Estimated number of lives directly saved by COVID-19 vaccination programs in the WHO European Region, December 2020 to March 2023 (preprint)

BackgroundBy March 2023, 54 countries, areas and territories (thereafter "CAT") reported over 2.2 million coronavirus disease 2019 (COVID-19) deaths to the World Health Organization (WHO) Regional Office for Europe (1). Here, we estimate how many lives were directly saved by vaccinating adults in the Region, from December 2020 through March 2023. MethodsWe estimated the number of lives directly saved by age-group, vaccine dose and circulating Variant of Concern (VOC) period, both regionally and nationally, using weekly data on COVID-19 mortality and COVID-19 vaccine uptake reported by 34 CAT, and vaccine effectiveness (VE) data from the literature. We calculated the percentage reduction in the number of expected and reported deaths. FindingsWe found that vaccines reduced deaths by 57% overall (CAT range: 15% to 75%), representing [~]1.4 million lives saved in those aged [≥]25 years (range: 0.7 million to 2.6 million): 96% of lives saved were aged [≥]60 years and 52% were aged [≥]80 years; first boosters saved 51%, and 67% were saved during the Omicron period. InterpretationOver nearly 2.5 years, most lives saved by COVID-19 vaccinationwere in older adults by first booster dose and during the Omicron period, reinforcing the importance of up-to-date vaccination among these most at-risk individuals. Further modelling work should evaluate indirect effects of vaccination and public health and social measures. FundingThis work was supported by a US Centers for Disease Control cooperative agreement (Grant number 6 NU511P000936-02-020), who had no role in data analysis or interpretation. DisclaimerThe authors affiliated with the World Health Organization (WHO) are alone responsible for the views expressed in this publication and they do not necessarily represent the decisions or policies of the WHO. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSSince first identified in late 2019, COVID-19 has caused disproportionately high mortality rates in older adults. With the rapid development and licensing of novel COVID-19 vaccines, immunization campaigns across the WHO European Region started in late 2020 and early 2021, initially targeting the most vulnerable and exposed populations, including older adults, people with comorbidities and healthcare professionals. Several studies have estimated the number of lives saved by COVID-19 vaccination, both at national and multi-country level in the earlier stages of the pandemic. However, only one multi-country study has assessed the number of lives saved beyond the first year of the pandemic, particularly when the Omicron variant of concern (VOC) circulated, a period when vaccination coverage was high in many countries, areas and territories (CAT), but COVID-19 transmission was at its highest. Added value of this studyHere we quantified the impact of COVID-19 vaccination in adults by age-group, vaccine dose and period of circulation of VOC, across diverse settings, using real world data reported by 34 CAT in the WHO European Region for the period December 2020 to April 2023. We estimated that COVID-19 vaccination programs were associated with a 57% reduction (CAT range: 15% to 75%) in the number of deaths among the [≥]25 years old, representing over 1.5 million lives saved (range: 0.7 million to 2.6 million) in 34 European CAT during the first 2.5 years following vaccine introduction. The first booster savedthe most lives (721,122 / 1,408,967, (57%) of all lives saved). The [≥]60 years old age group accounted for 96% of the total lives saved (1,349,617 / 1,408,967) whereas the [≥]80 years old age group represented 52% of the total lives saved (728,858 / 1,408,967 lives saved) and 67% of all lives were saved during the Omicron period (942,571 / 1,408,967). Implications of all the available evidenceOur results reinforce the importance of up-to-date COVID-19 vaccination, particularly among older age-groups. Communication campaigns supporting COVID-19 vaccination should stress the value of COVID-19 vaccination in saving lives to ensure vulnerable groups are up-to-date with vaccination ahead of periods of potential increased transmission.

Increasing situational awareness through nowcasting of the reproduction number (preprint)

The time varying reproduction number R is a critical variable for situational awareness during infectious disease outbreaks, but delays between infection and reporting hinder its accurate estimation in real time. We propose a nowcasting method for improving the timeliness and accuracy of R estimates, based on comparisons of successive versions of surveillance databases. The method was validated against COVID-19 surveillance data collected in Italy over an 18-month period. Compared to traditional methods, the nowcasted reproduction number reduced the estimation delay from 13 to 8 days, while maintaining a better accuracy. Moreover, it allowed anticipating the detection of periods of epidemic growth by between 6 and 23 days. The method offers a simple and generally applicable tool to improve situational awareness during an epidemic outbreak, allowing for informed public health response planning.

