Influenza Infection Research Articles

Optimization of timing for maternal immunization to protect newborns from influenza infection

Objectives The primary objective of this systematic review was to identify the optimal timing for immunizing pregnant women to confer the most protection by reducing the incidence of laboratory-confirmed influenza or influenza-like illness in infants less than 6 months of age. Currently, there are gaps in research regarding the timing of administration during the gestational period to provide maximum immunogenicity to the infant. The research question being addressed is: ‘When considering immunization of pregnant mothers with the influenza vaccine, implementing a vaccination program during which trimester in pregnancy would optimize benefits for infants less than 6 months of age in terms of the incidence of laboratory-confirmed influenza and influenza-like illness?’ Design Systematic review/Meta-analysis Methods Randomized controlled trials (RCT’s) and observational studies comparing health outcomes of infants and children up to 6 months of age born to women who received inactivated influenza vaccine during pregnancy with mothers who did not receive the vaccine or received a control vaccine. The primary outcome was laboratory-confirmed influenza infection in infants. Secondary outcome measures included influenza –like illness diagnosed by a clinician and acute respiratory illness. Results 7 studies were included: 2 primary RCT’s and 5 observational studies (prospective and retrospective cohort studies).5 of the 7 studies were suitable to be included in the quantitative synthesis part and and were compared. Forrest plot analysis revealed that vaccinating pregnant mothers in the second and third trimester when compared with any trimester (1,2 and 3) (OR 0.18 vs. 0.65) conferred less protection, promoting vaccination in the first trimester. Conclusions Vaccinating pregnant mothers in the first trimester conferred greater protection to infants than any other trimester.

Resurgence of influenza and enterovirus infections in Taiwan post-COVID-19: A nationwide surveillance study

BackgroundThe global impact of COVID-19 has prompted profound shifts in public health policies. The epidemiology of respiratory infectious disease may change in the post-covid era. This study investigates the repercussions of these policies on respiratory infectious diseases, specifically the resurgence of severe influenza and enterovirus infections in the post-COVID-19 era. MethodsExamining the period from January 2020 to December 2023, our nationwide study analyzes data from the Taiwan Centers for Disease Control and Our World in Data. Two distinct phases, containing (Week 1, 2020, to Week 43, 2022) and coexisting (Week 44, 2022, to Week 50, 2023), are scrutinized, emphasizing policy changes and their potential impact on epidemiology. ResultsEpidemiological trends reveal a decline in COVID-19 and all-cause pneumonia during the co-existing period but a notable rise in severe influenza and enterovirus infections. Interrupted time series analysis confirms the surge in severe influenza and enterovirus cases post-restriction ease. ConclusionThe post-COVID-19 era introduces challenges with the resurgence of traditional respiratory diseases, necessitating continuous surveillance, timely non-pharmaceutical interventions, and vaccination as crucial strategies. Vigilance and targeted measures by policymakers and healthcare providers are imperative to navigate the evolving landscape of respiratory infectious diseases in the aftermath of the pandemic.

