key: cord-0811306-9vljilvn authors: Yanardag Acik, Didar; Bankir, Mehmet title: Relationship of SARS-CoV-2 Pandemic with Blood Groups date: 2021-04-07 journal: Transfus Med Hemother DOI: 10.1159/000515609 sha: 33a3a983364f71b1291ec138187008d837fbb9f7 doc_id: 811306 cord_uid: 9vljilvn INTRODUCTION: SARS-CoV attaches to human angiotensin-converting enzyme 2 receptor with the spike protein and infects cells. It can play a direct role in infection by acting as a receptor and/or co-receptor for blood group antigens, microorganisms, parasites, and viruses. OBJECTIVES: We aimed to compare the blood group distribution of patients with SARS-CoV-2 infection admitted to hospital and that of healthy donors. METHODS: A total of 823 patients with a positive SARS-CoV-2 test and clinical symptoms were included in the study. The results were compared with the normal blood group distribution in the region. RESULTS: While the prevalence of COVID-19 in the A, B, and AB blood groups was higher than that in the healthy blood donors, it was lower in the O blood group (p = 0.009). The distribution of demographic and clinical characteristics based on blood groups did not differ significantly. CONCLUSION: Our results are in agreement with other studies suggesting that blood group O individuals are somewhat more resistant to clinically overt infection with SARS-CoV-2 than other blood groups. However, this tendency is not sufficiently established to allow special prophylaxis recommendations for non-O individuals. On March 11, 2020, coronavirus disease 2019 (CO VID19), caused by the severe acute respiratory syn drome coronavirus 2 (SARSCoV2), was declared a pan demic by the World Health Organisation (WHO) [1] . Evidence obtained from phylogenetic analysis shows that SARSCoV2, which belongs to the Betacoronavirus ge nus, can infect humans, bats, and wild animals [2] . SARS CoV attaches to the human angiotensinconverting en zyme 2 (ACE2) receptor with the spike protein and in fects cells [3, 4] . COVID19 spread rapidly around the world. There is a poor prognosis observed in the elderly, which is most commonly associated with hypertension, diabetes melli tus, coronary artery disease, and immunosuppression [1, 5] . The relationship of infectious agents with human blood groups was investigated previously [6] [7] [8] [9] [10] [11] [12] [13] [14] . It has been indicated that the blood group antigens found in erythrocytes and other tissues interact with microorgan isms such as bacteria, viruses, parasites, and fungi. Differ ences in blood group antigen expression can increase or decrease host susceptibility to many infections. This can play a direct role in infection by acting as a receptor and/ or coreceptor for blood group antigens, microorganisms, parasites, and viruses [6, 7] . ABO antibodies can also be considered as part of the innate immune system against some bacterial pathogens and enveloped viruses carrying ABOactive antigens [8] . Helicobacter pylori [9] , Vibrio cholerae [10, 11] , hepatitis C virus [12] , human immuno deficiency virus [13] , and SARS [8, 14, 15] are some of the infectious agents that have been shown to be associated with human blood groups. Clinical studies have also been conducted examining the relationship between SARSCoV2 and blood groups [16] [17] [18] [19] . However, more studies will be useful for com paring results and to understanding whether findings dif fer in different populations because the frequency of blood groups is variable between populations [20] . In this study, we aimed to compare blood group distribution in patients with SARSCoV2 infection who presented to our hospital with an indication for hospitalization and healthy donors from the same region. A distinctive fea ture of the Çukurova region is that haemoglobinopathies are endemic in this area [21, 22] . Investigating the rela tionship between blood groups and SARSCoV2 infec tion is important in this region because the human popu lation living here has been determined by malaria infec tion throughout history. A total of 823 patients followed up at our hospital with a posi tive PCR test for SARSCoV2 RNA between 25 March and 21 December 2020 were included in this study. The BioSpeedy ® (Bioexen, Istanbul, Turkey) nucleic acid isolation kit was used for nucleic acid isolation from respiratory tract (nasopharyngeal swab) samples obtained from the patients. Reverse transcription (RT) and quantitative RTqPCR procedures were performed with QuantStudio RealTime PCR Systems (Thermo Fisher Scientific, USA) using the BioSpeedy ® COVID19 RTqPCR detection kit, which was developed to detect the Wuhan CoV RdRPgene region according to the protocol proposed by the WHO [23] . Molecular analysis results were interpreted as SARSCoV2positive if Wu han RdRP was positive, and SARSCoV2negative if Wuhan RdRP was negative. The medical records of the patients were ret rospectively reviewed. Patients' age, sex, white blood cell (WBC), neutrophil, and lymphocyte counts, comorbidities, intubation and intensive care needs, and hospitalization duration were obtained from the medical records. To make the laboratory values of the patient independent from the effects of the drugs, their values at the time of first admission to the hospital were recorded. The clin ical results were determined based on the hospitalization duration, the need for intubation and intensive care, and death. Comorbid diseases came under the following headings. Coro nary artery disease, hypertension, cerebrovascular disease, and pe ripheral artery disease were classified as "cardiovascular disease," and asthma and chronic obstructive pulmonary disease as "respi