On November 10, 2020, Shenzhen Third People’s Hospital and BGI Research published a titled “Initial whole-genome sequencing and analysis of the host genetic” in the internationally renowned academic journal “Cell Discovery”. The research results of "contribution to COVID-19 severity and susceptibility" found that the severity of COVID-19 symptoms is related to the patient’s own genetic factors, which provides a reference for understanding the mechanism of COVID-19 and scientific prevention and control of the COVID-19 epidemic. 

Article link: https://www.nature.com/articles/s41421-020-00231-4 

The novel coronavirus pneumonia (COVID-19) caused by the SARS-CoV-2 virus is pandemic worldwide. As of November 9, 2020, there have been more than 50.1 million infections and 1.25 million deaths worldwide. According to reports, the symptoms of different individuals after being infected with the new coronavirus (SARS-CoV-2) are quite different. About 80-85% of the infected people are asymptomatic or mild, and 15-20% of the patients suffer from severe symptoms, critical illness, or even death. In addition to known high-risk factors such as age, gender, and complications, the patient's own genetic background is also an important factor affecting the severity of symptoms.

Since the outbreak, a number of studies on the genetic background and immune response, severity, and susceptibility of COVID-19 patients have been carried out in different countries. Among them, a recent twin study in the United Kingdom showed that the clinical manifestations and susceptibility of patients with COVID-19 are strongly affected by genetic factors [1]; studies in Spain and Italy have found loci that are significantly associated with severe illness on chromosomes 3 and 9 [2], the relevant region on chromosome 3 may be related to the extinct Neanderthals [3]; statistical analysis based on clinical data of the Chinese population has shown that there is a difference in the proportion of ABO blood types between COVID-19 patients and normal people [4], which indirectly suggests the influence of genetic factors on symptoms.

The joint research team of this project explored the influence of the Chinese population's genetic background on the severity and susceptibility of COVID-19 symptoms based on MGI's autonomous and controllable gene sequencing technology (DNBSEQTM technology). The research team recruited 332 patients with COVID-19 with nucleic acid positive but manifested as asymptomatic, mild, normal, severe, and critical. Through in-depth sequencing and analysis of patients and natural control populations, it was discovered that the specific haplotype of the human leukocyte antigen region (HLA) located on chromosome 6, and the lack of gene functions such as GOLGA3 and DPP7 would increase the risk of severe new coronary disease. In addition, although epidemiological studies have shown that Chinese and European populations of COVID-19 patients have a similar symptom distribution ratio, the chromosome 3 related gene polymorphism site rs11385942, which is significantly associated with severe illness, has been found in the patients in this study. The frequency in the population is 0, and the frequency in other Chinese population databases such as ChinaMAP [5] is also extremely low. The associated signals cannot be repeated, suggesting that people with different genetic backgrounds may have different symptoms after infection, and further research and comparison are needed.

The release of the research results will strongly promote the basic scientific research related to the COVID-19. The genetic background differences found will provide guidance for researchers to further understand the COVID-19 virus and its interaction mechanism with the human body, thereby providing a reference for scientific prevention and control of the COVID-19 pneumonia epidemic.

“This is the first study analysis host genetics of COVID-19 in Chinese population. We identified some of the alleles in HLA region significantly predispose the worst outcome of COVID-19 patients.” Said Dr. Xin JIN, Director of the Institute of Precision Heath at BGI Research, “The discovery may help guide targeted efforts in containing the outbreak.”

Dr. Xin JIN, and Dr. Siyang LIU, Researcher at BGI Research are the co-corresponding authors of the paper. The project was supported by the Shenzhen National Gene Bank.

Reference materials:

[1] Williams, F. M. et al. Self-reported symptoms of covid-19 including symptoms most predictive of SARS-CoV-2 infection, are heritable. medRxiv https://doi.org/10.1101/2020.04.22.20072124 (2020).

[2] Ellinghaus, D.et al. Genomewide Association Study of Severe Covid-19 with Respiratory Failure. N. Engl. J. Med. (2020). doi:10.1056/NEJMoa2020283

[3] Zeberg, H., Pääbo, S. The major genetic risk factor for severe COVID-19 is inherited from Neanderthals. Nature (2020).

[4] Wu, Y., Feng, Z., Li, P. & Yu, Q. Relationship between ABO blood group distribution and clinical characteristics in patients with COVID-19. Clin. Chim. Acta (2020). doi:10.1016/j.cca.2020.06.026

[5] Cao, Yanan, et al. The ChinaMAP analytics of deep whole genome sequences in 10,588 individuals. Cell Research (2020).<span style="color:#555555;font-family:;" "="">