Examining the effectiveness and duration of adjuvanted vs. non-adjuvanted influenza vaccines in protecting older adults against symptomatic SARS-CoV-2 infection.

Annual influenza vaccination is one of the main public health measures able to drastically reduce the burden of this infectious disease. Some evidence suggests 'trained immunity' triggered by influenza vaccine might reduce the risk of SARS-CoV-2 infection. Adjuvanted influenza vaccines are known to induce a broader cross-reactive immunity. No studies investigated the effect of adjuvanted vs. non-adjuvanted influenza vaccines on the risk of symptomatic SARS-CoV-2 infection. A case-control analysis nested in a cohort of subjects aged ≥65 years and immunized with adjuvanted or non-adjuvanted influenza vaccines was conducted. Although no statistically significant (OR = 0.87; P = .082) difference between the two vaccine types was observed for the 9-month follow-up period, a 17% (OR = 0.83; P = .042) reduction in the odds of COVID-19 was observed for adjuvanted vaccines with a 6-month follow-up. Further evidence is needed, but these results might have implications given the complexity of the upcoming winter seasons, in which the co-occurrence of influenza, SARS-CoV-2 and other respiratory infections (e.g., syncytial virus) might be unpredictable.

Declining number of general practitioners can impair influenza vaccination uptake among Italian older adults: Results from a panel analysis.

BACKGROUND: Seasonal influenza vaccination coverage in Italian older adults is insufficient and well below the minimum target of 75%. In Italy, most influenza vaccine doses are administered by general practitioners (GPs), whose number has been declining. In parallel, the number of patients per GP and GP workload increased dramatically, which theoretically may impair vaccination counselling. In this ecological study, we aimed to assess whether influenza vaccination coverage in older adults is associated with the density of GPs having high number of patients. METHODS: The study outcome was the influenza vaccination coverage rate in adults aged ≥ 65 years and registered in 20 Italian regions over the last 23 years. The independent variable of interest was the proportion of GPs with more than 1,500 adult patients, which is an imposed normative ceiling. This latter variable was considered as a proxy of GP overload. By adopting a panel regression approach, different specifications of fixed- and random-effects models were run to assess the association of interest, when adjusted for several social structural, economic and healthcare-related variables. RESULTS: Over the last two decades, most regions showed a negative association between influenza vaccination coverage rates and the density of GPs with a high number of patients. This latter negative association was confirmed (P < 0.05) in different panel model specifications. In particular, in the fully adjusted two-way fixed-effects model, each 10% increase in the number of GPs with more than 1,500 patients was associated with a 1.7% decrease in influenza vaccination coverage. However, this association was present only in region-years where at least 18% of GPs were deemed overloaded. CONCLUSIONS: In the upcoming years, the number of Italian GPs is projected to decline further. At the same time, the aging Italian population will determine an even greater workload for GPs. This study demonstrated that increased GP workload may partially explain the spatiotemporal variation in influenza vaccination uptake in the Italian elderly. With the imperative of increasing or at least maintaining influenza vaccination coverage rates, several short- and mid-term initiatives should be implemented in order to optimize GP workload during seasonal immunization campaigns.

Diagnostic Accuracy of Five Molecular Assays for the Detection of Dengue Virus.

