Implications of liver injury in risk-stratification and management of patients with COVID-19.

BACKGROUND: Infection with SARS-CoV-2 has been associated with liver dysfunction, aggravation of liver burden, and liver injury. This study aimed to assess the effects of liver injuries on the clinical outcomes of patients with COVID-19. METHODS: A total of 1520 patients with severe or critical COVID-19 from Huoshenshan Hospital, Wuhan, were enrolled. Chronic liver disease (CLD) was confirmed by consensus diagnostic criteria. Laboratory test results were compared between different groups. scRNA-seq data and bulk gene expression profiles were used to identify cell types associated with liver injury. RESULTS: A total of 10.98% of patients with severe or critical COVID-19 developed liver injury after admission that was associated with significantly higher rates of mortality (21.74%, p < 0.001) and intensive care unit admission (26.71%, p < 0.001). Pre-existing CLDs were not associated with a higher risk. However, fatty liver disease and cirrhosis were associated with higher risks, supported by evidences from single cell and bulk transcriptome analysis that showed more TMPRSS2+ cells in these tissues. By generating a model, we were able to predict the risk and severity of liver injury during hospitalization. CONCLUSION: We demonstrate that liver injury occurring during therapy as well as pre-existing CLDs like fatty liver disease and cirrhosis in patients with COVID-19 is significantly associated with the severity of disease and mortality, but the presence of other CLD is not associated. We provide a risk-score model that can predict whether patients with COVID-19 will develop liver injury or proceed to higher-risk stages during subsequent hospitalizations.