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In the early stage of an infectious disease outbreak, public health strategies tend to gravitate towards non-pharmaceutical interventions (NPIs) given the time required to develop targeted treatments and vaccines. One of the most common NPIs is Test-Trace-Isolate (TTI). One of the factors determining the effectiveness of TTI is the ability to identify contacts of infected individuals. In this study, we propose a multi-layer temporal contact network to model transmission dynamics and assess the impact of different TTI implementations, using SARS-CoV-2 as a case study. The model was used to evaluate TTI effectiveness both in containing an outbreak and mitigating the impact of an epidemic. We estimated that a TTI strategy based on home isolation and testing of both primary and secondary contacts can contain outbreaks only when the reproduction number is up to 1.3, at which the epidemic prevention potential is 88.2% (95% CI: 87.9%-88.5%). On the other hand, for higher value of the reproduction number, TTI is estimated to noticeably mitigate disease burden but at high social costs (e.g., over a month in isolation/quarantine per person for reproduction numbers of 1.7 or higher). We estimated that strategies considering quarantine of contacts have a larger epidemic prevention potential than strategies that either avoid tracing contacts or require contacts to be tested before isolation. Combining TTI with other social distancing measures can improve the likelihood of successfully containing an outbreak but the estimated epidemic prevention potential remains lower than 50% for reproduction numbers higher than 2.1., Comment: 17 pages 6 figures

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.

The potential tradeoff between health outcomes and economic impact has been a major challenge in the policy making process during the COVID-19 pandemic. Epidemic-economic models designed to address this issue are either too aggregate to consider heterogeneous outcomes across socio-economic groups, or, when sufficiently fine-grained, not well grounded by empirical data. To fill this gap, we introduce a data-driven, granular, agent-based model that simulates epidemic and economic outcomes across industries, occupations, and income levels with geographic realism. The key mechanism coupling the epidemic and economic modules is the reduction in consumption demand due to fear of infection. We calibrate the model to the first wave of COVID-19 in the New York metropolitan area, showing that it reproduces key epidemic and economic statistics, and then examine counterfactual scenarios. We find that: (a) both high fear of infection and strict restrictions similarly harm the economy but reduce infections; (b) low-income workers bear the brunt of both the economic and epidemic harm; (c) closing non-customer-facing industries such as manufacturing and construction only marginally reduces the death toll while considerably increasing unemployment; and (d) delaying the start of protective measures does little to help the economy and worsens epidemic outcomes in all scenarios. We anticipate that our model will help designing effective and equitable non-pharmaceutical interventions that minimize disruptions in the face of a novel pandemic.

Background School closures and distance learning have been extensively applied to control SARS-CoV-2 transmission. Despite evidence of viral circulation in schools, the contribution of students and of in-person schooling to the transmission remains poorly quantified. Methods We analyze 976 exposure events, involving 460 positive individuals, as identified in early 2021 by routine surveillance and through an extensive screening conducted on students, school personnel, and their household members during an outbreak in a small municipality of Italy. Results From the analysis of potential transmission chains, we estimated that, on average, 55.1%, 17.3% and 27.6% infection episodes were linked to household, school, and community contacts, respectively. Clusters originated from students or school personnel showed a larger average cluster size (3.32 vs 1.15), a larger average number of generations in the transmission chain (1.56 vs 1.17) and a larger set of associated close contacts (11.3 vs 3.15, on average). We found substantial transmission heterogeneities, with 20% positive individuals seeding 75-80 of all transmission. A higher proportion of infected individuals causing onward transmission was found among students (48.8% vs 29.9%, on average), who also caused a markedly higher number of secondary cases (mean: 1.3 vs 0.5). Conclusions Uncontrolled 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.

Background. During 2021, the COVID-19 pandemic was characterized by the emergence of lineages with increased fitness. For most of these variants, quantitative information is scarce on epidemiological quantities such as the incubation period and generation time, which are critical for both public health decisions and scientific research. Method. We analyzed a dataset collected during contact tracing activities in the province of Reggio Emilia, Italy, throughout 2021. We determined the distributions of the incubation period using information on negative PCR tests and the date of last exposure from 282 symptomatic cases. We estimated the distributions of the intrinsic generation time (the time between the infection dates of an infector and its secondary cases under a fully susceptible population) using a Bayesian inference approach applied to 4,435 SARS-CoV-2 cases clustered in 1,430 households where at least one secondary case was recorded. Results. We estimated a mean incubation period of 4.9 days (95% credible intervals, CrI, 4.4-5.4; 95 percentile of the mean distribution: 1-12) for Alpha and 4.5 days (95%CrI 4.0-5.0; 95 percentile: 1-10) for Delta. The intrinsic generation time was estimated to have a mean of 6.0 days (95% CrI 5.6-6.4; 95 percentile: 1-15) for Alpha and of 6.6 days (95%CrI 6.0-7.3; 95 percentile: 1-18) for Delta. The household serial interval was 2.6 days (95%CrI 2.4-2.7) for Alpha and 2.4 days (95%CrI 2.2-2.6) for Delta, and the estimated proportion of pre-symptomatic transmission was 54-55% for both variants. Conclusions. 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., Comment: 11 pages, 3 figures, 2 tables, supplementary material