12375 Rhabdomyolysis As A Cause Of PTH-independent Hypocalcemia In A Child With Acute Influenza Infection

Abstract Disclosure: S. Bhattarai: None. K. Halpin: None. Introduction: Hypocalcemia is characterized by low blood calcium level. Normal range for calcium for ages 12- 19-year is 8.5-10.6 mg/dli . Severe hypocalcemia is considered as serum calcium level of <7 mg/dl. Hypoparathyroidism, pseudohypoparathyroidism and Vitamin D deficiency are some of the most common causes encountered by pediatrician endocrinologists. Rhabdomyolysis with hypocalcemia and elevated PTH is a rare presentation that should be considered, particularly for children presenting with acute viral illness. We present a rare case of rhabdomyolysis associated with hypocalcemia not related to hypoparathyroidism. Case: A 12-year-old female presented to the ED with body ache, poor oral intake and vomiting. She was found to be influenza positive. Labs showed hypocalcemia (4.8 mg/dl). She had an undetectable 25-OH vitamin D level (<5 ng/ml) and elevated iPTH level (609 pg/ml). We discussed the possibility of her etiology of hypocalcemia as Vitamin D deficiency although her presentation was atypical at an older age with negative imaging for rickets, hyperphosphatemia (6.0 mg/dl), and normal ALP (334 unit/L). She did not have any phenotypic features of Albright’s hereditary osteodystrophy with normal renal function. She had elevated CK (4829 U/L) supporting rhabdomyolysis secondary to acute influenza as a cause of her hypocalcemia. Rhabdomyolysis, a known complication of influenza infection, causes cell membrane destruction which impairs the normal function of Na-K-ATPase channel leading to increase in intracellular sodium activating Na/Ca exchanger. This in turn causes influx of calcium intracellularly causing hypocalcemia. Additionally, any injury leads to high phosphorus release from cells due to its lysis. High phosphorus is also caused by reduced oxidative metabolism in muscles impairing phosphate use. This excess of phosphate then combines with calcium and causes calcium-phosphate complex in soft tissues. Hyperphosphatemia additionally inhibits 1 alpha hydroxylase limiting formation of calcitriol leading to hypocalcemia. iiConclusion: Our patient had severe hypocalcemia due to influenza-related rhabdomyolysis. Rhabdomyolysis is an important cause of hypocalcemia in children, especially with acute viral illness. Accordingly, it is also important to obtain serum electrolytes in patients presenting with rhabdomyolysis as hypocalcemia may lead to complications like seizures and cardiac arrhythmia. Endnotes:i Roizen, Jeffrey & Shah, Vipul & Levine, Michael & Carlow, Dean. (2013). Determination of Reference Intervals for Serum Total Calcium in the Vitamin D-Replete Pediatric Population. The Journal of clinical endocrinology and metabolism. 98. 10.1210/jc.2013-3105.ii Ding LN, Wang Y, Tian J, Ye LF, Chen S, Wu SM, Shang WB. Primary hypoparathyroidism accompanied by rhabdomyolysis induced by infection: A case report. World J Clin Cases. 2019 Oct 6;7(19) Presentation: 6/2/2024

Notch4 regulatory T cells and SARS-CoV-2 viremia shape COVID19 survival outcome.

Immune dysregulation and SARS-CoV-2 plasma viremia have been implicated in fatal COVID-19 disease. However, how these two factors interact to shape disease outcomes is unclear. We carried out viral and immunological phenotyping on a prospective cohort of 280 patients with COVID-19 presenting to acute care hospitals in Boston, Massachusetts and Genoa, Italy between June 1, 2020 and February 8, 2022. Disease severity, mortality, plasma viremia, and immune dysregulation were assessed. A mouse model of lethal H1N1 influenza infection was used to analyze the therapeutic potential of Notch4 and pyroptosis inhibition in disease outcome. Stratifying patients based on %Notch4+ Treg cells and/or the presence of plasma viremia identified four subgroups with different clinical trajectories and immune phenotypes. Patients with both high %Notch4+ Treg cells and viremia suffered the most disease severity and 90-day mortality compared to the other groups even after adjusting for baseline comorbidities. Increased Notch4 and plasma viremia impacted different arms of the immune response in SARS-CoV-2 infection. Increased Notch4 was associated with decreased Treg cell amphiregulin expression and suppressive function whereas plasma viremia was associated with increased monocyte cell pyroptosis. Combinatorial therapies using Notch4 blockade and pyroptosis inhibition induced stepwise protection against mortality in a mouse model of lethal H1N1 influenza infection. The clinical trajectory and survival outcome in hospitalized patients with COVID-19 is predicated on two cardinal factors in disease pathogenesis: viremia and Notch4+ Treg cells. Intervention strategies aimed at resetting the immune dysregulation in COVID-19 by antagonizing Notch4 and pyroptosis may be effective in severe cases of viral lung infection.