Background and Objectives: The steady spread of dengue virus (DENV) poses a profound public health threat worldwide. Reverse transcription real-time polymerase chain reaction (RT2-PCR) has been increasingly recognized as a reference method for the diagnosis of acute dengue infection. The goal of this study was to assess the diagnostic accuracy of five different RT2-PCR kits for the detection of DENV in a historically processed set of sera samples. Materials and Methods: In this retrospective study, 25 sera samples from routinely processed unique adult patients with a known DENV status (previously tested in both molecular and serological assays) were tested in parallel using four conventional (RealStar Dengue PCR Kit 3.0, Clonit'ngo Zika, Dengue & Chikungunya, BioPerfectus Zika Virus/Dengue Virus/Chikungunya Virus Real Time PCR Kit and Novaplex Tropical fever virus) and one sample-to-result (STANDARD M10 Arbovirus Panel) RT2-PCR assays. Additionally, an end-point dilution analysis was conducted in quintuplicate on six serial dilutions of an RNA preparation obtained from a culture-grown DENV serotype 1 strain for a total of 150 tests. Results: The overall accuracy of the evaluated tests ranged from 84% to 100%. In particular, the sensitivity of three conventional RT2-PCR assays (RealStar, Clonit'ngo and Novaplex) was 100% (95% CI: 79.6-100%), while it was lower (73.3%; 95% CI: 48.1-89.1%) for the BioPerfectus kit. The sample-to-result STANDARD M10 panel performed comparatively well, showing a sensitivity of 92.9% (95% CI: 68.5-98.7%). No false positive results were registered in any assay. The end-point dilution analysis suggested that the RealStar kit had the lowest limit of detection. Conclusions: Available RT2-PCR kits for the detection of DENV are highly specific and generally sensitive and, therefore, their implementation in diagnostic pathways is advisable.

Epidemiology and molecular characteristics of respiratory syncytial virus (RSV) among italian community-dwelling adults, 2021/22 season.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infections worldwide. While historically RSV research has been focused on children, data on RSV infection in adults are limited. The goal of this study was to establish the prevalence of RSV in community-dwelling Italian adults and analyze its genetic variability during the 2021/22 winter season. METHODS: In this cross-sectional study, a random sample of naso-/oropharyngeal specimens from symptomatic adults seeking for SARS-CoV-2 molecular testing between December 2021 and March 2022 were tested for RSV and other respiratory pathogens by means of reverse-transcription polymerase chain reaction. RSV-positive samples were further molecularly characterized by sequence analysis. RESULTS: Of 1,213 samples tested, 1.6% (95% CI: 0.9-2.4%) were positive for RSV and subgroups A (44.4%) and B (55.6%) were identified in similar proportions. The epidemic peak occurred in December 2021, when the RSV prevalence was as high as 4.6% (95% CI: 2.2-8.3%). The prevalence of RSV detection was similar (p = 0.64) to that of influenza virus (1.9%). All RSV A and B strains belonged to the ON1 and BA genotypes, respectively. Most (72.2%) RSV-positive samples were also positive for other pathogens being SARS-CoV-2, Streptococcus pneumoniae and rhinovirus the most frequent. RSV load was significantly higher among mono-detections than co-detections. CONCLUSION: During the 2021/22 winter season, characterized by the predominant circulation of SARS-CoV-2 and some non-pharmaceutical containment measures still in place, a substantial proportion of Italian adults tested positive for genetically diversified strains of both RSV subtypes. In view of the upcoming registration of vaccines, establishment of the National RSV surveillance system is urgently needed.

Exploring missed opportunities for influenza vaccination and influenza vaccine co-administration patterns among Italian older adults: a retrospective cohort study.

BACKGROUND: Missed opportunities constitute a main driver of suboptimal seasonal influenza vaccination (SIV) coverage in older adults. Vaccine co-administration is a way to reduce these missed opportunities. In this study, we quantified missed opportunities for SIV, identified some of their socio-structural correlates and documented SIV co-administration patterns. METHODS: In this registry-based retrospective cohort study, we verified the SIV status of all subjects aged ≥65 years who received at least one dose of coronavirus disease 2019 (COVID-19), pneumococcal or herpes zoster vaccines during the 2022/23 influenza season. The frequency of concomitant same-day administration of SIV with other target vaccines was also assessed. RESULTS: Among 41 112, 5482 and 3432 older adults who received ≥1 dose of COVID-19, pneumococcal and herpes zoster vaccines, missed opportunities for SIV accounted for 23.3%, 5.0% and 13.2%, respectively. Younger, male and foreign-born individuals were generally more prone to missing SIV. The co-administration of SIV with other recommended vaccines was relatively low, being 11.0%, 53.1% and 17.1% in COVID-19, pneumococcal and herpes zoster cohorts, respectively. CONCLUSIONS: A sizeable proportion of older adults who received other recommended vaccines during the last influenza season did not receive SIV. This share of missed opportunities, which are subject to some social inequalities, may be addressed by increasing vaccine co-administration rates and implementing tailored health promotion interventions.

