Quantitative Biology

OBJECTIVES: to describe the first wave of the COVID-19 pandemic with a focus on undetected cases and to evaluate different post-lockdown scenarios. DESIGN: the study introduces a SEIR compartmental model, taking into account the region-specific fraction of undetected cases, the effects of mobility restrictions, and the personal protective measures adopted, such as wearing a mask and washing hands frequently. SETTING AND PARTICIPANTS: the model is experimentally validated with data of all the Italian regions, some European countries, and the US. MAIN OUTCOME MEASURES: the accuracy of the model results is measured through the mean absolute percentage error (MAPE) and Lewis criteria; fitting parameters are in good agreement with previous literature. RESULTS: the epidemic curves for different countries and the amount of undetected and asymptomatic cases are estimated, which are likely to represent the main source of infections in the near future. The model is applied to the Hubei case study, which is the first place to relax mobility restrictions. Results show different possible scenarios. Mobility and the adoption of personal protective measures greatly influence the dynamics of the infection, determining either a huge and rapid secondary epidemic peak or a more delayed and manageable one. CONCLUSIONS: mathematical models can provide useful insights for healthcare decision makers to determine the best strategy in case of future outbreaks.

The Susceptible-Exposed-Infected-Recovered (SEIR) epidemiological model is one of the standard models of disease spreading. Here we analyse an extended SEIR model that accounts for asymptomatic carriers, believed to play an important role in COVID-19 transmission. For this model we derive a number of analytic results for important quantities such as the peak number of infections, the time taken to reach the peak and the size of the final affected population. We also propose an accurate way of specifying initial conditions for the numerics (from insufficient data) using the fact that the early time exponential growth is well-described by the dominant eigenvector of the linearized equations. Secondly we explore the effect of different intervention strategies such as social distancing (SD) and testing-quarantining (TQ). The two intervention strategies (SD and TQ) try to reduce the disease reproductive number, R 0 , to a target value R target 0 <1 , but in distinct ways, which we implement in our model equations. We find that for the same R target 0 <1 , TQ is more efficient in controlling the pandemic than SD. However, for TQ to be effective, it has to be based on contact tracing and our study quantifies the required ratio of tests-per-day to the number of new cases-per-day. Our analysis shows that the largest eigenvalue of the linearised dynamics provides a simple understanding of the disease progression, both pre- and post- intervention, and explains observed data for many countries. We apply our results to the COVID data for India to obtain heuristic projections for the course of the pandemic, and note that the predictions strongly depend on the assumed fraction of asymptomatic carriers.

We develop a novel hybrid epidemiological model and a specific methodology for its calibration to distinguish and assess the impact of mobility restrictions (given by Apple's mobility trends data) from other complementary non-pharmaceutical interventions (NPIs) used to control the spread of COVID-19. Using the calibrated model, we estimate that mobility restrictions contribute to 47 % (US States) and 47 % (worldwide) of the overall suppression of the disease transmission rate using data up to 13/08/2020. The forecast capacity of our model was evaluated doing four-weeks ahead predictions. Using data up to 30/06/20 for calibration, the mean absolute percentage error (MAPE) of the prediction of cumulative deceased individuals was 5.0 % for the United States (51 states) and 6.7 % worldwide (49 countries). This MAPE was reduced to 3.5% for the US and 3.8% worldwide using data up to 13/08/2020. We find that the MAPE was higher for the total confirmed cases at 11.5% worldwide and 10.2% for the US States using data up to 13/08/2020. Our calibrated model achieves an average R-Squared value for cumulative confirmed and deceased cases of 0.992 using data up to 30/06/20 and 0.98 using data up to 13/08/20.

Timely estimation of the current value for COVID-19 reproduction factor R has become a key aim of efforts to inform management strategies. R is an important metric used by policy-makers in setting mitigation levels and is also important for accurate modelling of epidemic progression. This brief paper introduces a method for estimating R from biased case testing data. Using testing data, rather than hospitalisation or death data, provides a much earlier metric along the symptomatic progression scale. This can be hugely important when fighting the exponential nature of an epidemic. We develop a practical estimator and apply it to Scottish case testing data to infer a current (20 May 2020) R value of 0.74 with 95% confidence interval [0.48−0.86] .

When the novel coronavirus disease SARS-CoV2 (COVID-19) was officially declared a pandemic by the WHO in March 2020, the scientific community had already braced up in the effort of making sense of the fast-growing wealth of data gathered by national authorities all over the world. However, despite the diversity of novel theoretical approaches and the comprehensiveness of many widely established models, the official figures that recount the course of the outbreak still sketch a largely elusive and intimidating picture. Here we show unambiguously that the dynamics of the COVID-19 outbreak belongs to the simple universality class of the SIR model and extensions thereof. Our analysis naturally leads us to establish that there exists a fundamental limitation to any theoretical approach, namely the unpredictable non-stationarity of the testing frames behind the reported figures. However, we show how such bias can be quantified self-consistently and employed to mine useful and accurate information from the data. In particular, we describe how the time evolution of the reporting rates controls the occurrence of the apparent epidemic peak, which typically follows the true one in countries that were not vigorous enough in their testing at the onset of the outbreak. The importance of testing early and resolutely appears as a natural corollary of our analysis, as countries that tested massively at the start clearly had their true peak earlier and less deaths overall.