A-239 Cxcl10 induced gut dysbiosis exacerbates acute lung injury and secondary infection in influenza by inhibiting il22

Abstract Background Secondary infections are the most cause of severe pulmonary injury and death in influenza. CXCL10, known as interferon γ-induced protein 10(IP-10), is highly upregulated in response to IFN-γstimulation during influenza. Previous studies show that CXCL10 contributes to bacteria co-infections and worse finales in influenza. However, the underlying mechanisms by which CXCL10 facilitate secondary infections remains unclear. Emerging evidences show that influenza virus infections disturb the composition and function of gut microbiota, which in turn influences the infection process. Herein, we aimed to explore whether CXCL10 could affect the progress of influenza infection and secondary infection in a gut microbiota dependent manner. Methods CXCL10 knockout mice were used to determine the role of CXCL10 in staphylococcus aureus co-infection after influenza A virus (IAV) infection. Lung tissues from CXCL10 knockout mice were collected for Transcriptomics sequencing. Feces from mice and clinicals including IAV patients and healthy individuals were collected for Metagenomic sequencing. Paired serum samples were collected for Metabolomic sequencing. QRT-PCR was performed to determine the expression of inflammatory factors in lung tissues from CXCL10 knockout mice. Elisa assays were used to measure the serum expression levels of CXCL10 and IL22. Flow cytometry was applied to detect the proportion of IL22+ cells. Fecal microbiota transplantation (FMT) was applied to confirm that CXCL10 plays an adverse role in acute lung injury and staphylococcus aureus co-infection after IAV infection by disrupting intestinal microbiome homeostasis. Results CXCL10 aggravated acute lung injury and promoted staphylococcus aureus coinfection after IAV infection. Transcriptomics sequencing results suggests improved cell membrane integrity and regeneration of epithelial cells after IAV infection in CXCL10 knockout mice with an upregulation of integrity proteins. CXCL10 knockout significantly increased the expression levels of IL22 without influencing virus duplication. rh-IL22 protects lung epithelial cell from staphylococcus aureus co-infection in influenza and increased the expression of tight junction proteins. The gut microbiome shows different structures between wild type mice and knockout mice, as well as clinical samples according to serum CXCL10 expression levels. We found some genera were markedly increased in knockout mice and patients with low serum CXCL10 expression levels including Lactobacillus, Lachnospiraceae, Oscillibacter, Odoribacter, Eubacterium. FMT from patients with low serum CXCL10 levels and healthy individuals ameliorating lung pathological damage. Conclusions This study interpreted that CXCL10 exacerbates acute lung injury and secondary infection in influenza by inducing gut dysbiosis, suggesting that balancing the gut flora could be assistant treatments to protect from acute lung injury and secondary infections in influenza. And IL22 may be a potential mediating factor between gut-lung axis to improve epithelial integrity.

Painless thyroiditis associated with SARS-CoV-2 and influenza infections in a patient with central hypothyroidism after pituitary surgery.

We present the case of a 50-year-old Japanese woman who was transferred to our hospital with a 2-day history of fever, sore throat, and malaise. She was diagnosed with acromegaly 9 months ago while being treated for diabetic ketoacidosis, for which she underwent pituitary surgery. She was diagnosed with hypopituitarism postoperatively and was prescribed hydrocortisone and levothyroxine. Her glycemic control was good on metformin. Tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza were positive in the emergency room. Other laboratory findings included thyrotoxicosis (free T3: 9.13 pg/mL; free T4: 3.64 ng/dL; and thyroid-stimulating hormone (TSH): <0.01 μIU/mL) and a high C-reactive protein (CRP) level (3.84 mg/dL). The test for the TSH receptor antibody was negative. She had no apparent goiter and reported no tenderness in response to thyroid palpation. 99m-Technetium scintigraphy revealed decreased tracer uptake. Ultrasonography showed no hypoechoic lesions. Her thyrotoxicosis spontaneously resolved after 6 weeks. Although both anti-thyroglobulin antibody (TgAb) and anti-thyroid peroxidase antibody (TPOAb) were negative 9 months ago, TgAb was positive at admission. The test for TPOAb became positive 6 weeks later. These findings were suggestive of painless thyroiditis. In this patient, painless thyroiditis was believed to be caused by SARS-CoV-2 and influenza infections. Screening tests of thyroid function in patients with viral infections such as SARS-CoV-2 or influenza are recommended, even when thyroid gland pain or tenderness is not observed. We describe a case of painless thyroiditis associated with SARS-CoV-2 and influenza infections. Although a few cases of painless thyroiditis associated with COVID-19 have been reported, no cases of painless thyroiditis associated with influenza have been reported. In this case, thyrotoxicosis developed immediately after the viral infection. In addition, tests for anti-thyroglobulin antibody and anti-thyroid peroxidase antibody were negative before the onset of symptoms. Tests for the former became positive at the time of onset of symptoms, whereas tests for the latter became positive several weeks after the onset of symptoms. Patients with viral infections such as SARS-CoV-2 and influenza, who had no goiter or thyroid tenderness, may develop painless thyroiditis; screening tests for thyroid function are recommended.

