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.

Socioeconomic Inequalities in SARS-CoV-2 Infection and COVID-19 Health Outcomes in Urban Italy During the COVID-19 Vaccine Rollout, January-November 2021.

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

Estimated Effectiveness of a Primary Cycle of Protein Recombinant Vaccine NVX-CoV2373 Against COVID-19.

Importance: Protein recombinant vaccine NVX-CoV2373 (Novavax) against COVID-19 was authorized for its use in adults in late 2021, but evidence on its estimated effectiveness in a general population is lacking. Objective: To estimate vaccine effectiveness of a primary cycle with NVX-CoV2373 against SARS-CoV-2 infection and symptomatic COVID-19. Design, Setting, and Participants: Retrospective cohort study linking data from the national vaccination registry and the COVID-19 surveillance system in Italy during a period of Omicron predominance. All adults starting a primary vaccination with NVX-CoV2373 between February 28 and September 4, 2022, were included, with follow-up ending on September 25, 2022. Data were analyzed in February 2023. Exposures: Partial (1 dose only) vaccination and full vaccination (2 doses) with NVX-CoV-2373. Main Outcomes and Measures: Notified SARS-CoV-2 infection and symptomatic COVID-19. Poisson regression models were used to estimate effectiveness against both outcomes. Adjusted estimated vaccine effectiveness was calculated as (1 - incidence rate ratio) × 100. Results: The study included 20 903 individuals who started the primary cycle during the study period. Median (IQR) age of participants was 52 (39-61) years, 10 794 (51.6%) were female, and 20 592 participants (98.5%) had no factors associated with risk for severe COVID-19. Adjusted estimated vaccine effectiveness against notified SARS-CoV-2 infection in those partially vaccinated with NVX-CoV2373 was 23% (95% CI, 13%-33%) and was 31% (95% CI, 22%-39%) in those fully vaccinated. Estimated vaccine effectiveness against symptomatic COVID-19 was 31% (95% CI, 16%-44%) in those partially vaccinated and 50% (95% CI, 40%-58%) in those fully vaccinated. Estimated effectiveness during the first 4 months after completion of the primary cycle decreased against SARS-CoV-2 infection but remained stable against symptomatic COVID-19. Conclusions and Relevance: This cohort study found that, in an Omicron-dominant period, protein recombinant vaccine NVX-CoV2373 was associated with protection against SARS-CoV-2 infection and symptomatic COVID-19. The use of this vaccine could remain an important element in reducing the impact of the SARS-CoV-2 pandemic.

A comparison of COVID-19 incidence rates across six European countries in 2021.

International comparisons of COVID-19 incidence rates have helped gain insights into the characteristics of the disease, benchmark disease impact, shape public health measures and inform potential travel restrictions and border control measures. However, these comparisons may be biased by differences in COVID-19 surveillance systems and approaches to reporting in each country. To better understand these differences and their impact on incidence comparisons, we collected data on surveillance systems from six European countries: Belgium, England, France, Italy, Romania and Sweden. Data collected included: target testing populations, access to testing, case definitions, data entry and management and statistical approaches to incidence calculation. Average testing, incidence and contextual data were also collected. Data represented the surveillance systems as they were in mid-May 2021. Overall, important differences between surveillance systems were detected. Results showed wide variations in testing rates, access to free testing and the types of tests recorded in national databases, which may substantially limit incidence comparability. By systematically including testing information when comparing incidence rates, these comparisons may be greatly improved. New indicators incorporating testing or existing indicators such as death or hospitalisation will be important to improving international comparisons.

Estimating SARS-CoV-2 infections and associated changes in COVID-19 severity and fatality.

Background: The difficulty in identifying SARS-CoV-2 infections has not only been the major obstacle to control the COVID-19 pandemic but also to quantify changes in the proportion of infections resulting in hospitalization, intensive care unit (ICU) admission, or death. Methods: We developed a model of SARS-CoV-2 transmission and vaccination informed by official estimates of the time-varying reproduction number to estimate infections that occurred in Italy between February 2020 and 2022. Model outcomes were compared with the Italian National surveillance data to estimate changes in the SARS-CoV-2 infection ascertainment ratio (IAR), infection hospitalization ratio (IHR), infection ICU ratio (IIR), and infection fatality ratio (IFR) in five different sub-periods associated with the dominance of the ancestral lineages and Alpha, Delta, and Omicron BA.1 variants. Results: We estimate that, over the first 2 years of pandemic, the IAR ranged between 15% and 40% (range of 95%CI: 11%-61%), with a peak value in the second half of 2020. The IHR, IIR, and IFR consistently decreased throughout the pandemic with 22-44-fold reductions between the initial phase and the Omicron period. At the end of the study period, we estimate an IHR of 0.24% (95%CI: 0.17-0.36), IIR of 0.015% (95%CI: 0.011-0.023), and IFR of 0.05% (95%CI: 0.04-0.08). Conclusions: Since 2021, changes in the dominant SARS-CoV-2 variant, vaccination rollout, and the shift of infection to younger ages have reduced SARS-CoV-2 infection ascertainment. The same factors, combined with the improvement of patient management and care, contributed to a massive reduction in the severity and fatality of COVID-19.

