Strong Association of ABO blood groups with COVID-19 associated mortality in Sudan

Strong Association of ABO blood groups with COVID-19 associated mortality in Sudan | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Strong Association of ABO blood groups with COVID-19 associated mortality in Sudan Adil Mergani, Rihab Muhammed Dafallah This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7168882/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: The SARS-CoV-2 pandemic, which began in late 2019, has had a significant impact on global health, economic, and social life, causing COVID-19 disease with a spectrum ranging from asymptomatic infection to mortality. The ABO blood group system polymorphism has been suggested as a potential mechanism influencing the severity and mortality of COVID-19. Research indicates that individuals with blood types O and B may experience decreased severity and mortality from SARS-CoV-2. Conversely, individuals with blood types A and AB have been shown to be at higher risk for serious outcomes from SARS-CoV-2. This suggests that the ABO blood group plays a crucial role in the epidemiology of COVID-19 Methods: A prospective cross-sectional study was carried out during the period, from October 2021 to October 2022, at the intensive care units (ICU) in Covid-19 Isolation Zones (Sugatra and Mycetoma Center) in Wad Medani - Gezira state, Sudan to study the association between ABO blood groups and the prognosis and associated mortality of Covid-19. Blood grouping of all selected subjects was done using slide agglutination method and structured questionnaire was used to collect personal, demographic and the disease prognosis data of the study subjects, Results: The study's findings indicate that individuals with blood types O and B are more protected against COVID-19 infection and may have a lower mortality rate. Specifically, blood group O offered more protection than blood group B. In contrast, individuals with blood types A and AB showed an increased severity and mortality rate from COVID-19 infection. Among these, individuals with blood type AB experienced less severe outcomes compared to those with blood type A. Conclusion: The study suggests a strong association between ABO blood groups and COVID-19 associated mortality, with blood types O and B offering more protection and blood types A and AB being associated with increased severity and mortality. Health sciences/Diseases Health sciences/Health care Health sciences/Medical research Biological sciences/Microbiology Health sciences/Risk factors Covid-19 ABO blood groups mortality Figures Figure 1 Figure 2 Introduction The novel coronavirus pandemic disease 2019 (COVID-19) has become a severe health issue. SARS-CoV-2 is one of the coronavirus family species, which are sub-divided into four genera, alpha (a), beta (b), gamma (g), and delta (d), of which only the a and b genera are known to cause infections in human, SARS-CoV-2 belonging to the b coronaviruses [ 1 ]. Coronaviruses are enveloped and have a positive sense of single-stranded RNA genome [ 2 ]. The complicated infections are most common in individuals with cardiovascular disorders, chronic pulmonary, hypertension, and diabetes [ 3 ]. The infected individuals show fever, anoxia, cough with sputum, headache, and diarrhea. Viral infection in complicated conditions leads to renal failure [ 4 ]. The ABO blood group was suggested to be the main factor that may play a role in determining Covid-19 susceptibility, severity, and mortality [ 5 ]. Therefore, ABO blood groups share in covid-19 epidemiology. The ABO blood group system was known in 1901[ 6 ], and it includes 3 alleles (A, B, O), which are coded by the ABO gene. These 3 alleles gathered on red blood cells as antigens (RBCs) present in 6 possible genotypes and four phenotypes, resulting in antigens on (RBCs) with antibodies in plasma [ 6 ]. ABO antibodies can be considered a section of the innate immune systems against some bacterial pathogens and enveloped viruses that may show a crucial role in the pathogenesis and personal susceptibility to certain diseases [ 7 ], COVID-19 may be one among these diseases. Pathophysiological Mechanisms of COVID-19 Infection : After the invasion of the SARS-CoV-2 through the cells lining the nose, viral replication (primary viremia) results in the migration of infection into targeting organs that express angiotensin-converting enzyme 2 (ACE2), such as the lungs, heart, renal system, and gastrointestinal tract [ 7 , 8 ]. In some individuals, robust immune responses to viral infiltration induced a release of pro-inflammatory cytokines, a cytokine storm. The viral structure and genome must be considered, the SARS-CoV-2 are enveloped positive-strand RNA with the largest known RNA genomes (30–32) kb—with a 50-cap structure and 30-poly-A tail [ 2 ]. The SARS-CoV-2 genome consists of ten open reading frames (ORFs) where ORF1a/b alone accounts for about two-thirds of the virus’s total RNA [ 9 , 10 ]. The translation of the genome RNA produced by ORF1a/b results in two polyproteins (ppla and pplab) [ 11 ], which are essential for further transcribed to 16 non-structural proteins (nsps) necessary for the production of the viral replicase transcriptase enzyme [ 12 ]. The last one-third of the viral RNA is required to transcript the virus’s structural proteins including Spike (S), Envelope (E), Matrix proteins (M), and Nucleocapsid (N) [ 11 , 12 ]. Some studies confirmed that (nsps) could block the host's innate immune response in the host [ 13 ], through the functions of the structural proteins, the envelope has a crucial role in virus pathogenicity as it raises viral assembly and release. The S protein resembles the antigenic region in the virus (spike), which consists of two subunits, the S1 subunit expresses the receptor-binding domain (RBD) required for the virus-host binding (attachment) and the S2 subunit is needed for the virus fusion with the host cell Membrane (invasion). The SARS-CoV-2 penetrated host cells by interacting with the angiotensin-converting enzyme 2 (ACE2) receptor located on human tissue cells. The virus binds to the ACE2 through the S1 glycoprotein, while the penetration is accomplished through the S2 glycoprotein (7,8). The hallmark of COVID-19 severity is pneumonia, mediated by viral binding to angiotensin-converting enzyme 2 receptors ( ACE-2) in the respiratory tract and alveoli, The mechanism of SARS-CoV-2 causing pneumonia is more complex [ 10 – 12 ], COVID-19-associated pneumonia could lead to acute respiratory distress syndrome (ARDS), and the viral replication can produce an exaggerated immune reaction in the patients. In some cases, the reaction takes place, which is called a “cytokine storm” that effecting in extensive tissue damage and this responsibility belongs to IL-6, which is produced by activated leukocytes and acts on a large number of cells and tissues [ 13 ]. IL-6 can promote the activation and differentiation of B-lymphocytes and inhibit the growth of other cells. It also plays an important role in pro-inflammatory and anti-inflammatory effects. It also stimulates the production of acute-phase proteins and plays an important role in thermoregulation, bone maintenance, and the functionality of the central nervous system [ 14 ]. IL-6 increases during inflammatory diseases, infections, autoimmune disorders, cardiovascular diseases, and some types of cancer [ 15 ]. Cytokine release syndrome (CRS) is an acute systemic inflammatory syndrome, characterized by fever and multiple organ dysfunction [ 16 ]. SARS-CoV-2 plays a potential role in triggering a hypoxic state in the lungs same as other pathogens, Hypoxia can damage several target organs and play a crucial role in severe pathological status [ 13 ]. Pulmonary vasoconstriction is confirmed as another potential mechanism contributing to hypoxia in COVID-19 pneumonia [ 13 ]. Hypoxia-inducible factor (HIF-1) is a dimeric transcription factor that acts as a master regulator of oxygen levels in cells. This factor includes the HIF-1α and HIF-1β subunits are activated when