IFN-γ and YAP lead epithelial cells astray after severe respiratory infection.

Ineffective recovery from pneumonia can lead to interstitial lung disease characterized by aberrant epithelial cells in fibrotic regions. In this issue of the JCI, Lin et al. define molecular pathways leading to the development and persistence of keratin 5+ (Krt5+) epithelial cells in the alveolar parenchyma when mice struggle to recover from influenza infection. The receptor for IFN-γ on lung epithelium was essential for the formation of aberrant Krt5+ cells and fibrotic lung disease. The transcription factor Yes-associated protein 1 (YAP) was necessary for persistence of these Krt5+ cells, and IFN-γ activated YAP in lung epithelial cells via JAK, focal adhesion kinase (FAK), and Src kinases. These findings establish a targetable pathway underlying some of the pulmonary postacute sequelae of pneumonia.

Epidemiological comparison of emergency department presentations with seasonal influenza or COVID-19 and an outcome of intensive care admission or death: A population-based records linkage study in New South Wales, Australia

COVID-19 and seasonal influenza are endemic causes of morbidity and mortality. This study aimed to compare the epidemiology of severe illness and risk of death among patients following emergency department (ED) presentation with either infection. De-identified, population-based, emergency department records in New South Wales, Australia, were probabilistically linked to population-level health outcome databases for the period 1 January 2015 to 28 February 2023. Included were patients allocated an ED diagnosis consistent with an acute respiratory infection. Logistic regression was used to examine the association of infecting virus with risk of a severe outcome (intensive care unit admission or death). Influenza infection was notified in 2335 and COVID-19 in 5053 patients with a severe outcome. The age distribution was similar for both viruses, except in <15-year-olds, where severe influenza was nearly three times more frequent. Overall, the odds of death among patients with COVID-19 was 1.65 (95% CI 1.43, 1.89) times higher than among those with influenza. This declined to 1.49 (95% CI 1.08, 2.06) times during the COVID-19 Omicron variant period. The Omicron variant arrived when background population COVID-19 vaccination coverage was >90%. Despite that, death was more frequent for COVID-19 than influenza.

Gestational influenza A virus infection elicits nonresolving vascular dysfunction and T-cell accumulation in the aorta of mice.

T-cell accumulation within the aorta promotes endothelial dysfunction and the genesis of cardiovascular disease, including hypertension and atherosclerosis. Viral infection during pregnancy is also known to mediate marked acute endothelial dysfunction, but it is not clear whether T cells are recruited to the aorta and whether the dysfunction persists postpartum. Here, we demonstrate that influenza A virus (IAV) infection during pregnancy in a murine model resulted in endothelial dysfunction of the aorta, which persisted for up to 60 days postinfection and was associated with higher levels of IFN-γ mRNA expression within the tissue. In the absence of infection, low numbers of naïve CD4+ and CD8+ T cells, central memory T cells, and effector memory T cells were observed in the aorta. However, with IAV infection, these T-cell subsets were significantly increased with a notable accumulation of IAV-specific CD8+ effector memory T cells. Critically, this increase was maintained out to at least 60 days. In contrast, IAV infection in nonpregnant female mice resulted in modest endothelial dysfunction with no accumulation of T cells within the aorta. These data, therefore, demonstrate that the aorta is a site of T-cell recruitment and retention after IAV infection during pregnancy. Although IAV-specific memory T cells could theoretically confer protection against future influenza infection, nonspecific memory T-cell activation and IFN-γ production in the aorta could also contribute to future endothelial dysfunction and cardiovascular disease.NEW & NOTEWORTHY Pregnancy is a risk factor for cardiovascular complications to influenza A virus (IAV) infection. We demonstrate that gestational IAV infection caused endothelial dysfunction of the maternal aorta, which persisted for 60 days postinfection in mice. Various T cells accumulated within the aorta at 60 days because of the infection, and this was associated with elevated levels of the proinflammatory cytokine, IFN-γ. Our study demonstrates a novel "long influenza" cardiovascular phenotype in female mice.

