A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, VOC 202012/01 (lineage B.1.1.7), emerged in southeast England in September 2020 and is rapidly spreading toward fixation. Using ...a variety of statistical and dynamic modeling approaches, we estimate that this variant has a 43 to 90% (range of 95% credible intervals, 38 to 130%) higher reproduction number than preexisting variants. A fitted two-strain dynamic transmission model shows that VOC 202012/01 will lead to large resurgences of COVID-19 cases. Without stringent control measures, including limited closure of educational institutions and a greatly accelerated vaccine rollout, COVID-19 hospitalizations and deaths across England in the first 6 months of 2021 were projected to exceed those in 2020. VOC 202012/01 has spread globally and exhibits a similar transmission increase (59 to 74%) in Denmark, Switzerland, and the United States.
Adjusting for delay from confirmation to death, we estimated case and infection fatality ratios (CFR, IFR) for coronavirus disease (COVID-19) on the Diamond Princess ship as 2.6% (95% confidence ...interval (CI): 0.89-6.7) and 1.3% (95% CI: 0.38-3.6), respectively. Comparing deaths on board with expected deaths based on naive CFR estimates from China, we estimated CFR and IFR in China to be 1.2% (95% CI: 0.3-2.7) and 0.6% (95% CI: 0.2-1.3), respectively.
The time-varying effective reproduction number Rt is a widely used indicator of transmission dynamics during infectious disease outbreaks. Timely estimates of Rt can be obtained from reported cases ...counted by their date of symptom onset, which is generally closer to the time of infection than the date of report. Case counts by date of symptom onset are typically obtained from line list data, however these data can have missing information and are subject to right truncation. Previous methods have addressed these problems independently by first imputing missing onset dates, then adjusting truncated case counts, and finally estimating the effective reproduction number. This stepwise approach makes it difficult to propagate uncertainty and can introduce subtle biases during real-time estimation due to the continued impact of assumptions made in previous steps. In this work, we integrate imputation, truncation adjustment, and Rt estimation into a single generative Bayesian model, allowing direct joint inference of case counts and Rt from line list data with missing symptom onset dates. We then use this framework to compare the performance of nowcasting approaches with different stepwise and generative components on synthetic line list data for multiple outbreak scenarios and across different epidemic phases. We find that under reporting delays realistic for hospitalization data (50% of reports delayed by more than a week), intermediate smoothing, as is common practice in stepwise approaches, can bias nowcasts of case counts and Rt, which is avoided in a joint generative approach due to shared regularization of all model components. On incomplete line list data, a fully generative approach enables the quantification of uncertainty due to missing onset dates without the need for an initial multiple imputation step. In a real-world comparison using hospitalization line list data from the COVID-19 pandemic in Switzerland, we observe the same qualitative differences between approaches. The generative modeling components developed in this work have been integrated and further extended in the R package epinowcast, providing a flexible and interpretable tool for real-time surveillance.
Isolation of cases and contact tracing is used to control outbreaks of infectious diseases, and has been used for coronavirus disease 2019 (COVID-19). Whether this strategy will achieve control ...depends on characteristics of both the pathogen and the response. Here we use a mathematical model to assess if isolation and contact tracing are able to control onwards transmission from imported cases of COVID-19.
We developed a stochastic transmission model, parameterised to the COVID-19 outbreak. We used the model to quantify the potential effectiveness of contact tracing and isolation of cases at controlling a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-like pathogen. We considered scenarios that varied in the number of initial cases, the basic reproduction number (R0), the delay from symptom onset to isolation, the probability that contacts were traced, the proportion of transmission that occurred before symptom onset, and the proportion of subclinical infections. We assumed isolation prevented all further transmission in the model. Outbreaks were deemed controlled if transmission ended within 12 weeks or before 5000 cases in total. We measured the success of controlling outbreaks using isolation and contact tracing, and quantified the weekly maximum number of cases traced to measure feasibility of public health effort.
Simulated outbreaks starting with five initial cases, an R0 of 1·5, and 0% transmission before symptom onset could be controlled even with low contact tracing probability; however, the probability of controlling an outbreak decreased with the number of initial cases, when R0 was 2·5 or 3·5 and with more transmission before symptom onset. Across different initial numbers of cases, the majority of scenarios with an R0 of 1·5 were controllable with less than 50% of contacts successfully traced. To control the majority of outbreaks, for R0 of 2·5 more than 70% of contacts had to be traced, and for an R0 of 3·5 more than 90% of contacts had to be traced. The delay between symptom onset and isolation had the largest role in determining whether an outbreak was controllable when R0 was 1·5. For R0 values of 2·5 or 3·5, if there were 40 initial cases, contact tracing and isolation were only potentially feasible when less than 1% of transmission occurred before symptom onset.
