Background: In 2021–22, influenza A viruses dominated in Europe. The I-MOVE primary care network conducted a multicentre test-negative study to measure influenza vaccine effectiveness (VE). Methods: Primary care practitioners collected information on patients presenting with acute respiratory infection. Cases were influenza A(H3N2) or A(H1N1)pdm09 RT-PCR positive and controls were influenza virus negative. We calculated VE using logistic regression, adjusting for study site, age, sex, onset date, and presence of chronic conditions. Results: Between week 40 2021 and week 20 2022, we included over 11,000 patients of whom 253 and 1595 were positive for influenza A(H1N1)pdm09 and A(H3N2), respectively. Overall VE against influenza A(H1N1)pdm09 was 75% (95%CI: 43–89) and 81% (95%CI: 44–93) among those aged 15–64 years. Overall VE against influenza A(H3N2) was 29% (95%CI: 12–42) and 25% (95%CI: -41–61), 33% (95%CI: 14–49) and 26% (95% CI: -22 to 55) among those aged 0–14, 15–64 and over 65 years, respectively. The A(H3N2) VE among the influenza vaccination target group was 20% (95%CI: -6–39). All 53 sequenced A(H1N1)pdm09 viruses belonged to clade 6B.1A.5a.1. Among 410 sequenced influenza A(H3N2) viruses, all but 8 belonged to clade 3C.2a1b.2a.2. Discussion: Despite antigenic mismatch between vaccine and circulating strains for influenza A(H3N2) and A(H1N1)pdm09, 2021–22 VE estimates against circulating influenza A(H1N1)pdm09 were the highest within the I-MOVE network since the 2009 influenza pandemic. VE against A(H3N2) was lower than A(H1N1)pdm09, but at least one in five individuals vaccinated against influenza were protected against presentation to primary care with laboratory-confirmed influenza.

Background Sarajevo Canton in the Federation of Bosnia and Herzegovina has recorded several waves of high SARS-CoV-2 transmission and has struggled to reach adequate vaccination coverage. We describe the evolution of infection- and vaccine-induced SARS-CoV-2 antibody response and persistence. Methods We conducted repeated cross-sectional analyses of blood donors aged 18-65 years in Sarajevo Canton in November-December 2020 and 2021. We analyzed serum samples for anti-nucleocapsid (anti-N) and anti-spike (anti-S) antibodies. To assess immune durability, we conducted longitudinal analyses of seropositive participants at 6 and 12 months. Results 1015 participants were included in Phase 1 (November-December 2020), and 1152 in Phase 2 (November-December 2021). Seroprevalence increased significantly from 19.2% (95% CI: 17.2-21.4%) in Phase 1 to 91.6% (95% CI: 89.8-93.1%) in Phase 2. Anti-S IgG titers were significantly higher among vaccinated (58.5%) than unvaccinated infected participants across vaccine products (p<0.001), though highest among those who received an mRNA vaccine. At 6 months, 78/82 (95.1%) participants maintained anti-spike seropositivity; at 12 months, 58/58 (100.0%) participants were seropositive and 33 (56.9%) had completed the primary vaccine series within 6 months. Among 11 unvaccinated participants who were not reinfected at 12 months, anti-S IgG declined from median 770.1 (IQR 615.0-1321.7) to 290.8 (IQR 175.7-400.3). Anti-N IgG antibodies waned earlier; from 35.4% seropositive at 6 months to 24.1% at 12 months. Conclusions SARS-CoV-2 seroprevalence increased significantly over 12 months from end of 2020 to end of 2021. Although individuals with previous infection may have residual protection, COVID-19 vaccination is vital to strengthening population immunity.

