The 2024/2025 influenza season in Italy was characterised by cocirculation of influenza A and B viruses. Monitoring influenza vaccine effectiveness (IVE) remains essential to guide public health policy due to antigenic shifts and varying strain circulation. In this study, we aimed to estimate IVE in primary care and hospital settings during the 2024/2025 season in Italy. A nationwide test-negative control design was used. Data were collected from the RespiVirNet surveillance system, encompassing both primary care and hospital settings. A total of 8842 participants were included in the primary care analysis and 2492 in the hospital analysis. Adjusted vaccine effectiveness (aVE) against any influenza virus was 69.0% (95% CI: 60.4%-75.9%) in primary care and 62.3% (95% CI: 45.9%-74.2%) in hospital settings. Effectiveness was highest among individuals under 18 years and decreased with age. Influenza B showed the highest aVE (83.6% in primary care; 95.0% in hospital settings), particularly among younger individuals. aVE for influenza A subtypes was lower, with A H1N1pdm09 (54.0% in primary care; 63.8% in hospital) and A H3N2 (60.1% in primary care; 45.5% in hospital) showing moderate effectiveness. The results suggest that influenza vaccines were effective in preventing medically attended influenza disease, both in primary care and hospital settings. These findings provide valuable insights for public health planning and vaccine policy in Italy.

BACKGROUND:We estimated the XBB.1.5 vaccine effectiveness (VE) against COVID-19 hospitalization and death in Belgium, Denmark, Italy, Portugal, Spain (Navarre), and Sweden following the 2023-24 fall vaccination campaign among immunocompromised persons (ICPs). RESEARCH DESIGN AND METHODS:We conducted a multi-country retrospective cohort study using electronic health records. Study sites identified ICPs aged ≥18 years through a common set of immunocompromising conditions and follow-up started the first day of the 2023 vaccination campaign until 12 months later. VE was calculated by time since vaccination (14-59, 60-119, 120-179, 180-365 days after vaccination) for ICPs by pooling study site level confounder adjusted hazard ratios (aHR) of vaccination, estimated with Cox proportional hazards regression models, using a random effect meta-analysis with VE = 100 × (1-pooled aHR). RESULTS:The XBB.1.5 VE was 52% (95% confidence interval (CI): 41 to 60) and 75% (95%CI: 60 to 84) against hospitalization and death, respectively, 14-59 days after vaccination, and VE decreased with time since vaccination with no remaining protection at 180-365 days after vaccination. CONCLUSION:Adapted XBB.1.5 vaccine provided moderate protection within 120 days after vaccination against severe COVID-19 outcomes among ICPs aged ≥18 years during a period with BA.2.86/JN.1 replacing the XBB.1.5 variant.

Global evidence on COVID-19 related inequalities remains temporally fragmented. In this study we investigated how the associations of socioeconomic deprivation (SED) and country of birth with severe COVID-19 evolved in COVID-19 vaccinated persons residing in small/medium sized municipalities in Italy in 2021–2024. We retrospectively analysed data of 22,131,245 adults, living in municipalities with <50,000 residents, extracted from the national COVID-19 surveillance and vaccination databases. Using multivariable Cox regression we estimated annual hazard ratios (HRs) of COVID-19 hospitalisation and/or death by municipal SED quintile (Q) (relative to the least deprived Q1), and by country of birth (foreign-born vs. Italian-born). Our analyses, spanning periods with mobility restrictions (2021), and COVID-19 vaccination programs (2021–2024), were adjusted for demographic characteristics, high-risk conditions and COVID-19 vaccination, excluding the latter upon exploring the impact of the vaccine rollout on the observed associations. Deprived areas experienced increased hazard of severe COVID-19 in 2021–2022, peaking in 2021 (Q5, HR: 1.74, 95