Optimizing influenza vaccination among oncology patients through quality improvement cycles.

285 Background: Influenza poses significant risks to cancer patients, who are especially vulnerable due to immunosuppression caused by both their disease and treatment. (Cooksley et al., 2005) Sidney Kimmel Cancer Center – Jefferson Health (SKCC)’s Quality Improvement (QI) initiative aimed to increase influenza vaccination rates among adult cancer patients in our Center City clinic from October 2023 to March 2024. At baseline in the 2022-2023 flu season, 49% of our patients had a documented vaccination against influenza, leaving most of our patient population at increased risk for influenza infection. Methods: A series of four Plan-Do-Study-Act (PDSA) cycles were implemented over the course of the vaccination season. Cycle 1 collected baseline data on vaccination status via electronic health records (EHRs) and identified gaps in patient knowledge and vaccine hesitancy. Cycle 2 trained medical assistants (MAs) to engage in effective vaccination conversations, emphasizing the use of presumptive communication techniques and the reconciliation of immunization records in EHRs. Cycle 3 integrated patient education materials on vaccination in the clinical encounter. Cycle 4 scaled assessment protocols across teams. Results: Cumulatively, 68% (2,592/3,824) of unique oncology patients had a documented influenza vaccination by the completion of the season in March 2024. Integration of vaccine reconciliation into the MA workflow was the iteration that led to the biggest increase in vaccination rate among the PDSA cycles tested. We surpassed our initial aim for the season (59%) in this metric. Conclusions: The QI project at SKCC demonstrates that layered strategies involving both patients and care teams can improve vaccination rates among adult cancer patients. Integration of vaccine assessment into clinic workflows was an effective tactic. Future efforts will focus on replicating these successes with other vaccines. Rates of influenza vaccination by PDSA cycle. Cycle # Date Cycle Description Outcome Metric: Cumulative Vaccination Rate (%) 1 Oct 2023 Provider perception survey of vaccination knowledge 65 2 Nov 2023 Integration of vaccine reconciliation in MA workflow 69 3 Dec 2023 Integration of patient education materials to clinical encounter 70 4 Jan 2024 – Mar 2024 Scaling of updated workflows to entire clinic 68

Meeting Report: Controlled Human Influenza Virus Infection Model Studies: Current Status and Future Directions for Innovation.

On November 13-14, 2023, the National Institute of Allergy and Infectious Diseases (NIAID) in partnership with the Task Force for Global Health, Flu Lab, the Canadian Institutes of Health Research, and the Centers for Disease Control and Prevention convened a meeting on controlled human influenza virus infection model (CHIVIM) studies to review the current research landscape of CHIVIM studies and to generate actionable next steps. Presentations and panel discussions highlighted CHIVIM use cases, regulatory and ethical considerations, innovations, networks and standardization, and the utility of using CHIVIM in vaccine development. This report summarizes the presentations, discussions, key takeaways, and future directions for innovations in CHIVIMs. Experts agreed that CHIVIM studies can be valuable for the study of influenza infection, immune response, and transmission. Furthermore, they may have utility in the development of vaccines and other medical countermeasures; however, the use of CHIVIMs to de-risk clinical development of investigational vaccines should employ a cautious approach. Endpoints in CHIVIM studies should be tailored to the specific use case. CHIVIM studies can provide useful supporting data for vaccine licensure but are not required and do not obviate the need for the conduct of field efficacy trials. Future directions in this field include the continued expansion of capacity to conduct CHIVIM studies, development of a broad panel of challenge viruses and assay reagents and standards that can be shared, streamlining of manufacturing processes, the exploration of targeted delivery of virus to the lower respiratory tract, efforts to more closely replicate natural influenza disease in CHIVIM, alignment on a definition of breadth to facilitate development of more broadly protective/universal vaccine approaches, and continued collaboration between stakeholders.

Improving influenza vaccination assessment and uptake, one step at a time in a cancer center.