the cell faces a deficiency of oxygen [ 19 ]. The HIF-1 remains inactivated under normal cellular conditions, but under abnormal condition, this factor with co-activators increase the transcription of several hypoxia response elements (HRE) containing genes which responsible for rising ventilation and improved vascularization during COVID [ 19 – 20 ]. The HIF-1α subunit is the prime mediator of hypoxia in cells; it migrates inside the nucleus leads the transcription of HRE genes, and reflects in several hypoxic symptoms [ 20 ]. HIF-1α subunit migrates inside the nucleus and leads the transcription of HRE genes, which is reflected in several hypoxic symptoms, it enhances the expression of the ACE-2 gene during COVID-19 infection, which worse the COVID-19 infection and damages the lung cells in the early stage [ 21 ]. In the late stage, the HIF-1α reduced expression of ACE-2; it can be beneficial for reducing the risk of enhanced tissue and organ damage from COVID-19 infection [22 ]. The variation in clinical features in SARS-Cov-2-infected individuals is commonly observed, so some individuals are more susceptible to the infection than others are. The epidemiological investigations confirmed that around 80% of the infected individuals are asymptomatic but contagious. Main COVID-19-associated symptoms such as cough and fever, Dyspnea, Headache, Sore throat, Rhinorrhea, or severe respiratory complications, such as acute respiratory distress syndrome (ARDS) [ 23 ], that need mechanical ventilation and support in an intensive care unit (ICU), systemic manifestations to multiorgan in terms of sepsis, septic shock, and multiple organs dysfunction syndromes (MODS) [ 17 ]. Gastrointestinal symptoms have also been reported such as nausea and diarrhea—this variation in COVID-19 clinical features is due to differences in the body's immune response to the infection. The primary effective immune response can reduce the viral load and prevent the infection from reaching the target organs [ 3 ], whereas an extreme immune response can cause an excessive inflammatory reaction leading to severe adverse consequences [ 24 ]. Moreover, statistics analysis suggests that metabolic disorders have a role in directing the response of the body to the infection, due to chronic diseases such as diabetes, hypertension, ion, and liver diseases among the severe COVID-19 cases. Materials and Methods Study design and selection of study subjects : A prospective cross-sectional study was carried out during the period, from October 2021 to October 2022, at the intensive care units (ICU) in Covid-19 Isolation Zones (Sugatra and Mycetoma Center) in Wad Medani - Gezira state, Sudan to study the association between ABO blood groups and the prognosis and associated mortality of Covid-19. All patients, who were admitted in the Zones and were confirmed by RT-PCR to have Covid-19, were invited to be included in the study. A structured questionnaire was designed to collect personal information about the study patients group, such as age, gender, and chronic disease. Blood grouping of selected study subjects : Blood grouping of all selected subjects was done using slide agglutination method. Two ml of venous blood were collected in a sterile tube from each patient. Three drops from each sample were added to one slide labeled with Anti-A, Anti-B, and Anti-D. Agglutination was observed on slides containing cells positive for the corresponding antigen when red cells were mixed with different antisera reagents. Suppose the agglutination wasn’t observed in the red cells that did not contain the corresponding antigen. Three drops from one blood sample were added to each labeled slide, followed by mixing one drop of anti-sera A, anti-sera B anti-sera D, and after 2 minutes we confirmed the positive by Hemagglutination, and the result was registered. The observed agglutination of patient or control blood samples with anti-D serum, detecting the presence of the D antigen on the red blood cells. The absence of agglutination suggests a negative test result, indicating that the D antigen is not detectable. If the result of Rh typing is negative, D” typing will done. 44 (22.1%), of the 198 study subjects, were having blood group A, 27 (13.6%) having group B, 30 (15.1%) having group AB while 98 (49.2%) having group O as shown in Table 1 . Table 1 Characteristics of Study subjects Characteristic Frequency (%) Gender Male 120 (60.6%) Female 78 (39.4%) Residence Urban 62 (31%) Rural 136 (69%) Past history of chronic diseases Diabetes 65 (32.7%) Hypertension 72 (36.2%) Past history of Covid-19 Yes 3(1.5%) No 195(98.5) Covid-19 vaccination Yes 17 (8.5%) no 182 (91.5%) ABO group A 44 (22.1%) B 27 (13.6%) AB 30 (15.1%) O 98 (49.2%) Statistical analysis: The Statistical Package for the Social Science (SPSS for Windows version 20) was used for statistical analysis. T- Test was used for comparing the distribution of a variables among different disease outcome. Blood groups phenotypes distributions among different disease outcome were determined. The magnitude of the blood group phenotypes association with mortality due to the covid-19 disease was assessed by deceptive analysis and Odds ratios will be calculated with 95% confidence intervals using Chi-square test with P < 0.05 values were considered as significant. Results Only 198 patients were confirmed to have Covod-19 had gave their consent to participate in the study. Table.1 is showing the characteristics of study subjects. The mean age of the study subjects was (69.87 ± 1.202) years old; the minimum age is 18 years old and the maximum one is 97 years old. 120 (60.6%) of the study subjects were males and 78 (39.4%) were females. Figure 1 . Is showing the distribution of study subjects according their age in years. The highest incidence of the disease was found among the age group (60–70 years) although, both sexes had shown similar peaks of incidence as shown in Fig. 2 , the mean age of male study subjects was 69.48 ± 17.278 and that of the female was 68.92 ± 16.1443 with no significant differences ( P = 0.828). Analysis of ABO Blood Groups association with mortality due convid-19 had revealed that; the most common blood group was O, accounting for 49.2% of participants (98 individuals) while blood group A was found in 22.1% (44 individuals), blood group AB was found in 15.1% (30 individuals) and blood group B was found in 13.6% (27 individuals) as showing in Table 1 . The Assessment of the role of blood group phenotype in mortality due to COVID-19 indicated that, as showing in Table 2 , individuals with blood group AB had a significantly higher risk of mortality from COVID-19 (OR = 5.570, 95% CI: 2.034–15.248, P = 0.001) compared to those with A, B, or O blood types. Among those with blood group AB, 24.0% (25 individuals) died, while 5.4% (5 individuals) were discharged alive. Further, individuals with blood group A also showed a significantly increased risk of COVID-19 mortality (OR = 6.785, 95% CI: 2.846–16.173, P = 0.0000) when compared to those with AB, B, or O blood types. Specifically, 35.6% (37 individuals) with blood group A died, while 7.5% (7 individuals) were discharged alive. Blood group B was associated with a lower risk of mortality from COVID-19 (OR = 0.395, 95% CI: 0.168–0.929, P = 0.024). For this group, 8.7% (9 individuals) died, and 19.4% (18 individuals) were discharged alive. Blood group O was significantly associated with a lower risk of COVID-19 mortality (OR = 0.221, 95% CI: 0.122–0.403, P = 0.0000). Among those with blood group O, 31.7% (33 individuals) died, and 67.7% (63 individuals) were discharged alive. This indicate that individual who admitted with covid-19 and have blood group phenotype A has seven-fold higher risk for dying that others (OR = 6.785, 95% CI: 2.846–16.173, P = 0.0000) while those who has blood group phenotype B or O are at lower risk of mortality from COVID-19 Table 2 Assessment of the role of blood group phenotype in mortality due to COVID-19 Blood group Disease`s outcome OR ( CI 95%) P -value Dead Discharged alive AB AB 25 (24.0%) 5 (5.4%) 5.570 (2.034–15.248) 0.001 A, B, O 79 (76.0%) 88 (94.6%) A A 37 (35.6%) 7 (7.5%) 6.785 (2.846–16.173) 0.0000 AB, B, O 67 (64.4%) 86 (92.5%) B B 9 (8.7%) 18 (19.4%) 0.395 (0.168–0.929) 0.024 AB, A, O 95 (91.3%) 75 (89.6%) O O 33 (31.7%) 63 (67.7%) 0.221 (0.122–0.403) 0.0000 AB, B, A 71 (68.3%) 30 (32.3%) DISCUSSION This study investigated the relationship between ABO blood groups and mortality in COVID-19 patients within the intensive unit care (ICU) setting. The findings highlight a significant association between ABO blood types and the severity of COVID-19 outcomes. The data indicates that blood groups A and AB are associated with higher mortality rates among COVID-19 patients. Specifically, group A showed the highest severity. Of the 30 patients with blood group AB, 25 (24.0%) died, and only 5 (5.4%) were discharged alive. The odds ratio for group AB was 5.570 (95% CI: 2.034 – 15.248, P-value = 0.0000), suggesting a strong association with increased mortality. Furthermore, among the 44 patients with blood group A, 37 (35.6%) died, and 7 (7.5%) were discharged alive. The odds ratio for group A was 6.785 (95% CI: 2.846 – 16.173, P-value = 0.0000), indicating the highest severity and a significant risk of mortality. In contrast, blood groups B and O appear to have a protective role against severe COVID-19 outcomes. Out of 27 patients with blood group B, 9 (8.7%) died, and 18 (19.4%) were discharged alive. The odds ratio for group B was 0.395 (95% CI: 0.168 – 0.929, P-value = 0.024), suggesting a protective effect. For the 96 patients with blood group O, 33 (31.7%) died, and 63 (67.7%) were discharged alive. The odds ratio for group O was 0.221 (95% CI: 0.122 – 0.403, P-value = 0.00), indicating a strong protective association. The results suggest that individuals with blood groups A and AB may be more susceptible to severe COVID-19 and have a higher risk of mortality. Conversely, individuals with blood groups B and O may have a degree of protection against severe outcomes. These findings align with other studies that have explored the relationship between ABO blood groups and COVID-19 susceptibility and severity. The precise mechanisms underlying these associations are still under investigation, but they may involve factors such as differences in blood group antigens, interactions with the virus, or variations in immune responses. These findings are similar to some previous studies in Sudan [25,26], that estimated the relationship between the ABO blood group and Covid-19 outcomes. The previous studies explained that the interaction between the SARS-CoV-2 S protein and Angiotensin Converting Enzyme 2 (ACE2) is expressed in tissue cells such as the lungs, heart, renal system, and gastrointestinal tract, could be inhibited by anti-A blood group antibodies that are naturally present in blood groups O and B individuals [27]. The anti-A antibodies have been suggested as one of the potential mechanisms, which are present in the plasma of blood groups O and B and absent in the groups A and AB that leads to reduced susceptibility of groups O and B individuals to the COVID-19 infection [28]. Due to interference with the adhesion of SARS-CoV-2 to host cells, thereby preventing the interaction between the S protein of the virus and the (ACE 2) on the cell surface of the target organs. For that, the individuals carry groups A and AB are more susceptible to catch the covid-19 than groups O and B. The protection conferred by group O and B against COVID-19 disease may due to presence of anti-A antibodies in individuals with blood group O and B although, the protection conferred with group O was higher than group B and this can be possibly because the anti-A present in blood group O is from the IgG class, while the anti-A present in blood group B is from the IgM class [28,29], Furthermore, it is reported that the antibody IgM class produces phenotypic glycosylation associated with reduced isoagglutinin activity that is not found in blood group O [30]. Our result found the individuals carrying blood group A showed more severity than blood group AB individuals. This may be due to the combination with blood group B (AB) that helps in reducing the severity. Another possible investigated mechanism is that during the SARS-CoV-2 replication in the host epithelium, it produces glycan antigens similar to those of the host A or B antigens, according to the blood group of the host [30]. When the SARS-CoV-2 produces a specific glycan antigen (A or B), which infects another individual with a different blood group, the corresponding antibodies if found will block attachment between the S protein of the virus and the ACE 2 of the host cells, means SARS-CoV-2 is expressing A antigens[31]. Then individuals with blood group B or O will show protection to some extent, as anti-A antibodies will inhibit the virus adhesion to the host cells. On the other hand, individuals with blood group A or AB will face a greater risk of infection, as they lack the anti-A antibodies. An additional proposed mechanism suggests that some factors of the coagulation system influence the severity of COVID-19 by expressing (A, B) antigens to increase their concentration and life span. Factor VIII and VWF express A antigens are available In individuals with blood group A, leading to the increased susceptibility of group A individuals [32]. CONCLUSION These findings have potential implications for risk stratification and clinical management of COVID-19 patients. Identifying blood groups as a potential risk factor could help in predicting disease severity and tailoring treatment strategies. However, it is crucial to consider these results in conjunction with other clinical factors and patient-specific characteristics. RECOMMENDATION: Further research is needed to elucidate the underlying biological mechanisms responsible for the observed associations. Additionally, studies with larger sample sizes and diverse populations are warranted to validate these findings and explore their generalizability. Declarations Ethics approval and consent to participate : Ethical approval for conducting this study was obtained from the Ministry of Health Department of Epidemics Administration, Gezira state a written consent was obtained from all study subjects before participated in the study. Consent for publication: All authors listed herein confirm their full consent to its publication. Availability of data and material: The datasets analyzed during the current study are available at NCI, University of Gezira Competing interest: All authors declare that they have no competing interests relevant to the content of this manuscript Funding: Not applicable Authors' contributions: Mergani A: Had Contributed in Methodology, data analysis and investigation, Writing original draft, Reviewing and editing. 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Guillon P, Cl_ement M, S_ebille V, Rivain JG, Chou CF, Ruvo€en- Clouet N, et al. Inhibition of the interaction between the SARS-CoV spike protein and its cellular receptor by anti-his blood group antibodies. Glycobiology. 2008;18(12):1085–93. https://doi.org/10.1093/glycob/cwn093. Zaidi FZ, Zaidi ARZ, Abdullah SM, Zaidi SZA. COVID-19 and the ABO blood group connection. Transfus Apher Sci. 2020;59 (5):102838-38. https://doi.org/10.1016/j.transci.2020.102838. Yamamoto F, Yamamoto M, Mu~niz-Diaz E. Blood group ABO polymorphism inhibits SARS-CoV-2 infection and affects COVID-19 progression. Vox Sanguinis. 