OBJECTIVES:Safety concerns might explain the low uptake of COVID-19 vaccination recently observed in several countries. This study aims to compare COVID-19-unrelated mortality between vaccinated and unvaccinated people. METHODS:We conducted a retrospective cohort analysis over 2021-2025 among 735,473 residents aged ≥12 years in the Treviso Province of Italy. We used Cox regression models, including vaccination as time-dependent exposure and adjusting for socio-demographic and clinical characteristics, to estimate the hazard ratios (HRs) of COVID-19-related and -unrelated death by number of doses and time since administration of COVID-19 vaccines. RESULTS:Despite decreasing over time, the HR of COVID-19-related death in vaccinated compared with unvaccinated participants showed a significant vaccine-induced protection after the primary cycle or any booster dose. To a lesser extent, we also observed a reduced COVID-19-unrelated mortality associated with vaccination, with the HR ranging from 0.72 (95% confidence interval [CI]: 0.69-0.75) after two or more booster doses to 0.83 (95% CI: 0.77-0.89) after the first dose. We estimated a lower HR of COVID-19-unrelated death ≤30 days after a vaccine dose (HR = 0.48, 95% CI: 0.44-0.51) than >30 days later (HR = 0.80, 95% CI: 0.77-0.83). CONCLUSIONS:These results are reassuring about safety of COVID-19 vaccines and confirm their high effectiveness against COVID-19-related death, thus supporting seasonal COVID-19 vaccination campaigns.

BACKGROUND:Accurate estimation of vaccine effectiveness (VE) in real-world settings is essential for guiding immunization strategies, especially in older populations. However, observational studies are prone to bias due to confounding factors, and the choice of statistical method can significantly influence VE estimates. MATERIALS AND METHODS:We compared the performance of a multivariable Cox proportional hazards model with seven propensity score (PS)-based models to estimate the relative vaccine effectiveness (rVE) of the bivalent Original/Omicron BA.4-5 mRNA vaccine as a second or third booster, compared to a first mRNA booster received ≥120 days earlier. Data from 11,879,461 individuals aged ≥60 in Italy (April-June 2023) were analyzed. RESULTS:All models produced consistent rVE estimates, with values ranging from 16.4% to 22.1%. Over time, booster effectiveness declined, with the reference model showing a drop in rVE from 45.6% (15-60 days) to 14.3% (181-265 days). PS-based methods improved covariate balance but did not outperform the Cox model in terms of precision or interpretability. CONCLUSIONS:In large, relatively balanced datasets, traditional multivariable models remain a robust and reliable choice for estimating VE. While PS-based methods offer theoretical advantages, their practical benefit may be limited when confounding is well controlled.

Background Toscana virus (TOSV) is transmitted to humans through bites of infected sand flies. Neuroinvasive TOSV infections are leading causes of meningitis/encephalitis in southern Europe and notifiable in Italy since 2016. In 2022–23, Italy experienced extreme climate anomalies and a concomitant increase in mosquito and tick-borne disease transmission. Aim To identify the spatiotemporal distribution and risk groups of neuroinvasive TOSV infections in Italy in 2022–23 vs 2016–21. Methods We retrospectively described all autochthonous, laboratory-confirmed neuroinvasive TOSV cases notified to the national surveillance system in 2016–23 using frequencies, proportions, incidences and incidence risk ratios (IRRs) with 95% CIs, stratified by year, sex, age, region/autonomous province (AP) of infection/exposure and infection/exposure municipality by urbanisation level. Results In 2022–23, 276 cases were notified (average annual incidence: 2.34/1,000,000 population) vs 331 cases in 2016–21 (0.92/1,000,000), with increased incidence extending into September. In 2022–23, infections were acquired in 12/21 regions/APs, predominantly in Emilia Romagna (57.6%; 159/276) as in 2016–21, including four regions/APs with no local infections in 2016–21. Similar to 2016–21, during 2022–23 residence in rural municipalities (vs urban), male sex, working age (19–67 years) and age > 67 years (vs ≤ 18 years) were identified as risk factors with IRRs of 2.89 (95% CI: 2.01–4.17), 2.17 (95% CI: 1.66–2.84), 5.31 (95% CI: 2.81–10.0) and 5.06 (95% CI: 2.59–9.86), respectively. Conclusion Italy experienced a nearly 2.6-fold increase in neuroinvasive TOSV incidence in 2022–23 vs 2016–21. Raising public awareness on risk factors and personal protection measures may enhance prevention efforts.