One health adoption within prevention, preparedness and response to health threats: Highlights from a scoping review.

Introduction: As the COVID-19 pandemic has demonstrated, the complexity of factors involved in the emergence of health threats requires a holistic One Health (OH) approach to enhance the effectiveness of prevention, preparedness, and response (PPR) strategies. Therefore, we conducted a scoping review to explore how the OH approach has been adopted in the context of PPR strategies to health threats, and the challenges and benefits deriving from its integration. Methods: We defined the research questions and a strategy to guide the peer-reviewed and grey literature search to identify relevant articles and documents (identification). We assessed them for eligibility according to predefined criteria (screening) and finally included the ones that answered the research questions (inclusion). We performed a descriptive and thematic analysis of the results. Results: A total of 138 records were included in the review (57 from the peer-reviewed literature and 81 from the grey literature). The OH approach was mainly adopted in prevention strategies, particularly within the governance area. Human and animal health were the most integrated disciplines in the OH approach, while environmental and social sciences were the less integrated. The most targeted threats were antimicrobial resistance and zoonoses, with the African region being the most represented. Conducive factors for the adoption of OH PPR strategies were identified in resolutions and guidance emanating from international organisations. Discussion: The global governance of OH should utilise conducive factors, such as international resolutions and guidance, to enhance the adoption of multisectoral and multi-actor PPR strategies, that focus on national and international priorities and neglected threats, such as environmental hazards and pandemic risk. Integrated frameworks and metrics for the implementation and evaluation of OH PPR strategies need to be consolidated to contribute to the growing body of evidence supporting the adoption of the OH approach.

Relative effectiveness of bivalent Original/Omicron BA.4-5 mRNA vaccine in preventing severe COVID-19 in persons 60 years and above during SARS-CoV-2 Omicron XBB.1.5 and other XBB sublineages circulation, Italy, April to June 2023.

During predominant circulation of SARS-CoV-2 Omicron XBB.1.5 and other XBB sublineages (April-June 2023), we found that a second or third booster of Comirnaty bivalent Original/Omicron BA.4-5 mRNA vaccine, versus a first booster received at least 120 days earlier, was effective in preventing severe COVID-19 for more than 6 months post-administration in persons 60 years and above. In view of autumn 2023 vaccination campaigns, use of bivalent Original/Omicron BA.4-5 mRNA vaccines might be warranted until monovalent COVID-19 vaccines targeting Omicron XBB.1 sublineages become available.

Relative effectiveness of monovalent and bivalent mRNA boosters in preventing severe COVID-19 due to omicron BA.5 infection up to 4 months post-administration in people aged 60 years or older in Italy: a retrospective matched cohort study.

BACKGROUND: Limited evidence is available on the additional protection conferred by second mRNA vaccine boosters against severe COVID-19 caused by omicron BA.5 infection, and whether the adapted bivalent boosters provide additional protection compared with the monovalent ones. In this study, we aimed to estimate the relative effectiveness of a second booster with monovalent or bivalent mRNA vaccines against severe COVID-19 in Italy. METHODS: Linking data from the Italian vaccination registry and the SARS-CoV-2 surveillance system, between Sept 12, 2022, and Jan 7, 2023, we matched 1:1 each person aged 60 years or older receiving a second booster with a person who had received the first booster only at least 120 days earlier. We used hazard ratios, estimated through Cox proportional hazard models, to compare the hazard of severe COVID-19 between the first booster group and each type of second booster (monovalent mRNA vaccine targeting the original strain of SARS-CoV-2, bivalent mRNA vaccine targeting the original strain plus omicron BA.1 [bivalent original/BA.1], and bivalent mRNA vaccine targeting the original strain plus omicron BA.4 and BA.5 [bivalent original/BA.4-5]). Relative vaccine effectiveness (rVE) was calculated as (1-hazard ratio) × 100. FINDINGS: We analysed a total of 2 129 559 matched pairs. The estimated rVE against severe COVID-19 with the bivalent original/BA.4-5 booster was 50·6% (95% CI 46·0-54·8) in the overall time interval 14-118 days post-administration. Overall, rVE was 49·3% (43·6-54·4) for the bivalent original/BA.1 booster and 26·9% (11·8-39·3) for the monovalent booster. For the bivalent original/BA.4-5 booster, we did not observe relevant differences in rVE between the 60-79-year age group (overall, 53·6%; 46·8-59·5) and those aged 80 years or older (overall, 48·3%; 41·9-54·0). INTERPRETATION: These findings suggest that a second booster with mRNA vaccines provides additional protection against severe COVID-19 due to omicron BA.5 (the predominant circulating subvariant in Italy during the study period) in people aged 60 years or older. Although rVE decreased over time, a second booster with the original/BA.4-5 mRNA vaccine, currently the most used in Italy, was found to be still providing protection 4 months post-administration. FUNDING: NextGenerationEU-MUR-PNRR Extended Partnership initiative on Emerging Infectious Diseases (project number PE00000007, INF-ACT). TRANSLATION: For the Italian translation of the abstract see Supplementary Materials section.

