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.

Assessing changes in incubation period, serial interval, and generation time of SARS-CoV-2 variants of concern: a systematic review and meta-analysis (preprint)

BackgroundAfter the first COVID-19 wave caused by the ancestral lineage, the pandemic has been fueled from the continuous emergence of new SARS-CoV-2 variants. Understanding key time-to-event periods for each emerging variant of concern is critical as it can provide insights into the future trajectory of the virus and help inform outbreak preparedness and response planning. Here, we aim to examine how the incubation period, serial interval, and generation time have changed from the ancestral SARS-CoV-2 lineage to different variants of concern. MethodsWe conducted a systematic review and meta-analysis that synthesized the estimates of incubation period, serial interval, and generation time (both realized and intrinsic) for the ancestral lineage, Alpha, Beta, and Omicron variants of SARS-CoV-2. ResultsOur study included 274 records obtained from 147 household studies, contact tracing studies or studies where epidemiological links were known. With each emerging variant, we found a progressive shortening of each of the analyzed key time-to-event periods. Specifically, we found that Omicron had the shortest pooled estimates for the incubation period (3.63 days, 95%CI: 3.25-4.02 days), serial interval (3.19 days, 95%CI: 2.95-3.43 days), and realized generation time (2.96 days, 95%CI: 2.54-3.38 days) whereas the ancestral lineage had the highest pooled estimates for each of them. We also observed shorter pooled estimates for the serial interval compared to the incubation period across the virus lineages. We found considerable heterogeneities (I2 > 80%) when pooling the estimates across different virus lineages, indicating potential unmeasured confounding from population factors (e.g., social behavior, deployed interventions). ConclusionOur study supports the importance of conducting contact tracing and epidemiological investigations to monitor changes in SARS-CoV-2 transmission patterns. Our findings highlight a progressive shortening of the incubation period, serial interval, and generation time, which can lead to epidemics that spread faster, with larger peak incidence, and harder to control. We also consistently found a shorter serial interval than incubation period, suggesting that a key feature of SARS-CoV-2 is the potential for pre-symptomatic transmission. These observations are instrumental to plan for future COVID-19 waves.

Heterogeneous changes in mobility in response to the SARS-CoV-2 Omicron BA.2 outbreak in Shanghai (preprint)

The coronavirus disease 2019 (COVID-19) pandemic and the measures taken by authorities to control its spread had altered human behavior and mobility patterns in an unprecedented way. However, it remains unclear whether the population response to a COVID-19 outbreak varies within a city or among demographic groups. Here we utilized passively recorded cellular signaling data at a spatial resolution of 1km x 1km for over 5 million users and epidemiological surveillance data collected during the SARS-CoV-2 Omicron BA.2 outbreak from February to June 2022 in Shanghai, China, to investigate the heterogeneous response of different segments of the population at the within-city level and examine its relationship with the actual risk of infection. Changes in behavior were spatially heterogenous within the city and population groups, and associated with both the infection incidence and adopted interventions. We also found that males and individuals aged 30-59 years old traveled more frequently, traveled longer distances, and their communities were more connected; the same groups were also associated with the highest SARS-CoV-2 incidence. Our results highlight the heterogeneous behavioral change of the Shanghai population to the SARS-CoV-2 Omicron BA.2 outbreak and the its effect on the heterogenous spread of COVID-19, both spatially and demographically. These findings could be instrumental for the design of targeted interventions for the control and mitigation of future outbreaks of COVID-19 and, more broadly, of respiratory pathogens.

The unequal effects of the health-economy tradeoff during the COVID-19 pandemic (preprint)

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.

Priority age targets for COVID-19 vaccination in Ethiopia under limited vaccine supply (preprint)

Background The worldwide inequitable access to vaccination claims for a re-assessment of policies that could minimize the COVID-19 burden in low-income countries. An illustrative example is what occurred in Ethiopia, where nine months after the launch of the national vaccination program in March 2021, only 3% of the population received two doses of COVID-19 vaccine. In the meantime, a new wave of cases caused by the emergence of Delta variant of SARS-CoV-2 was observed between July and November 2021. Methods 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 socio-demographic settings. Results We found that, during the first year of the pandemic, 46.1-58.7% of SARS-CoV-2 infections and 24.9-48% of critical cases occurred in SWSZ were likely associated with infectors under 30 years of age. During the Delta wave, the contribution of this age group in causing critical cases was estimated to increase to 66.7-70.6%. However, 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 to the number of available doses. Vaccination of all individuals aged 50 years or older would have averted 40 (95%CI: 18-60), 90 (95%CI: 61-111), and 62 (95%CI: 21-108) critical cases per 100,000 residents in urban, rural, and remote areas, respectively. Vaccination of all individuals aged 30 years or more would have averted an average of 86-152 critical cases per 100,000 individuals, depending on the setting considered. Conclusions 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.

