This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. BLOOD RESEARCH VOLUME 58ㆍNUMBER 3 September 2023 ORIGINAL ARTICLE ABO blood group and rhesus factor association with inpatient COVID-19 mortality and severity: a two-year retrospective review Alexander T. Phan 1 , Ari A. Ucar 1 , Aldin Malkoc 2 , Janie Hu 1 , Luke Buxton 3 , Alan W. Tseng 1 , Fanglong Dong 4 , Julie P.T. Nguyễn 5 , Arnav P. Modi 5 , Ojas Deshpande 5 , Johnson Lay 5 , Andrew Ku 5 , Dotun Ogunyemi 4 , Sarkis Arabian 3 1 Department of Internal Medicine, 2 Department of General Surgery, 3 Department of Critical Care Medicine, 4 Department of Graduate Medical Education, Arrowhead Regional Medical Center, 5 School of Medicine, California University of Science and Medicine, Colton, CA, USA p-ISSN 2287-979X / e-ISSN 2288-0011 https://doi.org/10.5045/br.2023.2023122 Blood Res 2023;58:138-144. Received on June 25, 2023 Revised on September 6, 2023 Accepted on September 14, 2023 Background Early reports have indicated a relationship between ABO and rhesus blood group types and infection with SARS-CoV-2. We aim to examine blood group type associations with COVID-19 mortality and disease severity. Methods This is a retrospective chart review of patients ages 18 years or older admitted to the hospi- tal with COVID-19 between January 2020 and December 2021. The primary outcome was COVID-19 mortality with respect to ABO blood group type. The secondary outcomes were 1. Severity of COVID-19 with respect to ABO blood group type, and 2. Rhesus factor association with COVID-19 mortality and disease severity. Disease severity was defined by degree of supplemental oxygen requirements (ambient air, low-flow, high-flow, non-invasive mechanical ventilation, and invasive mechanical ventilation). Results The blood type was collected on 596 patients with more than half (54%, N=322) being O+. The ABO blood type alone was not statistically associated with mortality (P =0.405), while the RH blood type was statistically associated with mortality (P ＜0.001). There was statistically significant association between combined ABO and RH blood type and mor- tality (P =0.014). Out of the mortality group, the O+ group had the highest mortality (52.3%), followed by A+ (22.8%). The combined ABO and RH blood type was statistically significantly associated with degree of supplemental oxygen requirements (P =0.005). The Kaplan-Meier curve demonstrated that Rh- patients had increased mortality. Conclusion ABO blood type is not associated with COVID-19 severity and mortality. Rhesus factor status is associated with COVID-19 severity and mortality. Rhesus negative patients were associated with increased mortality risk. Key Words COVID-19, Infectious disease, Pulmonary medicine, Mechanical ventilation, SARS-CoV-2 Correspondence to Alexander T. Phan, M.D. Department of Internal Medicine, Arrowhead Regional Medical Center, 400 N. Pepper Avenue, Colton, CA 92324, USA E-mail: PhanA1@armc.sbcounty.gov Ⓒ 2023 Korean Society of Hematology INTRODUCTION The ABO blood group, which includes the 4 blood types A, AB, B, and O, plays a role in various infectious and non-in- fectious human diseases. Histo-blood group antigens located on the surface of red blood cells represent inherited poly- morphic traits, and differences in the expression of these antigens affect susceptibility to many infections [1]. Blood group antigens act as receptors or coreceptors for pathogens such as hepatitis B virus, middle east respiratory syndrome associated coronavirus (MERS-CoV), severe acute respiratory syndrome associated coronavirus (SARS-CoV), norovirus, malaria, other microorganisms, and parasites [1-4]. Additionally,