Economic burden and secondary complications of influenza-related hospitalization among adults in the US: a retrospective cohort study.

OBJECTIVE: This study aims to describe the healthcare resource utilization (HCRU) and direct medical cost of influenza-related hospitalizations to illustrate the persistent economic burden of influenza among adults in the US. METHODS: A retrospective cohort study was conducted using the PINC AI Healthcare Database. Adults hospitalized with a diagnosis of influenza between August 1-May 31 from 2016-2023 were identified and stratified by age (18-49, 50-64 and ≥65 years). The index hospitalization was defined as the individual's first influenza-related hospitalization during each season. Patient demographics, comorbidities, and hospitalization characteristics were assessed during the index hospitalization. Index hospitalization length of stay (LOS), in-hospital mortality, intensive care unit (ICU) admissions, mechanical ventilation (MV) usage, and costs were evaluated overall and by MV usage, ICU admission, and secondary complication status. Pre-index influenza-related outpatient and emergency department (ED) visits (7 days prior) were also evaluated. RESULTS: Primarily initiated in the ED, the median LOS for influenza-related hospitalizations was 3-4 days. Inpatient mortality increased with age (2.2-4.4%). Combined mean hospitalization and initial ED visit costs were $12,556-$14,494 (2017/18; high severity season) and $11,384-$12,896 (2022/23; most recent season). Compared to other age groups, adults ≥65 years had higher proportions of hospitalization with no MV or ICU usage. Adults 18-49 years had the highest proportion of ICU admission only, whereas adults 50-64 years had the highest MV usage only and both MV and ICU admission. MV and/or ICU usage was associated with higher hospitalization costs. Increasing proportionally with age, the majority of influenza-related hospitalizations had a secondary complication diagnosis, which were associated with elevated costs. LIMITATIONS: Analysis of this hospital-based administrative database relied on coding accuracy. Only hospital system-associated outpatient/ED visits were captured; the full scope of HCRU was under-ascertained. CONCLUSIONS: The economic burden of influenza-related hospitalizations remains substantial, driven by underlying conditions, MV/ICU usage and secondary complications.

This study described the healthcare resource utilization (HCRU) and costs for US adults ≥18 years old hospitalized with influenza and associated secondary complications such as pneumonia, asthma exacerbation and malignant hypertension between 2016­2023. The researchers analyzed a hospital admission database and found that, for the healthcare system, average cost per influenza-related hospitalization ranged from $11,384 to $14,494, depending on the influenza season and age of the patient. Over 96% of patients admitted to a hospital initially presented at the emergency department, 20­30% of patients required mechanical ventilation (MV) or intensive care unit (ICU) admission, and the median hospital length of stay was 3­4 days. This study adds to the existing evidence by providing economic burden estimates for the 2022/23 influenza season, the most recent influenza season after the COVID-19 pandemic, and found slightly lower HCRU and cost for influenza hospitalizations relative to prior seasons. Also, the study comprehensively analyzed economic burden by patient age groups and found lower HCRU and costs among patients ≥65 years compared to adults 18­49 years and 50­64 years consistently for all seasons. Additionally, the study found that the proportion of patients with MV usage alone, with MV usage and an ICU admission, and average hospitalization costs were greatest among patients 50­64 years, highlighting the potential benefit of increasing rates of seasonal influenza vaccination among this age group. Finally, the study found higher costs among patients with complications related to their influenza infection compared to patients without complications. Overall, the study found that influenza-related hospitalization can contribute to substantial economic burden in the US in the most recent time period.

Effectiveness of BNT162b2 BA.4/5 Bivalent COVID-19 Vaccine against Long COVID Symptoms: A US Nationwide Study.