Estimation of disease burden and clinical severity of COVID-19 caused by Omicron BA.2 in Shanghai, February-June 2022 (preprint)

Summary Background An outbreak of COVID-19 caused by the SARS-CoV-2 Omicron BA.2 sublineage occurred in Shanghai, China from February to June 2022. The government organized multiple rounds of molecular test screenings for the entire population, providing a unique opportunity to capture the majority of subclinical infections and better characterize disease burden and the full spectrum of Omicron BA.2 clinical severity. Methods Using daily reports from the websites of the Shanghai Municipal Health Commission, we estimated the incidence of infections, severe/critical infections, and deaths to assess the disease burden. By adjusting for right censoring and Reverse Transcription-Polymerase Chain Reaction (RT□PCR) sensitivity, we provide estimates of clinical severity, including the infection fatality risk, symptomatic case fatality risk, and risk of developing severe/critical disease upon infection. Findings From February 26 to June 30, 2022, the overall infection rate, severe/critical infection rate, and mortality rate were 2.74 (95% CI: 2.73-2.74) per 100 individuals, 6.34 (95% CI: 6.02-6.66) per 100,000 individuals and 2.42 (95% CI: 2.23-2.62) per 100,000 individuals, respectively. The severe/critical infection rate and mortality rate increased with age with the highest rates of 125.29 (95% CI: 117.05-133.44) per 100,000 and 57.17 (95% CI: 51.63-62.71) per 100,000 individuals, respectively, noted in individuals aged 80 years or older. The overall fatality risk and risk of developing severe/critical disease upon infection were 0.09% (95% CI: 0.08-0.10%) and 0.23% (95% CI: 0.20-0.25%), respectively. Having received at least one vaccine dose led to a 10-fold reduction in the risk of death for infected individuals aged 80 years or older. Interpretation Under the repeated population-based screenings and strict intervention policies implemented in Shanghai, our results found a lower disease burden and mortality of the outbreak compared to other settings and countries, showing the impact of the successful outbreak containment in Shanghai. The estimated low clinical severity of this Omicron BA.2 epidemic in Shanghai highlight the key contribution of vaccination and availability of hospital beds to reduce the risk of death. Funding Key Program of the National Natural Science Foundation of China (82130093). Research in context Evidence before this study We searched PubMed and Europe PMC for manuscripts published or posted on preprint servers after January 1, 2022 using the following query: (“SARS-CoV-2 Omicron”) AND (“burden” OR “severity”). No studies that characterized the whole profile of disease burden and clinical severity during the Shanghai Omicron outbreak were found. One study estimated confirmed case fatality risk between different COVID-19 waves in Hong Kong; other outcomes, such as fatality risk and risk of developing severe/critical illness upon infection, were not estimated. One study based on 21 hospitals across the United States focused on Omicron-specific in-hospital mortality based on a limited sample of inpatients (565). In southern California, United States, a study recruited more than 200 thousand Omicron-infected individuals and estimated the 30-day risk of hospital admission, intensive care unit admission, mechanical ventilation, and death. None of these studies estimated infection and mortality rates or other indictors associated with disease burden. Overall, the disease burden and clinical severity of the Omicron BA.2 variant have not been fully characterized, especially in populations predominantly immunized with inactivated vaccines. Added value of this study The large-scale and multiround molecular test screenings conducted on the entire population during the Omicron BA.2 outbreak in Shanghai, leading to a high infection ascertainment ratio, provide a unique opportunity to capture the majority of subclinical infections. As such, our study provides a comprehensive assessment of both the disease burden and clinical severity of the SARS-CoV-2 Omicron BA.2 sublineage, which are especially lacking for populations predominantly immunized with inactivated vaccines. Implications of all the available evidence We estimated the disease burden and clinical severity of the Omicron BA.2 outbreak in Shanghai in February-June 2022. These estimates are key to properly interpreting field evidence and assessing the actual spread of Omicron in other settings. Our results also provide support for the importance of strategies to prevent overwhelming the health care system and increasing vaccine coverage to reduce mortality.