BackgroundAlbania is considered endemic for cystic echinococcosis (CE). Recent data on prevalence and incidence of CE in Europe suggests that the Balkan region is the epicentre of this neglected parasitic disease in Europe. In Albania, a retrospective study has estimated a mean incidence of 1.49 cases/100,000 people. We aimed to assess the prevalence of CE in eight municipalities across the country.Methodology/principal findingsWe enrolled participants aged >5 years in an ultrasound (US)-based screening for CE in 23 villages in eight municipalities from three prefectures. Participants were enrolled in the study after signing an informed consent and underwent a complete abdominal US. CE cysts were classified according to the WHO-IWGE ultrasound classification. A total of 3,710 participants were included in the study, of whom 2,685 (72.4%) were female. The median age of participants was 55 years (interquartile range, 42-64). Six confirmed CE cases were identified by US with cysts in the liver (1 CE2, 2 CE3a, 1 CE4 and 2 CE5). The crude prevalence of CE detected by US was 0.16% (95% CI 0.06-0.35), with a standardized prevalence of 0.11% (95% CI 0.02-0.21) according to the reference rural population 2023 in Albania. We calculated that the number of individuals who might currently be infected with CE in the rural area of this country was 908 (95% CI 138-1,678).ConclusionsThis was the first population-based US field survey on CE conducted in Albania. Our screening yielded a lower prevalence than expected. However, the presence of active cysts points to ongoing transmission. Our study had several limitations including the use of a convenience sample that limited the attendance of males and children. In the future, surveillance activities for CE should be strengthened in Albania to better characterize the epidemiology of the disease.

BACKGROUND:After a period of low SARS-CoV-2 activity, viral circulation increased in Europe from May 2024, driven by immune-evasive KP sublineages of the JN.1 variant. We estimated vaccine effectiveness (VE) of the XBB.1.5 dose administered in autumn 2023 against COVID-19-related hospitalisations and deaths in individuals 65 years of age or older during this period. METHODS:We conducted a multi-country cohort study across six EU nations in the VEBIS-EHR network using linked electronic health records. VE against COVID-19-related hospitalisation and death during June-August 2024 was estimated using Cox regression in a two-stage analysis, adjusting for demographics, comorbidities and prior vaccination history. RESULTS:Among individuals 65-79 and ≥ 80 years old, respectively, VE of the XBB.1.5 dose ≥ 6 months post administration was 13% (95% CI: -12% to 33%) and 7% (95% CI: -7% to 19%) against hospitalisation and 39% (95% CI: -7% to 65%) and 3% (95% CI: -23% to 23%) against deaths. CONCLUSIONS:XBB.1.5 vaccination provided minimal residual protection against severe COVID-19 outcomes among adults aged ≥ 65 years more than 6 months after vaccination, during the summer 2024 period of increased SARS-CoV-2 activity.

