Association between complement system, pulmonary fibrosis, and ABO system gene variants and COVID-19 severity and susceptibility: a Moroccan case–control study

Abstract Background SARS-CoV-2 infection manifests in a wide range of clinical outcomes, ranging from asymptomatic or mild respiratory symptoms to severe forms of COVID-19. This variability highlights the influence of various factors, such as age, gender, and pre-existing health conditions. Additionally, exploring genetic factors can offer valuable insights into the mechanisms and pathogenesis of COVID-19. This study aimed to investigate the possible link between genetic variants in the complement system ( MBL2 , MASP2 , and CCL2 ), pulmonary fibrosis ( MUC5B and TERT ), and the ABO system ( ABO and FUT2 ) and susceptibility to infection or severe outcomes of COVID-19 in a Moroccan cohort. Patients and methods Our case–control study involved 324 participants, consisting of 101 asymptomatic or experienced mild symptoms, 105 presented moderate to severe symptoms, and 118 healthy controls negative for SARS-CoV-2 infection. The 324 samples were analyzed using gene-panel next-generation sequencing (NGS) that included eight genes. Results A total of 139 variants were identified, including 99 in MUC5B , 12 in ABO , 9 in FUT2 , 9 in MASP2 , 7 in TERT , and 3 in MBL2 . Only variants with a minor allele frequency (MAF) > 10% are included in the association analysis. Following the common disease/common variant hypothesis, the study revealed nine candidate variants: MBL2 rs1800450, MASP2 rs2273346, MASP2 rs12711521, MUC5B rs2943531, MUC5B rs2075853, ABO rs512770, ABO rs8176719, ABO rs8176740, and FUT2 rs601338. Statistical analysis indicates that the MUC5B rs2943531 G allele may increase the risk of severe COVID-19 (p = 0.027) in the Moroccan population. Additionally, the CT genotype of MUC5B rs2075853 seems to have a potential protective effect against COVID-19 severity (p = 0.032). Moreover, the CA heterozygous genotype of the MASP2 rs12711521 variant, in the dominant/recessive model, was significantly associated with increased COVID-19 severity (p = 0.023). Conclusion Carriers of the MUC5B rs2943531 G allele were at an increased risk of developing severe forms of COVID-19. Similarly, the CA genotype of the MASP2 rs12711521 variant was associated with a higher risk of disease severity. In contrast, the CT genotype of MUC5B rs2075853 may confer protection against severe outcomes.