Reduced levels of ABO anti-A and anti-B of IGM, IGG and IGA isotypes in the serum but not the saliva of individuals recovered from COVID-19

ABSTRACT

Background: Recent studies reported that individuals with ABO blood type O are underrepresented among patients infected with severe acute respiratory syndrome coronavirus SARS-CoV-2 compared with controls. Our preceding study results indicated a lower proportion of individuals with blood type O accompanied by a higher incidence of blood type AB in patients hospitalized with COVID-19 than in healthy blood donors. Thus, we hypothesized that the variable susceptibility to infection with SARS-CoV-2 might be related to interference caused by circulating ABO antibodies and further may be influenced by the antibody titers which vary widely between individuals. Aims: Therefore, we aimed to investigate ABO antibody levels, including IgM, IgG and IgA subclasses, in the serum and saliva of Caucasians (n = 187), who recovered from mild COVID-19 and to compare them with those of individuals who had never been infected with the virus. Further, a possible association between ABO antibodies and virusspecific total antibody concentrations in the COVID-19 convalescents as well as a potential relationship between the total IgA secreted in saliva and anti-A/anti-B specific IgA in saliva specimens were addressed. Methods: The convalescent study participants were recruited between June 2020 and February 2021. Individuals who had been hospitalized with COVID-19 or who were pregnant were excluded from the study. Two samples were collected within 2 months after the diagnosis (median days 44) and approximately 2 months later (median days 66 days). Isotype specific anti-A and anti-B were determined by flow cytometry on a FACS Canto II. The results were compared with the levels in samples from blood and saliva donors. The antibodies specific to SARS-CoV-2 as well as total IgA in saliva were tested by ELISA. Results: COVID-19 convalescents had significantly lower levels of anti-A and anti-B IgM, IgG and IgA in their serum than control subjects (p < 0.001). ABO antibody levels tested in saliva of participants who previously suffered from COVID-19 did not differ significantly from antibody levels tested in saliva controls (p ≥ 0.338). ABO antibody levels remained stable over the period considered. No significant association between the level of ABO antibodies and SARS-CoV-2-specific antibodies was observed (-0.44 < rho < 0.42, p > 0.053). Total IgA in saliva was lower in convalescents than in controls (p = 0.038). Summary/Conclusions: We observed consistently lower serum concentrations of anti-A and anti-B in COVID-19 convalescents than in healthy controls, suggesting ABO antibodies to conferring a degree of protection against SARS-CoV-2 infection. There may be an increased susceptibility to SARS-CoV-2 infection due to individual preexisting low ABO antibody levels. However, the mechanism underlying our observation of significantly reduced ABO antibodies in the serum, but not in the saliva of affected individuals remains unresolved. Further studies to better understand the molecular mechanism underlying our observation are needed.