Spatial spread of COVID-19 during the early pandemic phase in Italy.

Quantifying the potential spatial spread of an infectious pathogen is key to defining effective containment and control strategies. The aim of this study is to estimate the risk of SARS-CoV-2 transmission at different distances in Italy before the first regional lockdown was imposed, identifying important sources of national spreading. To do this, we leverage on a probabilistic model applied to daily symptomatic cases retrospectively ascertained in each Italian municipality with symptom onset between January 28 and March 7, 2020. Results are validated using a multi-patch dynamic transmission model reproducing the spatiotemporal distribution of identified cases. Our results show that the contribution of short-distance ( ≤ 10 k m ) transmission increased from less than 40% in the last week of January to more than 80% in the first week of March 2020. On March 7, 2020, that is the day before the first regional lockdown was imposed, more than 200 local transmission foci were contributing to the spread of SARS-CoV-2 in Italy. At the time, isolation measures imposed only on municipalities with at least ten ascertained cases would have left uncontrolled more than 75% of spillover transmission from the already affected municipalities. In early March, national-wide restrictions were required to curb short-distance transmission of SARS-CoV-2 in Italy.

Characterization of the internal working-life exposome using minimally and non-invasive sampling methods - a narrative review.

During recent years, we are moving away from the 'one exposure, one disease'-approach in occupational settings and towards a more comprehensive approach, taking into account the totality of exposures during a life course by using an exposome approach. Taking an exposome approach however is accompanied by many challenges, one of which, for example, relates to the collection of biological samples. Methods used for sample collection in occupational exposome studies should ideally be minimally invasive, while at the same time sensitive, and enable meaningful repeated sampling in a large population and over a longer time period. This might be hampered in specific situations e.g., people working in remote areas, during pandemics or with flexible work hours. In these situations, using self-sampling techniques might offer a solution. Therefore, our aim was to identify existing self-sampling techniques and to evaluate the applicability of these techniques in an occupational exposome context by conducting a literature review. We here present an overview of current self-sampling methodologies used to characterize the internal exposome. In addition, the use of different biological matrices was evaluated and subdivided based on their level of invasiveness and applicability in an occupational exposome context. In conclusion, this review and the overview of self-sampling techniques presented herein can serve as a guide in the design of future (occupational) exposome studies while circumventing sample collection challenges associated with exposome studies.

Population-wide measures due to the COVID-19 pandemic and exposome changes in the general population of Cyprus in March-May 2020.

Non-pharmacological interventions (e.g., stay-at-home orders, school closures, physical distancing) implemented during the COVID-19 pandemic are expected to have modified routines and lifestyles, eventually impacting key exposome parameters, including, among others, physical activity, diet and cleaning habits. The objectives were to describe the exposomic profile of the general Cypriot population and compliance to the population-wide measures implemented during March-May 2020 to lower the risk of SARS-CoV-2 transmission, and to simulate the population-wide measures' effect on social contacts and SARS-CoV-2 spread. A survey was conducted in March-May 2020 capturing different exposome parameters, e.g., individual characteristics, lifestyle/habits, time spent and contacts at home/work/elsewhere. We described the exposome parameters and their correlations. In an exposome-wide association analysis, we used the number of hours spent at home as an indicator of compliance to the measures. We generated synthetic human proximity networks, before and during the measures using the dynamic-[Formula: see text]1 model and simulated SARS-CoV-2 transmission (i.e., to identify possible places where higher transmission/number of cases could originate from) on the networks with a dynamic Susceptible-Exposed-Infectious-Recovered model. Overall, 594 respondents were included in the analysis (mean age 45.7 years, > 50% in very good health and communicating daily with friends/family via phone/online). The median number of contacts at home and at work decreased during the measures (from 3 to 2 and from 12 to 0, respectively) and the hours spent at home increased, indicating compliance with the measures. Increased time spent at home during the measures was associated with time spent at work before the measures (ß= -0.87, 95% CI [-1.21,-0.53]) as well as with being retired vs employed (ß= 2.32, 95% CI [1.70, 2.93]). The temporal network analysis indicated that most cases originated at work, while the synthetic human proximity networks adequately reproduced the observed SARS-CoV-2 spread. Exposome approaches (i.e., holistic characterization of the spatiotemporal variation of multiple exposures) would aid the comprehensive description of population-wide measures' impact and explore how behaviors and networks may shape SARS-CoV-2 transmission.

