Abstract
Background: Genetic variation at a multigene cluster at chromosome 3p21.31 and the ABO blood group have been associated with the risk of developing severe COVID-19, but the mechanism remains unclear. Complement activation has been associated with COVID-19 severity.
Objective: The aim of this study was to examine whether chromosome 3p21.31 and the ABO variants are linked to the activation of the complement cascade in COVID-19 patients.
Methods: We considered 72 unrelated European hospitalized patients with genetic data and evaluation of circulating C5a and soluble terminal complement complex C5b-9 (SC5b-9). Twenty-six (36.1%) patients carried the rs11385942 G>GA variant and 44 (66.1%) non-O blood group associated with increased risk of severe COVID-19.
Results: C5a and SC5-b9 plasma levels were higher in rs11385949 GA carriers than in non-carriers (P = 0.041 and P = 0.012, respectively), while C5a levels were higher in non-O group than in O group patients (P = 0.019). The association between rs11385949 and SC5b-9 remained significant after adjustment for ABO and disease severity (P = 0.004) and further correction for C5a (P = 0.018). There was a direct relationship between upper airways viral load and SC5b-9 in carriers of the rs11385949 risk allele (P = 0.032), which was not observed in non-carriers.
Conclusions: The rs11385949 G>GA variant, tagging the chromosome 3 gene cluster variation and predisposing to severe COVID-19, is associated with enhanced complement activation, both with C5a and terminal complement complex, while non-O blood group with C5a levels. These findings provide a link between genetic susceptibility to more severe COVID-19 and complement activation.
Keywords: ABO group; C5a; COVID-19; Complement; SC5b-9; rs11385942 G>GA variant.
【저자키워드】 COVID-19, complement, C5a, SC5b-9, ABO group, rs11385942 G>, GA variant., 【초록키워드】 severe COVID-19, severity, disease severity, Variation, variant, COVID-19 severity, risk, complement, SC5b-9, Complement activation, Viral, Viral load, Genetic variation, Patient, Cluster, genetic susceptibility, plasma, Complement cascade, upper airway, mechanism, COVID-19 patients, Blood Group, association, genetic data, ABO, Plasma levels, chromosome 3, upper airways, Activation, chromosome, increased risk, carriers, risk allele, circulating, cascade, gene cluster, carrier, European, terminal complement complex, carried, remained, hospitalized patient, with COVID-19, 【제목키워드】 variant, Complement activation, Cluster, chromosome 3, Activation,