Background: Measures introduced during the COVID-19 pandemic intended to address the spread of SARS-CoV-2 may also influence the incidence of other common seasonal respiratory viruses (SRV). This evaluation reports laboratory confirmed cases of common SRV in a well-defined region of central Canada to address this issue. Methods: Surveillance data for common non-SARS-CoV-2 SRV in the Ottawa, Canada region was provided by the Eastern Ontario Regional Laboratory Association (EORLA) reference virology lab. Weekly reports of the number of positive tests and proportion that yielded positive results was analyzed from August 26, 2018 to January 2, 2022. Results: A drastic reduction in influenza and other common SRV was observed during the 2020-2021 influenza season in the Ottawa region. Influenza was virtually undetected post SARS-CoV-2 emergence. Rhinoviruses and enteroviruses were the only viruses that remained relatively unaffected during this period. Conclusions: We speculated that the introduction of non-pharmaceutical measures including masking to prevent SARS-CoV-2 transmission contributed to the near absence of SRV in the Ottawa region. These measures should remain a key component in addressing spikes in SRV activity and future pandemics.

Background. Respiratory syncytial virus (RSV) infection is a cause of substantial morbidity and mortality in young children. There is currently no effective therapy available. Methods. This was a phase 2 study of the oral RSV fusion protein inhibitor AK0529 in infants aged 1-24 months, hospitalized with RSV infection. In part 1 patients (n=24) were randomized 2:1 to receive a single dose of AK0529 up to 4 mg/kg or placebo. In part 2 patients (n=48) were randomized 2:1 to receive AK0529 at 0.5, 1 or 2 mg/kg bid or placebo for five days. Sparse pharmacokinetic samples were assessed using population pharmacokinetics modelling. Safety, tolerability, viral load, signs and symptoms were assessed daily during treatment. Results. No safety or tolerability signals were detected for AK0529: grade ≥3 treatment-emergent adverse events occurred in 4.1% of patients in AK0529 and 4.2% in placebo groups, respectively, and none led to death or withdrawal from the study. In part 2, targeted drug exposure was reached with 2 mg/kg bid. A numerically greater reduction in median viral load with 2 mg/kg bid AK0529 than with placebo at 96 hours was observed. A -4.0 (95% CI: -4.51, -2.03) median reduction in RSV signs and symptom score from baseline to 96 hours was observed in the 2 mg/kg group, compared with -2.0 (95% CI: -3.42, -1.82) in the placebo group. Conclusions. AK0529 was well tolerated in hospitalized RSV-infected infants. Treatment with AK0529 2 mg/kg bid was observed to reduce viral load and clinical signs and symptoms.

Background Respiratory syncytial virus (RSV) seasonality is dependent on the local climate. We assessed the stability of RSV seasonality prior to the SARS-CoV-2 pandemic in Western Australia (WA), a state spanning temperate and tropical regions. Method RSV laboratory testing data were collected from January 2012 to December 2019. WA was divided into three regions determined by population density and climate; Metropolitan, Northern and Southern. Season threshold was calculated per region at 1.2% annual cases, with onset the first of ≥2 weeks above this threshold and offset as the last week before ≥2 weeks below. Results The incidence of RSV in WA was 6.3/10,000. The Northern region had the highest incidence (15/10,000), more than 2.5 times the Metropolitan region (IRR 2.7; 95% CI, 2.6-2.9). Test percentage positive was similar in the Metropolitan (8.6%) and Southern (8.7%) regions, with the lowest in the Northern region (8.1%). RSV seasons in the Metropolitan and Southern regions occurred annually, with a single peak and had consistent timing and intensity. The Northern tropical region did not experience a distinct season. Proportion of RSV A to RSV B in the Northern region differed from the Metropolitan region in 5 of the 8 years studied. Conclusions Incidence of RSV in WA is high, especially in the Northern region, where climate, an expanded at-risk population, and increased testing may have contributed to greater numbers. Before the SARS-CoV-2 pandemic, RSV seasonality WA was consistent in timing and intensity for the Metropolitan and Southern regions.