Background: Electronic health record (EHR)-based observational studies can rapidly provide real-world data on vaccine effectiveness (VE), particularly key during the COVID-19 pandemic. However, EHR data may be prone to misclassification and unmeasured confounding, requiring systematic mitigation to ensure robust findings. Methods: In VEBIS-EHR, a retrospective multi-country COVID-19 VE cohort study, we examined unmeasured confounding using a negative control outcome (death not related to COVID-19) and misclassification from varying data extraction intervals. The evaluation spanned two periods (November-December 2023, January-February 2024), encompassing up to 18.7 million individuals across six EU/EEA countries. Vaccine confounding-adjusted hazard ratios (aHRs) were pooled using random-effects meta-analysis. Results: aHRs against non-COVID-19 mortality ranged from 0.35 (95% CI: 0.28-0.44) to 0.70 (0.66-0.73) when comparing vaccinated versus unvaccinated. Delaying EHR data extraction modestly increased the capture of outcome and exposure events, with some variation by vaccination status. Site-level fluctuations in aHRs did not meaningfully alter the overall pooled VE, suggesting stable estimates despite misclassification related to extraction timing. Conclusions: We observed some evidence of unmeasured confounding when using non-COVID-19 deaths as a negative outcome, though the specificity of our negative control must be considered. This result may suggest overestimation of VE, but also the need for further analysis with more specific negative control outcomes and confounding-adjustment techniques. Addressing such confounding using richer data sources and more refined approaches remains critical to ensure accurate, timely VE estimates when using real-world EHR-based data. Extending the delay between the end of observation and data extraction modestly improves the completeness of exposure and outcome data, with limited effect on pooled VE estimates. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols ### Funding Statement All public health organizations involved received funding from the European Centre for Disease Prevention and Control (ECDC) implementing Framework Contract [ECDC/2021/018] "Vaccine effectiveness and impact of COVID-19 vaccines through routinely collected exposure and outcome using health registries" [RS/2022/DTS/24104]. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Belgium: Data linkage and collection within the data-warehouse have been approved by the information security committee. The study was conducted in accordance with the Declaration of Helsinki. Ethical approval was granted for the gathering of data from hospitalised patients by the Committee for Medical Ethics from the Ghent University Hospital (reference number BC-07507) and authorisation for possible individual data linkage using the national register number from the Information Security Committee (ISC) Social Security and Health (reference number IVC/KSZG/20/384). Linkage of hospitalised patient data to vaccination and testing within the LINK-VACC project was approved by the Medical Ethics Committee UZ Brussels, VUB on 3 February 2021 (reference number 2020/523), and authorisation from the ISC Social Security and Health (reference number IVC/KSZG/21/034). Denmark: Only administrative register data was used for the study. According to Danish law, ethics approval is exempt for such research, and the Danish Data Protection Agency, which is dedicated ethics and legal oversight body, thus waives ethical approval for the study of administrative register data when no individual contact of participants is necessary, and only aggregate results are included as findings. The study is, therefore, fully compliant with all legal and ethical requirements, and there are no further processes available regarding such studies. Navarre (Spain): The study was approved by Navarres Ethical Committee for Clinical Research, which waived the requirement of obtaining informed consent. Norway: Ethical approval was granted by Regional Committees for Medical and Health Research Ethics (REC) Southeast (reference number 122745). The Norwegian Institute of Public Health has performed a Data Protection Impact Assessment (DPIA) for Beredt C19. Portugal: The study received approval from the Ethical Committee and the Data Protection Officer of the Instituto Nacional de Saude Doutor Ricardo Jorge. Given that data was irreversibly anonymised, the need for the participants informed consent was waived by the Ethical Committee. Italy: This study, based on routinely collected data, was not submitted for approval to an ethical committee because the dissemination of COVID-19 surveillance data was authorised by the Italian law N. 52 of 19 May 2022, following the law decree N. 24 of 24 March 2022 (Article n. 13). Based on the same acts, the information on COVID-19 vaccination was retrieved by the Italian National Institute of Health using data from the National Immunisation Information System of the Italian Ministry of Health. Because of the retrospective design and the large size of the population under study, in accordance with the Authorisation n. 9 released by the Italian data protection authority on 15 December 2016, the individual informed consent was not requested for the conduction of this study. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Authors cannot share the data used for this study, access to which should be requested from the data owner institutions following their respective procedures.

