Impact Of Influenza Infection Research Articles

Impact of Influenza Infection and Environmental Factors on Sepsis

Impact of Influenza Infection and Environmental Factors on Sepsis

Risk of preterm birth in maternal influenza or SARS-CoV-2 infection: a systematic review and meta-analysis.

Influenza is a major threat to global health and is an important cause of respiratory diseases. However, there was a controversy on the impacts of influenza infection on adverse pregnancy outcomes and the infant's health. This meta-analysis aimed to investigate the impact of maternal influenza infection on preterm birth. Five databases, including PubMed, Embase, Cochrane Library, Web of Science, and China National Knowledge Infrastructure (CNKI) were searched for eligible studies on December 29, 2022. The Newcastle-Ottawa Scale (NOS) was used to assess the included quality of the included studies. As for the incidence of preterm birth, odds ratios (OR) and 95% confidence intervals (CIs) were pooled, and the results of the current meta-analysis were displayed in forest plots. Subgroup analyses based on similarity in different aspects were conducted for further analysis. A funnel plot was used to assess the publication bias. All of the above data analyses were performed using STATA SE 16.0 software. A total of 24 studies involving 24,760,890 patients were included in this meta-analysis. Through the analysis, we found that maternal influenza infection significantly increased the risk of preterm birth (OR =1.52, 95% CI: 1.18 to 1.97, I2=97.35%, P=0.00). After subgroup analysis based on different types of influenzas, we found that women infected with influenza A and B (OR =2.05, 95% CI: 1.26 to 3.32, I2=96.14%, P<0.1), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (OR =2.16, 95% CI: 1.75 to 2.66, I2=0.00%, P<0.1) in pregnancy were at an increased risk of preterm birth, while those infected with influenza A alone or seasonal influenza were not (P>0.1). Women should take active steps to avoid influenza infection during pregnancy, especially influenza A and B and SARS-CoV-2, to reduce the possibility of preterm birth.

Decreased expression of surfactant Protein-C and CD74 in alveolar epithelial cells during influenza virus A(H1N1)pdm09 and H3N2 infection

The primary replication site of Influenza A virus (IAV) is type II alveolar epithelial cells (AECII), which are central to normal lung function and present important immune functions. Surfactant components are synthesized primarily by AECII, which play a crucial role in host defense against infection.The aim of this study was to analyze if the impact of influenza infection is differential between A(H1N1)pdm09 and A/Victoria/3/75 (H3N2) on costimulatory molecules and ProSP-C expression in AECII from BALB/c mice infected and A549 cell line infected with both strains.Pandemic A(H1N1)pdm09 and A/Victoria/3/75 (H3N2) were used to infect BALB/c mice and the A549 cell line. We evaluated the surface expression of co-stimulatory molecules (CD45/CD31/CD74/ProSP-C) in AECII and A549 cell lines. Our results showed a significant decrease in ProSP-C+ CD31− CD45– and CD74+ CD31− CD45− expression in AECII and A549 cell line with the virus strain A(H1N1)pdm09 versus A/Victoria/3/75 (H3N2) and controls (non-infection conditions).Our findings indicate that changes in the expression of ProSP-C in AECII and A549 cell lines in infection conditions could result in dysfunction leading to decreased lung compliance, increased work of breathing and increased susceptibility to injury.

Impact of influenza infection on the short- and long-term health of patients with chronic obstructive pulmonary disease

