Researchers are cultivating organoids in the laboratory to study the infectivity of SARS-CoV-2 on human organs and the effects of drugs. Previous autopsy results have shown that SARS-CoV-2 can have destructive effects on organs. However, it is still unclear whether this damage is directly caused by the virus or by secondary complications resulting from the infection. Since the outbreak of the pandemic, multiple groups have been using organoids to study which tissues and cells the virus can infect and what damage it causes. While using cell lines or animal cells to study viruses is a commonly used method, it does not accurately simulate the real infection situation of SARS-CoV-2 in vivo. Both Thomas Efferth, a cell biologist at the University of Mainz, and Núria Montserrat, a stem cell biologist at the Catalan Institute of Bioengineering, emphasize the advantages of organoids, which are their extremely similar appearance to real tissues, low cost, and lack of ethical issues.
Human intestinal organoid infected with SARS-CoV-2 (white). Image source: Joep Beumer / Clevers group / Hubrecht Institute
As early as March, Zhao Bing and other members of Professor Lin Xinhua's team at Fudan University published the first study on human-derived organoids after the outbreak of the pandemic. They found that SARS-CoV-2 can directly attack the liver and cause liver damage by infecting biliary epithelial cells, downregulating the expression of genes related to cell tight junctions and bile acid transport in biliary tissues. This study was later published in Protein & Cell [1]. (For more details, please click on BioArt: Protein & Cell | Human-derived Organoids Confirm SARS-CoV-2 Infection and Damage to Biliary Tissues)
Human liver-biliary organoid infected with SARS-CoV-2. Photo source: ZHAO Bing
SARS-CoV-2 has the greatest impact on cells in the respiratory system. Kazuo Takayama, a stem cell biologist at Kyoto University in Japan, developed bronchial organoids and found that the virus mainly infects basal cells [2]. CHEN Shuibing, a stem cell biologist at Cornell Medical Center, used organoids to discover that pancreatic cells, liver cells, cardiomyocytes, and dopamine neurons are susceptible to SARS-CoV-2 [3]. (For more details, please click on BioArt: Cell Stem Cell | CHEN Shuibing et al. First Demonstrate that Human Pancreatic Alpha and Beta Cells Can Be Infected by SARS-CoV-2) In addition, Chen also cultured lung-like organoids and found that cells died after being infected with SARS-CoV-2, and the virus induced cells to produce chemokines and cytokines, triggering a massive immune response, also known as a cytokine storm. However, Chen believes that the mechanism of lung cell death in patients is still unclear. Although organoids can generate many cell types, they are not very mature and therefore not representative. She is now studying lung-like organoids of immune cell types [4].
SARS-CoV-2 can spread from the lungs to other organs. Montserrat's research shows that SARS-CoV-2 can infect vascular endothelial cells, and then virus particles leak into the bloodstream and circulate in the body [5]. Pathological reports of vascular damage in COVID-19 patients also support this view [6]. In addition, the virus can also infect intestinal cells [7]. (For more details, please click on BioArt: Nat Med | SARS-CoV-2 Can Infect Intestinal Organoids of Humans and Bats; Science | SARS-CoV-2 Efficiently Infects Human Small Intestinal Enterocytes)
Chen is also using organoids to screen potential drugs and found that the cancer drug imatinib can inhibit SARS-CoV-2 in lung organoids [4]. (For more details, please click on BioArtReports: High-Throughput Screening of SARS-CoV-2 Candidate Drugs Using Lung Organoid Models) Several clinical trials of this drug as a treatment for COVID-19 have been initiated. Other research groups are also testing the effects of existing drugs in the body against coronaviruses and have achieved some success [2, 8], but there is still a long way to go in the future.