ratory system diseases." Cancer patients were not divided accord ing to their types, and they were recorded as a general title. Less common comorbid diseases were classified as "others." In the study by Yildiz [24] , the blood type distribution in Çu kurova region was determined. This study was conducted with healthy blood donors. In this study, the blood groups of 136,038 individuals were determined as A in 38.90%, O in 37.10%, B in 17.00%, and AB in 6.90%. Of the same individuals, 89.90% were Rh(+) and 10.10% were Rh(-). The results of this study were com pared with those of our study in terms of blood group distribution. Statistical evaluation was conducted using SPSS for Windows 20 (IBM SPSS Inc., Chicago, IL, USA). Normality of the distribu tion of data was evaluated by the KolmogorovSmirnov test. Nu merical variables with normal distribution are given as mean ± SD and numerical variables without normal distribution as median (interquartile range, 25th-75th percentiles). Categorical variables are indicated as numbers and percentages. The χ 2 and Fisher exact tests were used to compare categorical data. The Student t test or MannWhitney U test was used for the comparison of numerical variables between 2 groups according to the normality of distribu tion. Based on the normality of distribution, analysis of variance or the KruskalWallis H test was used for the comparison of nu merical variables among blood group ABO patients. The findings associated with the prognosis were analyzed using the Cox regres sion analysis. The survival chart was evaluated using the Kaplan Meier analysis. p < 0.05 was considered statistically significant. The study population consisted of 823 patients (aged 18 Figure 1 . Accordingly, while A, B, and AB blood groups were seen more frequently in COVID19 cases than in the healthy blood donors, the incidence of COVID19 was lower in the O blood group than in healthy blood donors (p = 0.009). Among all the patients, 510 (62%) had a co morbidity. The demographic and clinical characteristics of pa tients with COVID19 are shown in Table 1 . Distribu tions of demographic and clinical characteristics did not differ significantly according to blood group. In intubat ed versus nonintubated patients, male sex ratio (63.4 vs. 45.5%; p = 0.019), mean age (67.0 ± 13.5 vs. 55.2 ± 17.1; p < 0.001), and comorbidity ratio (80.3 vs. 54.5%; p < 0.001) as well as mortality rate (89.9 vs. 1.5%; p < 0.001) were found to be higher. The median WBC (13.2 vs. 7.6; p < 0.001) and neutrophil (11.8 vs. 5.2; p < 0.001) counts were higher and lymphocyte count (0.5 vs. 1.3; p < 0.001) lower in intubated patients than in nonintubated pa tients ( Table 2 ). The multivariable Cox regression model included age, comorbid diseases, admission to the inten sive care unit, intubation status as well as WBC, neutro phil, and lymphocyte counts, all of which were found to be associated with mortality; older age (hazard ratio [HR] 1.02; p = 0.038), T2DM (HR 1.72; p = 0.022), T2DM and cardiovascular disease (HR 1.64; p = 0.029), being intubated (HR 22.84; p < 0.001), and a higher neutrophil count (HR 1.02; p = 0.020) were independent predictors for mortality. There was no significant correlation be tween blood groups (Fig. 2) and other demographic characteristics and other clinical findings and mortality (Table 3 ). In our study, compared with the blood group distri bution of healthy blood donors in the region, the preva lence of COVID19 was higher in blood groups A, B, and AB and lower in blood group O. Our results are in agree ment with other studies suggesting that blood group O individuals are somewhat more resistant to clinically overt infection with SARSCoV2 than other blood groups [16] [17] [18] [19] 25] . Dzik et al. [26] have stated that the fact that the blood donors were selected particularly from among those with blood group O could be a reason why blood group O was detected less often in the patient group. This is a very reasonable interpretation. How ever, blood group A was more common than blood group O in the blood group distribution of our donors, even though this was not statistically significant. Never theless, blood donors cannot accurately reflect the ac tual blood type in this area. There are both healthy peo ple and patients in the blood group population that rep resents the whole society. In addition to the higher O blood group in the donor population, the male gender is also higher. The population mobility of the region may also change the distribution of blood groups over time. Therefore, blood group distribution should be done by screening the whole society and should be up to date. Individuals infected with asymptomatic SARSCoV2 should also be identified by screening the whole popula tion. Blood group studies done in this way will give us the most accurate result. Good organization, a long time, a serious workload, and high costs are required to perform this work. It is therefore an ideal but difficult way of working. In the SARSCoV1 epidemic, it was shown that anti A antibodies in individuals with blood group O prevent ed the invasion of the S protein into the tissues [14] , and it has been claimed that, due to the same mechanism, this will cause less infection in individuals with blood group O in the SARSCoV2 pandemic [19, 25] . Although there are antiA antibodies in blood group B, there are no pub lished studies that show that blood group B is less suscep tible to SARSCoV2. This situation was explained by Gé rard et al. [27] , with the antiA antibodies in blood group O being the IgG type and the antiA antibodies in blood group B being the IgM type. The importance