Last year, a new coronavirus (SARS-CoV-2) struck countries around the world. More than 1.9 million deaths have been reported worldwide in just a year since the first known fatality. With the increase in the COVID-19 death toll, cytokine storms have emerged as an issue. A cytokine storm is the phenomenon of excessive release of immune signaling molecules known as cytokines in reaction to viral infections, where the cytokines cause hyperinflammation and injure hosts. Some patients infected with COVID-19 develop severe conditions, and certain cases that result in death have been traced to the cytokine
storm. However, the specific cause of the cytokine storm remains unknown, making the treatment of severe COVID-19 patients highly challenging.

The joint research team led by Professor Eui-Cheol Shin has come under the spotlight by discovering the cause behind hyperinflammatory responses observed in severe COVID-19 patients. The team applied the latest research techniques to patients’ blood samples, and succeeded in identifying the cause behind hyperinflammatory responses.


Interferons found to cause hyperinflammatory responses

The joint research team led by Professor Eui-Cheol Shin separated immune cells from the blood samples of patients with mild and severe COVID-19, and employed single-cell RNA sequencing to analyze their properties. Detailed observations of each cell revealed that inflammatory cytokines and
interleukin-1 (IL-1) were present in the immune cells of both mild and severe COVID-19 patients. Through a comparative analysis of mild and severe cases, the team found that type I interferon, a cytokine response, was exhibited in the latter group only. Interferons are cytokines synthesized and released
during viral infections. Previously, interferons were considered beneficial due to their antiviral activity, but the team proved that interferon response can be a cause of hyperinflammation in COVID-19 patients.

While non-specific anti-inflammatory drugs such as steroids are being used to alleviate hyperinflammatory symptoms in severe COVID-19 patients, the team has paved the way for new treatments with interferons as a target.

Working weekends for three months to “lay the basis for COVID-19 treatment strategies”

According to Professor Eui-Cheol Shin, the significance of the study lies in laying the basis for the development of effective treatment strategies. He said, “Interferons were previously known as beneficial cytokines for their antiviral effects, but our study showed that interferon response can, on the contrary,
lead to hyperinflammation in COVID-19 patients.”

The study was given a short time frame to urgently address medical issues of severe COVID-19 patients, and the results were obtained in just three months. The team plans to continue research on immune mechanisms and individual patientspecific anti-inflammatory drugs to improve the survival rate
of COVID-19.

Conducted jointly with the research team led by Professor Inkyung Jung of the Department of Biological Sciences at KAIST, Asan Medical Center, Severance Hospital, and Professor Hyewon Jeong of Chungbuk National University Hospital, the study was published in the international journal Science Immunology on July 10, 2020.

Prof. Eui-Cheol Shin
2020 KI Annual Report