Evaluation of extraction-free RT-qPCR methods for SARS-CoV-2 diagnostics.

Extraction-based real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) is currently the "gold standard" in SARS-CoV-2 diagnostics. However, some extraction-free RT-qPCR techniques have recently been developed. In this study, we compared the sensitivity of traditional extraction-based, heated extraction-free, and unheated extraction-free RT-qPCR methods for SARS-CoV-2 detection in nasopharyngeal swabs from symptomatic individuals. The unheated extraction-free method showed perfect agreement with the standard extraction-based RT-qPCR. By contrast, the heat-treated technique was associated with an 8.2% false negativity rate. Unheated extraction-free RT-qPCR for the molecular diagnosis of SARS-CoV-2 is a valuable alternative to the traditional extraction-based methods and may accelerate turnaround times by about two hours.

Clustering of health-related behaviors among early and mid-adolescents in Tuscany: results from a representative cross-sectional study.

Background: A huge amount of literature suggests that adolescents' health-related behaviors tend to occur in clusters, and the understanding of such behavioral clustering may have direct implications for the effective tailoring of health-promotion interventions. Despite the usefulness of analyzing clustering, Italian data on this topic are scant. This study aimed to evaluate the clustering patterns of health-related behaviors. Methods: The present study is based on data from the Health Behaviors in School-aged Children (HBSC) study conducted in Tuscany in 2010, which involved 3291 11-, 13- and 15-year olds. To aggregate students' data on 22 health-related behaviors, factor analysis and subsequent cluster analysis were performed. Results: Factor analysis revealed eight factors, which were dubbed in accordance with their main traits: 'Alcohol drinking', 'Smoking', 'Physical activity', 'Screen time', 'Signs & symptoms', 'Healthy eating', 'Violence' and 'Sweet tooth'. These factors explained 67% of variance and underwent cluster analysis. A six-cluster κ-means solution was established with a 93.8% level of classification validity. The between-cluster differences in both mean age and gender distribution were highly statistically significant. Conclusions: Health-compromising behaviors are common among Tuscan teens and occur in distinct clusters. These results may be used by schools, health-promotion authorities and other stakeholders to design and implement tailored preventive interventions in Tuscany.

An eHealth Project on Invasive Pneumococcal Disease: Comprehensive Evaluation of a Promotional Campaign.

BACKGROUND: The recently launched Pneumo Rischio eHealth project, which consists of an app, a website, and social networking activity, is aimed at increasing public awareness of invasive pneumococcal disease (IPD). The launch of this project was prompted by the inadequate awareness of IPD among both laypeople and health care workers, the heavy socioeconomic burden of IPD, and the far from optimal vaccination coverage in Italy, despite the availability of safe and effective vaccines. OBJECTIVE: The objectives of our study were to analyze trends in Pneumo Rischio usage before and after a promotional campaign, to characterize its end users, and to assess its user-rated quality. METHODS: At 7 months after launching Pneumo Rischio, we established a 4-month marketing campaign to promote the project. This intervention used various approaches and channels, including both traditional and digital marketing strategies. To highlight usage trends, we used different techniques of time series analysis and modeling, including a modified Mann-Kendall test, change-point detection, and segmented negative binomial regression of interrupted time series. Users were characterized in terms of demographics and IPD risk categories. Customer-rated quality was evaluated by means of a standardized tool in a sample of app users. RESULTS: Over 1 year, the app was accessed by 9295 users and the website was accessed by 143,993 users, while the project's Facebook page had 1216 fans. The promotional intervention was highly effective in increasing the daily number of users. In particular, the Mann-Kendall trend test revealed a significant (P ≤.01) increasing trend in both app and website users, while change-point detection analysis showed that the first significant change corresponded to the start of the promotional campaign. Regression analysis showed a significant immediate effect of the intervention, with a mean increase in daily numbers of users of 1562% (95% CI 456%-4870%) for the app and 620% (95% CI 176%-1777%) for the website. Similarly, the postintervention daily trend in the number of users was positive, with a relative increase of 0.9% (95% CI 0.0%-1.8%) for the app and 1.4% (95% CI 0.7%-2.1%) for the website. Demographics differed between app and website users and Facebook fans. A total of 69.15% (10,793/15,608) of users could be defined as being at risk of IPD, while 4729 users expressed intentions to ask their doctor for further information on IPD. The mean app quality score assigned by end users was approximately 79.5% (397/500). CONCLUSIONS: Despite its specific topic, Pneumo Rischio was accessed by a considerable number of users, who ranked it as a high-quality project. In order to reach their target populations, however, such projects should be promoted.

