ABSTRACT
Background The unprecedented public health impact of the COVID-19 pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. Methods and Findings We develop a mathematical model of SARS-CoV-2 transmission, COVID-19 disease and clinical care to explore the potential public-health impact of a range of different potential therapeutics, under a range of different scenarios varying: i) healthcare capacity, ii) epidemic trajectories; and iii) drug efficacy in the absence of supportive care. In each case, the outcome of interest was the number of COVID-19 deaths averted in scenarios with the therapeutic compared to scenarios without. We find the impact of drugs like dexamethasone (which are delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R=1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalisation) could have much greater benefits, particularly in resource-poor settings facing large epidemics. Conclusions There is a global asymmetry in who is likely to benefit from advances in the treatment of COVID-19 to date, which have been focussed on hospitalised-patients and predicated on an assumption of adequate access to supportive care. Therapeutics that can feasibly be delivered to those earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.
Subject(s)
COVID-19ABSTRACT
Background: The unprecedented public health impact of the COVID-19 pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of current and proposed treatments, and consequently research and procurement priorities, have not been clear. Methods: First, we used a model of SARS-CoV-2 transmission, COVID-19 disease and clinical care pathways to explore the potential impact of dexamethasone - the main treatment currently for hospitalised COVID-19 patients - under scenarios varying: i) healthcare capacity, ii) epidemic trajectories; and iii) the efficacy of dexamethasone in the absence of supportive care. We then fit the model to the observed epidemic trajectory to-date in 165 countries and analysed the potential future impact of dexamethasone in different countries, regions, and country-income strata. Finally, we constructed hypothetical profiles of novel therapeutics based on current trials, and compared the potential impact of each under different circumstances. In each case, the outcome of interest was the number of COVID-19 deaths averted in scenarios with the therapeutic compared to scenarios without. Findings: We find the potential benefit dexamethasone is severely limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R=1.35). However, therapeutics for different patient populations (in particular, those not in hospital and early in the course of infection) and types of benefit (in particular, reducing disease severity or infectiousness) could have much greater benefits. Such therapeutics would have particular value in resource-poor settings facing large epidemics, even if the efficacy or achievable coverage of such therapeutics is lower in comparison to other types. Interpretation: People in low-income countries will benefit the least from advances in the treatment of COVID-19 to date, which have focussed on hospitalised-patients with adequate access to supportive care. Therapeutics that can feasibly be delivered to those earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have much greater impact. Such therapeutics may be feasible and research into their efficacy and means of delivery should be a priority. Funding: None to declare. Declaration of Interest: None to declare.
Subject(s)
COVID-19ABSTRACT
Background: A range of case fatality ratio (CFR) estimates for COVID 19 have been produced that differ substantially in magnitude. Methods: We used individual-case data from mainland China and cases detected outside mainland China to estimate the time between onset of symptoms and outcome (death or discharge from hospital). We next obtained age-stratified estimates of the CFR by relating the aggregate distribution of cases by dates of onset to the observed cumulative deaths in China, assuming a constant attack rate by age and adjusting for the demography of the population, and age and location-based under ascertainment. We additionally estimated the CFR from individual linelist data on 1,334 cases identified outside mainland China. We used data on the PCR prevalence in international residents repatriated from China at the end of January 2020 to obtain age-stratified estimates of the infection fatality ratio (IFR). Using data on age stratified severity in a subset of 3,665 cases from China, we estimated the proportion of infections that will likely require hospitalisation. Findings: We estimate the mean duration from onset-of-symptoms to death to be 17.8 days (95% credible interval, crI 16.9,19.2 days) and from onset-of-symptoms to hospital discharge to be 22.6 days (95% crI 21.1,24.4 days). We estimate a crude CFR of 3.67% (95% crI 3.56%,3.80%) in cases from mainland China. Adjusting for demography and under-ascertainment of milder cases in Wuhan relative to the rest of China, we obtain a best estimate of the CFR in China of 1.38% (95% crI 1.23%,1.53%) with substantially higher values in older ages. Our estimate of the CFR from international cases stratified by age (under 60 or 60 and above) are consistent with these estimates from China. We obtain an overall IFR estimate for China of 0.66% (0.39%,1.33%), again with an increasing profile with age. Interpretation: These early estimates give an indication of the fatality ratio across the spectrum of COVID-19 disease and demonstrate a strong age-gradient in risk.