key: cord-0960882-1fix1ooj
authors: Bauer, Philippe R.
title: Influence of Geopolitics on Severity and Outcome in COVID-19*
date: 2021-10-05
journal: Crit Care Med
DOI: 10.1097/ccm.0000000000005325
sha: 47a12f6847f2b5cc33c586344cb32f02e3e6c50d
doc_id: 960882
cord_uid: 1fix1ooj

nan

G eopolitics can be defined as the analysis of the geographic influences on power relationships in international relations (1) . The Meuse-Rhine Euroregion is one of the oldest cross-border regions in the European Union. It has brought together five partner regions in three countries with different languages and cultures, the southern and central parts of the Dutch Province of Limburg, the German Zweckverband of the Aachen Region, the German-speaking community of Belgium, and the Belgian provinces of Liège and Limburg. This cross-border partnership has created new opportunities for the population and contributes to the quality of life of its approximately 4 million inhabitants (2). The propagation of coronavirus disease 2019 (COVID-19) follows the travel paths of the population. Therefore, in a pandemic like COVID-19, a region with close cross-border interaction would be expected to treat similar patients unless effective and multiple interventions were implemented at various levels (border control measures, community transmission control measures, and case-based control measures) like in New Zealand (3) . When healthcare capacity is not overwhelmed by the COVID-19 pandemic, patient's factors such as age, sex, and comorbidities influence outcome (4, 5) . Furthermore, the quality of healthcare may be affected by national policies, prioritization of resources, clusters and degree of propagation of the infection, capacity of the healthcare system to regulate a massive influx of patients, and use of established networks of regional coordination across hospital systems (6) . Other factors such as race, ethnicity, and other social determinants of health may play a role as well (7), although, in a large U.S. study of 11,210 patients, race was not associated with a different outcome after adjusting for sociodemographic status and comorbidities for those able to access hospital care (8) .

In this issue of Critical Care Medicine, Mesotten et al (9) report on a cohort of patients with COVID-19 as part of the Corona Data driven interventions & data Platform (CoDaP) program, supported by Interreg Euregio Meuse-Rhine with funding from the European Regional Development Fund (10) . CoDaP is a project aimed at developing cross-border consensus treatment guidelines, establishing a COVID-19 data platform, anticipate new waves, and building an efficient and secure information technology infrastructure. The specific goal of the present study by Mesotten et al (9) was to evaluate practice variation within the Euroregion. The authors' hypothesis was that variable healthcare system responses to a pandemic drive variability in patient characteristics and disease severity, support strategies, therapies, and complications and impact outcome within a cohort of COVID-19 patients admitted to ICUs in a well-defined region of Western Europe. The authors studied 551 patients with COVID-19 pneumonia who were admitted to seven ICUs within the Meuse-Rhine Euroregion between March 2, 2020, and August 12, 2020. Comorbidities were more frequent in the German patients than the Dutch patients, and severity was lower in the Belgian patients. Overall, there was a predominance of males, and many patients required invasive mechanical ventilation and vasopressor use. In general, German patients needed more critical care support. A large majority received antibiotics, and corticosteroids were rarely given, especially in the German group. ICU mortality varied between countries and was 22%, 42%, and 44% in the Belgian, Dutch, and German parts, respectively. The German group had the highest risk of mortality when adjusting for multiple factors such as age, sex, severity, comorbidities, management strategy, and complications. Of note, the German part encompassed a single university hospital with the largest number of ICU beds (n = 104); it was also the only hospital who did not (have to) increase its capacity to adapt to the pandemic needs. The authors concluded that there was a large variability in patient's characteristics, severity, interventions, complications, and outcome between countries despite close cross-border interaction and called for more cooperation across the borders within the Euroregion.

Geopolitics and consequential impact on healthcare can have a profound influence on outcomes from illness, particularly in critically ill patients with COVID-19. What can we learn from the findings of the study by Mesotten et al (9) ? Aside well-established risk factors such as age, sex, or obesity, the burden of viral load is a major contributor of severity and risk of intubation and is associated with social behaviors (11) . During the study period, measures of social distancing were implemented in various forms and degrees across the countries, but the details were not provided. Race and ethnicity, not provided neither, seem only affecting outcome when access to hospital care is impaired. It is likely that migrants (e.g., from Turkey or the middle East) were infected by COVID-19 as well as the traditional population from this part of Europe, and therefore, the people in the study by Mesotten et al (9) may represent less a commonality in race, ethnicity, or genetic background per se than a shared socioeconomic background. The German hospital had more patients on extracorporeal membrane oxygenation support. It appears that this center received more critical patients:

100% of them were intubated; none of them had received either high-flow nasal cannula or a trial of noninvasive ventilation; a majority of them were on pressure control mode of ventilation, suggesting a more advanced degree of pulmonary involvement with less compliance (albeit also possibly reflecting providers' preference), and more patients were on (higher dose of) vasopressor and renal support. Of interest, there was very limited use of corticosteroids even though the Surviving Sepsis Campaign Guidelines suggested the use of corticosteroids in protracted forms of acute respiratory distress syndrome by the end of March 2020 (12) , before the preliminary report of the Randomized Evaluation of Covid-19 Therapy (RECOVERY) study was published on July 17, 2020 (13) . In the Dutch group, a relatively large number (n = 29) were transferred outside the Euroregion which may have introduced a selection bias. Surprisingly, the strain on the system did not seem to affect ICU mortality. Although the availability of ICU beds in The Netherlands was 6.4, compared with 15.9 and 29.2 per 100,000 inhabitants for Belgium and Germany, respectively, the lower mortality in the Dutch and Belgian parts may have simply reflected adaptation to the surge, by increasing ICU bed capacity, facilitating interhospital transfer or other measures to face the pandemic. It may also have not been representative of each individual in the entire country. The lower severity in the Belgian group may have also reflected other factors such as a possibly lower number of COVID-19 cases in Belgium at that time. Overall, there was clearly a difference in severity: according to the World Health Organization classification, the Belgian and Dutch parts had more severe than critical COVID-19 cases, whereas the German part had more critical cases. Interestingly, mortality when adjusted for severity was no different suggesting that management, tailored to the severity, did not differ significantly between centers, some having simply more critical cases than others. Mortality in COVID-19 is directly related to the degree of respiratory failure, and there were less patients on invasive mechanical ventilation in the Belgian and the Dutch group than in the German group, 53%, 89%, and 100%, respectively. Mortality may also vary independently of patient features, as reflected in the literature by the large across-the-nations Viral Infection and Respiratory Illness Universal Study (VIRUS) registry showing that interhospital variation in mortality of mechanically ventilated patients is present and not explained by patient characteristics (14) . Whether or not the findings by Mesotten et al (9) truly reflect a variance in practice leading to/or different stages and severity of the disease remains to be elucidated. The authors clearly demonstrated that variation exists between different healthcare systems within a geographically well-delimited region which reinforces a contrario the importance of a common model of care (15) . The study by Mesotten et al (9) also emphasizes the role of interhospital transfers as overflow in case of surge, to maintain optimal care by sharing resources and prevent or limit triaging.

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