Biliary injury in patients with severe COVID-19 is most likely not caused by direct viral damage

Introduction Infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has developed into a pandemic with millions of infected people worldwide. Although an elevation of liver enzymes has often been observed especially in severe cases, we were able to document the first case of secondary sclerosing cholangitis (SSC) after coronavirus disease 2019 (COVID-19). The correlation between hepatobiliary injury and the infection is not fully understood yet.

Methods A patient was diagnosed with SSC by MRCP, ERCP and liver histopathology. COVID-19 RNA was detected by PCR-analysis of the patient’s nasal/throat swabs, tracheal fluid and stool samples. Post-mortem tissue as well as swab-material of liver, bile ducts, gallbladder, duodenum and lung samples of people deceased after SARS-CoV-2 were analyzed for COVID-19 viral load.

Results We are describing the world’s first case of secondary sclerosing cholangitis (SSC) following severe acute respiratory distress syndrome due to COVID-19 confirmed by liver imaging and histopathology. Most likely causes of SSC in this patient include direct viral damage to the biliary epithelium, drug toxicity and immune-mediated- or hypoxia-associated cell injury. To investigate the role of direct viral damage to the biliary epithelium, we were measuring COVID-19 levels in the patient”s stool sample as well as COVID-19 levels in bile and duodenum of five patients deceased after severe COVID-19 infection and in one patient undergoing cholecystectomy and ERC for acute cholecystitis with choledocholithiasis during infection with SARS-CoV-2.

Our index patient tested positive for COVID-19 RNA in a stool sample. However, we were not able to find viral RNA in biliary tissue or bile samples from deceased or cholecystectomized SARS-CoV-2 positive patients, so that we were not able to find direct proof for viral replication of COVID-19 in biliary cells in vivo. While direct biliary damage in our patient with SSC due to COVID-19 cannot be ruled out, histopathological findings of the liver are most consistent with SSC in the critically ill caused by hypoxia.

Conclusion In conclusion, we investigated the first case of SSC in a patient after severe COVID-19 infection emphasizing the importance of follow-up care to recovered patients to determine the full complexity of its long-term effects.

Publication History

Article published online:
04 January 2021