AUTHOR=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 

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

JOURNAL=Frontiers in Medicine

VOLUME=8

YEAR=2022

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.759648

DOI=10.3389/fmed.2021.759648

ISSN=2296-858X

ABSTRACT=<p><bold>Introduction:</bold> Coronavirus disease 2019 (COVID-19) disease severity differs widely due to numerous factors including <italic>ABO</italic> 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 <italic>ABO</italic> 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).</p><p><bold>Methods:</bold> 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 (<italic>n</italic> = 453) and critical [intensive care unit (ICU) patients] (<italic>n</italic> = 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<italic>:</italic> 136125788-136150617) in the <italic>ABO</italic> gene, in association with critical COVID-19 hospital presentation.</p><p><bold>Results:</bold> Patients with blood group O [odds ratio (OR): 0.51 (0.33, 0.79); <italic>p</italic> = 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 <italic>ABO</italic> 3'untranslated region (UTR): rs199969472 (<italic>p</italic> = 0.0052), rs34266669 (<italic>p</italic> = 0.0052), rs76700116 (<italic>p</italic> = 0.0052), rs7849280 (<italic>p</italic> = 0.0052), rs34039247 (<italic>p</italic> = 0.0104), rs10901251 (<italic>p</italic> = 0.0165), rs9411475 (<italic>p</italic> = 0.0377), and rs13291798 (<italic>p</italic> = 0.0377).</p><p><bold>Conclusion:</bold> Our findings suggest that there are novel allelic variants that link genetic variants of the <italic>ABO</italic> 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 <italic>ABO gene</italic> allelic associations with COVID-19 severity within the Middle Eastern population.</p>