Anthropometric data of both groups were comparable except for nominally higher percentage of females and higher high-density lipoprotein-cholesterol in the COVID-neg group (table 1).

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Participants’ characteristics at baseline

None of the participants of the COVID-pos group had severe COVID-19 according to the classification by the WHO, that is, none was hospitalized or had impaired pulmonary function defined by oxygenation <90% during the infection.20 The interval between PCR-confirmed COVID-19 diagnosis and follow-up visits was 12±2 months (range 7–14 months).

At the baseline visit, HL-PDFF values were comparable between both groups (COVID-neg 8% (95% CI 5%, 14%), COVID-pos 5% (95% CI 3%, 9%)). At follow-up, HL-PDFF slightly decreased in COVID-neg (relative decrease: −4%), but increased in COVID-pos (relative increase: +80%). Thus, COVID-19 resulted in a relative increase in HL-PDFF of 56% (95% CI 18%, 106%; p=0.04), corrected for the time course in the absence of COVID-19 (figure 2A). No such difference was found for the surrogate steatosis index FLI (2.3 (4.5, 9.1); p=0.24).

(A) Effect of history of COVID-19 on HL-PDFF. (B) Prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) in the studied groups based on HL-PDFF measurements. Unadjusted values of HL-PDFF are shown as mean±SD. *P≤0.05, indicating significance level for effect of COVID-19, corrected for the time course in the absence of COVID-19, based on analysis of covariance (ANCOVA) with adjustment for changes in body mass index (BMI), the time interval between the baseline and the follow-up visits, and the baseline value of the respective parameter. BL, baseline; FU, follow-up; HL-PDFF, hepatic lipid content measured as proton density fat fraction; ns, non-significant.

MRE-based hepatic stiffness (−0.11 kPa (−0.44, 0.23); p=0.43) as well as surrogate indices of liver fibrosis risk FIB-4 (−0.14 (−0.46, 0.19); p=0.10), APRI (−0.06 (−0.19, 0.06); p=0.14), NAFLD score (−0.52 (−0.89, –0.17); p=0.18) and Forns index (−0.10 (−0.54, 0.35); p=0.95) did not change in the COVID-pos group, when corrected for the time course in the absence of COVID-19. Similarly, no change in liver volume (−13 cm3 (−180, 154); p=0.22) and the surrogate of hepatic iron content, T2* (−0.41 ms (−1.94, 1.12); p=0.34), was detected for the COVID-pos group, when corrected for the time course in the absence of COVID-19.

Also, absolute concentrations of hepatic γATP and Pi remained unaffected by COVID-19 (ATP: 0.08 mmol/L (−0.87, 1.02); p=0.40 and Pi: −0.31 mmol/L (−0.99, 0.36); p=0.39, respectively).

To investigate the impact of MASLD at the baseline visit of the current study, the COVID-neg and COVID-pos groups were stratified into participants with and without MASLD, and the interaction term of COVID-19 history and MASLD status (yes/no) was added to the model. MASLD, as defined by HL-PDFF ≥5%, was present in 79% COVID-neg and in 58% COVID-pos participants at baseline. However, at the follow-up visit the proportion of participants with MASLD increased to 77% in the COVID-pos group, while it decreased in the COVID-neg group to 71%, and the interaction between a history of COVID-19 and MASLD status has reached statistical significance (p=0.05) (figure 2B).

HOMA-IR decreased in both groups from baseline to follow-up (relative reduction: COVID-neg –33%, COVID-pos –19%) to a similar extent; therefore, there was no effect of COVID-19, as there was no change in the COVID-pos group, when corrected for the time course in the absence of COVID-19 (−19% (−42, 13); p=0.49). HOMA-B similarly increased in both groups at follow-up (relative increase COVID-neg 8%, COVID-pos 4%); therefore, again, no changes in COVID-pos individuals were detected, when corrected for the time course in the absence of COVID-19 (4% (−25, 43); p=0.86).

COVID-19 did not result in changes when corrected for the time course in the absence of COVID-19 in WBF (−2 cm3 (−1814, 1809); p=0.21), SAT (148 cm3 (−1339, 1635); p=0.45) and VAT (61 cm3 (−695, 816); p=0.41) compartments. The same holds true for IMCL (−0.03 (−0.2, 0.1); p=0.47).