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.

Risk of breakthrough infection and hospitalisation after COVID-19 primary vaccination by HIV status in four Italian regions during 2021.

BACKGROUND: As of 2024, vaccination remains the main mitigation measure against COVID-19, but there are contradictory results on whether people living with HIV (PLWH) are less protected by vaccines than people living without HIV (PLWoH). In this study we compared the risk of SARS-CoV-2 infection and COVID-19 hospitalisation following full vaccination in PLWH and PLWoH. METHODS: We linked data from the vaccination registry, the COVID-19 surveillance system and from healthcare/pharmacological registries in four Italian regions. We identified PLWH fully vaccinated (14 days post completion of the primary cycle) and matched them at a ratio of 1:4 with PLWoH by week of vaccine administration, age, sex, region of residence and comorbidities. Follow-up started on January 24, 2021, and lasted for a maximum of 234 days. We used the Kaplan-Meier estimator to calculate the cumulative incidence of infection and COVID-19 hospitalisation in both groups, and we compared risks using risk differences and ratios taking PLWoH as the reference group. RESULTS: We matched 42,771 PLWH with 171,084 PLWoH. The overall risk of breakthrough infection was similar in both groups with a rate ratio (RR) of 1.10 (95% confidence interval (CI):0.80-1.53). The absolute difference between groups at the end of the study period was 8.28 events per 10,000 person-days in the PLWH group (95%CI:-18.43-40.29). There was a non-significant increase the risk of COVID-19 hospitalisation among PLWH (RR:1.90; 95%CI:0.93-3.32) which corresponds to 6.73 hospitalisations per 10,000 individuals (95%CI: -0.57 to 14.87 per 10,000). CONCLUSIONS: Our findings suggest PLWH were not at increased risk of breakthrough SARS-CoV-2 infection or COVID-19 hospitalisation following a primary cycle of mRNA vaccination.

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.

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.

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.

Winning during a pandemic: epidemiology of SARS-CoV-2 during EURO2020 in Italy.

INTRODUCTION: EURO2020 generated a growing media and population interest across the month period, that peaked with large spontaneous celebrations across the country upon winning the tournament. METHODS: We retrospectively analysed data from the national surveillance system (indicator-based) and from event-based surveillance to assess how the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) changed in June-July 2021 and to describe cases and clusters linked with EURO2020. RESULTS: Widespread increases in transmission and case numbers, mainly among younger males, were documented in Italy, none were linked with stadium attendance. Vaccination coverage against SARS-CoV-2 was longer among cases linked to EURO2020 than among the general population. CONCLUSIONS: Transmission increased across the country, mainly due to gatherings outside the stadium, where, conversely, strict infection control measures were enforced. These informal 'side' gatherings were dispersed across the entire country and difficult to control. Targeted communication and control strategies to limit the impact of informal gatherings occurring outside official sites of mass gathering events should be further developed.

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.

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.

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.

Italian National Surveillance of Alcohol-Based Hand Rub Consumption in a Healthcare Setting-A Three-Year Analysis: 2020-2022.

Background/Objectives: Hand hygiene (HH) is pivotal in mitigating infectious disease transmission and enhancing public health outcomes. This study focuses on detailing the national surveillance system for alcohol-based hand rub (ABHR) consumption in healthcare facilities across Italy, presenting results from a comprehensive three-year evaluation period, from 2020 to 2022. It aims to delineate this surveillance system and report on ABHR consumption trends in various Regions/Autonomous Provinces (Rs/APs). Methods: ABHR consumption data, collected through the ABHR Italian national surveillance system, coordinated by the Istituto Superiore di Sanità (ISS), were analyzed. Statistical methods, e.g., the Mann-Whitney test, were used to assess trends in ABHR consumption, expressed in liters per 1000 patient days (L/1000PD). Results: The results show significant variation in ABHR consumption across Rs/APs and over the years studied. National median ABHR consumption decreased from 2020 to 2022, with a significant reduction from a median of 24.5 L/1000PD in 2020 to 20.4 L/1000PD in 2021 and 15.6 L/1000PD in 2022. Conclusions: The decline in ABHR consumption raises concerns about the ongoing adherence to HH practices in Italian healthcare settings. This underscores the essential role that systematic ABHR monitoring and improved surveillance play in enhancing HH compliance, suggesting that sustained and strategic efforts are fundamental to uphold high standards of hygiene and to effectively respond to fluctuating ABHR usage trends over time. Further research is needed to explore barriers to effective ABHR use and to develop targeted strategies to improve HH practices.

Effectiveness against severe COVID-19 of a seasonal booster dose of bivalent (original/Omicron BA.4-5) mRNA vaccines in persons aged ≥60 years: Estimates over calendar time and by time since administration during prevalent circulation of different Omicron subvariants, Italy, 2022-2023.

