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

Osuchowski, Marcin F; Winkler, Martin S; Skirecki, Tomasz; Cajander, Sara; Shankar-Hari, Manu; Lachmann, Gunnar; Monneret, Guillaume; Venet, Fabienne; Bauer, Michael; Brunkhorst, Frank M; Weis, Sebastian; Garcia-Salido, Alberto; Kox, Matthijs; Cavaillon, Jean-Marc; Uhle, Florian; Weigand, Markus A; Flohé, Stefanie B; Wiersinga, W Joost; Almansa, Raquel; de la Fuente, Amanda; ... (2021). The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity. The lancet. Respiratory medicine, 9(6), pp. 622-642. Elsevier 10.1016/S2213-2600(21)00218-6

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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 affected, 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-inflammatory, 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-inflammatory derangements across the range of phenotypes to enable optimum care for patients with COVID-19.

Item Type:

Journal Article (Review Article)


04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic of Intensive Care

UniBE Contributor:

Spinetti, Thibaud, Schefold, Jörg Christian


600 Technology > 610 Medicine & health








Isabelle Arni

Date Deposited:

08 Jun 2021 11:10

Last Modified:

05 Dec 2022 15:51

Publisher DOI:


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