The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity. Issue 6 (June 2021)

• Record Type: Journal Article
• Authors: 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; Martin-Loeches, Ignacio; Meisel, Christian; Spinetti, Thibaud; Schefold, Joerg C; Cilloniz, Catia; Torres, Antoni; Giamarellos-Bourboulis, Evangelos J; Ferrer, Ricard; Girardis, Massimo; Cossarizza, Andrea; Netea, Mihai G; van der Poll, Tom; Bermejo-Martín, Jesús F; Rubio, Ignacio;
• Is Part Of: Lancet. Volume 9:Issue 6(2021)
• Page Start: 622
• Page End: 642
• Publication Date: 2021-06
• Subjects: Respiratory organs -- Diseases -- Periodicals; 616.2005
• DOI: 10.1016/S2213-2600(21)00218-6
• Languages: English
• ISSNs: 2213-2600

Abstract

Summary: 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.