Influenza Mortality Research Articles

CLINICAL OUTCOMES OF INFLUENZA INFECTION AMONG SOLID ORGAN TRANSPLANT RECIPIENTS IN ICU

Introduction: Influenza is usually a self-limited illness in healthy adults, but influenza virus infection can cause severe illness in certain high-risk groups like solid organ transplant recipients (SOTR). We aimed to evaluate the clinical results of SOTR with influenza admitted to the intensive care unit (ICU). Materials and Methods: Data of SOTR with influenza related ICU admission in a single center were analyzed between May 2016 to September 2019 retrospectively. Demographics, type of influenza virus, treatment duration, complications and mortality in ICU were assessed. Results: A total of 115 cases of influenza with SOTR were hospitalized. Out of these 17, %35 were female and 1 was a pediatric patient admitted to ICU due to acute respiratory failure. The median age of 17 patients consisting of 11 kidney and 6 liver recipients was 41 years (range 12-81years). Seven (41%) patients were in chronic rejection. Mean APACHE II and SOFA scores at ICU admission were 17±7.1 and 6.6±2.0 respectively. Except for one patient (<3 months), all were infected with influenza in the late period (>1 year) after transplantation. While real-time polymerase chain reaction (PCR) test was positive in 13 (76.5%) patients, other 4 (23.5%) were diagnosed with rapid antigen testing. The subtypes of influenza were revealed as: 2 (11.8%) influenza A, 13 (76.5%) influenza B, 2 (11.8%) influenza A and B. Simultaneous respiratory syncytial virus (RSV) positivity was seen in 9 SOTR (1 influenza A, 1 influenza A and B, 7 influenza B). Five patients were isolated due to extensively drug-resistant infections. Oseltamivir treatment was applied 5 or 10 days according to disease severity which was 58.8% and 41.2% respectively. Three (17.6%) patients received invasive mechanical ventilation and 10 (58.8%) high flow oxygen therapy for acute respiratory failure. Eight (47.0%) had vasopressor support due to shock and 7 (41.1%) patients received renal replacement therapy. The length of ICU and hospital stay were as 5.6±7.6 days and 18.2±19.0 days respectively. According to APACHE II scoring, mean predicted mortality was 17.0%, while 2 (11.7%) actual deaths were observed. Discussion: Most of the patients admitted to ICU for influenza were infected after the first year. Influenza B subtype was more common than A, and this was high in RSV accompaniment. Conclusion: Our study highlightes that, when the symptoms of influenza appear in high risk groups like solid organ transplant recipients, the early initiation of antiviral therapy can be a significantly lifesaving approach.

A comparison of epidemiology and clinical outcomes between influenza A H1N1pdm09 and H3N2 based on multicenter surveillance from 2014 to 2018 in South Korea.

BackgroundAfter pandemic, A(H1N1)pdm09 is generally known to be associated with younger adults' infection and greater severity than seasonal A(H3N2) but some inconsistences between recent studies exist.ObjectivesWe aimed to compare the epidemiology and clinical outcomes of A(H1N1)pdm09 and A(H3N2) to verify and consolidate about the knowledge of known differences of subtypes.MethodsData were retrospectively collected from the hospital‐based influenza morbidity and mortality surveillance in South Korea in nine tertiary care hospitals, from August 31, 2014, to August 25, 2018. Patients with H1N1pdm09 or H3N2 infection admitted in the emergency room or ward were recruited.ResultsA total of 1747 patients had influenza A and were divided into two groups those with A(H1N1)pdm09 (n = 240) and those with A(H3N2) (n = 1507). A(H1N1)pdm09 group had younger age (mean age ± standard deviation 50.0 ± 18.8 in H1N1 vs 53.4 ± 21.1 in H3N2, P = .030), lower influenza vaccination (27.9% vs 43.9%, P < .001) and pneumococcal vaccination rates (41.0% vs 51.9%, P < .001), and fewer underlying diseases (67.5% vs 74.0%, P = .035) than the A(H3N2) group. Influenza A subtypes were not associated with pneumonia risk (adjusted odds ratios [AOR] of A(H1N1)pdm09: 0.7 [95% confidence interval [CI]: 0.4‐1.2, P = .172]) and in‐hospital mortality (hazard ratio (HR) of A(H1N1)pdm09: 1.0 (95% CI: 0.3‐3.1, P = .983)). Influenza vaccination reduced in‐hospital mortality in hospitalized patients (HR: 0.3 (95% CI: 0.1‐0.7), P = .005).ConclusionsA(H1N1)pdm09 infection was more common in younger patients without significant difference in pneumonia risk and in‐hospital mortality between subtypes. Influenza vaccination was associated with reduced in‐hospital mortality.