Background Influenza is a common cause of acute respiratory infection that leads to exacerbation of underlying chronic obstructive pulmonary disease (COPD). To elucidate the short- and long-term effects of influenza in patients with COPD, we examined health care resource utilization (HRU) and costs up to 13 months following influenza infection. Methods We conducted a retrospective cohort study using U.S. insurance claims data from MarketScan. Patients with an influenza diagnosis during the 2012–2014 influenza seasons and continuous enrollment in a health plan from 12 months before to 13 months after the index influenza diagnosis were identified and propensity score–matched 1:5 to controls without evidence of influenza. COPD- and pneumonia-related outcomes were assessed over 13 months following influenza diagnosis. Results COPD-associated outcomes after diagnosis were significantly worse in patients with influenza (n = 7,087) vs. controls (n = 35,435) during the first month (exacerbation: 16.1 vs. 3.4%; outpatient visits: 57.1 vs. 35.2%; emergency department (ED) visits: 10.5 vs. 1.8%; and inpatient visits: 5.6 vs. 0.7%) and months 2–13 (exacerbation: 25.1 vs. 21.1%; outpatient visits: 86.1 vs. 85.8%; ED visits: 20.0 vs. 15.7%; and inpatient visits: 6.5 vs. 5.3%). COPD- and pneumonia-associated costs for months 1 and 2–13 were higher in patients with influenza. Limitations The study was subject to a residual imbalance between cohorts despite propensity score matching. The use of diagnostic codes to select patients and identify complications could introduce inaccuracies in estimating events. Conclusions HRU and costs were higher in COPD patients with influenza during the first month and over the entire year following infection. This suggests influenza has an impact on respiratory health in patients with COPD that lasts beyond the acute infection.

Impact of Influenza Infection Among Adult and Pediatric Populations With Hematologic Malignancy and Hematopoietic Stem Cell Transplant: A Systematic Review and Meta-Analysis

PurposeInfluenza is increasingly recognized as a leading cause of morbidity and mortality in patients with hematologic malignancies and recipients of hematopoietic stem cell transplantation (HSCT). However, the impact of influenza on this population has not been previously evaluated in a systematic review. This study systematically reviewed and summarized the outcomes of influenza infection as to in-hospital influenza-related mortality, development of lower respiratory tract infection and acute respiratory distress syndrome, need for hospitalization, intensive care unit admission, and mechanical ventilation. MethodsWe conducted a systematic search of literature using the PubMed and EMBASE databases for articles published from January 1989 through January 19, 2020, reporting laboratory-confirmed influenza in patients of any age with hematologic malignancies and HSCT. Time from transplantation was not included in the search criteria. The impact of antiviral therapy on influenza outcomes was not assessed due to heterogeneity in antiviral treatment provision across the studies. Patients with influenza-like illness, solid-tumor cancers, or nonmalignant hematologic diseases were excluded from the study. A random-effects meta-analysis was performed to estimate the prevalences and 95% CIs of each outcome of interest. A subgroup analysis was carried out to assess possible sources of heterogeneity and to evaluate the potential impact of age on the influenza infection outcomes. Heterogeneity was assessed using the I2 statistic. FindingsData from 52 studies providing data on 1787 patients were included in this analysis. During seasonal epidemics, influenza-related in-hospital mortality was 16.60% (95% CI, 7.49%–27.7%), with a significantly higher death rate in adults compared to pediatric patients (19.55% [95% CI, 10.59%–29.97%] vs 0.96% [95% CI, 0%–6.77%]; P < 0.001). Complications from influenza, such as lower respiratory tract infection, developed in 35.44% of patients with hematologic malignancies and HSCT recipients, with a statistically significant difference between adults and children (46.14% vs 19.92%; P < 0.001). However, infection resulted in a higher hospital admission rate in pediatric patients compared to adults (61.62% vs 22.48%; P < 0.001). For the 2009 H1N1 pandemic, no statistically significant differences were found between adult and pediatric patients when comparing the rates of influenza-related in-hospital mortality, lower respiratory tract infection, and hospital admission. Similarly, no significant differences were noted in any of the outcomes of interest when comparing H1N1 pandemic with seasonal epidemics. ImplicationsRegardless of influenza season, patients, and especially adults, with underlying hematologic malignancies and HSCT recipients with influenza are at risk for severe outcomes including lower respiratory tract infection and in-hospital mortality.

Influenza in hospitalized cancer patients: A propensity score matching analysis.