Development and validation of the Italian version of the Mobile Application Rating Scale and its generalisability to apps targeting primary prevention.

BACKGROUND: A growing body of literature affirms the usefulness of mobile technologies, including mobile applications (apps), in the primary prevention field. The quality of health apps, which today number in the thousands, is a crucial parameter, as it may affect health-related decision-making and outcomes among app end-users. The mobile application rating scale (MARS) has recently been developed to evaluate the quality of such apps, and has shown good psychometric properties. Since there is no standardised tool for assessing the apps available in Italian app stores, the present study developed and validated an Italian version of MARS in apps targeting primary prevention. METHODS: The original 23-item version of the MARS assesses mobile app quality in four objective quality dimensions (engagement, functionality, aesthetics, information) and one subjective dimension. Validation of this tool involved several steps; the universalist approach to achieving equivalence was adopted. Following two backward translations, a reconciled Italian version of MARS was produced and compared with the original scale. On the basis of sample size estimation, 48 apps from three major app stores were downloaded; the first 5 were used for piloting, while the remaining 43 were used in the main study in order to assess the psychometric properties of the scale. The apps were assessed by two raters, each working independently. The psychometric properties of the final version of the scale was assessed including the inter-rater reliability, internal consistency, convergent, divergent and concurrent validities. RESULTS: The intralingual equivalence of the Italian version of the MARS was confirmed by the authors of the original scale. A total of 43 apps targeting primary prevention were tested. The MARS displayed acceptable psychometric properties. The MARS total score showed an excellent level of both inter-rater agreement (intra-class correlation coefficient of .96) and internal consistency (Cronbach's α of .90 and .91 for the two raters, respectively). Other types of validity, including convergent, divergent, discriminative, known-groups and scalability, were also established. CONCLUSIONS: The Italian version of MARS is a valid and reliable tool for assessing the health-related primary prevention apps available in Italian app stores.

Uncontrolled Web-based administration of surveys on factual health-related knowledge: a randomized study of untimed versus timed quizzing.

BACKGROUND: Health knowledge and literacy are among the main determinants of health. Assessment of these issues via Web-based surveys is growing continuously. Research has suggested that approximately one-fifth of respondents submit cribbed answers, or cheat, on factual knowledge items, which may lead to measurement error. However, little is known about methods of discouraging cheating in Web-based surveys on health knowledge. OBJECTIVE: This study aimed at exploring the usefulness of imposing a survey time limit to prevent help-seeking and cheating. METHODS: On the basis of sample size estimation, 94 undergraduate students were randomly assigned in a 1:1 ratio to complete a Web-based survey on nutrition knowledge, with or without a time limit of 15 minutes (30 seconds per item); the topic of nutrition was chosen because of its particular relevance to public health. The questionnaire consisted of two parts. The first was the validated consumer-oriented nutrition knowledge scale (CoNKS) consisting of 20 true/false items; the second was an ad hoc questionnaire (AHQ) containing 10 questions that would be very difficult for people without health care qualifications to answer correctly. It therefore aimed at measuring cribbing and not nutrition knowledge. AHQ items were somewhat encyclopedic and amenable to Web searching, while CoNKS items had more complex wording, so that simple copying/pasting of a question in a search string would not produce an immediate correct answer. RESULTS: A total of 72 of the 94 subjects started the survey. Dropout rates were similar in both groups (11%, 4/35 and 14%, 5/37 in the untimed and timed groups, respectively). Most participants completed the survey from portable devices, such as mobile phones and tablets. To complete the survey, participants in the untimed group took a median 2.3 minutes longer than those in the timed group; the effect size was small (Cohen's r=.29). Subjects in the untimed group scored significantly higher on CoNKS (mean difference of 1.2 points, P=.008) and the effect size was medium (Cohen's d=0.67). By contrast, no significant between-group difference in AHQ scores was documented. Unexpectedly high AHQ scores were recorded in 23% (7/31) and 19% (6/32) untimed and timed respondents, respectively, very probably owing to "e-cheating". CONCLUSIONS: Cribbing answers to health knowledge items in researcher-uncontrolled conditions is likely to lead to overestimation of people's knowledge; this should be considered during the design and implementation of Web-based surveys. Setting a time limit alone may not completely prevent cheating, as some cheats may be very fast in Web searching. More complex and contextualized wording of items and checking for the "findability" properties of items before implementing a Web-based health knowledge survey may discourage help-seeking, thus reducing measurement error. Studies with larger sample sizes and diverse populations are needed to confirm our results.

