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Preprint in English | medRxiv | ID: ppmedrxiv-21259078


BackgroundThe 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 FindingsWe 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. ConclusionsThere 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.

Preprint in English | medRxiv | ID: ppmedrxiv-21249564


We fitted a model of SARS-CoV-2 transmission in care homes and the community to regional surveillance data for England. Among control measures implemented, only national lockdown brought the reproduction number below 1 consistently; introduced one week earlier it could have reduced first wave deaths from 36,700 to 15,700 (95%CrI: 8,900-26,800). Improved clinical care reduced the infection fatality ratio from 1.25% (95%CrI: 1.18%-1.33%) to 0.77% (95%CrI: 0.71%-0.84%). The infection fatality ratio was higher in the elderly residing in care homes (35.9%, 95%CrI: 29.1%-43.4%) than those residing in the community (10.4%, 95%CrI: 9.1%-11.5%). England is still far from herd immunity, with regional cumulative infection incidence to 1st December 2020 between 4.8% (95%CrI: 4.4%-5.1%) and 15.4% (95%CrI: 14.9%-15.9%) of the population. One-sentence summaryWe fit a mathematical model of SARS-CoV-2 transmission to surveillance data from England, to estimate transmissibility, severity, and the impact of interventions

Preprint in English | medRxiv | ID: ppmedrxiv-20152355


As of 1st June 2020, the US Centers for Disease Control and Prevention reported 104,232 confirmed or probable COVID-19-related deaths in the US. This was more than twice the number of deaths reported in the next most severely impacted country. We jointly modelled the US epidemic at the state-level, using publicly available death data within a Bayesian hierarchical semi-mechanistic framework. For each state, we estimate the number of individuals that have been infected, the number of individuals that are currently infectious and the time-varying reproduction number (the average number of secondary infections caused by an infected person). We used changes in mobility to capture the impact that non-pharmaceutical interventions and other behaviour changes have on the rate of transmission of SARS-CoV-2. Nationally, we estimated 3.7% [3.4%-4.0%] of the population had been infected by 1st June 2020, with wide variation between states, and approximately 0.01% of the population was infectious. We also demonstrated that good model forecasts of deaths for the next 3 weeks with low error and good coverage of our credible intervals.

Preprint in English | medRxiv | ID: ppmedrxiv-20096701


1Brazil is currently reporting the second highest number of COVID-19 deaths in the world. Here we characterise the initial dynamics of COVID-19 across the country and assess the impact of non-pharmaceutical interventions (NPIs) that were implemented using a semi-mechanistic Bayesian hierarchical modelling approach. Our results highlight the significant impact these NPIs had across states, reducing an average Rt > 3 to an average of 1.5 by 9-May-2020, but that these interventions failed to reduce Rt < 1, congruent with the worsening epidemic Brazil has experienced since. We identify extensive heterogeneity in the epidemic trajectory across Brazil, with the estimated number of days to reach 0.1% of the state population infected since the first nationally recorded case ranging from 20 days in Sao Paulo compared to 60 days in Goias, underscoring the importance of sub-national analyses in understanding asynchronous state-level epidemics underlying the national spread and burden of COVID-19.

Preprint in English | medRxiv | ID: ppmedrxiv-20089359


Italy was the first European country to experience sustained local transmission of COVID-19. As of 1st May 2020, the Italian health authorities reported 28,238 deaths nationally. To control the epidemic, the Italian government implemented a suite of non-pharmaceutical interventions (NPIs), including school and university closures, social distancing and full lockdown involving banning of public gatherings and non essential movement. In this report, we model the effect of NPIs on transmission using data on average mobility. We estimate that the average reproduction number (a measure of transmission intensity) is currently below one for all Italian regions, and significantly so for the majority of the regions. Despite the large number of deaths, the proportion of population that has been infected by SARS-CoV-2 (the attack rate) is far from the herd immunity threshold in all Italian regions, with the highest attack rate observed in Lombardy (13.18% [10.66%-16.70%]). Italy is set to relax the currently implemented NPIs from 4th May 2020. Given the control achieved by NPIs, we consider three scenarios for the next 8 weeks: a scenario in which mobility remains the same as during the lockdown, a scenario in which mobility returns to pre-lockdown levels by 20%, and a scenario in which mobility returns to pre-lockdown levels by 40%. The scenarios explored assume that mobility is scaled evenly across all dimensions, that behaviour stays the same as before NPIs were implemented, that no pharmaceutical interventions are introduced, and it does not include transmission reduction from contact tracing, testing and the isolation of confirmed or suspected cases. New interventions, such as enhanced testing and contact tracing are going to be introduced and will likely contribute to reductions in transmission; therefore our estimates should be viewed as pessimistic projections. We find that, in the absence of additional interventions, even a 20% return to pre-lockdown mobility could lead to a resurgence in the number of deaths far greater than experienced in the current wave in several regions. Future increases in the number of deaths will lag behind the increase in transmission intensity and so a second wave will not be immediately apparent from just monitoring of the daily number of deaths. Our results suggest that SARS-CoV-2 transmission as well as mobility should be closely monitored in the next weeks and months. To compensate for the increase in mobility that will occur due to the relaxation of the currently implemented NPIs, adherence to the recommended social distancing measures alongside enhanced community surveillance including swab testing, contact tracing and the early isolation of infections are of paramount importance to reduce the risk of resurgence in transmission. SUGGESTED CITATIONMichaela A. C. Vollmer, Swapnil Mishra, H Juliette T Unwin, Axel Gandy et al. Using mobility to estimate the transmission intensity of COVID-19 in Italy: a subnational analysis with future scenarios. Imperial College London (2020) doi: This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Preprint in English | medRxiv | ID: ppmedrxiv-20033357


BackgroundA range of case fatality ratio (CFR) estimates for COVID-19 have been produced that differ substantially in magnitude. MethodsWe 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 line-list 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. FindingsWe 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 / 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. InterpretationThese early estimates give an indication of the fatality ratio across the spectrum of COVID-19 disease and demonstrate a strong age-gradient in risk.