Web-based surveillance of respiratory infection outbreaks: retrospective analysis of Italian COVID-19 epidemic waves using Google Trends.

Introduction: Large-scale diagnostic testing has been proven insufficient to promptly monitor the spread of the Coronavirus disease 2019. Electronic resources may provide better insight into the early detection of epidemics. We aimed to retrospectively explore whether the Google search volume has been useful in detecting Severe Acute Respiratory Syndrome Coronavirus outbreaks early compared to the swab-based surveillance system. Methods: The Google Trends website was used by applying the research to three Italian regions (Lombardy, Marche, and Sicily), covering 16 million Italian citizens. An autoregressive-moving-average model was fitted, and residual charts were plotted to detect outliers in weekly searches of five keywords. Signals that occurred during periods labelled as free from epidemics were used to measure Positive Predictive Values and False Negative Rates in anticipating the epidemic wave occurrence. Results: Signals from "fever," "cough," and "sore throat" showed better performance than those from "loss of smell" and "loss of taste." More than 80% of true epidemic waves were detected early by the occurrence of at least an outlier signal in Lombardy, although this implies a 20% false alarm signals. Performance was poorer for Sicily and Marche. Conclusion: Monitoring the volume of Google searches can be a valuable tool for early detection of respiratory infectious disease outbreaks, particularly in areas with high access to home internet. The inclusion of web-based syndromic keywords is promising as it could facilitate the containment of COVID-19 and perhaps other unknown infectious diseases in the future.

Are we equally at risk of changing smoking behavior during a public health crisis? Impact of educational level on smoking from the TEMPO cohort.

BACKGROUND: The COVID-19 pandemic as a public health crisis has led to a significant increase in mental health difficulties. Smoking is strongly associated with mental health conditions, which is why the pandemic might have influenced the otherwise decline in smoking rates. Persons belonging to socioeconomically disadvantaged groups may be particularly affected, both because the pandemic has exacerbated existing social inequalities and because this group was more likely to smoke before the pandemic. We examined smoking prevalence in a French cohort study, focusing on differences between educational attainment. In addition, we examined the association between interpersonal changes in tobacco consumption and educational level from 2018 to 2021. METHODS: Using four assessments of smoking status available from 2009 to 2021, we estimated smoking prevalence over time, stratified by highest educational level in the TEMPO cohort and the difference was tested using chi2 test. We studied the association between interpersonal change in smoking status between 2018 and 2021 and educational attainment among 148 smokers, using multinomial logistic regression. RESULTS: Smoking prevalence was higher among those with low education. The difference between the two groups increased from 2020 to 2021 (4.8-9.4%, p < 0.001). Smokers with high educational level were more likely to decrease their tobacco consumption from 2018 to 2021 compared to low educated smokers (aOR = 2.72 [1.26;5.89]). CONCLUSION: Current findings showed a widening of the social inequality gap in relation to smoking rates, underscoring the increased vulnerability of persons with low educational level to smoking and the likely inadequate focus on social inequalities in relation to tobacco control policies during the pandemic.

Natural and vaccine-induced immunity are equivalent for the protection against SARS-CoV-2 infection.

OBJECTIVES: To compare the long-term cumulative risk of SARS-CoV-2 infection associated with natural and vaccine-induced immunity. METHODS: Retrospective population-based cohort study based on registry of COVID-19 vaccinations and SARS-CoV-2 infections among 9.1 million citizens of Lombardy, Italy, eligible for vaccination on 27th December 2020. Those who developed SARS-CoV-2 infection from 24th May to 14th September 2021, provided they did not yet receive the COVID-19 vaccine when infection was confirmed, and those who received the second mRNA vaccine dose, provided they had not yet developed the infection, were selected to be 1:1 matched for sex, age and index date. The latter corresponded to 90 days after confirmed infection or 14 days after vaccine administration. A control cohort including citizens who, on the index date, had neither developed infection nor received vaccination was also selected. Kaplan-Meier curves were used for comparing the cumulative incidence of new SARS-CoV-2 infection from the index date until 22nd June 2022. RESULTS: Overall, 19,418 1:1:1 risk-sets were included. After 9 months of follow-up, the cumulative risk of new SARS-CoV-2 infection was 21.8%, 22.0%, and 25.9%, respectively, among exposed to natural immunity, vaccine-induced immunity and unexposed. CONCLUSIONS: Equivalent potential for protecting against new SARS-CoV-2 infection was observed.

