Association of the rs2814778 variant in the ACKR1 gene, responsible for the Duffy erythrocyte antigen "null" phenotype, with COVID-19 severity in Southern Brazil

Einstein (Sao Paulo). 2026 Jan 12:24:eAO1543. doi: 10.31744/einstein_journal/2026AO1543. eCollection 2026.

Abstract

Objective: This study aimed to analyze the possible association between rs2814778, rs12075 ( ACKR1 gene), and rs4073 ( CXCL8 gene) single nucleotide variants and COVID-19 severity.

Methods: This cross-sectional study included 319 COVID-19 diagnosed patients at two hospitals in Paraná, Brazil between 2020 and 2021. Among them, 171 cases were classified as severe or critical and 148 were classified as non-severe. Genotyping was performed using polymerase chain reaction.

Results: We found an association between the rs2814778 variant of the ACKR1 gene and COVID-19 severity. The C allele in both the T/C and C/C genotypes was identified as a risk factor for severe COVID-19, independent of sex, age, smoking status, cardiovascular disease, diabetes, or obesity. No evidence of an association was observed for the other variants.

Conclusion: The presence of the C allele in the rs2814778 variant indicated an increased risk of severe or critical COVID-19 in the southern Brazilian population across all possible genotypes and genetic inheritance models.

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Brazil
  • COVID-19* / genetics
  • Cross-Sectional Studies
  • Duffy Blood-Group System* / genetics
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide* / genetics
  • Receptors, Cell Surface* / genetics
  • Risk Factors
  • SARS-CoV-2
  • Severity of Illness Index

Substances

  • ACKR1 protein, human
  • Receptors, Cell Surface
  • Duffy Blood-Group System