Background. Prior to the introduction of vaccines, COVID-19 hospitalizations of non-institutionalized persons in Connecticut disproportionately affected communities of color and individuals of low socioeconomic status (SES). Whether the magnitude of these disparities changed 7-9 months after vaccine rollout during the Delta wave is not well documented. Methods. All initially hospitalized patients with laboratory-confirmed COVID-19 during July-September 2021, were obtained from the Connecticut COVID-NET database, including patients’ geocoded residential addresses. Census tract measures of poverty and crowding were determined by linking geocoded residential addresses to the 2014-2018 American Community Survey. Age-adjusted incidence and relative rates of COVID-19 hospitalization were calculated and compared to those from July-December 2020. Vaccination levels by age and race/ethnicity at the beginning and end of the study period were obtained from Connecticut’s COVID vaccine registry and age-adjusted average values were determined. Results. There were 708 COVID-19 hospitalizations among community residents of the two counties, July-September 2021. Age-adjusted incidence was highest among non-Hispanic Blacks and Hispanic/Latinx compared to non-Hispanic Whites ((RR 4.10 (95% CI 3.41-4.94) and 3.47 (95% CI 2.89-4.16)). While RR decreased significantly among Hispanic/Latinx and among the lowest SES groups, it increased among non-Hispanic Blacks (from RR 3.1 (95% CI 2.83-3.32) to RR 4.10). Average age-adjusted vaccination rates among those >12 years were lowest among non-Hispanic Blacks compared to Hispanic/Latinx and non-Hispanic Whites (50.6% vs 64.7% and 66.6%). Conclusions. While racial/ethnic and SES disparities in COVID-19 hospitalization have mostly decreased over time, disparities among non-Hispanic Blacks increased, possibly due to differences in vaccination rates.

Since late 2021, the highly transmissible SARS-CoV-2 Omicron variant has driven a new surge of infections across the world. We used a case-ascertained study to determine the features of household transmission of SARS-CoV-2 Omicron variant in Shanghai, China. We collected detailed information on 323 pediatric cases and their 951 household members, all received consecutively intensive RT-PCR testing. We estimated the transmission parameters. Both secondary infection attack rates (SARI) and secondary clinical attack rates (SARC) among adult household contacts were computed, through which the transmission heterogeneities in infectivity and susceptibility were characterized and the vaccine effectiveness were estimated. The mean incubation period and serial interval of Omicron variant were estimated to be 4.6±2.1 days and 3.9±3.7 days. The overall SARI and SARC among adult household contacts were 77.11% (95% confidence interval [CI]: 73.58%-80.63%) and 67.03% (63.09%-70.98%). We found higher household susceptibility in females, while infectivity was not significantly different in primary cases by age, sex, vaccination status and clinical severity. Full vaccination and booster vaccination of inactivated vaccines were 14.8% (5.8%-22.9%) and 18.9% (9.0%-27.7%) effective against Omicron infection and 21.5% (10.4%-31.2%) and 24.3% (12.3%-34.7%) effective against symptomatic disease. Overall, we found high household transmission during the Omicron wave in Shanghai due to asymptomatic and pre-symptomatic transmission in the context of city-wide lockdown, indicating the importance of early detection and timely isolation of SARS-CoV-2 infections and quarantine of close contacts. Marginal effectiveness of inactivated vaccines against Omicron infection poses great challenge for prevention and control of the SARS-CoV-2 Omicron variant.

Rapid influenza diagnostic tests (RIDTs) have variable sensitivity. In a community-based population of kindergarten through 12th grade (K-12) students, we assessed factors that may influence RIDT performance using 2,368 paired results from Sofia® Influenza A + B fluorescent immunoassay and reverse transcription polymerase chain reaction (RT-PCR). RIDT sensitivity and specificity were 76.1% (95% CI: 72.8—79.1) and 97.2% (96.2—97.9), respectively. Factors associated with sensitivity included runny nose (OR=3.0, p<0.001), nasal congestion (1.59, p=0.045), days from symptom onset (per day; 0.75; p<0.001), myalgia (0.61; p=0.014), age (per 5 years; 0.55; p=0.001), and detection of another virus (0.50; p=0.043). Understanding these factors can aid in interpreting negative results.

