Coronavirus disease 2019 severity in obesity: Metabolic dysfunction-associated fatty liver disease in the spotlight

Abstract

The coronavirus disease 2019 (COVID-19) outbreak has drawn the scientific community's attention to pre-existing metabolic conditions that could aggravate the infection, causing extended viral shedding, prolonged hospitalization, and high death rates. Metabolic dysfunction-associated fatty liver disease (MAFLD) emerges as a surrogate for COVID-19 severity due to the constellation of metabolic alterations it entails. This review outlines the impact MAFLD exerts on COVID-19 severity in obese subjects, besides the possible mechanistic links to the poor outcomes. The data collected showed that MAFLD patients had poorer COVID-19 outcomes than non-MAFLD obese subjects. MAFLD is generally accompanied by impaired glycemic control and systemic arterial hypertension, both of which can decompensate during the COVID-19 clinical course. Also, MAFLD subjects had higher plasma inflammatory marker concentrations than non-MAFLD subjects, which might be related to an intensified cytokine storm syndrome frequently associated with the need for mechanical ventilation and death. In conclusion, MAFLD represents a higher risk than obesity for COVID-19 severity, resulting in poor outcomes and even progression to non-alcoholic steatohepatitis. Hepatologists should include MAFLD subjects in the high-risk group, intensify preventive measurements, and prioritize their vaccination.

Keywords: COVID-19; Cytokine storm syndrome; Metabolic dysfunction-associated fatty liver disease; Obesity; Severity.

Figure 1

Most common infection and propagation pathways of severe acute respiratory syndrome coronavirus 2 in the human body. SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; ACE2: Angiotensin-converting enzyme 2.

Figure 2

Clinical features and hepatological changes due to severe acute respiratory syndrome coronavirus 2 infection (upper panel) and hepatotoxic effects of some drugs used as an attempt to treat coronavirus disease 2019 (lower panel). SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; AST: Aspartate aminotransferase.

Figure 3

Mild symptoms, inflammatory markers, and serious developments of coronavirus disease 2019. ALT: Alanine aminotransferase; CRP: C reactive protein; ICU: Intensive care unit.

Figure 4

Graphical abstract. Metabolic dysfunction-associated fatty liver disease (MAFLD) patients usually show a constellation of metabolic impairments that include altered adipokine profile, glucolipotoxicity with ectopic lipid accumulation, and gut dysbiosis, besides a genetic background that favors these hepatic alterations and pre-existing mechanical lung dysfunction when obese. These clinical conditions before coronavirus disease 2019 (COVID-19) infection can aggravate the cytokine storm syndrome, with activation of macrophages that reside in the liver (Kupffer cells), resulting in inflammasome activation and cell death by pyroptosis. MAFLD patients are at high risk of complications and severe COVID-19 clinical course, with frequent mechanical ventilation, prolonged hospitalizations, and extended viral shedding. Upon survival, COVID-19 may act as a surrogate for MAFLD-non-alcoholic steatohepatitis progression, and hepatocellular hypoxia seems to underlie this process. ACE2: Angiotensin-converting enzyme 2; FFA: Free Fatty Acid; IL: Interleukin; MAFLD: Metabolic dysfunction-associated fatty liver disease; MCP1: Monocyte chemoattractant protein 1; NASH: Non-alcoholic steatohepatitis; NEFAs: Non-esterified fatty acids; NLRP: NLR family pyrin domain-containing; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; SCFA: Short-chain fatty acid; TNF-α: Tumor necrosis factor.