Epidemiology and burden of respiratory syncytial virus in Italian adults: A systematic review and meta-analysis.

OBJECTIVE: Respiratory syncytial virus (RSV) is a common respiratory pathogen not only in children, but also in adults. In view of a recent authorization of adult RSV vaccines in Italy, our research question was to quantify the epidemiology and burden of RSV in Italian adults. METHODS: Observational studies on the epidemiology and clinical burden of laboratory-confirmed or record-coded RSV infection in Italian adults of any age were eligible. Studies with no separate data for Italian adults, modeling and other secondary publications were excluded. A literature search was performed in MEDLINE, Biological Abstracts, Global Health, Scopus and Web of Science on 22 November 2023. Critical appraisal was performed by means of a Joanna Briggs Institute checklist. Random-effects (RE) meta-analysis was performed to obtain pooled estimates and the observed heterogeneity was investigated by subgroup and meta-regression analyses. The protocol was prospectively registered (doi.org/10.17504/protocols.io.5qpvo32odv4o/v1). RESULTS: Thirty-five studies were identified, most of which had at least one possible quality concern. RSV seasonal attack rates ranged from 0.8 ‰ in community-dwelling older adults to 10.9% in hematological outpatients. In the RE model, 4.5% (95% CI: 3.2-5.9%) of respiratory samples tested positive for RSV. This positivity prevalence was higher in older adults (4.4%) than in working-age adults (3.5%) and in outpatient (4.9%) than inpatient (2.9%) settings. According to the meta-regression, study location and sample size were also significant predictors of RSV detection frequency. The pooled estimate of in-hospital mortality was as high as 7.2% (95% CI: 4.7-10.3%). Data on other indicators of the diseases burden, such as complication and hospitalization rates, were unavailable. CONCLUSION: RSV poses a measurable burden on Italian adults, especially those of older age and with some co-morbidities. However, several data on the natural history of RSV disease are missing and should be established by future large-scale studies.

Multiplex molecular assays for the laboratory-based and point-of-care diagnosis of infections caused by seasonal influenza, COVID-19, and RSV.

INTRODUCTION: SARS-CoV-2, seasonal influenza, and respiratory syncytial virus (RSV) are major causes of acute respiratory infections in all age groups and responsible for an enormous socio-economic burden. The recently coined term 'tripledemic' describes co-circulation of these three viruses, a novel epidemiological paradigm that poses profound public health implications. AREAS COVERED: Real-time reverse transcription polymerase chain reaction (RT-PCR) is now considered the reference method for the diagnosis of SARS-CoV-2, influenza, and RSV infections. Syndromic-based multiplex RT-PCR panels that simultaneously detect several respiratory viruses have become increasingly common. This review explores available molecular diagnostics (MDx) platforms for the diagnosis of SARS-CoV-2, influenza, and RSV in the same biological sample. Within some limitations of the published validation and diagnostic accuracy studies, both laboratory-based and point-of-care multiplex panels proved highly performant in identifying SARS-CoV-2, influenza A, influenza B, and RSV. Improved operational efficiency and faster turnaround times make these assays potentially cost-effective or even cost-saving. EXPERT OPINION: The adoption of multiplex MDx assays for the contemporary detection of SARS-CoV-2, influenza, RSV, and other respiratory pathogens will likely increase in the next few years. To maximize the clinical usefulness and cost-effectiveness of these assays, locally issued guidelines and protocols on their implementation should be adopted.

