The UK and Sweden have among the worst per-capita COVID-19 mortality in Europe. Sweden stands out for its greater reliance on voluntary, rather than mandatory, control measures. We explore how the ...timing and effectiveness of control measures in the UK, Sweden and Denmark shaped COVID-19 mortality in each country, using a counterfactual assessment: what would the impact have been, had each country adopted the others' policies? Using a Bayesian semi-mechanistic model without prior assumptions on the mechanism or effectiveness of interventions, we estimate the time-varying reproduction number for the UK, Sweden and Denmark from daily mortality data. We use two approaches to evaluate counterfactuals which transpose the transmission profile from one country onto another, in each country's first wave from 13th March (when stringent interventions began) until 1st July 2020. UK mortality would have approximately doubled had Swedish policy been adopted, while Swedish mortality would have more than halved had Sweden adopted UK or Danish strategies. Danish policies were most effective, although differences between the UK and Denmark were significant for one counterfactual approach only. Our analysis shows that small changes in the timing or effectiveness of interventions have disproportionately large effects on total mortality within a rapidly growing epidemic.
Following the detection of the new coronavirus
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its spread outside of China, Europe has experienced large epidemics of coronavirus ...disease 2019 (COVID-19). In response, many European countries have implemented non-pharmaceutical interventions, such as the closure of schools and national lockdowns. Here we study the effect of major interventions across 11 European countries for the period from the start of the COVID-19 epidemics in February 2020 until 4 May 2020, when lockdowns started to be lifted. Our model calculates backwards from observed deaths to estimate transmission that occurred several weeks previously, allowing for the time lag between infection and death. We use partial pooling of information between countries, with both individual and shared effects on the time-varying reproduction number (R
). Pooling allows for more information to be used, helps to overcome idiosyncrasies in the data and enables more-timely estimates. Our model relies on fixed estimates of some epidemiological parameters (such as the infection fatality rate), does not include importation or subnational variation and assumes that changes in R
are an immediate response to interventions rather than gradual changes in behaviour. Amidst the ongoing pandemic, we rely on death data that are incomplete, show systematic biases in reporting and are subject to future consolidation. We estimate that-for all of the countries we consider here-current interventions have been sufficient to drive R
below 1 (probability R
< 1.0 is greater than 99%) and achieve control of the epidemic. We estimate that across all 11 countries combined, between 12 and 15 million individuals were infected with SARS-CoV-2 up to 4 May 2020, representing between 3.2% and 4.0% of the population. Our results show that major non-pharmaceutical interventions-and lockdowns in particular-have had a large effect on reducing transmission. Continued intervention should be considered to keep transmission of SARS-CoV-2 under control.
On 21 February 2020, a resident of the municipality of Vo', a small town near Padua (Italy), died of pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection
. This was ...the first coronavirus disease 19 (COVID-19)-related death detected in Italy since the detection of SARS-CoV-2 in the Chinese city of Wuhan, Hubei province
. In response, the regional authorities imposed the lockdown of the whole municipality for 14 days
. Here we collected information on the demography, clinical presentation, hospitalization, contact network and the presence of SARS-CoV-2 infection in nasopharyngeal swabs for 85.9% and 71.5% of the population of Vo' at two consecutive time points. From the first survey, which was conducted around the time the town lockdown started, we found a prevalence of infection of 2.6% (95% confidence interval (CI): 2.1-3.3%). From the second survey, which was conducted at the end of the lockdown, we found a prevalence of 1.2% (95% CI: 0.8-1.8%). Notably, 42.5% (95% CI: 31.5-54.6%) of the confirmed SARS-CoV-2 infections detected across the two surveys were asymptomatic (that is, did not have symptoms at the time of swab testing and did not develop symptoms afterwards). The mean serial interval was 7.2 days (95% CI: 5.9-9.6). We found no statistically significant difference in the viral load of symptomatic versus asymptomatic infections (P = 0.62 and 0.74 for E and RdRp genes, respectively, exact Wilcoxon-Mann-Whitney test). This study sheds light on the frequency of asymptomatic SARS-CoV-2 infection, their infectivity (as measured by the viral load) and provides insights into its transmission dynamics and the efficacy of the implemented control measures.