BACKGROUND: Long COVID has become a central public health concern. This study characterized the effectiveness of BNT162b2 BA.4/5 bivalent COVID-19 vaccine (bivalent) against long COVID symptoms. METHODS: Symptomatic US adult outpatients testing positive for SARS-CoV-2 were recruited between 2 March and 18 May 2023. Symptoms were assessed longitudinally using a CDC-based symptom questionnaire at Week 4, Month 3, and Month 6 following infection. The odds ratio (OR) of long COVID between vaccination groups was assessed by using mixed-effects logistic models, adjusting for multiple covariates. RESULTS: At Week 4, among 505 participants, 260 (51%) were vaccinated with bivalent and 245 (49%) were unvaccinated. Mean age was 46.3 years, 70.7% were female, 25.1% had ≥1 comorbidity, 43.0% prior infection, 23.0% reported Nirmatrelvir/Ritonavir use. At Month 6, the bivalent cohort had 41% lower risk of long COVID with ≥3 symptoms (OR: 0.59, 95% CI, 0.36-0.96, p = 0.034) and 37% lower risk of ≥2 symptoms (OR: 0.63, 95% CI, 0.41-0.96, p = 0.030). The bivalent cohort reported fewer and less durable symptoms throughout the six-month follow-up, driven by neurologic and general symptoms, especially fatigue. CONCLUSIONS: Compared with unvaccinated participants, participants vaccinated with the bivalent were associated with approximately 40% lower risk of long COVID and less symptom burden over the six-month study duration.

The Cost of Seasonal Influenza: A Systematic Literature Review on the Humanistic and Economic Burden of Influenza in Older (≥ 65 Years Old) Adults.

INTRODUCTION: Adults aged ≥ 65 years contribute a large proportion of influenza-related hospitalizations and deaths due to increased risk of complications, which result in high medical costs and reduced health-related quality of life (HRQoL). Although seasonal influenza vaccines are recommended for older adults, the effectiveness of current vaccines is dependent on several factors including strain matching and recipient demographic factors. This systemic literature review aimed to explore the economic and humanistic burden of influenza in adults aged ≥ 65 years. METHODS: An electronic database search was conducted to identify studies assessing the economic and humanistic burden of influenza, including influenza symptoms that impact the HRQoL and patient-related outcomes in adults aged ≥ 65 years. Studies were to be published in English and conducted in Germany, France, Spain, and Italy, the UK, USA, Canada, China, Japan, Brazil, Saudi Arabia, and South Africa. RESULTS: Thirty-eight studies reported on the economic and humanistic burden of influenza in adults aged ≥ 65 years. Higher direct costs were reported for people at increased risk of influenza-related complications compared to those at low risk. Lower influenza-related total costs were found in those vaccinated with adjuvanted inactivated trivalent influenza vaccine (aTIV) compared to high-dose trivalent influenza vaccine (TIV-HD). Older age was associated with an increased occurrence and longer duration of certain influenza symptoms. CONCLUSION: Despite the limited data identified, results show that influenza exerts a high humanistic and economic burden in older adults. Further research is required to confirm findings and to identify the unmet needs of current vaccines.

Enabling methanol fixation of pediatric nasal wash during respiratory illness for single cell sequencing in comparison with fresh samples.

BACKGROUND: Lower respiratory tract infection (LRTI) including pneumonia, bronchitis, and bronchiolitis is the sixth leading cause of mortality around the world and leading cause of death in children under 5 years. Systemic immune response to viral infection is well characterized. However, there is little data regarding the immune response at the upper respiratory tract mucosa. The upper respiratory mucosa is the site of viral entry, initial replication and the first barrier against respiratory infections. Lower respiratory tract samples can be challenging to obtain and require more invasive procedures. However, nasal wash (NW) samples from the upper respiratory tract can be obtained with minimal discomfort to the patient. METHOD: In a pilot study, we developed a protocol using NW samples obtained from hospitalized children with LRTI that enables single cell RNA sequencing (scRNA-seq) after the NW sample is methanol-fixed. RESULTS: We found no significant changes in scRNA-seq qualitative and quantitative parameters between methanol-fixed and fresh NW samples. CONCLUSIONS: We present a novel protocol to enable scRNA-seq in NW samples from children admitted with LRTI. With the inherent challenges associated with clinical samples, the protocol described allows for processing flexibility as well as multicenter collaboration. IMPACT: There are no significant differences in scRNA-seq qualitative and quantitative parameters between methanol fixed and fresh Pediatric Nasal wash samples. The study demonstrates the effectiveness of methanol fixation process on preserving respiratory samples for single cell sequencing. This enables Pediatric Nasal wash specimen for single cell RNA sequencing in pediatric patients with respiratory tract infection and allows processing flexibility and multicenter collaboration.

Impact of Bivalent BA.4/5 BNT162b2 COVID-19 Vaccine on Acute Symptoms, Quality of Life, Work Productivity and Activity Levels among Symptomatic US Adults Testing Positive for SARS-CoV-2 at a National Retail Pharmacy.