170 Background: Cancer patients are vulnerable to influenza viruses and are at great risk of developing related complications. However, few studies have assessed the impact of influenza infection among hospitalized cancer patients in the United States. Methods: We identified cancer-related hospitalizations from National Inpatient Sample between 2012 and 2014. A 1:1 propensity score matching analysis was conducted to compare the clinical outcomes between hospitalized cancer patients with and without influenza. Results: We identified 13,186,849 cancer-related hospitalizations, and 47,850 of them (0.36%) had a concomitant diagnosis of influenza. After propensity score matching, cancer patients with influenza had a higher mortality (5.4% vs. 4.2%; odds ratio [OR]: 1.3; 95% confidence interval [CI], 1.13 to 1.49; P &lt; 0.001), longer length of stay (6.3 vs. 5.6 days; P &lt; 0.001) but lower costs (14605.9 vs. 14625.5 dollars; P &lt; 0.001) in hospital than those without influenza. In addition, patients with influenza had a higher incidence of pneumonia (18.4% vs. 13.2%; OR, 1.49; 95% CI, 1.37 to 1.62; P &lt; 0.001), neutropenia (7.1% vs. 3.4%; OR, 2.18; 95% CI, 1.91 to 2.50; P &lt; 0.001), sepsis (19.5% vs. 9.3%; OR, 2.36; 95% CI, 2.16 to 2.58; P &lt; 0.001), dehydration (14.8% vs. 8.8%; OR, 1.80; 95% CI, 1.65 to 1.97; P &lt; 0.001), and acute kidney injury (19.9% vs. 17.6%; OR, 1.16; 95% CI, 1.08 to 1.25; P &lt; 0.001) than those without influenza. Conclusions: Influenza is associated with worse clinical outcomes among hospitalized cancer patients. Influenza vaccination is recommended in this population.

Influenza infection rewires energy metabolism and induces browning features in adipose cells and tissues

Like all obligate intracellular pathogens, influenza A virus (IAV) reprograms host cell’s glucose and lipid metabolism to promote its own replication. However, the impact of influenza infection on white adipose tissue (WAT), a key tissue in the control of systemic energy homeostasis, has not been yet characterized. Here, we show that influenza infection induces alterations in whole-body glucose metabolism that persist long after the virus has been cleared. We report depot-specific changes in the WAT of IAV-infected mice, notably characterized by the appearance of thermogenic brown-like adipocytes within the subcutaneous fat depot. Importantly, viral RNA- and viral antigen-harboring cells are detected in the WAT of infected mice. Using in vitro approaches, we find that IAV infection enhances the expression of brown-adipogenesis-related genes in preadipocytes. Overall, our findings shed light on the role that the white adipose tissue, which lies at the crossroads of nutrition, metabolism and immunity, may play in influenza infection.

Influenza increases invasive meningococcal disease risk in temperate countries

ObjectivesInvasive meningococcal disease (IMD) is a severe bacterial infection that displays wintertime seasonality in temperate countries. Mechanisms driving seasonality are poorly understood and may include environmental conditions and/or respiratory virus infections. We evaluated the contribution of influenza and environmental conditions to IMD risk, using standardized methodology, across multiple geographical regions. MethodsWe evaluated 3276 IMD cases occurring between January 1999 and December 2011 in 11 jurisdictions in Australia, Canada, France and the United States. Effects of environmental exposures and normalized weekly influenza activity on IMD risk were evaluated using a case-crossover design. Meta-analytic methods were used to evaluate homogeneity of effects and to identify sources of between-region heterogeneity. ResultsAfter adjustment for environmental factors, elevated influenza activity at a 2-week lag was associated with increased IMD risk (adjusted odds ratio (OR) per standard deviation increase 1.29; 95% confidence interval, 1.04–1.59). This increase was homogeneous across the jurisdictions studied. By contrast, although associations between environmental exposures and IMD were identified in individual jurisdictions, none was generalizable. ConclusionsUsing a self-matched design that adjusts for both coseasonality and case characteristics, we found that surges in influenza activity result in an acute increase in population-level IMD risk. This effect is seen across diverse geographic regions in North America, France and Australia. The impact of influenza infection on downstream meningococcal risk should be considered a potential benefit of influenza immunization programmes.

The impact of influenza infection on young children, their family and the health care system.

