Increasing situational awareness through nowcasting of the reproduction number.

Background: The time-varying reproduction number R is a critical variable for situational awareness during infectious disease outbreaks; however, delays between infection and reporting of cases hinder its accurate estimation in real-time. A number of nowcasting methods, leveraging available information on data consolidation delays, have been proposed to mitigate this problem. Methods: In this work, we retrospectively validate the use of a nowcasting algorithm during 18 months of the COVID-19 pandemic in Italy by quantitatively assessing its performance against standard methods for the estimation of R. Results: Nowcasting significantly reduced the median lag in the estimation of R from 13 to 8 days, while concurrently enhancing accuracy. Furthermore, it allowed the detection of periods of epidemic growth with a lead of between 6 and 23 days. Conclusions: Nowcasting augments epidemic awareness, empowering better informed public health responses.

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.

Estimating the potential risk of transmission of arboviruses in the Americas and Europe: a modelling study.

BACKGROUND: Estimates of the spatiotemporal distribution of different mosquito vector species and the associated risk of transmission of arboviruses are key to design adequate policies for preventing local outbreaks and reducing the number of human infections in endemic areas. In this study, we quantified the abundance of Aedes albopictus and Aedes aegypti and the local transmission potential for three arboviral infections at an unprecedented spatiotemporal resolution in areas where no entomological surveillance is available. METHODS: We developed a computational model to quantify the daily abundance of Aedes mosquitoes, leveraging temperature and precipitation records. The model was calibrated on mosquito surveillance data collected in 115 locations in Europe and the Americas between 2007 and 2018. Model estimates were used to quantify the reproduction number of dengue virus, Zika virus, and chikungunya in Europe and the Americas, at a high spatial resolution. FINDINGS: In areas colonised by both Aedes species, A aegypti was estimated to be the main vector for the transmission of dengue virus, Zika virus, and chikungunya, being associated with a higher estimate of R0 when compared with A albopictus. Our estimates highlighted that these arboviruses were endemic in tropical and subtropical countries, with the highest risks of transmission found in central America, Venezuela, Colombia, and central-east Brazil. A non-negligible potential risk of transmission was also estimated for Florida, Texas, and Arizona (USA). The broader ecological niche of A albopictus could contribute to the emergence of chikungunya outbreaks and clusters of dengue autochthonous cases in temperate areas of the Americas, as well as in mediterranean Europe (in particular, in Italy, southern France, and Spain). INTERPRETATION: Our results provide a comprehensive overview of the transmission potential of arboviral diseases in Europe and the Americas, highlighting areas where surveillance and mosquito control capacities should be prioritised. FUNDING: EU and Ministero dell'Università e della Ricerca, Italy (Piano Nazionale di Ripresa e Resilienza Extended Partnership initiative on Emerging Infectious Diseases); EU (Horizon 2020); Ministero dell'Università e della Ricerca, Italy (Progetti di ricerca di Rilevante Interesse Nazionale programme); Brazilian National Council of Science, Technology and Innovation; Ministry of Health, Brazil; and Foundation of Research for Minas Gerais, Brazil.

A 12-month follow-up of the immune response to SARS-CoV-2 primary vaccination: evidence from a real-world study.

A real-world population-based longitudinal study, aimed at determining the magnitude and duration of immunity induced by different types of vaccines against COVID-19, started in 2021 by enrolling a cohort of 2,497 individuals at time of their first vaccination. The study cohort included both healthy adults aged ≤65 years and elderly subjects aged >65 years with two or more co-morbidities. Here, patterns of anti-SARS-CoV-2 humoral and cell-mediated specific immune response, assessed on 1,182 remaining subjects, at 6 (T6) and 12 months (T12) after the first vaccine dose, are described. At T12 median anti-Spike IgG antibody levels were increased compared to T6. The determinants of increased anti-Spike IgG were the receipt of a third vaccine dose between T6 and T12 and being positive for anti-Nucleocapside IgG at T12, a marker of recent infection, while age had no significant effect. The capacity of T12 sera to neutralize in vitro the ancestral B strain and the Omicron BA.5 variant was assessed in a subgroup of vaccinated subjects. A correlation between anti-S IgG levels and sera neutralizing capacity was identified and higher neutralizing capacity was evident in healthy adults compared to frail elderly subjects and in those who were positive for anti-Nucleocapside IgG at T12. Remarkably, one third of T12 sera from anti-Nucleocapside IgG negative older individuals were unable to neutralize the BA.5 variant strain. Finally, the evaluation of T-cell mediated immunity showed that most analysed subjects, independently from age and comorbidity, displayed Spike-specific responses with a high degree of polyfunctionality, especially in the CD8 compartment. In conclusion, vaccinated subjects had high levels of circulating antibodies against SARS-CoV-2 Spike protein 12 months after the primary vaccination, which increased as compared to T6. The enhancing effect could be attributable to the administration of a third vaccine dose but also to the occurrence of breakthrough infection. Older individuals, especially those who were anti-Nucleocapside IgG negative, displayed an impaired capacity to neutralize the BA.5 variant strain. Spike specific T-cell responses, able to sustain immunity and maintain the ability to fight the infection, were present in most of older and younger subjects assayed at T12.

