Estimates of the severity of coronavirus disease 2019: a model-based analysis

Abstract

Background: In the face of rapidly changing data, a range of case fatality ratio estimates for coronavirus disease 2019 (COVID-19) have been produced that differ substantially in magnitude. We aimed to provide robust estimates, accounting for censoring and ascertainment biases.

Methods: We collected individual-case data for patients who died from COVID-19 in Hubei, mainland China (reported by national and provincial health commissions to Feb 8, 2020), and for cases outside of mainland China (from government or ministry of health websites and media reports for 37 countries, as well as Hong Kong and Macau, until Feb 25, 2020). These individual-case data were used to estimate the time between onset of symptoms and outcome (death or discharge from hospital). We next obtained age-stratified estimates of the case fatality ratio by relating the aggregate distribution of cases to the observed cumulative deaths in China, assuming a constant attack rate by age and adjusting for demography and age-based and location-based under-ascertainment. We also estimated the case fatality ratio from individual line-list data on 1334 cases identified outside of mainland China. Using data on the prevalence of PCR-confirmed cases in international residents repatriated from China, we obtained age-stratified estimates of the infection fatality ratio. Furthermore, data on age-stratified severity in a subset of 3665 cases from China were used to estimate the proportion of infected individuals who are likely to require hospitalisation.

Findings: Using data on 24 deaths that occurred in mainland China and 165 recoveries outside of China, we estimated the mean duration from onset of symptoms to death to be 17·8 days (95% credible interval [CrI] 16·9-19·2) and to hospital discharge to be 24·7 days (22·9-28·1). In all laboratory confirmed and clinically diagnosed cases from mainland China (n=70 117), we estimated a crude case fatality ratio (adjusted for censoring) of 3·67% (95% CrI 3·56-3·80). However, after further adjusting for demography and under-ascertainment, we obtained a best estimate of the case fatality ratio in China of 1·38% (1·23-1·53), with substantially higher ratios in older age groups (0·32% [0·27-0·38] in those aged <60 years vs 6·4% [5·7-7·2] in those aged ≥60 years), up to 13·4% (11·2-15·9) in those aged 80 years or older. Estimates of case fatality ratio from international cases stratified by age were consistent with those from China (parametric estimate 1·4% [0·4-3·5] in those aged <60 years [n=360] and 4·5% [1·8-11·1] in those aged ≥60 years [n=151]). Our estimated overall infection fatality ratio for China was 0·66% (0·39-1·33), with an increasing profile with age. Similarly, estimates of the proportion of infected individuals likely to be hospitalised increased with age up to a maximum of 18·4% (11·0-37·6) in those aged 80 years or older.

Interpretation: These early estimates give an indication of the fatality ratio across the spectrum of COVID-19 disease and show a strong age gradient in risk of death.

Funding: UK Medical Research Council.

Figure 1

Spectrum of COVID-19 cases At the top of the pyramid, those meeting the WHO case criteria for severe or critical cases are likely to be identified in the hospital setting, presenting with atypical viral pneumonia. These cases will have been identified in mainland China and among those categorised internationally as local transmission. Many more cases are likely to be symptomatic (ie, with fever, cough, or myalgia), but might not require hospitalisation. These cases will have been identified through links to international travel to high-risk areas and through contact-tracing of contacts of confirmed cases. They might also be identified through population surveillance of, for example, influenza-like illness. The bottom part of the pyramid represents mild (and possibly asymptomatic) cases. These cases might be identified through contact tracing and subsequently via serological testing.

Figure 2

Onset-to-death and onset-to-recovery distributions (A) Onset-to-death data from 24 cases in mainland China early in the epidemic. (B) Onset-to-recovery data from 169 cases outside of mainland China. Red lines show the best fit (posterior mode) gamma distributions, uncorrected for epidemic growth, which are biased towards shorter durations. Blue lines show the same distributions corrected for epidemic growth. The black line (panel A) shows the posterior estimate of the onset-to-death distribution following fitting to the aggregate case data.

Figure 3

Estimates of case fatality ratio by age, obtained from aggregate data from mainland China (A) Age-distribution of cases in Wuhan and elsewhere in China. (B) Estimates of the case fatality ratio by age group, adjusted for demography and under-ascertainment. Boxes represent median (central horizontal line) and IQR, vertical lines represent 1·5 × IQR, and individual points represent any estimates outside of this range. (C) Estimated proportions of cases ascertained in the rest of China and in Wuhan relative to the 50–59 years age group elsewhere in China. Error bars represent 95% CrIs.