Epidemiology and public health response in early phase of COVID-19 pandemic, Veneto Region, Italy, 21 February to 2 April 2020.

BackgroundVeneto was one of the Italian regions hit hardest by the early phase of the coronavirus disease (COVID-19) pandemic.AimThis paper describes the public health response and epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in the Veneto Region from 21 February to 2 April 2020.MethodsInformation on the public health response was collected from regional health authorities' official sources. Epidemiological data were extracted from a web-based regional surveillance system. The epidemic curve was represented by date of testing. Characteristics of hospitalised COVID-19 cases were described and compared to those never admitted to hospital. Age- and sex-stratified case-fatality ratios (CFRs) were calculated.ResultsKey elements of the regional public health response were thorough case-finding and contact tracing, home care for non-severe cases, creation of dedicated COVID-19 healthcare facilities and activation of sub-intensive care units for non-invasive ventilation. As at 2 April 2020, 91,345 individuals were tested for SARS-CoV-2 and 10,457 (11.4%) were positive. Testing and attack rates were 18.6 per 1,000 and 213.2 per 100,000 population, respectively. The epidemic peaked around 20 to 24 March, with case numbers declining thereafter. Hospitalised cases (n = 3,623; 34.6%) were older and more frequently male compared with never-hospitalised cases. The CFR was 5.6% overall, and was higher among males and people > 60 years of age.ConclusionIn the Veneto Region, the strict social distancing measures imposed by the Italian government were supported by thorough case finding and contact tracing, as well as well-defined roles for different levels of care.

Adverse events following Measles-Mumps-Rubella and varicella immunization: A safety profile analysis and comparison of different vaccination schedules based on the Italian Pharmacovigilance Network in the Veneto Region.

Objective: The vaccines for measles, mumps, rubella and varicella (MMR and V) have been mandatory in Italy since 2017. Two different vaccination strategies are suggested for the first dose: trivalent MMR and a separate V vaccine or the tetravalent MMRV vaccine. Our aim is to compare the safety profile of MMRV and MMR-V vaccines through the passive adverse event reporting system in the Veneto region and to perform a case-by-case review of a few conditions of interest (febrile and afebrile seizures, ataxia, encephalitis, Guillain-Barré Syndrome, thrombocytopenia, neutropenia and Henoch-Schönlein Purpura). Age and sex differences were also explored. Methods: We identified all reports following MMRV or MMR-V vaccination in the Veneto Region and received into the National Pharmacovigilance Network between 2007 and April 30, 2022. Results: 9,510 reports were retrieved, of which 5,662 (59.5 %) were related to MMRV and 3,848 (40.5 %) to MMR-V. No safety signals were detected supporting the evidence that MMRV and MMR-V vaccinations have a good safety profile. The reporting rate (RR) for serious events between 2007 and 2022 resulted in 13.67 per 10,000 administered doses for MMRV and 10.90 for MMR-V. Conclusion: Passive surveillance data show a significantly higher rate of serious events for males 0-2 years old, both overall and stratified per vaccination strategy. Further studies are needed to confirm this observation. The analyses suggest that retrieved differences do not have a significant impact on the overall safety of both formulations.

Improving the Quality of Healthcare Provision Regarding HPV Immunization for Women with CIN2+ Lesions: The Experience of the Veneto Region in Italy.

