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

BackgroundThe 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. MethodsWe 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. ResultsWe 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{square}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{square}years or more would have averted an average of 86-152 critical cases per 100,000 individuals, depending on the setting considered. ConclusionsDespite 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

BackgroundAn 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. MethodsUsing 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{square}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. FindingsFrom 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. InterpretationUnder 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. FundingKey Program of the National Natural Science Foundation of China (82130093). Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe 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 studyThe 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 evidenceWe 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

BackgroundThe 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. MethodsWe 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. FindingsOur 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. ConclusionsThis 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

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

BackgroundIn 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. MethodsWe 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). FindingsA 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. InterpretationOur 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. FundingKey Program of the National Natural Science Foundation of China (82130093). Research in contextO_ST_ABSEvidence before this studyC_ST_ABSOn May 24, 2022, we searched PubMed and Europe PMC for papers published or posted on preprint servers after January 1, 2022, using the following query: ("SARS-CoV-2" OR "Omicron" OR "BA.2") AND ("epidemiology" OR "epidemiological" OR "transmission dynamics") AND ("Shanghai"). A total of 26 studies were identified; among them, two aimed to describe or project the spread of the 2022 Omicron outbreak in Shanghai. One preprint described the epidemiological and clinical characteristics of 376 pediatric SARS-CoV-2 infections in March 2022, and the other preprint projected the epidemic progress in Shanghai, without providing an analysis of field data. In sum, none of these studies provided a comprehensive description of the epidemiological characteristics and spatiotemporal transmission dynamics of the outbreak. Added value of this studyWe collected individual information on SARS-CoV-2 infection and the timeline of the public health response. Population-based screenings were repeatedly implemented during the outbreak, which allowed us to investigate the spatiotemporal spread of the Omicron BA.2 variant as well as the impact of the implemented interventions, all without enduring significant amounts of underreporting from surveillance systems, as experienced in other areas. This study provides the first comprehensive assessment of the Omicron outbreak in Shanghai, China. Implications of all the available evidenceThis descriptive study provides a comprehensive understanding of the epidemiological features and transmission dynamics of the Omicron outbreak in Shanghai, China. The empirical evidence from Shanghai, which was ultimately able to curtail the outbreak, provides invaluable information to policymakers on the impact of the containment strategies adopted by the Shanghai public health officials to prepare for potential outbreaks caused by Omicron or novel variants.

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

We developed a spatially structured, fully stochastic, individual-based SARS-CoV-2 transmission model to evaluate the feasibility of sustaining SARS-CoV-2 local containment in mainland China considering currently dominant Omicron variants, Chinas current immunization level, and non-pharmaceutical interventions (NPIs). We also built a statistical model to estimate the overall disease burden under various hypothetical mitigation scenarios. We found that due to high transmissibility, neither Omicron BA.1 or BA.2 could be contained by Chinas pre-Omicron NPI strategies which were successful prior to the emergence of the Omicron variants. However, increased intervention intensity, such as enhanced population mobility restrictions and multi-round mass testing, could lead to containment success. We estimated that an acute Omicron epidemic wave in mainland China would result in significant number of deaths if China were to reopen under current vaccine coverage with no antiviral uptake, while increasing vaccination coverage and antiviral uptake could substantially reduce the disease burden. As Chinas current vaccination has yet to reach high coverage in older populations, NPIs remain essential tools to maintain low levels of infection while building up protective population immunity, ensuring a smooth transition out of the pandemic phase while minimizing the overall disease burden.

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

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

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.

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

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

BackgroundAfter 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 findingsWe 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. ConclusionsOur 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.

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

BackgroundTo 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. However, it remains to be seen whether herd immunity will be within reach of these programs. MethodsWe developed a data-driven model of SARS-CoV-2 transmission for China, a population with low prior immunity from natural infection. The model is calibrated considering COVID-19 natural history and the estimated transmissibility of the Delta variant. Three vaccination programs are tested, including the one currently enacted in China and model-based estimates of the herd immunity level are provided. ResultsWe found that it is unlike to reach herd immunity for the Delta variant given the relatively low efficacy of the vaccines used in China throughout 2021, the exclusion of underage individuals from the targeted population, and the lack of prior natural immunity. We estimate that, assuming a vaccine efficacy of 90% against the infection, vaccine-induced herd immunity would require a coverage of 93% or higher of the Chinese population. However, even when vaccine-induced herd immunity is not reached, we estimated that vaccination programs can reduce SARS-CoV-2 infections by 53-58% in case of an epidemic starts to unfold in the fall of 2021. ConclusionsEfforts should be taken to increase populations confidence and willingness to be vaccinated and to guarantee highly efficacious vaccines for a wider age range.