2020;116(1):15–7. https://doi.org/10.1111/vox.13004. Ewald DR, Sumner SC. Blood type biochemistry and human disease. WIREs Syst Biol Med. 2016;8(6):517–35. https://doi.org/10.1002/wsbm.1355 Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7168882","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":489084613,"identity":"49f77784-4a94-4d3a-9c2e-aee97a49faa6","order_by":0,"name":"Adil Mergani","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7ElEQVRIiWNgGAWjYFCCxMYDEAZj48MGA+K0NMC0NBsSqSWBAaqFgU2ygRgN/O3JDYduVNyz65/d3FY5o+AwUOQAm+QXPFokzjxsOJxzpjh5xp2DbTc3GBwGiiSwScvgs+ZGYsPh3LaEZCCj7eYDoBaGGwxs0hJ4dMiDtfxLSAYy2gpBWuQJaTEAa2lIsAMy2hhBDjMAapH8gEeLIdgvxxISDG8kNkvOMEjnMTyT2GyNzytyx9MfPs6pSbCXu5H+8GPPH2s5ueOHD978gU8PFCQ2QBk8wDhtYOYhQos9Co+RGFtGwSgYBaNgxAAA7lNYgKo7dPEAAAAASUVORK5CYII=","orcid":"","institution":"Kampala International University (KIU-WC)","correspondingAuthor":true,"prefix":"","firstName":"Adil","middleName":"","lastName":"Mergani","suffix":""},{"id":489084614,"identity":"4598f976-4c08-4411-8532-ad59b4def2bb","order_by":1,"name":"Rihab Muhammed Dafallah","email":"","orcid":"","institution":"University of Gezira","correspondingAuthor":false,"prefix":"","firstName":"Rihab","middleName":"Muhammed","lastName":"Dafallah","suffix":""}],"badges":[],"createdAt":"2025-07-20 09:53:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7168882/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7168882/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":87465317,"identity":"20461740-3fbc-4402-b7c8-46efe93c1a88","added_by":"auto","created_at":"2025-07-24 07:14:37","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":15672,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of study subjects according to their age in year\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7168882/v1/62cdae390110cbbff7e2da7b.png"},{"id":87464569,"identity":"873df3de-bcf9-43ed-ad66-1e035a6688ba","added_by":"auto","created_at":"2025-07-24 06:58:37","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":37960,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of study subjects according to their age in year and Gender\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7168882/v1/f0e590bf880dd488d6d0906f.png"},{"id":102746186,"identity":"10c9520c-32d4-4070-8f6b-51724b21b3fa","added_by":"auto","created_at":"2026-02-16 08:56:02","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":643836,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7168882/v1/6817898b-e661-474b-9bd8-8d8655fc5423.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Strong Association of ABO blood groups with COVID-19 associated mortality in Sudan","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe novel coronavirus pandemic disease 2019 (COVID-19) has become a severe health issue. SARS-CoV-2 is one of the coronavirus family species, which are sub-divided into four genera, alpha (a), beta (b), gamma (g), and delta (d), of which only the a and b genera are known to cause infections in human, SARS-CoV-2 belonging to the b coronaviruses [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Coronaviruses are enveloped and have a positive sense of single-stranded RNA genome [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The complicated infections are most common in individuals with cardiovascular disorders, chronic pulmonary, hypertension, and diabetes [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The infected individuals show fever, anoxia, cough with sputum, headache, and diarrhea. Viral infection in complicated conditions leads to renal failure [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe ABO blood group was suggested to be the main factor that may play a role in determining Covid-19 susceptibility, severity, and mortality [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Therefore, ABO blood groups share in covid-19 epidemiology. The ABO blood group system was known in 1901[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], and it includes 3 alleles (A, B, O), which are coded by the ABO gene. These 3 alleles gathered on red blood cells as antigens (RBCs) present in 6 possible genotypes and four phenotypes, resulting in antigens on (RBCs) with antibodies in plasma [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. ABO antibodies can be considered a section of the innate immune systems against some bacterial pathogens and enveloped viruses that may show a crucial role in the pathogenesis and personal susceptibility to certain diseases [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], COVID-19 may be one among these diseases.\u003c/p\u003e\u003cp\u003e\u003cb\u003ePathophysiological Mechanisms of COVID-19 Infection\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eAfter the invasion of the SARS-CoV-2 through the cells lining the nose, viral replication (primary viremia) results in the migration of infection into targeting organs that express angiotensin-converting enzyme 2 (ACE2), such as the lungs, heart, renal system, and gastrointestinal tract [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In some individuals, robust immune responses to viral infiltration induced a release of pro-inflammatory cytokines, a cytokine storm.\u003c/p\u003e\u003cp\u003eThe viral structure and genome must be considered, the SARS-CoV-2 are enveloped positive-strand RNA with the largest known RNA genomes (30\u0026ndash;32) kb\u0026mdash;with a 50-cap structure and 30-poly-A tail [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The SARS-CoV-2 genome consists of ten open reading frames (ORFs) where ORF1a/b alone accounts for about two-thirds of the virus\u0026rsquo;s total RNA [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The translation of the genome RNA produced by ORF1a/b results in two polyproteins (ppla and pplab) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], which are essential for further transcribed to 16 non-structural proteins (nsps) necessary for the production of the viral replicase transcriptase enzyme [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The last one-third of the viral RNA is required to transcript the virus\u0026rsquo;s structural proteins including Spike (S), Envelope (E), Matrix proteins (M), and Nucleocapsid (N) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Some studies confirmed that (nsps) could block the host's innate immune response in the host [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], through the functions of the structural proteins, the envelope has a crucial role in virus pathogenicity as it raises viral assembly and release. The S protein resembles the antigenic region in the virus (spike), which consists of two subunits, the S1 subunit expresses the receptor-binding domain (RBD) required for the virus-host binding (attachment) and the S2 subunit is needed for the virus fusion with the host cell Membrane (invasion). The SARS-CoV-2 penetrated host cells by interacting with the angiotensin-converting enzyme 2 (ACE2) receptor located on human tissue cells. The virus binds to the ACE2 through the S1 glycoprotein, while the penetration is accomplished through the S2 glycoprotein (7,8).\u003c/p\u003e\u003cp\u003eThe hallmark of COVID-19 severity is pneumonia, mediated by viral binding to angiotensin-converting enzyme 2 receptors ( ACE-2) in the respiratory tract and alveoli, The mechanism of SARS-CoV-2 causing pneumonia is more complex [\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], COVID-19-associated pneumonia could lead to acute respiratory distress syndrome (ARDS), and the viral replication can produce an exaggerated immune reaction in the patients. In some cases, the reaction takes place, which is called a \u0026ldquo;cytokine storm\u0026rdquo; that effecting in extensive tissue damage and this responsibility belongs to IL-6, which is produced by activated leukocytes and acts on a large number of cells and tissues [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. IL-6 can promote the activation and differentiation of B-lymphocytes and inhibit the growth of other cells. It also plays an important role in pro-inflammatory and anti-inflammatory effects. It also stimulates the production of acute-phase proteins and plays an important role in thermoregulation, bone maintenance, and the functionality of the central nervous system [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. IL-6 increases during inflammatory diseases, infections, autoimmune disorders, cardiovascular diseases, and some types of cancer [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Cytokine release syndrome (CRS) is an acute systemic inflammatory syndrome, characterized by fever and multiple organ dysfunction [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eSARS-CoV-2 plays a potential role in triggering a hypoxic state in the lungs same as other pathogens, Hypoxia can damage several target organs and play a crucial role in severe pathological status [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Pulmonary vasoconstriction is confirmed as another potential mechanism contributing to hypoxia in COVID-19 pneumonia [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Hypoxia-inducible factor (HIF-1) is a dimeric transcription factor that acts as a master regulator of oxygen levels in cells. This factor includes the HIF-1α and HIF-1β subunits are activated when the cell faces a deficiency of oxygen [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The HIF-1 remains inactivated under normal cellular conditions, but under abnormal condition, this factor with co-activators increase the transcription of several hypoxia response elements (HRE) containing genes which responsible for rising ventilation and improved vascularization during COVID [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. The HIF-1α subunit is the prime mediator of hypoxia in cells; it migrates inside the nucleus leads the transcription of HRE genes, and reflects in several hypoxic symptoms [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. HIF-1α subunit migrates inside the nucleus and leads the transcription of HRE genes, which is reflected in several hypoxic symptoms, it enhances the expression of the ACE-2 gene during COVID-19 infection, which worse the COVID-19 infection and damages the lung cells in the early stage [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. In the late stage, the HIF-1α reduced expression of ACE-2; it can be beneficial for reducing the risk of enhanced tissue and organ damage from COVID-19 infection [22 ].\u003c/p\u003e\u003cp\u003eThe variation in clinical features in SARS-Cov-2-infected individuals is commonly observed, so some individuals are more susceptible to the infection than others are. The epidemiological investigations confirmed that around 80% of the infected individuals are asymptomatic but contagious. Main COVID-19-associated symptoms such as cough and fever, Dyspnea, Headache, Sore throat, Rhinorrhea, or severe respiratory complications, such as acute respiratory distress syndrome (ARDS) [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], that need mechanical ventilation and support in an intensive care unit (ICU), systemic manifestations to multiorgan in terms of sepsis, septic shock, and multiple organs dysfunction syndromes (MODS) [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Gastrointestinal symptoms have also been reported such as nausea and diarrhea\u0026mdash;this variation in COVID-19 clinical features is due to differences in the body's immune response to the infection. The primary effective immune response can reduce the viral load and prevent the infection from reaching the target organs [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], whereas an extreme immune response can cause an excessive inflammatory reaction leading to severe adverse consequences [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Moreover, statistics analysis suggests that metabolic disorders have a role in directing the response of the body to the infection, due to chronic diseases such as diabetes, hypertension, ion, and liver diseases among the severe COVID-19 cases.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e\u003cb\u003eStudy design and selection of study subjects\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eA prospective cross-sectional study was carried out during the period, from October 2021 to October 2022, at the intensive care units (ICU) in Covid-19 Isolation Zones (Sugatra and Mycetoma Center) in Wad Medani - Gezira state, Sudan to study the association between ABO blood groups and the prognosis and associated mortality of Covid-19. All patients, who were admitted in the Zones and were confirmed by RT-PCR to have Covid-19, were invited to be included in the study. A structured questionnaire was designed to collect personal information about the study patients group, such as age, gender, and chronic disease.\u003c/p\u003e\u003cp\u003e\u003cb\u003eBlood grouping of selected study subjects\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eBlood grouping of all selected subjects was done using slide agglutination method. Two ml of venous blood were collected in a sterile tube from each patient. Three drops from each sample were added to one slide labeled with Anti-A, Anti-B, and Anti-D. Agglutination was observed on slides containing cells positive for the corresponding antigen when red cells were mixed with different antisera reagents. Suppose the agglutination wasn\u0026rsquo;t observed in the red cells that did not contain the corresponding antigen. Three drops from one blood sample were added to each labeled slide, followed by mixing one drop of anti-sera A, anti-sera B anti-sera D, and after 2 minutes we confirmed the positive by Hemagglutination, and the result was registered. The observed agglutination of patient or control blood samples with anti-D serum, detecting the presence of the D antigen on the red blood cells. The absence of agglutination suggests a negative test result, indicating that the D antigen is not detectable. If the result of Rh typing is negative, D\u0026rdquo; typing will done. 44 (22.1%), of the 198 study subjects, were having blood group A, 27 (13.6%) having group B, 30 (15.1%) having group AB while 98 (49.2%) having group O as shown in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCharacteristics of Study subjects\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eCharacteristic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFrequency (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003eGender\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e120 (60.6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e78 (39.4%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003eResidence\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eUrban\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e62 (31%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRural\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e136 (69%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003ePast history of chronic diseases\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDiabetes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e65 (32.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e72 (36.2%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003ePast history of Covid-19\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3(1.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e195(98.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003eCovid-19 vaccination\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17 (8.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eno\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e182 (91.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e\u003cb\u003eABO group\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e44 (22.1%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27 (13.6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e30 (15.1%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eO\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e98 (49.2%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis:\u003c/h2\u003e\u003cp\u003eThe Statistical Package for the Social Science (SPSS for Windows version 20) was used for statistical analysis. \u003cem\u003eT- Test\u003c/em\u003e was used for comparing the distribution of a variables among different disease outcome. Blood groups phenotypes distributions among different disease outcome were determined. The magnitude of the blood group phenotypes association with mortality due to the covid-19 disease was assessed by deceptive analysis and Odds ratios will be calculated with 95% confidence intervals using Chi-square test with \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 values were considered as significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eOnly 198 patients were confirmed to have Covod-19 had gave their consent to participate in the study. \u003cb\u003eTable.1\u003c/b\u003e is showing the characteristics of study subjects. The mean age of the study subjects was (69.87\u0026thinsp;\u0026plusmn;\u0026thinsp;1.202) years old; the minimum age is 18 years old and the maximum one is 97 years old. 120 (60.6%) of the study subjects were males and 78 (39.4%) were females. