Representatives with 23andMe, a direct-to-consumer genetic testing service, have reported that people who have type 0 blood are slightly less likely to get COVID-19. The work has not yet been peer-reviewed, and their study has not been published in a journal.

On June 9, Anne Wojcicki, CEO of 23andMe, discussed the results of a study her company conducted on the television show “Bloomberg Technology” (rebroadcast on YouTube).

During the interview, she reported that she and others at her company became curious after learning how different people have such wildly different symptoms when infected with the SARS-CoV-2 virus.

They wondered if there might be a genetic component to the story. To learn more, she and her team carried out a study this past April that involved surveying customers regarding their experiences with COVID-19.

The team received surveys back from approximately 750,000 customers. Analysis of that data showed that people with type O blood were between 9 and 18% less likely to test positive for the SARS-CoV-2 virus than people with other blood types.

She noted that their findings held when adjusted for sex, body mass and age. She also noted that her team did not find any other blood-type-related differences.

This is not the first time the company has conducted research – three years ago, a team at the company published results of a study in the journal Nature Communications reporting that nearly 60% of genetic variants in humans could be associated with susceptibility to one of 17 types of infectious diseases.

In another interview, Adam Auton, lead researcher on the COVID-19 research team, told Fox News that reports by other groups suggesting cardiovascular disease and blood clotting may also play a role in disease severity also hint at a genetic component to the pandemic.

He also noted that it is still early in the study of the SARS-CoV-2 virus, and that there is much more to learn. He suggests that researchers in different disciplines may wind up pooling resources to understand why the virus has such dramatically different impacts on different people.

---

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 GalNAca1-3-(Fuca1,2)-Galb- and Gala1-3-(Fuca1,2)-Galb-, while O blood group antigen is Fuca1,2-Galb-.

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 susceptibility^2,3.

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

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, respectively^5-6. 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%

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 associated with a lower risk of infection, with an OR of 0.644 (95% CI 0.418~0.993,P = 0.045, Table 1).

The ABO blood group in 23,368 normal people in Shenzhen displayed a percentage distribution of 28.77%, 25.14%, 7.32% and 38.77% for A, B, AB and O, respectively. Analysis of 285 patients with COVID-19 from Shenzhen showed proportions of blood groups A, B, AB and O to be 28.77%, 29.12%, 13.68% and 28.42%, respectively.

These results similarly showed a significantly lower risk of infection associated with blood group O (OR, 0.627; 95% CI 0.484~0.812). These results also showed blood group AB to have an increased risk of infection (OR, 2.008; 95% CI 1.427~2.824, Table 1).

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 trend of higher risk for infection, but the association did not reach statistical significance.

We next investigated whether patient age and sex might influence the ABO blood group distribution among patients with COVID-19. We used the ABO blood group

distribution of 3,694 normal people in Wuhan area as control to compare with different age and sex groups. When all patients from Jinyintan Hospital and Renmin Hospital in Wuhan city were combined (1,888 patients in total) and grouped into three age groups (<40, 41-59, >60 years old), the ABO blood group distribution was similar among the three age groups (Table S1).

The ABO blood group distribution was also similar between male and female patients with COVID-19 (Table S1). These results are consistent with the fact that the distribution of ABO blood groups is known to have no sex and age predilections.

For example, by analyzing the blood type of more than ninety thousands normal people, it was found that the percentage of A, B, AB and O blood types were essentially the same among different age groups and among different sexes.⁷

Conclusions

In this novel study, we for the first time report an association between the ABO blood group and COVID-19 susceptibility, demonstrating the latter to be a biomarker differentiating the former.

Specifically, people with blood group A have a higher risk whereas people with blood group O have a lower risk for SARS-Cov-2 infection and COVID-19 severity. If verified by future studies, the findings in the present study would have several potential clinical implications.