Rapid increase in neuroinvasive West Nile virus infections in humans, Italy, July 2022.

As in 2018, when a large West Nile virus (WNV) epidemic occurred, the 2022 vector season in Italy was marked by an early onset of WNV circulation in mosquitoes and birds. Human infections were limited until early July, when we observed a rapid increase in the number of cases. We describe the epidemiology of human infections and animal and vector surveillance for WNV and compare the more consolidated data of June and July 2022 with the same period in 2018.

An exposome-wide association study on body mass index in adolescents using the National Health and Nutrition Examination Survey (NHANES) 2003-2004 and 2013-2014 data.

Excess weight is a public health challenge affecting millions worldwide, including younger age groups. The human exposome concept presents a novel opportunity to comprehensively characterize all non-genetic disease determinants at susceptible time windows. This study aimed to describe the association between multiple lifestyle and clinical exposures and body mass index (BMI) in adolescents using the exposome framework. We conducted an exposome-wide association (ExWAS) study using U.S. National Health and Nutrition Examination Survey (NHANES) 2003-2004 wave for discovery of associations between study population characteristics and zBMI, and used the 2013-2014 wave to replicate analysis. We included non-diabetic and non-pregnant adolescents aged 12-18 years. We performed univariable and multivariable linear regression analysis adjusted for age, sex, race/ethnicity, household smoking, and income to poverty ratio, and corrected for false-discovery rate (FDR). A total of 1899 and 1224 participants were eligible from 2003-2004 and 2013-2014 survey waves. Weighted proportions of overweight were 18.4% and 18.5% whereas those for obese were 18.1% and 20.6% in 2003-2004 and 2013-2014, respectively. Retained exposure agents included 75 laboratory (clinical and biomarkers of environmental chemical exposures) and 64 lifestyle (63 dietary and 1 physical activity) variables. After FDR correction, univariable regression identified 27 and 12 predictors in discovery and replication datasets, respectively, while multivariable regression identified 22 and 9 predictors in discovery and replication datasets, respectively. Six were significant in both datasets: alanine aminotransferase, gamma glutamyl transferase, segmented neutrophils number, triglycerides; uric acid and white blood cell count. In this ExWAS study using NHANES data, we described associations between zBMI, nutritional, clinical and environmental factors in adolescents. Future studies are warranted to investigate the role of the identified predictors as early-stage biomarkers of increased BMI and associated pathologies among adolescents and to replicate findings to other populations.

A population-based cohort approach to assess excess mortality due to the spread of COVID-19 in Italy, January-May 2020.

