Distribution of ABO blood groups and association to low risk of COVID-19 infection in patients

Minfei Peng Zhejiang Taizhou Hospital a liated to Wenzhou Medical University 317000, Taizhou, China Shigao Huang (  shigao.huang@connect.um.edu.mo ) University of Macau Shitu Zhu Linhai Maternity and Child Health Care Hospital, Linhai 317000, China Chaochao Chen Zhejiang Taizhou Hospital a liated to Wenzhou Medical University 317000, Taizhou, China Jiajia Qin Zhejiang Taizhou Hospital a liated to Wenzhou Medical University 317000, Taizhou, China Minmin He Zhejiang Taizhou Hospital a liated to Wenzhou Medical University 317000, Taizhou, China Jie Yang Department of Computer and Information Science, University of Macau 999078, Macau SAR, China Qi Zhao (  qizhao@um.edu.mo ) Cancer Centre, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau 999078, Macau SAR, China


Results
The laboratory results were signi cantly difference between type O and non-type O COVID19 patients (P < 0.05). Patients with blood type O had lower risk of severe COVID-19 infection (χ 2 = 4.066, p = 0.044, OR = 0.380), and especially, female with the type O blood had lower risk in deteriorating severe COVID19 infection (p = 0.049).

Conclusion
Patients with the blood group of type O had relatively lower risk of COVID19 infection, especially, female with the type O blood had lower risk in deteriorating severe COVID19 infection. We should concern more to the patients with non-type O blood to minimize the risk of COVID19 infection.

Background
With the wide spread of COVID-19 pandemic in all over world, we can't quickly know whether the people around us were infected with COVID-19, especially in the large recovery of working and studying. As not every country can afford testing nucleic acid to con rm the COVID-19 infected. In China, the rst wave of COVID-19 outside of Hubei has abated because of aggressive non-pharmaceutical interventions.
However, particularly from overseas importation, the second wave of COVID-19 propagation is possible [1]. Which was studied by Xu, et al and his colleages [2], Vulnerable people need protection, The ABO blood group system, the most extensively investigated erythrocyte antigen system, which in uences the host susceptibility and widely used in clinical practice, ABO blood groups have already been biologically associated with many chronic diseases such as Cancer [3][4][5], which indicated the ABO blood type in uenced the long-term outcomes of Japanese patients with Pancreatic, presumably due to its impact on disease onset and tumor behavior and the ABO blood group showed no signi cant effect on the clinicopathological parameters of gastric cancer, The O blood group may be a prognostic factor for gastric cancer patients. ABO blood group is also related to the prognosis of many diseases [6][7][8][9].
Prospective studies included ABO blood group associated with other disease, which may be clinically signi cant [10][11][12]. But, the association ABO blood group and COVID-19 infected risk has rarely reported.
With this in mind, we set out to de nitively describe the ABO blood groups distribution and evaluate the correlation between ABO blood group and COVID-19 infected risk. Basically up to this clinical signi cance value, we should concern more to the patients with blood types O to minimize the risk of COVID19 infection in patients for effectively assisting to protect susceptible population. the results were followed up to March 11. The study was approved by the institutional review board and the Ethics Committee of the Zhejiang Taizhou Hospital a liated to Wenzhou Medical University (K20200112) and the informed written consent from all participants were obtained.
The majority of suspected patients were being diagnosed as con rmed COVID-19 positive patients with CT and ET-PCR then regrouped con rmed cases into severe and non-severe patients.

Study population
Positive and negative stereotypes are detected automatically by AutoVue automatic blood group analyzer (Johnson & Johnson, USA) . 220 ABO Blood group data were collected between January 21 and February 20 in 2020 in Taizhou Hospital, of Zhejiang province, which divided into three groups included Severe , Non-severe, Non-COVID19 patients groups .

Statistical methods
Statistical analyses were performed using SPSS version 25.0 software (IBM, US). Frequency rates and percentages were described as the categorical variables, and median and interquartile range (IQR) values were described as continuous variables. Medians for continuous variables if the data were nonnormally distributed were compared using independent group Mann-Whitney U test; categorical variables were compared using the Chi-square test, P value < 0 .05 was considered statistically signi cant. The gures were plotted using GraphPad Prism version 8.0. were retuned from Wuhan or had the history of contacting with people returned from the epidemic area collected during the same period, Complete demographic information for the study populationis provided in Table 1 ABO blood group distribution  (Fig 2).  Figure 3),and patients with the blood group of type O had lower risk of severe COVID19 infection.

Gender distribution and correlation analysis
Compared gender distribution and correlation analysis in ABO blood group of Severe, Non-severe and Non-COVID19 patients. It indicated that severe female COVID19 patients with the type O blood group compared with severe female non-COVID19 patients was considered statistically signi cant (p=0.049), (  Table 4, Figure 4), which showed female with the type O blood had lower risk in deteriorating severe COVID19 infection.

