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.
The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity / Osuchowski, M. F.; Winkler, M. S.; Skirecki, T.; Cajander, S.; Shankar-Hari, M.; Lachmann, G.; Monneret, G.; Venet, F.; Bauer, M.; Brunkhorst, F. M.; Weis, S.; Garcia-Salido, A.; Kox, M.; Cavaillon, J. -M.; Uhle, F.; Weigand, M. A.; Flohe, S. B.; Wiersinga, W. J.; Almansa, R.; de la Fuente, A.; Martin-Loeches, I.; Meisel, C.; Spinetti, T.; Schefold, J. C.; Cilloniz, C.; Torres, A.; Giamarellos-Bourboulis, E. J.; Ferrer, R.; Girardis, M.; Cossarizza, A.; Netea, M. G.; van der Poll, T.; Bermejo-Martin, J. F.; Rubio, I.. - In: THE LANCET RESPIRATORY MEDICINE. - ISSN 2213-2600. - 9:6(2021), pp. 622-642. [10.1016/S2213-2600(21)00218-6]
The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity
Girardis M.;Cossarizza A.;
2021
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.
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