Immunogenicity of Enhanced Influenza Vaccines Against Mismatched Influenza Strains in Older Adults: A Review of Randomized Controlled Trials.

Antigenic drift is a major driver of viral evolution and a primary reason why influenza vaccines must be reformulated annually. Mismatch between vaccine and circulating viral strains negatively affects vaccine effectiveness and often contributes to higher rates of influenza-related hospitalizations and deaths, particularly in years dominated by A(H3N2). Several countries recommend enhanced influenza vaccines for older adults, who are at the highest risk of severe influenza complications and mortality. The immunogenicity of enhanced vaccines against heterologous A(H3N2) strains has been examined in nine studies to date. In six studies, an enhanced, licensed MF59-adjuvanted trivalent inactivated influenza vaccine (aIIV3) consistently increased heterologous antibody titers relative to standard influenza vaccine, with evidence of a broad heterologous immune response across multiple genetic clades. In one study, licensed high-dose trivalent inactivated influenza vaccine (HD-IIV3) also induced higher heterologous antibody titers than standard influenza vaccine. In a study comparing a higher dose licensed quadrivalent recombinant influenza vaccine (RIV4) with HD-IIV3 and aIIV3, no significant differences in antibody titers against a heterologous strain were observed, although seroconversion rates were higher with RIV4 versus comparators. With the unmet medical need for improved influenza vaccines, the paucity of studies especially with enhanced vaccines covering mismatched strains highlights a need for further investigation of cross-protection in older adults.

Web search volume as a near-real-time complementary surveillance tool of tick-borne encephalitis (TBE) in Italy.

The Internet is an important gateway for accessing health-related information, and data generated through web queries have been increasingly used as a complementary source for monitoring and forecasting of infectious diseases and they may partially address the issue of underreporting. In this study, we assessed whether tick-borne encephalitis (TBE)-related Internet search volume may be useful as a complementary tool for TBE surveillance in Italy. Monthly Google Trends (GT) data for TBE-related information were extracted for the period between January 2017 and September 2022, corresponding to the available time series of TBE notifications in Italy. Time series modeling was performed by applying seasonal autoregressive integrated moving average (SARIMA) models with or without GT data. The search terms relative to tick bites reflected best the observed temporal distribution of TBE cases, showing a correlation coefficient of 0.81 (95 % CI: 0.71-0.88). Particularly, both the reported number of TBE cases and GT searches occurred mainly during the summer. The peak of disease notifications coincided with that of Google searches in 4 of 6 years. Once calibrated, SARIMA models with or without GT data were applied to a validation set. Retrospective forecast made by the model with GT data was associated with a lower prediction error and accurately predicted the peak timing. By contrast, the traditional SARIMA model underestimated the actual number of TBE notifications by 65 %. Timeliness, easy availability, low cost and transparency make monitoring of the TBE-related Internet search queries a promising addition to the traditional methods of TBE surveillance in Italy.

Supporting vaccine (co)-administration decisions: Development and validation of a tool for assessing the risk of severe outcomes due to lower respiratory tract infections.

OBJECTIVE: To develop and validate a score to predict the 90-day risk of hospitalization/death in patients with low respiratory tract infections (LRTIs) with the aim to support clinical decision making on vaccine (co)-administration. METHODS: We formed a cohort of patients aged 18 years or older being diagnosed with LRTIs in the period between January 1, 2012 and December 31, 2022. Each patient was followed until occurrence of respiratory-related hospitalization/death up to the end of the study period (December 31, 2022). Along with age and sex, forty determinants were adopted to assemble the respiratory tract infection (RTI)-Health Search (HS) core using the development sub-cohort. The prediction accuracy of the score was therefore assessed in the validation sub-cohort. RESULTS: We identified 252,319 patients being diagnosed with LRTIs (females: 54.7 %; mean age: 60 (SD:18.1)). When the risk of LRTIs-related hospitalizations/deaths was estimated via RTI-HScore, its predicted value was equal to 1.4 % over a 90-day event horizon. The score showed explained variation and discrimination accuracy were equal to 45 % (95 % CI: 44-47 %) and 81 % (95 % CI: 79-84 %), respectively. The calibration slope did not significantly differ from the unit (p = 0.8314). CONCLUSIONS: The RTI-HScore was featured by good accuracy for prediction of LRTIs-related complications over a 90-day follow-up. Such a tool might therefore support general practitioners to enhance patients' care by facilitating approaches for (co)-administration of vaccines for respiratory infections through a score-based decision support system.

