The FLURESP European commission project: cost-effectiveness assessment of ten public health measures against influenza in Italy: is there an interest in COVID-19 pandemic?

BACKGROUND: The FLURESP project is a public health research funded by the European Commission, with the objective to design a methodological framework to assess the cost-effectiveness of existing public health measures against human influenza pandemics. A dataset has been specifically collected in the frame of the Italian health system. As most of interventions against human influenza are relavant against other respiratory diseases pandemics, potential interests in COVID-19 are discussed. METHODS: Ten public health measures against human influenza pandemics pandemic were selected to be also relevant to other respiratory virus pandemics such as COVID 19: individual (hand washing, using masks), border control (quarantine, fever screening, border closure), community infection (school closure, class dismissal, social distancing, limitation of public transport), reduction of secondary infections (implementation of antibiotic therapy guidelines), pneumococcal vaccination for at-risk people, development of Intensive Care Unit (ICU) capacity, implementation of life support equipments in ICU, screening interventions, vaccination programs targeting health professional and targeting general population. RESULTS: Using mortality reduction as effectiveness criteria, the most cost-effective strategies are "reduction of secondary infections" and "implementation of life support equipment in ICU". The least cost-effective option whatever the level of pandemic events are screening interventions and mass vaccination. CONCLUSIONS: A number of intervention strategies against human influenza pandemics appears relevant against every respiratory virus, including the COVID-19 event. Measures against pandemics should be considered according to their expected effectiveness but also their costs for the society because they impose substantial burden to the population, confirming the interest of considering cost-effectiveness of public health measures to enlighten decision making.

Acute respiratory infection emergency access in a tertiary care children hospital in Italy, prior and after the SARS-CoV-2 emergence.

Background: The COVID-19 pandemic has changed the epidemiology of acute respiratory infections (ARIs) in children. The aims of the present study were to describe the epidemiological trend of ARI emergency visits and virology results prior and after the SARS-CoV-2 emergence and to estimate the association of ARI emergency department (ED) visits with respiratory viruses. Methods: This study was conducted at the Bambino Gesù Children's Hospital, a tertiary care children's hospital in the Lazio Region, Italy. The demographic and clinical information of children who accessed the ED and were diagnosed with ARI from January 1, 2018 to June 30, 2022 was retrospectively extracted from the electronic health records. The observed temporal trends in viruses diagnosed from respiratory samples were compared with the number of ARI ED visits over the same period through a multivariable linear regression model. Results: During the study period, there were 72,959 ED admissions for ARIs and 33,355 respiratory samples resulted positive for viruses. Prior to the pandemic, respiratory syncytial virus (RSV) and influenza had a clear seasonal pattern, which was interrupted in 2020. In 2021-2022, RSV reached the highest peak observed during the study period, whereas influenza activity was minimal. The peaks of ARI ED visits corresponded to peaks of influenza, RSV, and rhinovirus in the 2018-2019 and 2019-2020 seasons, to SARS-CoV-2 and rhinovirus in 2020, and to RSV and parainfluenza in 2021-2022. Conclusions: ARI resulting in ED visits should be included in the ARI disease burden measurement for a more accurate measure of the impact of preventive measures.

Vaccinations in Children and Adolescents Treated With Immune-Modifying Biologics: Update and Current Developments.

Treatment with immune-modifying biologics has positively impacted disease control and quality of life in many patients with immune-mediated disorders. However, the higher susceptibility to common and opportunistic pathogens is of concern. Thus, immunization strategies to control vaccine-preventable diseases represent a critical issue in this population. However, limited data exist on the safety, immunogenicity, and efficacy of available vaccines in patients on biologics, particularly in children. Here, according to published literature and real-life experience and practice, we report the interim indications of the Italian Society of Pediatric Allergology and Immunology (SIAIP) Vaccine Committee and of the Italian Primary Immunodeficiency Network (IPINet) Centers on immunization of children and adolescents receiving biologics. Our aim is to provide a practical guidance for the clinician to ensure optimal protection for patients and the community.

The value of public-private collaborative real-world evidence platforms to monitor vaccine performance post authorization: DRIVE - a European initiative.

