Coupled models of genomic surveillance and evolving pandemics with applications for timely public health interventions

Author:

Espinoza Baltazar1,Adiga Aniruddha1,Venkatramanan Srinivasan1,Warren Andrew Scott1,Chen Jiangzhuo1,Lewis Bryan Leroy1ORCID,Vullikanti Anil12,Swarup Samarth1,Moon Sifat1,Barrett Christopher Louis12ORCID,Athreya Siva34,Sundaresan Rajesh567,Chandru Vijay89,Laxminarayan Ramanan1011ORCID,Schaffer Benjamin1213,Poor H. Vincent12ORCID,Levin Simon A.12ORCID,Marathe Madhav V.12ORCID

Affiliation:

1. Network Systems Science and Advanced Computing Division, Biocomplexity Institute, University of Virginia, Charlottesville, VA 22904

2. Department of Computer Science, University of Virginia, Charlottesville, VA 22904

3. Indian Statistical Institute, Bengaluru, Karnataka 560059, India

4. International Centre for Theoretical Sciences, Bengaluru, Karnataka 560089, India

5. Department of Electrical and Communication Engineering, Indian Institute of Science, Bengaluru, Karnataka 560012, India

6. Robert Bosch Centre for Cyber-Physical Systems, Indian Institute of Science, Bengaluru, Karnataka 560012, India

7. Centre for Networked Intelligence, Indian Institute of Science, Bengaluru, Karnataka 560012, India

8. Strand Life Sciences, Bengaluru, Karnataka 560024, India

9. BioSystems Science and Engineering, Indian Institute of Science, Bengaluru, Karnataka 560012, India

10. Princeton University, Princeton, NJ 08542

11. One Health Trust, Washington, DC 20015

12. Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544

13. Department of Electrical and Computer Engineering, Princeton University, Princeton, NJ 08544

Abstract

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.

Funder

University of Virginia

HHS | National Institutes of Health

National Science Foundation

C3.ai Digital Transformation Institute

Google, Inc.

Indian Institute of Science

Indian Institute of Science, Centre for Networked Intelligence

International Centre for Theoretical Sciences

William H. Miller III 2018 Trust

Centers for Disease Control and Prevention Foundation

Virginia Department of Health

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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5. Time series modeling for syndromic surveillance;Reis B. Y.;BMC Med. Inf. Decis. Making,2003

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