key: cord-0916562-28ah3nig authors: Zhao, Jiao; Yang, Yan; Huang, Hanping; Li, Dong; Gu, Dongfeng; Lu, Xiangfeng; Zhang, Zheng; Liu, Lei; Liu, Ting; Liu, Yukun; He, Yunjiao; Sun, Bin; Wei, Meilan; Yang, Guangyu; Wang, Xinghuan; Zhang, Li; Zhou, Xiaoyang; Xing, Mingzhao; Wang, Peng George title: Relationship between the ABO Blood Group and the COVID-19 Susceptibility date: 2020-08-04 journal: Clin Infect Dis DOI: 10.1093/cid/ciaa1150 sha: dc53ba7ecefce66835619d15f0fdbdfc0fcaccd1 doc_id: 916562 cord_uid: 28ah3nig To explore any relationship between the ABO blood group and the COVID-19 susceptibility, we compared ABO blood group distributions in 2,173 COVID-19 patients with local control populations, and found that blood group A was associated with an increased risk of infection, whereas group O was associated with a decreased risk. The novel coronavirus SARS-CoV-2, causing the new infectious disease COVID-19, has spread widely around the world. Current clinical observation suggest that people's age and gender are two risk factors in the susceptibility to COVID-19 1 . Older people and men are more susceptible to infection and development of more severe disease. However, no biological markers have been identified to predict the susceptibility to COVID-19 so far. 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 GalNAc1-3-(Fuc1,2)-Gal-and Gal1-3-(Fuc1,2)-Gal-, while O blood group antigen is Fuc1,2-Gal-. 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 found to be related to ABO blood group. For example, Norwalk virus and Hepatitis B have clear blood group susceptibility 2,3 . It was also reported that blood group O individuals were less likely to become infected by SARS coronavirus 4 . 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. non-COVID-19 people from Shenzhen City were used as comparison controls for the Wuhan and Shenzhen patients with COVID-19, respectively 5-6 . Statistical analyses were performed using 2-tailed χ 2 . 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). The ABO blood group in 3,694 people in Wuhan displayed a percentage distribution of 32.2%, 24.9%, 9.1% and 33.8% for A, B, AB and O, respectively, while the 1,775 patients with COVID-19 from Wuhan Jinyintan Hospital showed an ABO distribution of 37.8%, 26.4%, 10 .0% and 25.8% for A, B, AB and O, respectively. The proportion of blood group A among patients with COVID-19 was significantly higher than that among the control group, being A c c e p t e d M a n u s c r i p t 6 37.8% in the former vs 32.2% in the later (P < 0.001). The proportion of blood group O in patients with COVID-19 was significantly lower than that in control group, being 25.80% in the former vs 33.84% in the later (P < 0.001, Table 1 ). These results showed associations between ABO blood groups and COVID-19 susceptibility. The COVID-19 risk significantly increased for blood group A ( Figure 1 shows the estimates of ORs of the risk of ABO blood groups for COVID-19 on the pooled data from the three hospitals by random effects models. Again, the results showed that blood group A was associated with a significantly higher risk for COVID-19 (OR 1.21; 95% CI 1.02~1.43, P = 0.027) compared with non-A blood groups, whereas blood group O was associated with a significantly lower risk for the infection (OR 0.67; 95% CI 0.60~0.75, P < 0.001) compared with non-O blood groups. Compared with other ABO blood groups, AB blood group (OR 1.48, 95% CI 0.97~2.24) and B blood group (OR 1.09, 95% CI 0.98~1.22) seemed to have a relatively higher risk of infection, although the associations did not reach statistical significance. In this study, we found that ABO blood groups displayed different association risks for the infection with SARS-CoV-2 resulting in COVID-19. Specifically, blood group A was associated with an increased risk whereas blood group O was associated with a decreased There may also be other mechanisms underlying the ABO blood group-differentiated susceptibility for COVID-19 that require further studies to elucidate. In the 285 patients from Shenzhen, we also found that blood group AB had an increased risk of infection. This result needs to be confirmed given the small size of this cohort of patients. After submission of our study, another study by Michael et al. using observational data on 1,559 SARS-CoV-2tested individuals came online, reporting that the odds for SARS-CoV-2 infection was significantly increased for blood group A and decreased for blood group O. This reproduced our findings of the associations between the ABO blood group and the COVID-19 status 12 . In summary, we report a link between COVID-19 susceptibility and the ABO blood group. Specifically, people with blood group A have a higher risk whereas people with blood A c c e p t e d M a n u s c r i p t 15 Figure 1 Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study Association of Abo And Rh Blood Group Types To Hepatitis B, Hepatitis C, Hiv And Syphilis Infection, A Five Year' Experience In Healthy Blood Donors In A Tertiary Care Hospital Human susceptibility and resistance to Norwalk virus infection ABO blood group and susceptibility to severe acute respiratory syndrome Distribution of ABO and RhD blood group among Healthy Han population in Wuhan Distribution of ABO and Rh (D) blood group and qualty analysis Inhibition of the interaction between the SARS-CoV spike protein and its cellular receptor by anti-histo-blood group antibodies Genomic characterization and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. J Nature The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells Receptor recognition by novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS Testing the association between blood type and COVID-19 infection, intubation, and death. medRxiv A c c e p t e d M a n u s c r i p t A c c e p t e d M a n u s c r i p t 12