Waning of SARS-CoV-2 vaccine-induced immunity: A systematic review and secondary data analysis (preprint)

The emergence of Omicron (B.1.1.529) variant of SARS-CoV-2 in late 2021 was followed by a marked increase of breakthrough infections. Estimates of vaccine effectiveness (VE) in the long term are key to assess potential resurgence of COVID-19 cases in the future. We conducted a systematic review of manuscripts published until June 21, 2022 to identify studies reporting the level of protection provided by COVID-19 vaccines against SARS-CoV-2 infection and symptomatic disease at different time points since vaccine administration. An exponential model was used to perform a secondary data analysis of the retrieved data to estimate the progressive waning of VE associated with different vaccine products, numbers of received doses, and SARS-CoV-2 variants. Our results show that VE of BNT162b2, mRNA-1273, ChAdOx1 nCoV-19 vaccines against any laboratory confirmed infection with Delta might have been lower than 70% at 9 months from second dose administration. We found a marked immune escape associated with Omicron infection and symptomatic disease, both after the administration of two and three doses. The half-life of protection against symptomatic infection provided by two doses was estimated in the range of 178-456 days for Delta, and between 66 and 73 days for Omicron. Booster doses were found to restore the VE to levels comparable to those acquired soon after administration of the second dose; however, a fast decline of booster VE against Omicron was observed, with less than 20% VE against infection and less than 25% VE against symptomatic disease at 9 months from the booster administration. This study provides a cohesive picture of the waning of vaccine protection; obtained estimates can inform the identification of appropriate targets and timing for future COVID-19 vaccination programs.

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.

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.

Epidemiological characteristics and transmission dynamics of the outbreak caused by the SARS-CoV-2 Omicron variant in Shanghai, China: a descriptive study (preprint)

Background In early March 2022, a major outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant spread rapidly throughout Shanghai, China. Here we aimed to provide a description of the epidemiological characteristics and spatiotemporal transmission dynamics of the Omicron outbreak under the population-based screening and lockdown policies implemented in Shanghai. Methods We extracted individual information on SARS-CoV-2 infections reported between January 1 and May 31, 2022, and on the timeline of the adopted non-pharmacological interventions. The epidemic was divided into three phases: i) sporadic infections (January 1-February 28), ii) local transmission (March 1-March 31), and iii) city-wide lockdown (April 1 to May 31). We described the epidemic spread during these three phases and the subdistrict-level spatiotemporal distribution of the infections. To evaluate the impact on the transmission of SARS-CoV-2 of the adopted targeted interventions in Phase 2 and city-wide lockdown in Phase 3, we estimated the dynamics of the net reproduction number (Rt). Findings A surge in imported infections in Phase 1 triggered cryptic local transmission of the Omicron variant in early March, resulting in the largest coronavirus disease 2019 (COVID-19) outbreak in mainland China since the original wave. A total of 626,000 SARS-CoV-2 infections were reported in 99.5% (215/216) of the subdistricts of Shanghai. The spatial distribution of the infections was highly heterogeneous, with 40% of the subdistricts accounting for 80% of all infections. A clear trend from the city center towards adjacent suburban and rural areas was observed, with a progressive slowdown of the epidemic spread (from 544 to 325 meters/day) prior to the citywide lockdown. During Phase 2, Rt remained well above 1 despite the implementation of multiple targeted interventions. The citywide lockdown imposed on April 1 led to a marked decrease in transmission, bringing Rt below the epidemic threshold in the entire city on April 14 and ultimately leading to containment of the outbreak. Interpretation Our results highlight the risk of widespread outbreaks in mainland China, particularly under the heightened pressure of imported infections. The targeted interventions adopted in March 2022 were not capable of halting transmission, and the implementation of a strict, prolonged city-wide lockdown was needed to successfully contain the outbreak, highlighting the challenges for successfully containing Omicron outbreaks.

Assessing the feasibility of sustaining a 'Zero-COVID' policy in China in the era of highly transmissible variants (preprint)

We developed a spatially structured, fully stochastic, individual-based SARS-CoV-2 transmission model to evaluate the feasibility of sustaining a 'Zero-COVID' policy in mainland China in light of currently dominant Omicron variants, China's current immunization level, and non-pharmaceutical intervention (NPI) strategies. We found that due to high transmissibility, neither Omicron BA.1 or BA.2 sublineages could be contained by China's Pre-Omicron non-pharmaceutical intervention strategies which were successful at sustaining the 'Zero-COVID' policy until March 2022. However, increased intervention intensity, such as enhanced population mobility restrictions and multi-round mass testing, could lead to containment success without the necessity of population-wide lockdown. As China's current vaccination has yet to reach high coverage in older populations, non-pharmaceutical interventions remain essential tools to maintain low levels of infection while building protective population immunity, ensuring a smooth transition out of the pandemic phase, and minimizing the overall disease burden and societal costs.

