Erythrocytes Induce Vascular Dysfunction in COVID-19 (preprint)

Background: Vascular injury has been implicated as a major cause of clinical complications in patients with coronavirus disease 2019 (COVID-19) based on autopsy studies showing destruction of the endothelial architecture. Red blood cells (RBCs) are affected by COVID-19 with alterations in their structure and function, possibly altering disease progress. Objectives: This study was designed to test the hypothesis of persistent endothelial dysfunction and that RBCs act as mediators of endothelial dysfunction in COVID-19. Methods and results: COVID-19 patients displayed profound endothelial dysfunction in vivo assessed with pulse amplitude tonometry, both in the acute phase and at follow-up four months later. RBCs but not plasma from COVID-19 patients in the acute phase incubated with healthy rat aorta induced severe endothelial dysfunction ex vivo compared to RBCs from healthy subjects. Further, these RBCs induced vascular arginase 1 and oxidative stress. Consequently, inhibition of vascular arginase or superoxide attenuated endothelial dysfunction induced by RBCs from COVID-19 patients. These RBCs were characterized by increased production of reactive oxygen species and reduced export of the nitric oxide metabolite nitrate. RBCs from COVID-19 patients at follow-up did not affect vascular function. Pre-incubation of RBCs from healthy subjects with interferon-γ impaired endothelial function.Conclusions: This study demonstrates the presence of persistent endothelial dysfunction in an otherwise mainly healthy population hospitalized for COVID-19, and implicates a role of RBCs as mediators of endothelial injury. These data shed light on a new pathological mechanism underlying vascular dysfunction in COVID-19 and lay the foundation for future therapeutic developments.

Longitudinal variability in mortality predicts Covid-19 deaths (preprint)

Within Europe, death rates due to covid-19 vary greatly, with some countries being hardly hit while others to date are almost unaffected. It would be of interest to pinpoint the factors that determine a country’s susceptibility to a pandemic such as covid-19. Here we present data demonstrating that mortality due to covid-19 in a given country could have been largely predicted even before the pandemic hit Europe, simply by looking at longitudinal variability of all-cause mortality rates in the years preceding the current outbreak. The variability in death rates during the influenza seasons of 2015-2019 correlate to excess mortality caused by covid-19 in 2020 (R 2 =0.48, p<0.0001). In contrast, we found no correlation between such excess mortality and age, population density, degree of urbanization, latitude, GNP, governmental health spendings or rates of influenza vaccinations. These data may be of some relevance when discussing the effectiveness of acute measures in order to limit the spread of the disease and ultimately deaths. They suggest that in some European countries there is an intrinsic susceptibility to fatal respiratory viral disease including covid-19; a susceptibility that was evident long before the arrival of the current pandemic.