Preprint Hypothesis Version 1 This version is not peer-reviewed

Hypothesis: mPGES-1-Derived Prostaglandin E2, a So Far Missing Link in COVID-19 Pathophysiology?

Version 1 : Received: 11 April 2020 / Approved: 12 April 2020 / Online: 12 April 2020 (04:36:48 CEST)

How to cite: Smeitink, J.; Jiang, X.; Pecheritsyna, S.; Renkema, H.; van Maanen, R.; Beyrath, J. Hypothesis: mPGES-1-Derived Prostaglandin E2, a So Far Missing Link in COVID-19 Pathophysiology?. Preprints 2020, 2020040180 (doi: 10.20944/preprints202004.0180.v1). Smeitink, J.; Jiang, X.; Pecheritsyna, S.; Renkema, H.; van Maanen, R.; Beyrath, J. Hypothesis: mPGES-1-Derived Prostaglandin E2, a So Far Missing Link in COVID-19 Pathophysiology?. Preprints 2020, 2020040180 (doi: 10.20944/preprints202004.0180.v1).

Abstract

With frequencies varying up to 20%, treatment resistant pulmonary failure is a major life-threatening complication in COVID-19 (SARS-CoV-2, HCoV19) disease pathology. Both acute respiratory distress syndrome (ARDS), proposed to be caused by an over-reacting immune system which floods the lung with edema, a liquid consisting of inflammatory cells, and diminished lung perfusion, have been postulated to cause this treatment resistant lung failure. Aging, co-morbidities, male gender and obesity are pre-existing factors associated with the more severe outcome. Thrombosis is more frequently observed than usually seen during ICU admission. Different hypotheses explaining the pathophysiological cascade leading to fast progressing severe COVID-19 disease and how to counteract it have been proposed. A variety of intervention studies to control severity are ongoing or planned. Not suggested so far, we here hypothesize that the inflammatory lipid modulator prostaglandin E2 (PGE2) executes a prominent role in COVID-19 pathophysiology. Based on this we suggest measuring PGE2 in patients and evaluating selective inhibition of the human microsomal prostaglandin E synthase-1 (mPGES-1) as a potential innovative therapeutic approach in this devastating condition for which sonlicromanol, a drug currently in phase 2b studies for mitochondrial disease, is a candidate.

Subject Areas

COVID-19; prostaglandins; mPGES1 inhibitor; ARDS; sonlicromanol; KH176

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