AIMS: To assess the impact of the COVID-19 pandemic on all-cause mortality in Italy during the first wave of the epidemic, taking into consideration the geographical heterogeneity of the spread of COVID-19. METHODS: This study is a retrospective, population-based cohort study using national statistics throughout Italy. Survival analysis was applied to data aggregated by day of death, age groups, sex, and Italian administrative units (107 provinces). We applied Cox models to estimate the relative hazards (RH) of excess mortality, comparing all-cause deaths in 2020 with the expected deaths from all causes in the same time period. The RH of excess deaths was estimated in areas with a high, moderate, and low spread of COVID-19. We reported the estimate also restricting the analysis to the period of March-April 2020 (first peak of the epidemic). RESULTS: The study population consisted of 57,204,501 individuals living in Italy as of January 1, 2020. The number of excess deaths was 36,445, which accounts for 13.4% of excess mortalities from all causes during January-May 2020 (i.e., RH = 1.134; 95% confidence interval (CI): 1.129-1.140). In the macro-area with a relatively higher spread of COVID-19 (i.e., incidence rate, IR): 450-1,610 cases per 100,000 residents), the RH of excess deaths was 1.375 (95% CI: 1.364-1.386). In the area with a relatively moderate spread of COVID-19 (i.e., IR: 150-449 cases) it was 1.049 (95% CI: 1.038-1.060). In the area with a relatively lower spread of COVID-19 (i.e., IR: 30-149 cases), it was 0.967 (95% CI: 0.959-0.976). Between March and April (peak months of the first wave of the epidemic in Italy), we estimated an excess mortality from all causes of 43.5%. The RH of all-cause mortality for increments of 500 cases per 100,000 residents was 1.352 (95% CI: 1.346-1.359), corresponding to an increase of about 35%. CONCLUSIONS: Our analysis, making use of a population-based cohort model, estimated all-cause excess mortality in Italy taking account of both time period and of COVID-19 geographical spread. The study highlights the importance of a temporal/geographic framework in analyzing the risk of COVID-19-epidemy related mortality.

COVID-19 response: effectiveness of weekly rapid risk assessments, Italy.

PROBLEM: After Italy's first national restriction measures in 2020, a robust approach was needed to monitor the emerging epidemic of coronavirus disease 2019 (COVID-19) at subnational level and provide data to inform the strengthening or easing of epidemic control measures. APPROACH: We adapted the European Centre for Disease Prevention and Control rapid risk assessment tool by including quantitative and qualitative indicators from existing national surveillance systems. We defined COVID-19 risk as a combination of the probability of uncontrolled transmission of severe acute respiratory syndrome coronavirus 2 and of an unsustainable impact of COVID-19 cases on hospital services, adjusted in relation to the health system's resilience. The monitoring system was implemented with no additional cost in May 2020. LOCAL SETTING: The infectious diseases surveillance system in Italy uses consistent data collection methods across the country's decentralized regions and autonomous provinces. RELEVANT CHANGES: Weekly risk assessments using this approach were sustainable in monitoring the epidemic at regional level from 4 May 2020 to 24 September 2021. The tool provided reliable assessments of when and where a rapid increase in demand for health-care services would occur if control or mitigation measures were not increased in the following 3 weeks. LESSONS LEARNT: Although the system worked well, framing the risk assessment tool in a legal decree hampered its flexibility, as indicators could not be changed without changing the law. The relative complexity of the tool, the impossibility of real-time validation and its use for the definition of restrictions posed communication challenges.

Co-circulation of SARS-CoV-2 Alpha and Gamma variants in Italy, February and March 2021.

BackgroundSeveral SARS-CoV-2 variants of concern (VOC) have emerged through 2020 and 2021. There is need for tools to estimate the relative transmissibility of emerging variants of SARS-CoV-2 with respect to circulating strains.AimWe aimed to assess the prevalence of co-circulating VOC in Italy and estimate their relative transmissibility.MethodsWe conducted two genomic surveillance surveys on 18 February and 18 March 2021 across the whole Italian territory covering 3,243 clinical samples and developed a mathematical model that describes the dynamics of co-circulating strains.ResultsThe Alpha variant was already dominant on 18 February in a majority of regions/autonomous provinces (national prevalence: 54%) and almost completely replaced historical lineages by 18 March (dominant across Italy, national prevalence: 86%). We found a substantial proportion of the Gamma variant on 18 February, almost exclusively in central Italy (prevalence: 19%), which remained similar on 18 March. Nationally, the mean relative transmissibility of Alpha ranged at 1.55-1.57 times the level of historical lineages (95% CrI: 1.45-1.66). The relative transmissibility of Gamma varied according to the assumed degree of cross-protection from infection with other lineages and ranged from 1.12 (95% CrI: 1.03-1.23) with complete immune evasion to 1.39 (95% CrI: 1.26-1.56) for complete cross-protection.ConclusionWe assessed the relative advantage of competing viral strains, using a mathematical model assuming different degrees of cross-protection. We found substantial co-circulation of Alpha and Gamma in Italy. Gamma was not able to outcompete Alpha, probably because of its lower transmissibility.