SARS-CoV-2 transmission patterns in educational settings during the Alpha wave in Reggio-Emilia, Italy.

Different monitoring and control policies have been implemented in schools to minimize the spread of SARS-CoV-2. Transmission in schools has been hard to quantify due to the large proportion of asymptomatic carriers in young individuals. We applied a Bayesian approach to reconstruct the transmission chains between 284 SARS-CoV-2 infections ascertained during 87 school outbreak investigations conducted between March and April 2021 in Italy. Under the policy of reactive quarantines, we found that 42.5% (95%CrI: 29.5-54.3%) of infections among school attendees were caused by school contacts. The mean number of secondary cases infected at school by a positive individual during in-person education was estimated to be 0.33 (95%CrI: 0.23-0.43), with marked heterogeneity across individuals. Specifically, we estimated that only 26.0% (95%CrI: 17.6-34.1%) of students and school personnel who tested positive during in-person education caused at least one secondary infection at school. Positive individuals who attended school for at least 6 days before being isolated or quarantined infected on average 0.49 (95%CrI: 0.14-0.83) secondary cases. Our findings provide quantitative insights on the contribution of school transmission to the spread of SARS-CoV-2 in young individuals. Identifying positive cases within 5 days after exposure to their infector could reduce onward transmission at school by at least 30%.

Prioritizing COVID-19 vaccine allocation in resource poor settings: Towards an Artificial Intelligence-enabled and Geospatial-assisted decision support framework.

OBJECTIVES: To propose a novel framework for COVID-19 vaccine allocation based on three components of Vulnerability, Vaccination, and Values (3Vs). METHODS: A combination of geospatial data analysis and artificial intelligence methods for evaluating vulnerability factors at the local level and allocate vaccines according to a dynamic mechanism for updating vulnerability and vaccine uptake. RESULTS: A novel approach is introduced including (I) Vulnerability data collection (including country-specific data on demographic, socioeconomic, epidemiological, healthcare, and environmental factors), (II) Vaccination prioritization through estimation of a unique Vulnerability Index composed of a range of factors selected and weighed through an Artificial Intelligence (AI-enabled) expert elicitation survey and scientific literature screening, and (III) Values consideration by identification of the most effective GIS-assisted allocation of vaccines at the local level, considering context-specific constraints and objectives. CONCLUSIONS: We showcase the performance of the 3Vs strategy by comparing it to the actual vaccination rollout in Kenya. We show that under the current strategy, socially vulnerable individuals comprise only 45% of all vaccinated people in Kenya while if the 3Vs strategy was implemented, this group would be the first to receive vaccines.

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.

A repeated cross-sectional analysis on the economic impact of SARS-CoV-2 pandemic at the hospital level in Italy.

