Elucidation of the liver pathophysiology of COVID-19 patients using liver-on-a-chips

• Published in: PNAS nexus Vol. 2; no. 3; p. pgad029
• Main Authors: Deguchi, Sayaka, Kosugi, Kaori, Hashimoto, Rina, Sakamoto, Ayaka, Yamamoto, Masaki, Krol, Rafal P, Gee, Peter, Negoro, Ryosuke, Noda, Takeshi, Yamamoto, Takuya, Torisawa, Yu-Suke, Nagao, Miki, Takayama, Kazuo
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-03-2023
• Subjects: Analysis; Biological, Health, and Medical Sciences; Development and progression; Health aspects; Liver diseases; Microfluidics; Risk factors; RNA; Scientific equipment and supplies industry; Tissue culture; Japan; United States; COVID-19; SARS-CoV-2; Remdesivir; Baricitinib; liver-on-a-chip; organs-on-a-chip
• ISSN: 2752-6542; 2752-6542
• DOI: 10.1093/pnasnexus/pgad029

SARS-CoV-2 induces severe organ damage not only in the lung but also in the liver, heart, kidney, and intestine. It is known that COVID-19 severity correlates with liver dysfunction, but few studies have investigated the liver pathophysiology in COVID-19 patients. Here, we elucidated liver pathophysiology in COVID-19 patients using organs-on-a-chip technology and clinical analyses. First, we developed liver-on-a-chip (LoC) which recapitulating hepatic functions around the intrahepatic bile duct and blood vessel. We found that hepatic dysfunctions, but not hepatobiliary diseases, were strongly induced by SARS-CoV-2 infection. Next, we evaluated the therapeutic effects of COVID-19 drugs to inhibit viral replication and recover hepatic dysfunctions, and found that the combination of anti-viral and immunosuppressive drugs (Remdesivir and Baricitinib) is effective to treat hepatic dysfunctions caused by SARS-CoV-2 infection. Finally, we analyzed the sera obtained from COVID-19 patients, and revealed that COVID-19 patients, who were positive for serum viral RNA, are likely to become severe and develop hepatic dysfunctions, as compared with COVID-19 patients who were negative for serum viral RNA. We succeeded in modeling the liver pathophysiology of COVID-19 patients using LoC technology and clinical samples.