INTRODUCTION: Fighting pandemics requires an established infrastructure for pandemic preparedness, with existing, sustainable platforms ready to be activated. This includes platforms for disease surveillance, virus circulation, and vaccine performance monitoring based on Real-World data, to complement clinical trial evidence. AREAS COVERED: Because of its complexity, this can best be done by combining efforts between public and private sectors, developing a multi-stakeholder approach. Public-Private-Partnerships increasingly play a critical role in combating infectious diseases but are still looked at with hesitancy. The Development of Robust and Innovative Vaccine Effectiveness (DRIVE) project, which established a platform for measuring brand-specific influenza vaccine effectiveness in Europe, exemplifies how to build a collaborative platform with transparent governance, state-of-the-art methodology, and a large network of participating sites. Lessons learned from DRIVE have been cardinal to set up COVIDRIVE, a platform for brand-specific COVID-19 vaccine effectiveness monitoring. EXPERT OPINION: The DRIVE partners propose that a debate on the benefits of Public-Private-Partnership-generated real-world evidence for vaccine effectiveness monitoring should be pursued to clarify roles and responsibilities, set up expectations, and decide the future environment for vaccine monitoring in Europe. In parallel, the driving factors behind PPP hesitancy should be studied.

Understanding the vaccine stance of Italian tweets and addressing language changes through the COVID-19 pandemic: Development and validation of a machine learning model.

Social media is increasingly being used to express opinions and attitudes toward vaccines. The vaccine stance of social media posts can be classified in almost real-time using machine learning. We describe the use of a Transformer-based machine learning model for analyzing vaccine stance of Italian tweets, and demonstrate the need to address changes over time in vaccine-related language, through periodic model retraining. Vaccine-related tweets were collected through a platform developed for the European Joint Action on Vaccination. Two datasets were collected, the first between November 2019 and June 2020, the second from April to September 2021. The tweets were manually categorized by three independent annotators. After cleaning, the total dataset consisted of 1,736 tweets with 3 categories (promotional, neutral, and discouraging). The manually classified tweets were used to train and test various machine learning models. The model that classified the data most similarly to humans was XLM-Roberta-large, a multilingual version of the Transformer-based model RoBERTa. The model hyper-parameters were tuned and then the model ran five times. The fine-tuned model with the best F-score over the validation dataset was selected. Running the selected fine-tuned model on just the first test dataset resulted in an accuracy of 72.8% (F-score 0.713). Using this model on the second test dataset resulted in a 10% drop in accuracy to 62.1% (F-score 0.617), indicating that the model recognized a difference in language between the datasets. On the combined test datasets the accuracy was 70.1% (F-score 0.689). Retraining the model using data from the first and second datasets increased the accuracy over the second test dataset to 71.3% (F-score 0.713), a 9% improvement from when using just the first dataset for training. The accuracy over the first test dataset remained the same at 72.8% (F-score 0.721). The accuracy over the combined test datasets was then 72.4% (F-score 0.720), a 2% improvement. Through fine-tuning a machine-learning model on task-specific data, the accuracy achieved in categorizing tweets was close to that expected by a single human annotator. Regular training of machine-learning models with recent data is advisable to maximize accuracy.

How the Italian Twitter Conversation on Vaccines Changed During the First Phase of the Pandemic: A Mixed-Method Analysis.

