Time to sustained control of the effective reproduction number as a failure-time estimand: a county-level analysis of the first SARS-CoV-2 wave in the United States.

Subnational analyses of emerging pathogen transmission typically model the reproduction number (Rt) as a continuous outcome and estimate average associations with its level. Operationally, however, response planning depends on a different quantity: which jurisdictions bring transmission below the epidemic threshold (Rt<1), and how quickly. We formulate time to control as a failure-time estimand and show that doing so exposes a structural feature that linear regression does not accommodate: a jurisdiction cannot enter the risk set until enough cases accumulate to estimate Rt. Cases accumulate faster where transmission is faster, so entry time depends on the outcome process itself and on factors that drive early spread. We account for this outcome-dependent observability using a mixed-effects Cox proportional hazards model with calendar-time left truncation and state-level Gaussian frailties, applied to 2,956 US counties observed between January 22 and July 15, 2020. The primary event was defined as the first three-day sustained reduction of mean Rt below one. Control was rare (171 counties, 5.8%). Each standard-deviation increase in log population density was associated with a lower rate of control (hazard ratio 0.54; 95% confidence interval 0.44 - 0.67) and higher policy stringency with a faster rate (HR 1.50; CI 1.09 - 2.05). Evaluating jurisdictions by their rate of reaching an operational target - rather than by average transmission level - provides a clearer, decision-relevant metric for prospective allocation decisions and public health interventions. Keywords: SARS-CoV-2, COVID-19, reproduction number, survival analysis, Cox model, county-level, United States, policy stringency, population density.

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Publication Details

Journal
medRxiv
Published
2026-11-06
DOI
https://doi.org/10.64898/2026.11.05.26367273
Primary Topic
COVID-19 epidemiological studies
Type
preprint
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preprint

Time to sustained control of the effective reproduction number as a failure-time estimand: a county-level analysis of the first SARS-CoV-2 wave in the United States.

Vana Sypsa, Athanasios Kakasis, Nikolaos Demiris, Evangelia Samoli et al.
medRxiv
COVID-19 epidemiological studies
preprint

Time to sustained control of the effective reproduction number as a failure-time estimand: a county-level analysis of the first SARS-CoV-2 wave in the United States.

Vana Sypsa, Athanasios Kakasis, Nikolaos Demiris, Evangelia Samoli, Marianna Panagiotidou
preprint en

Abstract

Subnational analyses of emerging pathogen transmission typically model the reproduction number (Rt) as a continuous outcome and estimate average associations with its level. Operationally, however, response planning depends on a different quantity: which jurisdictions bring transmission below the epidemic threshold (Rt<1), and how quickly. We formulate time to control as a failure-time estimand and show that doing so exposes a structural feature that linear regression does not accommodate: a jurisdiction cannot enter the risk set until enough cases accumulate to estimate Rt. Cases accumulate faster where transmission is faster, so entry time depends on the outcome process itself and on factors that drive early spread. We account for this outcome-dependent observability using a mixed-effects Cox proportional hazards model with calendar-time left truncation and state-level Gaussian frailties, applied to 2,956 US counties observed between January 22 and July 15, 2020. The primary event was defined as the first three-day sustained reduction of mean Rt below one. Control was rare (171 counties, 5.8%). Each standard-deviation increase in log population density was associated with a lower rate of control (hazard ratio 0.54; 95% confidence interval 0.44 - 0.67) and higher policy stringency with a faster rate (HR 1.50; CI 1.09 - 2.05). Evaluating jurisdictions by their rate of reaching an operational target - rather than by average transmission level - provides a clearer, decision-relevant metric for prospective allocation decisions and public health interventions. Keywords: SARS-CoV-2, COVID-19, reproduction number, survival analysis, Cox model, county-level, United States, policy stringency, population density.

medRxiv
National and Kapodistrian University of Athens (GR), Athens University of Economics and Business (GR)
Good health and well-being
COVID-19 epidemiological studies
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