BackgroundInfluenza is a major cause of respiratory illness in young children. Assessing the impact of infection on children and the community is required to guide immunisation policies.ObjectivesTo describe the impact of laboratory‐proven influenza in young children and to compare its impact with that of other respiratory viruses on the child, their family and the health care system.MethodsPreschool children presenting for care or admission to a tertiary paediatric hospital during the 2008‐2014 influenza seasons were tested for respiratory virus by polymerase chain reaction and culture. Parental surveys were used to determine the impact of infection on illness duration, medication use, absenteeism and health service utilisation. Multivariate regression analyses were used to assess the impact of influenza and to evaluate the association between influenza status and outcomes.ResultsAmong 1191 children assessed, 238 had influenza. Among children with influenza, 87.8% were administered antipyretics and 40.9% antibiotics. 28.6% had secondary complications. 65.4% of children missed school/day care, and 53.4% of parents missed work. When influenza and other viruses were compared, significant differences were noted including duration of illness (influenza: 9.54 days, other viruses: 8.50 days; P = 0.005) and duration of absenteeism for both the child (23.1 vs 17.3 hours; P = 0.015) and their parents (28.5 vs 22.7 hours; P = 0.012).ConclusionsInfluenza infection in young children has a significant impact on medication use, absenteeism and the use of health care service. Significant differences are identified when compared with other ILI. These data demonstrate that influenza prevention strategies including immunisation are likely to have wide and significant impacts.

Influenza vaccine-mediated protection in older adults: Impact of influenza infection, cytomegalovirus serostatus and vaccine dosage

Age-related changes in T-cell function are associated with a loss of influenza vaccine efficacy in older adults. Both antibody and cell-mediated immunity plays a prominent role in protecting older adults, particularly against the serious complications of influenza. High dose (HD) influenza vaccines induce higher antibody titers in older adults compared to standard dose (SD) vaccines, yet its impact on T-cell memory is not clear.The aim of this study was to compare the antibody and T-cell responses in older adults randomized to receive HD or SD influenza vaccine as well as determine whether cytomegalovirus (CMV) serostatus affects the response to vaccination, and identify differences in the response to vaccination in those older adults who subsequently have an influenza infection.Older adults (≥65years) were enrolled (n=106) and randomized to receive SD or HD influenza vaccine. Blood was collected pre-vaccination, followed by 4, 10 and 20weeks post-vaccination. Serum antibody titers, as well as levels of inducible granzyme B (iGrB) and cytokines were measured in PBMCs challenged ex vivo with live influenza virus. Surveillance conducted during the influenza season identified those with laboratory confirmed influenza illness or infection.HD influenza vaccination induced a high antibody titer and IL-10 response, and a short-lived increase in Th1 responses (IFN-γ and iGrB) compared to SD vaccination in PBMCs challenged ex vivo with live influenza virus. Of the older adults who became infected with influenza, a high IL-10 and iGrB response in virus-challenged cells was observed post-infection (week 10 to 20), as well as IFN-γ and TNF-α at week 20. Additionally, CMV seropositive older adults had an impaired iGrB response to influenza virus-challenge, regardless of vaccine dose.This study illustrates that HD influenza vaccines have little impact on the development of functional T-cell memory in older adults. Furthermore, poor outcomes of influenza infection in older adults may be due to a strong IL-10 response to influenza following vaccination, and persistent CMV infection.

Capturing a Fusion Intermediate of Influenza Hemagglutinin with a Cholesterol-conjugated Peptide, a New Antiviral Strategy for Influenza Virus

We previously described fusion-inhibitory peptides that are targeted to the cell membrane by cholesterol conjugation and potently inhibit enveloped viruses that fuse at the cell surface, including HIV, parainfluenza, and henipaviruses. However, for viruses that fuse inside of intracellular compartments, fusion-inhibitory peptides have exhibited very low antiviral activity. We propose that for these viruses, too, membrane targeting via cholesterol conjugation may yield potent compounds. Here we compare the activity of fusion-inhibitory peptides derived from the influenza hemagglutinin (HA) and show that although the unconjugated peptides are inactive, the cholesterol-conjugated compounds are effective inhibitors of infectivity and membrane fusion. We hypothesize that the cholesterol moiety, by localizing the peptides to the target cell membrane, allows the peptides to follow the virus to the intracellular site of fusion. The cholesterol-conjugated peptides trap HA in a transient intermediate state after fusion is triggered but before completion of the refolding steps that drive the merging of the viral and cellular membranes. These results provide proof of concept for an antiviral strategy that is applicable to intracellularly fusing viruses, including known and emerging viral pathogens.