In the context of the European Joint Action on Vaccination, we analyzed, through quantitative and qualitative methods, a random sample of vaccine-related tweets published in Italy between November 2019 and June 2020, with the aim of understanding how the Twitter conversation on vaccines changed during the first phase of the pandemic, compared to the pre-pandemic months. Tweets were analyzed by a multidisciplinary team in terms of kind of vaccine, vaccine stance, tone of voice, population target, mentioned source of information. Multiple correspondence analysis was used to identify variables associated with vaccine stance. We analyzed 2,473 tweets. 58.2% mentioned the COVID-19 vaccine. Most had a discouraging stance (38.1%), followed by promotional (32.5%), neutral (22%) and ambiguous (2.5%). The discouraging stance was the most represented before the pandemic (69.6%). In February and March 2020, discouraging tweets decreased intensely and promotional and neutral tweets dominated the conversation. Between April and June 2020, promotional tweets remained more represented (36.5%), followed by discouraging (30%) and neutral (24.3%). The tweets' tone of voice was mainly polemical/complaining, both for promotional and for discouraging tweets. The multiple correspondence analysis identified a definite profile for discouraging and neutral tweets, compared to promotional and ambiguous tweets. In conclusion, the emergence of SARS-CoV-2 caused a deep change in the vaccination discourse on Twitter in Italy, with an increase of promotional and ambiguous tweets. Systematic monitoring of Twitter and other social media, ideally combined with traditional surveys, would enable us to better understand Italian vaccine hesitancy and plan tailored, data-based communication strategies.

Out-of-Season Epidemic of Respiratory Syncytial Virus during the COVID-19 Pandemic: The High Burden of Child Hospitalization in an Academic Hospital in Southern Italy in 2021.

Respiratory syncytial virus (RSV) infection is the most common cause of hospitalization in young children. In the last 2 years, public health measures aimed at controlling the spread of SARS-CoV-2 have affected the epidemiology and seasonality of RSV worldwide. The aim of this descriptive retrospective observational study was to describe the characteristics of children hospitalized with RSV in an academic tertiary care hospital in Southern Italy in 2021. We also investigate the seasonal trends of RSV from 2017 to 2021. The demographic characteristics, comorbidities, clinical data, and coinfections were retrospectively evaluated. Compared with previous seasons, the 2021 outbreak of RSV was characterized by an increased number of patients, with a delayed peak observed in November. Overall, 179 children, including 128 (71.5%) aged <12 months, were hospitalized for RSV infection between August and December 2021. Ten children (5.6%) were admitted to the intensive care unit (ICU), all aged <5 months. One patient (0.5%) aged <1 month with severe comorbidities died. The severity of symptoms was significantly associated with younger age, underlying chronic disease, and the length of hospital stay (p < 0.05 each). History of prematurity was not significantly associated with the presence of coinfections. Because of the high burden of RSV infection and the expected larger RSV epidemics resulting from a greater number of RSV-naïve children, systematic epidemiological and virological surveillance is needed. Appropriate pathways for access to RSV prevention in all infants should also be introduced.

Severity of the clinical presentation of hepatitis A in five European countries from 1995 to 2014.

OBJECTIVES: We analysed hepatitis A (HepA) notifications and hospitalisations in Italy, the Netherlands, Norway, Spain, and Sweden for available periods between 1995 and 2014. We aimed to investigate whether decreasing HepA incidence is associated with increasing age at infection and worsening HepA presentation and to identify groups at risk of severe disease. METHODS: We performed a retrospective cohort study including 36 734 notified and 36 849 hospitalised patients. We used negative binomial regressions to identify over time: i) trends in hospitalisation and notification rates; ii) proportion of hospitalised and notified patients aged ≥40 years; iii) proportion of "severe hospitalisations"; and iv) risk factors for severe hospitalisation. RESULTS: During the study period both HepA notifications and hospitalisations decreased, with notification rates decreasing faster, patients aged ≥40 years increased, however, the proportion of severe HepA hospitalisations remained stable. Older patients and patients with comorbidities, particularly liver diseases, were more likely to experience severe disease. CONCLUSIONS: We used digitalised health information to confirm decreasing trends in HepA hospitalisations and notifications, and the increasing age of patients with HepA in Europe. We did not identify an increase in the severity of the clinical presentation of patients with HepA. Older patients with liver diseases are at increased risk of severe disease and should be prioritised for vaccination.

Persistent B cell memory after SARS-CoV-2 vaccination is functional during breakthrough infections.