Contact patterns play a key role in the spread of respiratory infectious diseases in human populations. During the COVID-19 pandemic the regular contact patterns of the population has been disrupted due to social distancing both imposed by the authorities and individual choices. Here we present the results of a contact survey conducted in Chinese provinces outside Hubei in March 2020, right after lockdowns were lifted. We then leveraged the estimated mixing patterns to calibrate a model of SARS-CoV-2 transmission, which was used to estimate different metrics of COVID-19 burden by age. Study participants reported 2.3 contacts per day (IQR: 1.0-3.0) and the mean per-contact duration was 7.0 hours (IQR: 1.0-10.0). No significant differences were observed between provinces, the number of recorded contacts did not show a clear-cut trend by age, and most of the recorded contacts occurred with family members (about 78%). Our findings suggest that, despite the lockdown was no longer in place at the time of the survey, people were still heavily limiting their contacts as compared to the pre-pandemic situation. Moreover, the obtained modeling results highlight the importance of considering age-contact patterns to estimate COVID-19 burden., Comment: 17 pages, 4 figures

Solid estimates describing the clinical course of SARS-CoV-2 infections are still lacking due to under-ascertainment of asymptomatic and mild-disease cases. In this work, we quantify age-specific probabilities of transitions between stages defining the natural history of SARS-CoV-2 infection from 1,965 SARS-CoV-2 positive individuals identified in Italy between March and April 2020 among contacts of confirmed cases. Infected contacts of cases were confirmed via RT-PCR tests as part of contact tracing activities or retrospectively via IgG serological tests and followed-up for symptoms and clinical outcomes. In addition, we provide estimates of time intervals between key events defining the clinical progression of cases as obtained from a larger sample, consisting of 95,371 infections ascertained between February and July 2020. We found that being older than 60 years of age was associated with a 39.9% (95%CI: 36.2-43.6%) likelihood of developing respiratory symptoms or fever >= 37.5 {\deg}C after SARS-CoV-2 infection; the 22.3% (95%CI: 19.3-25.6%) of the infections in this age group required hospital care and the 1% (95%CI: 0.4-2.1%) were admitted to an intensive care unit (ICU). The corresponding proportions in individuals younger than 60 years were estimated at 27.9% (95%CI: 25.4-30.4%), 8.8% (95%CI: 7.3-10.5%) and 0.4% (95%CI: 0.1-0.9%), respectively. The infection fatality ratio (IFR) ranged from 0.2% (95%CI: 0.0-0.6%) in individuals younger than 60 years to 12.3% (95%CI: 6.9-19.7%) for those aged 80 years or more; the case fatality ratio (CFR) in these two age classes was 0.6% (95%CI: 0.1-2%) and 19.2% (95% CI: 10.9-30.1%), respectively. The median length of stay in hospital was 10 (IQR 3-21) days; the length of stay in ICU was 11 (IQR 6-19) days. The obtained estimates could be instrumental to refine mathematical modeling work supporting public health decisions., Comment: 20 pages, 4 figures

We analyzed 5,484 close contacts of COVID-19 cases from Italy, all of them tested for SARS-CoV-2 infection. We found an infection fatality ratio of 2.2% (95%CI 1.69-2.81%) and identified male sex, age >70 years, cardiovascular comorbidities, and infection early in the epidemics as risk factors for death.

We quantified the probability of developing symptoms (respiratory or fever \geq 37.5 {\deg}C) and critical disease (requiring intensive care or resulting in death) of SARS-CoV-2 positive subjects. 5,484 contacts of SARS-CoV-2 index cases detected in Lombardy, Italy were analyzed, and positive subjects were ascertained via nasal swabs and serological assays. 73.9% of all infected individuals aged less than 60 years did not develop symptoms (95% confidence interval: 71.8-75.9%). The risk of symptoms increased with age. 6.6% of infected subjects older than 60 years had critical disease, with males at significantly higher risk., Comment: sample increased: results updated with new records coming from the ongoing serological surveys

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.

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., Comment: 6 pages, 3 figures; submitted

Mathematical and computational modeling approaches are increasingly used as quantitative tools in the analysis and forecasting of infectious disease epidemics. The growing need for realism in addressing complex public health questions is however calling for accurate models of the human contact patterns that govern the disease transmission processes. Here we present a data-driven approach to generate effective descriptions of population-level contact patterns by using highly detailed macro (census) and micro (survey) data on key socio-demographic features. We produce age-stratified contact matrices for 277 sub-national administrative regions of countries covering approximately 3.5 billion people and reflecting the high degree of cultural and societal diversity of the focus countries. We use the derived contact matrices to model the spread of airborne infectious diseases and show that sub-national heterogeneities in human mixing patterns have a marked impact on epidemic indicators such as the reproduction number and overall attack rate of epidemics of the same etiology. The contact patterns derived here are made publicly available as a modeling tool to study the impact of socio-economic differences and demographic heterogeneities across populations on the epidemiology of infectious diseases., Comment: 18 pages, 7 figures