Geographic heterogeneity of the epidemiological impact of the COVID-19 pandemic in Italy using a socioeconomic proxy-based classification of the national territory.

Objectives: This study aimed to evaluate the differences in incidence, non-intensive care unit (non-ICU) and intensive care unit (ICU) hospital admissions, and COVID-19-related mortality between the "inner areas" of Italy and its metropolitan areas. Study design: Retrospective population-based study conducted from the beginning of the pandemic in Italy (20 February 2020) to 31 March 2022. Methods: The municipalities of Italy were classified into metropolitan areas, peri-urban/intermediate areas and "inner areas" (peripheral/ultra-peripheral). The exposure variable was residence in an "inner area" of Italy. Incidence of diagnosis of SARS-CoV-2 infection, non-ICU and ICU hospital admissions and death within 30 days from diagnosis were the outcomes of the study. COVID-19 vaccination access was also evaluated. Crude and age-standardized rates were calculated for all the study outcomes. The association between the type of area of residence and each outcome under study was evaluated by calculating the ratios between the standardized rates. All the analyses were stratified by period of observation (original Wuhan strain, Alpha variant, Delta variant, Omicron variant). Results: Incidence and non-ICUs admissions rates were lower in "inner areas." ICU admission and mortality rates were much lower in "inner areas" in the early phases of the pandemic, but this protection progressively diminished, with a slight excess risk observed in the "inner areas" during the Omicron period. The greater vaccination coverage in metropolitan areas may explain this trend. Conclusion: Prioritizing healthcare planning through the strengthening of the primary prevention policies in the peripheral areas of Italy is fundamental to guarantee health equity policies.

Protection against severe COVID-19 after second booster dose of adapted bivalent (original/Omicron BA.4-5) mRNA vaccine in persons ≥ 60 years, by time since infection, Italy, 12 September to 11 December 2022.

Effectiveness against severe COVID-19 of a second booster dose of the bivalent (original/BA.4-5) mRNA vaccine 7-90 days post-administration, relative to a first booster dose of an mRNA vaccine received ≥ 120 days earlier, was ca 60% both in persons ≥ 60 years never infected and in those infected > 6 months before. Relative effectiveness in those infected 4-6 months earlier indicated no significant additional protection (10%; 95% CI: -44 to 44). A second booster vaccination 6 months after the latest infection may be warranted.

Relative effectiveness of a 2nd booster dose of COVID-19 mRNA vaccine up to four months post administration in individuals aged 80 years or more in Italy: A retrospective matched cohort study.

Several countries started a 2nd booster COVID-19 vaccination campaign targeting the elderly population, but evidence around its effectiveness is still scarce. This study aims to estimate the relative effectiveness of a 2nd booster dose of COVID-19 mRNA vaccine in the population aged ≥ 80 years in Italy, during predominant circulation of the Omicron BA.2 and BA.5 subvariants. We linked routine data from the national vaccination registry and the COVID-19 surveillance system. On each day between 11 April and 6 August 2022, we matched 1:1, according to several demographic and clinical characteristics, individuals who received the 2nd booster vaccine dose with individuals who received the 1st booster vaccine dose at least 120 days earlier. We used the Kaplan-Meier method to compare the risks of SARS-CoV-2 infection and severe COVID-19 (hospitalisation or death) between the two groups, calculating the relative vaccine effectiveness (RVE) as (1 - risk ratio)X100. Based on the analysis of 831,555 matched pairs, we found that a 2nd booster dose of mRNA vaccine, 14-118 days post administration, was moderately effective in preventing SARS-CoV-2 infection compared to a 1st booster dose administered at least 120 days earlier [14.3 %, 95 % confidence interval (CI): 2.2-20.2]. RVE decreased from 28.5 % (95 % CI: 24.7-32.1) in the time-interval 14-28 days to 7.6 % (95 % CI: -14.1 to 18.3) in the time-interval 56-118 days. However, RVE against severe COVID-19 was higher (34.0 %, 95 % CI: 23.4-42.7), decreasing from 43.2 % (95 % CI: 30.6-54.9) to 27.2 % (95 % CI: 8.3-42.9) over the same time span. Although RVE against SARS-CoV-2 infection was much reduced 2-4 months after a 2nd booster dose, RVE against severe COVID-19 was about 30 %, even during prevalent circulation of the Omicron BA.5 subvariant. The cost-benefit of a 3rd booster dose for the elderly people who received the 2nd booster dose at least four months earlier should be carefully evaluated.