We estimated the vaccine effectiveness (VE) of the XBB.1.5 dose given in the autumn 2023 against COVID-19-related hospitalisations and deaths in individuals 65 years of age or older across six EU countries reported following the 2024 summer peak in SARS-CoV-2 test positivity. A historical cohort study was performed by linking electronic health record databases. VE was estimated using Cox regression. Among individuals 65-79 years-old and ≥80 years-old, respectively, VE of the XBB.1.5 dose after ≥6 months post-administration was 13% (95%CI: -12%; 33%) and 7% (95%CI: -7%; 19%) against hospitalisation; and 39% (95%CI: -7%; 65%) and 3% (95%CI: -23%; 23%) against deaths. The 2023 autumnal dose showed very low to no effectiveness at the time of the period of increased SARS-CoV-2 spanning summer 2024. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols ### Funding Statement All the public health organisations involved received funding from the European Centre for Disease Prevention and Control (ECDC) implementing Framework Contract ECDC/2021/018 "Vaccine effectiveness and impact of COVID-19 vaccines through routinely collected exposure and outcome using health registries" (RS/2022/DTS/24104). In Portugal, this work was also supported by FCT, Fundacao para a Ciencia e Tecnologia, I.P. by project reference CEECINST/00049/2021/CP2817/CT0001 and DOI identifier 10.54499/CEECINST/00049/2021/CP2817/CT0001 ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Belgium: Data linkage and collection within the data-warehouse have been approved by the information security committee. The study was conducted in accordance with the Declaration of Helsinki. Ethical approval was granted for the gathering of data from hospitalised patients by the Committee for Medical Ethics from the Ghent University Hospital (reference number BC-07507) and authorisation for possible individual data linkage using the national register number from the Information Security Committee (ISC) Social Security and Health (reference number IVC/KSZG/20/384). Linkage of hospitalised patient data to vaccination and testing within the LINK-VACC project was approved by the Medical Ethics Committee UZ Brussels VUB on 3 February 2021 (reference number 2020/523), and authorisation from the ISC Social Security and Health (reference number IVC/KSZG/21/034). Denmark: Only administrative register data was used for the study. According to Danish law, ethics approval is exempt for such research, and the Danish Data Protection Agency, which is dedicated ethics and legal oversight body, thus waives ethical approval for the study of administrative register data when no individual contact of participants is necessary, and only aggregate results are included as findings. The study is, therefore, fully compliant with all legal and ethical requirements, and there are no further processes available regarding such studies. Navarre (Spain): The study was approved by Navarres Ethical Committee for Clinical Research, which waived the requirement of obtaining informed consent. Portugal: The study received approval from the Ethical Committee and the Data Protection Officer of the Instituto Nacional de Saude Doutor Ricardo Jorge. Given that data was irreversibly anonymised, the need for the participants informed consent was waived by the Ethical Committee. Italy: This study, based on routinely collected data, will not be submitted for approval to an ethical committee because the dissemination of COVID-19 surveillance data was authorised by the Italian law N. 52 of 19 May 2022, following the law decree N. 24 of 24 March 2022 (Article n. 13). Based on the same acts, the information on COVID-19 vaccination was retrieved by the Italian National Institute of Health using data from the National Immunisation Information System of the Italian Ministry of Health. Because of the retrospective design and the large size of the population under study, in accordance with the Authorisation n. 9 released by the Italian data protection authority on 15 December 2016, the individual informed consent was not requested for the conduction of this study. Sweden: The Swedish study is approved by the Swedish Ethical Review Authority (2020 06859, 2021 02186) and has conformed to the principles embodied in the Declaration of Helsinki. Consent to participate is not applicable as this is a register-based study. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Authors cannot share the data used for this study, which should instead be requested to the data owner institutions following their respective procedures.