1) People with blood group A might need particularly strengthened personal protection to reduce the chance of infection;

2) SARS-CoV-2-infected patients with blood group A might need to receive more vigilant surveillance and aggressive treatment;

3) It might be helpful to introduce ABO blood typing in the management of SARS-CoV-2 infection and COVID-19.

It should be emphasized, however, that given the above limitations, it would be premature to use this study to guide clinical practice at this time. Large replication studies with complete information should be encouraged to pursue and are needed to verify the present findings. Obviously, people with any blood type all need to exercise the wisdom of careful practice to avoid SARS-CoV-2 infection.

Author contributions statement

P.G.W and G.Y.Y conceived, designed and supervised the overall study. P.G.W, M.X, G.Y.Y, L.Z , and X.Y.Z supervised and administered the project. L.Z, H.P.H and T.L collected and verified ABO blood types of patients from Wuhan Jinyintan Hospital.

X.Y.Z and D.L collected and verified ABO blood types of patients from Renmin Hospital of Wuhan University. Z.Z, L.L and Y.Y collected and verified ABO blood types of patients from Second Affiliated Hospital, Southern University of Science and Technology. Y.J.H, B.S, M.L.W, X.H.W collected and verified the data. D.F.G, X.F.L, Y.K.L, Z.J, M.X, and P.G.W analyzed the data. P.G.W, J.Z, G.Y.Y and M.X, wrote and revised the paper. All authors read and approved the final manuscript.

Reference

1. Chen N Zhou M Dong X et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet.    2020;               (published              online              Jan               29.) https://doi.org/10.1016/S0140-6736(20)30211-7.
2. Batool Z, Durrani SH, Tariq S. 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.  J  Ayub  Med  Coll Abbottabad. 2017 Jan-Mar;29(1):90-92.
3. Lindesmith L, Moe C, Marionneau S, Ruvoen N, Jiang X, Lindblad L, Stewart P, LePendu J, Baric R. Human susceptibility and resistance to Norwalk virus infection.J Nat Med. 2003 May;9(5):548-53. Epub 2003 Apr 14.
4. Cheng Y, Cheng G, Chui CH, Lau FY, Chan PK, Ng MH, Sung JJ, Wong RS. ABO blood group and susceptibility to severe acute respiratory syndrome. JAMA. 2005 Mar 23;293(12):1450-1.
5. Xu P, Xiong Y, Cao K.Distribution of ABO and RhD blood group among Healthy Han population in Wuhan. J Clin Hematol (China). 2015(28):837.
6. Chen, C. Distribution of ABO and Rh (D) blood group and qualty analysis. Int J Lab Med, 2010 Jan; 31(1):77-8.
7. Guillon P, Clément M, Sébille V, Rivain JG, Chou CF, Ruvoën-Clouet N, Le Pendu J. Inhibition of the interaction between the SARS-CoV spike protein and its cellular receptor by anti-histo-blood group antibodies. Glycobiology. 2008 Dec;18(12):1085-93.
8. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, Wang W, Song H, Huang B, Zhu N, Bi Y, Ma X, Zhan F, Wang L, Hu T, Zhou H, Hu Z, Zhou W, Zhao L, Chen J, Meng Y, Wang J, Lin Y, Yuan J, Xie Z, Ma J, Liu WJ, Wang D, Xu W, Holmes EC, Gao GF, Wu G, Chen W, Shi W, Tan W. Genomic characterization and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020 Jan 30;. doi: 10.1016/S0140-6736(20)30251-8.
9. Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. J Nature. 2003 Nov 27;426(6965):450-4.
10. Hoffmann M, Kleine-Weber H, Krüger N, Müller M, Drosten C, Pöhlmann S, The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2
11. and the cellular protease TMPRSS2 for entry into target cells. bioRxiv 929042 [Preprint]. 31 January 2020. .doi:10.1101/2020.01.31.929042.
12. Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS. J. Virol. JVI.00127-20 (2020). doi:10.1128/JVI.00127-20pmid:31996437.

---

More information: blog.23andme.com/23andme-resea … -a-role-in-covid-19/