Impact of the First and Second Lockdown for COVID-19 Pandemic on Preterm Birth, Low Birth Weight, Stillbirth, Mode of Labor, and of Delivery in Lombardy, Italy.

We investigated the effect of lockdown measures implemented in Lombardy on selected obstetric and perinatal outcomes. Births that occurred during the two lockdowns imposed (i.e., the first from 16 March to 2 June 2020 and the second from 3 November 2020 to 5 April 2021) and the comparison periods (i.e., the first from 16 March to 2 June 2018 and the second from 3 November 2018 to 5 April 2019) were identified using regional healthcare databases. The distribution of births according to the selected outcomes was computed and the Chi-square test was used for testing differences in the periods compared. During the two lockdowns, we observed a lower proportion of low birth weight, from 6.8% in the comparison period to 6.1% in the first lockdown (p = 0.019), and from 6.5% to 6.1% in the second one (p = 0.109). The proportion of preterm births decreased from 6.8% to 6.3% in the first lockdown (p = 0.097), and from 6.2% to 6.0% in the second one (p = 0.172). No differences in stillbirth rate emerged for both lockdowns. Induction of labor was more frequent during both lockdowns, from 28.6% to 32.7% in the first (p < 0.0001), and from 29.9% to 33.2% in the second one (p < 0.0001). Cesarean section was less frequent during the second lockdown.

Research strategies in treatment of hypertension: value of retrospective real-life data.

This review will discuss the limitations of data collected by RCTs in relation to their applicability to daily life clinical management. It will then argue that these limitations are only partially overcome by modifications of RCT design and conduction (e.g. 'pragmatic trials') while being substantially attenuated by real-life-derived research, which can fill many gaps left by trial-collected evidence and have thus an important complementary value. The focus will be on the real-life research approach based on the retrospective analysis of the now widely available healthcare utilization databases (formerly known as administrative databases), which will be discussed in detail for their multiple advantages as well as challenges. Emphasis will be given to the potential of these databases to provide low-cost information over long periods on many different healthcare issues, drug therapies in particular, from the general population to clinically important subgroups, including (i) prognostic aspects of treatments implemented at the medical practice level via hospitalization and fatality data and (ii) medical practice-related phenomena such as low treatment adherence and therapeutic inertia (unsatisfactorily evaluated by RCTs). It will also be mentioned that thanks to the current availability of these data in electronic format, results can be obtained quickly, helping timely decisions under emergencies. The potential shortcomings of this approach (confounding by indication, misclassification, and selection bias) will also be discussed along with their possible minimization by suitable analytic means. Finally, examples of the contributions of studies on hypertension and other cardiovascular risk factors will be offered based on retrospective healthcare utilization databases that have provided information on real-life cardiovascular treatments unavailable via RCTs.

Detecting early signals of COVID-19 outbreaks in 2020 in small areas by monitoring healthcare utilisation databases: first lessons learned from the Italian Alert_CoV project.

BackgroundDuring the COVID-19 pandemic, large-scale diagnostic testing and contact tracing have proven insufficient to promptly monitor the spread of infections.AimTo develop and retrospectively evaluate a system identifying aberrations in the use of selected healthcare services to timely detect COVID-19 outbreaks in small areas.MethodsData were retrieved from the healthcare utilisation (HCU) databases of the Lombardy Region, Italy. We identified eight services suggesting a respiratory infection (syndromic proxies). Count time series reporting the weekly occurrence of each proxy from 2015 to 2020 were generated considering small administrative areas (i.e. census units of Cremona and Mantua provinces). The ability to uncover aberrations during 2020 was tested for two algorithms: the improved Farrington algorithm and the generalised likelihood ratio-based procedure for negative binomial counts. To evaluate these algorithms' performance in detecting outbreaks earlier than the standard surveillance, confirmed outbreaks, defined according to the weekly number of confirmed COVID-19 cases, were used as reference. Performances were assessed separately for the first and second semester of the year. Proxies positively impacting performance were identified.ResultsWe estimated that 70% of outbreaks could be detected early using the proposed approach, with a corresponding false positive rate of ca 20%. Performance did not substantially differ either between algorithms or semesters. The best proxies included emergency calls for respiratory or infectious disease causes and emergency room visits.ConclusionImplementing HCU-based monitoring systems in small areas deserves further investigations as it could facilitate the containment of COVID-19 and other unknown infectious diseases in the future.