Emerging Role of Mucosal Vaccine in Preventing Infection with Avian Influenza A Viruses.

Avian influenza A viruses (AIVs), as a zoonotic agent, dramatically impacts public health and the poultry industry. Although low pathogenic avian influenza virus (LPAIV) incidence and mortality are relatively low, the infected hosts can act as a virus carrier and provide a resource pool for reassortant influenza viruses. At present, vaccination is the most effective way to eradicate AIVs from commercial poultry. The inactivated vaccines can only stimulate humoral immunity, rather than cellular and mucosal immune responses, while failing to effectively inhibit the replication and spread of AIVs in the flock. In recent years, significant progresses have been made in the understanding of the mechanisms underlying the vaccine antigen activities at the mucosal surfaces and the development of safe and efficacious mucosal vaccines that mimic the natural infection route and cut off the AIVs infection route. Here, we discussed the current status and advancement on mucosal immunity, the means of establishing mucosal immunity, and finally a perspective for design of AIVs mucosal vaccines. Hopefully, this review will help to not only understand and predict AIVs infection characteristics in birds but also extrapolate them for distinction or applicability in mammals, including humans.

Investigation of Human IFITM3 Polymorphisms rs34481144A and rs12252C and Risk for Influenza A(H1N1)pdm09 Severity in a Brazilian Cohort.

Influenza is a major public health problem that causes acute respiratory infection in humans. Identification of host factors influencing in disease outcome is critical for recognition of individuals with increased risk. Investigations on the role of rs34481144A and rs12252C IFITM3 polymorphisms in influenza A(H1N1)pdm09 severity is not yet conclusively determined. This study aimed to evaluate such polymorphisms frequencies and IFITM3 levels in an infected Brazilian cohort of 314 influenza A(H1N1)pdm09 cases and its putative association with clinical, epidemiological and virological data. Individuals were clinically classified into mild, severe and fatal cases. IFITM3 polymorphisms were detected by specific Taqman probes in real time PCR reactions. IFITM3 levels were determined by quantitative real time PCR. Thus, the different clinical groups presented similar distribution of rs34481144 and rs12252 genotypes and allelic frequencies. There was no significant association between the polymorphisms with severity of disease by using distinct genetic models. Additionally, geographic distribution of mutants showed that rs34481144A allele was more predominant in Brazilian Southern region. In contrast, rs12252C allele presented similar frequencies in all regions. Individuals with the distinct rs34481144 and rs12252 genotypes showed similar levels of IFITM3 and viral load in their respiratory specimens. Furthermore, IFITM3 levels were comparable in the distinct clinical groups and were not correlated with influenza viral load in analyzed samples. Thereby, rs34481144A and rs12252C polymorphisms were not associated with severity or mortality of influenza A(H1N1)pdm09 infection nor with IFITM3 transcript levels and influenza viral load in upper respiratory tract samples in a Brazilian cohort.