HPV is the most common cause of sexually-transmitted infections the world over. The aim of this study was to assess the impact of a healthcare quality improvement strategy designed to increase the rate of vaccination against HPV in women diagnosed with cervical lesions graded as CIN2 or higher (CIN2+) during routine screening. The Veneto Regional Health Service developed a 22-item questionnaire to measure the gap between ideal procedure and real practice regarding the offer of vaccination against HPV for women undergoing routine cervical screening. The questionnaire was administered to nine expert doctors, one at each of the region's Local Health Units (LHUs). An additional specific assessment concerned the quality of the related web pages available on the LHU websites. Strategies to close the gap between ideal procedure and real practice were decided collegially, and a checklist to support good practices was developed and shared with operators at the LHUs. Changes in practice were measured using data relating to women diagnosed with CIN2+ lesions extracted from the regional oncological screening database before and after the publication of a Regional Procedure on the topic. The LHUs differed considerably in how they managed each step, in terms of training for healthcare personnel, organization and assessment of the pathway from cervical screening to HPV vaccination, and in dedicated website communication. After implementing the quality improvement strategy, the proportion of women given a first dose of HPV vaccine within 3 months of being diagnosed with CIN2+ lesions at 1st-level screening rose to 50% (compared with 30.85% beforehand), and the median time elapsing between a diagnosis of CIN2+ lesion and a first dose of HPV vaccine dropped from 158 to 90 days. These findings underscore the importance of providing training to promote vaccination for general practitioners and other clinicians. The study also confirms the need for more efforts in communication to ensure that any citizen has the opportunity to access preventive healthcare.

The incidence and risk factors of selected drug prescriptions and outpatient care after SARS-CoV-2 infection in low-risk subjects: a multicenter population-based cohort study.

Background: Knowledge about the dynamics of transmission of SARS-CoV-2 and the clinical aspects of COVID-19 has steadily increased over time, although evidence of the determinants of disease severity and duration is still limited and mainly focused on older adult and fragile populations. Methods: The present study was conceived and carried out in the Emilia-Romagna (E-R) and Veneto Regions, Italy, within the context of the EU's Horizon 2020 research project called ORCHESTRA (Connecting European Cohorts to increase common and effective response to SARS-CoV-2 pandemic) (www.orchestra-cohort.eu). The study has a multicenter retrospective population-based cohort design and aimed to investigate the incidence and risk factors of access to specific healthcare services (outpatient visits and diagnostics, drug prescriptions) during the post-acute phase from day-31 to day-365 after SARS-CoV-2 infection, in a healthy population at low risk of severe acute COVID-19. The study made use of previously recorded large-scale healthcare data available in the administrative databases of the two Italian Regions. The statistical analysis made use of methods for competing risks. Risk factors were assessed separately in the two Regions and results were pooled using random effects meta-analysis. Results: There were 35,128 subjects in E-R and 88,881 in Veneto who were included in the data analysis. The outcome (access to selected health services) occurred in a high percentage of subjects in the post-acute phase (25% in E-R and 21% in Veneto). Outpatient care was observed more frequently than drug prescriptions (18% vs. 12% in E-R and 15% vs. 10% in Veneto). Risk factors associated with the outcome were female sex, age greater than 40 years, baseline risk of hospitalization and death, moderate to severe acute COVID-19, and acute extrapulmonary complications. Conclusion: The outcome of interest may be considered as a proxy for long-term effects of COVID-19 needing clinical attention. Our data suggest that this outcome occurs in a substantial percentage of cases, even among a previously healthy population with low or mild severity of acute COVID-19. The study results provide useful insights into planning COVID-19-related services.

Increasing Number of Cases Due to Candida auris in North Italy, July 2019-December 2022.

Candida auris is an emerging fungus that represents a serious health threat globally. In Italy, the first case was detected in July 2019. Then, one case was reported to the Ministry of Health (MoH) on January 2020. Nine months later, a huge number of cases were reported in northern Italy. Overall, 361 cases were detected in 17 healthcare facilities between July 2019 and December 2022 in the Liguria, Piedmont, Emilia-Romagna, and Veneto regions, including 146 (40.4%) deaths. The majority of cases (91.8%) were considered as colonised. Only one had a history of travel abroad. Microbiological data on seven isolates showed that all but one strain (85.7%) were resistant to fluconazole. All the environmental samples tested negative. Weekly screening of contacts was performed by the healthcare facilities. Infection prevention and control (IPC) measures were applied locally. The MoH nominated a National Reference Laboratory to characterise C. auris isolates and store the strains. In 2021, Italy posted two messages through the Epidemic Intelligence Information System (EPIS) to inform on the cases. On February 2022, a rapid risk assessment indicated a high risk for further spread within Italy, but a low risk of spread to other countries.

