Early detection of the emergence of a new variant of concern (VoC) is essential to develop strategies that contain epidemic outbreaks. For example, knowing in which region a VoC starts spreading enables prompt actions to circumscribe the geographical area where the new variant can spread, by containing it locally. This paper presents ‘funnel plots’ as a statistical process control method that, unlike tools whose purpose is to identify rises of the reproduction number (R_t), detects when a regional R_t departs from the national average and thus represents an anomaly. The name of the method refers to the funnel-like shape of the scatter plot that the data take on. Control limits with prescribed false alarm rate are derived from the observation that regional R_t's are normally distributed with variance inversely proportional to the number of infectious cases. The method is validated on public COVID-19 data demonstrating its efficacy in the early detection of SARS-CoV-2 variants in India, South Africa, England, and Italy, as well as of a malfunctioning episode of the diagnostic infrastructure in England, during which the Immensa lab in Wolverhampton gave 43,000 incorrect negative tests relative to South West and West Midlands territories.

We formulate a control problem for positive compartmental systems formed by nodes (buffers) and arcs (flows). Our main result is that, on a finite horizon, we can solve the Pontryagin equations in one shot without resorting to trial and error via shooting. As expected, the solution is bang–bang and the switching times can be easily determined. We are also able to find a cost-to-go-function, in an analytic form, by solving a simple nonlinear differential equation. On an infinite horizon, we consider the Hamilton–Jacobi–Bellman theory and we show that the HJB equation can be solved exactly. Moreover, we show that the optimal solution is constant and the cost-to-go function is linear and copositive. This function is the solution of a nonlinear equation. We propose an iterative scheme for solving this equation, which converges in finite time. We also show that an exact solution can be found if there is a positive external disturbance affecting the process and the problem is formulated in a minsup framework. We finally provide illustrative examples related to flood control and epidemiology.

We consider a class of epidemiological models with an arbitrary number of infected compartments. We show that the logarithmic derivatives of the infected states converge to a consensus; this property rigorously explains the feature empirically observed in real epidemic data: the logarithms of the state variables associated with infected categories tend to behave as "parallel lines". We introduce and characterise the class of contagion functions, i.e., linear co-positive functions of the state variables that decrease (resp. increase) when the reproduction number is smaller (resp. larger) than 1. Finally, we analyse the generalised epidemiological model by considering the susceptible state variable along with a variable that aggregates all the infected compartments: this leads to an auxiliary planar system, governed by two differential inclusions, which has the same structure as the two-dimensional SI model and whose coefficients are functions of the original variables. We prove that well known properties of the classical SI model still hold in this generalised case.

We consider the problem of assessing the sensitivity of uncertain biochemical systems in the presence of input perturbations (either constant or periodic) around a stable steady state. In particular, we propose approaches for the robust sensitivity analysis of systems with uncertain parameters assumed to take values in a hyper-rectangle. We highlight vertex results, which allow us to check whether a property is satisfied for all parameter choices in the hyper-rectangle by simply checking whether it is satisfied for all parameter choices at the vertices of the hyper-rectangle. We show that, for a vast class of systems, including (bio)chemical reaction networks with mass-action kinetics, the system Jacobian has a totally multiaffine structure (namely, all minors of the Jacobian matrix are multiaffine functions of the uncertain parameters), which can be exploited to obtain several vertex results. We consider different problems: robust non-singularity; robust stability of the steady-state; robust steady-state sensitivity analysis, in the case of constant perturbations; robust frequency-response sensitivity analysis, in the presence of periodic perturbations; and robust adaptation analysis. The developed theory is then applied to gain insight into some examples of uncertain biochemical systems, including the incoherent feed-forward loop, the coherent feed-forward loop, the Brusselator oscillator and the Goldbeter oscillator.