280 Background: Influenza immunization has shown to decrease morbidity and mortality of influenza infections. From September to December 2022, at the infectious diseases (ID) clinic at our institution, 73% of the patients did not undergo influenza immunization assessment during their clinical encounters and only 3% of the patients had the influenza vaccine administered. Furthermore, documentation of vaccine discussion was done in 73% of cases. Our aim was to improve vaccination assessment from 73% noncompliant to 50%. Methods: A multidisciplinary team of nurses, nurse leaders, pharmacists, and quality specialists was assembled to analyze baseline data on influenza vaccination assessment, administration, and documentation at the ID clinic from Sept to Dec 2022 using The Model for Improvement. Quality tools were utilized including Cause and Effect Diagram, Current State Process Flow Chart and Prioritization Matrix, to identify and prioritize opportunities for improvement creating a worklist for improvement focus. Vaccine assessment measured via EPIC immunization tab marked as reviewed, discrete areas to document vaccination and their administration were not a part of nursing or provider’s workflow. Using the Plan, Do, Study, Act (PDSA) method, the following changes were tested: PDSA Cycle 1; A green sticker highlighted those patients needing vaccine assessment. PDSA Cycle 2; A smart phrase was created for documentation in nurses’ notes and PDSA Cycle 3; provider’s notes regarding vaccine recommendations. Results: Interventions were associated with an improvement of influenza assessment via the immunization tab marked as reviewed in the ID outpatient clinic from 73% noncompliance to 3% noncompliance from September 2023 to March 2024. Concurrent with improvement of our assessment process, our on-site vaccination rate increased from 97% error to 89% error (Table) and there was 50% improvement in provider’s documentation. Conclusions: The formation of a multidisciplinary working group and implementation of quality tools interventions resulted in timely significant improvement in vaccination assessment, documentation, and administration. Subsequently, we were granted institutional approval to add an EPIC clinical decision support tool to standardize influenza vaccination documentation. Future strategies include implementation and evaluation of the utilization of Health Maintenance tool in the ID clinic before expansion to other clinics in our institution. Influenza vaccine administration vs outpatient visits in the ID clinic. Month/Year # Outpatient visits # Vaccines administered in clinic % of vaccines administered Influenza Sep-Dec 2022 1827* 54 2.95% Influenza Sept 2023-March 2024 2682 251 9.36% *Includes video and telephone visits.

Effect of Mixed Probiotics on Alleviating H1N1 Influenza Infection and Regulating Gut Microbiota.

Influenza and other respiratory infections cause annual epidemics worldwide, with high incidence and mortality rates reported among immunocompromised infants and elderly individuals. Probiotics can modulate the immune system through their bacterial compositions and metabolites, affecting influenza infections and effectively responding to viral mutations. Therefore, we evaluated the anti-influenza effects of mixed probiotics administered orally before and after influenza infection. The results showed that the mixed probiotics consisting of Lacticaseibacillus rhamnosus CCFM1279, Limosilactobacillus reuteri CCFM1145, and Lacticaseibacillus casei CCFM1127 inhibited viral replication and reduced lung inflammatory damage against influenza. In addition, the mixed-probiotics treatment activated the systemic immune response of the host. The gut microbiota analysis revealed a notable increase in the abundance of Alistipes and Rikenella following mixed-probiotic supplementation. The metabolomic analysis indicated a significant increase in adenosine levels, which was positively correlated with the abundance of Parvibacter. These findings highlight the effectiveness of mixed probiotics in fighting influenza viruses and suggest that certain gut microbiota and their metabolites may play a significant role in influencing the outcomes of influenza infections.

Efficacy and feasibility of a novel semi-facial respirator with chitosan nanoparticles on the incidence of SARS-CoV-2 infection in healthcare professionals: randomized controlled trial