Excess Mortality in Italy During the COVID-19 Pandemic: Assessing the Differences Between the First and the Second Wave, Year 2020.

COVID-19 dramatically influenced mortality worldwide, in Italy as well, the first European country to experience the Sars-Cov2 epidemic. Many countries reported a two-wave pattern of COVID-19 deaths; however, studies comparing the two waves are limited. The objective of the study was to compare all-cause excess mortality between the two waves that occurred during the year 2020 using nationwide data. All-cause excess mortalities were estimated using negative binomial models with time modeled by quadratic splines. The models were also applied to estimate all-cause excess deaths "not directly attributable to COVD-19", i.e., without a previous COVID-19 diagnosis. During the first wave (25th February-31st May), we estimated 52,437 excess deaths (95% CI: 49,213-55,863) and 50,979 (95% CI: 50,333-51,425) during the second phase (10th October-31st December), corresponding to percentage 34.8% (95% CI: 33.8%-35.8%) in the second wave and 31.0% (95%CI: 27.2%-35.4%) in the first. During both waves, all-cause excess deaths percentages were higher in northern regions (59.1% during the first and 42.2% in the second wave), with a significant increase in the rest of Italy (from 6.7% to 27.1%) during the second wave. Males and those aged 80 or over were the most hit groups with an increase in both during the second wave. Excess deaths not directly attributable to COVID-19 decreased during the second phase with respect to the first phase, from 10.8% (95% CI: 9.5%-12.4%) to 7.7% (95% CI: 7.5%-7.9%), respectively. The percentage increase in excess deaths from all causes suggests in Italy a different impact of the SARS-CoV-2 virus during the second wave in 2020. The decrease in excess deaths not directly attributable to COVID-19 may indicate an improvement in the preparedness of the Italian health care services during this second wave, in the detection of COVID-19 diagnoses and/or clinical practice toward the other severe diseases.

Socioeconomic patterns and COVID-19 outcomes before, during and after the lockdown in Italy (2020).

The objective was to investigate the association between deprivation and COVID-19 outcomes in Italy during pre-lockdown, lockdown and post-lockdown periods using a retrospective cohort study with 38,534,169 citizens and 222,875 COVID-19 cases. Multilevel negative binomial regression models, adjusting for age, sex, population-density and region of residence were conducted to evaluate the association between area-level deprivation and COVID-19 incidence, case-hospitalisation rate and case-fatality. During lockdown and post-lockdown, but not during pre-lockdown, higher incidence of cases was observed in the most deprived municipalities compared with the least deprived ones. No differences in case-hospitalisation and case-fatality according to deprivation were observed in any period under study.

Impact of tiered restrictions on human activities and the epidemiology of the second wave of COVID-19 in Italy.

To counter the second COVID-19 wave in autumn 2020, the Italian government introduced a system of physical distancing measures organized in progressively restrictive tiers (coded as yellow, orange, and red) imposed on a regional basis according to real-time epidemiological risk assessments. We leverage the data from the Italian COVID-19 integrated surveillance system and publicly available mobility data to evaluate the impact of the three-tiered regional restriction system on human activities, SARS-CoV-2 transmissibility and hospitalization burden in Italy. The individuals' attendance to locations outside the residential settings was progressively reduced with tiers, but less than during the national lockdown against the first COVID-19 wave in the spring. The reproduction number R(t) decreased below the epidemic threshold in 85 out of 107 provinces after the introduction of the tier system, reaching average values of about 0.95-1.02 in the yellow tier, 0.80-0.93 in the orange tier and 0.74-0.83 in the red tier. We estimate that the reduced transmissibility resulted in averting about 36% of the hospitalizations between November 6 and November 25, 2020. These results are instrumental to inform public health efforts aimed at preventing future resurgence of cases.

