Killer‐cell immunoglobulin‐like receptor polymorphism is associated with COVID‐19 outcome: Results of a pilot observational study

Abstract

The pathogenesis of COVID‐19 warrants unravelling. Genetic polymorphism analysis may help answer the variability in disease outcome. To determine the role of KIR and HLA polymorphisms in susceptibility, progression, and severity of SARS‐CoV‐2 infection, 458 patients and 667 controls enrolled in this retrospective observational study from April to December 2020. Mild/moderate and severe/death study groups were established. HLA‐A, ‐B, ‐C, and KIR genotyping were performed using the Lifecodes® HLA‐SSO and KIR‐SSO kits on the Luminex® 200™ xMAP fluoroanalyser. A probability score using multivariate binary logistic regression analysis was calculated to estimate the likelihood of severe COVID‐19. ROC analysis was used to calculate the best cut‐off point for predicting a worse clinical outcome with high sensitivity and specificity. A p ≤ 0.05 was considered statistically significant. KIR AA genotype protected positively against severity/death from COVID‐19. Furthermore, KIR3DL1, KIR2DL3 and KIR2DS4 genes protected patients from severe forms of COVID‐19. KIR Bx genotype, as well as KIR2DL2, KIR2DS2, KIR2DS3 and KIR3DS1 were identified as biomarkers of severe COVID‐19. Our logistic regression model, which included clinical and KIR/HLA variables, categorised our cohort of patients as high/low risk for severe COVID‐19 disease with high sensitivity and specificity (Se = 94.29%, 95% CI [80.84–99.30]; Sp = 84.55%, 95% CI [79.26–88.94]; OR = 47.58, 95%CI [11.73–193.12], p < 0.0001). These results illustrate an association between KIR/HLA ligand polymorphism and different COVID‐19 outcomes and remarks the possibility of use them as a surrogate biomarkers to detect severe patients in possible future infectious outbreaks.