Motivation: Early detection and isolation of COVID-19 patients are essential for successful implementation of mitigation strategies and eventually curbing the disease spread. With a limited number of daily COVID19 tests performed in every country, simulating the COVID-19 spread along with the potential effect of each mitigation strategy currently remains one of the most effective ways in managing the healthcare system and guiding policy-makers. We introduce COVIDHunter, a flexible and accurate COVID-19 outbreak simulation model that evaluates the current mitigation measures that are applied to a region and provides suggestions on what strength the upcoming mitigation measure should be. The key idea of COVIDHunter is to quantify the spread of COVID-19 in a geographical region by simulating the average number of new infections caused by an infected person considering the effect of external factors, such as environmental conditions (e.g., climate, temperature, humidity) and mitigation measures. Results: Using Switzerland as a case study, COVIDHunter estimates that the policy-makers need to keep the current mitigation measures for at least 30 days to prevent demand from quickly exceeding existing hospital capacity. Relaxing the mitigation measures by 50% for 30 days increases both the daily capacity need for hospital beds and daily number of deaths exponentially by an average of 23.8x, who may occupy ICU beds and ventilators for a period of time. Unlike existing models, the COVIDHunter model accurately monitors and predicts the daily number of cases, hospitalizations, and deaths due to COVID-19. Our model is flexible to configure and simple to modify for modeling different scenarios under different environmental conditions and mitigation measures. Availability: this https URL

The World Health Organisation (WHO) has very strongly recommended testing and isolation as a strategy for controlling the ongoing COVID-19 pandemic. The goal of this paper is to quantify the effects of detection and isolation in formal models of epidemics of varying complexity. A key parameter of such models is the basic reproduction ratio. We show that an effective detection and isolation strategy leads to a reduction of the basic reproduction ratio and can even lead to this ratio becoming lower than one.

The "New York State on Pause" executive order came into effect on March 22 with the goal of ensuring adequate social distancing to alleviate the spread of COVID-19. Pause will remain effective in New York City in some form until early June. We use a compartmentalized model to study the effects of testing capacity and social distancing measures on the evolution of the pandemic in the "post-Pause" period in the City. We find that testing capacity must increase dramatically if it is to counterbalance even relatively small relaxations in social distancing measures in the immediate post-Pause period. In particular, if the City performs 20,000 tests per day and relaxes the social distancing measures to the pre-Pause norms, then the total number of deaths by the end of September can reach 250,000. By keeping the social distancing measures to somewhere halfway between the pre- and in-Pause norms and performing 100,000 tests per day, the total number of deaths by the end of September can be kept at around 27,000. Going back to the pre-Pause social distancing norms quickly must be accompanied by an exorbitant testing capacity, if one is to suppress excessive deaths. If the City is to go back to the "pre-Pause" social distancing norms in the immediate post-Pause period and keep the total number of deaths by the end of September at around 35,000, then it should be performing 500,000 tests per day. Our findings have important implications on the magnitude of the testing capacity the City needs as it relaxes the social distancing measures to reopen its economy.

Aims: Nonpharmaceutical interventions against the spread of SARS-CoV-2 in Germany included the cancellation of mass events (from March 8), closures of schools and child day care facilities (from March 16) as well as a "lockdown" (from March 23). This study attempts to assess the effectiveness of these interventions in terms of revealing their impact on infections over time. Methods: Dates of infections were estimated from official German case data by incorporating the incubation period and an empirical reporting delay. Exponential growth models for infections and reproduction numbers were estimated and investigated with respect to change points in the time series. Results: A significant decline of daily and cumulative infections as well as reproduction numbers is found at March 8 (CI [7, 9]), March 10 (CI [9, 11] and March 3 (CI [2, 4]), respectively. Further declines and stabilizations are found in the end of March. There is also a change point in new infections at April 19 (CI [18, 20]), but daily infections still show a negative growth. From March 19 (CI [18, 20]), the reproduction numbers fluctuate on a level below one. Conclusions: The decline of infections in early March 2020 can be attributed to relatively small interventions and voluntary behavioural changes. Additional effects of later interventions cannot be detected clearly. Liberalizations of measures did not induce a re-increase of infections. Thus, the effectiveness of most German interventions remains questionable. Moreover, assessing of interventions is impeded by the estimation of true infection dates and the influence of test volume.

The novel Coronavirus (COVID-19) incidence in India is currently experiencing exponential rise but with apparent spatial variation in growth rate and doubling time rate. We classify the states into five clusters with low to the high-risk category and study how the different states moved from one cluster to the other since the onset of the first case on 30 th January 2020 till the end of unlock 1 that is 30 th June 2020. We have implemented a new clustering technique called the incrementalKMN (Prasad, R. K., Sarmah, R., Chakraborty, S.(2019))