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.

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.

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.

Diagnosis of Imported Dengue and Zika Virus Infections in Italy from November 2015 to November 2022: Laboratory Surveillance Data from a National Reference Laboratory.

Dengue (DENV) and Zika (ZIKV) viruses are mosquito-borne human pathogens. In Italy, the presence of the competent vector Aedes albopictus increases the risk of autochthonous transmission, and a national plan for arboviruses prevention, surveillance, and response (PNA 2020-2025) is in place. The results of laboratory diagnosis of both viruses by the National Reference Laboratory for arboviruses (NRLA) from November 2015 to November 2022 are presented. Samples from 655 suspected cases were tested by both molecular and serological assays. Virus and antibody kinetics, cross-reactivity, and diagnostic performance of IgM ELISA systems were analysed. Of 524 cases tested for DENV, 146 were classified as confirmed, 7 as probable, while 371 were excluded. Of 619 cases tested for ZIKV, 44 were classified as confirmed, while 492 were excluded. All cases were imported. Overall, 75.3% (110/146) of DENV and 50% (22/44) of ZIKV cases were confirmed through direct virus detection methods. High percentages of cross reactivity were observed between the two viruses. The median lag time from symptoms onset to sample collection was 7 days for both DENV molecular (range 0-20) and NS1 ELISA (range 0-48) tests, with high percentages of positivity also after 7 days (39% and 67%, respectively). For ZIKV, the median lag time was 5 days (range 0-22), with 16% positivity after 7 days. Diagnostic performance was assessed with negative predictive values ranging from 92% to 95% for the anti-DENV systems, and of 97% for the ZIKV one. Lower positive predictive values were seen in the tested population (DENV: 55% to 91%, ZIKV: 50%). DENV and ZIKV diagnosis by molecular test is the gold standard, but sample collection time is a limitation. Serological tests, including Plaque Reduction Neutralization Test, are thus necessary. Co-circulation and cross-reactivity between the two viruses increase diagnostic difficulty. Continuous evaluation of diagnostic strategies is essential to improve laboratory testing.

Estimation of the incubation period and generation time of SARS-CoV-2 Alpha and Delta variants from contact tracing data.

Quantitative information on epidemiological quantities such as the incubation period and generation time of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is scarce. We analysed a dataset collected during contact tracing activities in the province of Reggio Emilia, Italy, throughout 2021. We determined the distributions of the incubation period for the Alpha and Delta variants using information on negative polymerase chain reaction tests and the date of last exposure from 282 symptomatic cases. We estimated the distributions of the intrinsic generation time using a Bayesian inference approach applied to 9724 SARS-CoV-2 cases clustered in 3545 households where at least one secondary case was recorded. We estimated a mean incubation period of 4.9 days (95% credible intervals, CrI, 4.4-5.4) for Alpha and 4.5 days (95% CrI 4.0-5.0) for Delta. The intrinsic generation time was estimated to have a mean of 7.12 days (95% CrI 6.27-8.44) for Alpha and of 6.52 days (95% CrI 5.54-8.43) for Delta. The household serial interval was 2.43 days (95% CrI 2.29-2.58) for Alpha and 2.74 days (95% CrI 2.62-2.88) for Delta, and the estimated proportion of pre-symptomatic transmission was 48-51% for both variants. These results indicate limited differences in the incubation period and intrinsic generation time of SARS-CoV-2 variants Alpha and Delta compared to ancestral lineages.

Characteristics of COVID-19 cases in Italy from a sex/gender perspective.

INTRODUCTION: Coronavirus disease 19 (COVID-19) is an infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). To date, few data on clinical features and risk factors for disease severity and death by gender are available. AIM: The current study aims to describe from a sex/gender perspective the characteristics of the SARS-CoV-2 cases occurred in the Italian population from February 2020 until October 2021. METHOD AND RESULTS: We used routinely collected data retrieved from the Italian National Surveillance System. The highest number of cases occurred among women between 40 and 59 years, followed by men in the same age groups. The proportion of deaths due to COVID-19 was higher in men (56.46%) compared to women (43.54%). Most of the observed deaths occurred in the elderly. Considering the age groups, the clinical outcomes differed between women and men in particular in cases over 80 years of age; with serious or critical conditions more frequent in men than in women. CONCLUSIONS: Our data clearly demonstrate a similar number of cases in women and men, but with more severe disease and outcome in men, thus confirming the importance to analyse the impact of sex and gender in new and emerging diseases.

