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.

COVID-19 infection and body weight: A deleterious liaison in a J-curve relationship

“… 11 Interestingly, metabolic dysfunction-associated fatty liver disease has been suggested as a surrogate for COVID-19 severity due to the accumulation of associated metabolic changes, representing a higher risk than obesity per se for COVID-19 severity. 81

Fig. 1 The schema illustrates the pathogenetic mechanisms involved in the interplay between obesity and COVID-19 infection (see text for discussion).

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COVID‐19, adaptative immune response and metabolic‐associated liver disease

“…40 Therefore, MAFLD subjects should be classified as high risk for COVID-19, intensifying preventive measurements, and prioritized for vaccination. 48 In fact, the COVID-19 vaccine appears to give a good immunogenicity in patients with NAFLD, with titres of neutralizing antibodies that persisted over time. This suggests that the pathogenicity of infiltrating macrophages may extend beyond the promotion of acute inflammation, which is also in line with the fibrotic complications observed in patients undergoing mechanical ventilation.…”

“…Therefore, MAFLD subjects should be classified as high risk for COVID‐19, intensifying preventive measurements, and prioritized for vaccination 48 . In fact, the COVID‐19 vaccine appears to give a good immunogenicity in patients with NAFLD, with titres of neutralizing antibodies that persisted over time 49 …”

“…Moreover, the presence of NASH is associated with a low‐grade inflammatory status involving cytokines, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress and Nod‐like receptor protein 3 (NLRP3) inflammasome activation 47 . Thus, NASH in COVID‐19 patients could boost the virus‐induced cytokine storm syndrome (CSS), 48 through the hepatic release of multiple inflammatory mediators, contributing to severe COVID‐19. The liver contains the largest number of macrophages, which are a powerful cytokine producer.…”

Interaction of metabolic dysfunction‐associated fatty liver disease and nonalcoholic fatty liver disease with advanced fibrosis in the death and intubation of patients hospitalized with coronavirus disease 2019

“…[ 7 , 8 ] MAFLD is characterized by “low‐grade chronic inflammation with endothelial dysfunction, changes in the function of monocytes, and altered antigen presentation.” In the case of COVID‐19, mechanisms involved in acute inflammation could overlap with the proinflammatory state of MAFLD, occasioning immune system dysregulation with excessive release of proinflammatory mediators (cytokine storm [CS]) that could increase the probability of organ damage or even multiple organ failure. [ 8 , 9 ]…”