Professional Sporting Events Increase Seasonal Influenza Mortality in US Cities

The COVID-19 pandemic shut down sporting events worldwide. Local policy makers and league officials face important decisions about restarting play, especially in professional leagues that draw large numbers of spectators to games. We analyze the impact of professional sporting events on local seasonal influenza mortality to develop evidence that will help inform sports league reopening policy decisions. Results from a difference-in-differences model applied to data from a sample of US cities that gained new professional sports teams over the period 1962-2016 show that the presence of games in these cities increased local influenza mortality by between 4% and 24%, depending on sport, relative to cities with no professional sports teams and relative to mortality in those cities before a new team arrived. Influenza mortality fell in cities with teams in some years when work stoppages occurred in sports leagues. Sports league reopening policies should take into account the role played by sporting events in increasing local seasonal flu mortality.

Influenza Virus in Community-Acquired Pneumonia: Current Understanding and Knowledge Gaps.

Influenza virus infection poses a heavy burden on global health and economics. With the advancement in viral pathogen detection methods, the role of virus infection in community-acquired pneumonia has been increasingly recognized. The disease spectrum of influenza ranges from asymptomatic infection to severe or even fatal illness. Progress has been made in recent years to identify risk factors including lymphopenia and hypoxia for influenza mortality. Immunopathology plays an important role in influenza pathogenesis. The disturbed homeostasis after virus infection consists of both an excessive inflammatory phase and an immune suppression phase, collectively described as viral sepsis. Multiple antiviral therapies have been tested and some were advanced to late-phase clinical trials, including polymerase inhibitors, hemagglutinin inhibitors, host-acting antivirals, monoclonal antibodies, and adjunctive immunomodulatory therapies. Combination therapies have been shown to increase antiviral efficacy and genetic resistance barrier. In this review, we summarized the recent advances in our understanding of the disease pathogenesis, as well as the progress in antiviral therapy development. We also pointed out current key knowledge gaps in influenza research. Hopefully, experience gained from seasonal influenza research will prepare us for the next influenza pandemic and emerging respiratory pathogens.

Modeling mitigation of influenza epidemics by baloxavir

Influenza viruses annually kill 290,000–650,000 people worldwide. Antivirals can reduce death tolls. Baloxavir, the recently approved influenza antiviral, inhibits initiation of viral mRNA synthesis, whereas oseltamivir, an older drug, inhibits release of virus progeny. Baloxavir blocks virus replication more rapidly and completely than oseltamivir, reducing the duration of infectiousness. Hence, early baloxavir treatment may indirectly prevent transmission. Here, we estimate impacts of ramping up and accelerating baloxavir treatment on population-level incidence using a new model that links viral load dynamics from clinical trial data to between-host transmission. We estimate that ~22 million infections and >6,000 deaths would have been averted in the 2017–2018 epidemic season by administering baloxavir to 30% of infected cases within 48 h after symptom onset. Treatment within 24 h would almost double the impact. Consequently, scaling up early baloxavir treatment would substantially reduce influenza morbidity and mortality every year. The development of antivirals against the SARS-CoV2 virus that function like baloxavir might similarly curtail transmission and save lives.

High-dose influenza vaccination and mortality among predominantly male, white, senior veterans, United States, 2012/13 to 2014/15.

IntroductionIt is unclear whether high-dose influenza vaccine (HD) is more effective at reducing mortality among seniors.AimThis study aimed to evaluate the relative vaccine effectiveness (rVE) of HD. MethodsWe linked electronic medical record databases in the Veterans Health Administration (VHA) and Medicare administrative files to examine the rVE of HD vs standard-dose influenza vaccines (SD) in preventing influenza/pneumonia-associated and cardiorespiratory mortality among VHA-enrolled veterans 65 years or older during the 2012/13, 2013/14 and 2014/15 influenza seasons. A multivariable Cox proportional hazards model was performed on matched recipients of HD vs SD, based on vaccination time, location, age, sex, ethnicity and VHA priority level. ResultsAmong 569,552 person-seasons of observation, 207,574 (36%) were HD recipients and 361,978 (64%) were SD recipients, predominantly male (99%) and white (82%). Pooling findings from all three seasons, the adjusted rVE estimate of HD vs SD during the high influenza periods was 42% (95% confidence interval (CI): 24–59) against influenza/pneumonia-associated mortality and 27% (95% CI: 23–32) against cardiorespiratory mortality. Residual confounding was evident in both early and late influenza periods despite matching and multivariable adjustment. Excluding individuals with high 1-year predicted mortality at baseline reduced the residual confounding and yielded rVE of 36% (95% CI: 10–62) and 25% (95% CI: 12–38) against influenza/pneumonia-associated and cardiorespiratory mortality, respectively. These were confirmed by results from two-stage residual inclusion estimations.DiscussionThe HD was associated with a lower risk of influenza/pneumonia-associated and cardiorespiratory death in men during the high influenza period.