COVID-19 infected risk factors
There was no statistically signi cant of the distribution between Type O and Non Type O (Table5 ), but there was statistically signi cant of laboratory indexes, and the group of Type O patients have lower indexes except MCV, MCH ( Figure 5). Discussion ABO blood group system is a very stable genetic material, which is located in the long arm three region four band (9q34) of chromosome 9. It is closely related to many disease [8,13,14]Davison Glenda M, et al [15] considered the expression of blood group antigens varies across human populations and geographical regions due to natural selection and the in uence of environment factors and disease. The red cell membrane is host to numerous surface antigens which are able to in uence susceptibility to disease. Liao ,et al [16], suggested that the blood type A, B and AB might not affect susceptibility to norovirus infection. However, blood type O appeared to be more susceptible to norovirus infection. Jing, et al [17]. performed a meta-analysis to investigate whether ABO blood groups were associated with HBV infection. Our team have done a research on correlation between ABO blood groups and incidence of eight kinds of cancers [18] In order to nd out whether there is a correlation between COVID19 and ABO blood group, and how to reduce the risk of infection, OR is odds ratio, also known as excellent potential ratio, when the occurrence of disease is known, compare disease group with non-disease group ,When the exposure of risk factors in the group is different, use the OR for quantitative description. In this paper, chi square test was used to compare the p value and OR value between severe, non-severe and Non-COVID19 patients. Whether the OR value is meaningful depends on p value. when the p value less than 0.05 and OR less than 1, it indicates that it may be a protective factor, and it reduces the risk of the event, On the contrary, if the p value less than 0.05 and OR more than 1, it indicates that it may be a risk factor, and that the risk increase [19,20] In our study, the blood group results of COVID19 patients between January 21 and February 20, 2020 were analyzed retrospectively, meanwhile, the Non-COVID19 patients were all returned from Wuhan or had the history of contacting with people returned from Wuhan. contact history was signi cant difference between the two groups, It may be due to the different epidemic situation in different areas of Wuhan and the different frequency of personal protective activities, but the electronic medical record did not record these information in detail. At the same, we found that patients with COVID19 were generally older than those Non-COVID19, and with the comorbidity of digestive system disease 17 ( (Table 2). While The distribution of blood group O in the severe group was statistically different from that in the non-COVID19 group, There was a negative correlation with the severity of COVID19, that means the patients with blood group of type O decreased the risk of infection of severe COVID19 (χ 2 = 4.066,p = 0.044, OR = 0.380), but there was no statistical difference in the distribution of other blood groups ( p > 0.05). we made a further analysis, gender distribution and correlation analysis in Severe, Non-severe and Non-COVID19 patients. Finally, we found the cases of female patients with type O in severe COVID patients was zero, which was signi cantly different from female non-COVID19 (P = 0.049), and there was no statistical difference in other blood groups.
At the same time, we further divided COVID19 patients into type O and non-type O groups, and analyzed the laboratory indexes of the two groups, and found alanine aminotransferase (ALT), Lactate dehydrogenase (LDH), Total CD19 + B cell ratio(TBCD19) were lower in type O COVID19 patients while had higher value in mean corpuscular volume (MCV), mean corpuscular hemoglobin mch (MCH), have Signi cant difference between the two groups. ALT is mainly distributed in liver, followed by skeletal muscle, kidney, heart muscle and other tissues, and it is one of the most sensitive indicators of liver damage. LDH is a detectable enzyme in the cytoplasm of nearly all cells in the human body, which is used to detect cell necrosis and tissue destruction [21], and research shows that The relationship between LDH and in-hospital mortality in acute aortic dissection patients is nonlinear. LDH was positively related with in-hospital mortality when LDH is more than 557 [17]. Other study show that in the case of idiopathic pulmonary arterial hypertension, patients with high levels of LDH had a low cumulative survival rate [22].CD19 is a common surface marker of all B cells. BC mainly mediates humoral immunity such as anti-infection, MCV, MCH and mean corpuscular hemoglobin contentration (MCHC) often show the pathological changes of red blood cells from different sides, which has certain value for the diagnosis of anemia. It is suggested that the damage of liver and myocardium in COVID19 patients with blood type O is less serious than that in patients with non-type O.
Some limitations could not be avoided in this study. To date, the association of blood group and COVID19 therefore remains a gap area of biological research and further large population studies should to be done to analyze all polymorphic blood groups which are required to add further knowledge to this subject.

Conclusion
In summary, the laboratory indexes were signi cantly difference between type O and non-type O COVID-19 patients which indicated that patients with the blood group of type O had relatively lower risk of COVID19 infection, especially, female with the type O blood had lower risk in deteriorating severe COVID19 infection. We should concern more to the patients with non-type O blood to minimize the risk of COVID19 infection.

Declarations
Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request Gender distribution and correlation analysis in ABO blood group of Severe, Non-severe and Non-COVID19 patients.
Page 14/16  ABO blood group distribution in Severe, Non-severe and Non-COVID19 patients.