In May 2020, the ACCESS (The vACCine covid-19 monitoring readinESS) project was launched to prepare real-world monitoring of COVID-19 vaccines. Within this project, this study aimed to generate background incidence rates of 41 adverse events of special interest (AESI) to contextualize potential safety signals detected following administration of COVID-19 vaccines. A dynamic cohort study was conducted using a distributed data network of 10 healthcare databases from 7 European countries (Italy, Spain, Denmark, The Netherlands, Germany, France and United Kingdom) over the period 2017 to 2020. A common protocol (EUPAS37273), common data model, and common analytics programs were applied for syntactic, semantic and analytical harmonization. Incidence rates (IR) for each AESI and each database were calculated by age and sex by dividing the number of incident cases by the total person-time at risk. Age-standardized rates were pooled using random effect models according to the provenance of the events. A total number of 63,456,074 individuals were included in the study, contributing to 211.7 million person-years. A clear age pattern was observed for most AESIs, rates also varied by provenance of disease diagnosis (primary care, specialist care). Thrombosis with thrombocytopenia rates were extremely low ranging from 0.06 to 4.53/100,000 person-years for cerebral venous sinus thrombosis (CVST) with thrombocytopenia (TP) and mixed venous and arterial thrombosis with TP, respectively. Given the nature of the AESIs and the setting (general practitioners or hospital-based databases or both), background rates from databases that show the highest level of completeness (primary care and specialist care) should be preferred, others can be used for sensitivity. The study was designed to ensure representativeness to the European population and generalizability of the background incidence rates. The project has received support from the European Medicines Agency under the Framework service contract nr EMA/2018/28/PE.

Concerns have been raised about intraseasonal waning of the protection conferred by influenza vaccination. During four influenza seasons, we consecutively recruited individuals aged 18years or older who had received seasonal influenza vaccine and were subsequently admitted to the hospital for influenza infection, asassessed by reverse transcription polymerase chain reaction. We estimated the adjusted odds ratio (aOR) of influenza infection by date of vaccination, defined by tertiles, as early, intermediate or late vaccination. We used a test-negative approach with early vaccination as reference to estimate the aOR of hospital admission with influenza among late vaccinees. We conducted sensitivity analyses by means of conditional logistic regression, Cox proportional hazards regression, and using days between vaccination and hospital admission rather than vaccination date. Among 3615 admitted vaccinees, 822 (23%) were positive for influenza. We observed a lower risk of influenza among late vaccinees during the 2011/2012 and 2014/2015A(H3N2)-dominant seasons: aOR=0.68 (95% CI: 0.47-1.00) and 0.69 (95% CI: 0.50-0.95). We found no differences in the risk of admission with influenza among late versus early vaccinees in the 2012/2013A(H1N1)pdm09-dominant or 2013/2014B/Yamagata lineage-dominant seasons: aOR=1.18 (95% CI: 0.58-2.41) and 0.98 (95% CI: 0.56-1.72). When we restricted our analysis to individuals aged 65years or older, we found a statistically significant lower risk of admission with influenza among late vaccinees during the 2011/2012 and 2014/2015A(H3N2)-dominant seasons: aOR=0.61 (95% CI: 0.41-0.91) and 0.69 (95% CI: 0.49-0.96). We observed 39% (95% CI: 9-59%) and 31% (95% CI: 5-50%) waning of vaccine effectiveness among participants aged 65years or older during the two A(H3N2)-dominant seasons. Similar results were obtained in the sensitivity analyses. Waning of vaccine protection was observed among individuals aged 65years old or over in two A(H3N2)-dominant influenza seasons.

The Global Influenza Hospital Surveillance Network was established in 2012 to obtain valid epidemiologic data on hospital admissions with influenza-like illness. Here we describe the epidemiology of admissions with influenza within the Northern Hemisphere sites during the 2013/2014 influenza season, identify risk factors for severe outcomes and complications, and assess the impact of different influenza viruses on clinically relevant outcomes in at-risk populations. Eligible consecutive admissions were screened for inclusion at 19 hospitals in Russia, Turkey, China, and Spain using a prospective, active surveillance approach. Patients that fulfilled a common case definition were enrolled and epidemiological data were collected. Risk factors for hospitalization with laboratory-confirmed influenza were identified by multivariable logistic regression. 5303 of 9507 consecutive admissions were included in the analysis. Of these, 1086 were influenza positive (534 A(H3N2), 362 A(H1N1), 130 B/Yamagata lineage, 3 B/Victoria lineage, 40 untyped A, and 18 untyped B). The risk of hospitalization with influenza (adjusted odds ratio [95% confidence interval]) was elevated for patients with cardiovascular disease (1.63 [1.33–2.02]), asthma (2.25 [1.67–3.03]), immunosuppression (2.25 [1.23–4.11]), renal disease (2.11 [1.48–3.01]), liver disease (1.94 [1.18–3.19], autoimmune disease (2.97 [1.58–5.59]), and pregnancy (3.84 [2.48–5.94]). Patients without comorbidities accounted for 60% of admissions with influenza. The need for intensive care or in-hospital death was not significantly different between patients with or without influenza. Influenza vaccination was associated with a lower risk of confirmed influenza (adjusted odds ratio = 0.61 [0.48–0.77]). Influenza infection was detected among hospital admissions with and without known risk factors. Pregnancy and underlying comorbidity increased the risk of detecting influenza virus in patients hospitalized with influenza-like illness. Our results support influenza vaccination as a measure for reducing the risk of influenza-associated hospital admission.

