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Bull Math Biol ; 84(8): 79, 2022 06 30.
Article in English | MEDLINE | ID: covidwho-1905515


We study the relative importance of two key control measures for epidemic spreading: endogenous social self-distancing and exogenous imposed quarantine. We use the framework of adaptive networks, moment-closure, and ordinary differential equations to introduce new model types of susceptible-infected-recovered (SIR) dynamics. First, we compare computationally expensive, adaptive network simulations with their corresponding computationally efficient ODE equivalents and find excellent agreement. Second, we discover that there exists a critical curve in parameter space for the epidemic threshold, which suggests a mutual compensation effect between the two mitigation strategies: as long as social distancing and quarantine measures are both sufficiently strong, large outbreaks are prevented. Third, we study the total number of infected and the maximum peak during large outbreaks using a combination of analytical estimates and numerical simulations. Also for large outbreaks we find a similar compensation mechanism as for the epidemic threshold. This means that if there is little incentive for social distancing in a population, drastic quarantining is required, and vice versa. Both pure scenarios are unrealistic in practice. The new models show that only a combination of measures is likely to succeed to control epidemic spreading. Fourth, we analytically compute an upper bound for the total number of infected on adaptive networks, using integral estimates in combination with a moment-closure approximation on the level of an observable. Our method allows us to elegantly and quickly check and cross-validate various conjectures about the relevance of different network control measures. In this sense it becomes possible to adapt also other models rapidly to new epidemic challenges.

Epidemics , Quarantine , Disease Outbreaks , Epidemics/prevention & control , Mathematical Concepts , Models, Biological
Crit Care Med ; 50(6): e526-e538, 2022 06 01.
Article in English | MEDLINE | ID: covidwho-1621691


OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) is a potentially lifesaving procedure in acute respiratory distress syndrome (ARDS) due to COVID-19. Previous studies have shown a high prevalence of clinically silent cerebral microbleeds in patients with COVID-19. Based on this fact, together with the hemotrauma and the requirement of therapeutic anticoagulation on ECMO support, we hypothesized an increased risk of intracranial hemorrhages (ICHs). We analyzed ICH occurrence rate, circumstances and clinical outcome in patients that received ECMO support due to COVID-19-induced ARDS in comparison to viral non-COVID-19-induced ARDS intracerebral hemorrhage. DESIGN: Multicenter, retrospective analysis between January 2010 and May 2021. SETTING: Three tertiary care ECMO centers in Germany and Switzerland. PATIENTS: Two-hundred ten ARDS patients on ECMO support (COVID-19, n = 142 vs viral non-COVID, n = 68). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Evaluation of ICH occurrence rate, parameters of coagulation and anticoagulation strategies, inflammation, and ICU survival. COVID-19 and non-COVID-19 ARDS patients showed comparable disease severity regarding Sequential Organ Failure Assessment score, while the oxygenation index before ECMO cannulation was higher in the COVID group (82 vs 65 mm Hg). Overall, ICH of any severity occurred in 29 of 142 COVID-19 patients (20%) versus four of 68 patients in the control ECMO group (6%). Fifteen of those 29 ICH events in the COVID-19 group were classified as major (52%) including nine fatal cases (9/29, 31%). In the control group, there was only one major ICH event (1/4, 25%). The adjusted subhazard ratio for the occurrence of an ICH in the COVID-19 group was 5.82 (97.5% CI, 1.9-17.8; p = 0.002). The overall ICU mortality in the presence of ICH of any severity was 88%. CONCLUSIONS: This retrospective multicenter analysis showed a six-fold increased adjusted risk for ICH and a 3.5-fold increased incidence of ICH in COVID-19 patients on ECMO. Prospective studies are needed to confirm this observation and to determine whether the bleeding risk can be reduced by adjusting anticoagulation strategies.

COVID-19 , Extracorporeal Membrane Oxygenation , Respiratory Distress Syndrome , Anticoagulants/therapeutic use , COVID-19/complications , COVID-19/therapy , Extracorporeal Membrane Oxygenation/adverse effects , Extracorporeal Membrane Oxygenation/methods , Humans , Intracranial Hemorrhages/drug therapy , Intracranial Hemorrhages/epidemiology , Intracranial Hemorrhages/etiology , Respiratory Distress Syndrome/epidemiology , Respiratory Distress Syndrome/therapy , Retrospective Studies