Italy was the first country in Europe to be hit by the Severe Acute Respiratory Syndrome Coronavirus 2. Little research has been conducted to understand the economic impact of providing care for SARS-CoV-2 patients during the pandemic. Our study aims to quantify the incremental healthcare costs for hospitalizations associated to being discharged before or after the first SARS-CoV-2 case was notified in Italy, and to a positive or negative SARS-CoV-2 notified infection. We used data on hospitalizations for 9 different diagnosis related groups at a large Italian Research Hospital with discharge date between 1st January, 2018 and 31st December 2021. The median overall costs for a hospitalization increased from 2410EUR (IQR: 1588-3828) before the start of the pandemic, to 2645EUR (IQR: 1885-4028) and 3834EUR (IQR: 2463-6413) during the pandemic, respectively for patients SARS-CoV-2 negative and positive patients. Interestingly, according to results of a generalized linear model, the highest increases in the average costs sustained for SARS-CoV-2 positive patients with respect to patients discharged before the pandemic was found among those with diagnoses unrelated to COVID-19, i.e. kidney and urinary tract infections with CC (59.71%), intracranial hemorrhage or cerebral infarction (53.33), and pulmonary edema and respiratory failure (47.47%). Our study highlights the economic burden during the COVID-19 pandemic on the hospital system in Italy based on individual patient data. These results contribute to the to the debate around the efficiency of the healthcare services provision during a pandemic.

Evaluation of Waning of SARS-CoV-2 Vaccine-Induced Immunity: A Systematic Review and Meta-analysis.

Importance: Estimates of the rate of waning of vaccine effectiveness (VE) against COVID-19 are key to assess population levels of protection and future needs for booster doses to face the resurgence of epidemic waves. Objective: To quantify the progressive waning of VE associated with the Delta and Omicron variants of SARS-CoV-2 by number of received doses. Data Sources: PubMed and Web of Science were searched from the databases' inception to October 19, 2022, as well as reference lists of eligible articles. Preprints were included. Study Selection: Selected studies for this systematic review and meta-analysis were original articles reporting estimates of VE over time against laboratory-confirmed SARS-CoV-2 infection and symptomatic disease. Data Extraction and Synthesis: Estimates of VE at different time points from vaccination were retrieved from original studies. A secondary data analysis was performed to project VE at any time from last dose administration, improving the comparability across different studies and between the 2 considered variants. Pooled estimates were obtained from random-effects meta-analysis. Main Outcomes and Measures: Outcomes were VE against laboratory-confirmed Omicron or Delta infection and symptomatic disease and half-life and waning rate associated with vaccine-induced protection. Results: A total of 799 original articles and 149 reviews published in peer-reviewed journals and 35 preprints were identified. Of these, 40 studies were included in the analysis. Pooled estimates of VE of a primary vaccination cycle against laboratory-confirmed Omicron infection and symptomatic disease were both lower than 20% at 6 months from last dose administration. Booster doses restored VE to levels comparable to those acquired soon after the administration of the primary cycle. However, 9 months after booster administration, VE against Omicron was lower than 30% against laboratory-confirmed infection and symptomatic disease. The half-life of VE against symptomatic infection was estimated to be 87 days (95% CI, 67-129 days) for Omicron compared with 316 days (95% CI, 240-470 days) for Delta. Similar waning rates of VE were found for different age segments of the population. Conclusions and Relevance: These findings suggest that the effectiveness of COVID-19 vaccines against laboratory-confirmed Omicron or Delta infection and symptomatic disease rapidly wanes over time after the primary vaccination cycle and booster dose. These results can inform the design of appropriate targets and timing for future vaccination programs.

Priority age targets for COVID-19 vaccination in Ethiopia under limited vaccine supply.

The worldwide inequitable access to vaccination claims for a re-assessment of policies that could minimize the COVID-19 burden in low-income countries. Nine months after the launch of the national vaccination program in March 2021, only 3.4% of the Ethiopian population received two doses of COVID-19 vaccine. We used a SARS-CoV-2 transmission model to estimate the level of immunity accrued before the launch of vaccination in the Southwest Shewa Zone (SWSZ) and to evaluate the impact of alternative age priority vaccination targets in a context of limited vaccine supply. The model was informed with available epidemiological evidence and detailed contact data collected across different geographical settings (urban, rural, or remote). We found that, during the first year of the pandemic, the mean proportion of critical cases occurred in SWSZ attributable to infectors under 30 years of age would range between 24.9 and 48.0%, depending on the geographical setting. During the Delta wave, the contribution of this age group in causing critical cases was estimated to increase on average to 66.7-70.6%. Our findings suggest that, when considering the vaccine product available at the time (ChAdOx1 nCoV-19; 65% efficacy against infection after 2 doses), prioritizing the elderly for vaccination remained the best strategy to minimize the disease burden caused by Delta, irrespectively of the number of available doses. Vaccination of all individuals aged ≥ 50 years would have averted 40 (95%PI: 18-60), 90 (95%PI: 61-111), and 62 (95%PI: 21-108) critical cases per 100,000 residents in urban, rural, and remote areas, respectively. Vaccination of all individuals aged ≥ 30 years would have averted an average of 86-152 critical cases per 100,000 individuals, depending on the setting considered. Despite infections among children and young adults likely caused 70% of critical cases during the Delta wave in SWSZ, most vulnerable ages should remain a key priority target for vaccination against COVID-19.