Background: Acute lower respiratory tract infections (ALRI) are one leading cause of morbidity and mortality among people of all ages worldwide, particularly in low- and middle-income countries (LMICs). The purpose of this study was to determine epidemiological characteristics of respiratory viruses in ARI patients during the SARS-CoV-2 pandemic in Yaoundé, Cameroon. Methods: Patients were monitored for respiratory symptoms as part of surveillance of SARS-CoV-2 and other respiratory viral infections. Patients of all ages with respiratory symptoms less than 5 days were considered. Sociodemographic and clinical data as well as nasopharyngeal samples was collected from patients. Nasopharyngeal samples were tested for SARS-CoV-2, Influenza and Respiratory Syncytial Virus (RSV) using real-time reverse-transcription polymerase chain reaction methods. Virus distribution and demographic data were analyzed with R version 2.15.1. Results: From July 2020 to October 2021, 1120 patients were included. The overall viral detection rate was 32.5%, including 9.5 % for RSV (Respiratory Syncytial Virus), 12.6 % for influenza virus and 12.8 % for SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). Co-infections were detected in 6.9% of positive cases. While RSV and influenza virus showed seasonal trends, SARS-CoV-2 was detected throughout the study period. Conclusion: We found that during SARS-CoV-2 pandemic, respiratory viruses play an important role in aetiology of influenza-like illness in Cameroon, and this observation was true for patients of all ages.

Background: Influenza-associated pulmonary aspergillosis (IAPA) is an important complication of severe influenza with high morbidity and mortality. Methods: We conducted a retrospective multicenter study in tertiary hospitals in Switzerland during 2017/18 and 2019/20 influenza seasons. All adults with PCR-confirmed influenza infection and treatment on intensive-care unit (ICU) for >24h were included. IAPA was diagnosed according to previously published clinical, radiological and microbiological criteria. We assessed risk factors for IAPA and predictors for poor outcome which was a composite of in-hospital mortality, ICU length of stay ≥7d, mechanical ventilation ≥7d or extracorporeal membrane oxygenation. Results: 158 patients (median age 64 years, 45% females) with influenza were included, of which 17 (10.8%) had IAPA. Asthma was more common in IAPA patients (17% vs. 4% in non-IAPA, p=0.05). Asthma (OR 12.0 (95% CI 2.1-67.2)) and days of mechanical ventilation (OR 1.1 (1.1 – 1.2)) were associated with IAPA. IAPA patients frequently required organ supportive therapies including mechanical ventilation (88% in IAPA vs. 53% in non-IAPA, p=0.001) and vasoactive support (75% vs. 45%, p=0.03) and had more complications including ARDS (53% vs. 26%, p=0.04), respiratory bacterial infections (65% vs. 37%, p=0.04) and higher ICU-mortality (35% vs. 16.4%, p=0.05). IAPA (OR 28.8 (3.3–253.4)), influenza A (OR 3.3 (1.4-7.8)) and higher SAPS II score (OR 1.07 (1.05—1.10)) were independent predictors of poor outcome. Interpretation: High clinical suspicion, early diagnostics and therapy are indicated in IAPA because of high morbidity and mortality. Asthma is likely an underappreciated risk factor for IAPA.

Background: Influenza is a persistent public health problem associated with severe morbidity and mortality. Drug use is related to myriad health complications, but the relationship between drug use and severe influenza outcomes is not well understood. The study objective was to evaluate the relationship between drug use and severe influenza-associated outcomes. Methods: Data were collected by the Influenza Hospitalization Surveillance Network (FluSurv-NET) from the 2016-2017 through 2018-2019 influenza seasons. Among persons hospitalized with influenza, descriptive statistics and logistic regression models were used to analyze differences in demographic characteristics, risk and behavioral factors, and severe outcomes (intensive care unit [ICU] admission, mechanical ventilation, or death) between people who used drugs (PWUD), defined as having documented drug use within the past year, and non-PWUD. Results: Among 48,430 eligible hospitalized influenza cases, 2,019 were PWUD and 46,411 were non-PWUD. PWUD were younger than non-PWUD and more likely to be male, non-Hispanic Black or Hispanic/Latino, smoke tobacco, abuse alcohol, and have chronic conditions including asthma, chronic liver disease, chronic lung disease, or immunosuppressive conditions. PWUD had greater odds of ICU admission and mechanical ventilation, but not death compared with non-PWUD. Opioid use specifically was associated with increased risk of ICU admission and mechanical ventilation. Conclusion: PWUD had greater odds of ICU admission and mechanical ventilation than non-PWUD hospitalized with influenza. These results support targeted initiatives to prevent influenza and associated severe outcomes among this population.

