No Underlying Conditions but Severe? ... Another Secret of COVID-19 [Reading Science]

KAIST Identifies Cause Through Industry-Academia-Research Collaboration
Clonal Hematopoiesis in Carriers of Specific Genomic Variants
Excessive Inflammatory Response Leads to Severe COVID-19 Infection

On the 17th, medical staff are caring for COVID-19 patients at Seoul Metropolitan Seobuk Hospital in Eunpyeong-gu, Seoul. According to the Korea Disease Control and Prevention Agency's Central Disaster and Safety Countermeasure Headquarters, as of midnight on the same day, the number of new COVID-19 cases reached 621,328, entering the 600,000 range for the first time. The number of critically ill patients was 1,159, down 85 from the previous day (1,244). The number of deaths was 429, marking the first time it reached the 400 range. Photo by Moon Honam munonam@

[Asia Economy Reporter Kim Bong-su] Some people without underlying conditions suffer severe symptoms or even die when infected with COVID-19. A domestic research team revealed that this phenomenon occurs when clonal hematopoiesis is present due to specific genes.

The Korea Advanced Institute of Science and Technology (KAIST) announced on the 29th that Professor Jeong In-kyung's research team in the Department of Biological Sciences, through industry-academia-research collaboration, discovered new risk factors for severe COVID-19 in low-risk groups without underlying diseases and proposed the molecular mechanism of excessive inflammatory responses caused by the identified factors.

The COVID-19 virus (SARS-CoV-2) has spread worldwide for over two years, infecting more than 600 million people globally, with over 6 million deaths. Due to this severity, research on the pathology of the COVID-19 virus has been actively conducted, revealing mechanisms of severe progression caused by excessive inflammatory responses of monocytes (large white blood cells).

However, the significant variation in immune responses among individual COVID-19 patients cannot be fully explained by previous research findings. For example, many severe COVID-19 patients do not have underlying conditions such as diabetes or hypertension, making it crucial to identify new risk factors that can lead to severe progression upon COVID-19 infection for personalized treatment.

To identify factors causing severe COVID-19 in patients without underlying conditions, the research team collaborated with four domestic hospitals to collect and analyze clinical data from a total of 243 COVID-19 patients. As a result, it was confirmed that severe patients within the group without underlying conditions exhibited the characteristic of 'clonal hematopoiesis.' This refers to a group with acquired genetic mutations in bone marrow stem cells that form blood and immune cells. Furthermore, single-cell gene expression analysis confirmed that severe patients with clonal hematopoiesis showed a specific excessive inflammatory response in monocytes. It was revealed that epigenetic changes caused by clonal hematopoiesis induce gene expression that triggers monocyte-specific excessive inflammatory responses.

Although overseas research groups have similarly focused on the relationship between clonal hematopoiesis and COVID-19, they have not clearly established the connection nor proposed a molecular model leading to excessive inflammatory responses. The research team applied a bioinformatics-based stratified patient classification method and single-cell omics biology techniques, which allow analysis of gene expression patterns and regulatory mechanisms at the single-cell level in various patient-derived immune cells, to clearly demonstrate that clonal hematopoiesis is a new risk factor for severe COVID-19.

The research team explained, "This means that even low-risk patients without underlying diseases require more systematic treatment and management if they have clonal hematopoiesis when infected with COVID-19."

The research results were published online on the 15th in the international journal Haematologica (IF=11.04). Earlier, on the 1st of last month, the study was approved for publication in Experimental & Molecular Medicine (IF=11.590).

Choi Baek-gyu, a KAIST integrated master's and doctoral course student who conducted the study, said, "The fusion of the latest molecular experimental techniques, such as single-cell omics experiments, and bioinformatics analysis technology enabled the identification of subtypes of new severe COVID-19 patients and related gene regulatory mechanisms." He added, "We will apply bio-data-based fusion research methods to other diseases as well."