Reduction of the risk of severe COVID-19 due to Omicron compared to Delta variant in Italy (November 2021 - February 2022).

OBJECTIVES: During 2022, Omicron became the dominant SARS-CoV-2 variant in Europe. This study aims to assess the impact of such variant on severe disease from SARS-CoV-2 compared with the Delta variant in Italy. METHODS: Using surveillance data, we assessed the risk of developing severe COVID-19 with Omicron infection compared with Delta in individuals aged ≥12 years using a multilevel negative binomial model adjusting for sex, age, vaccination status, occupation, previous infection, weekly incidence, and geographical area. We also analyzed the interaction between the sequenced variant, age, and vaccination status. RESULTS: We included 21,645 cases of SARS-CoV-2 infection where genome sequencing found Delta (10,728) or Omicron (10,917), diagnosed from November 15, 2021 to February 01, 2022. Overall, 3,021 cases developed severe COVID-19. We found that Omicron cases had a reduced risk of severe COVID-19 compared with Delta cases (incidence rate ratio [IRR] = 0.77; 95% confidence interval [CI]: 0.70-0.86). The largest difference was observed in cases aged 40-59 (IRR = 0.66; 95% CI: 0.55-0.79), while no protective effect was found in those aged 12-39 (IRR = 1.03; 95% CI: 0.79-1.33). Vaccination was associated with a lower risk of developing severe COVID-19 in both variants. CONCLUSION: The Omicron variant is associated with a lower risk of severe COVID-19 compared to infection with the Delta variant, but the degree of protection varies with age.

Surveillance, contact tracing and characteristics of SARS-CoV-2 transmission in educational settings in Northern Italy, September 2020 to April 2021.

BACKGROUND: The role of school contacts in the spread of the virus and the effectiveness of school closures in controlling the epidemic is still debated. We aimed to quantify the risk of transmission of SARS-CoV-2 in the school setting by type of school, characteristics of the index case and calendar period in the Province of Reggio Emilia (RE), Italy. The secondary aim was to estimate the speed of implementation of contact tracing. METHODS: A population-based analysis of surveillance data on all COVID-19 cases occurring in RE, Italy, from 1 September 2020, to 4 April 2021, for which a school contact and/or exposure was suspected. An indicator of the delay in contact tracing was calculated as the time elapsed since the index case was determined to be positive and the date on which the swab test for classmates was scheduled (or most were scheduled). RESULTS: Overall, 30,184 and 13,608 contacts among classmates and teachers/staff, respectively, were identified and were recommended for testing, and 43,214 (98.7%) underwent the test. Secondary transmission occurred in about 40% of the investigated classes, and the overall secondary case attack rate was 4%. This rate was slightly higher when the index case was a teacher but with almost no differences by type of school, and was stable during the study period. Speed of implementation of contact tracing increased during the study period, with the time from index case identification to testing of contacts being reduced from seven to three days. The ability to identify the possible source of infection in the index case also increased. CONCLUSIONS: Despite the spread of the Alpha variant during the study period in RE, the secondary case attack rate remained stable from school reopening in September 2020 until the beginning of April 2021.

Effectiveness of BNT162b2 vaccine against SARS-CoV-2 infection and severe COVID-19 in children aged 5-11 years in Italy: a retrospective analysis of January-April, 2022.

