costs, and discharge dispositions. Multivariable logistic regression and propensity score matching were used to adjust for confounders, enhancing the analytical rigor of our study. The study cohort comprised 12,025 patients-10,560 with COVID-19 and 1465 with influenza. COVID-19 patients with CP had a higher in-hospital mortality rate (10.8% vs. 3.1%, p = 0.001), with an adjusted odds ratio of 3.2 (95% CI: 1.6-6.4). They also experienced an extended LOS by an average of 2.7 days. COVID-19 substantially increases the health burden for hospitalized CP patients compared to influenza, as evidenced by higher mortality rates, longer hospital stays, and increased costs. These findings highlight the urgent need for tailored strategies to effectively manage and reduce the impact of COVID-19 on this high-risk group.

Cardio-cerebrovascular adverse outcomes in patients with influenza with and without preexisting cardiovascular disease: Oral antiviral agents impact.

This study aimed to compare the 2-year cardio-cerebrovascular adverse outcomes of patients with influenza with and without preexisting cardiovascular disease (preCVD) treated with oral antiviral agents in the outpatient clinic. Oral antiviral agents are routinely prescribed to treat influenza infection with a positive rapid-antigen test in the outpatient clinic; however, influenza-associated cardio-cerebrovascular outcomes have not yet been characterized in patients with preCVD treated with oral antiviral agents. Data between 2006 and 2016 were extracted from the National Health Database of South Korea. A total of 865,522 patients with influenza treated with oral antiviral agents were selected in South Korea and classified as preexisting ischemic heart disease (IHD), heart failure (HF), or atrial fibrillation (AF), and 2-year cardio-cerebrovascular outcomes were analyzed using a Cox proportional hazard regression model. Among the participants, 96,433 had preCVD (11.1%; mean age, 46 years) including IHD (86.4%), HF (23.1%), and AF (12.5%). The incidence of new-onset IHD, AF, HF, and death was similar between patients with influenza with and without preCVD. The incidences of IHD and stroke were 0.489 and 0.047 per 100-person year in the preCVD group, respectively. The incidence of cardiovascular mortality was 0.489 per 100-person year in the preCVD group, and the hazard ratio for cardiovascular mortality in the preCVD group was not significantly different from that in patients without preCVD. Based on the national health data, 2-year cardio-cerebrovascular adverse outcomes were not significantly different between patients with and without preCVD treated with oral antiviral agents.

Changes in the incidence, clinical features and outcomes of tuberculosis during COVID-19 pandemic.

BACKGROUND: COVID-19 pandemic has disrupted tuberculosis (TB) services in many countries, but the impacts on sites of involvement, drug susceptibility, smear positivity and clinical outcomes, and clinical outcomes of co-infection with influenza and COVID-19 remain unclear. METHODS: Descriptive epidemiological study using episode-based and patient unique data of tuberculosis from Hospital Authority's territory-wide electronic medical record database, comparing baseline (January 2015-December 2019) and COVID-19 period (January 2020-December 2022), followed by univariate and multivariate analyses. Effects of co-infection with influenza and COVID-19 were investigated. RESULTS: The study included 10,473 episodes of laboratory-confirmed TB, with 6818 in baseline period and 3655 during COVID-19 period. During COVID-19 period, TB patients had a lower proportion of smear positivity (49.2 % vs 54.7 %, P < 0.001), and fewer cases of extrapulmonary TB (7.0 % vs 8.0 %, P = 0.078) and multidrug resistant TB (1.0 % vs 1.6 %, P = 0.020). Mortality was higher in TB patients with COVID-19 coinfection (OR 1.7, P = 0.003) and influenza coinfection (OR 2.6, P = 0.004). During COVID-19 period, there were higher rates of treatment delay (20.5 % vs 15.5 %, P < 0.001) and episodic death (15.1 % vs 13.3 %, P = 0.006). Factors associated with higher mortality included age ≥ 70 years (OR 7.24), treatment delay (OR 2.16), extrapulmonary TB (OR 2.13). smear positivity (OR 1.71) and Charlson comorbidity index score ≥ 3 (OR 1.37). Higher mortality was observed with co-infection by influenza (OR 1.18) and COVID-19 (OR 1.7). CONCLUSIONS: The epidemiology and outcomes of TB were changed during COVID-19 period. Mortality was higher during COVID-19 period and with co-infection by influenza and COVID-19.