Background: Despite the WHO recommendation that pregnant women be prioritised for seasonal influenza vaccination, coverage in the Western Pacific Region remains low. Our goal was to provide additional data for the Western Pacific region about the value of maternal influenza vaccination to pregnant women and their families. Methods: We conducted a 16-year retrospective cohort to evaluate risks associated with influenza-associated maternal acute respiratory infection (ARI) in New Zealand. ARI hospitalisations during the May-September influenza season were identified using select ICD-10-AM primary and secondary discharge codes from chapter J00-J99 (diseases of the respiratory system). Cox proportional hazards models were used to calculate crude and adjusted hazard ratios (aHR) and 95% confidence intervals (CI). Results: We identified 822,391 pregnancies among New Zealand residents between 2003 and 2018; 5,095 (0.6%) had >1 associated ARI hospitalisation during the influenza season; these pregnancies were at greater risk of preterm birth (aHR 1.5, 95% CI 1.3-1.7), and low birthweight (aHR 1.7, 95% CI 1.5-2.0) than pregnancies without such hospitalisations. We did not find an association between maternal ARI hospitalisation and fetal death (aHR 1.1, 95% CI 0.6-1.4) during the influenza season. Maternal influenza vaccination was associated with reduced risk of preterm birth (aHR 0.8, 95% CI 0.7-0.9), and low birthweight (aHR 0.9, 95%CI 0.8-0.9), and fetal death (aHR 0.5%, 95% CI 0.3-0.7). Conclusion: In this population-based cohort, being hospitalised for an ARI during the influenza season while pregnant was a risk-factor for delivering a preterm or a low birthweight infant and vaccination reduced this risk.

Objectives: To understand the epidemiological and clinical characteristics of pediatric SARS-CoV-2 infection during the early stage of Omicron variant outbreak in Shanghai. Study designs: This study included local COVID-19 cases<18 years in Shanghai referred to the exclusively designated hospital by the end of March 2022 since emergence of Omicron epidemic. Clinical data, epidemiological exposure and COVID-19 vaccination status were collected. Relative risks (RR) were calculated to assess the effect of vaccination on symptomatic infection and febrile disease. Results: A total of 376 pediatric cases of COVID-19 (median age:6.0±4.2 years) were referred to the designated hospital during the period of March 7-31, including 257 (68.4%) symptomatic cases and 119 (31.6%) asymptomatic cases. Of the 307 (81.6%) children ≥3 years eligible for COVID-19 vaccination, 110 (40.4%) received 2-dose vaccines and 16 (4.0%) received 1-dose vaccine. The median interval between 2-dose vaccination and infection was 3.5 (IQR: 3, 4.5) months (16 days-7 months). Two-dose COVID-19 vaccination reduced the risks of symptomatic infection and febrile disease by 35%(RR 0.65, 95% CI: 0.53-0.79) and 33% (RR 0.64, 95% CI: 0.51-0.81). Two hundred and sixteen (83.4%) symptomatic cases had fever (mean duration:1.7±1.0.8 days), 104 (40.2%) had cough, 16.4% had transient leukopenia; 307 (81.6%) had an epidemiological exposure in household (69.1%) , school (21.8%) and residential area (8.8%). Conclusion: The surge of pediatric COVID-19 cases and multiple transmission model reflect wide dissemination of Omicron variant in the community. Asymptomatic infection is common among Omicron-infected children. COVID-19 vaccination can offer some protection against symptomatic infection and febrile dise