BACKGROUND: By April 13, 2022, more than 4 months after the approval of BNT162b2 (Pfizer-BioNTech) for children, less than 40% of 5-11-year-olds in Italy had been vaccinated against COVID-19. Estimating how effective vaccination is in 5-11-year-olds in the current epidemiological context dominated by the omicron variant (B.1.1.529) is important to inform public health bodies in defining vaccination policies and strategies. METHODS: In this retrospective population analysis, we assessed vaccine effectiveness against SARS-CoV-2 infection and severe COVID-19, defined as an infection leading to hospitalisation or death, by linking the national COVID-19 surveillance system and the national vaccination registry. All Italian children aged 5-11 years without a previous diagnosis of infection were eligible for inclusion and were followed up from Jan 17 to April 13, 2022. All children with inconsistent vaccination data, diagnosed with SARS-CoV-2 infection before the start date of the study or without information on the municipality of residence were excluded from the analysis. With unvaccinated children as the reference group, we estimated vaccine effectiveness in those who were partly vaccinated (one dose) and those who were fully vaccinated (two doses). FINDINGS: By April 13, 2022, 1 063 035 (35·8%) of the 2 965 918 children aged 5-11 years included in the study had received two doses of the vaccine, 134 386 (4·5%) children had received one dose only, and 1 768 497 (59·6%) were unvaccinated. During the study period, 766 756 cases of SARS-CoV-2 infection and 644 cases of severe COVID-19 (627 hospitalisations, 15 admissions to intensive care units, and two deaths) were notified. Overall, vaccine effectiveness in the fully vaccinated group was 29·4% (95% CI 28·5-30·2) against SARS-CoV-2 infection and 41·1% (22·2-55·4) against severe COVID-19, whereas vaccine effectiveness in the partly vaccinated group was 27·4% (26·4-28·4) against SARS-CoV-2 infection and 38·1% (20·9-51·5) against severe COVID-19. Vaccine effectiveness against infection peaked at 38·7% (37·7-39·7) at 0-14 days after full vaccination and decreased to 21·2% (19·7-22·7) at 43-84 days after full vaccination. INTERPRETATION: Vaccination against COVID-19 in children aged 5-11 years in Italy showed a lower effectiveness in preventing SARS-CoV-2 infection and severe COVID-19 than in individuals aged 12 years and older. Effectiveness against infection appears to decrease after completion of the current primary vaccination cycle. FUNDING: None. TRANSLATION: For the Italian translation of the summary see Supplementary Materials section.

Risk and protective factors for SARS-CoV-2 reinfections, surveillance data, Italy, August 2021 to March 2022.

We explored the risk factors associated with SARS-CoV-2 reinfections in Italy between August 2021 and March 2022. Regardless of the prevalent virus variant, being unvaccinated was the most relevant risk factor for reinfection. The risk of reinfection increased almost 18-fold following emergence of the Omicron variant compared with Delta. A severe first SARS-CoV-2 infection and age over 60 years were significant risk factors for severe reinfection.

Effectiveness of an mRNA vaccine booster dose against SARS-CoV-2 infection and severe COVID-19 in persons aged ≥60 years and other high-risk groups during predominant circulation of the delta variant in Italy, 19 July to 12 December 2021.

BACKGROUND: Consolidated information on the effectiveness of COVID-19 booster vaccination in Europe are scarce. RESEARCH DESIGN AND METHODS: We assessed the effectiveness of a booster dose of an mRNA vaccine against any SARS-CoV-2 infection (symptomatic or asymptomatic) and severe COVID-19 (hospitalization or death) after over two months from administration among priority target groups (n = 18,524,568) during predominant circulation of the Delta variant in Italy (July-December 2021). RESULTS: Vaccine effectiveness (VE) against SARS-CoV-2 infection and, to a lesser extent, against severe COVID-19, among people ≥60 years and other high-risk groups (i.e. healthcare workers, residents in long-term-care facilities, and persons with comorbidities or immunocompromised), peaked in the time-interval 3-13 weeks (VE against infection = 67.2%, 95% confidence interval (CI): 62.5-71.3; VE against severe disease = 89.5%, 95% CI: 86.1-92.0) and then declined, waning 26 weeks after full primary vaccination (VE against infection = 12.2%, 95% CI: -4.7-26.4; VE against severe disease = 65.3%, 95% CI: 50.3-75.8). After 3-10 weeks from the administration of a booster dose, VE against infection and severe disease increased to 76.1% (95% CI: 70.4-80.7) and 93.0% (95% CI: 90.2-95.0), respectively. CONCLUSIONS: These results support the ongoing vaccination campaign in Italy, where the administration of a booster dose four months after completion of primary vaccination is recommended.