Background: During the first year of the COVID-19 pandemic, vaccination programmes targeted children and adolescents to prevent severe outcomes of SARS-CoV-2 infection. Aim: To estimate COVID-19 vaccine effectiveness (VE) against hospitalisation due to COVID-19 in the paediatric population, among those with and without previously documented SARS-CoV-2 infection. Methods: We established a fixed cohort followed for 12 months in Denmark, Norway, Italy, Luxembourg, Navarre (Spain) and Portugal using routine electronic health registries. The study commenced with paediatric COVID-19 vaccination campaign at each site between June 2021 and January 2022. The outcome was hospitalisation with a laboratory-confirmed SARS-CoV-2 infection or COVID-19 as the main diagnosis. Using Cox proportional hazard models, VE was estimated as 1 minus the confounder-adjusted hazard ratio of COVID-19 hospitalisation between vaccinated and unvaccinated. A random-effects meta- analysis was used to pool VE estimates. Results: We included 4,144,667 5-11-year-olds and 3,861,841 12-17-year-olds. In 12-17-year-olds without previous infection, overall VE was 69% (95% CI: 40 to 84). VE declined with time since vaccination from 77%<= 3 months to 48% 180-365 days after immunisation. VE was 94% (95% CI: 90 to 96), 56% (95% CI: 3 to 80) and 41% (95% CI: -14 to 69) in the Delta, Omicron BA.1/BA.2 and BA.4/BA.5 periods, respectively. In 12-17-year-olds with previous infection, one dose VE was 80% (95% CI: 18 to 95). VE estimates were similar for 5-11-year-olds but with lower precision. Conclusion: Vaccines recommended for 5-17-year-olds provided protection against COVID-19 hospitalisation, regardless of a previously documented infection of SARS-CoV-2, with high levels of protection in the first 3 months of the vaccination.

Within an infrastructure to monitor vaccine effectiveness (VE) against hospitalization due to COVID-19 and COVID-19 related deaths from November 2022 to July 2023 in seven countries in real-world conditions (VEBIS network), we compared two approaches: (a) estimating VE of the first, second or third COVID-19 booster doses administered during the autumn of 2022, and (b) estimating VE of the autumn vaccination dose regardless of the number of prior doses (autumnal booster approach). Retrospective cohorts were constructed using Electronic Health Records at each participating site. Cox regressions with time-changing vaccination status were fit and site-specific estimates were combined using random-effects meta-analysis. VE estimates with both approaches were mostly similar, particularly shortly after the start of the vaccination campaign, and showed a similar timing of VE waning. However, autumnal booster estimates were more precise and showed a clearer trend, particularly compared to third booster estimates, as calendar time increased after the vaccination campaign and during periods of lower SARS-CoV-2 activity. Moreover, the decrease in protection by increasing calendar time was more clear and precise than when comparing protection by number of doses. Therefore, estimating VE under an autumnal booster framework emerges as a preferred method for future monitoring of COVID-19 vaccination campaigns.

INTRODUCTION:West Nile Virus (WNV) is a significant public health concern in southern Europe, with meteorological, climatic, and environmental factors playing a critical role in its transmission dynamics. This study aims to assess the short-term effects of meteorological variables on the incidence of WNV in five Italian regions in Northern Italy from 2012 to 2021. METHODS:Linking epidemiological data from the national surveillance system and local meteorological data, we conducted a Case-Time Series analysis to examine the association between WNV incident cases and temperature, humidity, and precipitation recorded up to ten weeks before case occurrence at the local administrative unit level. We employed conditional quasi-Poisson regression and distributed lag non-linear models to explore delayed effects. RESULTS:Our study analyzed 1110 autochthonous human cases of WNV. We found a positive association between WNV incidence and weekly mean temperature recorded between one to nine weeks before the diagnosis, with the highest effect at one week lag (IRR: 1.16; 95% CI 1.11-1.21). An increase in weekly precipitations between the sixth and ninth weeks before diagnosis was also positively associated with WNV incidence. Variations in minimum weekly humidity did not show a consistent impact. CONCLUSIONS:Our findings underscore the influence of temperature and, to a lesser extent, precipitation on WNV incidence in Northern Italy, highlighting the potential of climatic data in developing early warning systems for WNV surveillance and public health interventions.

