A model integrating Killer Immunoglobulin-like Receptor (KIR) haplotypes for risk prediction of COVID-19 clinical disease severity


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Beksac M., Akin H. Y., Gencer-Oncul E. B., Yousefzadeh M., Cengiz Seval G., Gulten E., ...More

Immunogenetics, vol.73, no.6, pp.449-458, 2021 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 73 Issue: 6
  • Publication Date: 2021
  • Doi Number: 10.1007/s00251-021-01227-4
  • Journal Name: Immunogenetics
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.449-458
  • Keywords: COVID-19, Killer Immunoglobulin-like Receptor (KIR), Natural killer (NK) cells, SARS-CoV-2
  • Lokman Hekim University Affiliated: No

Abstract

Associations between inherited Killer Immunoglobulin-like Receptor (KIR) genotypes and the severity of multiple RNA virus infections have been reported. This prospective study was initiated to investigate if such an association exists for COVID-19. In this cohort study performed at Ankara University, 132 COVID-19 patients (56 asymptomatic, 51 mild-intermediate, and 25 patients with severe disease) were genotyped for KIR and ligands. Ankara University Donor Registry (n:449) KIR data was used for comparison. Clinical parameters (age, gender, comorbidities, blood group antigens, inflammation biomarkers) and KIR genotypes across cohorts of asymptomatic, mild-intermediate, or severe disease were compared to construct a risk prediction model based on multivariate binary logistic regression analysis with backward elimination method. Age, blood group, number of comorbidities, CRP, D-dimer, and telomeric and centromeric KIR genotypes (tAA, tAB1, and cAB1) along with their cognate ligands were found to differ between cohorts. Two prediction models were constructed; both included age, number of comorbidities, and blood group. Inclusion of the KIR genotypes in the second prediction model exp (-3.52 + 1.56 age group - 2.74 blood group (type A vs others) + 1.26 number of comorbidities - 2.46 tAB1 with ligand + 3.17 tAA with ligand) increased the predictive performance with a 92.9% correct classification for asymptomatic and 76% for severe cases (AUC: 0.93; P < 0.0001, 95% CI 0.88, 0.99). This novel risk model, consisting of KIR genotypes with their cognate ligands, and clinical parameters but excluding earlier published inflammation-related biomarkers allow for the prediction of the severity of COVID-19 infection prior to the onset of infection. This study is listed in the National COVID-19 clinical research studies database. Graphical abstract: [Figure not available: see fulltext.]