The Effectiveness of a Diverse COVID-19 Vaccine Portfolio and Its Impact on the Persistence of Positivity and Length of Hospital Stays: The Veneto Region's Experience.

The vaccination campaign for the Veneto region (northeastern Italy) started on 27 December 2020. As of early December 2021, 75.1% of the whole Veneto population has been fully vaccinated. Vaccine efficacy has been demonstrated in many clinical trials, but reports on real-world contexts are still necessary. We conducted a retrospective cohort study on 2,233,399 residents in the Veneto region to assess the reduction in the COVID-19 burden, taking different outcomes into consideration. First, we adopted a non-brand-specific approach borrowed from survival analysis to estimate the effectiveness of vaccination against SARS-CoV-2 in preventing infections, hospitalizations, and deaths. We used t-tests and multivariate regressions to examine vaccine impact on breakthrough infections, in terms of the persistence of positivity and the length of hospital stays. Evidence emerging from this study suggests that unvaccinated individuals are significantly more likely to become infected, need hospitalization, and are at a higher risk of death from COVID-19 than those given at least one dose of vaccine. Cox models indicate that the effectiveness of full vaccination is 88% against infection, 94% against hospitalization, and 95% against death. Multivariate regressions suggest that vaccination is significantly correlated with a shorter period of positivity and shorter hospital stays, with each step toward completion of the vaccination cycle coinciding with a reduction of 3.3 days in the persistence of positivity and 2.3 days in the length of hospital stay.

"Would You Get Vaccinated against COVID-19?" The Picture Emerging from a Study on the Prevalence of SARS-CoV-2 Infection in the General Population of the Veneto Region.

COVID-19 disease, caused by the SARS-CoV-2 virus, continues to cause high hospitalization and death rates. Vaccination campaigns have been key to controlling the pandemic, but vaccine hesitancy is on the rise. This study investigated the general population's attitude to vaccination in Veneto (northeast Italy) in January 2021 as part of a study on the prevalence of SARS-CoV-2 infection. An ad hoc questionnaire collected 4467 respondents' sociodemographic data and propensity to be vaccinated, and findings were analyzed using logistic multivariable regression. The 48.9% of respondents were male, and the mean age was 46.8 ± 16.0 years. Asked whether they would get vaccinated against COVID-19, 84.3% said yes, 5.0% were uncertain, and 10.7% said no. Vaccine acceptance was higher in males than in females (85.8% vs. 82.8%), in people 70+ years old (92.3%), and among people with more than 14 years of schooling (89.6%). Multivariable analysis with adjOR (95% CI) showed a significantly greater vaccine reluctance in females (0.68 (0.57−0.81)), people 30−49 or 50−69 years old (0.69 (0.54−0.87)), and (0.76 (0.58−0.99)); and those with <9 or 9−13 years of schooling (0.62 (0.46−0.82)), and (0.72 (0.57−0.91)). As people refusing vaccination undeniably hinder efforts to control the pandemic, specific strategies are needed to overcome their doubts.

Differences in Immunological Evasion of the Delta (B.1.617.2) and Omicron (B.1.1.529) SARS-CoV-2 Variants: A Retrospective Study on the Veneto Region's Population.

In December 2021-January 2022 the Veneto region in Italy faced an unprecedented wave of SARS-CoV-2 infections, even though both the vaccine coverage and the number of previously infected individuals keep increasing. In this study we address the protection against the SARS-CoV-2 infection offered by natural immunity and a three-dose regimen through a retrospective study based on Veneto's regional databases. In particular, we compared these protection levels during two distinct periods respectively representative of the Delta (B.1.617.2) and the Omicron (B.1.1.529) variants, in order to investigate and quantify the immunological evasion, especially of the Omicron. For each period we compared the incidence rate of infection among the population with various immunological protections against SARS-CoV-2 and performed a multivariable proportional hazard Cox binomial regression to assess the effectiveness afforded by both forms of active immunization. We found out that a previous SARS-CoV-2 infection (irrespective of its timing) offers 85% (83-87%) and 36% (33-39%) protection against being reinfected by Delta and Omicron, respectively. In addition, we estimated the third dose to be more effective in both periods and to have a minor proportional loss of effectiveness due to the rise of the Omicron variant, with an afforded effectiveness against SARS-CoV-2 Delta and Omicron infection of 97% (96-97%) and 47% (45-48%), respectively. Our findings suggest that viral variant factors may affect any form of active immunization but that receiving a booster vaccination cycle is more effective and less variable than natural immunity in terms of afforded protection against SARS-CoV-2 infections.