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.

Effectiveness of mRNA vaccines and waning of protection against SARS-CoV-2 infection and severe covid-19 during predominant circulation of the delta variant in Italy: retrospective cohort study.

OBJECTIVES: To estimate the effectiveness of mRNA vaccines against SARS-CoV-2 infection and severe covid-19 at different time after vaccination. DESIGN: Retrospective cohort study. SETTING: Italy, 27 December 2020 to 7 November 2021. PARTICIPANTS: 33 250 344 people aged ≥16 years who received a first dose of BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine and did not have a previous diagnosis of SARS-CoV-2 infection. MAIN OUTCOME MEASURES: SARS-CoV-2 infection and severe covid-19 (admission to hospital or death). Data were divided by weekly time intervals after vaccination. Incidence rate ratios at different time intervals were estimated by multilevel negative binomial models with robust variance estimator. Sex, age group, brand of vaccine, priority risk category, and regional weekly incidence in the general population were included as covariates. Geographic region was included as a random effect. Adjusted vaccine effectiveness was calculated as (1-IRR)×100, where IRR=incidence rate ratio, with the time interval 0-14 days after the first dose of vaccine as the reference. RESULTS: During the epidemic phase when the delta variant was the predominant strain of the SARS-CoV-2 virus, vaccine effectiveness against SARS-CoV-2 infection significantly decreased (P<0.001) from 82% (95% confidence interval 80% to 84%) at 3-4 weeks after the second dose of vaccine to 33% (27% to 39%) at 27-30 weeks after the second dose. In the same time intervals, vaccine effectiveness against severe covid-19 also decreased (P<0.001), although to a lesser extent, from 96% (95% to 97%) to 80% (76% to 83%). High risk people (vaccine effectiveness -6%, -28% to 12%), those aged ≥80 years (11%, -15% to 31%), and those aged 60-79 years (2%, -11% to 14%) did not seem to be protected against infection at 27-30 weeks after the second dose of vaccine. CONCLUSIONS: The results support the vaccination campaigns targeting high risk people, those aged ≥60 years, and healthcare workers to receive a booster dose of vaccine six months after the primary vaccination cycle. The results also suggest that timing the booster dose earlier than six months after the primary vaccination cycle and extending the offer of the booster dose to the wider eligible population might be warranted.

Estimating averted COVID-19 cases, hospitalisations, intensive care unit admissions and deaths by COVID-19 vaccination, Italy, January-September 2021.

We assessed the impact of COVID-19 vaccination in Italy, by estimating numbers of averted COVID-19 cases, hospitalisations, ICU admissions and deaths between January and September 2021, by age group and geographical macro areas. Timing and speed of vaccination programme implementation varied slightly between geographical areas, particularly for older adults. We estimated that 445,193 (17% of expected; range: 331,059-616,054) cases, 79,152 (32%; range: 53,209-148,756) hospitalisations, 9,839 ICU admissions (29%; range: 6,434-16,276) and 22,067 (38%; range: 13,571-48,026) deaths were prevented by vaccination.

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.

Risk of SARS-CoV-2 infection and subsequent hospital admission and death at different time intervals since first dose of COVID-19 vaccine administration, Italy, 27 December 2020 to mid-April 2021.

To assess the real-world impact of vaccines on COVID-19 related outcomes, we analysed data from over 7 million recipients of at least one COVID-19 vaccine dose in Italy. Taking 0-14 days post-first dose as reference, the SARS-CoV-2 infection risk subsequently decreased, reaching a reduction by 78% (incidence rate ratios (IRR): 0.22; 95% CI: 0.21-0.24) 43-49 days post-first dose. Similarly, hospitalisation and death risks decreased, with 89% (IRR: 0.11; 95% CI: 0.09-0.15) and 93% (IRR: 0.07; 95% CI: 0.04-0.11) reductions 36-42 days post-first dose. Our results support ongoing vaccination campaigns.

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.