Social Contact Patterns and Implications for Infectious Disease Transmission: A Systematic Review and Meta-Analysis of Contact Surveys

BackgroundTransmission of respiratory pathogens such as SARS-CoV-2 depends on patterns of contact and mixing across populations. Understanding this is crucial to predict pathogen spread and the effectiveness of control efforts. Most analyses of contact patterns to date have focussed on high-income settings. MethodsHere, we conduct a systematic review and individual-participant meta-analysis of surveys carried out in low- and middle-income countries and compare patterns of contact in these settings to surveys previously carried out in high-income countries. Using individual-level data from 28,503 participants and 413,069 contacts across 27 surveys we explored how contact characteristics (number, location, duration and whether physical) vary across income settings. ResultsContact rates declined with age in high- and upper-middle-income settings, but not in low-income settings, where adults aged 65+ made similar numbers of contacts as younger individuals and mixed with all age-groups. Across all settings, increasing household size was a key determinant of contact frequency and characteristics, but low-income settings were characterised by the largest, most intergenerational households. A higher proportion of contacts were made at home in low-income settings, and work/school contacts were more frequent in high-income strata. We also observed contrasting effects of gender across income-strata on the frequency, duration and type of contacts individuals made. ConclusionsThese differences in contact patterns between settings have material consequences for both spread of respiratory pathogens, as well as the effectiveness of different non-pharmaceutical interventions. FundingThis work is primarily being funded by joint Centre funding from the UK Medical Research Council and DFID (MR/R015600/1).

Model-based evaluation of alternative reactive class closure strategies against COVID-19

There are contrasting results concerning the effect of reactive school closure on SARS-CoV-2 transmission. To shed light on this controversy, here we develop a data-driven computational model of SARS-CoV-2 transmission to investigate mechanistically the effect on COVID-19 outbreaks of school closure strategies based on syndromic surveillance and antigen screening of students. We found that by reactively closing classes based on syndromic surveillance, SARS-CoV-2 infections are reduced by no more than 13.1% (95%CI: 8.6%-20.2 %), due to the low probability of timely symptomatic case identification among the young population. We thus investigated an alternative triggering mechanism based on repeated screening of students using antigen tests. Should population-level social distancing measures unrelated to schools enable maintaining the reproduction number (R) at 1.3 or lower, an antigen-based screening strategy is estimated to fully prevent COVID-19 outbreaks in the general population. Depending on the contribution of schools to transmission, this strategy can either prevent COVID-19 outbreaks for R up to 1.9 or to at least greatly reduce outbreak size in very conservative scenarios about school contribution to transmission. Moving forward, the adoption of antigen-based screenings in schools could be instrumental to limit COVID-19 burden while vaccines continue to roll out through 2021, especially in light of possible continued emergence of SARS-CoV-2 variants.

The risk of symptomatic reinfection during the second COVID-19 wave in individuals previously exposed to SARS-CoV-2

To what extent infection with SARS-CoV-2 protects against subsequent reinfection or symptomatic reinfection is still unclear. In this cohort study, we analyzed surveillance records of COVID-19 cases identified between June 2020 and January 2021 in five Italian municipalities, where 77.7% of the entire population was screened for IgG antibodies in May 2020. We compared the risk of observing symptomatic infections in two mutually exclusive groups defined by the initial serological response. We estimated that the cumulative incidence of identified symptomatic infections in the IgG negative and positive cohorts was 2.67% (95%CI: 2.12% - 3.37%) and 0.14% (95%CI: 0.04% - 0.58%), respectively. The adjusted odd ratio of developing symptomatic infection in individuals previously exposed to SARS-CoV-2 was estimated at 0.054 (95%CI: 0.009 - 0.169). Quantifying protective immunity against COVID-19 disease elicited by natural infection with SARS-CoV-2 is essential to inform strategies for controlling the pandemic in the forthcoming months.

Co-circulation of SARS-CoV-2 variants B.1.1.7 and P.1

SARS-CoV-2 variants of concern (B.1.1.7, P.1 and B.1.351) have emerged in different continents of the world. To date, little information is available on their ecological interactions. Based on two genomic surveillance surveys conducted on February 18 and March 18, 2021 across the whole Italian territory and covering over 3,000 clinical samples, we found significant co-circulation of B.1.1.7 and P.1. We showed that B.1.1.7 was already dominant on February 18 in a majority of regions/autonomous provinces (national prevalence 54%) and almost completely replaced historical lineages by March 18 (dominant in all regions/autonomous provinces, national prevalence 86%). At the same time, we found a substantial proportion of cases of the P.1 lineage on February 18, almost exclusively in Central Italy (with an overall prevalence in the macro-area of 18%), which remained at similar values on March 18, suggesting the inability by this lineage to outcompete B.1.1.7. Only 9 cases from variant B.1.351 were identified in the two surveys. At the national level, we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66). The relative transmissibility of P.1 estimated at the national level varied according to the assumed degree of cross-protection granted by infection with other lineages and ranged from 1.12 (95%CI 1.03-1.23) in the case of complete immune evasion by P.1 to 1.39 (95%CI 1.26-1.56) in the case of complete cross-protection. These observations may have important consequences on the assessment of future pandemic scenarios.