Impact of work arrangements during the COVID-19 pandemic on mental health in France.

•Symptoms of anxiety/depression were found in 28.8% of the participants at least once.•Unemployment and financial difficulties were associated with anxiety/depression.•Targeted mental health support could lessen mental health impact.

Increased risk of myocarditis and pericarditis and reduced likelihood of severe clinical outcomes associated with COVID-19 vaccination: a cohort study in Lombardy, Italy.

INTRODUCTION: We aimed to assess harms (post-vaccine myocarditis and pericarditis) and benefits (preventing severe disease) of COVID-19 vaccination. METHODS: We conducted a population-based retrospective cohort study. Using the integrated platform of the vaccination campaign of Lombardy Region (Italy), after the exclusion of 24,188 individuals not beneficiaries of the Regional Health Service, 9,184,146 citizens candidates to vaccine at December 27, 2020 were followed until November 30, 2021 (the loss to follow-up rate was 0.5%). From the date of administration of each vaccine dose to day 28 post-administration, three periods that covered exposure to the first, second, and third dose were defined. The benefit-risk profile of vaccines was performed by comparing the number needed to harm (NNH) and number needed to treat (NNT) by sex, age, and vaccine type. RESULTS: Incidence rates of myocarditis were 9.9 and 5.2 per million person-months during the exposure and no-exposure periods, respectively, and the incidence rates of pericarditis were 19.5 and 15.9 per million person-months, respectively. The risk of myocarditis was highest following exposure to the second dose of the Moderna vaccine (adjusted HR: 5.5, 95% CI: 3.7 to 8.1). Exposure to the Moderna vaccine was also associated with an increased risk of pericarditis (adjusted HR 2.2, 1.5 to 3.1). NNT was higher than NNH (9471 vs. 7213) for 16 to 19-year-old men who received the Moderna vaccine, while all other sex, age, and vaccine subgroups had a favourable harm-benefit profile. CONCLUSIONS: Men 16 to 19 years of age has the highest rates of myocarditis within a few days after receiving the Moderna vaccines. The balance between harms and benefits was almost always in favour of vaccination.

Early Detection of SARS-CoV-2 Epidemic Waves: Lessons from the Syndromic Surveillance in Lombardy, Italy.

We evaluated the performance of the exponentially weighted moving average (EWMA) model for comparing two families of predictors (i.e., structured and unstructured data from visits to the emergency department (ED)) for the early detection of SARS-CoV-2 epidemic waves. The study included data from 1,282,100 ED visits between 1 January 2011 and 9 December 2021 to a local health unit in Lombardy, Italy. A regression model with an autoregressive integrated moving average (ARIMA) error term was fitted. EWMA residual charts were then plotted to detect outliers in the frequency of the daily ED visits made due to the presence of a respiratory syndrome (based on coded diagnoses) or respiratory symptoms (based on free text data). Alarm signals were compared with the number of confirmed SARS-CoV-2 infections. Overall, 150,300 ED visits were encoded as relating to respiratory syndromes and 87,696 to respiratory symptoms. Four strong alarm signals were detected in March and November 2020 and 2021, coinciding with the onset of the pandemic waves. Alarm signals generated for the respiratory symptoms preceded the occurrence of the first and last pandemic waves. We concluded that the EWMA model is a promising tool for predicting pandemic wave onset.

Factors associated with severe or fatal clinical manifestations of SARS-CoV-2 infection after receiving the third dose of vaccine.