Background: Acute respiratory infections (ARIs) result in millions of illnesses and hundreds of thousands of hospitalizations annually in the US. The responsible viruses include influenza, parainfluenza, human metapneumovirus, coronaviruses, respiratory syncytial virus (RSV), and human rhinoviruses. This study estimated the population-based hospitalization burden of 18 respiratory viruses (RV) over 4 years, from 7/1/2015 to 6/30/2019 among adults ≥18 years of age for Allegheny County (Pittsburgh), Pennsylvania. Methods: We used population-based statewide hospital discharge data, health system electronic medical record (EMR) data for RV tests, census data, and a published method to calculate burden. Results: Among 26,211 eligible RV tests, 67.6% were negative for any virus. The viruses detected were rhinovirus/enterovirus (2,552; 30.1%), influenza A (2,299; 27.1%), RSV (1,082; 12.7%), human metapneumovirus (832; 9.8%), parainfluenza (601; 7.1%), influenza B (565; 6.7%), non-SARS-CoV-2 coronavirus (420; 4.9% 1.5 years of data available), and adenovirus (136; 1.6%). Most tests were among female (58%) and white (71%) patients with 60% of patients ≥65 years, 24% 50-64 years and 16% 18-49 years. The annual burden, ranged from 137-174/100,000 population for rhinovirus/enterovirus; 99-182/100,000 for influenza A; 56-81/100,000 for RSV. Among adults <65 years, rhinovirus/enterovirus hospitalization burden was higher than influenza A; whereas the reverse was true for adults ≥65 years. RV hospitalization burden increased with increasing age. Conclusions: These virus-specific ARI population-based hospital burden estimates showed significant non-influenza burden. These estimates can serve as the basis for several areas of research that are essential for setting funding priorities and guiding public health policy.

Introduction: Case definitions are used to guide clinical practice, surveillance, and research protocols. However, how they identify COVID-19-hospitalised patients is not fully understood. We analysed the proportion of hospitalised patients with laboratory-confirmed COVID-19, in the ISARIC prospective cohort study database, meeting widely used case definitions. Methods: Patients were assessed using the CDC, ECDC, WHO, and UKHSA case definitions by age, region, and time. Case fatality ratios (CFR) and symptoms of those who did and who did not meet the case definitions were evaluated. Patients with incomplete data and non-laboratory-confirmed test-result were excluded. Results: 263,218 of the patients (42%) in the ISARIC database were included. Most patients (90.4%) were from Europe and Central Asia. The proportions of patients meeting the case definitions were 56.8% (WHO), 74.4% (UKHSA), 81.6% (ECDC), and 82.3% (CDC). For each case definition, patients at the extremes of age distribution met the criteria less frequently than those aged 30 to 70 years; geographical and time variations were also observed. Estimated CFRs were similar for the patients that met the case definitions. However, when more patients did not meet the case definition, the CFR increased. Conclusions: The performance of case definitions might be different in different regions and may change over time. Similarly concerning is the fact that older patients often did not meet case definitions. While epidemiologists must balance their analytics with field applicability, ongoing revision of case definitions is necessary to improve patient care through early diagnosis and limit potential nosocomial spread.

Abstract Background. Still now, COVID-19 is a public health concern in both developed and developing countries. Risk perception has been studied in different countries with different population groups. However, there have been few studies conducted risk perception on elderly people and there is no study on elderly people’ in Ethiopia including this study area.This study aimed to assess coronavirus disease low risk perception level and associated factors among the elderly. Methods. To carry out this study among elders in Areka town from 01 August 2021 to 30 August 2021, a community-based cross-sectional study was used. Multi-stage sampling method was applied to select study participants. The data were collected through a structured questionnaire with the mobile application of Open Data Kit mobile(ODK). Results. This study showed that individuals with age range of 65 to 74 [AOR= 4.76, 95% CI (2.35-9.64)], poor practice on preventing coronavirus disease [AOR= 2.39, 95% CI (1.51-3.78), low trust level in medical professionals [AOR=2.44, 95%CI (1.45-4.10)], no history of coronavirus disease [AOR=6.45, 95%CI (2.02-20.58)], poor perceived self-efficacy for preventive practice [AOR=2.25, 95% CI (1.43-3.54)] were identified as associated factors of low risk perception. Conclusions. In the current study area, the perception of risk of coronavirus disease was affected by age, perceived self-efficacy, trust in medical professionals, preventive practice, and history of coronavirus disease. Including Ethiopia, the findings of this study would help for developing countries to generate evidence-based policy decisions for elderly people during COVI-D-19 pandemic and future pandemic(s). Keywords: Associated factors, Coronavirus, Elderly, Ethiopia, Perception