A Vulnerability Index to Assess the Risk of SARS-CoV-2-Related Hospitalization/Death: Urgent Need for an Update after Diffusion of Anti-COVID Vaccines.

Background: There are algorithms to predict the risk of SARS-CoV-2-related complications. Given the spread of anti-COVID vaccination, which sensibly modified the burden of risk of the infection, these tools need to be re-calibrated. Therefore, we updated our vulnerability index, namely, the Health Search (HS)-CoVulnerabiltyIndex (VI)d (HS-CoVId), to predict the risk of SARS-CoV-2-related hospitalization/death in the primary care setting. Methods: We formed a cohort of individuals aged ≥15 years and diagnosed with COVID-19 between 1 January and 31 December 2021 in the HSD. The date of COVID-19 diagnosis was the study index date. These patients were eligible if they had received an anti-COVID vaccine at least 15 days before the index date. Patients were followed up from the index date until one of the following events, whichever came first: COVID-19-related hospitalization/death (event date), end of registration with their GPs, and end of the study period (31 December 2022). To calculate the incidence rate of COVID-19-related hospitalization/death, a patient-specific score was derived through linear combination of the coefficients stemming from a multivariate Cox regression model. Its prediction performance was evaluated by obtaining explained variation, discrimination, and calibration measures. Results: We identified 2192 patients who had received an anti-COVID vaccine from 1 January to 31 December 2021. With this cohort, we re-calibrated the HS-CoVId by calculating optimism-corrected pseudo-R2, AUC, and calibration slope. The final model reported a good predictive performance by explaining 58% (95% CI: 48-71%) of variation in the occurrence of hospitalizations/deaths, the AUC was 83 (95% CI: 77-93%), and the calibration slope did not reject the equivalence hypothesis (p-value = 0.904). Conclusions: Two versions of HS-CoVId need to be differentially adopted to assess the risk of COVID-19-related complications among vaccinated and unvaccinated subjects. Therefore, this functionality should be operationalized in related patient- and population-based informatic tools intended for general practitioners.

Influenza-like illness surveillance may underestimate the incidence of respiratory syncytial virus in adult outpatients.

OBJECTIVES: Although respiratory syncytial virus (RSV) is a leading cause of acute respiratory infections (ARIs), it is unclear which of the case definitions that prompt swab collection predicts RSV best. We aimed to profile RSV-positive adults and to identify possible RSV case definitions. METHODS: This individual-based pooled analysis was based on influenza-like illness (ILI) surveillance conducted among Italian outpatient adults. All samples were tested for influenza, RSV and other respiratory viruses. RESULTS: RSV was detected in 5.2% of the 1240 ILI adults tested. The prevalence of fever/feverishness was significantly lower (83.3%) in individuals positive for RSV and those negative for both viruses (79.4%) than in influenza-positive subjects (96.2%). Conversely, 98.3% of RSV-positive adults reported cough. Compared with subjects who tested negative, the adjusted relative risk ratio of cough in RSV-positive subjects was much higher than in influenza-positive subjects (6.89 vs 2.79). Using ARI with cough as the RSV case definition increased specificity. CONCLUSION: As fever/feverishness is more common among influenza than RSV cases, ILI-based surveillance may underestimate RSV incidence in adult outpatients. While broad ARI definitions are useful for routine RSV surveillance, their low specificity may hamper vaccine effectiveness studies. The use of further ARI qualifiers like cough increases specificity.