Background As of 2024, vaccination remains the main mitigation measure against COVID-19, but there are contradictory results on whether people living with HIV (PLWH) are less protected by vaccines than people living without HIV (PLWoH). In this study we compared the risk of SARS-CoV-2 infection and COVID-19 hospitalisation following full vaccination in PLWH and PLWoH.Methods We linked data from the vaccination registry, the COVID-19 surveillance system and from healthcare/pharmacological registries in four Italian regions. We identified PLWH fully vaccinated (14 days post completion of the primary cycle) and matched them at a ratio of 1:4 with PLWoH by week of vaccine administration, age, sex, region of residence and comorbidities. Follow-up started on January 24, 2021, and lasted for a maximum of 234 days. We used the Kaplan-Meier estimator to calculate the cumulative incidence of infection and COVID-19 hospitalisation in both groups, and we compared risks using risk differences and ratios taking PLWoH as the reference group.Results We matched 42,771 PLWH with 171,084 PLWoH. The overall risk of breakthrough infection was similar in both groups with a rate ratio (RR) of 1.10 (95% confidence interval (CI):0.80-1.53). The absolute difference between groups at the end of the study period was 8.28 events per 10,000 person-days in the PLWH group (95%CI:-18.43-40.29). There was a non-significant increase the risk of COVID-19 hospitalisation among PLWH (RR:1.90; 95%CI:0.93-3.32) which corresponds to 6.73 hospitalisations per 10,000 individuals (95%CI: -0.57 to 14.87 per 10,000).Conclusions Our findings suggest PLWH were not at increased risk of breakthrough SARS-CoV-2 infection or COVID-19 hospitalisation following a primary cycle of mRNA vaccination.

This study analysed the evolution of the association of socioeconomic deprivation (SED) with SARS-CoV-2 infection and COVID-19 outcomes in urban Italy during the vaccine rollout in 2021. We conducted a retrospective cohort analysis between January and November 2021, comprising of 16,044,530 individuals aged ≥ 20 years, by linking national COVID-19 surveillance system data to the Italian SED index calculated at census block level. We estimated incidence rate ratios (IRRs) of infection and severe COVID-19 outcomes by SED tercile relative to the least deprived tercile, over three periods defined as low (0–10%); intermediate (> 10–60%) and high (> 60–74%) vaccination coverage. We found patterns of increasing relative socioeconomic inequalities in infection, hospitalisation and death as COVID-19 vaccination coverage increased. Between the low and high coverage periods, IRRs for the most deprived areas increased from 1.09 (95%CI 1.03–1.15) to 1.28 (95%CI 1.21–1.37) for infection; 1.48 (95%CI 1.36–1.61) to 2.02 (95%CI 1.82–2.25) for hospitalisation and 1.57 (95%CI 1.36–1.80) to 1.89 (95%CI 1.53–2.34) for death. Deprived populations in urban Italy should be considered as vulnerable groups in future pandemic preparedness plans to respond to COVID-19 in particular during mass vaccination roll out phases with gradual lifting of social distancing measures.

Evaluating how a COVID-19 seasonal vaccination program performed might help to plan future campaigns. This study aims to estimate the relative effectiveness (rVE) against severe COVID-19 of a seasonal booster dose over calendar time and by time since administration. We conducted a retrospective cohort analysis among 13,083,855 persons aged >= 60 years who were eligible to receive a seasonal booster at the start of the 2022-2023 vaccination campaign in Italy. We estimated rVE against severe COVID-19 (hospitalization or death) of a seasonal booster dose of bivalent (original/Omicron BA.4-5) mRNA vaccines by two-month calendar interval and at different times post-administration. We used multivariable Cox regression models, including vaccination as time-dependent exposure, to estimate adjusted hazard ratios (HR) and rVEs as [(1-HR)X100]. The rVE of a seasonal booster decreased from 64.9% (95% CI: 59.8-69.4) in October-November 2022 to 22.0% (95% CI: 15.4-28.0) in April-May 2023, when the majority of vaccinated persons (67%) had received the booster at least 4-6 months earlier. During the epidemic phase with prevalent circulation of the Omicron BA.5 subvariant, rVE of a seasonal booster received <= 90 days earlier was 83.0% (95% CI: 79.1-86.1), compared to 37.4% (95% CI: 25.5-47.5) during prevalent circulation of the Omicron XBB subvariant. During the XBB epidemic phase, rVE was estimated at 15.8% (95% CI: 9.1-20.1) 181-369 days post-administration of the booster dose. In all the analyses we observed similar trends of rVE between persons aged 60-79 and those >= 80 years, although estimates were somewhat lower for the oldest group. A seasonal booster dose received during the vaccination campaign provided additional protection against severe COVID-19 up to April-May 2023, after which the incidence of severe COVID-19 was much reduced. The results also suggest that the Omicron XBB subvariant might have partly escaped the immunity provided by the seasonal booster targeting the original and Omicron BA.4-5 strains of SARS-CoV-2.