In most scenarios, highly effective contact tracing and case isolation is enough to control a new outbreak of COVID-19 within 3 months. The probability of control decreases with long delays from symptom onset to isolation, fewer cases ascertained by contact tracing, and increasing transmission before symptoms. This model can be modified to reflect updated transmission characteristics and more specific definitions of outbreak control to assess the potential success of local response efforts.
Wellcome Trust, Global Challenges Research Fund, and Health Data Research UK.
Estimation of the effective reproductive number Rt is important for detecting changes in disease transmission over time. During the Coronavirus Disease 2019 (COVID-19) pandemic, policy makers and ...public health officials are using Rt to assess the effectiveness of interventions and to inform policy. However, estimation of Rt from available data presents several challenges, with critical implications for the interpretation of the course of the pandemic. The purpose of this document is to summarize these challenges, illustrate them with examples from synthetic data, and, where possible, make recommendations. For near real-time estimation of Rt, we recommend the approach of Cori and colleagues, which uses data from before time t and empirical estimates of the distribution of time between infections. Methods that require data from after time t, such as Wallinga and Teunis, are conceptually and methodologically less suited for near real-time estimation, but may be appropriate for retrospective analyses of how individuals infected at different time points contributed to the spread. We advise caution when using methods derived from the approach of Bettencourt and Ribeiro, as the resulting Rt estimates may be biased if the underlying structural assumptions are not met. Two key challenges common to all approaches are accurate specification of the generation interval and reconstruction of the time series of new infections from observations occurring long after the moment of transmission. Naive approaches for dealing with observation delays, such as subtracting delays sampled from a distribution, can introduce bias. We provide suggestions for how to mitigate this and other technical challenges and highlight open problems in Rt estimation.
Background:
A novel coronavirus disease (COVID-19) outbreak has now spread to a number of countries worldwide. While sustained transmission chains of human-to-human transmission suggest high basic ...reproduction number
R
0
, variation in the number of secondary transmissions (often characterised by so-called superspreading events) may be large as some countries have observed fewer local transmissions than others.
Methods:
We quantified individual-level variation in COVID-19 transmission by applying a mathematical model to observed outbreak sizes in affected countries. We extracted the number of imported and local cases in the affected countries from the World Health Organization situation report and applied a branching process model where the number of secondary transmissions was assumed to follow a negative-binomial distribution.
Results:
Our model suggested a high degree of individual-level variation in the transmission of COVID-19. Within the current consensus range of
R
0
(2-3), the overdispersion parameter
k
of a negative-binomial distribution was estimated to be around 0.1 (median estimate 0.1; 95% CrI: 0.05-0.2 for R0 = 2.5), suggesting that 80% of secondary transmissions may have been caused by a small fraction of infectious individuals (~10%). A joint estimation yielded likely ranges for
R
0
and
k
(95% CrIs:
R
0
1.4-12;
k
0.04-0.2); however, the upper bound of
R
0
was not well informed by the model and data, which did not notably differ from that of the prior distribution.
Conclusions:
Our finding of a highly-overdispersed offspring distribution highlights a potential benefit to focusing intervention efforts on superspreading. As most infected individuals do not contribute to the expansion of an epidemic, the effective reproduction number could be drastically reduced by preventing relatively rare superspreading events.
Mathematical and statistical models can be used to make predictions of how epidemics may progress in the near future and form a central part of outbreak mitigation and control. Renewal equation based ...models allow inference of epidemiological parameters from historical data and forecast future epidemic dynamics without requiring complex mechanistic assumptions. However, these models typically ignore interaction between age groups, partly due to challenges in parameterising a time varying interaction matrix. Social contact data collected regularly during the COVID-19 epidemic provide a means to inform interaction between age groups in real-time. We developed an age-specific forecasting framework and applied it to two age-stratified time-series: incidence of SARS-CoV-2 infection, estimated from a national infection and antibody prevalence survey; and, reported cases according to the UK national COVID-19 dashboard. Jointly fitting our model to social contact data from the CoMix study, we inferred a time-varying next generation matrix which we used to project infections and cases in the four weeks following each of 29 forecast dates between October 2020 and November 2021. We evaluated the forecasts using proper scoring rules and compared performance with three other models with alternative data and specifications alongside two naive baseline models. Overall, incorporating age interaction improved forecasts of infections and the CoMix-data-informed model was the best performing model at time horizons between two and four weeks. However, this was not true when forecasting cases. We found that age group interaction was most important for predicting cases in children and older adults. The contact-data-informed models performed best during the winter months of 2020–2021, but performed comparatively poorly in other periods. We highlight challenges regarding the incorporation of contact data in forecasting and offer proposals as to how to extend and adapt our approach, which may lead to more successful forecasts in future.