of the antiA antibody titre in SARS CoV1 infection has also been emphasized [14] . How ever, no increase in susceptibility to COVID19 infection was detected in individuals with blood group AB without any blood group antibodies. In this case, the increased susceptibility of blood group A to infection and lower susceptibility of blood group O to infection must involve other mechanisms. One of these may be that thrombo embolic diseases are more common in blood group A, which therefore shows more disease symptoms [28] . In fact, knowing the blood group distribution of SARS CoV2infected asymptomatic cases in the community would help elucidate the relationship between SARS CoV2 and the blood group of infected individuals more objectively. However, no such study has yet been pub lished. There is a symbiotic relationship between blood group expression and maturation of the gastrointestinal microbiome. Bacteria can induce antibodies against blood group antigens, including ABO. Blood group an tibodies are stimulated by the intestinal flora, and blood group antibody titres are lower in hyperhygienic popu lations and those following Western diets [8, 29, 30] . Guillon et al. [14] showed that SARSCoV1 can be blocked with monoclonal antiA and human antiA an tibodies; this can be accomplished using a high antiA antibody titre but a lower antiA antibody titre is inef fective. This finding may indicate that SARSCoV2 in fection will spread faster in industrialized countries with people who follow Western diets and live in extremely hygienic conditions. Our results are in agreement with other studies sug gesting that blood group O individuals are somewhat more resistant to clinically overt infection with SARS CoV2 than others. However, this tendency is not suf ficiently established to allow special prophylaxis rec ommendations for nonO individuals. Of course, blood group is not the only factor that determines contagious ness. For instance, all South American Indians have the O blood type [31] . However, there is no information that the frequency of COVID19 is lower or the rate of spread is slower in areas where South American natives live. There are many factors, other than blood groups, that determine the contagiousness and severity of SARS CoV2 infection. Many of these are still unexplained. More comprehensive studies are needed to explain the relationship of SARSCoV2 infection and blood groups. Our study has limitations. The blood group distribu tion of donors was made 11 years ago. The COVID19 patients were compared with healthy blood donors. Only hospitalized COVID19 cases were included in the study. This study was conducted ethically in accordance with the World Medical Association Declaration of Helsinki and was ap proved by our institutional ethics commission (EC No. 49/2020). There was no specific funding for this study. Clinical course and risk factors for mortality of adult inpatients with COVID19 in Wuhan, China: a retro spective cohort study A novel coronavirus from patients with pneumonia in China Coronavirus patho genesis The novel coronavirus 2019 (2019nCoV) uses the SARScoronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into tar get cells Clinical course and outcomes of critically ill patients with SARSCoV2 pneumonia in Wuhan, China: a singlecentered, retrospec tive, observational study How malaria parasites reduce the deformability of infected red blood cells Blood groups and susceptibility to virus infection: new developments Blood Groups in Infection and Host Susceptibility ABH and Lewis anti gen distributions in blood, saliva and gastric mucosa and H pylori infection in gastric ulcer patients The relationship between ABO blood groups and susceptibility to diarrhea due to Vibrio cholerae 0139 Biologic roles of the ABH and Lewis histoblood group antigens Part I: infection and immunity. Vox Sang Varia tion in the host ABO blood group may be as sociated with susceptibility to hepatitis C vi rus infection The higher frequency of blood group b in a Brazilian population with HIV Infection Inhibition of the interaction between the SARSCoV spike protein and its cellular receptor by anti histoblood group antibodies ABO blood group and sus ceptibility to severe acute respiratory syn drome As sociation between ABO blood groups and COVID19 infection, severity and demise: A systematic review and metaanalysis Relationship be tween ABO blood group distribution and clinical characteristics in patients with COV ID19 Association between ABO blood groups and risk of SARSCoV2 pneumonia Relationship between the ABO Blood Group and the COVID19 Susceptibility Henry's Clinical Diagnosis and Management by Labo ratory Methods. 21st ed. Philadelphia: Saun ders Elsevier Genetic heterogeneity of be tathalassemia at Cukurova in southern Tur key The frequency of anaemia, iron deficiency, hemoglobin S and beta thalassemia in the south of Turkey Diagnostic de tection of Wuhan coronavirus 2019 by real time RTPCR Distribution of ABO and Rh blood group systems in Cukurova region The effects of blood group types on the risk of COVID19 infection and its clinical out come COVID19 and ABO blood groups CO VID19 and ABO blood group: another view point Implications of AB0 blood group in hypertensive patients with co vid19 Differences in ABO antibody levels among blood donors: a com parison between past and present Japanese, Laotian, and Thai populations. Immunohe matology Racial and ethnic distribu tion of ABO blood types The authors declare no conflict of interest. D.Y.A. designed the study and collected data. M.B. collected and analyzed the data. Both authors read and approved the final version.