AbstractBackgroundCOVID-19 mitigation strategies have been challenging to implement in resource-limited settings such as Malawi due to the potential for widespread disruption to social and economic well-being. Here we estimate the clinical severity of COVID-19 in Malawi, quantifying the potential impact of intervention strategies and increases in health system capacity.MethodsThe infection fatality ratios (IFR) in Malawi were estimated by adjusting reported IFR for China accounting for demography, the current prevalence of comorbidities and health system capacity. These estimates were input into an age-structured deterministic model, which simulated the epidemic trajectory with non-pharmaceutical interventions. The impact of a novel therapeutic agent and increases in hospital capacity and oxygen availability were explored, given different assumptions on mortality rates.FindingsThe estimated age-specific IFR in Malawi are higher than those reported for China, however the younger average age of the population results in a slightly lower population-weighted IFR (0.48%, 95% uncertainty interval [UI] 0.30% – 0.72% compared with 0.60%, 95% CI 0.4% – 1.3% in China). The current interventions implemented, (i.e. social distancing, workplace closures and public transport restrictions) could potentially avert 3,100 deaths (95% UI 1,500 – 4,500) over the course of the epidemic. Enhanced shielding of people aged ≥ 60 years could avert a further 30,500 deaths (95% UI 17,500 – 45,600) and halve ICU admissions at the peak of the outbreak. Coverage of face coverings of 60% under the assumption of 50% efficacy could be sufficient to control the epidemic. A novel therapeutic agent, which reduces mortality by 0.65 and 0.8 for severe and critical cases respectively, in combination with increasing hospital capacity could reduce projected mortality to 2.55 deaths per 1,000 population (95% UI 1.58 – 3.84).ConclusionThe risks due to COVID-19 vary across settings and are influenced by age, underlying health and health system capacity.Summary BoxWhat is already known?As COVID-19 spreads throughout Sub-Saharan Africa, countries are under increasing pressure to protect the most vulnerable by suppressing spread through, for example, stringent social distancing measures or shielding of those at highest risk away from the general population.There are a number of studies estimating infection fatality ratio due to COVID-19 but none use data from African settings. The estimated IFR varies across settings ranging between 0.28-0.99%, with higher values estimated for Europe (0.77%, 95% CI 0.55 – 0.99%) compared with Asia (0.46%, 95% CI 0.38 – 0.55).The IFR for African settings are still unknown, although several studies have highlighted the potential for increased mortality due to comorbidities such as HIV, TB and malaria.There are a small number of studies looking at the impact of non-pharmaceutical interventions in Africa, particularly South Africa, but none to date have combined this with country-specific estimates of IFR adjusted for comorbidity prevalence and with consideration to the prevailing health system constraints and the impact of these constraints on mortality rates.What are the new findings?After accounting for the health system constraints and differing prevalences of underlying comorbidities, the estimated infection fatality ratio (IFR) for Malawi (0.48%, 95% uncertainty interval 0.30% – 0.72%) is within the ranges reported for the Americas, Asia and Europe (overall IFR 0.70, 95% CI 0.57 – 0.82, range 0.28 – 0.89).Introducing enhanced shielding of people aged ≥ 60 years could avert up to 30,500 deaths (95% UI 17,500 – 45,600) and significantly reduce demand on ICU admissions.Maintaining coverage of face coverings at 60%, under the assumption of 50% efficacy, could be sufficient to control the epidemic.Combining the introduction of a novel therapeutic agent with increases in hospital capacity could reduce projected mortality to 2.55 deaths per 1,000 population (95% UI 1.58 – 3.84).What do the new findings imply?Adjusting estimates of COVID-19 severity to account for underlying health is crucial for predicting health system demands.A multi-pronged approach to controlling transmission, including face coverings, increasing hospital capacity and using new therapeutic agents could significantly reduce deaths to COVID-19, but is not as effective as a theoretical long-lasting lockdown.