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Disease surveillance systems provide early warnings of disease outbreaks before they become public health emergencies. However, pandemics containment would be challenging due to the complex immunity landscape created by multiple variants. Genomic surveillance is critical for detecting novel variants with diverse characteristics and importation/emergence times. Yet, a systematic study incorporating genomic monitoring, situation assessment, and intervention strategies is lacking in the literature. We formulate an integrated computational modeling framework to study a realistic course of action based on sequencing, analysis, and response. We study the effects of the second variant's importation time, its infectiousness advantage and, its cross-infection on the novel variant's detection time, and the resulting intervention scenarios to contain epidemics driven by two-variants dynamics. Our results illustrate the limitation in the intervention's effectiveness due to the variants' competing dynamics and provide the following insights: i) There is a set of importation times that yields the worst detection time for the second variant, which depends on the first variant's basic reproductive number; ii) When the second variant is imported relatively early with respect to the first variant, the cross-infection level does not impact the detection time of the second variant. We found that depending on the target metric, the best outcomes are attained under different interventions' regimes. Our results emphasize the importance of sustained enforcement of Non-Pharmaceutical Interventions on preventing epidemic resurgence due to importation/emergence of novel variants. We also discuss how our methods can be used to study when a novel variant emerges within a population.
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COVID-19 , Pandemias , Humanos , Pandemias/prevenção & controle , Saúde Pública , Surtos de Doenças/prevenção & controle , GenômicaRESUMO
[This corrects the article DOI: 10.1016/j.ijregi.2021.10.008.].
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We provide a methodology by which an epidemiologist may arrive at an optimal design for a survey whose goal is to estimate the disease burden in a population. For serosurveys with a given budget of C rupees, a specified set of tests with costs, sensitivities, and specificities, we show the existence of optimal designs in four different contexts, including the well known c-optimal design. Usefulness of the results are illustrated via numerical examples. Our results are applicable to a wide range of epidemiological surveys under the assumptions that the estimate's Fisher-information matrix satisfies a uniform positive definite criterion.
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Objective: Demonstrate the feasibility of using the existing sentinel surveillance infrastructure to conduct the second round of the serial cross-sectional sentinel-based population survey. Assess active infection, seroprevalence, and their evolution in the general population across Karnataka. Identify local variations for locally appropriate actions. Additionally, assess the clinical sensitivity of the testing kit used on account of variability of antibody levels in the population. Methods: The cross-sectional study of 41,228 participants across 290 healthcare facilities in all 30 districts of Karnataka was done among three groups of participants (low, moderate, and high-risk). The geographical spread was sufficient to capture local variations. Consenting participants were subjected to real-time reverse transcription-polymerase chain reaction (RT-PCR) testing, and antibody (IgG) testing. Clinical sensitivity was assessed by conducting a longitudinal study among participants identified as COVID-19 positive in the first survey round. Results: Overall weighted adjusted seroprevalence of IgG was 15.6% (95% CI: 14.9-16.3), crude IgG prevalence was 15.0% and crude active infection was 0.5%. Statewide infection fatality rate (IFR) was estimated as 0.11%, and COVID-19 burden estimated between 26.1 to 37.7% (at 90% confidence). Further, Cases-to-infections ratio (CIR) varied 3-35 across units and IFR varied 0.04-0.50% across units. Clinical sensitivity of the IgG ELISA test kit was estimated as ≥38.9%. Conclusion: We demonstrated the feasibility and simplicity of sentinel-based population survey in measuring variations in subnational and local data, useful for locally appropriate actions in different locations. The sentinel-based population survey thus helped identify districts that needed better testing, reporting, and clinical management. The state was far from attaining natural immunity during the survey and hence must step up vaccination coverage and enforce public health measures to prevent the spread of COVD-19.
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OBJECTIVE: To estimate the burden of active infection and anti-SARS-CoV-2 IgG antibodies in Karnataka, India, and to assess variation across geographical regions and risk groups. METHODS: A cross-sectional survey of 16,416 people covering three risk groups was conducted between 3-16 September 2020 using the state of Karnataka's infrastructure of 290 healthcare facilities across all 30 districts. Participants were further classified into risk subgroups and sampled using stratified sampling. All participants were subjected to simultaneous detection of SARS-CoV-2 IgG using a commercial ELISA kit, SARS-CoV-2 antigen using a rapid antigen detection test (RAT) and reverse transcription-polymerase chain reaction (RT-PCR) for RNA detection. Maximum-likelihood estimation was used for joint estimation of the adjusted IgG, active and total prevalence (either IgG or active or both), while multinomial regression identified predictors. RESULTS: The overall adjusted total prevalence of COVID-19 in Karnataka was 27.7% (95% CI 26.1-29.3), IgG 16.8% (15.5-18.1) and active infection fraction 12.6% (11.5-13.8). The case-to-infection ratio was 1:40 and the infection fatality rate was 0.05%. Influenza-like symptoms or contact with a COVID-19-positive patient were good predictors of active infection. RAT kits had higher sensitivity (68%) in symptomatic people compared with 47% in asymptomatic people. CONCLUSION: This sentinel-based population survey was the first comprehensive survey in India to provide accurate estimates of the COVID-19 burden. The findings provide a reasonable approximation of the population immunity threshold levels. Using existing surveillance platforms coupled with a syndromic approach and sampling framework enabled this model to be replicable.
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COVID-19 , Anticorpos Antivirais , Estudos Transversais , Humanos , Imunoglobulina G , Índia/epidemiologia , Prevalência , SARS-CoV-2RESUMO
The Mumbai Suburban Railways, locals, are a key transit infrastructure of the city and is crucial for resuming normal economic activity. Due to high density during transit, the potential risk of disease transmission is high, and the government has taken a wait and see approach to resume normal operations. To reduce disease transmission, policymakers can enforce reduced crowding and mandate wearing of masks. Cohorting - forming groups of travelers that always travel together, is an additional policy to reduce disease transmission on locals without severe restrictions. Cohorting allows us to: (i) form traveler bubbles, thereby decreasing the number of distinct interactions over time; (ii) potentially quarantine an entire cohort if a single case is detected, making contact tracing more efficient, and (iii) target cohorts for testing and early detection of symptomatic as well as asymptomatic cases. Studying impact of cohorts using compartmental models is challenging because of the ensuing representational complexity. Agent-based models provide a natural way to represent cohorts along with the representation of the cohort members with the larger social network. This paper describes a novel multi-scale agent-based model to study the impact of cohorting strategies on COVID-19 dynamics in Mumbai. We achieve this by modeling the Mumbai urban region using a detailed agent-based model comprising of 12.4 million agents. Individual cohorts and their inter-cohort interactions as they travel on locals are modeled using local mean field approximations. The resulting multi-scale model in conjunction with a detailed disease transmission and intervention simulator is used to assess various cohorting strategies. The results provide a quantitative trade-off between cohort size and its impact on disease dynamics and well being. The results show that cohorts can provide significant benefit in terms of reduced transmission without significantly impacting ridership and or economic & social activity.
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We highlight the usefulness of city-scale agent-based simulators in studying various non-pharmaceutical interventions to manage an evolving pandemic. We ground our studies in the context of the COVID-19 pandemic and demonstrate the power of the simulator via several exploratory case studies in two metropolises, Bengaluru and Mumbai. Such tools may in time become a common-place item in the tool kit of the administrative authorities of large cities.