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Is showing the distribution of study subjects according their age in years. The highest incidence of the disease was found among the age group (60\u0026ndash;70 years) although, both sexes had shown similar peaks of incidence as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, the mean age of male study subjects was 69.48\u0026thinsp;\u0026plusmn;\u0026thinsp;17.278 and that of the female was 68.92\u0026thinsp;\u0026plusmn;\u0026thinsp;16.1443 with no significant differences (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.828).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eAnalysis of ABO Blood Groups association with mortality due convid-19 had revealed that; the most common blood group was O, accounting for 49.2% of participants (98 individuals) while blood group A was found in 22.1% (44 individuals), blood group AB was found in 15.1% (30 individuals) and blood group B was found in 13.6% (27 individuals) as showing in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The Assessment of the role of blood group phenotype in mortality due to COVID-19 indicated that, as showing in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, individuals with blood group AB had a significantly higher risk of mortality from COVID-19 (OR\u0026thinsp;=\u0026thinsp;5.570, 95% CI: 2.034\u0026ndash;15.248, P\u0026thinsp;=\u0026thinsp;0.001) compared to those with A, B, or O blood types. Among those with blood group AB, 24.0% (25 individuals) died, while 5.4% (5 individuals) were discharged alive. Further, individuals with blood group A also showed a significantly increased risk of COVID-19 mortality (OR\u0026thinsp;=\u0026thinsp;6.785, 95% CI: 2.846\u0026ndash;16.173, P\u0026thinsp;=\u0026thinsp;0.0000) when compared to those with AB, B, or O blood types. Specifically, 35.6% (37 individuals) with blood group A died, while 7.5% (7 individuals) were discharged alive. Blood group B was associated with a lower risk of mortality from COVID-19 (OR\u0026thinsp;=\u0026thinsp;0.395, 95% CI: 0.168\u0026ndash;0.929, P\u0026thinsp;=\u0026thinsp;0.024). For this group, 8.7% (9 individuals) died, and 19.4% (18 individuals) were discharged alive. Blood group O was significantly associated with a lower risk of COVID-19 mortality (OR\u0026thinsp;=\u0026thinsp;0.221, 95% CI: 0.122\u0026ndash;0.403, P\u0026thinsp;=\u0026thinsp;0.0000). Among those with blood group O, 31.7% (33 individuals) died, and 67.7% (63 individuals) were discharged alive. This indicate that individual who admitted with covid-19 and have blood group phenotype A has seven-fold higher risk for dying that others (OR\u0026thinsp;=\u0026thinsp;6.785, 95% CI: 2.846\u0026ndash;16.173, P\u0026thinsp;=\u0026thinsp;0.0000) while those who has blood group phenotype B or O are at lower risk of mortality from COVID-19\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eAssessment of the role of blood group phenotype in mortality due to COVID-19\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e\u003cp\u003eBlood group\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003eDisease`s outcome\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cem\u003eOR\u003c/em\u003e\u003c/p\u003e\u003cp\u003e(\u003cem\u003eCI\u003c/em\u003e 95%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eDead\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDischarged alive\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003eAB\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eAB\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e25 (24.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5 (5.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003e5.570\u003c/b\u003e\u003c/p\u003e\u003cp\u003e(2.034\u0026ndash;15.248)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eA, B, O\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e79 (76.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e88 (94.6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003eA\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eA\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e37 (35.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7 (7.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003e6.785\u003c/b\u003e\u003c/p\u003e\u003cp\u003e(2.846\u0026ndash;16.173)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003e0.0000\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eAB, B, O\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e67 (64.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e86 (92.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003eB\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eB\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (8.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e18 (19.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003e0.395\u003c/b\u003e\u003c/p\u003e\u003cp\u003e(0.168\u0026ndash;0.929)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003e0.024\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eAB, A, O\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e95 (91.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e75 (89.6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003eO\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eO\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e33 (31.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e63 (67.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003e0.221\u003c/b\u003e\u003c/p\u003e\u003cp\u003e(0.122\u0026ndash;0.403)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003e0.0000\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eAB, B, A\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e71 (68.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e30 (32.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis study investigated the relationship between ABO blood groups and mortality in COVID-19 patients within the intensive unit care (ICU) setting. The findings highlight a significant association between ABO blood types and the severity of COVID-19 outcomes. The data indicates that blood groups A and AB are associated with higher mortality rates among COVID-19 patients. Specifically, group A showed the highest severity. Of the 30 patients with blood group AB, 25 (24.0%) died, and only 5 (5.4%) were discharged alive. The odds ratio for group AB was 5.570 (95% CI: 2.034 \u0026ndash; 15.248, P-value = 0.0000), suggesting a strong association with increased mortality. Furthermore, among the 44 patients with blood group A, 37 (35.6%) died, and 7 (7.5%) were discharged alive. The odds ratio for group A was 6.785 (95% CI: 2.846 \u0026ndash; 16.173, P-value = 0.0000), indicating the highest severity and a significant risk of mortality. In contrast, blood groups B and O appear to have a protective role against severe COVID-19 outcomes. Out of 27 patients with blood group B, 9 (8.7%) died, and 18 (19.4%) were discharged alive. The odds ratio for group B was 0.395 (95% CI: 0.168 \u0026ndash; 0.929, P-value = 0.024), suggesting a protective effect. For the 96 patients with blood group O, 33 (31.7%) died, and 63 (67.7%) were discharged alive. The odds ratio for group O was 0.221 (95% CI: 0.122 \u0026ndash; 0.403, P-value = 0.00), indicating a strong protective association. The results suggest that individuals with blood groups A and AB may be more susceptible to severe COVID-19 and have a higher risk of mortality. Conversely, individuals with blood groups B and O may have a degree of protection against severe outcomes. These findings align with other studies that have explored the relationship between ABO blood groups and COVID-19 susceptibility and severity. The precise mechanisms underlying these associations are still under investigation, but they may involve factors such as differences in blood group antigens, interactions with the virus, or variations in immune responses.