BackgroundEvidence suggests that semi-facial respirators provide protection against contamination in high-risk environments, although the COVID-19 pandemic called for greater protection and viral inactivation capacity. Thus, the aim of this study was to investigate the efficacy of a novel semi-facial respirator containing chitosan nanoparticles, compared with a conventional N95 respirator on the incidence of laboratory-confirmed SARS-CoV-2 in healthcare professionals. The secondary outcomes were influenza infection, usability and comfort.MethodsRandomized controlled trial within a large public hospital (reference for COVID-19 patients) carried out between March 2021 and June 2023. We included 230 healthcare professionals exposed to SARS-Cov-2 and influenza, working in emergency departments, hospital wards, and intensive care units. Participants were assessed at baseline, after 10 days, and 21 days of follow-up. Researchers, participants, and outcome assessors were blinded to the allocated groups. Outcomes were analyzed by bivariate and multivariate comparisons using logistic regression. Crude (cOR) and adjusted odds ratios (aOR) were estimated, followed by 95% confidence intervals (CIs 95%). We adopted intention-to-treat (ITT) and complete-case (CC) analyses.ResultsBaseline characteristics were considered homogeneous between groups, and usability and comfort were reported as excellent in both groups. Non-significant differences were found for all outcomes, both in the ITT and CC analyses. The incidence of COVID-19 and influenza were, respectively, cOR: 0.96 [CI95%: 0.21–4.42] and cOR: 1.25 [CI95%: 0.34–4.62]; and aOR: 1.08 [CI95%: 0.21–5.47] and aOR: 1.11 [CI95%: 0.17–7.01].ConclusionsWe found that the incidence of SARS-Cov-2 and influenza infections were similar between the new respirator compared to the conventional respirator. Furthermore, we observed that usability and comfort were similar and considered excellent for both respirators.Trial registrationClinicaltrials.gov (NCT04490200, 29/07/2020).

Taking AIM at Influenza: The Role of the AIM2 Inflammasome.

Influenza A viruses (IAV) are dynamic and highly mutable respiratory pathogens that present persistent public health challenges. Inflammasomes, as components of the innate immune system, play a crucial role in the early detection and response to infections. They react to viral pathogens by triggering inflammation to promote immune defences and initiate repair mechanisms. While a strong response is necessary for early viral control, overactivation of inflammasomes can precipitate harmful hyperinflammatory responses, a defining characteristic observed during severe influenza infections. The Absent in Melanoma 2 (AIM2) inflammasome, traditionally recognised for its role as a DNA sensor, has recently been implicated in the response to RNA viruses, like IAV. Paradoxically, AIM2 deficiency has been linked to both enhanced and reduced vulnerability to IAV infection. This review synthesises the current understanding of AIM2 inflammasome activation during IAV and explores its clinical implications. Understanding the nuances of AIM2's involvement could unveil novel therapeutic avenues for mitigating severe influenza outcomes.

Pregnancy enhances antiviral immunity independent of type I IFN but dependent on IL-17-producing γδ+ T cells in the nasal mucosa.

Pregnancy is associated with profound changes in immunity. However, pregnancy-related respiratory immune adaptations in response to influenza infection and their impact on disease severity remain unclear. Here, we describe, in a preclinical model of mid-gestation pregnancy, a mechanism of enhanced host defense against influenza A virus (IAV) localized to the nasal cavity that limits viral replication and reduces the magnitude of intrapulmonary immune responses. Consequently, the pregnant mice show reduced pulmonary pathology and preserved airway function after IAV infection. The early restriction of viral replication is independent of type I interferon (IFN) but dependent on increased antimicrobial peptides (AMPs) driven by interleukin-17+ (IL-17+) γδ+ T cells within the nasal passages. This pathway of host defense against IAV infection in the upper airways during pregnancy restricts early viral infection and prevents virus dissemination into the lung supporting maternal fitness.

Characterizing the seasonal influenza disease burden attributable to climate variability: A nationwide time-series modelling study in Japan, 2000−2019

BackgroundAmbient temperature and humidity are established environmental stressors with regard to influenza infections; however, mapping disease burden is difficult owing to the complexities of the underlying associations and differences in vulnerable population distributions. In this study, we aimed to quantify the burden of influenza attributable to non-optimal ambient temperature and absolute humidity in Japan considering geographical differences in vulnerability. MethodsThe exposure−lag−response relationships between influenza incidence, ambient temperature, and absolute humidity in all 47 Japanese prefectures for 2000−2019 were quantified using a distributed lag non-linear model for each prefecture; the estimates from all the prefectures were then pooled using a multivariate mixed-effects meta-regression model to derive nationwide average associations. Association between prefecture-specific indicators and the risk were also examined. Attributable risks were estimated for non-optimal ambient temperature and absolute humidity according to the exposure−lag−response relationships obtained before. ResultsA total of 25,596,525 influenza cases were reported during the study period. Cold and dry conditions significantly increased influenza incidence risk. Compared with the minimum incidence weekly mean ambient temperature (29.8 °C) and the minimum incidence weekly mean absolute humidity (20.2 g/m3), the cumulative relative risks (RRs) of influenza in cold (2.5 °C) and dry (3.6 g/m3) conditions were 2.79 (95% confidence interval [CI]: 1.78−4.37) and 3.20 (95% CI: 2.37−4.31), respectively. The higher RRs for cold and dry conditions were associated with geographical and climatic indicators corresponding to the central and northern prefectures; demographic, socioeconomic, and health resources indicators showed no clear trends. Finally, 27.25% (95% empirical CI [eCI]: 5.54−36.35) and 32.35% (95% eCI: 22.39−37.87) of all cases were attributable to non-optimal ambient temperature and absolute humidity (6,976,300 [95% eCI: 1,420,068−9,306,128] and 8,280,981 [95% eCI: 8,280,981−9,693,532] cases), respectively. ConclusionsThese findings could help identify the most vulnerable populations in Japan and design adaptation policies to reduce the attributable burden of influenza due to climate variability.