Assessing COVID-19-Related Excess Mortality Using Multiple Approaches-Italy, 2020-2021.

INTRODUCTION: Excess mortality (EM) is a valid indicator of COVID-19's impact on public health. Several studies regarding the estimation of EM have been conducted in Italy, and some of them have shown conflicting values. We focused on three estimation models and compared their results with respect to the same target population, which allowed us to highlight their strengths and limitations. METHODS: We selected three estimation models: model 1 (Maruotti et al.) is a Negative-Binomial GLMM with seasonal patterns; model 2 (Dorrucci et al.) is a Negative Binomial GLM epidemiological approach; and model 3 (Scortichini et al.) is a quasi-Poisson GLM time-series approach with temperature distributions. We extended the time windows of the original models until December 2021, computing various EM estimates to allow for comparisons. RESULTS: We compared the results with our benchmark, the ISS-ISTAT official estimates. Model 1 was the most consistent, model 2 was almost identical, and model 3 differed from the two. Model 1 was the most stable towards changes in the baseline years, while model 2 had a lower cross-validation RMSE. DISCUSSION: Presently, an unambiguous explanation of EM in Italy is not possible. We provide a range that we consider sound, given the high variability associated with the use of different models. However, all three models accurately represented the spatiotemporal trends of the pandemic waves in Italy.

Tracking the progressive spread of the SARS-CoV-2 Omicron variant in Italy, December 2021 to January 2022.

BackgroundThe SARS-CoV-2 variant of concern Omicron was first detected in Italy in November 2021.AimTo comprehensively describe Omicron spread in Italy in the 2 subsequent months and its impact on the overall SARS-CoV-2 circulation at population level.MethodsWe analyse data from four genomic surveys conducted across the country between December 2021 and January 2022. Combining genomic sequencing results with epidemiological records collated by the National Integrated Surveillance System, the Omicron reproductive number and exponential growth rate are estimated, as well as SARS-CoV-2 transmissibility.ResultsOmicron became dominant in Italy less than 1 month after its first detection, representing on 3 January 76.9-80.2% of notified SARS-CoV-2 infections, with a doubling time of 2.7-3.3 days. As of 17 January 2022, Delta variant represented < 6% of cases. During the Omicron expansion in December 2021, the estimated mean net reproduction numbers respectively rose from 1.15 to a maximum of 1.83 for symptomatic cases and from 1.14 to 1.36 for hospitalised cases, while remaining relatively stable, between 0.93 and 1.21, for cases needing intensive care. Despite a reduction in relative proportion, Delta infections increased in absolute terms throughout December contributing to an increase in hospitalisations. A significant reproduction numbers' decline was found after mid-January, with average estimates dropping below 1 between 10 and 16 January 2022.ConclusionEstimates suggest a marked growth advantage of Omicron compared with Delta variant, but lower disease severity at population level possibly due to residual immunity against severe outcomes acquired from vaccination and prior infection.

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.

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.

Intrinsic generation time of the SARS-CoV-2 Omicron variant: An observational study of household transmission.

Background: Starting from the final months of 2021, the SARS-CoV-2 Omicron variant expanded globally, swiftly replacing Delta, the variant that was dominant at the time. Many uncertainties remain about the epidemiology of Omicron; here, we aim to estimate its generation time. Methods: We used a Bayesian approach to analyze 23,122 SARS-CoV-2 infected individuals clustered in 8903 households as determined from contact tracing operations in Reggio Emilia, Italy, throughout January 2022. We estimated the distribution of the intrinsic generation time (the time between the infection dates of an infector and its secondary cases in a fully susceptible population), realized household generation time, realized serial interval (time between symptom onset of an infector and its secondary cases), and contribution of pre-symptomatic transmission. Findings: We estimated a mean intrinsic generation time of 6.84 days (95% credible intervals, CrI, 5.72-8.60), and a mean realized household generation time of 3.59 days (95%CrI: 3.55-3.60). The household serial interval was 2.38 days (95%CrI 2.30-2.47) with about 51% (95%CrI 45-56%) of infections caused by symptomatic individuals being generated before symptom onset. Interpretation: These results indicate that the intrinsic generation time of the SARS-CoV-2 Omicron variant might not have shortened as compared to previous estimates on ancestral lineages, Alpha and Delta, in the same geographic setting. Like for previous lineages, pre-symptomatic transmission appears to play a key role for Omicron transmission. Estimates in this study may be useful to design quarantine, isolation and contact tracing protocols and to support surveillance (e.g., for the accurate computation of reproduction numbers). Funding: The study was partially funded by EU grant 874850 MOOD.