Pandemics Change Cities: Municipal Spending and Voter Extremism in Germany, 1918-1933

We merge several historical data sets from Germany to show that influenza mortality in 1918-1920 is correlated with societal changes, as measured by municipal spending and city-level extremist voting, in the subsequent decade. First, influenza deaths are associated with lower per capita spending, especially on services consumed by the young. Second, influenza deaths are correlated with the share of votes received by extremist parties in 1932 and 1933. Our election results are robust to controlling for city spending, demographics, war-related population changes, city-level wages, and regional unemployment, and to instrumenting influenza mortality. We conjecture that our findings may be the consequence of long-term societal changes brought about by a pandemic.

100 years of influenza research seen through the lens of Covid-19.

100 years of influenza research seen through the lens of Covid-19.

The Value of Health Insurance During a Crisis: Effects of Medicaid Implementation on Pandemic Influenza Mortality

This paper studies how better access to public health insurance affects infant mortality during pandemics. Our analysis combines cross-state variation in mandated eligibility for Medicaid with two influenza pandemics — the 1957-58 Asian Flu pandemic and the 1968-69 Hong Kong Flu — that arrived shortly before and after the program's introduction. Exploiting heterogeneity in the underlying severity of these two shocks across counties, we find no relationship between Medicaid eligibility and pandemic infant mortality during the 1957-58 outbreak. After Medicaid implementation, we find that better access to insurance in high-eligibility states substantially reduced infant mortality during the 1968-69 pandemic. The reductions in pandemic infant mortality are too large to be attributable solely to new Medicaid recipients, suggesting that the expansion in health insurance coverage mitigated disease transmission among the broader population. Institutional subscribers to the NBER working paper series, and residents of developing countries may download this paper without additional charge at www.nber.org.

Cytokine storm intervention in the early stages of COVID-19 pneumonia

Clinical intervention in patients with corona virus disease 2019 (COVID-19) has demonstrated a strong upregulation of cytokine production in patients who are critically ill with SARS-CoV2-induced pneumonia. In a retrospective study of 41 patients with COVID-19, most patients with SARS-CoV-2 infection developed mild symptoms, whereas some patients later developed aggravated disease symptoms, and eventually passed away because of multiple organ dysfunction syndrome (MODS), as a consequence of a severe cytokine storm. Guidelines for the diagnosis and treatment of SARS-CoV-2 infected pneumonia were first published January 30th, 2020; these guidelines recommended for the first time that cytokine monitoring should be applied in severely ill patients to reduce pneumonia related mortality. The cytokine storm observed in COVID-19 illness is also an important component of mortality in other viral diseases, including SARS, MERS and influenza. In view of the severe morbidity and mortality of COVID-19 pneumonia, we review the current understanding of treatment of human coronavirus infections from the perspective of a dysregulated cytokine and immune response.

Comparison of influenza hospitalization outcomes among adults, older adults, and octogenarians: a US national population-based study

