Hepatic Failure in COVID-19: Is Iron Overload the Dangerous Trigger?

Franca Del Nonno,Ubaldo Visco-Comandini,Laura Falasca,Daniele Colombo,Andrea Antinori,Gianpiero D’Offizi,Roberta Nardacci,Stefania Cicalini,Mauro Piacentini,Luisa Marchioni

doi:10.3390/cells10051103

Abstract

Liver injury in COVID-19 patients has progressively emerged, even in those without a history of liver disease, yet the mechanism of liver pathogenicity is still controversial. COVID-19 is frequently associated with increased serum ferritin levels, and hyperferritinemia was shown to correlate with illness severity. The liver is the major site for iron storage, and conditions of iron overload have been established to have a pathogenic role in development of liver diseases. We presented here six patients who developed severe COVID-19, with biochemical evidence of liver failure. Three cases were survived patients, who underwent liver biopsy; the other three were deceased patients, who were autopsied. None of the patients suffered underlying liver pathologies. Histopathological and ultrastructural analyses were performed. The most striking finding we demonstrated in all patients was iron accumulation into hepatocytes, associated with degenerative changes. Abundant ferritin particles were found enclosed in siderosomes, and large aggregates of hemosiderin were found, often in close contact with damaged mitochondria. Iron-caused oxidative stress may be responsible for mitochondria metabolic dysfunction. In agreement with this, association between mitochondria and lipid droplets was also found. Overall, our data suggest that hepatic iron overload could be the pathogenic trigger of liver injury associated to COVID-19.

Highlights

SARS-CoV-2 causes a wide spectrum of illness ranging from mild symptoms to severe presentation, and death
COVID-19 causes pneumonia; clinical and epidemiological studies have established that COVID-19 presents as a spectrum of clinical manifestations [1,2], and studies performed on whole-body autopsies in patients who died of COVID-19 revealed that SARS-CoV-2 infection causes significant alterations in most body organs [3]
In critical COVID-19 patients, it has been proposed that liver dysfunction may occur as a consequence of hemodynamic alterations caused by cardiac failure and/or by mechanic ventilation, resulting in vascular pathology, endotheliitis and coagulopathy

Summary

Introduction

SARS-CoV-2 causes a wide spectrum of illness ranging from mild symptoms to severe presentation, and death. COVID-19 causes pneumonia; clinical and epidemiological studies have established that COVID-19 presents as a spectrum of clinical manifestations [1,2], and studies performed on whole-body autopsies in patients who died of COVID-19 revealed that SARS-CoV-2 infection causes significant alterations in most body organs [3]. In patients with COVID-19, symptoms of gastrointestinal and hepatic involvement have been progressively recognized [4]. The incidence of hepatic injury ranges from 14.8% to 53%, but in severe COVID-19 patients the incidence of liver injury may increase to 58–78% [5,6]. The exact cause of liver injury has not yet been clarified [7]

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