Mortality Rates of the Spanish Flu and Coronavirus Disease 2019 in the Netherlands: A Historical Comparison.

The coronavirus disease 2019 (COVID-19) pandemic has been called the deadliest disease event in history. In this study, we compared the cause-specific mortality rate of the Spanish flu (1918-1920) with that of COVID-19 (2020-2022) in the Netherlands. During the periods of exposure, about 50 000 people died of COVID-19 and 32 000 people of the Spanish flu. In absolute numbers, COVID-19 seems to be deadlier than Spanish flu. However, the crude mortality rates for COVID-19 and Spanish flu were 287 and 486 per 100 000 inhabitants, respectively. Comparing age-standardized mortality rates, there would have been 28 COVID-19- and 194 Spanish flu-related deaths in 1918-1920, or 214 Spanish flu- and 98 COVID-19-related deaths in 2020-2022 per 100 000 inhabitants per year. Thus, taking the population differences into account, the Spanish flu would have been deadlier than COVID-19.

Birth Patterns in the Aftermath of the 1918 Influenza Pandemic in India: The Case of Madras City.

This paper examines the timing of one-time fluctuations in births subsequent to the 1918 influenza pandemic in Madras (now Chennai), India. After seasonally decomposing key demographic aggregates, we identified abrupt one-time fluctuations in excess births, deaths, and infant deaths. We found a contemporaneous spike in excess deaths and infant deaths and a 40-week lag between the spike in deaths and a subsequent deficit in births. The results suggest that India experienced the same kind of short-term postpandemic "baby bust" that was observed in the United States and other countries. Identifying the mechanisms underlying this widespread phenomenon remains an open question and an important topic for future research.

Low-Dose Corticosteroids for Critically Ill Adults With Severe Pulmonary Infections: A Review.

Importance: Severe pulmonary infections, including COVID-19, community-acquired pneumonia, influenza, and Pneumocystis pneumonia, are a leading cause of death among adults worldwide. Pulmonary infections in critically ill patients may cause septic shock, acute respiratory distress syndrome, or both, which are associated with mortality rates ranging between 30% and 50%. Observations: Corticosteroids mitigate the immune response to infection and improve outcomes for patients with several types of severe pulmonary infections. Low-dose corticosteroids, defined as less than or equal to 400 mg hydrocortisone equivalent daily, can reduce mortality of patients with severe COVID-19, community-acquired pneumonia, and Pneumocystis pneumonia. A randomized clinical trial of 6425 patients hospitalized with COVID-19 who required supplemental oxygen or noninvasive or invasive mechanical ventilation reported that dexamethasone 6 mg daily for 10 days decreased 28-day mortality (23% vs 26%). A meta-analysis that included 7 randomized clinical trials of 1689 patients treated in the intensive care unit for severe bacterial community-acquired pneumonia reported that hydrocortisone equivalent less than or equal to 400 mg daily for 8 days or fewer was associated with lower 30-day mortality compared with placebo (10% vs 16%). In a meta-analysis of 6 randomized clinical trials, low-dose corticosteroids were associated with lower mortality rates compared with placebo for patients with HIV and moderate to severe Pneumocystis pneumonia (13% vs 25%). In a predefined subgroup analysis of a trial of low-dose steroid treatment for septic shock, patients with community-acquired pneumonia randomized to 7 days of intravenous hydrocortisone 50 mg every 6 hours and fludrocortisone 50 µg daily had decreased mortality compared with the placebo group (39% vs 51%). For patients with acute respiratory distress syndrome caused by various conditions, low-dose corticosteroids were associated with decreased in-hospital mortality (34% vs 45%) according to a meta-analysis of 8 studies that included 1091 patients. Adverse effects of low-dose corticosteroids may include hyperglycemia, gastrointestinal bleeding, neuropsychiatric disorders, muscle weakness, hypernatremia, and secondary infections. Conclusions and Relevance: Treatment with low-dose corticosteroids is associated with decreased mortality for patients with severe COVID-19 infection, severe community-acquired bacterial pneumonia, and moderate to severe Pneumocystis pneumonia (for patients with HIV). Low-dose corticosteroids may also benefit critically ill patients with respiratory infections who have septic shock, acute respiratory distress syndrome, or both.

