A critical evaluation of glucocorticoids in the management of severe COVID-19

Cinzia Solinas, Laura Perra, Marco Aiello, Edoardo Migliori, Nicola Petrosillo, Cinzia Solinas, Laura Perra, Marco Aiello, Edoardo Migliori, Nicola Petrosillo

Abstract

The viral infection by SARS-CoV-2 has irrevocably altered the life of the majority of human beings, challenging national health systems worldwide, and pushing researchers to rapidly find adequate preventive and treatment strategies. No therapies have been shown effective with the exception of dexamethasone, a glucocorticoid that was recently proved to be the first life-saving drug in this disease. Remarkably, around 20 % of infected people develop a severe form of COVID-19, giving rise to respiratory and multi-organ failures requiring subintensive and intensive care interventions. This phenomenon is due to an excessive immune response that damages pulmonary alveoli, leading to a cytokine and chemokine storm with systemic effects. Indeed glucocorticoids' role in regulating this immune response is controversial, and they have been used in clinical practice in a variety of countries, even without a previous clear consensus on their evidence-based benefit.

Keywords: ARDS; COVID-19; Glucocorticoids; Immune response; SARS-CoV-2.

Copyright © 2020 Elsevier Ltd. All rights reserved.

Figures

Graphical abstract
Graphical abstract
Fig. 1
Fig. 1
Physiology and pathophysiology of pulmonary alveoli during SARS-CoV-2 infection. (A) Anatomy and physiology of healthy pulmonary alveoli, representing small air spaces in the lungs where carbon dioxide leaves and oxygen enters the blood. During inhalation air enters the lungs, travels through bronchi, bronchioles and then flows into approximately 300,000,000 alveoli. During exhalation, the carbon-dioxide-laden air is forced out of the alveoli through the same passageways. (B) Pathophysiology of pulmonary alveoli during SARS-CoV-2 infection. Infection of the novel Coronavirus, named SARS-CoV-2 creates an epithelial damage, followed by an immune response that is generated by a cytokine and chemokine release. This could lead to immune cell activation that might give rise to either resolution and severe COVID-19 with the consequent development of ARDS and of multi-organ failure. (C) Severe COVID-19: immune biological aspects. A sustained cytokine storm generates an inflammation that causes damage to the alveolar epithelium, giving rise to ARDS, shock, kidney injury, other organ failure and secondary infection. Legend: ARDS: Adult Respiratory Distress Syndrome; CCL: C-C motif chemokine ligand; CXCL: C-X-C motif chemokine ligand; CO2:carbon dioxide; COVID-19: CoronaVirus Disease-19; GC: glucocorticoid; GM-CSF: granulocyte-monocyte colony stimulating factor; IL: interleukin; TNF: tumor necrosis factor.
Fig. 2
Fig. 2
Severity and phases of COVID-19. (A) COVID-19 severity: frequency of degrees of clinical manifestations in a Chinese cohort (>44.000 patients) (ref: Wu Z. et al., 2020). (B) Phases of COVID-19 disease and timing for the use of glucocorticoids. Legend: ARDS: Adult Respiratory Distress Syndrome; COVID-19: CoronaVirus Disease-19; MOF: multi-organ failure; pts: patients; SIRS: systemic inflammatory response syndrome.
Fig. 3
Fig. 3
Mechanisms of action of synthetic glucocorticoids (GC). (A) Genomic mechanism. (B) Non-genomic mechanism. Legend: GC: glucocorticoid; GCR: glucocorticoid receptor; mRNA: messanger RNA; TF: transcription factor.

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