LAUSR

Simple Summary A novel coronavirus that causes a worldwide pandemic poses a significant threat to patients. The virus can induce not only a cytokine storm and thrombosis but also various extra-respiratory diseases such as liver dysfunction, strong headaches, loss of smell and even psychiatric disorders. However, information on whether SARS-CoV-2 can infect liver or brain tissues is still contradictory. Here, we show that the coronavirus efficiently infects liver cancer cells but does not replicate in non-tumor hepatocyte-like cells. SARS-CoV-2 was also found to infect some glioblastoma cells, which is the most common type of brain tumor. In conclusion, we show that SARS-CoV-2 can infect tumor tissues. Abstract Severe acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 and rapidly caused a pandemic that led to the death of >6 million people due to hypercoagulation and cytokine storm. In addition, SARS-CoV-2 triggers a wide array of pathologies, including liver dysfunction and neurological disorders. It remains unclear if these events are due to direct infection of the respective tissues or result from systemic inflammation. Here, we explored the possible infection of hepatic and CNS cell lines by SARS-CoV-2. We show that even moderate expression levels of the angiotensin-converting enzyme 2 (ACE2) are sufficient for productive infection. SARS-CoV-2 infects hepatoma Huh7.5 and HepG2 cells but not non-transformed liver progenitor or hepatocyte/cholangiocyte-like HepaRG cells. However, exposure to the virus causes partial dedifferentiation of HepaRG cells. SARS-CoV-2 can also establish efficient replication in some low-passage, high-grade glioblastoma cell lines. In contrast, embryonal primary astrocytes or neuroblastoma cells did not support replication of the virus. Glioblastoma cell permissiveness is associated with defects in interferon production. Overall, these results suggest that liver dysfunction during COVID-19 is not due to infection of these tissues by SARS-CoV-2. Furthermore, tumors may potentially serve as reservoirs for the virus during infection.