The case for chronotherapy in Covid-19-induced acute respiratory distress syndrome

Abstract

Coronavirus disease 2019 (COVID-19), the disease resulting from infection by a novel coronavirus, SARS-Cov2, has rapidly spread since November 2019 leading to a global pandemic. SARS-Cov2 has infected over four million people and caused over 290,000 deaths worldwide. Although most cases are mild, a subset of patients develop a severe and atypical presentation of acute respiratory distress syndrome (ARDS) that is characterised by a cytokine release storm (CRS). Paradoxically, treatment with anti-inflammatory agents and immune regulators has been associated with worsening of ARDS. We hypothesize that the intrinsic circadian clock of the lung and the immune system may regulate individual components of CRS, and thus, chronotherapy may be used to effectively manage ARDS in COVID-19 patients. LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc.

FIGURE 1

Diagram showing , over 24 h, the peak of cytokines and immune responses involved in the cytokine release storm (CRS) of COVID‐19. Peak detrimental inflammatory mediators (red) and beneficial adaptive immune response against viral infections (green) are shown during a 24‐h time period. The dotted line and the red clock indicate the period between 4:00 p.m. and midnight in which the detrimental effects of CRS outweighs the beneficial effect of the adaptive immune response. This period of time could be the ideal target for anti‐inflammatory treatments. On the other hand, the green clocks indicate the periods of anti‐viral activity of the immune system; these are the periods in which anti‐inflammatory therapy should be avoided