Long-term measles antibody profiles following different vaccine schedules in China, a longitudinal study.

Characterizing the long-term kinetics of maternally derived and vaccine-induced measles immunity is critical for informing measles immunization strategies moving forward. Based on two prospective cohorts of children in China, we estimate that maternally derived immunity against measles persists for 2.4 months. Following two-dose series of measles-containing vaccine (MCV) at 8 and 18 months of age, the immune protection against measles is not lifelong, and antibody concentrations are extrapolated to fall below the protective threshold of 200 mIU/ml at 14.3 years. A catch-up MCV dose in addition to the routine doses between 8 months and 5 years reduce the cumulative incidence of seroreversion by 79.3-88.7% by the age of 6 years. Our findings also support a good immune response after the first MCV vaccination at 8 months. These findings, coupled with the effectiveness of a catch-up dose in addition to the routine doses, could be instrumental to relevant stakeholders when planning routine immunization schedules and supplemental immunization activities.

Estimating SARS-CoV-2 transmission in educational settings: A retrospective cohort study.

BACKGROUND: School closures and distance learning have been extensively adopted to counter the COVID-19 pandemic. However, the contribution of school transmission to the spread of SARS-CoV-2 remains poorly quantified. METHODS: We analyzed transmission patterns associated with 976 SARS-CoV-2 exposure events, involving 460 positive individuals, as identified in early 2021 through routine surveillance and an extensive screening conducted on students, school personnel, and their household members in a small Italian municipality. In addition to population screenings and contact-tracing operations, reactive closures of class and schools were implemented. RESULTS: From the analysis of 152 clear infection episodes and 584 exposure events identified by epidemiological investigations, we estimated that approximately 50%, 21%, and 29% of SARS-CoV-2 transmission was associated with household, school, and community contacts, respectively. We found substantial transmission heterogeneities, with 20% positive individuals causing 75% to 80% of ascertained infection episodes. A higher proportion of infected individuals causing onward transmission was found among students (46.2% vs. 25%, on average), who also caused a markedly higher number of secondary cases (mean: 1.03 vs. 0.35). By reconstructing likely transmission chains from the entire set of exposures identified during contact-tracing operations, we found that clusters originated from students or school personnel were associated with a larger average cluster size (3.32 vs. 1.15) and a larger average number of generations in the transmission chain (1.56 vs. 1.17). CONCLUSIONS: Uncontrolled SARS-CoV-2 transmission at school could disrupt the regular conduct of teaching activities, likely seeding the transmission into other settings, and increasing the burden on contact-tracing operations.

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.

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.

Evaluation of humoral and cellular response to four vaccines against COVID-19 in different age groups: A longitudinal study.

To date there has been limited head-to-head evaluation of immune responses to different types of COVID-19 vaccines. A real-world population-based longitudinal study was designed with the aim to define the magnitude and duration of immunity induced by each of four different COVID-19 vaccines available in Italy at the time of this study. Overall, 2497 individuals were enrolled at time of their first vaccination (T0). Vaccine-specific antibody responses induced over time by Comirnaty, Spikevax, Vaxzevria, Janssen Ad26.COV2.S and heterologous vaccination were compared up to six months after immunization. On a subset of Comirnaty vaccinees, serology data were correlated with the ability to neutralize a reference SARS-CoV-2 B strain, as well as Delta AY.4 and Omicron BA.1. The frequency of SARS-CoV-2-specific CD4+ T cells, CD8+ T cells, and memory B cells induced by the four different vaccines was assessed six months after the immunization. We found that mRNA vaccines are stronger inducer of anti-Spike IgG and B-memory cell responses. Humoral immune responses are lower in frail elderly subjects. Neutralization of the Delta AY.4 and Omicron BA.1 variants is severely impaired, especially in older individuals. Most vaccinees display a vaccine-specific T-cell memory six months after the vaccination. By describing the immunological response during the first phase of COVID-19 vaccination campaign in different cohorts and considering several aspects of the immunological response, this study allowed to collect key information that could facilitate the implementation of effective prevention and control measures against SARS-CoV-2.

