Quantitative Biology

Bayesian analysis of publicly available time series of cases and fatalities in different geographical regions of India during April 2020 is reported. It is found that the initial apparent rapid growthin infections could be partly due to confounding factors such as initial rapid ramp-up of disease surveillance. A brief discussion is given of the fallacies which arise if this possibility is neglected. The growth after April 10 is consistent with a time independent but region dependent exponential. From this, R0 is extracted using both known cases and fatalities. The two estimates are seen to agree in many cases; for these CFR is reported. It is seen that CFR and R0 increase together. Some public health implications of this observation are discussed, including a target doubling interval if medical facilities are to remain adequate.

Battling a widespread pandemic is an arms race between our mitigation efforts, e.g., social distancing or vaccination, and the pathogen's evolving persistence. This is being observed firsthand during the current COVID-19 crisis, as novel mutations challenge our global vaccination race. To address this, we introduce here a general framework to model epidemic spreading under pathogen evolution, finding that mutations can fundamentally alter the projection of the spread. Specifically, we detect a new pandemic phase - the mutated phase - in which, despite the fact that the pathogen is initially non-pandemic (R0 < 1), it may still spread due to the emergence of a critical mutation. The boundaries of this phase portray a balance between the epidemic and the evolutionary time-scales. If the mutation rate is too low, the pathogen prevalence decays prior to the appearance of a critical mutation. On the other hand, if mutations are too rapid, the pathogen evolution becomes volatile and, once again, it fails to spread. Between these two extremes, however, we observe a broad range of conditions in which an initially sub-pandemic pathogen will eventually gain prevalence. This is especially relevant during vaccination, which creates, as it progresses, increasing selection pressure towards vaccine-resistance. To overcome this, we show that vaccination campaigns must be accompanied by fierce mitigation efforts, to suppress the potential rise of a resistant mutant strain.

To better predict the dynamics of spread of COVID-19 epidemics, it is important not only to investigate the network of local and long-range contagious contacts, but also to understand the temporal dynamics of infectiousness and detectable symptoms. Here we present a model of infection spread in a well-mixed group of individuals, which usually corresponds to a node in large-scale epidemiological networks. The model uses delay equations that take into account the duration of infection and is based on experimentally-derived time courses of viral load, virus shedding, severity and detectability of symptoms. We show that because of an early onset of infectiousness, which is reported to be synchronous or even precede the onset of detectable symptoms, the tracing and immediate testing of everyone who came in contact with the detected infected individual reduces the spread of epidemics, hospital load, and fatality rate. We hope that this more precise node dynamics could be incorporated into complex large-scale epidemiological models to improve the accuracy and credibility of predictions.

Mass public quarantining, colloquially known as a lock-down, is a non-pharmaceutical intervention to check spread of disease. This paper presents ESOP (Epidemiologically and Socio-economically Optimal Policies), a novel application of active machine learning techniques using Bayesian optimization, that interacts with an epidemiological model to arrive at lock-down schedules that optimally balance public health benefits and socio-economic downsides of reduced economic activity during lock-down periods. The utility of ESOP is demonstrated using case studies with VIPER (Virus-Individual-Policy-EnviRonment), a stochastic agent-based simulator that this paper also proposes. However, ESOP is flexible enough to interact with arbitrary epidemiological simulators in a black-box manner, and produce schedules that involve multiple phases of lock-downs.

Cyclic dominance offers not just a way to maintain biodiversity, but also serves as a sort of defensive alliance against an external invader. Interestingly, a new level of competition can be observed when two cyclic loops are present. Here the inner invasion speed plays a decisive role on the evolutionary outcome, because faster invasion rate provides an evolutionary advantage to an alliance. In this Letter we demonstrate that the heterogeneity of inner invasion rates makes an alliance vulnerable against a loop where group members are equal. Quite surprisingly, a loop where invasion rates are uniform can still dominate an alliance formed by heteregeneous rates even if the average speed of invasion is significantly higher in the latter group. At a specific range of parameter space, when intergroup invasion or the average inner invasion is moderate, the heterogeneous alliance with higher internal invasion speed may prevail, or the system terminates onto a novel 4- or 5-species solution.

