COVID-19 and blood group-related antigens: can natural anti-carbohydrate antibodies provide innate protection from symptomatic SARS-CoV-2 infection?

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily targets respiratory mucosa, causing coronavirus disease 2019 (COVID-19). Susceptibility and severity of COVID-19 may be influenced by predisposing factors including blood groups. In this study, we investigated whether natural anti-carbohydrate antibodies provide innate protection against SARS-CoV-2 and influence disease severity.

Methodology: We used samples (plasma and saliva) from a longitudinal cohort study in Bangladesh that enrolled 100 COVID-19 symptomatic and asymptomatic patients. We also enrolled 21 and 38 healthy controls during the pandemic period and pre-pandemic period, respectively. We phenotype ABO blood grouping from blood and determined Lewis and secretor status (H antigen) from the saliva samples. We quantified natural anti-carbohydrate antibodies (anti-A, anti-B, anti-Tn-Mono and anti-αGal IgG, IgA, and IgM) from plasma collected at enrollment. We also explored the trend of natural anti-carbohydrate antibodies until 3 months of convalescence period among the COVID-19 patients (day 14 and day 90 from enrollment). Antibody quantification and ABH/Lewis phenotyping were performed using enzyme-linked immunosorbent assay (ELISA).

Results: We included 99 COVID-19 patients and 59 healthy controls assessing the differences of natural antibody titer during enrollment, while 95 patients were analyzed exploring Lewis and secretor status with natural antibody titer and disease status. We did not find significant difference in the distribution for neither ABO blood groups nor non-secretors and Lewis-negative individuals among asymptomatic or symptomatic patients and healthy controls. Nonetheless, we observed lower anti-A antibody titers among symptomatic patients compared to healthy controls. We also identified slight differences in antibody titers linked to age and gender. Anti-A and anti-B antibodies among asymptomatic patients had a higher trend up to 3 months from infection compared to symptomatic patients.

Conclusion: Higher natural anti-A and anti-B antibody titers may offer protection against symptomatic COVID-19 infections. Gender and blood group differences indicate potential innate immune factors influencing disease severity, but larger studies are needed to confirm these findings.

Keywords: Bangladesh; COVID-19; HBGA; Lewis status; SARS-CoV-2; blood group; natural anti-carbohydrate antibodies; secretor status.

Figure 1

Participant flow diagram for blood and saliva sample collection.

Figure 2

Anti-A antibody titer in O and B blood group patients and controls. Comparison of anti-A antibody (A-Tri) titer between healthy control (n = 39), asymptomatic patients (n = 15), symptomatic patients (n = 50), and combined (asymptomatic+ symptomatic) patients (n = 65) of individuals with O and B blood groups. (A) Anti-A IgG antibody, (B) anti-A IgA antibody, and (C) anti-A IgM antibody. *** and ** denote p < 0.005.

Figure 3

Anti-B antibody titer in O and A blood group patients and controls. Comparison of anti-B antibody (B-Tri) titer between healthy control (n = 39), asymptomatic patients (n = 16), symptomatic patients (n = 39), and combined (asymptomatic+ symptomatic) patients (n = 56) of individuals with O and A blood groups. (A) Anti-A IgG antibody, (B) anti-A IgA antibody, and (C) anti-A IgM antibody. *** and ** denote p < 0.005.

Figure 4

Gender-based analysis of natural antibody. Comparison of natural anti-A (A-Tri), anti-B (B-Tri), anti α-Gal, and anti-Tn-Mono (Tn-Mono) IgG (A–D), IgA (E–H) and IgM (I–L) antibodies between healthy controls, asymptomatic, and symptomatic patients stratified by gender. For anti-A antibody: healthy male (M) n = 18, female (F) n = 21; asymptomatic male (M) n = 6, female (F) n = 8; symptomatic male (M) n = 33, female (F) n = 15. Anti-B IgG antibody (healthy male = 21, female = 18), asymptomatic male (M) n = 3, female (F) n = 13; symptomatic male (M) n = 24, female (F) n = 15; Alpha-Gal or Tn-Mono (healthy male = 32, female = 27); asymptomatic male (M) n = 8, female (F) n = 16; symptomatic male (M) n = 49, female (F) n = 23. Asterisks *** and ** denote statistical significance, p < 0.005.

Figure 5

Trend of natural antibodies over 3 months post-SARS-CoV-2 infection. Comparing the trend of natural antibody dynamics over the convalescence period from date of disease onset of exposure. The follow-up period, displayed on the x-axis, was calculated from the date of disease onset to each study follow-up time point. (A) Anti-A IgG antibody titer (asymptomatic, n = 15; symptomatic, n = 50; control, n = 39), (B) anti-B IgG antibody titer (asymptomatic, n = 16; symptomatic, n = 39; control, n = 39), (C) anti-Tn-Mono IgG antibody titer (asymptomatic, n = 25; symptomatic, n = 74; control, n = 59), and (D) anti-αGal IgG antibody titer (asymptomatic, n = 25; symptomatic, n = 74; control, n = 59). (E) Anti-A IgA antibody titer (asymptomatic, n = 15; symptomatic, n = 50; control, n = 39), (F) anti-B IgA antibody titer (asymptomatic, n = 16; symptomatic, n = 39; control, n = 39), (G) anti-Tn-Mono IgA antibody titer (asymptomatic, n = 25; symptomatic, n = 74; control, n = 59), and (H) anti-αGal IgA antibody titer (asymptomatic, n = 25; symptomatic, n = 74; control, n = 59). (I) Anti-A IgM antibody titer (asymptomatic, n = 15; symptomatic, n = 50; control, n = 39), (J) anti-B IgM antibody titer (asymptomatic, n = 16; symptomatic, n = 39; control, n = 39), (K) anti-Tn-Mono IgM antibody titer (asymptomatic, n = 25; symptomatic, n = 74; control, n = 59), and (L) anti-αGal IgM antibody titer (asymptomatic, n = 25; symptomatic, n = 74; control, n = 59). The purple asterisks denote geometric mean of antibody titer comparisons between two time points among symptomatic patients, while black asterisks denote difference in geometric mean antibody titer between the asymptomatic and symptomatic patients at a single time point. * denotes p = 0.05–0.01; ** denotes p = 0.01–0.001; and *** denotes p < 0.001.