Impact of influenza infection on children's hospital admissions during two seasons in Athens, Greece

A prospective epidemiologic surveillance of hospitalizations associated with influenza was conducted in order to calculate population-based hospitalization rates. Eligible children were 6 months to 13 years of age and were admitted to one of the two large children's hospitals in the Athens area during two influenza seasons. Nasopharyngeal aspirates were tested for influenza by a polymerase reaction assay. Influenza accounted for 9.9–11.8% of all admissions during the influenza season and the overall annual rate of hospitalizations was 13.6–16.8 cases per 10,000 children being highest for children under 5 years of age (26–31.2/10,000 children). Febrile seizures and acute otitis media were the two most common complications associated with influenza and antibiotics were administered to 61% of flu positive patients. Influenza is associated with high hospitalization rates among young children and these may be substantially reduced with the introduction of routine immunization.

Impact of influenza infection in healthy children examined as outpatients and their families

Decisions regarding the introduction of influenza immunization in healthy children require an accurate evaluation of influenza disease burden not only in the inpatient but also in the outpatient setting. We prospectively examined the impact of virologically confirmed influenza in 1462 outpatient children (≥6 months to <14 years) and their families, during two consecutive influenza seasons. Influenza was documented in 573/1462 (39%) outpatients with febrile respiratory illness and accounted for 13.5% of all outpatient visits during the 14 weeks of each season. Acute otitis media (AOM) was the most common complication (18.5%) and about 40% of influenza positive patients received antibiotics. AOM and antibiotic use were more common in children younger than 5 years of age who accounted for 58% of all patients. For each child sick with influenza a mean of 1.34 workdays were lost by the parents. Family members of influenza positive children were more likely to develop a secondary respiratory illness and to require medical visits and antibiotic prescriptions. Influenza is associated with a heavy morbidity burden in the community that may be reduced considerably with the implementation of immunization in children younger than 5 years of age.

Neuraminidase Inhibitors for Influenza

he impact of influenza infection is felt globally each year when the disease develops in approximately 20 percent of the world’s population. In the United States, influenza infections occur in epidemics each winter, generally between late December and early March. Recent events, including human cases of avian influenza, have heightened awareness of the threat of a pandemic and have spurred efforts to develop plans for its control. Although vaccination is the primary strategy for the prevention of influenza, there are a number of likely scenarios for which vaccination is inadequate and effective antiviral agents would be of the utmost importance. During any influenza season, antigenic drift in the virus may occur after formulation of the year’s vaccine has taken place, rendering the vaccine less protective, and outbreaks can more easily occur among highrisk populations. In the course of a pandemic, vaccine supplies would be inadequate. Vaccine production by current methods cannot be carried out with the speed required to halt the progress of a new strain of influenza virus; therefore, it is likely that vaccine would not be available for the first wave of spread of virus. 1 Antiviral agents thus form an important part of a rational approach to epidemic influenza and are critical to planning for a pandemic. Four drugs are currently available for the treatment or prophylaxis of influenza infections: the adamantanes (amantadine and rimantadine) and the newer class of neuraminidase inhibitors (zanamivir [Relenza] and oseltamivir [Tamiflu]). The adamantanes interfere with viral uncoating inside the cell. They are effective only against influenza A and are associated with several toxic effects and with rapid emergence of drug-resistant variants. Adamantane-resistant isolates of influenza A are genetically stable, can be transmitted to susceptible contacts, are as pathogenic as wild-type virus isolates, and can be shed for prolonged periods in immunocompromised patients taking the drug. This potential for the development of resistance especially limits the use of the adamantanes for the treatment of influenza, although the drugs still have a place in planning for prophylaxis during an epidemic. The neuraminidase inhibitors zanamivir and oseltamivir interfere with the release of progeny influenza virus from infected host cells, a process that prevents infection of new host cells and thereby halts the spread of infection in the respiratory tract (Fig. 1). Since replication of influenza virus in the respiratory tract reaches its peak between 24 and 72 hours after the onset of the illness, drugs such as the neuraminidase inhibitors that act at the stage of viral replication must be administered as early as possible. In contrast to the adamantanes, the neuraminidase inhibitors are associated with very little toxicity and are far less likely to promote the development of drug-resistant influenza. As a class, the neuraminidase inhibitors are effective against all neuraminidase subtypes t

