Time-dependent recovery of brain hypometabolism in neuro-COVID-19 patients.

PURPOSE: We evaluated brain metabolic dysfunctions and associations with neurological and biological parameters in acute, subacute and chronic COVID-19 phases to provide deeper insights into the pathophysiology of the disease. METHODS: Twenty-six patients with neurological symptoms (neuro-COVID-19) and [¹⁸F]FDG-PET were included. Seven patients were acute (< 1 month (m) after onset), 12 subacute (4 ≥ 1-m, 4 ≥ 2-m and 4 ≥ 3-m) and 7 with neuro-post-COVID-19 (3 ≥ 5-m and 4 ≥ 7-9-m). One patient was evaluated longitudinally (acute and 5-m). Brain hypo- and hypermetabolism were analysed at single-subject and group levels. Correlations between severity/extent of brain hypo- and hypermetabolism and biological (oxygen saturation and C-reactive protein) and clinical variables (global cognition and Body Mass Index) were assessed. RESULTS: The "fronto-insular cortex" emerged as the hypometabolic hallmark of neuro-COVID-19. Acute patients showed the most severe hypometabolism affecting several cortical regions. Three-m and 5-m patients showed a progressive reduction of hypometabolism, with limited frontal clusters. After 7-9 months, no brain hypometabolism was detected. The patient evaluated longitudinally showed a diffuse brain hypometabolism in the acute phase, almost recovered after 5 months. Brain hypometabolism correlated with cognitive dysfunction, low blood saturation and high inflammatory status. Hypermetabolism in the brainstem, cerebellum, hippocampus and amygdala persisted over time and correlated with inflammation status. CONCLUSION: Synergistic effects of systemic virus-mediated inflammation and transient hypoxia yield a dysfunction of the fronto-insular cortex, a signature of CNS involvement in neuro-COVID-19. This brain dysfunction is likely to be transient and almost reversible. The long-lasting brain hypermetabolism seems to reflect persistent inflammation processes.

The Stochastic Approach for SIR Epidemic Models: Do They Help to Increase Information from Raw Data?

The recent outbreak of COVID-19 underlined the need for a fast and trustworthy methodology to identify the features of a pandemic, whose early identification is of help for designing non-pharmaceutical interventions (including lockdown and social distancing) to limit the progression of the disease. A common approach in this context is the parameter identification from deterministic epidemic models, which, unfortunately, cannot take into account the inherent randomness of the epidemic phenomenon, especially in the initial stage;on the other hand, the use of raw data within the framework of a stochastic model is not straightforward. This note investigates the stochastic approach applied to a basic SIR (Susceptible, Infected, Recovered) epidemic model to enhance information from raw data generated in silico. The stochastic model consists of a Continuous-Time Markov Model, describing the epidemic outbreak in terms of stochastic discrete infection and recovery events in a given region, and where independent random paths are associated to different provinces of the same region, which are assumed to share the same set of model parameters. The estimation procedure is based on the building of a loss function that symmetrically weighs first-order and second-order moments, differently from the standard approach that considers a highly asymmetrical choice, exploiting only first-order moments. Instead, we opt for an innovative symmetrical identification approach which exploits both moments. The new approach is specifically proposed to enhance the statistical information content of the raw epidemiological data.

Optimal design of lock-down and reopening policies for early-stage epidemics through SIR-D models.

The diffusion of COVID-19 represents a real threat for the health and economic system of a country. Therefore the governments have to adopt fast containment measures in order to stop its spread and to prevent the related devastating consequences. In this paper, a technique is proposed to optimally design the lock-down and reopening policies so as to minimize an aggregate cost function accounting for the number of individuals that decease due to the spread of COVID-19. A constraint on the maximal number of concomitant infected patients is also taken into account in order to prevent the collapse of the health system. The optimal procedure is built on the basis of a simple SIR model that describes the outbreak of a generic disease, without attempting to accurately reproduce all the COVID-19 epidemic features. This modeling choice is motivated by the fact that the containing measurements are actuated during the very first period of the outbreak, when the characteristics of the new emergent disease are not known but timely containment actions are required. In fact, as a consequence of dealing with poor preliminary data, the simplest modeling choice is able to reduce unidentifiability problems. Further, the relative simplicity of this model allows to compute explicitly its solutions and to derive closed-form expressions for the maximum number of infected and for the steady-state value of deceased individuals. These expressions can be then used to design static optimization problems so to determine the (open-loop) optimal lock-down and reopening policies for early-stage epidemics accounting for both the health and economic costs.