Background:
A novel coronavirus disease (COVID-19) outbreak has now spread to a number of countries worldwide. While sustained transmission chains of human-to-human transmission suggest high basic ...reproduction number
R
0
, variation in the number of secondary transmissions (often characterised by so-called superspreading events) may be large as some countries have observed fewer local transmissions than others.
Methods:
We quantified individual-level variation in COVID-19 transmission by applying a mathematical model to observed outbreak sizes in affected countries. We extracted the number of imported and local cases in the affected countries from the World Health Organization situation report and applied a branching process model where the number of secondary transmissions was assumed to follow a negative-binomial distribution.
Results:
Our model suggested a high degree of individual-level variation in the transmission of COVID-19. Within the current consensus range of
R
0
(2-3), the overdispersion parameter
k
of a negative-binomial distribution was estimated to be around 0.1 (median estimate 0.1; 95% CrI: 0.05-0.2 for R0 = 2.5), suggesting that 80% of secondary transmissions may have been caused by a small fraction of infectious individuals (~10%). A joint estimation yielded likely ranges for
R
0
and
k
(95% CrIs:
R
0
1.4-12;
k
0.04-0.2); however, the upper bound of
R
0
was not well informed by the model and data, which did not notably differ from that of the prior distribution.
Conclusions:
Our finding of a highly-overdispersed offspring distribution highlights a potential benefit to focusing intervention efforts on superspreading. As most infected individuals do not contribute to the expansion of an epidemic, the effective reproduction number could be drastically reduced by preventing relatively rare superspreading events.
The distribution of the generation time (the interval between individuals becoming infected and transmitting the virus) characterises changes in the transmission risk during SARS-CoV-2 infections. ...Inferring the generation time distribution is essential to plan and assess public health measures. We previously developed a mechanistic approach for estimating the generation time, which provided an improved fit to data from the early months of the COVID-19 pandemic (December 2019-March 2020) compared to existing models (Hart et al., 2021). However, few estimates of the generation time exist based on data from later in the pandemic. Here, using data from a household study conducted from March to November 2020 in the UK, we provide updated estimates of the generation time. We considered both a commonly used approach in which the transmission risk is assumed to be independent of when symptoms develop, and our mechanistic model in which transmission and symptoms are linked explicitly. Assuming independent transmission and symptoms, we estimated a mean generation time (4.2 days, 95% credible interval 3.3-5.3 days) similar to previous estimates from other countries, but with a higher standard deviation (4.9 days, 3.0-8.3 days). Using our mechanistic approach, we estimated a longer mean generation time (5.9 days, 5.2-7.0 days) and a similar standard deviation (4.8 days, 4.0-6.3 days). As well as estimating the generation time using data from the entire study period, we also considered whether the generation time varied temporally. Both models suggest a shorter mean generation time in September-November 2020 compared to earlier months. Since the SARS-CoV-2 generation time appears to be changing, further data collection and analysis is necessary to continue to monitor ongoing transmission and inform future public health policy decisions.
: The current novel coronavirus outbreak appears to have originated from a point-source exposure event at Huanan seafood wholesale market in Wuhan, China. There is still uncertainty around the scale ...and duration of this exposure event. This has implications for the estimated transmissibility of the coronavirus and as such, these potential scenarios should be explored.
: We used a stochastic branching process model, parameterised with available data where possible and otherwise informed by the 2002-2003 Severe Acute Respiratory Syndrome (SARS) outbreak, to simulate the Wuhan outbreak. We evaluated scenarios for the following parameters: the size, and duration of the initial transmission event, the serial interval, and the reproduction number (R0). We restricted model simulations based on the number of observed cases on the 25th of January, accepting samples that were within a 5% interval on either side of this estimate.
: Using a pre-intervention SARS-like serial interval suggested a larger initial transmission event and a higher R0 estimate. Using a SARs-like serial interval we found that the most likely scenario produced an R0 estimate between 2-2.7 (90% credible interval (CrI)). A pre-intervention SARS-like serial interval resulted in an R0 estimate between 2-3 (90% CrI). There were other plausible scenarios with smaller events sizes and longer duration that had comparable R0 estimates. There were very few simulations that were able to reproduce the observed data when R0 was less than 1.
: Our results indicate that an R0 of less than 1 was highly unlikely unless the size of the initial exposure event was much greater than currently reported. We found that R0 estimates were comparable across scenarios with decreasing event size and increasing duration. Scenarios with a pre-intervention SARS-like serial interval resulted in a higher R0 and were equally plausible to scenarios with SARs-like serial intervals.
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