Viral-Induced T Helper Type 1 Responses Enhance Allergic Disease by Effects on Lung Dendritic Cells

Dahl ME, Dabbagh K, Liggitt D, Kim S, Lewis DB. Nat Immunol. 2004;5:337–343To determine the role of interferon (IFN)-γ and dendritic cells in allergic pulmonary disease after influenza A infection.IFN-γ knockout and wild-type mice completely recovered from influenza A infection were studied.Mice were inoculated intranasally with influenza A virus. The postinfluenza mice were then sensitized and challenged with allergen. Airway inflammatory cells, specific antibody responses, and pulmonary dendritic cell functions were examined. In some of the wild-type mice, a neutralizing IFN-γ monoclonal antibody was administered repeatedly after the viral inoculation.Pulmonary dendritic cells of postinfluenza mice enhanced allergen-specific T-helper (Th)2 responses via an IFN-γ-dependent mechanism.The Th1 immune response caused by an influenza infection perpetuates Th2-dependent allergic asthma by altering pulmonary dendritic cell function.The role of respiratory viral infections in the development of allergen sensitization and asthma has been perplexing. Acute viral respiratory tract infections are the primary cause of asthma exacerbations in children and adults; however, the influence of viral respiratory infections on subsequent allergic sensitization and disease in young children is unclear. Viral infections are simplistically thought to augment Th1 (interleukin [IL]-12 and IFN-γ) responses and, as a result, antagonize Th2 (IL-4, IL-5, and IL-13) responses and decrease the risk of developing atopic diseases and asthma (ie, the hygiene hypothesis). Based on mouse models of allergic asthma, the impact of influenza infection on Th2 development and allergen sensitization has resulted in both beneficial and detrimental outcomes. The factors accounting for the different results are likely to be differences in experimental methods, including the timing of infections relative to allergen sensitization, the type and dose of allergen used, and the strain of the mouse. The findings of the Dahl et al study indicate that a preceding influenza infection with subsequent Th1 immune responses can amplify subsequent Th2 immunity. Thus, the Th1-Th2 paradigm of mutual exclusivity (ie, Th1 inhibits Th2, and vice versa) seems to be overly simplistic in the circumstance in which Th1 begets Th2. Although the result of the study has not been observed or correlated in humans, the finding may provide a mechanistic explanation for a recent report of the increased risk of asthma/reactive airways disease in young children <36 months of age who received a live attenuated intranasal influenza vaccine (published by Bergen et al in Pediatr Infect Dis J. 2004;23:138-144).

Harmonisation of the acute respiratory infection reporting system in the Czech Republic with the European community networks

Respiratory virus activity is detected in Europe each winter, yet the precise timing and size of this activity is highly unpredictable. The impact of influenza infection and/or acute respiratory infection in European countries is continuously monitored through a variety of surveillance systems. All of these sources of information are used to assess the nature and extent of activity of influenza and other respiratory viruses, and to offer guidance on the prevention and control of morbidity and mortality due to influenza at a local, national and international level. The early warning system for a forthcoming influenza epidemic is mainly based on the use of a set of thresholds. In the Czech Republic, the acute respiratory infection (ARI) reporting system, with automated data processing, uses a statistical model for the early detection of unusual increased rates of the monitored indicators. The collected data consists of the number of ARI, the number of complications due to ARI and the population registered with the reporting general practitioners and paediatricians, all collected separately in five age groups. To improve the reporting system in the Czech Republic, clinical data on the weekly incidence of influenza-like illness (ILI) within the same population and the same age groups was started in January 2004. These data fit the European Commission's recently adopted ILI case definition and allows a better comparison of data with other countries in Europe, in particular those participating in EISS (European Influenza Surveillance Scheme).