Background Human Metapneumovirus (hMPV) is an important cause of pediatric respiratory infection. We leveraged the Nicaraguan Pediatric Influenza Cohort Study (NPICS) to assess the burden and seasonality of symptomatic hMPV infection in children. Methods NPICS is an ongoing prospective study of children in Managua, Nicaragua. We assessed children for hMPV infection via RT-PCR. We used classical additive decomposition analysis to assess the temporal trends and Generalized Growth Models (GGMs) were used to estimate effective reproduction numbers. Results From 2011-2016 there were 564 hMPV symptomatic infections yielding an incidence rate of 5.74 cases per 100 person-years (95% CI 5.3, 6.2). Children experienced 3,509 Acute Lower Respiratory Infections (ALRIs), of which 160 (4.6%) were associated with hMPV infection. Children under the age of one had 55% of all symptomatic hMPV infections (62/112) develop into hMPV-associated ALRIs and were five times as likely as children over one to have an hMPV-associated ALRI (Rate Ratio 5.5 95% CI 4.1, 7.4 p <0.001). Additionally, symptomatic reinfection with hMPV was common. In total, 87 (15%) of all observed symptomatic infections were reinfections. The seasonality of symptomatic hMPV outbreaks varied considerably. From 2011-2016, four epidemic periods were observed, following a biennial seasonal pattern. The mean ascending phase of the epidemic periods were 7.7 weeks, with an overall mean estimated reproductive number of 1.2 (95% CI 1.1, 1.4). Conclusions Symptomatic hMPV infection was associated with substantial burden among children in the first year of life. Timing and frequency of symptomatic hMPV incidence followed biennial patterns.

Background: Anaphylaxis following influenza vaccination is a rare but serious problem. The underlying immune responses are not well understood. This study elucidated the IgE and IgG antibody responses in healthy children and adolescents following inactivated influenza vaccines (IIVs). Methods: The efficacy and safety of quadrivalent IIV (QIV) and trivalent IIV (TIV) were compared in healthy subjects aged 0-18 years. Serum IIV-specific IgE, IgG and IgG4 levels (sIgE, sIgG, sIgG4) were measured with ImmunoCAP. Hemagglutinin inhibition (HI) assay was performed for each influenza virus subtype. Sera from earlier patients who developed anaphylaxis to different IIVs were similarly tested. Results: A total of 393 subjects were enrolled: 96 were 6 months -2 years old, 100 were 3-5 years old, 100 were 6-12 years old, and 97 were 13-18 years old. No anaphylaxis was observed. Generally, QIV and TIV induced similar antibody responses. IIV-sIgE levels rose significantly after vaccination in the 6m-2y and 3-5y groups, did not change in the 6-12y group, and decreased in the 13-18y group. In contrast, the IIV-sIgG4/sIgE ratio increased significantly after vaccination in all age groups. Sensitized subjects had significantly higher HI titers and IIV-sIgG levels in the youngest age group and higher IIV-sIgG4 levels in all age groups compared with the non-sensitized. The IIV-sIgG4/sIgE ratio in 5 patients with anaphylaxis was significantly lower than in age-matched healthy subjects. Conclusion: IIVs induce IgE sensitization in healthy children, but also robust IgG4 responses that may protect them from anaphylaxis.