Assessing epidemic curves for evidence of superspreading

The expected number of secondary infections arising from each index case, the reproduction number, or R number is a vital summary statistic for understanding and managing epidemic diseases. There are many methods for estimating R; however, few of these explicitly model heterogeneous disease reproduction, which gives rise to superspreading within the population. Here we propose a parsimonious discrete-time branching process model for epidemic curves that incorporates heterogeneous individual reproduction numbers. Our Bayesian approach to inference illustrates that this heterogeneity results in less certainty on estimates of the time-varying cohort reproduction number Rt. Leave-future-out cross-validation evaluates the predictive performance of the proposed model, allowing us to assess epidemic curves for evidence of superspreading. We apply these methods to a COVID-19 epidemic curve for the Republic of Ireland and find some support for heterogeneous disease reproduction. We conclude that the 10% most infectious index cases account for approximately 40-80% of the expected secondary infections. Our analysis highlights the difficulties in identifying heterogeneous disease reproduction from epidemic curves and that heterogeneity is a vital consideration when estimating Rt.

[1]  T. Britton,et al.  Statistical studies of infectious disease incidence , 1999 .

[2]  L. Dwivedi,et al.  Estimates of serial interval for COVID-19: A systematic review and meta-analysis , 2020, Clinical Epidemiology and Global Health.

[3]  Aki Vehtari,et al.  Approximate leave-future-out cross-validation for Bayesian time series models , 2019, 1902.06281.

[4]  Elisa Franco,et al.  The challenges of modeling and forecasting the spread of COVID-19 , 2020, Proceedings of the National Academy of Sciences.

[5]  Katriona Shea,et al.  Modeling infectious epidemics , 2020, Nature Methods.

[6]  S. Bhatt,et al.  Estimating the effects of non-pharmaceutical interventions on COVID-19 in Europe , 2020, Nature.

[7]  Jiqiang Guo,et al.  Stan: A Probabilistic Programming Language. , 2017, Journal of statistical software.

[8]  J. M. Griffin,et al.  Rapid review of available evidence on the serial interval and generation time of COVID-19 , 2020, BMJ Open.

[9]  C. Dye,et al.  Heterogeneities in the transmission of infectious agents: implications for the design of control programs. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[10]  Sebastian Funk,et al.  Extended data: Estimating the overdispersion in COVID-19 transmission using outbreak sizes outside China , 2020 .

[11]  Tom Britton,et al.  Stochastic epidemic models: a survey. , 2009, Mathematical biosciences.

[12]  J. Wallinga,et al.  Different Epidemic Curves for Severe Acute Respiratory Syndrome Reveal Similar Impacts of Control Measures , 2004, American journal of epidemiology.

[13]  J. Collins,et al.  Evidence that coronavirus superspreading is fat-tailed , 2020, Proceedings of the National Academy of Sciences.

[14]  Frank Ball,et al.  A mathematical model reveals the influence of population heterogeneity on herd immunity to SARS-CoV-2 , 2020, Science.

[15]  J. Knight,et al.  Estimating effective reproduction number using generation time versus serial interval, with application to covid-19 in the Greater Toronto Area, Canada , 2020, Infectious Disease Modelling.

[16]  Aki Vehtari,et al.  Implicitly adaptive importance sampling , 2021, Stat. Comput..

[17]  Claire Donnat,et al.  Modeling the heterogeneity in COVID-19's reproductive number and its impact on predictive scenarios , 2020, Journal of Applied Statistics.

[18]  C. Fraser,et al.  A New Framework and Software to Estimate Time-Varying Reproduction Numbers During Epidemics , 2013, American journal of epidemiology.

[19]  M. Keeling,et al.  Modeling Infectious Diseases in Humans and Animals , 2007 .

[20]  L Forsberg White,et al.  A likelihood‐based method for real‐time estimation of the serial interval and reproductive number of an epidemic , 2008, Statistics in medicine.