Effectiveness of a Counseling Intervention to Increase Vaccination Uptake among Men Who Have Sex with Men during the Mpox Outbreak.

Men who have sex with men (MSM) are disproportionately impacted by sexually transmitted infections (STIs), including HIV and those preventable through vaccination such as mpox, HPV, HAV, and HBV. A retrospective cohort study was conducted to evaluate the effectiveness of counseling provided during mpox vaccination on the uptake of other recommended vaccines (HPV, HAV, and HBV) and to identify associated factors. Relevant covariates such as nationality, age, HIV status, and use of PrEP were retrieved from electronic medical records. Vaccination status data were retrieved from the regional vaccination registry. Of the 330 participants, 98.8% were males and the mean age was 40.6 years (SD: 11.2). Following consultation, a statistically significant increase for both HPV (from 25.8% to 39.1%) and HAV (from 26.7% to 36.1%) was observed (p < 0.001). The multivariate analysis showed a significant negative association between the uptake of HPV and HBV vaccines and foreign nationality (aOR 0.25 (95%CI 0.08-0.69), p = 0.012; and aOR 0.31 (95%CI 0.11-0.81), p = 0.021). The HBV vaccine uptake was negatively associated with increasing age. Our results suggest that tailored counseling can effectively bridge the gap in vaccine acceptance among vulnerable populations, thereby improving overall public health outcomes.

Influenza epidemiology and vaccine effectiveness during the 2023/2024 season in Italy: A test-negative case-control study.

OBJECTIVES: In order to support policymakers in allocating resources, we aimed to assess vaccine effectiveness (VE) of inactivated influenza vaccines (IIVs) available for Italian adults in the 2023/2024 season. METHODS: A hospital-based test-negative case-control study was conducted in Genoa between mid-October 2023 and mid-April 2024. Adult (≥18 years) inpatients with prescription of a polymerase chain reaction test for influenza were eligible. RESULTS: Of 1,664 adults analyzed, most (82%) of which were ≥65 years, 114 (6.9%) tested positive for influenza A. Most (92%) cases were caused by subclades 6B.1A.5a.2a and 6B.1A.5a.2a.1 of the A(H1N1)pdm09 subtype. In older adults aged ≥65 years vaccination was effective at 51% (95% CI: 8%, 74%) against any influenza A and 49% (95% CI: 2%, 73%) against A(H1N1)pdm09. Compared with non-vaccinated older adults, VE point estimates for the adjuvanted and, especially, high-dose IIVs were higher than those for the standard-dose non-adjuvanted IIV. CONCLUSION: The 2023/2024 seasonal influenza vaccination proved moderately effective in preventing hospitalization for laboratory-confirmed influenza. Being more appropriate for older adults, local policymakers and vaccinating physicians should maximize adoption of the enhanced IIVs.

Waning intra-season vaccine effectiveness against influenza A(H3N2) underlines the need for more durable protection.

BACKGROUND: The question of whether influenza vaccine effectiveness (VE) wanes over the winter season is still open and some contradictory findings have been reported. This study investigated the possible decline in protection provided by the available influenza vaccines. RESEARCH DESIGN AND METHODS: An individual-level pooled analysis of six test-negative case-control studies conducted in Italy between the 2018/2019 and 2022/2023 seasons was performed. Multivariable logistic regression analyses were performed to estimate weekly change in the odds of testing positive for influenza 14 days after vaccination. RESULTS: Of 6490 patients included, 1633 tested positive for influenza. Each week that had elapsed since vaccination was associated with an increase in the odds of testing positive for any influenza (4.9%; 95% CI: 2.0-8.0%) and for A(H3N2) (6.5%; 95% CI: 2.9-10.3%). This decline in VE was, however, significant only in children and older adults. A similar increase in the odds of testing positive was seen when the dataset was restricted to vaccinees only. Conversely, VE waning was less evident for A(H1N1)pdm09 or B strains. CONCLUSIONS: Significant waning of VE, especially against influenza A(H3N2), may be one of the factors associated with suboptimal end-of-season VE. Next-generation vaccines should provide more durable protection against A(H3N2).