Insights from Local Genomic Epidemiology Investigations and a Global Genomic Surveillance Program during the COVID-19 Pandemic
Open Access DepositedModernizing Pandemic Response using Genomics
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The COVID-19 pandemic highlighted both the potential of pathogen genomics to inform public health decision-making and the persistent challenges of integrating genomic data into routine surveillance and outbreak response. Although genomic sequencing technologies were widely available before 2020, their application within applied public health practice was inconsistent, and systems for linking genomic, epidemiologic, and operational data remained underdeveloped. This dissertation examines how genomics was used to support response during the COVID-19 pandemic and how these experiences can inform the modernization of pandemic preparedness systems. The dissertation comprises two complementary studies. The first is a global systematic review of peer-reviewed literature describing the use of whole-genome sequencing in local SARS-CoV-2 outbreak investigations during the first year of the pandemic. Thirty-two studies from 18 countries were analyzed to assess study settings, sequencing and analytic methods, integration with epidemiologic data, and reporting quality. Findings demonstrate that genomic epidemiology enhanced traditional outbreak investigations by confirming or refuting transmission links, identifying multiple introductions, detecting asymptomatic and presymptomatic transmission, and evaluating infection prevention and control measures. However, the review also reveals substantial disparities in implementation between high-income and low- and middle-income countries, as well as inconsistent reporting of sampling strategies, data representativeness, and analytic methods. The second study examines the implementation and outcomes of a large-scale SARS-CoV-2 genomic surveillance program within the U.S. Military Health System from 2020 to 2023. This descriptive analysis demonstrates the feasibility of integrating whole-genome sequencing into a globally distributed, operational health system, enabling early detection of emerging variants, sustained situational awareness, and identification of high-value sentinel surveillance sites. Together, these studies demonstrate that genomics is most impactful when embedded within integrated surveillance systems that align laboratory infrastructure, analytic capacity, standardized practices, and public health decision-making. The findings provide practical insights for strengthening genomic surveillance and modernizing pandemic preparedness and response for future biological threats.
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