Effect of an enhanced public health contact tracing intervention on the secondary transmission of SARS-CoV-2 in educational settings: the four-way decomposition analysis (preprint)

Background: We assessed the impact of testing contacts immediately instead of at the end of quarantine on the transmission of SARS-CoV-2 in schools in Reggio Emilia Province. Methods: We analysed surveillance data on notification of COVID-19 cases in schools between 1 September 2020 and 4 April 2021. Results: Median tracing delay decreased from 7 to 3.1 days and the percentage of the known infection source increased from 34% to 54.8% (IRR 1.61 1.40-1.86). Implementation of prompt contact tracing was associated with a 10% decrease in the number of secondary cases (excess relative risk, EER -0.1 95%CI -0.35 to 0.15). Knowing the source of infection of the index case led to a decrease in secondary transmission (IRR 0.75 95% CI 0.63-0.91) while the decrease in tracing delay was associated with decreased risk of secondary cases (1/IRR 0.97 95%CI 0.94-1.01 per one day of delay). The direct effect of the intervention accounted for the 29% decrease in the number of secondary cases (EER -0.29 95% -0.61 to 0.03). Conclusions: Prompt contact testing in the community seems to reduce the time of contact tracing and increases the ability to identify the source of infection in school outbreaks. Yet, observed differences can be also due to differences in the force of infection and to other control measures put in place.Funding: This project was carried out with the technical and financial support of the Italian46 Ministry of Health - CCM 2020 and Ricerca Corrente Annual Program 2023

The decline of COVID-19 severity and lethality over two years of pandemic (preprint)

Undernotification of SARS-CoV-2 infections has been a major obstacle to the tracking of critical quantities such as infection attack rates and the probability of severe and lethal outcomes. We use a model of SARS-CoV-2 transmission and vaccination informed by epidemiological and genomic surveillance data to estimate the number of daily infections occurred in Italy in the first two years of pandemic. We estimate that the attack rate of ancestral lineages, Alpha, and Delta were in a similar range (10-17%, range of 95% CI: 7-23%), while that of Omicron until February 20, 2022, was remarkably higher (51%, 95%CI: 33-70%). The combined effect of vaccination, immunity from natural infection, change in variant features, and improved patient management massively reduced the probabilities of hospitalization, admission to intensive care, and death given infection, with 20 to 40-fold reductions during the period of dominance of Omicron compared to the initial acute phase.

Secondary transmission of SARS-CoV-2 in educational settings in Northern Italy from September 2020 to April 2021: a population-based study (preprint)

BackgroundWe 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 Reggio Emilia province (RE), Italy. The secondary aim was to estimate the promptness of contact tracing. MethodsA population-based analysis of surveillance data of all COVID-19 cases occurring in RE, Italy, from September 1, 2020, to April 4th, 2021, for which a school contact and/or exposure was suspected. Indicator of the delay in contact tracing was computed as the time elapsed since positivity of the index case and the date on which the swab for classmates was scheduled (or most were scheduled). ResultsOverall, 30,184 and 13,608 contacts among classmates and teachers/staff, respectively, were identified and received recommendation for testing; 43,214 (98.7%) performed the test. Secondary transmission occurred in about 40% of the investigated classes, and the overall secondary case attack rate was 4%, slightly higher when the index case was a teacher, but with almost no differences by type of school and stable during the study period. Promptness of contact tracing increased during the study period, reducing the time from index case identification and testing of contacts from 7 to 3 days, as well the ability to identify possible source of infection in the index case. ConclusionsDespite 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.

Socio-Economic Patterns of COVID-19 During the Pandemic in Italy (preprint)

Objective: To investigate the association between deprivation and COVID-19 outcomes in Italy during pre-lockdown, lockdown and post-lockdown periods.Design: Retrospective cohort study.Setting: All municipalities in Italy with less than 50,000 population.Participants: 38,534,169 citizens and 222,875 COVID-19 cases reported to the Italian epidemiological surveillance were assigned to quintiles based on the deprivation index of their municipality of residence.Interventions: The COVID-19 pandemic during pre-lockdown, lockdown and post-lockdown from the 20th of February to the 15th of October of 2020.Main outcome measures: Multilevel negative binomial regression models, adjusting for age, sex, population-density and region of residence were conducted to evaluate the association between deprivation and COVID-19 incidence, case-hospitalisation rate and case-fatality. The association measure was the rate ratio.Results: During pre-lockdown, lockdown and post-lockdown, the incidence rate ratios (IRR) with 95% confidence interval (CI) in the most deprived quintile with respect to the least deprived quintile were 1.17 (95% CI 0.98 to 1.41), 1.14 (1.03 to 1.27) and 1.47 (1.32 to 1.63), respectively. In those three periods, the case-hospitalization IRR were 0.68 (0.51 to 0.92), 0.89 (0.72 to 1.11) and 0.99 (0.81 to 1.22) and the case-fatality IRR were 0.92 (0.75 to 1.13), 0.95 (0.85 to 1.07) and 1.02 (0.73 to 1.41), respectively.Conclusions: During lockdown and post-lockdown, but not during pre-lockdown, a 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.

