Allelic Variants Within the ABO Blood Group Phenotype Confer Protection Against Critical COVID-19 Hospital Presentation

• Published in: Frontiers in medicine 2022-01, Vol.8, p.759648-759648
• Main Authors: Jelinek, Herbert F, Mousa, Mira, Alkaabi, Nawal, Alefishat, Eman, Daw Elbait, Gihan, Kannout, Hussein, AlHumaidan, Hiba, Selvaraj, Francis Amirtharaj, Imambaccus, Hala, Weber, Stefan, Uddin, Maimunah, Abdulkarim, Fatema, Mahboub, Bassam, Tay, Guan, Alsafar, Habiba
• Format: Article
• Language: English
• Subjects: ABO blood group; COVID-19 pandemic; disease severity; infection–immunology; Medicine; SARS-CoV-2; UAE
• ISSN: 2296-858X; 2296-858X
• DOI: 10.3389/fmed.2021.759648

Coronavirus disease 2019 (COVID-19) disease severity differs widely due to numerous factors including gene-derived susceptibility or resistance. The objective of this study was to investigate the association of the ABO blood group and genetic variations of the gene with COVID-19 severity in a heterogeneous hospital population sample from the United Arab Emirates, with the use of an epidemiological and candidate gene approach from a genome-wide association study (GWAS). In this cross-sectional study, a total of 646 participants who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were recruited from multiple hospitals and population-based (quarantine camps) recruitment sites from March 2020 to February 2021. The participants were divided into two groups based on the severity of COVID-19: noncritical ( = 453) and critical [intensive care unit (ICU) patients] ( = 193), as per the COVID-19 Reporting and Data System (CO-RADS) classification. The multivariate logistic regression analysis demonstrated the association of ABO blood type as well as circulating anti-A antibodies and anti-B antibodies as well as A and B antigens, in association with critical COVID-19 hospital presentation. A candidate gene analysis approach was conducted from a GWAS where we examined 240 single nucleotide polymorphisms (SNPs) (position in chr9 136125788-136150617) in the gene, in association with critical COVID-19 hospital presentation. Patients with blood group O [odds ratio (OR): 0.51 (0.33, 0.79); = 0.003] were less likely to develop critical COVID-19 symptoms. Eight alleles have been identified to be associated with a protective effect of blood group O in 3'untranslated region (UTR): rs199969472 ( = 0.0052), rs34266669 ( = 0.0052), rs76700116 ( = 0.0052), rs7849280 ( = 0.0052), rs34039247 ( = 0.0104), rs10901251 ( = 0.0165), rs9411475 ( = 0.0377), and rs13291798 ( = 0.0377). Our findings suggest that there are novel allelic variants that link genetic variants of the gene and ABO blood groups contributing to the reduced risk of critical COVID-19 disease. This study is the first study to combine genetic and serological evidence of the involvement of the ABO blood groups and the allelic associations with COVID-19 severity within the Middle Eastern population.