Initial impact of SARS-Cov-2 vaccination on healthcare workers in Italy- Update on the 28th of March 2021.

In Italy, the COVID-19 vaccination campaign started in December 2020 with the vaccination of healthcare workers (HCW). To analyse the real-life impact that vaccination is having on this population group, we measured the association between week of diagnosis and HCW status using log-binomial regression. By the week 22-28 March, we observed a 74% reduction (PPR 0.26; 95% CI 0.22-0.29) in the proportion of cases reported as HCW and 81% reduction in the proportion of symptomatic cases reported as HCW, compared with the week with the lowest proportion of cases among HCWs prior to the vaccination campaign (31 August-7 September). The reduction, both in relative and absolute terms, of COVID-19 cases in HCWs that started around 30 days after the start of the vaccination campaign suggest that COVID-19 vaccines are being effective in preventing infection in this group.

SARS-CoV-2 population-based seroprevalence studies in Europe: a scoping review.

OBJECTIVES: We aimed to review SARS-CoV-2 seroprevalence studies conducted in Europe to understand how they may be used to inform ongoing control strategies for COVID-19. DESIGN: Scoping review of peer-reviewed publications and manuscripts on preprint servers from January 2020 to 15 September 2020. PRIMARY MEASURE: Seroprevalence estimate (and lower and upper CIs). For studies conducted across a country or territory, we used the seroprevalence estimate and the upper and lower CIs and compared them to the total number of reported infections to calculate the ratio of reported to expected infections. RESULTS: We identified 23 population-based seroprevalence studies conducted in Europe. Among 12 general population studies, seroprevalence ranged from 0.42% among residual clinical samples in Greece to 13.6% in an area of high transmission in Gangelt, Germany. Of the eight studies in blood donors, seroprevalence ranged from 0.91% in North-Western Germany to 23.3% in a high-transmission area in Lombardy region, Italy. In three studies which recruited individuals through employment, seroprevalence ranged from 0.5% among factory workers in Frankfurt, Germany, to 10.2% among university employees in Milan, Italy. In comparison to nationally reported cases, the extent of infection, as derived from these seroprevalence estimates, is manyfold higher and largely heterogeneous. CONCLUSION: Exposure to the virus in Europe has not reached a level of infection that would prevent further circulation of the virus. Effective vaccine candidates are urgently required to deliver the level of immunity in the population.

Evolution of Pathology Patterns in Persons Who Died From COVID-19 in Italy: A National Study Based on Death Certificates.

Background: In Italy, during the first epidemic wave of 2020, the peak of coronavirus disease 2019 (COVID-19) mortality was reached at the end of March. Afterward, a progressive reduction was observed until much lower figures were reached during the summer, resulting from the contained circulation of SARS-CoV-2. This study aimed to determine if and how the pathological patterns of the individuals deceased from COVID-19 changed during the phases of epidemic waves in terms of: (i) main cause of death, (ii) comorbidities, and (iii) complications related to death. Methods: Death certificates of persons who died and tested positive for SARS-CoV-2, provided by the National Surveillance system, were coded according to ICD rev10. Deaths due to COVID-19 were defined as those in which COVID-19 was the underlying cause of death. Results: The percentage of COVID-19 deaths varied over time. It decreased in the downward phase of the epidemic curve (76.6 vs. 88.7%). In February-April 2020, hypertensive heart disease was mentioned as a comorbidity in 18.5% of death certificates, followed by diabetes (15.9% of cases), ischemic heart disease (13.1%), and neoplasms (12.1%). In May-September, the most frequent comorbidity was neoplasms (17.3% of cases), followed by hypertensive heart disease (14.9%), diabetes (14.8%), and dementia/Alzheimer's disease (11.9%). The most mentioned complications in both periods were pneumonia and respiratory failure with a frequency far higher than any other condition (78.4% in February-April 2020 and 63.7% in May-September 2020). Discussion: The age of patients dying from COVID-19 and their disease burden increased in the May-September 2020 period. A more serious disease burden was observed in this period, with a significantly higher frequency of chronic pathologies. Our study suggests better control of the virus' lethality in the second phase of the epidemic, when the health system was less burdened. Moreover, COVID-19 care protocols had been created in hospitals, and knowledge about the diagnosis and treatment of COVID-19 had improved, potentially leading to more accurate diagnosis and better treatment. All these factors may have improved survival in patients with COVID-19 and led to a shift in mortality to older, more vulnerable, and complex patients.