Effectiveness of regional restrictions in reducing SARS-CoV-2 transmission during the second wave of COVID-19, Italy. (preprint)

To counter the second COVID-19 wave, the Italian government has adopted a scheme of three sets of restrictions (coded as yellow, orange, and red) imposed on a regional basis. We estimate that milder restrictions in regions at lower risk (yellow) resulted in a transmissibility reduction of about 18%, leading to a reproduction number Rt of about 0.99. Stricter measures (orange and red) led to reductions of 34% and 45% and Rt values of about 0.89 and 0.77 respectively.

Epidemiological characteristics of COVID-19 cases in non-Italian nationals notified to the Italian surveillance system (preprint)

BackgroundInternational 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. MethodsWe analysed 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 rate 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. ResultsWe analysed 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 hospitalised [(adjusted relative risk (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 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). ConclusionsA 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.

The relationship between human mobility and viral transmissibility during the COVID-19 epidemics in Italy (preprint)

In 2020, countries affected by the COVID-19 pandemic implemented various non-pharmaceutical interventions to contrast the spread of the virus and its impact on their healthcare systems and economies. Using Italian data at different geographic scales, we investigate the relationship between human mobility, which subsumes many facets of the population's response to the changing situation, and the spread of COVID-19. Leveraging mobile phone data from February through September 2020, we find a striking relationship between the decrease in mobility flows and the net reproduction number. We find that the time needed to switch off mobility and bring the net reproduction number below the critical threshold of 1 is about one week. Moreover, we observe a strong relationship between the number of days spent above such threshold before the lockdown-induced drop in mobility flows and the total number of infections per 100k inhabitants. Estimating the statistical effect of mobility flows on the net reproduction number over time, we document a 2-week lag positive association, strong in March and April, and weaker but still significant in June. Our study demonstrates the value of big mobility data to monitor the epidemic and inform control interventions during its unfolding.

The impact of a nation-wide lockdown on COVID-19 transmissibility in Italy (preprint)

On March 10, 2020, Italy imposed a national lockdown to curtail the spread of COVID-19. Here we estimate that, fourteen days after the implementation of the strategy, the net reproduction number has dropped below the epidemic threshold - estimated range 0.4-0.7. Our findings provide a timeline of the effectiveness of the implemented lockdown, which is relevant for a large number of countries that followed Italy in enforcing similar measures.

Epidemiological characteristics of COVID-19 cases in Italy and estimates of the reproductive numbers one month into the epidemic (preprint)

Background In February 2020, a locally-acquired COVID-19 case was detected in Lombardia, Italy. This was the first signal of ongoing transmission of SARS-CoV-2 in the country. The outbreak rapidly escalated to a national level epidemic, amid the WHO declaration of a pandemic. Methods We analysed data from the national case-based integrated surveillance system of all RT-PCR confirmed COVID-19 infections as of March 24th 2020, collected from all Italian regions and autonomous provinces. Here we provide a descriptive epidemiological summary on the first 62,843 COVID-19 cases in Italy as well as estimates of the basic and net reproductive numbers by region. Findings Of the 62,843 cases of COVID-19 analysed, 71.6% were reported from three Regions (Lombardia, Veneto and Emilia-Romagna). All cases reported after February 20th were locally acquired. Estimates of R0 varied between 2.5 (95%CI: 2.18-2.83) in Toscana and 3 (95%CI: 2.68-3.33) in Lazio, with epidemic doubling time of 3.2 days (95%CI: 2.3-5.2) and 2.9 days (95%CI: 2.2-4.3), respectively. The net reproduction number showed a decreasing trend starting around February 20-25, 2020 in northern regions. Notably, 5,760 cases were reported among health care workers. Of the 5,541 reported COVID-19 associated deaths, 49% occurred in people aged 80 years or above with an overall crude CFR of 8.8%. Male sex and age were independent risk factors for COVID-19 death. Interpretation The COVID-19 infection in Italy emerged with a clustering onset similar to the one described in Wuhan, China and likewise showed worse outcomes in older males with comorbidities. Initial R0 at 2.96 in Lombardia, explains the high case-load and rapid geographical spread observed. Overall Rt in Italian regions is currently decreasing albeit with large diversities across the country, supporting the importance of combined non-pharmacological control measures.