BACKGROUND: Little is known about vulnerability to severe COVID-19 illness after vaccination completion with three doses of vaccine against COVID-19. OBJECTIVES: To identify individual features associated with increased risk of severe clinical manifestation of SARS-CoV-2 infections after receiving the third dose of vaccine against COVID-19. METHODS: We performed a nested case-control study based on 3,360,116 citizens from Lombardy, Italy, aged 12 years or older who received the third dose of vaccine against COVID-19 from 20 September through 31 December 2021. Individuals were followed from 14 days after vaccination completion until the occurrence of severe COVID-19 illness, death unrelated to COVID-19, emigration or 15 March 2022. For each case, controls were randomly selected to be 1:10 matched for the date of vaccination completion and municipality of residence. The association between candidate predictors and outcome was assessed through multivariable conditional logistic regression models. RESULTS: During 12,538,330 person-months of follow-up, 5171 cases of severe illness occurred. As age increased, a trend towards increasing odds of severe illness was observed. Male gender was a significant risk factor. As the number of contacts with the Regional Health Service increased, a trend towards increasing odds of severe illness was observed. Having had a previous SARS-CoV-2 infection was a significant protective factor. Having received the Moderna vaccine significantly decreased the odds of severe illness. Significant higher odds were associated with 42 diseases/conditions. Odds ratios ranged from 1.23 (diseases of the musculoskeletal system) to 5.00 (autoimmune disease). CONCLUSIONS: This study provides useful insights for establishing priority in fourth-dose vaccination programs.

Vulnerability Predictors of Post-Vaccine SARS-CoV-2 Infection and Disease-Empirical Evidence from a Large Population-Based Italian Platform.

We aimed to identify individual features associated with increased risk of post-vaccine SARS-CoV-2 infection and severe COVID-19 illness. We performed a nested case-control study based on 5,350,295 citizens from Lombardy, Italy, aged ≥ 12 years who received a complete anti-COVID-19 vaccination from 17 January 2021 to 31 July 2021, and followed from 14 days after vaccine completion to 11 November 2021. Overall, 17,996 infections and 3023 severe illness cases occurred. For each case, controls were 1:1 (infection cases) or 1:10 (severe illness cases) matched for municipality of residence and date of vaccination completion. The association between selected predictors (sex, age, previous occurrence of SARS-CoV-2 infection, type of vaccine received, number of previous contacts with the Regional Health Service (RHS), and the presence of 59 diseases) and outcomes was assessed by using multivariable conditional logistic regression models. Sex, age, previous SARS-CoV-2 infection, type of vaccine and number of contacts with the RHS were associated with the risk of infection and severe illness. Moreover, higher odds of infection and severe illness were significantly associated with 14 and 34 diseases, respectively, among those investigated. These results can be helpful to clinicians and policy makers for prioritizing interventions.

Influenza Vaccination Effectiveness in Paediatric 'Healthy' Patients: A Population-Based Study in Italy.

BACKGROUND: Seasonal influenza can cause serious morbidity, mortality, and financial burden in pediatric and adult populations. The influenza vaccine (IV) is considered the most effective way to prevent influenza and influenza-like-illness (ILI) complications. OBJECTIVE: To assess the effectiveness of the IV in a cohort of healthy children in Italy. METHODS: From the Pedianet database, all healthy children aged six months-14 years between 2009-2019 were enrolled. Cox proportional-hazards models were fitted to estimate hazard ratios and the 95% confidence interval for the association between IV exposure during each season of interest (from October to April of each year) with incident influenza/ILI. Exposure was considered as a time-varying variable. Vaccine effectiveness (VE) was calculated as (1-HR) × 100. The additive and prolonged effects of IV were evaluated across the seasons. RESULTS: We found a high IV effectiveness among healthy children. No additional or prolonged effects were found. CONCLUSION: Our data indicates that IV was effective in preventing influenza/ILI in healthy children. Therefore, IV should be encouraged and provided free of charge to healthy children in all the Italian regions every year, reducing disease spread and lowering the burden on the pediatric population.

