Weber, Florian and Pavel, Vlad and Mueller, Martina and Boor, Peter and Laber, Lea and von Stillfried, Saskia and Buechler, Christa (2025) Profiles of PCSK9, SREBP-2, and histopathology in COVID-19 and non-COVID-19 critical illness. BMC INFECTIOUS DISEASES, 25 (1): 1573. ISSN , 1471-2334
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Background Severe illness caused by SARS-CoV-2 infection is associated with dysregulated cholesterol homeostasis. Proprotein convertase subtilisin/kexin type 9 (PCSK9), which regulates serum cholesterol levels, is induced in the plasma of patients with severe SARS-CoV-2 infection, compared to critically ill patients with other conditions. PCSK9 is primarily expressed in the liver, which is susceptible to damage during severe illness. Sterol regulatory element-binding protein 2 (SREBP-2) regulates PCSK9 expression, and higher activity of both PCSK9 and SREBP-2 is associated with liver injury and inflammation.<br /> Methods Liver tissues from 20 COVID-19 and 20 pre-pandemic autopsy cases were analysed, matched for age, sex, and intensive care treatment. Hepatic PCSK9 and SREBP-2 protein levels were assessed via immunohistochemistry. Histological scores for steatosis, fibrosis, and cholestasis were recorded. Additionally, plasma SREBP-2 levels were measured by ELISA in 25 septic COVID-19 and 34 septic non-COVID-19 patients.<br /> Results Across all cases, hepatocellular PCSK9 protein level was increased in the presence of cholestasis and positively correlated with hepatic SREBP-2 expression. No significant differences were observed between the COVID-19 and control groups regarding liver histology or hepatic PCSK9 and SREBP-2 protein levels. Plasma SREBP-2 levels were similar between COVID-19 and non-COVID-19 septic patients. Correlation analysis revealed positive associations between plasma SREBP-2, plasma PCSK9, and cholesteryl ester levels in the entire cohort, suggesting preserved SREBP-2 function during critical illness. Laboratory measures of liver disease in patients with and without SARS-CoV-2 infection were similar.<br /> Conclusion Critically ill patients with and without SARS-CoV-2 infection exhibit comparable hepatic expression of PCSK9 and SREBP-2, as well as similar liver histology and comparable levels of aminotransferases, bilirubin, and gamma-glutamyl transferase, which suggests that SARS-CoV-2 does not directly cause liver injury. As our cohort was small, this suggestion needs to be confirmed by studying larger groups.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INTERNATIONAL CONSENSUS DEFINITIONS; LIVER; SEPSIS; CHOLESTEROL; DISEASE; DYSFUNCTION; EXPRESSION; SARS-CoV-2; Sepsis; PCSK9; SREBP-2; Cholestasis |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Jun 2026 09:05 |
| Last Modified: | 09 Jun 2026 09:05 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65943 |
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