Background: RSV is the leading cause of hospital admissions in infants and the principal cause of bronchiolitis in young children. There is a lack of granular data on RSV‐associated hospitalization per season using laboratory confirmed results. Our current study addresses this issue and intends to fill this gap.Methods: The study was conducted from 2014 through 2018, in 4 to 10 hospitals in the Valencia Region, Spain. Infants included in this study were admitted in hospital through the Emergency Department with a respiratory complaint and tested by RT‐PCR for RSV in a central laboratory.Results: Incidence rates of RSV‐associated hospitalization varied by season and hospital. Overall, the highest incidence rates were observed in 2017/2018. RSV‐associated hospitalization was highest in infants below 3 months of age and in those born before or at the beginning of the RSV season. Almost 54% of total infants hospitalized with laboratory confirmed RSV were found to be born outside the season, from April to October. The RSV positivity rate by ICD‐10 discharged codes varied by season and age with results from 48% to 57% among LRI (J09‐J22).Conclusion: The study was instrumental in bringing forth the time unpredictability of RSV epidemics, the critical impact of age, and the comparable distribution of RSV‐associated hospitalization in infants born on either side of the RSV season. These data could help in better characterization of the population that drives the healthcare burden and is crucial for the development of future immunization strategies, especially with upcoming vaccines in against RSV.

The Global Influenza Hospital Surveillance Network is an international platform whose primary objective is to study severe cases of influenza requiring hospitalization. During the 2015–2016 influenza season, 11 sites in the Global Influenza Hospital Surveillance Network in nine countries (Russian Federation, Czech Republic, Turkey, France, China, Spain, Mexico, India, and Brazil) participated in a prospective, active-surveillance, hospital-based epidemiological study. Influenza infection was confirmed by reverse transcription-polymerase chain reaction. Influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza was estimated using a test-negative approach. 9882 patients with laboratory results were included of which 2415 (24.4%) were positive for influenza, including 1415 (14.3%) for A(H1N1)pdm09, 235 (2.4%) for A(H3N2), 180 (1.8%) for A not subtyped, 45 (0.5%) for B/Yamagata-lineage, 532 (5.4%) for B/Victoria-lineage, and 33 (0.3%) for B not subtyped. Of included admissions, 39% were < 5 years of age and 67% had no underlying conditions. The odds of being admitted with influenza were higher among pregnant than non-pregnant women (odds ratio, 2.82 [95% confidence interval (CI), 1.90 to 4.19]). Adjusted IVE against influenza-related hospitalization was 16.3% (95% CI, 0.4 to 29.7). Among patients targeted for influenza vaccination, adjusted IVE against hospital admission with influenza was 16.2% (95% CI, − 3.6 to 32.2) overall, 23.0% (95% CI, − 3.3 to 42.6) against A(H1N1)pdm09, and − 25.6% (95% CI, − 86.3 to 15.4) against B/Victoria lineage. The 2015–2016 influenza season was dominated by A(H1N1)pdm09 and B/Victoria-lineage. Hospitalization with influenza often occurred in healthy and young individuals, and pregnant women were at increased risk of influenza-related hospitalization. Influenza vaccines provided low to moderate protection against hospitalization with influenza and no protection against the predominant circulating B lineage, highlighting the need for more effective and broader influenza vaccines.

Background: Respiratory viruses are known to represent a high burden in winter, yet the seasonality of many viruses remains poorly understood. Better knowledge of co‐circulation and interaction between viruses is critical to prevention and management. We use > 10‐year active surveillance in the Valencia Region to assess seasonality and co‐circulation.Methods: Over 2010–2021, samples from patients hospitalised for acute respiratory illness were analysed using multiplex real‐time PCR to test for 9 viruses: influenza, respiratory syncytial virus (RSV), parainfluenza virus (PIV), rhino/enteroviruses (HRV/ENV), metapneumovirus (MPV), bocavirus, adenovirus, SARS‐CoV‐2 and non‐SARS coronaviruses (HCoV). Winter seasonal patterns of incidence were examined. Instances of co‐detection of multiple viruses in a sample were analysed and compared with expected values under a crude model of independent circulation.Results: Most viruses exhibited consistent patterns between years. Specifically, RSV and influenza seasons were clearly defined, peaking in December–February, as did HCoV and SARS‐CoV‐2. MPV, PIV and HRV/ENV showed less clear seasonality, with circulation outside the observed period. All viruses circulated in January, suggesting any pair had opportunity for co‐infection. Multiple viruses were found in 4% of patients, with more common co‐detection in children under 5 (9%) than older ages. Influenza co‐detection was generally observed infrequently relative to expectation, while RSV co‐detections were more common, particularly among young children.Conclusions: We identify characteristic patterns of viruses associated with acute respiratory hospitalisation during winter. Simultaneous circulation permits extensive co‐detection of viruses, particularly in young children. However, virus combinations appear to differ in their rates of co‐detection, meriting further study.