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The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity

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  • The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity


    Published Online May 6, 2021
    https://doi.org/10.1016/ S2213-2600(21)00218-6

    Marcin F Osuchowski*, Martin S Winkler*, Tomasz Skirecki, Sara Cajander, Manu Shankar-Hari, Gunnar Lachmann, Guillaume Monneret, Fabienne Venet, Michael Bauer, Frank M Brunkhorst, Sebastian Weis, Alberto Garcia-Salido, Matthijs Kox, Jean-Marc Cavaillon, Florian Uhle, Markus A Weigand, Stefanie B Flohe?, W Joost Wiersinga, Raquel Almansa, Amanda de la Fuente, Ignacio Martin-Loeches, Christian Meisel, Thibaud Spinetti, Joerg C Schefold, Catia Cilloniz, Antoni Torres, Evangelos J Giamarellos-Bourboulis, Ricard Ferrer, Massimo Girardis, Andrea Cossarizza, Mihai G Netea, Tom van der Poll, Jesu?s F Bermejo-Marti?n, Ignacio Rubio

    The zoonotic SARS-CoV-2 virus that causes COVID-19 continues to spread worldwide, with devastating consequences. While the medical community has gained insight into the epidemiology of COVID-19, important questions remain about the clinical complexities and underlying mechanisms of disease phenotypes. Severe COVID-19 most commonly involves respiratory manifestations, although other systems are also a ected, and acute disease is often followed by protracted complications. Such complex manifestations suggest that SARS-CoV-2 dysregulates the host response, triggering wide-ranging immuno-in ammatory, thrombotic, and parenchymal derangements. We review the intricacies of COVID-19 pathophysiology, its various phenotypes, and the anti-SARS-CoV-2 host response at the humoral and cellular levels. Some similarities exist between COVID-19 and respiratory failure of other origins, but evidence for many distinctive mechanistic features indicates that COVID-19 constitutes a new disease entity, with emerging data suggesting involvement of an endotheliopathy-centred pathophysiology. Further research, combining basic and clinical studies, is needed to advance understanding of pathophysiological mechanisms and to characterise immuno-in ammatory derangements across the range of phenotypes to enable optimum care for patients with COVID-19.
    ...

    PDF Format: https://www.thelancet.com/action/sho...2821%2900218-6
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