Reconstructing the early global dynamics of under-ascertained COVID-19 cases and infections
Authors: Russell Timothy W. , Golding Nick , Hellewell Joel , Abbott Sam , Wright Lawrence , Pearson Carl A. B. , van Zandvoort Kevin , Jarvis Christopher I. , Gibbs Hamish , Liu Yang , Eggo Rosalind M. , Edmunds W. John , Kucharski Adam J. ,   CMMID COVID-19 working group, Deol Arminder K. , Villabona-Arenas C. Julian , Jombart Thibaut , O’Reilly Kathleen , Munday James D. , Meakin Sophie R. , Lowe Rachel , Gimma Amy , Endo Akira , Nightingale Emily S. , Medley Graham , Foss Anna M. , Knight Gwenan M. , Prem Kiesha , Hué Stéphane , Diamond Charlie , Rudge James W. , Atkins Katherine E. , Auzenbergs Megan , Flasche Stefan , Houben Rein M. G. J. , Quilty Billy J. , Klepac Petra , Quaife Matthew , Funk Sebastian , Leclerc Quentin J. , Emery Jon C. , Jit Mark , Simons David , Bosse Nikos I. , Procter Simon R. , Sun Fiona Yueqian , Clifford Samuel , Sherratt Katharine , Rosello Alicia , Davies Nicholas G. , Brady Oliver , Tully Damien C. , Gore-Langton Georgia R. 
Published: October 2020

Abstract
Background
Asymptomatic or subclinical SARS-CoV-2 infections are often unreported, which means that confirmed case counts may not accurately reflect underlying epidemic dynamics. Understanding the level of ascertainment (the ratio of confirmed symptomatic cases to the true number of symptomatic individuals) and undetected epidemic progression is crucial to informing COVID-19 response planning, including the introduction and relaxation of control measures. Estimating case ascertainment over time allows for accurate estimates of specific outcomes such as seroprevalence, which is essential for planning control measures.

Methods
Using reported data on COVID-19 cases and fatalities globally, we estimated the proportion of symptomatic cases (i.e. any person with any of fever ≥ 37.5 °C, cough, shortness of breath, sudden onset of anosmia, ageusia or dysgeusia illness) that were reported in 210 countries and territories, given those countries had experienced more than ten deaths. We used published estimates of the baseline case fatality ratio (CFR), which was adjusted for delays and under-ascertainment, then calculated the ratio of this baseline CFR to an estimated local delay-adjusted CFR to estimate the level of under-ascertainment in a particular location. We then fit a Bayesian Gaussian process model to estimate the temporal pattern of under-ascertainment.

Results
Based on reported cases and deaths, we estimated that, during March 2020, the median percentage of symptomatic cases detected across the 84 countries which experienced more than ten deaths ranged from 2.4% (Bangladesh) to 100% (Chile). Across the ten countries with the highest number of total confirmed cases as of 6 July 2020, we estimated that the peak number of symptomatic cases ranged from 1.4 times (Chile) to 18 times (France) larger than reported. Comparing our model with national and regional seroprevalence data where available, we find that our estimates are consistent with observed values. Finally, we estimated seroprevalence for each country. As of 7 June, our seroprevalence estimates range from 0% (many countries) to 13% (95% CrI 5.6–24%) (Belgium).

Conclusions
We found substantial under-ascertainment of symptomatic cases, particularly at the peak of the first wave of the SARS-CoV-2 pandemic, in many countries. Reported case counts will therefore likely underestimate the rate of outbreak growth initially and underestimate the decline in the later stages of an epidemic. Although there was considerable under-reporting in many locations, our estimates were consistent with emerging serological data, suggesting that the proportion of each country’s population infected with SARS-CoV-2 worldwide is generally low.