Persistence of protection against SARS-CoV-2 clinical outcomes up to 9 months since vaccine completion: a retrospective observational analysis in Lombardy, Italy.

BACKGROUND: Scarce information is available on the duration of the protective effect of COVID-19 vaccination against the risk of SARS-CoV-2 infection and its severe clinical consequences. We investigated the effect of time since vaccine completion on the SARS-CoV-2 infection and its severe forms. METHODS: In this retrospective observational analysis using the vaccination campaign integrated platform of the Italian region of Lombardy, 5 351 085 individuals aged 12 years or older who received complete vaccination from Jan 17 to July 31, 2021, were followed up from 14 days after vaccine completion until Oct 20, 2021. Changes over time in outcome rates (ie, SARS-CoV-2 infection and severe illness among vaccinated individuals) were analysed with age-period-cohort models. Trends in vaccine effectiveness (ie, outcomes comparison in vaccinated and unvaccinated individuals) were also measured. FINDINGS: Overall, 14 140 infections and 2450 severe illnesses were documented, corresponding to incidence rates of 6·7 (95% CI 6·6-6·8) and 1·2 (1·1-1·2) cases per 10 000 person-months, respectively. From the first to the ninth month since vaccine completion, rates increased from 4·6 to 10·2 infections, and from 1·0 to 1·7 severe illnesses every 10 000 person-months. These figures correspond to relative reduction of vaccine effectiveness of 54·9% (95% CI 48·3-60·6) for infection and of 40·0% (16·2-57·0) for severe illness. The increasing infection rate was greater for individuals aged 60 years or older who received adenovirus-vectored vaccines (from 4·0 to 23·5 cases every 10 000 person-months). The increasing severe illness rates were similar for individuals receiving mRNA-based vaccines (from 1·1 to 1·5 every 10 000 person-months) and adenovirus-vectored vaccines (from 0·5 to 0·9 every 10 000 person-months). INTERPRETATION: Although the risk of infection after vaccination, and even more of severe illness, remains low, the gradual increase in clinical outcomes related to SARS-CoV-2 infection suggests that the booster campaign should be accelerated and that social and individual protection measures against COVID-19 spread should not be abandoned. FUNDING: None.

Balancing Benefits and Harms of COVID-19 Vaccines: Lessons from the Ongoing Mass Vaccination Campaign in Lombardy, Italy.

Background. Limited evidence exists on the balance between the benefits and harms of the COVID-19 vaccines. The aim of this study is to compare the benefits and safety of mRNA-based (Pfizer-BioNTech and Moderna) and adenovirus-vectored (Oxford-AstraZeneca) vaccines in subpopulations defined by age and sex. Methods. All citizens who are newly vaccinated from 27 December 2020 to 3 May 2021 are matched to unvaccinated controls according to age, sex, and vaccination date. Study outcomes include the events that are expected to be avoided by vaccination (i.e., hospitalization and death from COVID-19) and those that might be increased after vaccine inoculation (i.e., venous thromboembolism). The incidence rate ratios (IRR) of vaccinated and unvaccinated citizens are separately estimated within strata of sex, age category and vaccine type. When suitable, number needed to treat (NNT) and number needed to harm (NNH) are calculated to evaluate the balance between the benefits and harm of vaccines within each sex and age category. Results. In total, 2,351,883 citizens are included because they received at least one dose of vaccine (755,557 Oxford-AstraZeneca and 1,596,326 Pfizer/Moderna). A reduced incidence of COVID-19-related outcomes is observed with a lowered incidence rate ranging from 55% to 89% and NNT values ranging from 296 to 3977. Evidence of an augmented incidence of harm-related outcomes is observed only for women aged <50 years within 28 days after Oxford-AstraZeneca (being the corresponding adjusted IRR of 2.4, 95% CI 1.1-5.6, and NNH value of 23,207, 95% CI 10,274-89,707). Conclusions. A favourable balance between benefits and harms is observed in the current study, even among younger women who received Oxford-AstraZeneca.

