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. MethodsWe 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.

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Highly pathogenic H5N1 influenza A viruses are now endemic in avian populations in Southeast Asia, and human cases continue to accumulate. Although currently incapable of sustained human-to-human transmission, H5N1 represents a serious pandemic threat owing to the risk of a mutation or reassortment generating a virus with increased transmissibility. Identifying public health interventions that might be able to halt a pandemic in its earliest stages is therefore a priority. Here we use a simulation model of influenza transmission in Southeast Asia to evaluate the potential effectiveness of targeted mass prophylactic use of antiviral drugs as a containment strategy. Other interventions aimed at reducing population contact rates are also examined as reinforcements to an antiviral-based containment policy. We show that elimination of a nascent pandemic may be feasible using a combination of geographically targeted prophylaxis and social distancing measures, if the basic reproduction number of the new virus is below 1.8. We predict that a stockpile of 3 million courses of antiviral drugs should be sufficient for elimination. Policy effectiveness depends critically on how quickly clinical cases are diagnosed and the speed with which antiviral drugs can be distributed.

The aim of this study is to identify general properties of emerging infectious agents that determine the likely success of two simple public health measures in controlling outbreaks, namely (i) isolating symptomatic individuals and (ii) tracing and quarantining their contacts. Because these measures depend on the recognition of specific disease symptoms, we investigate the relative timing of infectiousness and the appearance of symptoms by using a mathematical model. We show that the success of these control measures is determined as much by the proportion of transmission occurring prior to the onset of overt clinical symptoms (or via asymptomatic infection) as the inherent transmissibility of the etiological agent (measured by the reproductive number R0). From published studies, we estimate these quantities for two moderately transmissible viruses, severe acute respiratory syndrome coronavirus and HIV, and for two highly transmissible viruses, smallpox and pandemic influenza. We conclude that severe acute respiratory syndrome and smallpox are easier to control using these simple public health measures. Direct estimation of the proportion of asymptomatic and presymptomatic infections is achievable by contact tracing and should be a priority during an outbreak of a novel infectious agent.epidemiology ͉ severe acute respiratory syndrome ͉ HIV ͉ smallpox ͉ influenza T he global spread of severe acute respiratory syndrome (SARS) in early 2003 caused at least 800 deaths and substantial morbidity and had a significant economic cost for the worse affected countries (1-4). Despite rapid early spread, the epidemic eventually was contained, reflecting in part a highly effective global public health response. However, containment was aided also by specific epidemiological and biological characteristics of the SARS virus. Evaluating whether the methods used to control SARS are likely to be equally effective for future outbreaks of other emerging infectious diseases requires a more detailed understanding of the factors that make containment feasible even when effective vaccines or treatment are not available.In the first instance, two basic public health policy options exist for controlling the spread of an infectious disease in the absence of effective vaccines or treatment: (i) effective isolation of symptomatic individuals and (ii) tracing and quarantining of the contacts of symptomatic cases. Both measures rely on rapid dissemination of information to facilitate accurate diagnosis of the symptoms of the disease based on a clear and precise case definition.For SARS, the timing of the onset of symptoms relative to peak infectivity is likely to have been a crucial factor in the success of simple public health interventions aimed at reducing transmission. In SARS patients, viremia (as measured in both fecal material and respiratory tract exudates) seems to peak between 5 and 10 days after the onset of illness and overt clinical symptoms such as elevated temperature (5). Although viremia does not always predict infectivity, t...

We present an analysis of the first 10 weeks of the severe acute respiratory syndrome (SARS) epidemic in Hong Kong. The epidemic to date has been characterized by two large clusters—initiated by two separate “super-spread” events (SSEs)—and by ongoing community transmission. By fitting a stochastic model to data on 1512 cases, including these clusters, we show that the etiological agent of SARS is moderately transmissible. Excluding SSEs, we estimate that 2.7 secondary infections were generated per case on average at the start of the epidemic, with a substantial contribution from hospital transmission. Transmission rates fell during the epidemic, primarily as a result of reductions in population contact rates and improved hospital infection control, but also because of more rapid hospital attendance by symptomatic individuals. As a result, the epidemic is now in decline, although continued vigilance is necessary for this to be maintained. Restrictions on longer range population movement are shown to be a potentially useful additional control measure in some contexts. We estimate that most currently infected persons are now hospitalized, which highlights the importance of control of nosocomial transmission.