Evidence on the impact of COVID-19 vaccination on symptoms, Health-Related Quality of Life (HRQoL) and Work Productivity and Activity Impairment (WPAI) is scarce. We analyzed associations between bivalent BA.4/5 BNT162b2 (BNT162b2) and these patient-reported outcomes (PROs). Symptomatic US adults testing positive for SARS-CoV-2 were recruited between 2 March and 18 May 2023 (CT.gov NCT05160636). PROs were assessed using four questionnaires measuring symptoms, HRQoL and WPAI (a CDC-based symptom survey, PROMIS Fatigue, EQ-5D-5L, WPAI-GH), from pre-COVID to Week 4 following infection. Multivariable analysis using mixed models for repeated measures was conducted, adjusting for several covariates. The study included 643 participants: 316 vaccinated with BNT162b2 and 327 unvaccinated/not up-to-date. Mean (SD) age was 46.5 years (15.9), 71.2% were female, 44.2% reported prior infection, 25.7% had ≥1 comorbidity. The BNT162b2 cohort reported fewer acute symptoms through Week 4, especially systemic and respiratory symptoms. All PROs were adversely affected, especially at Week 1; however, at that time point, the BNT162b2 cohort reported better work performance, driven by less absenteeism, and fewer work hours lost. No significant differences were observed for HRQoL COVID-19 negatively impacted patient outcomes. Compared with unvaccinated/not up-to-date participants, those vaccinated with bivalent BA.4/5 BNT162b2 reported fewer and less persistent symptoms and improved work performance.

Impact of COVID-19 Infection on Health-Related Quality of Life, Work Productivity and Activity Impairment by Symptom-Based Long COVID Status and Age in the US.

COVID-19 infection adversely impacts patients' wellbeing and daily lives. This survey-based study examined differences in patient-reported COVID-19 symptoms, Health-Related Quality of Life (HRQoL) and Work Productivity and Activity Impairment (WPAI) among groups of patients defined based on age and symptom-based long COVID status. Symptomatic, COVID-19-positive US outpatients were recruited from 31 January-30 April 2022. Outcomes were collected via validated instruments at pre-COVID, Day 3, Week 1, Week 4, Month 3 and Month 6 following infection, with changes assessed from pre-COVID and between groups, adjusting for covariates. EQ-5D-5L HRQoL and WPAI scores declined in all groups, especially during the first week. Long COVID patients reported significantly higher symptoms burden and larger drops in HRQoL and WPAI scores than patients without long COVID. Their HRQoL and WPAI scores did not return to levels comparable to pre-COVID through Month 6, except for absenteeism. Patients without long COVID generally recovered between Week 4 and Month 3. Older (>50) and younger adults generally reported comparable symptoms burden and drops in HRQoL and WPAI scores. During the first week of infection, COVID-19-related health issues caused loss of 14 to 26 work hours across the groups. These data further knowledge regarding the differential impacts of COVID-19 on clinically relevant patient groups.

Clinical outcomes of COVID-19 and influenza in hospitalized children <5 years in the US.

Introduction: We compared hospitalization outcomes of young children hospitalized with COVID-19 to those hospitalized with influenza in the United States. Methods: Patients aged 0-<5 years hospitalized with an admission diagnosis of acute COVID-19 (April 2021-March 2022) or influenza (April 2019-March 2020) were selected from the PINC AI Healthcare Database Special Release. Hospitalization outcomes included length of stay (LOS), intensive care unit (ICU) admission, oxygen supplementation, and mechanical ventilation (MV). Inverse probability of treatment weighting was used to adjust for confounders in logistic regression analyses. Results: Among children hospitalized with COVID-19 (n = 4,839; median age: 0 years), 21.3% had an ICU admission, 19.6% received oxygen supplementation, 7.9% received MV support, and 0.5% died. Among children hospitalized with influenza (n = 4,349; median age: 1 year), 17.4% were admitted to the ICU, 26.7% received oxygen supplementation, 7.6% received MV support, and 0.3% died. Compared to children hospitalized with influenza, those with COVID-19 were more likely to have an ICU admission (adjusted odds ratio [aOR]: 1.34; 95% confidence interval [CI]: 1.21-1.48). However, children with COVID-19 were less likely to receive oxygen supplementation (aOR: 0.71; 95% CI: 0.64-0.78), have a prolonged LOS (aOR: 0.81; 95% CI: 0.75-0.88), or a prolonged ICU stay (aOR: 0.56; 95% CI: 0.46-0.68). The likelihood of receiving MV was similar (aOR: 0.94; 95% CI: 0.81, 1.1). Conclusions: Hospitalized children with either SARS-CoV-2 or influenza had severe complications including ICU admission and oxygen supplementation. Nearly 10% received MV support. Both SARS-CoV-2 and influenza have the potential to cause severe illness in young children.