ObjectivesThis study sought to more fully elucidate the age-related trends in influenza mortality with a secondary goal of uncovering implications for treatment and prevention. MethodsIn this retrospective cohort analysis of data from the Nationwide Readmission Database, patients with influenza as a primary or secondary discharge diagnosis were separated into three age groups: 55 638 adults aged 20–64 years, 36 862 adults aged 65–79 years and 41 806 octogenarians aged ≥80 years. Propensity score (PS) weighting was performed to isolate age from other baseline differences. Crude and PS-weighted hazard ratios (HR) were calculated from the in-hospital all-cause 30-day mortality rate. Admission threshold bias was minimized by comparison of influenza with bacterial pneumonia mortality. ResultsAdults aged 20–64 years experienced higher in-hospital 30-day mortality compared with older adults aged 65–79 years (HR 0.66; 95% CI 0.55–0.79). Octogenarians had the highest mortality rate, but this was statistically insignificant compared with the adult cohort (HR 1.09; 95% CI 0.94–1.27). This trend was not explained by admission threshold bias: the 30-day mortality rate due to in-hospital bacterial pneumonia increased consistently with age (older adult HR 1.45; 95% CI 1.32–1.59; octogenarian HR 1.99; 95% CI 1.82–2.18). ConclusionsAdults aged 20–64 years and octogenarians were more likely to experience all-cause 30-day mortality during influenza hospitalization compared with older adults aged 65–79 years. These data emphasize the importance of prevention and suggest the need for more tailored treatment interventions based on risk stratification that includes age.

Epidemiological parallels of community-acquired pneumonia, influenza and ARVI in Moscow

The problem of community-acquired pneumonia continues to be urgent due to high incidence, hospital admission rates, and mortality. The objective of the study is to characterize epidemiological parameters of incidence and mortality of community-acquired pneumonia, influenza, and ARVI in Moscow. Subjects and methods . The incidence and mortality of community-acquired pneumonia, influenza, and ARVI among different population groups in Moscow were analyzed. The Pearson correlation coefficient (rxy) was calculated to assess the relationship between incidence of pneumonia, influenza, and ARVI. Data were analyzed using IBM SPSS Statistics IBM statistics, version 23.0. Results. Over the studied period of long-term changes in the incidence of community-acquired pneumonia among all population groups, a pronounced upward trend is observed. The highest incidence rates of community-acquired pneumonia in Moscow are registered among under in infants one year, 1-2 years old and 3-6 years old pediatric patients. The months of the maximum incidence of community-acquired pneumonia in adults coincide with the months of the maximum incidence of influenza (January - February). The maximum incidence of community-acquired pneumonia among children 15-17 years old and 0-14 years old is registered 2 months earlier than with influenza. The highest mortality of pneumonia is observed after 1-2 months after the maximum incidence of ARVI and influenza, which is due to delayed mortality as a result of the exacerbation of chronic diseases. The authors suggest considering simultaneous vaccinations against influenza and pneumococcal infection among people over 65 years old and high-risk groups during the pre-season vaccination against influenza.

The COVID-19 pandemic in the USA: what might we expect?

The COVID-19 pandemic in the USA: what might we expect?

COVID-19, diabetes mellitus and ACE2: The conundrum

COVID-19, diabetes mellitus and ACE2: The conundrum

Inhaled biguanides and mTOR inhibition for influenza and coronavirus (Review).

The mammalian target of rapamycin (mTOR) signaling pathway senses and responds to nutrient availability, energy sufficiency, stress, hormones and mitogens to modulate protein synthesis. Rapamycin is a bacterial product that can inhibit mTOR via the PI3K/AKT/mTOR pathway. mTOR signaling is necessary for the development of influenza and modulates the antibody response to provide cross-protective immunity to lethal infection with influenza virus. In one human study, it was found that the treatment of severe H1N1 influenza‑related pneumonia with rapamycin and steroids improved the outcome. However, in other studies, immunosuppression with systemic steroids, and possibly rapamycin as well, was associated with an increased morbidity/mortality and a prolonged viral replication. In order to avoid the systemic side-effects, some investigators have postulated that the inhalation of rapamycin would be desirable. However, the inhalation of rapamycin, with its well-documented lung toxicity, could be contraindicated. Another class of drug, biguanides, can also inhibit mTOR, but have no lung toxicity. Biguanides are widely used small molecule drugs prescribed as oral anti-diabetics that have exhibited considerable promise in oncology. During the 1971 outbreak of influenza, diabetic patients treated with the biguanides, phenformin and buformin, had a lower incidence of infection than diabetics treated with sulfonylureas or insulin. Both buformin and phenformin reduce the mortality of influenza in mice; phenformin is less effective than buformin. The inhalation of buformin or phenformin for influenza may be an effective novel treatment strategy that would limit the risk of systemic side-effects associated with biguanides due to the low inhaled dose. Coronavirus disease 2019 (COVID-19) is an infectious disease caused by SARS-CoV-2, a virus closely related to the SARS virus. The disease is the cause of the 2019–2020 coronavirus outbreak. It is primarily spread between individuals via small droplets emitted from infected individuals when breathing or coughing. PI3K/AKT/mTOR signaling responses play important roles in MERS-CoV infection and may represent a novel drug target for therapeutic intervention strategies. The present review article discusses the effects of biguanides on influenza and coronavirus.

