A Timely Call to Arms: COVID-19, the Circadian Clock, and Critical Care

Abstract

We currently find ourselves in the midst of a global coronavirus disease 2019 (COVID-19) pandemic, caused by the highly infectious novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we discuss aspects of SARS-CoV-2 biology and pathology and how these might interact with the circadian clock of the host. We further focus on the severe manifestation of the illness, leading to hospitalization in an intensive care unit. The most common severe complications of COVID-19 relate to clock-regulated human physiology. We speculate on how the pandemic might be used to gain insights on the circadian clock but, more importantly, on how knowledge of the circadian clock might be used to mitigate the disease expression and the clinical course of COVID-19.

Circadian disturbances, sleep difficulties and the COVID-19 pandemic

“…At the physiological level, different aspects of the disease process—from infection to pathology— are associated with circadian rhythmicity. This means that a misaligned circadian clock can intensify or prolong disease duration and the recovery process, while an undisturbed circadian clock can mitigate disease expression and the clinical course of COVID-19 [ 47 ].…”

Association of Circadian Clock and Severe Acute Respiratory Syndrome Coronavirus 2 Infection

“…In one of the study, it was concluded that ACE2 expression followed circadian pattern and it has been stated by the authors that time of day of viral encounter may significantly influence the COVID-19 entry and replication mechanism [39]. Viral clearance within the body exhibit circadian oscillations as concluded by recently published study [40].…”

“…Hypoxemic respiratory failure is major cause of death in CO-VID-19 that involves circadian rhythm and molecular biology of gene expressions involved in it. It is evident that cellular oxygenation actively influence the circadian clocks by the process mediated through hypoxia inducible factor 1 alpha [40]. In another study, alteration in the circadian clock regulated gene expression causes respiratory failure in COVID-19 particularly in lungs thereby causing acute lung injuries [41].…”

Frontiers in Chronobiology: Endogenous Clocks at the Core of Signaling Pathways in Physiology

“…Moreover, rhythmicity over different time scales–most likely circadian and seasonal–may modulate the likelihood of acquisition and/or the course of infection and disease. Similarly, the intensive care arrhythmic environment may have unexpected effects on disease evolution (Haspel et al, 2021 ). The time of administration of approved treatments may impinge on the entity of their desired and side effects, in relation to both the nature of treatment itself, and to the patient's response to it (Haspel et al, 2021 ).…”

“…The time of administration of approved treatments may impinge on the entity of their desired and side effects, in relation to both the nature of treatment itself, and to the patient's response to it (Haspel et al, 2021 ). These and other aspects of the complex and yet largely unexplored relationship between the pandemic and rhythmicity over different time scales have been considered by eminent colleagues in a collection of articles recently published in the Journal of Biological Rhythms (Sengupta et al, 2020 , 2021 ; Borrmann et al, 2021 ; Cermakian and Harrington, 2021 ; Haspel et al, 2021 ; Kronfeld-Schor et al, 2021 ). As the pandemic continues to unfold, chronobiologists and scientists in related fields have become more sensitive to this relationship, and are examining available laboratory/clinical data retrospectively, and collecting them prospectively.…”