Understanding the Global Burden of Influenza in Adults Aged 18-64 years: A Systematic Literature Review from 2012 to 2022.

INTRODUCTION: Adults aged 18-64 years comprise most of the working population, meaning that influenza infection can be disruptive, causing prolonged absence from the workplace, and reduced productivity and the ability to care for dependents. Influenza vaccine uptake is relatively low, even among the older adults in this population (i.e., aged 50-64 years), reflecting a lack of perceived need for vaccination. This systematic literature review (SLR) aimed to characterize the global burden of influenza in the 18-64 years population. METHODS: An electronic database search was conducted and supplemented with conference and gray literature searches. Eligible studies described at least one of clinical, humanistic, or economic outcomes in adults aged 18-64 years and conducted across several global regions. Included studies were published in English, between January 1, 2012, and September 20, 2022. RESULTS: A total of 40 publications were included, with clinical, humanistic, and economic outcomes reported in 39, 5, and 15, respectively. Risk of influenza-associated clinical outcomes were reported to increase with age among the 18-64 years population, including hospitalizations (Yamana et al. in Intern Med 60:3401-3408, 2021; Derqui et al. in Influenza Other Respir Viruses 16:862-872, 2022; Fuller et al. in Influenza Other Respir Viruses 16:265-275, 2022; Ortiz et al. in Crit Care Med 42:2325-2332, 2014; Yandrapalli et al. in Ann Transl Med 6:318, 2018; Zimmerman et al. in Influenza Other Respir Viruses 16:1133-1140, 2022). ICU admissions, mortality, ER/outpatient visits, and use of mechanical ventilation were recorded. Adults aged 18-64 years with underlying comorbidities were at higher risk of influenza-related hospitalizations, ICU admission, and mortality than otherwise healthy individuals. Length of hospital stay increased with age, although a lack of stratification across other economic outcomes prevented identification of further trends across age groups. CONCLUSIONS: High levels of hospitalization and outpatient visits demonstrated a clinical influenza-associated burden on patients and healthcare systems, which is exacerbated by comorbidities. Considering the size and breadth of the general population aged 18-64 years, the limited humanistic and economic findings of this SLR likely reflect an underreported burden. Greater investigation into indirect costs and prolonged absenteeism associated with influenza infection is required to fully understand the economic burden in this population.

High Clinical Burden of Influenza Disease in Adults Aged ≥ 65 Years: Can We Do Better? A Systematic Literature Review.

INTRODUCTION: Influenza is a respiratory infection associated with a significant clinical burden globally. Adults aged ≥ 65 years are at increased risk of severe influenza-related symptoms and complications due to chronic comorbidity and immunosenescence. Annual influenza vaccination is recommended; however, current influenza vaccines confer suboptimal protection, in part due to antigen mismatch and poor durability. This systematic literature review characterizes the global clinical burden of seasonal influenza among adults aged ≥ 65 years. METHODS: An electronic database search was conducted and supplemented with a conference abstract search. Included studies described clinical outcomes in the ≥ 65 years population across several global regions and were published in English between January 1, 2012 and February 9, 2022. RESULTS: Ninety-nine publications were included (accounting for > 156,198,287 total participants globally). Clinical burden was evident across regions, with most studies conducted in the USA and Europe. Risk of influenza-associated hospitalization increased with age, particularly in those aged ≥ 65 years living in long-term care facilities, with underlying comorbidities, and infected with A(H3N2) strains. Seasons dominated by circulating A(H3N2) strains saw increased risk of influenza-associated hospitalization, intensive care unit admission, and mortality within the ≥ 65 years population. Seasonal differences in clinical burden were linked to differences in circulating strains. CONCLUSIONS: Influenza exerts a considerable burden on adults aged ≥ 65 years and healthcare systems, with high incidence of hospitalization and mortality. Substantial influenza-associated clinical burden persists despite increasing vaccination coverage among adults aged ≥ 65 years across regions included in this review, which suggests limited effectiveness of currently available seasonal influenza vaccines. To reduce influenza-associated clinical burden, influenza vaccine effectiveness must be improved. Next generation vaccine production using mRNA technology has demonstrated high effectiveness against another respiratory virus-SARS-CoV-2-and may overcome the practical limitations associated with traditional influenza vaccine production.