\u0026nbsp;These findings are similar\u0026nbsp;to some previous studies in Sudan [25,26], that estimated the relationship between the ABO blood group and Covid-19 outcomes. The previous studies explained that the interaction between the SARS-CoV-2 S protein and Angiotensin Converting Enzyme 2 (ACE2) is expressed in tissue cells such as the lungs, heart, renal system, and gastrointestinal tract, could be inhibited by anti-A blood group antibodies that are naturally present in blood groups O and B individuals [27]. The anti-A antibodies have been suggested as one of the potential mechanisms, which are present in the plasma of blood groups O and B and absent in the groups A and AB that leads to reduced susceptibility of groups O and B individuals to the COVID-19 infection [28]. Due to interference with the adhesion of SARS-CoV-2 to host cells, thereby preventing the interaction between the S protein of the virus and the (ACE 2) on the cell surface of the target organs. For that, the individuals carry groups A and AB are more susceptible to catch the covid-19 than groups O and B.\u003c/p\u003e\n\u003cp\u003eThe protection conferred by group O and B against COVID-19 disease may due to presence of anti-A antibodies in individuals with blood group O and B although, the protection conferred with group O was higher than group B and this can be possibly because the anti-A present in blood group O is from the IgG class, while the anti-A present in blood group B is from the IgM class [28,29], Furthermore, it is reported that the antibody IgM class produces phenotypic glycosylation associated with reduced isoagglutinin activity that is not found in blood group O [30]. Our result found the individuals carrying blood group A showed more severity than blood group AB individuals. This may be due to the combination with blood group B (AB) that helps in reducing the severity. Another possible investigated mechanism is that during the SARS-CoV-2 replication in the host epithelium, it produces glycan antigens similar to those of the host A or B antigens, according to the blood group of the host [30]. When the SARS-CoV-2 produces a specific glycan antigen (A or B), which infects another individual with a different blood group, the corresponding antibodies if found will block attachment between the S protein of the virus and the ACE 2 of the host cells, means SARS-CoV-2 is expressing A antigens[31]. Then individuals with blood group B or O will show protection to some extent, as anti-A antibodies will inhibit the virus adhesion to the host cells. On the other hand, individuals with blood group A or AB will face a greater risk of infection, as they lack the anti-A antibodies. An additional proposed mechanism suggests that some factors of the coagulation system influence the severity of COVID-19 by expressing (A, B) antigens to increase their concentration and life span. Factor VIII and VWF express A antigens are available In individuals with blood group A, leading to the increased susceptibility of group A individuals [32].\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThese findings have potential implications for risk stratification and clinical management of COVID-19 patients. Identifying blood groups as a potential risk factor could help in predicting disease severity and tailoring treatment strategies. However, it is crucial to consider these results in conjunction with other clinical factors and patient-specific characteristics.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRECOMMENDATION:\u003c/strong\u003e Further research is needed to elucidate the underlying biological mechanisms responsible for the observed associations. Additionally, studies with larger sample sizes and diverse populations are warranted to validate these findings and explore their generalizability.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003cstrong\u003e: \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval for conducting this study was obtained from the Ministry of Health Department of Epidemics Administration, Gezira state a written consent was obtained from all study subjects before participated in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors listed herein confirm their full consent to its publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets analyzed during the current study are available at NCI, University of Gezira\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interest:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare that they have no competing interests relevant to the content of this manuscript\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e Not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003eMergani A: Had Contributed in Methodology, data analysis and investigation, Writing original draft, Reviewing and editing. \u003c/li\u003e\n\u003cli\u003eDafallah MR: Had Contributed in Methodology, Reviewing and editing. \u003c/li\u003e\n\u003cli\u003eAll authors: reading and approval of the manuscript. \u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe extend our sincere gratitude to all participants for their invaluable contributions to this study. Our thanks also go to the healthcare workers and institutions who supported this research.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eGuo Y-R, Cao Q-D, Hong Z-S, Yuan-Yang T, Shou-Deng C, Hong- Jun J, et al. The Origin, transmission, and clinical therapies on Coronavirus disease 2019 (COVID-19) outbreak - an update on the status. Mil Med Res. 2020;7(1):11. https://doi.org/10.1186/s40779-020-00240-0.\u003c/li\u003e\n \u003cli\u003eFehr AR, Perlman S. Coronaviruses: an overview of their replication and pathogenesis. Methods Mol Biol. 2015;1282:1\u0026ndash;23. https://doi.org/10.1007/978-1-4939-2438-7_1.\u003c/li\u003e\n \u003cli\u003eShibeeb S, Khan A. Thrombotic and Hypercoagulability Complications of COVID-19: An Update. J Blood Med. 2021;2021 (12):785\u0026ndash;93. https://doi.org/10.2147/JBM.S316014.\u003c/li\u003e\n \u003cli\u003eHansrivijit, P., Gadhiya, K. P., Gangireddy, M. \u0026amp; Goldman, J. D. Risk factors, clinical characteristics, and prognosis of acute kidney injury in hospitalized COVID-19 patients: a retrospective cohort study. \u003cem\u003eMedicines\u0026nbsp;\u003c/em\u003e\u003cstrong\u003e8\u003c/strong\u003e, 4 (2021).\u003c/li\u003e\n \u003cli\u003eMiotto M, Di Rienzo L, Gosti G, Milanetti E, Ruocco G. Does blood type affect the COVID-19 infection pattern? PLoS ONE. 2021;16(5):e0251535.\u003c/li\u003e\n \u003cli\u003eLesky E. Viennese serological research about the year 1900: its contribution to the development of clinical medicine. Bull N Y Acad Med. 1973;49(2):100\u0026ndash;11.\u003c/li\u003e\n \u003cli\u003eWalls AC, Park Y-J, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell. 2020;181(2):281\u0026minus;92.e6. https://doi.org/10.1016/j.cell.2020.02.058.\u003c/li\u003e\n \u003cli\u003eZhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270\u0026ndash;3. https://doi.org/10.1038/s41586-020-2012-7.\u003c/li\u003e\n \u003cli\u003eLi X, Geng M, Peng Y, Meng L, Lu S. Molecular immune pathogenesis and diagnosis of COVID-19. J Pharm Anal. 2020;10 (2):102 8. https://doi.org/10.1016/j.jpha.2020.03.001.\u003c/li\u003e\n \u003cli\u003eLei, J.; Kusov, Y.; Hilgenfeld, R. Nsp3 of coronaviruses: Structures and functions of a large multi-domain protein. Antivir. Res. 2018, 149, 58\u0026ndash;74.\u003c/li\u003e\n \u003cli\u003eLetko, M.; Marzi, A.; Munster, V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat. Microbiol. 2020, 5, 562\u0026ndash;569.\u003c/li\u003e\n \u003cli\u003eCascella, M.; Rajnik, M.; Cuomo, A.; Dulebohn, S.C.; Di Napoli, R. Features, evaluation and treatment coronavirus (COVID-19). In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2020. Available online: http://www.ncbi.nlm.nih.gov/books/NBK554776/ (accessed on 31 March 2020).