In response to the COVID-19 pandemic, countries have sought to control SARS-CoV-2 transmission by restricting population movement through social distancing interventions, thus reducing the number of ...contacts. Mobility data represent an important proxy measure of social distancing, and here, we characterise the relationship between transmission and mobility for 52 countries around the world. Transmission significantly decreased with the initial reduction in mobility in 73% of the countries analysed, but we found evidence of decoupling of transmission and mobility following the relaxation of strict control measures for 80% of countries. For the majority of countries, mobility explained a substantial proportion of the variation in transmissibility (median adjusted R-squared: 48%, interquartile range - IQR - across countries 27-77%). Where a change in the relationship occurred, predictive ability decreased after the relaxation; from a median adjusted R-squared of 74% (IQR across countries 49-91%) pre-relaxation, to a median adjusted R-squared of 30% (IQR across countries 12-48%) post-relaxation. In countries with a clear relationship between mobility and transmission both before and after strict control measures were relaxed, mobility was associated with lower transmission rates after control measures were relaxed indicating that the beneficial effects of ongoing social distancing behaviours were substantial.
After initial declines, in mid-2020 a resurgence in transmission of novel coronavirus disease (COVID-19) occurred in the United States and Europe. As efforts to control COVID-19 disease are ...reintensified, understanding the age demographics driving transmission and how these affect the loosening of interventions is crucial. We analyze aggregated, age-specific mobility trends from more than 10 million individuals in the United States and link these mechanistically to age-specific COVID-19 mortality data. We estimate that as of October 2020, individuals aged 20 to 49 are the only age groups sustaining resurgent SARS-CoV-2 transmission with reproduction numbers well above one and that at least 65 of 100 COVID-19 infections originate from individuals aged 20 to 49 in the United States. Targeting interventions-including transmission-blocking vaccines-to adults aged 20 to 49 is an important consideration in halting resurgent epidemics and preventing COVID-19-attributable deaths.
WHO has called for increased testing in response to the COVID-19 pandemic, but countries have taken different approaches and the effectiveness of alternative strategies is unknown. We aimed to ...investigate the potential impact of different testing and isolation strategies on transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
We developed a mathematical model of SARS-CoV-2 transmission based on infectiousness and PCR test sensitivity over time since infection. We estimated the reduction in the effective reproduction number (R) achieved by testing and isolating symptomatic individuals, regular screening of high-risk groups irrespective of symptoms, and quarantine of contacts of laboratory-confirmed cases identified through test-and-trace protocols. The expected effectiveness of different testing strategies was defined as the percentage reduction in R. We reviewed data on the performance of antibody tests reported by the Foundation for Innovative New Diagnostics and examined their implications for the use of so-called immunity passports.
If all individuals with symptoms compatible with COVID-19 self-isolated and self-isolation was 100% effective in reducing onwards transmission, self-isolation of symptomatic individuals would result in a reduction in R of 47% (95% uncertainty interval UI 32–55). PCR testing to identify SARS-CoV-2 infection soon after symptom onset could reduce the number of individuals needing to self-isolate, but would also reduce the effectiveness of self-isolation (around 10% would be false negatives). Weekly screening of health-care workers and other high-risk groups irrespective of symptoms by use of PCR testing is estimated to reduce their contribution to SARS-CoV-2 transmission by 23% (95% UI 16–40), on top of reductions achieved by self-isolation following symptoms, assuming results are available at 24 h. The effectiveness of test and trace depends strongly on coverage and the timeliness of contact tracing, potentially reducing R by 26% (95% UI 14–35) on top of reductions achieved by self-isolation following symptoms, if 80% of cases and contacts are identified and there is immediate testing following symptom onset and quarantine of contacts within 24 h. Among currently available antibody tests, performance has been highly variable, with specificity around 90% or lower for rapid diagnostic tests and 95–99% for laboratory-based ELISA and chemiluminescent assays.
Molecular testing can play an important role in prevention of SARS-CoV-2 transmission, especially among health-care workers and other high-risk groups, but no single strategy will reduce R below 1 at current levels of population immunity. Immunity passports based on antibody tests or tests for infection face substantial technical, legal, and ethical challenges.
UK Medical Research Council.
COVID-19 has the potential to cause substantial disruptions to health services, due to cases overburdening the health system or response measures limiting usual programmatic activities. We aimed to ...quantify the extent to which disruptions to services for HIV, tuberculosis, and malaria in low-income and middle-income countries with high burdens of these diseases could lead to additional loss of life over the next 5 years.
Assuming a basic reproduction number of 3·0, we constructed four scenarios for possible responses to the COVID-19 pandemic: no action, mitigation for 6 months, suppression for 2 months, or suppression for 1 year. We used established transmission models of HIV, tuberculosis, and malaria to estimate the additional impact on health that could be caused in selected settings, either due to COVID-19 interventions limiting activities, or due to the high demand on the health system due to the COVID-19 pandemic.