Growth and neurodevelopment in low birth weight versus normal birth weight infants from birth to 24 months, born in an obstetric emergency hospital in Haiti, a prospective cohort study.

BACKGROUND: Low birthweight (LBW) infants are at higher risk of mortality and morbidity (growth, chronic disease and neurological problems) during their life. Due to the high incidence of (pre-) eclampsia in Haiti, LBW infants are common. We assessed the anthropometric growth (weight and length) and neurodevelopmental delay in LBW and normal birthweight (NBW) infants born at an obstetric emergency hospital in Port au Prince, Haiti, between 2014 and 2017. METHODS: Infants were followed at discharge and 3, 6, 12, 15, 18, 21 and 24 months of corrected gestational age. At each visit they underwent a physical checkup (weight, length, physical abnormalities, identification of morbidities). At 6, 12, 18 and 24 months they underwent a neurodevelopmental assessment using the Bayley Scale III (motor, cognitive and communication skills). We modelled the trajectories between birth and 24 months of age of NBW compared to LBW infants for weight, length, and raw scores for Bayley III assessments using mixed linear models. RESULTS: In total 500 LBW and 210 NBW infants were recruited of which 333 (46.7%) were followed up for 24 months (127 NBW; 60.5% and 206 LBW; 41.2%) and 150 died (LBW = 137 and NBW = 13). LBW and NBW babies gained a mean 15.8 g and 11.4 g per kg of weight from discharge per day respectively. The speed of weight gain decreased rapidly after 3 months in both groups. Both groups grow rapidly up to 6 months of age. LBW grew more than the NBW group during this period (22.8 cm vs. 21.1 cm). Both groups had WHZ scores <- 2 up to 15 months. At 24 months NBW babies scored significantly higher on the Bayley scales for gross motor, cognitive and receptive and expressive communication skills. There was no difference between the groups for fine motor skills. CONCLUSION: LBW babies that survive neonatal care in urban Haiti and live up to 24 months of age, perform similar to their NBW for weight, length and fine motor skills. LBW babies are delayed in gross motor, cognitive and communication skills development. Further research on the clinical significance of these findings and long term implications of this neurodevelopmental delay is needed.

Exposome changes in primary school children following the wide population non-pharmacological interventions implemented due to COVID-19 in Cyprus: A national survey.

BACKGROUND: Non-pharmacological interventions (NPI), including lockdowns, have been used to address the COVID-19 pandemic. We describe changes in the environment and lifestyle of school children in Cyprus before the lockdown and during school re-opening, and assess compliance to NPI, using the exposome concept. METHODS: During June 2020, parents completed an online questionnaire about their children's lifestyle/behaviours for two periods; school re-opening (May 21-June 26) following the population-wide lockdown, and the school period before lockdown (before March). FINDINGS: Responses were received for 1509 children from over 180 primary schools. More than 72% of children complied with most NPI measures; however, only 48% decreased the number of vulnerable contacts at home. Sugary food consumption was higher in the post-lockdown period with 37% and 26% of the children eating sugary items daily and 4-6 times/week, compared to 33% and 19%, respectively, for the pre-lockdown period (p<0.001). Children's physical activity decreased compared to pre-lockdown (p<0.001), while screen time increased in the post-lockdown period, with 25% of children spending 4-7 hours/day in front of screens vs. 10% in the pre-lockdown period (p<0.001). About half of the children washed their hands with soap 4-7 times/day post-lockdown vs. 30% in the pre-lockdown period (p<0.001). INTERPRETATION: This national survey showed a high degree of compliance to NPI measures among school children. Furthermore, the exposome profile of children may be affected in the months following NPI measures due to alterations in diet, physical activity, sedentary behaviour, and hand hygiene habits. FUNDING: Partial funding by the EXPOSOGAS project, H2020 Research and Innovation Programme (grant #810995).