"Hot Tub Lung" With M. avium complex in an Immunocompetent Adolescent.

We describe a case of pulmonary Mycobacterium avium complex (MAC) infection in an immunocompetent pediatric patient after a hot tub near drowning event with a literature review of pediatric MAC-associated disease after hot tub exposure.

Disparities in Outcomes During Lower Respiratory Tract Infection in American Indian Children: A 9-Year Retrospective Analysis in a Rural Population in South Dakota.

BACKGROUND: American Indian (AI) children are at increased risk for severe disease during lower respiratory tract infection (LRTI). The reasons for this increased severity are poorly understood. The objective of this study was to define the clinical presentations of LRTI and highlight the differences between AI and non-AI previously healthy patients under the age of 24 months. METHODS: We performed a retrospective chart review between October 2010 and December 2019. We reviewed 1245 patient charts and 691 children met inclusion criteria for this study. Data records included demographics, clinical, laboratory data, and illness outcomes. RESULTS: Of 691 patients, 120 were AI and 571 were non-AI. There was a significant difference in breast-feeding history (10% of AI vs. 28% of non-AI, P < 0.0001) and in secondhand smoke exposure (37% of AI vs. 21% of non-AI, P < 0.0001). AI children had increased length of hospitalization compared with non-AI children (median of 3 vs. 2 days, P < 0.001). In addition, AI children had higher rates of pediatric intensive unit admission (30%, n = 37) compared with non-AI children (11%; n = 67, P < 0.01). AI children also had higher rates (62.5%, n = 75) and duration of oxygen supplementation (median 3 days) than non-AI children (48%, n = 274, P = 0.004; median 2 days, P = 0.0002). On a multivariate analysis, AI race was an independent predictor of severe disease during LRTI. CONCLUSIONS: AI children have increased disease severity during LRTI with longer duration of hospitalization and oxygen supplementation, a higher rate of oxygen requirement and Powered by Editorial Manager and ProduXion Manager from Aries Systems Corporation pediatric intensive care unit admissions, and a greater need for mechanical ventilation. These results emphasize the need for improvement in health policies and access to health care in this vulnerable population.

Viral Coinfection and Nasal Cytokines in Children With Clinically Diagnosed Acute Sinusitis.

Objective: Children with no pathogenic bacteria in the nasopharynx are unlikely to have acute bacterial sinusitis. We evaluated whether information on clinical presentation, viral co-detection, and mucosal cytokine levels could be used to predict presence of bacteria in the nasopharynx. Method: We obtained nasopharyngeal (NP) swabs from children diagnosed with acute sinusitis. NP swabs were processed for bacterial culture, viral PCR testing, and cytokine expression. We examined whether results of the bacterial culture could be predicted based on the presence of clinical information, presence of viruses or mucosal cytokine levels. Results: We enrolled 174 children; 123 (71%) had a positive culture for potentially pathogenic bacteria and 51 (29%) had normal flora. 122/174 (70%) tested positive for one or more viruses. Compared to children with normal flora, children with pathogenic bacteria were more likely to have viruses (p < 0.01), but this relationship disappeared when we adjusted for age. Children with pathogenic bacteria in their nasopharynx and children with normal flora had similar levels of nasal cytokines. Conclusion: In children with clinically diagnosed acute sinusitis, clinical presentation, levels of nasal cytokines, and presence of viruses do not differentiate children with and without pathogenic bacteria in their nasopharynx.

A method of processing nasopharyngeal swabs to enable multiple testing.