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.

Excess multi-cause mortality linked to influenza virus infection in China, 2012-2021: a population-based study.

Objectives: The aim of this study is to estimate the excess mortality burden of influenza virus infection in China from 2012 to 2021, with a concurrent analysis of its associated disease manifestations. Methods: Laboratory surveillance data on influenza, relevant population demographics, and mortality records, including cause of death data in China, spanning the years 2012 to 2021, were incorporated into a comprehensive analysis. A negative binomial regression model was utilized to calculate the excess mortality rate associated with influenza, taking into consideration factors such as year, subtype, and cause of death. Results: There was no evidence to indicate a correlation between malignant neoplasms and any subtype of influenza, despite the examination of the effect of influenza on the mortality burden of eight diseases. A total of 327,520 samples testing positive for influenza virus were isolated between 2012 and 2021, with a significant decrease in the positivity rate observed during the periods of 2012-2013 and 2019-2020. China experienced an average annual influenza-associated excess deaths of 201721.78 and an average annual excess mortality rate of 14.53 per 100,000 people during the research period. Among the causes of mortality that were examined, respiratory and circulatory diseases (R&C) accounted for the most significant proportion (58.50%). Fatalities attributed to respiratory and circulatory diseases exhibited discernible temporal patterns, whereas deaths attributable to other causes were dispersed over the course of the year. Conclusion: Theoretically, the contribution of these disease types to excess influenza-related fatalities can serve as a foundation for early warning and targeted influenza surveillance. Additionally, it is possible to assess the costs of prevention and control measures and the public health repercussions of epidemics with greater precision.

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.

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.

Vaccinations, cardiovascular drugs, hospitalization, and mortality in COVID-19 and Long COVID.

OBJECTIVE: To identify highest-risk subgroups for COVID-19 and Long COVID(LC), particularly in contexts of influenza and cardiovascular disease(CVD). METHODS: Using national, linked electronic health records for England (NHS England Secure Data Environment via CVD-COVID-UK/COVID-IMPACT Consortium), we studied individuals (of all ages) with COVID-19 and LC (2020-2023). We compared all-cause hospitalization and mortality by prior CVD, high CV risk, vaccination status (COVID-19/influenza), and CVD drugs, investigating impact of vaccination and CVD prevention using population preventable fractions. RESULTS: Hospitalization and mortality were 15.3% and 2.0% among 17,373,850 individuals with COVID-19 (LC rate 1.3%), and 16.8% and 1.4% among 301,115 with LC. Adjusted risk of mortality and hospitalization were reduced with COVID-19 vaccination ≥ 2 doses(COVID-19:HR 0.36 and 0.69; LC:0.44 and 0.90). With influenza vaccination, mortality was reduced, but not hospitalization (COVID-19:0.86 and 1.01, and LC:0.72 and 1.05). Mortality and hospitalization were reduced by CVD prevention in those with CVD, e.g., anticoagulants- COVID:19:0.69 and 0.92; LC:0.59 and 0.88; lipid lowering- COVID-19:0.69 and 0.86; LC:0.68 and 0.90. COVID-19 vaccination averted 245044 of 321383 and 7586 of 8738 preventable deaths after COVID-19 and LC, respectively. INTERPRETATION: Prior CVD and high CV risk are associated with increased hospitalization and mortality in COVID-19 and LC. Targeted COVID-19 vaccination and CVD prevention are priority interventions. FUNDING: NIHR. HDR UK.

How Does the Burden of Respiratory Syncytial Virus Compare to Influenza in Spanish Adults?