Breakthrough SARS-CoV-2 infections in fully vaccinated individuals are considered a consequence of waning immunity. Serum antibodies represent the most measurable outcome of vaccine-induced B cell memory. When antibodies decline, memory B cells are expected to persist and perform their function, preventing clinical disease. We investigated whether BNT162b2 mRNA vaccine induces durable and functional B cell memory in vivo against SARS-CoV-2 3, 6, and 9 months after the second dose in a cohort of health care workers (HCWs). While we observed physiological decline of SARS-CoV-2-specific antibodies, memory B cells persist and increase until 9 months after immunization. HCWs with breakthrough infections had no signs of waning immunity. In 3-4 days, memory B cells responded to SARS-CoV-2 infection by producing high levels of specific antibodies in the serum and anti-Spike IgA in the saliva. Antibodies to the viral nucleoprotein were produced with the slow kinetics typical of the response to a novel antigen.

No evidence of SARS-CoV-2 in hospitalized patients with severe acute respiratory syndrome in five Italian hospitals from 1st November 2019 to 29th February 2020.

BACKGROUND: On 9th January 2020, China CDC reported a novel coronavirus (later named SARS-CoV-2) as the causative agent of the coronavirus disease 2019 (COVID-19). Identifying the first appearance of virus is of epidemiological importance to tracking and mapping the spread of SARS-CoV-2 in a country. We therefore conducted a retrospective observational study to detect SARS-CoV-2 in oropharyngeal samples collected from hospitalized patients with a Severe Acute Respiratory Infection (SARI) enrolled in the DRIVE (Development of Robust and Innovative Vaccine Effectiveness) study in five Italian hospitals (CIRI-IT BIVE hospitals network) (1st November 2019 - 29th February 2020). OBJECTIVES: To acquire new information on the real trend in SARS-CoV-2 infection during pandemic phase I and to determine the possible early appearance of the virus in Italy. MATERIALS AND METHODS: Samples were tested for influenza [RT-PCR assay (A/H1N1, A/H3N2, B/Yam, B/Vic)] in accordance with the DRIVE study protocol. Subsequently, swabs underwent molecular testing for SARS-COV-2. [one-step real-time multiplex retro-transcription (RT) PCR]. RESULTS: In the 1683 samples collected, no evidence of SARS-CoV-2 was found. Moreover, 28.3% (477/1683) of swabs were positive for influenza viruses, the majority being type A (358 vs 119 type B). A/H3N2 was predominant among influenza A viruses (55%); among influenza B viruses, B/Victoria was prevalent. The highest influenza incidence rate was reported in patients aged 0-17 years (40.3%) followed by those aged 18-64 years (24.4%) and ≥65 years (14.8%). CONCLUSIONS: In Italy, some studies have shown the early circulation of SARS-CoV-2 in northern regions, those most severely affected during phase I of the pandemic. In central and southern regions, by contrast no early circulation of the virus was registered. These results are in line with ours. These findings highlight the need to continue to carry out retrospective studies, in order to understand the epidemiology of the novel coronavirus, to better identify the clinical characteristics of COVID-19 in comparison with other acute respiratory illnesses (ARI), and to evaluate the real burden of COVID-19 on the healthcare system.

Digital Surveillance Through an Online Decision Support Tool for COVID-19 Over One Year of the Pandemic in Italy: Observational Study.