The 1918 "Spanish Flu" Pandemic in the Ottoman Capital, Istanbul.

Although the general course, possible transmission routes, and actual sociodemographic destruction of the 1918 influenza pandemic in the Western world are well documented, the literature lacks similar data about the Middle East. On the calamity's centenary, this article aims to contribute to filling this gap, investigating the presence and effects of the pandemic in Istanbul, the city bridging the West and East, then as the capital of the Ottoman Empire. After the retrieval of the most relevant articles in Vakit, a daily Istanbul newspaper active throughout the pandemic, a variety of items, including articles with firsthand pronouncements from contemporaneous medical authorities and a clinical account of supportive autopsy findings, are scrutinized and interpreted. The reviewed data are concluded to indicate no epidemiological or factual exception, showing significant parallelism with the Western experience of the pandemic in terms of increased influenza mortality and morbidity, severe clinical presentation, common misinformation and misdiagnosis, and failure to provide effective prevention and medical treatment.

Influenza morbidity and mortality in Kerala: Hotspots that go unnoticed

Influenza morbidity and mortality in Kerala: Hotspots that go unnoticed

The impact of new universal child influenza programs in Australia: Vaccine coverage, effectiveness and disease epidemiology in hospitalised children in 2018

BackgroundNew jurisdictionally-based vaccination programs were established providing free quadrivalent influenza vaccine (QIV) for preschool Australian children in 2018. This was in addition to the National Immunisation Program (NIP) funded QIV for Indigenous children and children with comorbid medical conditions. We assessed the impact of this policy change on influenza disease burden and vaccine coverage, as well as report on 2018 vaccine effectiveness in a hospital-based surveillance system. MethodsSubjects were recruited prospectively from twelve PAEDS-FluCAN sentinel hospital sites (April until October 2018). Children aged ≤16 years hospitalised with an acute respiratory illness (ARI) and laboratory-confirmed influenza were considered cases. Hospitalised children with ARI who tested negative for influenza were considered controls. VE estimates were calculated from the adjusted odds ratio of vaccination in cases and controls. ResultsA total of 458 children were hospitalised with influenza: 31.7% were <2 years, 5.0% were Indigenous, and 40.6% had medical comorbidities predisposing to severe influenza. Influenza A was detected in 90.6% of children (A/H1N1: 38.0%; A/H3N2: 3.1%; A/unsubtyped 48.6%). The median length of stay was 2 days (IQR: 1,3) and 8.1% were admitted to ICU. Oseltamivir use was infrequent (16.6%). Two in-hospital deaths occurred (0.45%). 12.0% of influenza cases were vaccinated compared with 36.0% of test-negative controls. Vaccine effectiveness of QIV for preventing influenza hospitalisation was estimated at 78.8% (95%CI: 66.9; 86.4). ConclusionsCompared with 2017 (n = 1268 cases), a significant reduction in severe influenza was observed in Australian children, possibly contributed to by improved vaccine coverage and high vaccine effectiveness. Despite introduction of jurisdictionally-funded preschool programs and NIP-funded vaccine for children with risk factors for severe disease, improved coverage is required to ensure adequate protection against paediatric influenza morbidity and mortality.