COVID-19 Vaccine Effectiveness against Omicron Variant among Underage Subjects: The Veneto Region's Experience.

Even if most of the complications due to COVID-19 are observed in the elderly, in Italy the impact of COVID-19 among young people has not been negligible. Furthermore, their contribution to SARS-CoV-2 circulation is still unclear. These reasons have driven policy makers to involve subjects aged 5 to 17 years in the COVID-19 vaccination campaign. However, the trade-off of vaccinating this age-group should be further investigated, especially in view of the rise of new immunologically evasive variants of concern (VOCs). We used regional databases to retrospectively estimate vaccine effectiveness over time of each approved vaccination schedule among children (5-11) and adolescents (12-17). Our findings suggest that COVID-19 vaccines were highly effective and their protection levels lasted longer during a period of Delta variant predominance, whereas they offered just mild to moderate levels of protection-apparently affected by a rapid waning effect-in a period of Omicron variant predominance. Considering these results, it is plausible to evaluate a reformulation of possible future COVID-19 vaccination campaigns among underage subjects. However, effectiveness against serious complications due to COVID-19, as well as indirect benefits of underage vaccinations, should first be addressed. Furthermore, vaccine effectiveness should be kept monitored, as new VOCs may arise, but also new adapted vaccines may start being administered.

Prevalence of Asymptomatic SARS-CoV-2 Infection in the General Population of the Veneto Region: Results of a Screening Campaign with Third-Generation Rapid Antigen Tests in the Pre-Vaccine Era.

The aim of our study was to ascertain the prevalence of SARS-CoV-2 infection in the general population during a period of moderate risk, just before Italy started to implement its vaccination campaign. A third-generation antigenic nasal swab sample was collected by a healthcare provider, and all individuals testing positive subsequently had a nasopharyngeal swab for molecular testing; the result was used to calculate the positive predictive value. The population consisted of 4467 asymptomatic adults with a mean age of 46.8 ± 16.00 years. The 62.2% tested for the first time, while 37.8% had previously undergone a mean 2.2 tests for SARS-CoV-2. With 77 of our overall sample reporting they had previously tested positive for COVID-19 and 14 found positive on our screening test, the overall estimated prevalence of the infection was 0.31%. Nine of the 14 cases were confirmed on molecular testing with a PPV of 64.3%. The mean age of the individuals testing positive was 38.1 ± 17.4. Based on the timing of symptom onset, six of the above cases were classified as false negatives, and the adjusted estimated prevalence was 0.34%. Describing levels of infection in a general population seems to be very difficult to achieve, and the universal screening proved hugely expensive particularly in a low-prevalence situation. Anyway, it is only thanks to mass screening efforts that epidemiological data have been collected. This would support the idea that routine screening may have an impact on mitigating the spread of the virus in higher-risk environments, where people come into contact more frequently, as in the workplace.

Surveillance of Outbreaks of SARS-CoV-2 Infections at School in the Veneto Region: Methods and Results of the Public Health Response during the Second and Third Waves of the Pandemic between January and June 2021.