Cryptic transmission of SARS-CoV-2 and the first COVID-19 wave in Europe and the United States

Given the narrowness of the initial testing criteria, the SARS-CoV-2 virus spread through cryptic transmission in January and February, setting the stage for the epidemic wave experienced in March and April, 2020. We use a global metapopulation epidemic model to provide a mechanistic understanding of the global dynamic underlying the establishment of the COVID-19 pandemic in Europe and the United States (US). The model is calibrated on international case introductions at the early stage of the pandemic. We find that widespread community transmission of SARS-CoV-2 was likely in several areas of Europe and the US by January 2020, and estimate that by early March, only 1 - 3 in 100 SARS-CoV-2 infections were detected by surveillance systems. Modeling results indicate international travel as the key driver of the introduction of SARS-CoV-2 with possible importation and transmission events as early as December, 2019. We characterize the resulting heterogeneous spatio-temporal spread of SARS-CoV-2 and the burden of the first COVID-19 wave (February-July 2020). We estimate infection attack rates ranging from 0.78%-15.2% in the US and 0.19%-13.2% in Europe. The spatial modeling of SARS-CoV-2 introductions and spreading provides insights into the design of innovative, model-driven surveillance systems and preparedness plans that have a broader initial capacity and indication for testing.

Data-driven estimate of SARS-CoV-2 herd immunity threshold in populations with individual contact pattern variations

The development of efficacious vaccines has made it possible to envision mass vaccination programs aimed at suppressing SARS-CoV-2 transmission around the world. Here we use a data-driven age-structured multilayer representation of the population of 34 countries to estimate the disease induced immunity threshold, accounting for the contact variability across individuals. We show that the herd immunization threshold of random (un-prioritized) mass vaccination programs is generally larger than the disease induced immunity threshold. We use the model to test two additional vaccine prioritization strategies, transmission-focused and age-based, in which individuals are inoculated either according to their behavior (number of contacts) or infection fatality risk, respectively. Our results show that in the case of a sterilizing vaccine the behavioral strategy achieves herd-immunity at a coverage comparable to the disease-induced immunity threshold, but it appears to have inferior performance in averting deaths than the risk vaccination strategy. The presented results have potential use in defining the effects that the heterogeneity of social mixing and contact patterns has on herd immunity levels and the deployment of vaccine prioritization strategies.

Return to normal: COVID-19 vaccination under mitigation measures

Vaccination campaigns against COVID-19 are allowing the progressive release of physical distancing restrictions in many countries. However, the global spread of the highly transmissible Delta variant has likely suppressed the residual chances of SARS-CoV-2 elimination through herd immunity alone. Here we assess the impact of the vaccination program in Italy since its start on December 27, 2020 and evaluate possible prospects for reopening the society while at the same time keeping COVID-19 under control. To this aim, we propose a mathematical modeling framework where levels of social activity are adjusted to match the time-series of the net reproduction number as estimated from surveillance data. We compared the estimated level of social contacts, number of deaths, and transmission potential with those of a counterfactual scenario where the same epidemic trajectory is obtained in absence of vaccination. We then evaluate the prospective impact of different scenarios of vaccination coverage and different social activity levels on SARS-CoV-2 reproduction number. We estimate that by June 30, 2021, the COVID-19 vaccination program allowed the resumption of about half the social contacts that were recorded in pre-pandemic times; in absence of vaccination, only about one third could have been resumed to obtain the same number of cases, with the added cost of about 12,100 (95%CI: 6,600-21,000) extra deaths (+27%; 95%CI: 15-47%) between December 27, 2020 and June 30, 2021. We show that the negative effect of the Delta variant diffusion in July was entirely offset by vaccination in the month of July and August 2021. Finally, we estimate that a complete return to the pre-pandemic life could be safely attained only if >90%, including children from 5 years on, will be vaccinated using mRNA vaccines developed in 2020. In any case, increasing the vaccination coverage will allow further margins for societal reopening even in absence of a pediatric vaccine. These results may support the definition of vaccination targets for countries that have already achieved a broad population coverage.

Estimating the spreading and dominance of SARS-CoV-2 VOC 202012/01 (lineage B.1.1.7) across Europe

We develop a two strain, age-structured, compartmental model to assess the spreading potential of the B.1.1.7 variant across several European metropolitan areas and countries. The model accounts for B.1.1.7 introductions from the UK and different locations, as well as local mitigation policies in the time period 2020/09 - 2021/02. In the case of an increase of transmissibility of 50%, the B.1.1.7 variant has the potential to become dominant in all investigated areas by the end of March 2021.

Can a COVID-19 vaccination program guarantee the return to a pre-pandemic lifestyle?

AbstractCOVID-19 vaccination is being conducted in over 190 countries/regions to control SARS-CoV-2 transmission and return to a pre-pandemic lifestyle. However, understanding when non-pharmaceutical interventions (NPIs) can be lifted as immunity builds up remain a key question for policy makers. To address it, we built a data-driven model of SARS-CoV-2 transmission for China. We estimated that to prevent the escalation of local outbreaks to widespread epidemics, stringent NPIs need to remain in place at least one year after the start of vaccination. Should NPIs alone be capable to keep the reproduction number (Rt) around 1.3, the synergetic effect of NPIs and vaccination could reduce up to 99% of COVID-19 burden and bring Rt below the epidemic threshold in about 9 months. Maintaining strict NPIs throughout 2021 is of paramount importance to reduce COVID-19 burden while vaccines are distributed to the population, especially in large populations with little natural immunity.