medRxiv preprint doi: https://doi.org/10.1101/2020.03.11.20031096; this version posted March 27, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Relationship between the ABO Blood Group and the COVID-19 Susceptibility Jiao Zhao1,#, Yan Yang 2,#, Hanping Huang3,#, Dong Li4,#, Dongfeng Gu1, Xiangfeng Lu5, Zheng Zhang2, Lei Liu2, Ting Liu3, Yukun Liu6, Yunjiao He1, Bin Sun1, Meilan Wei1, Guangyu Yang7,* , Xinghuan Wang8,* , Li Zhang3,*, Xiaoyang Zhou4,*, Mingzhao Xing1,*, Peng George Wang1,* 1School of Medicine, The Southern University of Science and Technology, Shenzhen, People’s Republic of China 2National Clinical Research Center for Infectious Diseases, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen Third People's Hospital, Shenzhen, People’s Republic of China 3Infection Disease Department, Wuhan Jinyintan Hospital, Wuhan, China 4Renmin Hospital of Wuhan University, Wuhan 430060, People’s Republic of China 5Department of Epidemiology, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China 6School of Statistics, East China Normal University, Shanghai, People’s Republic of China 7School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, People’s Republic of China 8Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China 1 NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2020.03.11.20031096; this version posted March 27, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. #These authors are considered as equally contributing first authors. *Corresponding authors: Yang ([email protected]); Wang ([email protected]); Zhang ([email protected]); Zhou ([email protected]); Xing ([email protected]); Wang ([email protected]) Running Title: ABO blood group and COVID-19 Key Words: ABO blood group, coronavirus, SARS-CoV-2, COVID-19, disease susceptibility 2 medRxiv preprint doi: https://doi.org/10.1101/2020.03.11.20031096; this version posted March 27, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Abstract: The novel coronavirus disease-2019 (COVID-19) has been spreading around the world rapidly and declared as a pandemic by WHO. Here, we compared the ABO blood group distribution in 2,173 patients with COVID-19 confirmed by SARS-CoV-2 test from three hospitals in Wuhan and Shenzhen, China with that in normal people from the corresponding regions. The results showed that blood group A was associated with a higher risk for acquiring COVID-19 compared with non-A blood groups, whereas blood group O was associated with a lower risk for the infection compared with non-O blood groups. This is the first observation of an association between the ABO blood type and COVID-19. It should be emphasized, however, that this is an early study with limitations. It would be premature to use this study to guide clinical practice at this time, but it should encourage further investigation of the relationship between the ABO blood group and the COVID-19 susceptibility. 3 medRxiv preprint doi: https://doi.org/10.1101/2020.03.11.20031096; this version posted March 27, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. INTRODUCTION The novel coronavirus SARS-CoV-2, causing the new infectious coronavirus disease-2019 (COVID-19), is currently spreading rapidly around the world; it has been recently declared as a pandemic by WHO. Recent clinical observation suggests that patient age, male sex and certain chronic medical conditions (e.g., cardiovascular disease, diabetes, COPD) seem to represent a risk for the infection of SARS-Cov-2 and higher disease severity1. There is currently no biological marker known to predict the susceptibility to COVID-19. Landsteiner’s ABO blood types are carbohydrate epitopes that are present on the surface of human cells. The antigenic determinants of A and B blood groups are trisaccharide moieties GalNAcα1-3-(Fucα1,2)-Galβ- and Galα1-3-(Fucα1,2)-Galβ-, while O blood group antigen is Fucα1,2-Galβ-. While blood types are genetically inherited, the environment factors can potentially influence which blood types in a population will be passed on more frequently to the next generation. Susceptibility of viral infection has been previously found to be related to ABO blood group. For example, Norwalk virus and Hepatitis B have clear blood group susceptibility2,3. It was also reported that blood group O individuals were less likely to become infected by SARS coronavirus4. Here, we investigated the relationship between the ABO blood type and the susceptibility to COVID-19 in patients from three hospitals in Wuhan and Shenzhen, China to test if the former may be a biomarker for the latter. METHODS 4 medRxiv preprint doi: https://doi.org/10.1101/2020.03.11.20031096; this version posted March 27, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. We collected and ABO-typed blood samples from 1,775 patients infected with SARS-CoV-2, including 206 dead cases, at the Jinyintan Hospital in Wuhan, Hubei province, China. Another 113 and 285 patients with COVID-19 were respectively recruited from Renmin Hospital of Wuhan University, Hubei province and Shenzhen Third People's Hospital, Guangdong province, China. The diagnosis of COVID-19 was confirmed by a positive real-time reverse transcriptase polymerase-chain-reaction test of SARS-CoV-2 on nasal and pharyngeal swab specimens from patients. Two recent surveys of ABO blood group distribution of 3,694 normal people from Wuhan City and 23,386 normal people from Shenzhen City were used as comparison controls for the Wuhan and Shenzhen patients with COVID-19, respectively5-6. Statistical analyses were performed using chi-squared test. Data from different hospitals were meta-analyzed using random effects models, with calculation of odds ratio (OR) and 95% confidence interval (CI). Statistical analyses were performed using SPSS software (version 16.0) and STATA software (version 13). RESULTS The ABO blood group in 3,694 normal people in Wuhan displayed a percentage distribution of 32.16%, 24.90%, 9.10% and 33.84% for A, B, AB and O, respectively, while the 1,775 patients with COVID-19 from Wuhan Jinyintan Hospital showed an ABO distribution of 37.75%, 26.42%, 10.03% and 25.80% for A, B, AB and O, respectively. The proportion of blood group A in patients with COVID-19 was significantly higher than that in normal people, being 37.75% in the former vs 32.16% 5 medRxiv preprint doi: https://doi.org/10.1101/2020.03.11.20031096; this version posted March 27, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. in the later (P < 0.001). The proportion of blood group O in patients with COVID-19 was significantly lower than that in normal people, being 25.80% in the former vs 33.84% in the later (P < 0.001, Table 1). These results corresponded to a significantly increased risk of blood group A for COVID-19 with an OR of 1.279 (95% CI 1.136~1.440) and decreased risk of blood group O for COVID-19 with an OR of 0.680 (95% CI 0.599~0.771, Table 1) in comparison with non-A groups and non-O groups, respectively. A similar distribution pattern of high-risk blood group A and low-risk blood group O was also observed in the dead patients. Specifically, the proportions of blood groups A, B, AB and O in the 206 dead patients were 41.26%, 24.27%, 9.22% and 25.24%, respectively. Blood group A was associated with a higher risk of death compared with non-A groups, with an OR of 1.482 (95% CI 1.113~1.972, P = 0.008, Table 1). To the contrary, blood group O was associated with a lower risk of death compared with non-O groups, with an OR of 0.660 (95% CI 0.479~0.911, P = 0.014, Table 1). We next examined 113 patients with COVID-19 from another hospital in Wuhan City, the Renmin Hospital of Wuhan University, and found a similar risk distribution trend of ABO blood groups for the infection. Specifically, compared with non-A blood groups, blood group A displayed higher relative risk (OR=1.396; 95% CI 0.952~2.048) than those observed in patients from Wuhan Jinyintan Hospital, although the associations did not reach statistical significance likely due to the small sample size. Compared with non-O groups, blood group O were significantly 6 medRxiv preprint doi: https://doi.org/10.1101/2020.03.11.20031096; this version posted March 27, 2020.