[21]  Sam Abbott,et al.  Practical considerations for measuring the effective reproductive number, Rt , 2020, PLoS computational biology.

[22]  E. Lau,et al.  Serial interval of SARS-CoV-2 was shortened over time by nonpharmaceutical interventions , 2020, Science.

[23]  A. Veen,et al.  Estimation of Space–Time Branching Process Models in Seismology Using an EM–Type Algorithm , 2006 .

[24]  K. Hadeler,et al.  A core group model for disease transmission. , 1995, Mathematical biosciences.

[25]  Roy M. Anderson,et al.  Transmission dynamics of HIV infection , 1987, Nature.

[26]  HighWire Press Proceedings of the Royal Society of London. Series A, Containing papers of a mathematical and physical character , 1934 .

[27]  Sang Woo Park,et al.  Forward-looking serial intervals correctly link epidemic growth to reproduction numbers , 2020, Proceedings of the National Academy of Sciences.

[28]  W. O. Kermack,et al.  A contribution to the mathematical theory of epidemics , 1927 .

[29]  C. Fraser Estimating Individual and Household Reproduction Numbers in an Emerging Epidemic , 2007, PloS one.

[30]  A. Gelman,et al.  Rank-normalization, folding, and localization: An improved R-hat for assessing convergence Rank-Normalization, Folding, and Localization: An Improved (cid:2) R for Assessing Convergence of MCMC An assessing for assessing An improved (cid:2) R for assessing convergence of MCMC , 2020 .

[31]  Aki Vehtari,et al.  Practical Bayesian model evaluation using leave-one-out cross-validation and WAIC , 2015, Statistics and Computing.

[32]  Joachim Hermisson,et al.  Disease momentum: Estimating the reproduction number in the presence of superspreading , 2021, Infectious Disease Modelling.

[33]  A. Vespignani,et al.  Transmission heterogeneities, kinetics, and controllability of SARS-CoV-2 , 2020, medRxiv.

[34]  T. McCormick,et al.  Quantifying heterogeneity in SARS-CoV-2 transmission during the lockdown in India , 2020, medRxiv.

[35]  M. Keeling,et al.  Networks and epidemic models , 2005, Journal of The Royal Society Interface.

[36]  Andrew Gelman,et al.  The No-U-turn sampler: adaptively setting path lengths in Hamiltonian Monte Carlo , 2011, J. Mach. Learn. Res..

[37]  N. Grassly,et al.  Mathematical models of infectious disease transmission , 2008, Nature Reviews Microbiology.

[38]  Carl E. Rasmussen,et al.  Gaussian processes for machine learning , 2005, Adaptive computation and machine learning.

[39]  Jim Koopman,et al.  Modeling infection transmission. , 2004, Annual review of public health.

[40]  P. Kaye Infectious diseases of humans: Dynamics and control , 1993 .

[41]  D. Rubin,et al.  Maximum likelihood from incomplete data via the EM - algorithm plus discussions on the paper , 1977 .

[42]  P. E. Kopp,et al.  Superspreading and the effect of individual variation on disease emergence , 2005, Nature.

[43]  David J. P. O'Sullivan,et al.  Calibrating COVID-19 SEIR models with time-varying effective contact rates , 2021, 2106.04705.

[44]  M. van Boven,et al.  Optimizing infectious disease interventions during an emerging epidemic , 2009, Proceedings of the National Academy of Sciences.

[45]  L. Meyers,et al.  Serial Interval of COVID-19 among Publicly Reported Confirmed Cases , 2020, Emerging infectious diseases.

[46]  M. Lipsitch,et al.  How generation intervals shape the relationship between growth rates and reproductive numbers , 2007, Proceedings of the Royal Society B: Biological Sciences.

[47]  C. Faes,et al.  Estimating the generation interval for coronavirus disease (COVID-19) based on symptom onset data, March 2020 , 2020, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.