Risk of severe illness from COVID-19 in patients with metabolic dysfunctionassociated fatty liver disease and increased fibrosis scores A recent study reported that patients with severe COVID-19 were more likely to have non-alcoholic fatty liver disease (NAFLD) compared with those with non-severe COVID-19 illness. 1 However, the prognosis of NAFLD (recently renamed metabolic dysfunction-associated fatty liver disease (MAFLD) 2) is determined by the severity of liver fibrosis. 3 4 We therefore postulated that patients with MAFLD with increased noninvasive liver fibrosis scores are at higher risk of severe illness from COVID-19. We studied 310 patients with laboratoryconfirmed COVID-19 who were consecutively hospitalised at four sites in Zhejiang Province, China, between January and February 2020. Some of these patients (n=150) have been included in a prior study examining the association between obesity and COVID-19 severity. 5 Patients with viral hepatitis, excessive alcohol consumption, chronic pulmonary diseases or active cancers were excluded. Clinical and laboratory data were collected at hospital admission. All patients were screened for hepatic steatosis by computed tomography and subsequently diagnosed as MAFLD. 6 The originally validated cut-points for fibrosis-4 (FIB-4) index and NAFLD fibrosis score (NFS) were used to categorise liver fibrosis probability as low, intermediate or high. 7 COVID-19 severity was classified as severe and non-severe. 8 The study protocol was approved by the local ethics committees of the four hospitals. In our cohort of 310 confirmed cases of COVID-19, 94 (30.3%) patients had MAFLD. As shown in table 1, patients with MAFLD with intermediate or high FIB-4 scores were more likely to be older, obese, have diabetes and have higher NFS, higher liver enzymes, higher C reactive protein, as well as lower levels of lymphocyte count, platelet count, triglycerides and high-density lipoprotein cholesterol compared with their counterparts with low FIB-4 score or those without MAFLD. Notably, the severity

We declare no competing interests.Please refer to the accompanying ICMJE disclosure forms for further details.Authors' contributions DJ, EQ, JX, and DZ treated the patients. DJ, GC, YW and GL processed statistical data and drafted the manuscript. DJ and GL had the idea for and designed the study.

Background and AimCoronavirus disease 2019 (COVID‐19) has attracted increasing worldwide attention. While diabetes is known to aggravate COVID‐19 severity, it is not known whether nondiabetic patients with metabolic dysfunction are also more prone to more severe disease. The association of metabolic associated fatty liver disease (MAFLD) with COVID‐19 severity in nondiabetic patients was investigated here.MethodsThe study cohort comprised 65 patients with (i.e. cases) and 65 patients without MAFLD (i.e. controls). Each case was randomly matched with one control by sex (1:1) and age (±5 years). The association between the presence of MAFLD (as exposure) and COVID‐19 severity (as the outcome) was assessed by binary logistic regression analysis.ResultsIn nondiabetic patients with COVID‐19, the presence of MAFLD was associated with a four‐fold increased risk of severe COVID‐19; the risk increased with increasing numbers of metabolic risk factors. The association with COVID‐19 severity persisted after adjusting for age, sex, and coexisting morbid conditions.ConclusionHealth‐care professionals caring for nondiabetic patients with COVID‐19 should be cognizant of the increased likelihood of severe COVID‐19 in patients with MAFLD.