Movement tracks of wild animals frequently fit models of anomalous rather than simple diffusion, mostly reported as ergodic superdiffusive motion combining area-restricted search within a local patch and larger-scale commuting between patches, as highlighted by the Lévy walk paradigm. Since Lévy walks are scale invariant, superdiffusive motion is also expected within patches, yet investigation of such local movements has been precluded by the lack of accurate high-resolution data at this scale. Here, using rich high-resolution movement datasets ( >7? 10 7 localizations) from 70 individuals and continuous-time random walk modeling, we found subdiffusive behavior and ergodicity breaking in the localized movement of three species of avian predators. Small-scale, within-patch movement was qualitatively different, not inferrable and separated from large-scale inter-patch movement via a clear phase transition. Local search is characterized by long power-law-distributed waiting times with diverging mean, giving rise to ergodicity breaking in the form of considerable variability uniquely observed at this scale. This implies that wild animal movement is scale specific rather than scale free, with no typical waiting time at the local scale. Placing these findings in the context of the static-ambush to mobile-cruise foraging continuum, we verify predictions based on the hunting behavior of the study species and the constraints imposed by their prey.

In this paper a Bayesian SEIR model is studied to estimate the proportion of the population infected with SARS-CoV-2, the virus responsible for COVID-19. To capture heterogeneity in the population and the effect of interventions to reduce the rate of epidemic spread, the model uses a time-varying contact rate, whose logarithm has a Gaussian process prior. A Poisson point process is used to model the occurrence of deaths due to COVID-19 and the model is calibrated using data of daily death counts in combination with a snapshot of the the proportion of individuals with an active infection, performed in Stockholm in late March. The methodology is applied to regions in Sweden. The results show that the estimated proportion of the population who has been infected is around 13.5% in Stockholm, by 2020-05-15, and ranges between 2.5% - 15.6% in the other investigated regions. In Stockholm where the peak of daily death counts is likely behind us, parameter uncertainty does not heavily influence the expected daily number of deaths, nor the expected cumulative number of deaths. It does, however, impact the estimated cumulative number of infected individuals. In the other regions, where random sampling of the number of active infections is not available, parameter sharing is used to improve estimates, but the parameter uncertainty remains substantial.

A quantitative COVID-19 model that incorporates hidden asymptomatic patients is developed, and an analytic solution in parametric form is given. The model incorporates the impact of lockdown and resulting spatial migration of population due to announcement of lockdown. A method is presented for estimating the model parameters from real-world data. It is shown that increase of infections slows down and herd immunity is achieved when symptomatic patients are 4-6\% of the population for the European countries we studied, when the total infected fraction is between 50-56 \%. Finally, a method for estimating the number of asymptomatic patients, who have been the key hidden link in the spread of the infections, is presented.

The COVID-19 pandemic has caused major disturbance to human life. An important reason behind the widespread social anxiety is the huge uncertainty about the pandemic. A fundamental uncertainty is how many or what percentage of people have been infected. There are published and frequently updated data on various statistics of the pandemic, at local, country or global level. However, due to various reasons, many cases were not included in those reported numbers. We propose a structured approach for the estimation of the number of unreported cases, where we distinguish cases that arrive late in the reported numbers and those who had mild or no symptoms and thus were not captured by any medical system at all. We use post-report data for the estimation of the former and population matching to the latter. We estimate that the reported number of infected cases in the US should be corrected by multiplying a factor of 220.54% as of Apr 20, 2020, while the infection ratio out of the US population is estimated to be 0.53%, implying a case mortality rate at 2.85% which is close to the 3.4% suggested by the WHO in Mar 2020. Towards the end of the summer of 2020, the overall infection ratio of the US rises to 2.49% while the case mortality decreases to 2.09%, and the ratio of asymptomatic cases out of all infected cases reduces from the pre-summer 35-40% to around 20-25%.

The effective reproduction number, R(t), is a central point in the study of infectious diseases. It establishes in an explicit way the extent of an epidemic spread process in a population. The current estimation methods for the time evolution of R(t), using incidence data, rely on the generation interval distribution, g(\tau), which is usually obtained from empirical data or already known distributions from the literature. However, there are systems, especially highly heterogeneous ones, in which there is a lack of data and an adequate methodology to obtain g(\tau). In this work, we use mathematical models to bridge this gap. We present a general methodology for obtaining an explicit expression of the reproduction numbers and the generation interval distributions provided by an arbitrary compartmental model. Additionally, we present the appropriate expressions to evaluate those reproduction numbers using incidence data. To highlight the relevance of such methodology, we apply it to the spread of Covid-19 in municipalities of the state of Rio de janeiro, Brazil. Using two meta-population models, we estimate the reproduction numbers and the contributions of each municipality in the generation of cases in all others. Our results point out the importance of mathematical modelling to provide epidemiological meaning of the available data.