Projecting the impact of the introduction of SARS-CoV-2 Omicron variant in China in the context of waning immunity after vaccination (preprint)

After the adoption of a dynamic zero-COVID strategy in China for nearly two years, whether and for how long this policy can remain in place is unclear. The debate has thus shifted towards the identification of mitigation strategies capable to prevent the disruption of the healthcare system, should a nationwide epidemic caused by the SARS-CoV-2 Omicron variant start to unfold. To this aim, we developed a mathematical model of SARS-CoV-2 transmission tailored to the unique immunization and epidemiological situation of China. We find that the level of immunity induced by the current vaccination campaign would be insufficient to prevent overwhelming the healthcare system and major losses of human lives. Instead, a synergetic strategy would be needed and based on 1) a heterologous booster vaccination campaign, 2) treating 50% of symptomatic cases with an antiviral with an 80% efficacy in preventing severe outcomes, and 3) the adoption of non-pharmaceutical interventions (NPIs) capable of reducing Rt to ≤2. Protecting vulnerable individuals by ensuring accessibility to vaccines and antivirals, and maintaining a certain degree of NPIs should be emphasised in a future mitigation policy, possibly supported by strengthening critical care capacity and the development of highly efficacious vaccines with long-lasting immunity.

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

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.

Tracking the progressive spread of the SARS-CoV-2 Omicron variant in Italy, December 2021 - January 2022 (preprint)

The SARS-CoV-2 variant of concern Omicron was first detected in Italy in November 2021. Data from three genomic surveys conducted in Italy between December 2021 and January 2022 suggest that Omicron became dominant in less than one month (prevalence on January 3: 78.6%-83.8%) with a doubling time of 2.7-3.1 days. The mean net reproduction number rose from about 1.15 in absence of Omicron to a peak of 1.83 for symptomatic cases and 1.33 for hospitalized cases, while it remained stable for critical cases.

Designing isolation guidelines for COVID-19 patients utilizing rapid antigen tests: a simulation study using viral dynamics models (preprint)

Appropriate isolation guidelines for COVID-19 patients are warranted. Currently, isolating for fixed time is adapted in most countries. However, given the variability in viral dynamics between patients, some patients may no longer be infectious by the end of isolation (thus they are redundantly isolated), whereas others may still be infectious. Utilizing viral test results to determine ending isolation would minimize both the risk of ending isolation of infectious patients and the burden due to redundant isolation of noninfectious patients. In our previous study, we proposed a computational framework using SARS-CoV-2 viral dynamics models to compute the risk and the burden of different isolation guidelines with PCR tests. In this study, we extend the computational framework to design isolation guidelines for COVID-19 patients utilizing rapid antigen tests. Time interval of tests and number of consecutive negative tests to minimize the risk and the burden of isolation were explored. Furthermore, the approach was extended for asymptomatic cases. We found the guideline should be designed considering various factors: the infectiousness threshold values, the detection limit of antigen tests, symptom presence, and an acceptable level of releasing infectious patients. Especially, when detection limit is higher than the infectiousness threshold values, more consecutive negative results are needed to ascertain loss of infectiousness. To control the risk of releasing of infectious individuals under certain levels, rapid antigen tests should be designed to have lower detection limits than infectiousness threshold values to minimize the length of prolonged isolation, and the length of prolonged isolation increases when the detection limit is higher than the infectiousness threshold values, even though the guidelines are optimized for given conditions.

Quantifying human mixing patterns in Chinese provinces outside Hubei after the 2020 lockdown was lifted (preprint)

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.