Evaluating how a COVID-19 seasonal vaccination program performed might help to plan future campaigns. This study aims to estimate the relative effectiveness (rVE) against severe COVID-19 of a seasonal booster dose over calendar time and by time since administration. We conducted a retrospective cohort analysis among 13,083,855 persons aged ≥60 years who were eligible to receive a seasonal booster at the start of the 2022-2023 vaccination campaign in Italy. We estimated rVE against severe COVID-19 (hospitalization or death) of a seasonal booster dose of bivalent (original/Omicron BA.4-5) mRNA vaccines by two-month calendar interval and at different times post-administration. We used multivariable Cox regression models, including vaccination as time-dependent exposure, to estimate adjusted hazard ratios (HR) and rVEs as [(1-HR)X100]. The rVE of a seasonal booster decreased from 64.9% (95% CI: 59.8-69.4) in October-November 2022 to 22.0% (95% CI: 15.4-28.0) in April-May 2023, when the majority of vaccinated persons (67%) had received the booster at least 4-6 months earlier. During the epidemic phase with prevalent circulation of the Omicron BA.5 subvariant, rVE of a seasonal booster received ≤90 days earlier was 83.0% (95% CI: 79.1-86.1), compared to 37.4% (95% CI: 25.5-47.5) during prevalent circulation of the Omicron XBB subvariant. During the XBB epidemic phase, rVE was estimated at 15.8% (95% CI: 9.1-20.1) 181-369 days post-administration of the booster dose. In all the analyses we observed similar trends of rVE between persons aged 60-79 and those ≥80 years, although estimates were somewhat lower for the oldest group. A seasonal booster dose received during the vaccination campaign provided additional protection against severe COVID-19 up to April-May 2023, after which the incidence of severe COVID-19 was much reduced. The results also suggest that the Omicron XBB subvariant might have partly escaped the immunity provided by the seasonal booster targeting the original and Omicron BA.4-5 strains of SARS-CoV-2.

SARS-CoV-2 Breakthrough Infections According to the Immune Response Elicited after mRNA Third Dose Vaccination in COVID-19-Naïve Hospital Personnel.

BACKGROUND: Vaccine-induced SARS-CoV-2-anti-spike antibody (anti-S/RBD) titers are often used as a marker of immune protection and to anticipate the risk of breakthrough infections, although no clear cut-off is available. We describe the incidence of SARS-CoV-2 vaccine breakthrough infections in COVID-19-free personnel of our hospital, according to B- and T-cell immune response elicited one month after mRNA third dose vaccination. METHODS: The study included 487 individuals for whom data on anti-S/RBD were available. Neutralizing antibody titers (nAbsT) against the ancestral Whuan SARS-CoV-2, and the BA.1 Omicron variant, and SARS-CoV-2 T-cell specific response were measured in subsets of 197 (40.5%), 159 (32.6%), and 127 (26.1%) individuals, respectively. RESULTS: On a total of 92,063 days of observation, 204 participants (42%) had SARS-CoV-2 infection. No significant differences in the probability of SARS-CoV-2 infection for different levels of anti-S/RBD, nAbsT, Omicron nAbsT, or SARS-CoV-2 T cell specific response, and no protective thresholds for infection were found. CONCLUSIONS: Routine testing for vaccine-induced humoral immune response to SARS-CoV-2 is not recommended if measured as parameters of 'protective immunity' from SARS-CoV-2 after vaccination. Whether these findings apply to new Omicron-specific bivalent vaccines is going to be evaluated.

The Impact of Rotavirus Vaccination on Discharges for Pediatric Gastroenteritis in Italy: An Eleven Year (2009-2019) Nationwide Analysis.

In Italy, despite the documented positive effects of rotavirus (RV) vaccination on reducing the burden of RV disease, an updated national assessment of its impact on clinical outcomes is still lacking. This study aims to analyze the implementation of RV vaccination in Italy, evaluating its impact on discharges for acute pediatric gastroenteritis (AGE). A retrospective analysis, including hospital discharge records and data on vaccination coverage for children aged 0-71 months from 2009 to 2019, was conducted. We examined trends in hospital discharge standardized incidence before and after vaccine introduction using a negative binomial mixture model with fixed effects to evaluate the impact of universal vaccination. The percentage of vaccination coverage increased over the years, from <5% between 2009 and 2013 to 26% in 2017, reaching 70% in 2019. The standardized incidence of discharges decreased over the period from 16.6/100,000 inhabitants in 2009-2013 to 9.9/100,000 inhabitants in 2018-2019. In this phase, about 15% of the estimated hospital discharges were avoided compared with those estimated in the first phase. The implementation of RV vaccination reduced AGE incidence discharges in children aged 0-71 months. Further efforts are needed to continue monitoring the vaccination effect over time and to increase vaccination coverage.

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.

Early Warning Systems for Emerging Profiles of Antimicrobial Resistance in Italy: A National Survey.

Antimicrobial resistance (AMR) national surveillance systems in Italy lack alert systems for timely detection of emerging profiles of AMR with potential relevance to public health. Furthermore, the existence of early warning systems (EWS) at subnational level is unclear. This study aims at mapping and characterizing EWS for microbiological threats available at regional level in Italy, focusing on emerging AMR, and at outlining potential barriers and facilitators to their development/implementation. To this end, a three-section, web-based survey was developed and administered to all Italian regional AMR representatives from June to August 2022. Twenty out of twenty-one regions and autonomous provinces (95.2%) responded to the survey. Among these, nine (45%) reported the implementation of EWS for microbiological threats at regional level, three (15%) reported that EWS are in the process of being developed, and eight (40%) reported that EWS are not currently available. EWS characteristics varied widely among the identified systems concerning both AMR profiles reported and data flow: the microorganisms most frequently included were extensively drug-resistant (XDR) Enterobacterales, with the lack of a dedicated regional IT platform reported in most cases. The results of this study depict a highly heterogeneous scenario and suggest that more efforts aimed at strengthening national AMR surveillance systems are needed.

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.

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.

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.