Zhifei Zeng ’23
COVID-19, which has ravaged the world, is still a public health concern and there are multiple theories about the cause of severe COVID-19 infection in young people. Previous research on genetic factors associated with severe COVID-19 has been limited to the gene pool of European populations. Coincidentally, while comparing the gene pools of Japanese and European patients, a large Japanese genetic research group inadvertently identified a gene that is prevalent in Asian populations and highly associated with severe COVID-19 in young people.
The researchers used genetic data on COVID-19 patients recruited from more than 100 hospitals in Japan during the initial phase of COVID, including patients with severe cases requiring oxygen support, artificial respiration, and/or intensive care units, as well as patients with less severe cases. All patients were younger than 65 years of age, classified as young adults with a low risk of severe COVID-19. The researchers extracted RNA from the patients’ blood and performed RNA sequencing to determine the expression levels of different genes. Then, by comparing the expression levels of different genes in patients with severe disease, patients with mild disease, and healthy people in different cell types, the researchers found that the expression of a gene called dedicator of cytokinesis 2 (DOCK2) was suppressed in patients with severe COVID pneumonia. To further confirm the association between low expression of DOCK2 and severe COVID-19, the researchers also analyzed lung tissue from people who died from COVID-19 and found that the expression of this gene was also suppressed in immune cells in the lungs. The researchers also used a Syrian hamster model with suppressed DOCK2 gene expression to determine this gene suppression led to dysregulation of the immune system, leading to worsening of COVID pneumonia. Finally, the researchers compared frequency data from European populations as well as non-Japanese Asian populations and found that the frequency of this mutation was highest in the Japanese population (p < 0.005).
This study identifies a genetic association between DOCK2 deficiency and severe COVID-19 and highlights the possibility that DOCK2 deficiency may lead to a higher probability of severe COVID-19 infection in young Asians, particularly in Japan. This study reminds us that public health policies for pandemics should be based on genetic studies in ethnically diverse and age-diverse populations to better identify biomarkers and treatment strategies for different populations.
 H. Namkoong, et al., DOCK2 is involved in the host genetics and biology of severe COVID-19. Nature 609 (2022). https://doi.org/10.1038/s41586-022-05163-5
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