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How deadly is an infection with SARS-CoV-2 worldwide over time? This information is critical for developing and assessing public health responses on the country and global levels. However, imperfect data have been the most limiting factor for estimating the COVID-19 infection fatality burden during the first year of the pandemic. Here we leverage recently emerged compelling data sources and broadly applicable modeling strategies to estimate the crude infection fatality rate (cIFR) in 77 countries from 28 March 2020 to 31 March 2021, using 2.4 million reported deaths and estimated 435 million infections by age, sex, country, and date. The global average of all cIFR estimates is 1.2% (10th to 90th percentile: 0.2% to 2.4%). The cIFR varies strongly across countries, but little within countries over time, and it is often lower for women than men. Cross-country differences in cIFR are largely driven by the age structures of both the general and the truly infected population. While the broad trends and patterns of the cIFR estimates are more robust, we show that their levels are uncertain and sensitive to input data and modeling choices. In consequence, increased efforts at collecting high-quality data are essential for accurately estimating the cIFR, which is a key indicator for better understanding the health and mortality consequences of this pandemic.
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BackgroundThe COVID-19 pandemic poses the risk of overburdening health care systems, and in particular intensive care units (ICUs). Non-pharmaceutical interventions (NPIs), ranging from wearing masks to (partial) lockdowns have been implemented as mitigation measures around the globe. However, especially severe NPIs are used with great caution due to their negative effects on the economy, social life and mental well-being. Thus, understanding the impact of the pandemic on ICU demand under alternative scenarios reflecting different levels of NPIs is vital for political decision-making on NPIs. ObjectiveThe aim is to support political decision-making by forecasting COVID-19-related ICU demand under alternative scenarios of COVID-19 progression reflecting different levels of NPIs. Substantial sub-national variation in COVID-19-related ICU demand requires a spatially disaggregated approach. This should not only take sub-national variation in ICU-relevant disease dynamics into account, but also variation in the population at risk including COVID-19-relevant risk characteristics (e.g. age), and factors mitigating the pandemic. The forecast provides indications for policy makers and health care stakeholders as to whether mitigation measures have to be maintained or even strengthened to prevent ICU demand from exceeding supply, or whether there is leeway to relax them. MethodsWe implement a spatial age-structured microsimulation model of the COVID-19 pandemic by extending the Susceptible-Exposed-Infectious-Recovered (SEIR) framework. The model accounts for regional variation in population age structure and in spatial diffusion pathways. In a first step, we calibrate the model by applying a genetic optimization algorithm against hospital data on ICU patients with COVID-19. In a second step, we forecast COVID-19-related ICU demand under alternative scenarios of COVID 19 progression reflecting different levels of NPIs. We apply the model to Germany and provide state-level forecasts over a 2-month period, which can be updated daily based on latest data on the progression of the pandemic. ResultsTo illustrate the merits of our model, we present here "forecasts" of ICU demand for different stages of the pandemic during 2020. Our forecasts for a quiet summer phase with low infection rates identified quite some variation in potential for relaxing NPIs across the federal states. By contrast, our forecasts during a phase of quickly rising infection numbers in autumn (second wave) suggested that all federal states should implement additional NPIs. However, the identified needs for additional NPIs varied again across federal states. In addition, our model suggests that during large infection waves ICU demand would quickly exceed supply, if there were no NPIs in place to contain the virus. ConclusionOur results provide evidence for substantial spatial variation in (1) the effect of the pandemic on ICU demand, and (2) the potential and need for NPI adjustments at different stages of the pandemic. Forecasts with our spatial age-structured microsimulation model allow to take this spatial variation into account. The model is programmed in R and can be applied to other countries, provided that reliable data on the number of ICU patients infected with COVID-19 are available at sub-national level.
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COVerAGE-DB is an open-access database including cumulative counts of confirmed COVID-19 cases, deaths, and tests by age and sex. The main goal of COVerAGE-DB is to provide a centralized, standardized, age-harmonized, and fully reproducible database of COVID-19 data. Original data and sources are provided alongside data and measures in age-harmonized formats. An international team, composed of more than 60 researchers, contributed to the collection of data and metadata in COVerAGE-DB from governmental institutions, as well as to the design and implementation of the data processing and validation pipeline. The database is still in development, and at this writing, it includes 89 countries, and 237 subnational areas. Cumulative counts of COVID-19 cases, deaths, and tests are recorded daily (when possible) since January 2020. Many time series thus fully capture the first pandemic wave and the beginning of later waves. Since collection efforts began for COVerAGE-DB several studies have used the data.
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Understanding how widely COVID-19 has spread is critical for examining the pandemics progression. Despite efforts to carefully monitor the pandemic, the number of confirmed cases may underestimate the total number of infections. We introduce a demographic scaling model to estimate COVID-19 infections using an broadly applicable approach that is based on minimal data requirements: COVID-19 related deaths, infection fatality rates (IFRs), and life tables. As many countries lack reliable estimates of age-specific IFRs, we scale IFRs between countries using remaining life expectancy as a marker to account for differences in age structures, health conditions, and medical services. Across 10 countries with most COVID-19 deaths as of May 13, 2020, the number of infections is estimated to be four [95% prediction interval: 2-11] times higher than the number of confirmed cases. Cross-country variation is high. The estimated number of infections is 1.4 million (six times the number of confirmed cases) for Italy; 3.1 million (2.2 times the number of confirmed cases) for the U.S.; and 1.8 times the number of confirmed cases for Germany, where testing has been comparatively extensive. Our prevalence estimates, however, are markedly lower than most others based on local seroprevalence studies. We introduce formulas for quantifying the bias that is required in our data on deaths in order to reproduce estimates published elsewhere. This bias analysis shows that either COVID-19 deaths are severely underestimated, by a factor of two or more; or alternatively, the seroprevalence based results are overestimates and not representative for the total population.
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The population-level case-fatality rate (CFR) associated with COVID-19 varies substantially, both across countries time and within countries over time. We analyze the contribution of two key determinants of the variation in the observed CFR: the age-structure of diagnosed infection cases and age-specific case-fatality rates. We use data on diagnosed COVID-19 cases and death counts attributable to COVID-19 by age for China, Germany, Italy, South Korea, Spain, the United States, and New York City. We calculate the CFR for each population at the latest data point and also for Italy over time. We use demographic decomposition to break the difference between CFRs into unique contributions arising from the age-structure of confirmed cases and the age-specific case-fatality. In late April 2020, CFRs varied from 2.2% in South Korea to 13.0% in Italy. The age-structure of detected cases often explains more than two thirds of cross-country variation in the CFR. In Italy, the CFR increased from 4.2% to 13.0% between March 9 and April 22, 2020, and more than 90% of the change was due to increasing age-specific case-fatality rates. The importance of the age-structure of confirmed cases likely reflects several factors, including different testing regimes and differences in transmission trajectories; while increasing age-specific case-fatality rates in Italy could indicate other factors, such as the worsening health outcomes of those infected with COVID-19. Our findings lend support to recommendations for data to be disaggregated by age, and potentially other variables, to facilitate a better understanding of population-level differences in CFRs. They also show the need for well designed seroprevalence studies to ascertain the extent to which differences in testing regimes drive differences in the age-structure of detected cases.