BACKGROUND: Italy has experienced severe consequences (ie, hospitalizations and deaths) during the COVID-19 pandemic. Online decision support systems (DSS) and self-triage applications have been used in several settings to supplement health authority recommendations to prevent and manage COVID-19. A digital Italian health tech startup, Paginemediche, developed a noncommercial, online DSS with a chat user interface to assist individuals in Italy manage their potential exposure to COVID-19 and interpret their symptoms since early in the pandemic. OBJECTIVE: This study aimed to compare the trend in online DSS sessions with that of COVID-19 cases reported by the national health surveillance system in Italy, from February 2020 to March 2021. METHODS: We compared the number of sessions by users with a COVID-19-positive contact and users with COVID-19-compatible symptoms with the number of cases reported by the national surveillance system. To calculate the distance between the time series, we used the dynamic time warping algorithm. We applied Symbolic Aggregate approXimation (SAX) encoding to the time series in 1-week periods. We calculated the Hamming distance between the SAX strings. We shifted time series of online DSS sessions 1 week ahead. We measured the improvement in Hamming distance to verify the hypothesis that online DSS sessions anticipate the trends in cases reported to the official surveillance system. RESULTS: We analyzed 75,557 sessions in the online DSS; 65,207 were sessions by symptomatic users, while 19,062 were by contacts of individuals with COVID-19. The highest number of online DSS sessions was recorded early in the pandemic. Second and third peaks were observed in October 2020 and March 2021, respectively, preceding the surge in notified COVID-19 cases by approximately 1 week. The distance between sessions by users with COVID-19 contacts and reported cases calculated by dynamic time warping was 61.23; the distance between sessions by symptomatic users was 93.72. The time series of users with a COVID-19 contact was more consistent with the trend in confirmed cases. With the 1-week shift, the Hamming distance between the time series of sessions by users with a COVID-19 contact and reported cases improved from 0.49 to 0.46. We repeated the analysis, restricting the time window to between July 2020 and December 2020. The corresponding Hamming distance was 0.16 before and improved to 0.08 after the time shift. CONCLUSIONS: Temporal trends in the number of online COVID-19 DSS sessions may precede the trend in reported COVID-19 cases through traditional surveillance. The trends in sessions by users with a contact with COVID-19 may better predict reported cases of COVID-19 than sessions by symptomatic users. Data from online DSS may represent a useful supplement to traditional surveillance and support the identification of early warning signals in the COVID-19 pandemic.

Brand-specific influenza vaccine effectiveness estimates during 2019/20 season in Europe - Results from the DRIVE EU study platform.

DRIVE (Development of Robust and Innovative Vaccine Effectiveness) is an IMI funded public-private platform that aims to annually estimate brand-specific influenza vaccine effectiveness (IVE), for public health and regulatory purposes. IVE analyses and reporting are conducted by public partners in the consortium. In 2019/20, four primary care-based test-negative design (TND) studies (Austria, England, Italy (n = 2)), eight hospital-based TND studies (Finland, France, Italy, Romania, Spain (n = 4)), and one population-based cohort study (Finland) were conducted. The COVID-19 pandemic affected influenza surveillance in all participating study sites, therefore the study period was truncated on February 29, 2020. Age-stratified (6 m-17y, 18-64y, ≥65y), confounder-adjusted, site-specific adjusted IVE estimates were calculated and pooled through meta-analysis. Parsimonious confounder-adjustment was performed, adjusting the estimates for age, sex and calendar time. TND studies included 3531 cases (351 vaccinated) and 5546 controls (1415 vaccinated) of all ages. IVE estimates were available for 8/11 brands marketed in Europe in 2019. Most children and adults < 64y were captured in primary care setting and the most frequently observed vaccine brand was Vaxigrip Tetra. The estimate against any influenza for Vaxigrip Tetra in primary care setting was 61% (95%CI 38-77) in children and 32% (95%CI -13-59) in adults up to 64y. Most adults ≥ 65y were captured in hospital setting and the most frequently observed brand was Fluad, with an estimate of 52% (95%CI 27-68). The population-based cohort covered 511,854 person-years and two vaccine brands. In children aged 2-6y, the IVE against any influenza was 68% (95%CI 58-75) for Fluenz Tetra and 71% (56-80) for Vaxigrip Tetra. In adults ≥ 65y, IVE against any influenza was 29% (20-36) for Vaxigrip Tetra. DRIVE is a growing platform. Public health institutes with surveillance data and hospitals in countries with high influenza vaccine coverage are encouraged to join DRIVE.

Sars-Cov2 Not Detected in a Pediatric Population With Acute Respiratory Infection in Primary Care in Central and Southern Italy From November 2019 to Early March 2020.