Coping with COVID: risk and resilience factors for mental health in a German representative panel study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic might affect mental health. Data from population-representative panel surveys with multiple waves including pre-COVID data investigating risk and protective factors are still rare. METHODS: In a stratified random sample of the German household population (n = 6684), we conducted survey-weighted multiple linear regressions to determine the association of various psychological risk and protective factors assessed between 2015 and 2020 with changes in psychological distress [(PD; measured via Patient Health Questionnaire for Depression and Anxiety (PHQ-4)] from pre-pandemic (average of 2016 and 2019) to peri-pandemic (both 2020 and 2021) time points. Control analyses on PD change between two pre-pandemic time points (2016 and 2019) were conducted. Regularized regressions were computed to inform on which factors were statistically most influential in the multicollinear setting. RESULTS: PHQ-4 scores in 2020 (M = 2.45) and 2021 (M = 2.21) were elevated compared to 2019 (M = 1.79). Several risk factors (catastrophizing, neuroticism, and asking for instrumental support) and protective factors (perceived stress recovery, positive reappraisal, and optimism) were identified for the peri-pandemic outcomes. Control analyses revealed that in pre-pandemic times, neuroticism and optimism were predominantly related to PD changes. Regularized regression mostly confirmed the results and highlighted perceived stress recovery as most consistent influential protective factor across peri-pandemic outcomes. CONCLUSIONS: We identified several psychological risk and protective factors related to PD outcomes during the COVID-19 pandemic. A comparison of pre-pandemic data stresses the relevance of longitudinal assessments to potentially reconcile contradictory findings. Implications and suggestions for targeted prevention and intervention programs during highly stressful times such as pandemics are discussed.

Protective action of natural and induced immunization against the occurrence of delta or alpha variants of SARS-CoV-2 infection: a test-negative case-control study.

BACKGROUND: The evolution of SARS-CoV-2 has led to the emergence of several new variants, and few data are available on the impact of vaccination on SARS-CoV-2 variants. We aimed to assess the association between natural (previous infection) and induced (partial or complete vaccination) exposure to SARS-CoV-2 and the onset of new infection supported by the delta variant, and of comparing it with that supported by alpha. METHODS: We performed a test-negative case-control study, by linking population-based registries of confirmed diagnoses of infection with SARS-CoV-2, vaccinations against Covid-19 and healthcare utilization databases of the Italian Lombardy Region. Four hundred ninety-six persons who between 27 December 2020 and 16 July 2021 had an infection by the delta variant were 1:1 matched with citizens affected by alphavariant and 1:10 matched with persons who had a negative molecular test, according to gender, age and date of molecular ascertainment. We used a conditional logistic regression for estimating relative risk reduction of either variants associated with natural and/or induced immunization and corresponding 95% confidence interval (CI). RESULTS: Previous infection was associated with 91% (95% CI 85% to 95%) reduced relative risk of reinfection, without evidence of significant differences between delta and alpha cases (p=0.547). Significant lower vaccinal protection against delta than alpha variant infection was observed with reduced relative risk associated with partial vaccination respectively of 29% (7% to 45%), and 62% (48% to 71%) (p=0.001), and with complete vaccination respectively of 75% (66% to 82%) and 90% (85% to 94%) (p=0.003). CONCLUSIONS: Lower protection towards infections caused by the delta variant with respect to alpha variant was noticed, even after the completion of the vaccination cycle. This finding would support efforts to maximize both vaccine uptake with two doses and fulfilment with individual protection measures, especially as the delta variant is rampant worldwide presently.

Eight Good Reasons for Careful Monitoring and Evaluation of the Vaccine Campaign against COVID-19: Lessons Learned through the Lombardy Experience for Dealing with Next Challenges.