Developmental Vitamin D Deficiency and the Vitamin D Receptor Control Hematopoiesis.

Vitamin D status, the vitamin D receptor (VDR), and the ability to produce active vitamin D [1,25(OH)2D, regulated by Cyp27b1] regulate fetal and adult hematopoiesis. Transgenic reporter mice that express the tdTomato RFP as an indication of Vdr expression were used to identify immune cells that express the Vdr. Vdr/tdTomato+ hematopoietic progenitors were identified as early as embryonic day (E)15.5, establishing that these cells have expressed the Vdr and are vitamin D targets. Maternal vitamin D deficiency [D-; serum 25(OH)D < 20 ng/ml] or Vdr knockout or Cyp27b1 knockout resulted in embryos with fewer fetal progenitors. Vdr/tdTomato+ expression was found to increase with age in CD8+ T cells and innate lymphoid cells (ILCs)1 and ILC3, suggesting that initial Vdr expression in these cells is dependent on environmental factors immediately postbirth. In adult tissues, the frequencies of mature T cells and ILCs as well as Vdr/tdTomato expression were reduced by D-. Maternal D- resulted in fewer progenitors that expressed Vdr/tdTomato+ at E15.5 and fewer Vdr/tdTomato+ immune cells in the adult spleen than offspring from D+ mice. We challenged D- mice with H1N1 influenza infection and found that D- mice were more susceptible than D+ mice. Treating D- mice with vitamin D restored Vdr/tdTomato+ expression in splenic T cells and partially restored resistance to H1N1 infection, which shows that developmental D- results in lingering effects on Vdr expression in the adult immune system that compromise the immune response to H1N1 infection. Vitamin D and the Vdr regulate hematopoiesis in both fetal and postnatal phases of immune cell development that impact the immune response to a viral infection.

Severe Bacterial Superinfection of Influenza Pneumonia in Immunocompetent Young Patients: Case Reports

Influenza can lead to or coexist with severe bacterial pneumonia, with the potential to permanently damage lung tissue, refractory to conservative treatment in the post-COVID-19 period. It can lead to serious complications; therefore, annual vaccinations are recommended. This case series with a literature review pertains to two young female patients with an insignificant past medical history, who required emergency lobectomy due to bacterial complications after influenza infection. Urgent lobectomy proves to be a feasible therapeutic option for selected patients with pleural complications.

A transgenic mouse with a humanised B cell repertoire mounts an antibody response to influenza infection and vaccination.

The development of a universal influenza vaccine likely requires an understanding of previous exposure to influenza virus (through vaccination or infection) and how that shapes the antibody repertoire to vaccination, sometimes called Original Antigenic Sin or antigenic imprinting. Whilst animal models can have a much more defined exposure history, they lack a human B cell repertoire. Transgenic mice with the complete human immunoglobulin locus enable studies of controlled infection history leading to human-like antibody evolution. Here we evaluated responses to influenza in the Intelliselect Transgenic mouse (the Kymouse). We show the Kymouse is susceptible to disease following infection with either H1N1, H3N2 or B/Yam influenza viruses and that it induces a robust binding and neutralising antibody response to all three strains of influenza virus. This study demonstrates that human B cell repertoire mice can be used for influenza virus studies, providing a tool for further interrogation of the antibody response.