Background: In December 2019, a novel coronavirus named SARS-CoV-2 started circulating in China and this led to a major epidemic in Northern Italy between February and May 2020. Young children (aged <5 years) seem to be less affected by this coronavirus disease (COVID-19) compared to adults, although there is very little information on the circulation of this new virus among children in Italy. We retrospectively tested nasopharyngeal swabs for SARS-CoV-2 in samples collected in young children between November, 2019 and March, 2020 in the context of the RSV ComNet study. Methods: Two networks of primary care pediatricians in Lazio (Central Italy) and Puglia (Southern Italy) collected nasopharyngeal swabs from children, aged <5 years, presenting with symptoms for an acute respiratory infection (ARI). The RSV ComNet study is a multicenter study implemented to estimate the burden of RSV in young children (aged <5 years) in the community. Swabs were sent to a central reference laboratory and tested for 14 respiratory viruses through RT-PCR. All collected samples were retrospectively tested for SARS-CoV-2 using RT-PCR (Istituto Superiore di Sanità protocol). Results: A total of 293 children with ARI were identified in the two participating networks. The highest number of cases were recruited in weeks 51/2019 and 3/2020. The majority of patients (57%) came from the Lazio region. All of the 293 samples tested negative for SARS-Cov2. Rhinovirus was the most frequently detected virus (44%), followed by RSV (41%) and influenza viruses (14%). Conclusions: Our study shows that in Lazio (a region of intermediate SARS-COV-2 incidence) and Puglia (a region of low incidence), the SARS-Cov2 virus did not circulate in a sample of ARI pediatric cases consulting primary care pediatricians between November 2019 and March 2020.

One step closer to influenza vaccine inclusiveness.

Flu virus infection is a common cause of acute respiratory illness, with the major incidence in pediatric age, high morbidity, and mortality. The flu vaccine is recommended for all people aged ≥6 months, unless specific contraindications are present. Younger and older age, pregnancy, chronic diseases like asthma, and immunodeficiency are risk factors for severe complications following flu infection. Thus, these categories represent the target for flu vaccine strategies in most countries. Inactivated influenza vaccine (IIV), recombinant influenza vaccine (RIV) or live-attenuated influenza virus (LAIV) are currently available, with specific precautions and contraindications. We aim to resume the current indications for vaccines in the vulnerable populations to support flu vaccination inclusiveness, in anticipation of a "universal vaccine" strategy.

Digital tools, multidisciplinarity and innovation for communicating vaccine safety in the COVID-19 era.

The research on the anti-SARS-CoV-2 vaccines and their commercialization is an opportunity to test and consolidate the current knowledge along with the diverse available tools related to vaccine communication.In this paper we explore the value of a multidisciplinary approach in this field: vaccine communication activities can be combined with insights from data science, risk communication, behavior change, design thinking and digital marketing. Methodologies derived from innovation and human-centered design can contribute to the development and testing of vaccine promotion campaigns, speeding up processes and streamlining the production of evidence in this area. The multiple activities involving the anti-SARS-CoV-2 vaccine could be the fertile ground in which to develop, test and refine effective frameworks to transfer data acquired through listening strategies into effective vaccine promotion campaigns. The World Health Organization's Vaccine Safety Net is an interesting example of trusted information sources that aim toward using digital tools and innovative methodologies for communicating science-based information on vaccine safety at the global level.

Attitudes and Beliefs on Influenza Vaccination during the COVID-19 Pandemic: Results from a Representative Italian Survey.

The last 2019/20 northern hemisphere influenza season overlapped with the first wave of coronavirus disease 2019 (COVID-19) pandemic. Italy was the first western country where severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread to a significant extent. In this representative cross-sectional survey, we aimed to describe some opinions and attitudes of the Italian general population towards both influenza vaccination and the COVID-19 pandemic, and to identify potential modifiers of the decision-making process regarding the uptake of the 2020/21 influenza vaccine. A total of 2543 responses were analyzed. Although most (74.8%) participants valued influenza vaccination positively and declared that it should be mandatory, some misconceptions around influenza persist. The general practitioner was the main source of trusted information on influenza vaccines, while social networks were judged to be the least reliable. Younger and less affluent individuals, subjects not vaccinated in the previous season, and those living in smaller communities showed lower odds of receiving the 2020/21 season influenza vaccination. However, the COVID-19 pandemic may have positively influenced the propensity of being vaccinated against 2020/21 seasonal influenza. In order to increase influenza vaccination coverage rates multidisciplinary targeted interventions are needed. The role of general practitioners remains crucial in increasing influenza vaccine awareness and acceptance by effective counselling.