Lewis and ABO histo‐blood types and the secretor status of patients hospitalized with COVID‐19 implicate a role for ABO antibodies in susceptibility to infection with SARS‐CoV‐2

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets the respiratory and gastric epithelium, causing coronavirus disease 2019 . Tissue antigen expression variations influence host susceptibility to many infections. This study aimed to investigate the closely linked Lewis (FUT3) and ABO histo-blood types, including secretor (FUT2) status, to infections with SARS-CoV-2 and the corresponding severity of COVID-19.Study Design and Methods: Patients (Caucasians, n = 338) were genotyped for ABO, FUT3, and FUT2, and compared to a reference population of blood donors (n = 250,298). The association between blood types and severity of COVID-19 was addressed by dividing patients into four categories: hospitalized individuals in general wards, patients admitted to the intensive care unit with and without intubation, and deceased patients. Comorbidities were considered in subsequent analyses. Results: Patients with blood type Lewis (aÀbÀ) or O were significantly less likely to be hospitalized (odds ratio [OR] 0.669, confidence interval [CI] 0.446-0.971, OR 0.710, CI 0.556-0.900, respectively), while type AB was significantly more prevalent in the patient cohort (OR 1.519, CI 1.014-2.203). The proportions of secretors/nonsecretors, and Lewis a+ or Lewis b+ types were consistent between patients and controls. The analyzed blood groups were not associated with the clinical outcome as defined.Discussion: Blood types Lewis (aÀbÀ) and O were found to be protective factors, whereas the group AB is suggested to be a risk factor for COVID-19. The antigens investigated may not be prognostic for disease severity, but a role for ABO isoagglutinins in SARS-CoV-2 infections is strongly suggested.

Rapid genotyping of 508G>A (rs3745635) and 1067T>A (rs3894326) of FUT3 by a duplex Eprobe‐mediated melting curve analysis

“…Several studies suggested that FUT3 polymorphisms are associated with Helicobacter pylori infection, enteric infections, COVID-19 susceptibility, ischemic heart diseases, inflammatory bowel diseases and ankylosing spondylitis [2,[13][14][15][16][17]. Large-scale replication studies in various populations are necessary to verify these associations.…”

Viral load at hospitalization is an independent predictor of severe COVID‐19

“…Still, any putative effect of blood group antigens on disease severity remains unclear 10 . Few studies have investigated the role of secretor status, an important susceptibility factor for many viruses infecting the mucosa, in COVID‐19, 11 and the results are conflicting 33,34 . The underlying mechanisms behind the observed findings of blood groups and risk of COVID‐19 are not fully understood, but several hypotheses have been proposed.…”

“… 10 Few studies have investigated the role of secretor status, an important susceptibility factor for many viruses infecting the mucosa, in COVID‐19, 11 and the results are conflicting. 33 , 34 The underlying mechanisms behind the observed findings of blood groups and risk of COVID‐19 are not fully understood, but several hypotheses have been proposed. These include a facilitation of binding of the SARS‐CoV‐2 virion to blood group A epitopes in the respiratory tract, 35 or inhibition of the SARS‐CoV‐2 virion by natural anti‐A and anti‐B antibodies in individuals with blood group O.…”

A large cohort study of the effects of Lewis, ABO, 13 other blood groups, and secretor status on COVID‐19 susceptibility, severity, and long COVID‐19

“…While the ABO blood group continues to be the main focus of such investigations, some studies have ventured beyond and also looked at secretor status 8 , 9 , 10 and some of the many other recognized blood group systems, such as Rh 5 , 11 , 12 , 13 , 14 , 15 and Lewis. 10 …”

“…However, limitations of these previous studies include, for example, matching patient cases with blood donor controls 4 , 10 and small cohort sizes. 13 , 14 , 16 , 17 In addition, so far, few studies have looked at the effects of the many existing blood groups beyond ABO and Rh.…”