BACKGROUND: Using the knowledge gained during the first eleven months of the vaccine campaign in Lombardy, Italy, we provide an overview of the benefits of using reliable, complete, and rapidly available observational data to monitor the progress of the vaccine strategy. METHODS: A population-based platform was implemented by linking four registries reporting individual data on: (i) date, type, and dose of vaccine dispensed; (ii) SARS-CoV-2 infections and hospital admissions and deaths due to COVID-19; (iii) inpatient diagnoses and outpatient services supplied by the Regional Health Services (RHS); and the (iv) health registry reporting and updating data on patient status. Background, methods, findings, and implications of eight COVID-19 relevant questions are reported. RESULTS: Before starting the vaccine campaign, we identified high-risk individuals who need to be prioritized. During the vaccine campaign, we: (i) monitored the trend in the speed of the vaccine campaign progression and the number of prevented clinical outcomes; (ii) verified that available vaccines work in real-life, assessed their effectiveness-harm profile, and measured their reduced effectiveness against the delta variant. Finally, we studied the reduced effectiveness of the vaccine over time and identified risk factors of post-vaccine infection and severe illness. CONCLUSIONS: The correct use of rapidly available observational data of good quality and completeness generates reliable evidence to promptly inform patients and policymakers.

Stratification of the risk of developing severe or lethal Covid-19 using a new score from a large Italian population: a population-based cohort study.

OBJECTIVES: To develop a population-based risk stratification model (COVID-19 Vulnerability Score) for predicting severe/fatal clinical manifestations of SARS-CoV-2 infection, using the multiple source information provided by the healthcare utilisation databases of the Italian National Health Service. DESIGN: Retrospective observational cohort study. SETTING: Population-based study using the healthcare utilisation database from five Italian regions. PARTICIPANTS: Beneficiaries of the National Health Service, aged 18-79 years, who had the residentship in the five participating regions. Residents in a nursing home were not included. The model was built from the 7 655 502 residents of Lombardy region. MAIN OUTCOME MEASURE: The score included gender, age and 29 conditions/diseases selected from a list of 61 conditions which independently predicted the primary outcome, that is, severe (intensive care unit admission) or fatal manifestation of COVID-19 experienced during the first epidemic wave (until June 2020). The score performance was validated by applying the model to several validation sets, that is, Lombardy population (second epidemic wave), and the other four Italian regions (entire 2020) for a total of about 15.4 million individuals and 7031 outcomes. Predictive performance was assessed by discrimination (areas under the receiver operating characteristic curve) and calibration (plot of observed vs predicted outcomes). RESULTS: We observed a clear positive trend towards increasing outcome incidence as the score increased. The areas under the receiver operating characteristic curve of the COVID-19 Vulnerability Score ranged from 0.85 to 0.88, which compared favourably with the areas of generic scores such as the Charlson Comorbidity Score (0.60). A remarkable performance of the score on the calibration of observed and predicted outcome probability was also observed. CONCLUSIONS: A score based on data used for public health management accurately predicted the occurrence of severe/fatal manifestations of COVID-19. Use of this score may help health decision-makers to more accurately identify high-risk citizens who need early preventive or treatment interventions.

Change in healthcare during Covid-19 pandemic was assessed through observational designs.

OBJECTIVE: Methodological challenges for investigating the changes in healthcare utilization during COVID-19 pandemic must be considered for obtaining unbiased estimates. STUDY DESIGN AND SETTING: A population-based study in the Lombardy region (Italy) measured the association between the level of epidemic restrictions (increasing exposure during pre-epidemic, post-lockdown, and lockdown periods) and the recommended healthcare (outcome) for patients with schizophrenia, heart failure, chronic obstructive pulmonary disease, breast cancer, and pregnancy women. Two designs are applied: the self-controlled case series (SCCS) and the usual cohort design. Adjustments for between-patients unmeasured confounders and seasonality of medical services delivering were performed. RESULTS: Compared with pre-epidemic, reductions in delivering recommended healthcare during lockdown up to 73% (95% confidence interval: 63%-80%) for timeliness of breast cancer surgery, and up to 20% (16%-23%) for appropriated gynecologic visit during pregnancy were obtained from SCCS and cohort design, respectively. Healthcare provision came back to pre-epidemic levels during the post-lockdown, with the exception of schizophrenic patients for whom the SCCS showed a reduction in continuity of care of 11% (11%-12%). CONCLUSION: Strategies for investigating the changes in healthcare utilization during pandemic must be implemented. Recommendations for taking into account sources of systematic uncertainty are discussed and illustrated by using motivating examples.