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Dec. 13, 2021

Factors leading to serious breakout COVID-19 infections

Masato Kubo, Team Leader

Image of Masato Kubo

Laboratory for Cytokine Regulation, Center for Integrative Medical Science

Can you give us an overview of your research project?

Most people who are infected with CoV-2 after being vaccinated are asymptomatic or mildly ill, but some people become seriously ill and die. However, it is not well known which people become seriously ill and in what cases. The symptoms of COVID-19 are determined by a conflict between tissue damage caused by viral replication and viral elimination by the immune responses. We are conducting research to understand how the human immune system reacts and responds to cells infected with CoV-2.

Why did you decide to launch this project?

Studying how the human immune system reacts and responds to cells infected with CoV-2 is essential for understanding the mechanisms of severe disease. However, it is difficult to trace the behavior and function of immune cells in the lungs of infected patients. The RIKEN Center for Integrative Medical Sciences has developed a humanized mouse with human immune cells and has used it for research on influenza virus infection. Under the recent pandemic of CoV-2, we thought it would be important to apply these technologies to the elucidation of the mechanism of severe COVID-19.

What methods are you using in your research?

Normally, CoV-2 does not infect mice due to the species barrier (coronaviruses infect human alveolar epithelial cells, but not those of mice). Therefore, in collaboration with the Jackson Laboratory in the U.S., we have created a novel humanized mouse system which expresses human CoV-2 receptors and has human immune cells. Using this humanized mice system with a susceptibility to CoV-2, we plan to study how immune cells behave in the lungs, which is the main tissue of infection, and in what cases they are able to overcome CoV-2 infection.

What have you learned so far?

We have found that the gene expression pattern in infected human lung cells is different between mice infected with the wild type strain (Wuhan) and the variant strain that more frequently leads to severe disease. In the future, we will use the humanized mice to verify whether a similar pattern in gene expression leads to severe COVID-19 in vivo.

What challenges do you still need to overcome?

Further studies with clinical samples are needed to verify whether the results obtained in the humanized mice also apply to the mechanism of severe disease in actual COVID-19 patients. We will continue this research in collaboration with hospital facilities.