During the COVID-19 pandemic, many countries adopted various non-pharmacological interventions to contain the number of infections. The most often used policy was school closures. We describe the strategy adopted by the Veneto Regional Authority to contain transmission in school settings. This included a detailed school surveillance system, strict contact tracing, and maintaining school attendance with self-monitoring for symptoms whenever possible. All analyzed COVID-19 cases among children, adolescents (0-19 years old), and school staff were registered using a web-based application between 4 January 2021 and 13 June 2021. During the study period, 6272 episodes of infection in schools were identified; 87% were linked to a student index case and 13% to school staff; 69% generated no secondary cases; 24% generated one or two; and only 7% caused more than two. Our data may help to clarify the role of school closures, providing useful input for decisions in the months to come. Good practice in public health management needs tools that provide a real-time interpretation of phenomena like COVID-19 outbreaks. The proposed measures should be easy to adopt and accessible to policymakers.

Preventive strategies in systemic lupus erythematosus.

Despite the improvement of systemic lupus erythematosus (SLE) survival observed in the last decades, the long-term prognosis of these patients remains poor mainly due to complications of the disease and/or of its treatment. Therefore, in order to improve SLE prognosis, we should try to avoid long-term complications by adopting, early in the disease course, some strategies directed to prevent infections, atherosclerosis and cancer. Moreover, since it has been shown that autoantibodies appear before clinical manifestations in SLE, the question of whether or not asymptomatic individuals with a reliable positive serology should be treated arises. Other than advising these individuals to avoid sun exposure, drugs implicated in drug-induced lupus and cigarette smoking, the use of vitamin D and hydroxychloroquine could be considered. Finally, early SLE diagnosis has led to a modification of disease clinical spectrum at disease onset with an increased frequency of mild disease manifestations over severe ones. Thus great effort should be made in order to identify early in the disease course risk factors for the development of severe SLE manifestations. Finally patients with mild disease carrying factors predictive of severe manifestations should be treated more aggressively than we have done up to now.

Infections and autoimmunity: the multifaceted relationship.

Multiple factors are thought to contribute to the development of immune response to self, including differences in genotypes, hormonal milieu, and environmental factors. This review focuses on the pivotal role of infection in the induction of autoimmune disorders. Although the development of autoimmune phenomena linked to infections is a common finding, the onset of autoimmune diseases is a rare event, arising from a combination of genetic susceptibility and environmental factors. There are several mechanisms through which pathogens can initiate or perpetuate autoimmunity. Some of them are antigen-specific, including molecular mimicry, expression of modified, cryptic, or new antigenic determinants, and superantigens. Others are nonspecific and collectively known as "bystander activation." They include enhanced processing and presentation of self-antigens, immune cell activation, cytokine release, and cell apoptosis/necrosis. Infections may also trigger organ-specific autoimmune diseases, but studies carried out until now have provided conflicting and inconclusive results regarding the role of viral and bacterial agents. Infections and autoimmune diseases have multifaceted and multidirectional relationships. It has been suggested recently that infections cannot only induce or precipitate autoimmune diseases, but they may also protect from autoimmunity or even abrogate an ongoing autoimmune process depending on the interaction between microorganisms and host. Therefore, we should look at microorganisms, not only as causes of infections but also as potential agents able to modulate the immune system. On the other hand, numerous evidences have emerged regarding the higher susceptibility of autoimmune patients to infections, possibly as a result of immunosuppressive therapy and treatment with biologic agents.

Hormones, immune response, and pregnancy in healthy women and SLE patients.

During pregnancy the maternal immune system is modified in order to achieve immune tolerance toward paternal antigen expressed on foetal cells. These modifications, which occur both at the foeto-maternal interface and in the systemic circulation, are driven by oestrogens and progesterone whose blood concentrations increase during pregnancy. The cytokine profile is also modified. Th2 cytokines are enhanced while the Th1 response is inhibited. This could explain why Th1-mediated autoimmune diseases tend to improve and Th2-mediated diseases, such as systemic lupus erythematosus (SLE), tend to worsen during pregnancy. However, whether or not SLE relapses more frequently during pregnancy is still a matter of debate. Steroid hormone and cytokine profiles differ in SLE patients compared with healthy subjects during pregnancy leading to a dysregulation of the balance between cell-mediated and humoral immune response, which, in turn, could explain the variability of the SLE course during gestation. This review focuses on hormonal-related cytokine changes observed during pregnancy in healthy subjects and SLE patients.