Epidemiological characteristics of COVID-19 cases in non-Italian nationals notified to the Italian surveillance system.

BACKGROUND: International literature suggests that disadvantaged groups are at higher risk of morbidity and mortality from SARS-CoV-2 infection due to poorer living/working conditions and barriers to healthcare access. Yet, to date, there is no evidence of this disproportionate impact on non-national individuals, including economic migrants, short-term travellers and refugees. METHODS: We analyzed data from the Italian surveillance system of all COVID-19 laboratory-confirmed cases tested positive from the beginning of the outbreak (20th of February) to the 19th of July 2020. We used multilevel negative-binomial regression models to compare the case fatality and the rate of admission to hospital and intensive care unit (ICU) between Italian and non-Italian nationals. The analysis was adjusted for differences in demographic characteristics, pre-existing comorbidities, and period of diagnosis. RESULTS: We analyzed 213 180 COVID-19 cases, including 15 974 (7.5%) non-Italian nationals. We found that, compared to Italian cases, non-Italian cases were diagnosed at a later date and were more likely to be hospitalized {[adjusted rate ratio (ARR)=1.39, 95% confidence interval (CI): 1.33-1.44]} and admitted to ICU (ARR=1.19, 95% CI: 1.07-1.32), with differences being more pronounced in those coming from countries with lower human development index (HDI). We also observed an increased risk of death in non-Italian cases from low-HDI countries (ARR=1.32, 95% CI: 1.01-1.75). CONCLUSIONS: A delayed diagnosis in non-Italian cases could explain their worse outcomes compared to Italian cases. Ensuring early access to diagnosis and treatment to non-Italians could facilitate the control of SARS-CoV-2 transmission and improve health outcomes in all people living in Italy, regardless of nationality.

Evaluation of the national surveillance system for invasive meningococcal disease, Italy, 2015-2018.

Enhanced laboratory-based surveillance of invasive meningococcal disease (IMD) in Italy was only assessed indirectly by numerically comparing surveillance data cases with hospital discharge records (HDR). In this study, we evaluated the completeness, timeliness and sensitivity of the IMD surveillance in Italy from 2015 to 2018. Completeness and timeliness were described at the national and subnational level. A capture-recapture analysis was conducted to evaluate the sensitivity and positive predictive value (PPV) using HDR as the external source with a combination of deterministic and probabilistic approaches. The characteristics of the unmatched vs. matched cases were compared using multivariable Poisson modeling. Overall, the completeness of data improved, except for specific variables. Timeliness of notifications also improved to a median of 4 days from onset to reporting. For the years 2015-2017, the sensitivity of the surveillance was estimated at 71.4% and the PPV at 77.5%, changing to 80.6% and 66.9% respectively after removing cases with a secondary meningitis diagnosis. We noted substantial sub-national differences. In 2018 sensitivity was 66.5% (135/203) and the PPV was 79.4% (135/170). The adjusted relative risk of being unmatched in 2015-2017 was higher in cases that were ≥60 years, had missing information or symptom onset in December. The IMD surveillance system overall performs well with completeness and timeliness improving in time. Specific challenges identified for individual variables should guide further improvement. Notwithstanding limitations posed by the comparison database, sensitivity and PPV are promising. The study highlights that promoting etiological ascertainment in people ≥60 years and addressing sub-national challenges are the main current challenges to address.