Estimates of the severity of COVID-19 disease

Robert Verity; Lucy C Okell; Ilaria Dorigatti; Peter Winskill; Charles Whittaker; Natsuko Imai; Gina Cuomo-Dannenburg; Hayley Thompson; Patrick Walker; Han Fu; Amy Dighe; Jamie Griffin; Anne Cori; Marc Baguelin; Sangeeta Bhatia; Adhiratha Boonyasiri; Zulma M Cucunuba; Rich Fitzjohn; Katy A M Gaythorpe; Will Green; Arran Hamlet; Wes Hinsley; Daniel Laydon; Gemma Nedjati-Gilani; Steven Riley; Sabine van-Elsand; Erik Volz; Haowei Wang; Yuanrong Wang; Xiayoue Xi; Christl Donnelly; Azra Ghani; Neil Ferguson

Secondly, surveillance of a newly emerged pathogen is typically biased towards detecting clinically severe cases, particularly at the start of an epidemic when diagnostic capacity is limited (Figure 1) . Estimates of the CFR may thus be biased upwards until the extent of clinically milder disease is determined 9 . Data from the epicentre of the outbreak in Wuhan, China have primarily been detected through hospital surveillance and hence are likely to represent moderate or severe illness, with atypical pneumonia and/or acute respiratory distress being used to define suspected cases eligible for testing 7 . In these individuals, clinical outcomes are likely to be more severe, and therefore any estimates of the CFR will be higher. Elsewhere in mainland China and outside, countries and administrative regions alert to the risk of infection being imported via travel initially instituted surveillance for COVID-19 with a broader set of clinical criteria for defining a suspected case. These typically include a combination of symptoms (e.g. cough and fever) combined with recent travel history to the affected region (Wuhan and/or Hubei Province) 2, 17 . Such surveillance is therefore likely to detect clinically milder cases but, by initially restricting testing to those with a travel history or link, may have missed other symptomatic cases. More recently, as epidemics have taken off in other countries, cases are now being detected in those with no reported travel links to Wuhan/Hubei province through broader surveillance systems. Some of these cases may represent a milder level of severity -including secondary cases identified via contact-tracing or those identified through sentinel surveillance of influenza-like-illness at primary care 18, 19 . In contrast, others will represent the severe end of the disease spectrum with an increasing number identified through hospital surveillance (for example, testing of viral pneumonia) or in a few cases, at post-mortem analysis.