Anatomy of the first six months of COVID-19 Vaccination Campaign in Italy (preprint)

We analyze the effectiveness of the first six months of vaccination campaign against SARS-CoV-2 in Italy by using a computational epidemic model which takes into account demographic, mobility, vaccines, as well as estimates of the introduction and spreading of the more transmissible Alpha variant. We consider six sub-national regions and study the effect of vaccines in terms of number of averted deaths, infections, and reduction in the Infection Fatality Rate (IFR) with respect to counterfactual scenarios with the actual non-pharmaceuticals interventions but no vaccine administration. Furthermore, we compare the effectiveness in counterfactual scenarios with different vaccines allocation strategies and vaccination rates. Our results show that, as of 2021/07/05, vaccines averted 29, 350 ( IQR [16, 454 − 42, 826]) deaths and 4, 256, 332 ( IQR [1, 675, 564 − 6, 980, 070]) infections and a new pandemic wave in the country. During the same period, they achieved a −22.2% ( IQR [−31.4%; −13.9%]) reduction in the IFR. We show that a campaign that would have strictly prioritized age groups at higher risk of dying from COVID-19, besides frontline workers, would have implied additional benefits both in terms of avoided fatalities and reduction in the IFR. Strategies targeting the most active age groups would have prevented a higher number of infections but would have been associated with more deaths. Finally, we study the effects of different vaccination intake scenarios by rescaling the number of available doses in the time period under study to those administered in other countries of reference. The modeling framework can be applied to other countries to provide a mechanistic characterization of vaccination campaigns worldwide.

Investigating the relationship between interventions, contact patterns, and SARS-CoV-2 transmissibility (preprint)

ABSTRACT 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 (AP). It is still unclear to what extent these different measures altered mixing patterns and how quickly the population adapted their social interactions to continuous changes in restrictions. 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 COVID-19 pandemic. The number of 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. 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 contacts recorded by study participants was observed: from 16.4% under mild restrictions (yellow tier), to 45.6% 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 18.7% (95%CI: 4.6-30.8), 33.4% (95%CI: 22.7-43.2), and 50.2% (95%CI: 40.9-57.7) 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.

Projecting the transition of COVID-19 burden towards the young population while vaccines are rolled out: a modelling study (preprint)

Objectives SARS-CoV-2 infection causes most cases of severe illness and fatality in older age groups. In China, over 99% of individuals aged ⩾12 years have been fully vaccinated against COVID-19 (albeit with vaccines developed against historical lineages), while 65.0% children aged 3–11 years have been vaccinated their first doses (as of November 12, 2021). Here, we aimed to assess whether, in this vaccination landscape, the importation of Delta variant infections could shift the COVID-19 burden from adults to children. Methods We developed an age-structured susceptible-infectious-removed model of SARS-CoV-2 transmission dynamics to simulate epidemics triggered by the importation of Delta variant infections and project the age-specific incidence of SARS-CoV-2 infections, cases, hospitalisations, intensive care unit (ICU) admissions, and deaths. Results In the context of the vaccination programme targeting individuals aged ≥12 years (as it was the case until mid-October 2021), and in the absence of non-pharmaceutical interventions, the importation of Delta variant infections could have led to widespread transmission and substantial disease burden in mainland China, even with vaccination coverage as high as 97% across the eligible age groups. Extending the vaccination roll-out to include children aged 3–11 years (as it was the case since the end of October 2021) is estimated to dramatically decrease the burden of symptomatic infections and hospitalisations within this age group (54% and 81%, respectively, when considering a vaccination coverage of 99%), but would have a low impact on protecting infants (aged 0–2 years). Conclusions Our findings highlight the importance of including children among the target population and the need to strengthen vaccination efforts by increasing vaccine effectiveness.

Herd immunity induced by COVID-19 vaccination programs to suppress epidemics caused by SARS-CoV-2 wild type and variants in China (preprint)

To allow a return to a pre-COVID-19 lifestyle, virtually every country has initiated a vaccination program to mitigate severe disease burden and control transmission; over 3.6 billion vaccine doses have been administered as of July 2021. However, it remains to be seen whether herd immunity will be within reach of these programs, especially as more transmissible SARS-CoV-2 variants continue to emerge. To address this question, we developed a data-driven model of SARS-CoV-2 transmission for Shanghai, China, a population with low prior immunity from natural infection. We found that extending the vaccination program to individuals aged 3-17 years plays a key role to reach herd immunity for the original SARS-CoV-2 lineages. With a vaccine efficacy 74% against infection, vaccine-induced herd immunity would require coverages of 93% or higher. Herd immunity for new variants, such as Alpha or Delta, can only be achieved with more efficacious vaccines and coverages above 80-90%. A continuation of the current pace of vaccination in China would reach 72% coverage by September 2021; although this program would fail to reach herd immunity it would reduce deaths by 95-100% in case of an outbreak. Efforts should be taken to increase population's confidence and willingness to be vaccinated and to guarantee highly efficacious vaccines against more transmissible variants of concern.