In high-burden settings, deaths due to HIV, tuberculosis, and malaria over 5 years could increase by up to 10%, 20%, and 36%, respectively, compared with if there was no COVID-19 pandemic. The greatest impact on HIV was estimated to be from interruption to antiretroviral therapy, which could occur during a period of high health system demand. For tuberculosis, the greatest impact would be from reductions in timely diagnosis and treatment of new cases, which could result from any prolonged period of COVID-19 suppression interventions. The greatest impact on malaria burden could be as a result of interruption of planned net campaigns. These disruptions could lead to a loss of life-years over 5 years that is of the same order of magnitude as the direct impact from COVID-19 in places with a high burden of malaria and large HIV and tuberculosis epidemics.
Maintaining the most critical prevention activities and health-care services for HIV, tuberculosis, and malaria could substantially reduce the overall impact of the COVID-19 pandemic.
Bill & Melinda Gates Foundation, Wellcome Trust, UK Department for International Development, and Medical Research Council.
After experiencing a sharp growth in COVID-19 cases early in the pandemic, South Korea rapidly controlled transmission while implementing less stringent national social distancing measures than ...countries in Europe and the USA. This has led to substantial interest in their "test, trace, isolate" strategy. However, it is important to understand the epidemiological peculiarities of South Korea's outbreak and characterise their response before attempting to emulate these measures elsewhere.
We systematically extracted numbers of suspected cases tested, PCR-confirmed cases, deaths, isolated confirmed cases, and numbers of confirmed cases with an identified epidemiological link from publicly available data. We estimated the time-varying reproduction number, R
, using an established Bayesian framework, and reviewed the package of interventions implemented by South Korea using our extracted data, plus published literature and government sources.
We estimated that after the initial rapid growth in cases, R
dropped below one in early April before increasing to a maximum of 1.94 (95%CrI, 1.64-2.27) in May following outbreaks in Seoul Metropolitan Region. By mid-June, R
was back below one where it remained until the end of our study (July 13th). Despite less stringent "lockdown" measures, strong social distancing measures were implemented in high-incidence areas and studies measured a considerable national decrease in movement in late February. Testing the capacity was swiftly increased, and protocols were in place to isolate suspected and confirmed cases quickly; however, we could not estimate the delay to isolation using our data. Accounting for just 10% of cases, individual case-based contact tracing picked up a relatively minor proportion of total cases, with cluster investigations accounting for 66%.
Whilst early adoption of testing and contact tracing is likely to be important for South Korea's successful outbreak control, other factors including regional implementation of strong social distancing measures likely also contributed. The high volume of testing and the low number of deaths suggest that South Korea experienced a small epidemic relative to other countries. Caution is needed in attempting to replicate the South Korean response in populations with larger more geographically widespread epidemics where finding, testing, and isolating cases that are linked to clusters may be more difficult.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Many kernel methods are only suitable for small/medium sized spatial problems.•Random Fourier features speeds up kernel method with a minimal drop in accuracy.•This speedup lets us efficiently work ...with large spatial problems.•They can be added into many common spatial methods with only a few lines of code.
Kernel methods are a popular technique for extending linear models to handle non-linear spatial problems via a mapping to an implicit, high-dimensional feature space. While kernel methods are computationally cheaper than an explicit feature mapping, they are still subject to cubic cost on the number of points. Given only a few thousand locations, this computational cost rapidly outstrips the currently available computational power. This paper aims to provide an overview of kernel methods from first-principals (with a focus on ridge regression) and progress to a review of random Fourier features (RFF), a method that enables the scaling of kernel methods to big datasets. We show how the RFF method is capable of approximating the full kernel matrix, providing a significant computational speed-up for a negligible cost to accuracy and can be incorporated into many existing spatial methods using only a few lines of code. We give an example of the implementation of RFFs on a simulated spatial data set to illustrate these properties. Lastly, we summarise the main issues with RFFs and highlight some of the advanced techniques aimed at alleviating them. At each stage, the associated R code is provided.
As of 1st June 2020, the US Centres 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 model 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 use 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. We estimate that R
was only below one in 23 states on 1st June. We also estimate that 3.7% 3.4%-4.0% of the total population of the US had been infected, with wide variation between states, and approximately 0.01% of the population was infectious. We demonstrate good 3 week model forecasts of deaths with low error and good coverage of our credible intervals.