Association of TNFRSF13B Gene Polymorphisms With SARS-CoV-2 Infection, Severity, and Humoral Immune Response in a Moroccan Population

Abstract

Background and Aims: Genetic factors, including polymorphisms in the TNFRSF13B gene, which regulates humoral immunity, can influence susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aims to investigate the association between two polymorphisms, rs12603708 and rs3751987, and SARS-CoV-2 susceptibility, disease severity, and humoral immune responses in a Moroccan population.

Materials and Methods: A total of 303 unvaccinated COVID-19 patients (151 severe cases and 152 asymptomatic/moderate cases) and 150 individuals from a SARS-CoV-2-negative group were included in the analysis. Genotyping was performed using TaqMan SNP assays. SARS-CoV-2 antibodies targeting the nucleocapsid protein and IgG antibodies specific to the receptor-binding domain (RBD) were quantified using chemiluminescence microparticles immunoassay. Complete blood counts and C-reactive protein levels were evaluated using an automated platform.

Results: Our analysis revealed that the A/A genotype of rs12603708 significantly increased the risk of SARS-CoV-2 infection in both codominant (p = 0.0055; OR = 3.74; adjusted p value = 0.022) and recessive (p = 0.0049; OR = 3.17; adjusted p value = 0.022) models, as well as the risk of severe disease (p = 0.014; OR = 3.43; adjusted p value = 0.049). For rs3751987, the G/G genotype was linked to higher susceptibility to infection (p = 0.0011; OR = 2.91; adjusted p value = 0.008), while the G/A genotype appeared protective (p = 0.0007; OR = 0.45; adjusted p value = 0.008). No association was found between rs3751987 and disease severity. Analysis of IgG anti-N and anti-RBD levels revealed no significant associations with either polymorphism (p > 0.05).

Conclusion: These findings highlight the role of TNFRSF13B polymorphisms in SARS-CoV-2 susceptibility and severity, while their impact on humoral immune responses appears limited.