TY - JOUR
T1 - The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity
AU - Osuchowski, Marcin F.
AU - Winkler, Martin S.
AU - Skirecki, Tomasz
AU - Cajander, Sara
AU - Shankar-Hari, Manu
AU - Lachmann, Gunnar
AU - Monneret, Guillaume
AU - Venet, Fabienne
AU - Bauer, Michael
AU - Brunkhorst, Frank M.
AU - Weis, Sebastian
AU - Garcia-Salido, Alberto
AU - Kox, Matthijs
AU - Cavaillon, Jean-Marc
AU - Uhle, Florian
AU - Weigand, Markus A.
AU - Flohé, Stefanie B.
AU - Wiersinga, W. Joost
AU - Almansa, Raquel
AU - de la Fuente, Amanda
AU - Martin-Loeches, Ignacio
AU - Meisel, Christian
AU - Spinetti, Thibaud
AU - Schefold, Joerg C.
AU - Cilloniz, Catia
AU - Torres, Antoni
AU - Giamarellos-Bourboulis, Evangelos J.
AU - Ferrer, Ricard
AU - Girardis, Massimo
AU - Cossarizza, Andrea
AU - Netea, Mihai G.
AU - van der Poll, Tom
AU - Bermejo-Martín, Jesús F.
AU - Rubio, Ignacio
N1 - Funding Information:
No funding was provided for this Series paper. TSk is supported by the Poland National Science Centre (UMO-2020/01/0/NZ6/00218). MS-H is funded by a UK National Institute for Health Research (NIHR) Clinician Scientist Award (CS-2016-16-011). GL is a participant of the Berlin Institute of Health (BIH) Charit? Clinician Scientist Programme, which receives grants from the Charit??Universit?tsmedizin Berlin and the Berlin Institute of Health. MB is supported by the Deutsche Forschungsgemeinschaft-funded Collaborative Research Centre PolyTarget (SFB 1278, Project ID 316213987). WJW is supported by the Netherlands Organisation for Scientific Research. AT and JFB-M acknowledge funding from CIBERES in the context of CIBERESUCICOVID (part of Instituto de Salud Carlos III). AC acknowledges funding from the Ministero della Salute, Bando Ricerca COVID-19 (2020?2021, grant number COVID-2020-12371808). The views expressed in this publication are those of the authors and not necessarily those of the UK National Health Service, the NIHR, or the Department of Health and Social Care. We thank Margit Leitner for technical help with figure design.
Funding Information:
MSW has received unrestricted funding from Sartorius. GL reports personal fees from Swedish Orphan Biovitrum. TSp and JCS disclose institutional funding (received by the University of Bern) from Orion Pharma, Abbott Nutrition International, B Braun Medical, CSEM, Edwards Lifesciences, Kenta Biotech, Maquet Critical Care, Omnicare Clinical Research, Nestlé, Pierre Fabre Pharma, Pfizer, Bard Medica, Abbott, Anandic Medical Systems, PanGas Healthcare, Bracco, Hamilton Medical, Fresenius Kabi, Getinge Group Maquet, Dräger, Teleflex Medical, GlaxoSmithKline, Merck Sharp and Dohme, Eli Lilly, Baxter, Astellas, AstraZeneca, CSL Behring, Novartis, Covidien, Nycomed, Phagenesis, and Hemotune. MGN reports grants from GlaxoSmithKline and ViiV Healthcare, and was a scientific founder of TTxD. All other authors declare no competing interests.
Publisher Copyright:
© 2021 Elsevier Ltd
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/6/1
Y1 - 2021/6/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85107130271
U2 - 10.1016/S2213-2600(21)00218-6
DO - 10.1016/S2213-2600(21)00218-6
M3 - Review article
C2 - 33965003
SN - 2213-2600
VL - 9
SP - 622
EP - 642
JO - lancet. Respiratory medicine
JF - lancet. Respiratory medicine
IS - 6
ER -
SDG 3 Good Health and Well-being