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

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. Flohé, W. Joost Wiersinga, Raquel Almansa, Amanda de la FuenteIgnacio 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, Jesús F. Bermejo-Martín, Ignacio Rubio

Research output: Contribution to journalReview articlepeer-review

358 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)622-642
Number of pages21
JournalThe Lancet Respiratory Medicine
Volume9
Issue number6
DOIs
StateIndexed - Jun 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2021 Elsevier Ltd

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