OBJECTIVE: To develop a method to perform multiple tests on a single nasopharyngeal (NP) swab. METHODS: We collected a NP swab on children aged 2-12 years with acute sinusitis and processed it for bacterial culture, viruses, cytokine expression, and 16S ribosomal RNA gene sequencing analysis. During the course of the study, we expand the scope of evaluation to include RNA-sequencing, which we accomplished by cutting the tip of the swab. RESULTS: Of the 174 children enrolled, 126 (72.4%) had a positive bacterial culture and 121 (69.5%) tested positive for a virus. Cytokine measurement, as judged by adequate levels of a housekeeping enzyme (glyceraldehyde 3-phosphate dehydrogenase), appeared successful. From the samples used for 16S ribosomal sequencing we recovered, on average, 16,000 sequences per sample, accounting for a total of 2646 operational taxonomic units across all samples sequenced. Samples used for RNA-sequencing had a mean RNA integrity number of 6.0. Cutting the tip of the swab did not affect the recovery yield for viruses or bacteria, nor did it affect species richness in microbiome analysis. CONCLUSION: We describe a minimally invasive sample collection protocol that allows for multiple diagnostic and research investigations in young children.

Oral Management for Pediatric Lyme Meningitis.

BACKGROUND: Guidelines for pediatric Lyme meningitis recommend treatment with parenteral therapy [1, 2]. Adult studies suggest that Lyme meningitis can be successfully treated with oral therapy. Our objective was to evaluate the clinical response, side effects and outcome of oral therapy for Lyme meningitis in the pediatric population compared with parenteral therapy in an area endemic for Lyme disease. METHODS: We conducted a case series chart review from January 2012 to May 2017 of pediatrics patient diagnosed and treated for Lyme meningitis. We recorded clinical presentation, laboratory values, antimicrobial therapy and follow up after therapy to compare the efficacy of oral versus parenteral route of therapy. RESULTS: We identified 38 patients diagnosed with Lyme meningitis. Thirty-two patients were discharge with exclusively oral therapy with: doxycycline and amoxicillin. We had only 2 patients developed potential adverse effects from oral doxycycline therapy. All patients treated with oral antibiotics had resolution of symptoms on follow up appointments. CONCLUSIONS: Oral therapy for Lyme meningitis yields no serious adverse events, was well tolerated and showed resolution of symptoms.

Adenovirus infection in pediatric transplant recipients: are effective antiviral agents coming our way?

PURPOSE OF REVIEW: Adenoviruses (AdVs) infection is a self-limited disease in the majority of immunocompetent children and adults, but can cause disseminated and life-threatening illness in immunocompromised hosts. This article will discuss therapeutic strategies for AdV infection in the pediatrics transplant recipient. RECENT FINDINGS: Currently, there is no FDA approved antiviral therapy for AdV infection. Accordingly, the primary initial therapy would be decreasing immunosuppression, whenever possible. Cidofovir (CDV) is an antiviral drug whose use has been associated with significant reductions of AdV viral load and, in some series improved survival in recipients of solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT). However, its use is also associated with significant toxicity. Brincidofovir (BCV) is a lipid formulation of CDV, which has an improved oral bioavailability and favorable toxicity profile compared with CDV. However, studies have only shown modest benefit from BCV for AdV disease or viremia. Immunotherapy is a growing field in the management of this virus infection on HSCT patients with promising results. SUMMARY: Current evidence support the use of CDV and BCV, as rescue therapy, on SOT and HSCT transplant patients. Immunotherapy had only been proven successful in HSCT patients, as an option for refractory cases or rescue therapy for AdV infection.

Differences in antibody responses between trivalent inactivated influenza vaccine and live attenuated influenza vaccine correlate with the kinetics and magnitude of interferon signaling in children.

BACKGROUND: Live attenuated influenza vaccine (LAIV) and trivalent inactivated influenza vaccine (TIV) are effective for prevention of influenza virus infection in children, but the mechanisms associated with protection are not well defined. METHODS: We analyzed the differences in B-cell responses and transcriptional profiles in children aged 6 months to 14 years immunized with these 2 vaccines. RESULTS: LAIV elicited a significant increase in naive, memory, and transitional B cells on day 30 after vaccination, whereas TIV elicited an increased number of plasmablasts on day 7. Antibody titers against the 3 vaccine strains (H1N1, H3N2, and B) were significantly higher in the TIV group and correlated with number of antibody-secreting cells. Both vaccines induced overexpression of interferon (IFN)-signaling genes but with different kinetics. TIV induced expression of IFN genes on day 1 after vaccination in all age groups, and LAIV induced expression of IFN genes on day 7 after vaccination but only in children <5 years old. IFN-related genes overexpressed in both vaccinated groups correlated with H3N2 antibody titers. CONCLUSIONS: These results suggest that LAIV and TIV induced significantly different B-cell responses in vaccinated children. Early induction of IFN appears to be important for development of antibody responses.