Liver Damage and Exposure to Toxic Concentrations of Endogenous Retinoids in the Pathogenesis of COVID-19 Disease: Hypothesis.

Anthony R Mawson,Ashley M Croft,Federico Gonzalez-Fernandez

doi:10.1089/vim.2020.0330

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a marked tropism for the biliary tract; it damages the bile ducts and hepatocytes and can lead to liver decompensation, cirrhosis, and sepsis. The pathogenesis of liver damage and its association with damage to the lung, heart, and brain and to the other protean manifestations of COVID-19 disease are not fully understood. In particular, tissue damage from thinning and leaky blood vessels appears to result from an inflammatory response to the virus rather than the virus itself. This article outlines a new hypothesis of the nature of the inflammatory factor responsible for tissue damage in COVID-19. Review of the literature reveals that COVID-19 disease closely resembles an endogenous form of hypervitaminosis A. We propose that SARS-CoV-2 virus-induced liver damage causes retinoic acid and stored retinyl esters to be released into the circulation in toxic concentrations, unbound to protein, with resulting damage to organs including the lungs, heart, blood vessels, and skin. Several lines of evidence support this model of disease causation. Subject to testing, strategies for the effective treatment and prevention of COVID-19 could include targeting the action and accumulation of retinoids.

Highlights

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19 disease, has a marked tropism for the biliary tract and is associated with sinusoidal congestion, cell-mediated apoptotic hepatitis, and damage to bile ducts and hepatocytes
This article presents empirical evidence suggesting that the inflammatory factor responsible for tissue damage in COVID-19 is a high concentration of retinoic acid or retinyl esters
Clues to the pathogenesis that we propose include the fact that >80% of vitamin A is stored in the stellate cells of the liver and its accumulation can lead to their activation and hypertrophy, followed by fibrosis and liver injury

Summary

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19 disease, has a marked tropism for the biliary tract and is associated with sinusoidal congestion, cell-mediated apoptotic hepatitis, and damage to bile ducts and hepatocytes. This article presents empirical evidence suggesting that the inflammatory factor responsible for tissue damage in COVID-19 is a high concentration of retinoic acid or retinyl esters.

Results

Conclusion