\u003c/li\u003e\n \u003cli\u003ePyle, C.J.; Uwadiae, F.I.; Swieboda, D.P.; Harker, J.A. Early IL-6 signaling promotes IL-27 dependent maturation of regulatory T cells in the lungs and resolution of viral immunopathology. PLoS Pathog. 2017, 13.\u003c/li\u003e\n \u003cli\u003eChen, C.; Zhang, X.R.; Ju, Z.Y.; He, W.F. Advances in the research of cytokine storm mechanism induced by Corona Virus Disease 2019 and the corresponding immunotherapies. Zhonghua Shao Shang Za Zhi 2020, 36.\u003c/li\u003e\n \u003cli\u003eBennardo, F.; Bu_one, C.; Giudice, A. New therapeutic opportunities for COVID-19 patients with Tocilizumab: Possible correlation of interleukin-6 receptor inhibitors with osteonecrosis of the jaws. Oral Oncol. 2020.\u003c/li\u003e\n \u003cli\u003eRose-John, S. Interleukin-6 family cytokines. Cold Spring Harb. Perspect. Biol. 2018, 10.\u003c/li\u003e\n \u003cli\u003eLupia, T.; Scabini, S.; Mornese Pinna, S.; Di Perri, G.; De Rosa, F.G.; Corcione, S. 2019 novel coronavirus (2019-nCoV) outbreak: A new challenge. J. Glob. Antimicrob. Resist. 2020, 21, 22\u0026ndash;27.\u003c/li\u003e\n \u003cli\u003eYang, Y.; Peng, F.; Wang, R.; Guan, K.; Jiang, T.; Xu, G.; Sun, J.; Chang, C. The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China. J. Autoimmune. 2020.\u003c/li\u003e\n \u003cli\u003eJennifer E. Ziello Y. Hypoxia-Inducible Factor (HIF)-1 Regulatory Pathway and its Potential for Therapeutic Intervention in Malignancy and Ischemia [Internet]. PubMed Central (PMC).2020 [cited 28 August 2020]. Available from: https://www.ncbi.nlm. nih.gov/pmc/articles/PMC2140184/ 27.\u003c/li\u003e\n \u003cli\u003eMarieb E, Hoehn K (2013) Chapter 22: The respiratory system. In: Human anatomy and physiology, 9th ed. Pearson, pp 801\u0026ndash;841.\u003c/li\u003e\n \u003cli\u003eOchs M, Timm S, Elezkurtaj S, Horst D, Meinhardt J, Heppner F, et al (2021) Collapse induration of alveoli is an ultra-structural finding in a COVID-19 patient. EurRespir J 14:2004165\u003c/li\u003e\n \u003cli\u003eZhang R, Wu Y, Zhao M, Liu C, Zhou L, Shen S et al (2009) Role of HIF-1\u0026alpha; in the regulation ACE and ACE2 expression in hypoxic human pulmonary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 297(4): L631\u0026ndash;L640\u003c/li\u003e\n \u003cli\u003eIng AJ, Cocks C, Green JP. COVID-19: in the footsteps of Ernest Shackleton. Thorax. 2020;75(8):693. https://doi.org/10.1136/ Thoraxjnl-2020-215091.\u003c/li\u003e\n \u003cli\u003eCosta FF, Ros_ario WR, Ribeiro Farias AC, de Souza RG, Duarte Gondim RS, Barroso WA. Metabolic syndrome and COVID-19: an update on the associated comorbidities and proposed therapies. Diabetes Metab Syndr. 2020;14(5):809\u0026ndash;14. https://doi.org/ 10.1016/j.dsx.2020.06.016.\u003c/li\u003e\n \u003cli\u003eMalaz F. M., Albara A., Osman. M.E, Asaad M. B. and Hisham. A. W, 2021. Susceptibility of Blood Group Infection with COVID-19 Disease Among Sudanese Patients Suffering from Different Chronic Diseases. \u003cem\u003ePakistan Journal of Biological Sciences, 24: 815-820\u003c/em\u003e\u003cem\u003e.\u003c/em\u003e31.\u003c/li\u003e\n \u003cli\u003eSudan: WHO Coronavirus Disease (COVID-19) Dashboard | WHO Coronavirus Disease (COVID-19) Dashboard (cited 2021 Jan 26). https:// covid 19. who. int/ region/ emro/ country/ sd\u003c/li\u003e\n \u003cli\u003eMiotto M, Di Rienzo L, Gosti G, Milanetti E, Ruocco G. Does blood type affect the COVID-19 infection pattern? PLoS ONE .2021;16(5):e0251535.\u003c/li\u003e\n \u003cli\u003eGerard C, Maggipinto G, Minon J-M. COVID-19 and ABO blood group: another viewpoint. Br J Haematol. 2020;190 (2):e93\u0026ndash;4. https://doi.org/10.1111/bjh.16884.\u003c/li\u003e\n \u003cli\u003eGuillon P, Cl_ement M, S_ebille V, Rivain JG, Chou CF, Ruvo\u0026euro;en- Clouet N, et al. Inhibition of the interaction between the SARS-CoV spike protein and its cellular receptor by anti-his blood group antibodies. Glycobiology. 2008;18(12):1085\u0026ndash;93. https://doi.org/10.1093/glycob/cwn093.\u003c/li\u003e\n \u003cli\u003eZaidi FZ, Zaidi ARZ, Abdullah SM, Zaidi SZA. COVID-19 and the ABO blood group connection. Transfus Apher Sci. 2020;59 (5):102838-38. https://doi.org/10.1016/j.transci.2020.102838.\u003c/li\u003e\n \u003cli\u003eYamamoto F, Yamamoto M, Mu~niz-Diaz E. Blood group ABO polymorphism inhibits SARS-CoV-2 infection and affects COVID-19 progression. Vox Sanguinis. 2020;116(1):15\u0026ndash;7. https://doi.org/10.1111/vox.13004.\u003c/li\u003e\n \u003cli\u003eEwald DR, Sumner SC. Blood type biochemistry and human disease. WIREs Syst Biol Med. 2016;8(6):517\u0026ndash;35. https://doi.org/10.1002/wsbm.1355\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Covid-19, ABO blood groups, mortality","lastPublishedDoi":"10.21203/rs.3.rs-7168882/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7168882/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eThe SARS-CoV-2 pandemic, which began in late 2019, has had a significant impact on global health, economic, and social life, causing COVID-19 disease with a spectrum ranging from asymptomatic infection to mortality. The ABO blood group system polymorphism has been suggested as a potential mechanism influencing the severity and mortality of COVID-19. Research indicates that individuals with blood types O and B may experience decreased severity and mortality from SARS-CoV-2. Conversely, individuals with blood types A and AB have been shown to be at higher risk for serious outcomes from SARS-CoV-2. This suggests that the ABO blood group plays a crucial role in the epidemiology of COVID-19\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e A prospective cross-sectional study was carried out during the period, from October 2021 to October 2022, at the intensive care units (ICU) in Covid-19 Isolation Zones (Sugatra and Mycetoma Center) in Wad Medani - Gezira\u003cstrong\u003e \u003c/strong\u003estate, Sudan to study the association between ABO blood groups and the prognosis and associated mortality of Covid-19. Blood grouping of all selected subjects was done using slide agglutination method and structured questionnaire was used to collect personal, demographic and the disease prognosis data of the study subjects,\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e The study's findings indicate that individuals with blood types O and B are more protected against COVID-19 infection and may have a lower mortality rate. Specifically, blood group O offered more protection than blood group B. In contrast, individuals with blood types A and AB showed an increased severity and mortality rate from COVID-19 infection. Among these, individuals with blood type AB experienced less severe outcomes compared to those with blood type A.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eThe study suggests a strong association between ABO blood groups and COVID-19 associated mortality, with blood types O and B offering more protection and blood types A and AB being associated with increased severity and mortality.\u003c/p\u003e","manuscriptTitle":"Strong Association of ABO blood groups with COVID-19 associated mortality in Sudan","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-24 06:58:32","doi":"10.21203/rs.3.rs-7168882/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fcb4e7b9-3fb2-4b7c-98d8-eac84f09d4e9","owner":[],"postedDate":"July 24th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":51921851,"name":"Health sciences/Diseases"},{"id":51921852,"name":"Health sciences/Health care"},{"id":51921853,"name":"Health sciences/Medical research"},{"id":51921854,"name":"Biological sciences/Microbiology"},{"id":51921855,"name":"Health sciences/Risk factors"}],"tags":[],"updatedAt":"2026-02-12T17:11:10+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-24 06:58:32","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7168882","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7168882","identity":"rs-7168882","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}