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.

Investigating the relationship between interventions, contact patterns, and SARS-CoV-2 transmissibility.

BACKGROUND: After a rapid upsurge of COVID-19 cases in Italy during the fall of 2020, the government introduced a three-tiered restriction system aimed at increasing physical distancing. The Ministry of Health, after periodic epidemiological risk assessments, assigned a tier to each of the 21 Italian regions and autonomous provinces. It is still unclear to what extent these different sets of measures altered the number of daily interactions and the social mixing patterns. METHODS AND FINDINGS: We conducted a survey between July 2020 and March 2021 to monitor changes in social contact patterns among individuals in the metropolitan city of Milan, Italy, which was hardly hit by the second wave of the COVID-19 pandemic. The number of daily contacts during periods characterized by different levels of restrictions was analyzed through negative binomial regression models and age-specific contact matrices were estimated under the different tiers of restrictions. By relying on the empirically estimated mixing patterns, we quantified relative changes in SARS-CoV-2 transmission potential associated with the different tiers. As tighter restrictions were implemented during the fall of 2020, a progressive reduction in the mean number of daily contacts recorded by study participants was observed: from 15.9 % under mild restrictions (yellow tier), to 41.8 % under strong restrictions (red tier). Higher restrictions levels were also found to increase the relative contribution of contacts occurring within the household. The SARS-CoV-2 reproduction number was estimated to decrease by 17.1 % (95 %CI: 1.5-30.1), 25.1 % (95 %CI: 13.0-36.0) and 44.7 % (95 %CI: 33.9-53.0) under the yellow, orange, and red tiers, respectively. CONCLUSIONS: Our results give an important quantification of the expected contribution of different restriction levels in shaping social contacts and decreasing the transmission potential of SARS-CoV-2. These estimates can find an operational use in anticipating the effect that the implementation of these tiered restriction can have on SARS-CoV-2 reproduction number under an evolving epidemiological situation.

The New Quadrivalent Adjuvanted Influenza Vaccine for the Italian Elderly: A Health Technology Assessment.

BACKGROUND: The elderly, commonly defined as subjects aged ≥65 years, are among the at-risk subjects recommended for annual influenza vaccination in European countries. Currently, two new vaccines are available for this population: the MF59-adjuvanted quadrivalent influenza vaccine (aQIV) and the high-dose quadrivalent influenza vaccine (hdQIV). Their multidimensional assessment might maximize the results in terms of achievable health benefits. Therefore, we carried out a Health Technology Assessment (HTA) of the aQIV by adopting a multidisciplinary policy-oriented approach to evaluate clinical, economic, organizational, and ethical implications for the Italian elderly. METHODS: A HTA was conducted in 2020 to analyze influenza burden; characteristics, efficacy, and safety of aQIV and other available vaccines for the elderly; cost-effectiveness of aQIV; and related organizational and ethical implications. Comprehensive literature reviews/analyses were performed, and a transmission model was developed in order to address the above issues. RESULTS: In Italy, the influenza burden on the elderly is high and from 77.7% to 96.1% of influenza-related deaths occur in the elderly. All available vaccines are effective and safe; however, aQIV, such as the adjuvanted trivalent influenza vaccine (aTIV), has proved more immunogenic and effective in the elderly. From the third payer's perspective, but also from the societal one, the use of aQIV in comparison with egg-based standard QIV (eQIV) in the elderly population is cost-effective. The appropriateness of the use of available vaccines as well as citizens' knowledge and attitudes remain a challenge for a successful vaccination campaign. CONCLUSIONS: The results of this project provide decision-makers with important evidence on the aQIV and support with scientific evidence on the appropriate use of vaccines in the elderly.