Background: Surveillance data and vaccination registries are widely used to provide real-time vaccine effectiveness (VE) estimates, which can be biased due to underreported (i.e. under-ascertained and under-notified) infections. Here, we investigate how the magnitude and direction of this source of bias in retrospective cohort studies vary under different circumstances, including different levels of underreporting, heterogeneities in underreporting across vaccinated and unvaccinated, and different levels of pathogen circulation. Methods: We developed a stochastic individual-based model simulating the transmission dynamics of a respiratory virus and a large-scale vaccination campaign. Considering a baseline scenario with 22.5% yearly attack rate and 30% reporting ratio, we explored fourteen alternative scenarios, each modifying one or more baseline assumptions. Using synthetic individual-level surveillance data and vaccination registries produced by the model, we estimated the VE against documented infection taking as reference either unvaccinated or recently vaccinated individuals (within 14 days post-administration). Bias was quantified by comparing estimates to the known VE assumed in the model. Results: VE estimates were accurate when assuming homogeneous reporting ratios, even at low levels (10%), and moderate attack rates (<50%). A substantial downward bias in the estimation arose with homogeneous reporting and attack rates exceeding 50%. Mild heterogeneities in reporting ratios between vaccinated and unvaccinated strongly biased VE estimates, downward if cases in vaccinated were more likely to be reported and upward otherwise, particularly when taking as reference unvaccinated individuals. Conclusions: In observational studies, high attack rates or differences in underreporting between vaccinated and unvaccinated may result in biased VE estimates. This study underscores the critical importance of monitoring data quality and understanding biases in observational studies, to more adequately inform public health decisions.

Since the beginning of mass vaccination campaign for COVID-19 in Italy (December 2020) and following the rapidly increasing vaccine administration, sex differences have been emphasized. Nevertheless, incomplete and frequently incoherent sex-disaggregated data for COVID-19 vaccinations are currently available, and vaccines clinical studies generally do not include sex-specific analyses for safety and efficacy. We looked at sex variations in the COVID-19 vaccine's effectiveness against infection and severe disease outcomes. We conducted a nationwide retrospective cohort study on Italian population, linking information on COVID-19 vaccine administrations obtained through the Italian National Vaccination Registry, with the COVID-19 integrated surveillance system, held by the Istituto Superiore di Sanità. The results showed that, in all age groups, vaccine effectiveness (VE) was higher in the time-interval ≤120 days post-vaccination. In terms of the sex difference in vaccination effectiveness, men and women were protected against serious illness by vaccination in a comparable way, while men were protected against infection to a somewhat greater extent than women. To fully understand the mechanisms underlying the sex difference in vaccine response and its consequences for vaccine effectiveness and development, further research is required. The sex-related analysis of vaccine response may contribute to adjust vaccination strategies, improving overall public health programmes.

To monitor relative vaccine effectiveness (rVE) against COVID-19-related hospitalisation of the first, second and third COVID-19 booster (vs complete primary vaccination), we performed monthly Cox regression models using retrospective cohorts constructed from electronic health registries in eight European countries, October 2021–July 2023. Within 12 weeks of administration, each booster showed high rVE (≥ 70% for second and third boosters). However, as of July 2023, most of the relative benefit has waned, particularly in persons ≥ 80-years-old, while some protection remained in 65–79-year-olds.