BACKGROUND: Respiratory syncytial virus (RSV) and influenza infections cause significant annual morbidity and mortality worldwide in at-risk populations. This study is aimed at assessing hospital burden and healthcare resource utilization (HRU) of RSV and influenza in adults in Spain. METHODS: Data were obtained from the Projected Hospitalisation Database of inpatient episodes (ages: younger adults 18-50 and 51-64 years; older adults 65-74, 75-84, and ≥ 85 years) during 2015, 2017, and 2018 in Spanish public hospitals. Incidence, mean hospitalization, and HRU assessments, including length of stay (LOS), intensive care unit (ICU) usage, and age-standardized mortality rates, were collected and stratified by age group, with analyses focusing on the adult population (≥ 18 years old). RESULTS: Mean hospitalization rate in the population across all years was lower in individuals with RSV versus influenza (7.2/100,000 vs. 49.7/100,000 individuals). ICU admissions and median LOS were similar by age group for both viruses. Age-standardized mortality was 6.3/100,000 individuals and 6.1/100,000 individuals in patients with RSV and influenza, respectively, and mortality rates were similar in older adults (≥ 65 years) for both viruses. CONCLUSIONS: RSV and influenza infection were associated with considerable HRU. There is a substantial disease burden for RSV infection in older adults ≥ 65 years. While RSV hospitalization rates in adults reported here appeared lower than influenza, RSV is still underdiagnosed in the hospital setting and its incidence might be similar to, or higher than, influenza.

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.

Influenza vaccination and COVID-19 infection risk and disease severity: A systematic review and multilevel meta-analysis of prospective studies.

BACKGROUND: In light of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, the influence of influenza vaccination on the risk and severity of Coronavirus Disease 19 (COVID-19) has been a subject of debate. This systematic review and meta-analysis of prospective studies aim to assess the association between influenza immunization and the risk of SARS-CoV-2 infection and subsequent COVID-19 disease severity. METHODS: A comprehensive search of PubMed and Embase databases was performed to identify prospective studies published before March 2024. We focused on evaluating the effect of influenza vaccination on SARS-CoV-2 infection risk and severe COVID-19 outcomes, such as hospitalization and mortality. The analysis employed a multilevel random effects meta-analysis approach. The risk of bias assessment was conducted using the Newcastle-Ottawa Scale. RESULTS: From an initial pool of 5,863 records, 14 studies were selected for inclusion. The aggregated data yielded a summary relative risk (SRR) that showed no significant protective correlation between influenza vaccination and SARS-CoV-2 infection risk (SRR 0.95, 95% confidence interval [CI] 0.81-1.11), COVID-19-associated hospitalization (SRR 0.90, 95% CI 0.68-1.19), or COVID-19-related mortality (SRR 0.83, 95% CI 0.56-1.23). CONCLUSIONS: This systematic review and meta-analysis, based exclusively on prospective studies, demonstrates the lack of a proven protective effect of influenza vaccination against COVID-19 and related outcomes. Our results do not support a significant protective effect of influenza vaccination against the risk or severe outcomes of COVID-19.

Two decades of influenza and pneumonia mortality trends: Demographics, regional shifts and disparities in the United States: 1999 to 2020.

BACKGROUND: In the 20th century, influenza and pneumonia constituted the largest proportion of infectious disease deaths in the United States. Despite progress in management, US mortality trends for these diseases have not been thoroughly investigated. OBJECTIVES: We aim to examine the patterns of influenza and pneumonia-related deaths among US residents. METHODS: Crude death rates and age-adjusted mortality rates (AAMRs) per 100,000 individuals were calculated using influenza and pneumonia mortality data (International Classification of Diseases, 10th revision codes: J09-J18) from the CDC WONDER database. Annual percentage changes with a 95% confidence interval were determined using joinpoint regression analysis. Average annual percentage changes were computed as the weighted average of annual percentage changes. RESULTS: From 1999 to 2020, US influenza and pneumonia deaths totaled 1,257,088 (AAMR: 17.09), with a significantly decreasing AAMR (-2.94). Males had a higher AAMR (20.13) than females (15.02). Non-Hispanic American Indians had the highest AAMR (20.44), while Hispanics had the lowest AAMR (13.91). The Northeast had the highest AAMR (18.02). All other regions had similar AAMRs. Rural regions had a consistently higher AAMR (19.80) than urban regions (AAMR: 16.51). CONCLUSION: Tailoring interventions toward high-risk groups can enhance the effectiveness of preventive measures, vaccination, and health care access.