Despite progress in clinical care for patients with coronavirus disease 2019 (COVID-19)¹, population-wide interventions are still crucial to manage the pandemic, which has been aggravated by the emergence of new, highly transmissible variants. In this study, we combined the SIDARTHE model², which predicts the spread of SARS-CoV-2 infections, with a new data-based model that projects new cases onto casualties and healthcare system costs. Based on the Italian case study, we outline several scenarios: mass vaccination campaigns with different paces, different transmission rates due to new variants and different enforced countermeasures, including the alternation of opening and closure phases. Our results demonstrate that non-pharmaceutical interventions (NPIs) have a higher effect on the epidemic evolution than vaccination alone, advocating for the need to keep NPIs in place during the first phase of the vaccination campaign. Our model predicts that, from April 2021 to January 2022, in a scenario with no vaccine rollout and weak NPIs (R = 1.27), as many as 298,000 deaths associated with COVID-19 could occur. However, fast vaccination rollouts could reduce mortality to as few as 51,000 deaths. Implementation of restrictive NPIs (R = 0.9) could reduce COVID-19 deaths to 30,000 without vaccinating the population and to 18,000 with a fast rollout of vaccines. We also show that, if intermittent open–close strategies are adopted, implementing a closing phase first could reduce deaths (from 47,000 to 27,000 with slow vaccine rollout) and healthcare system costs, without substantive aggravation of socioeconomic losses.

We consider a class of epidemiological models in which a compartmental linear system, including various categories of infected individuals (e.g. asymptomatic, symptomatic, quarantined), is fed back by a positive feedback, representing contagion. The positive feedback gain decreases (in a sort of negative feedback) as the epidemic evolves, due to the decrease in the number of susceptible individuals. We first propose a convergence result based on a special copositive Lyapunov function. Then, we address a major problem for this class of systems: the deep uncertainty affecting parameter values. We face the problem adopting techniques from optimal and robust control theory to assess the sensitivity of the model. For this class of systems, the optimal control solution has a peculiar decoupling property that no shooting procedure is required. Finally, we exploit the obtained bounds to assess the effectiveness of possible epidemic control strategies, including intermittent restrictions adopted during the COVID-19 pandemic.

In Italy, 128,948 confirmed cases and 15,887 deaths of people who tested positive for SARS-CoV-2 were registered as of 5 April 2020. Ending the global SARS-CoV-2 pandemic requires implementation of multiple population-wide strategies, including social distancing, testing and contact tracing. We propose a new model that predicts the course of the epidemic to help plan an effective control strategy. The model considers eight stages of infection: susceptible (S), infected (I), diagnosed (D), ailing (A), recognized (R), threatened (T), healed (H) and extinct (E), collectively termed SIDARTHE. Our SIDARTHE model discriminates between infected individuals depending on whether they have been diagnosed and on the severity of their symptoms. The distinction between diagnosed and non-diagnosed individuals is important because the former are typically isolated and hence less likely to spread the infection. This delineation also helps to explain misperceptions of the case fatality rate and of the epidemic spread. We compare simulation results with real data on the COVID-19 epidemic in Italy, and we model possible scenarios of implementation of countermeasures. Our results demonstrate that restrictive social-distancing measures will need to be combined with widespread testing and contact tracing to end the ongoing COVID-19 pandemic.

State convergence is essential in many scientific areas, e.g. multi-agent consensus/disagreement, distributed optimization, computational game theory, multi-agent learning over networks. In this paper, we study for the first time the state convergence problem in uncertain linear systems. Preliminarily, we characterize state convergence in linear systems via equivalent linear matrix inequalities. In the presence of uncertainty, we complement the canonical definition of (weak) convergence with a stronger notion of convergence, which requires the existence of a common kernel among the generator matrices of the difference/differential inclusion (strong convergence). We investigate under which conditions the two definitions are equivalent. Then, we characterize strong and weak convergence via Lyapunov arguments, (linear) matrix inequalities and separability of the eigenvalues of the generator matrices. Finally, we show that, unlike asymptotic stability, state convergence lacks of duality.

In this letter we show how the problem of assessing structural local stability of BDC-decomposable systems, left open in recent literature, can be solved via convex optimisation. First we give a simple test, based on a sufficient condition, that requires checking the strict co-positivity of a multivariate polynomial. Then we provide a stronger test, based on a necessary and sufficient condition, which can be numerically implemented via LMI-based convex optimisation. The proposed approach certifies the structural stability of non-trivial systems, including a biological network discussed in the literature.

In systems biology, perfect adaptation (adaptation) denotes the property of a system reacting to a step input stimulus by completely (partially) restoring the pre-stimulus output value at steady state. We address the problem of predicting adaptation for uncertain dynamical systems. To this aim, we introduce a formal definition of adaptation tailored to the robust analysis of dynamical systems. Whilst the definition is more general and valid also for the step response analysis of nonlinear systems, in the linear case such a definition of adaptation reduces to the presence of a single real zero that dominates all poles. Based on this definition, we can assess robust adaptation by means of the robust real plot, which characterises the position of real zeros and poles for linear systems with parametric uncertainties.