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.
摘要：
COVID-19的发病机制值得揭开。遗传多态性分析可能有助于回答疾病结果的变异性。为了确定KIR和HLA多态性在易感性中的作用，programming,SARS-CoV-2感染的严重程度，2020年4月至12月，458名患者和667名对照者参加了这项回顾性观察研究。建立轻度/中度和重度/死亡研究组。HLA-A,-B,-C,和KIR基因分型使用Luminex®200™xMAP荧光分析仪上的Lifcodes®HLA-SSO和KIR-SSO试剂盒进行。使用多元二元逻辑回归分析计算概率评分，以估计严重COVID-19的可能性。使用ROC分析以高灵敏度和特异性计算用于预测更差的临床结果的最佳截止点。p≤0.05被认为具有统计学意义。KIRAA基因型对COVID-19的严重程度/死亡具有积极保护作用。此外，KIR3DL1、KIR2DL3和KIR2DS4基因保护患者免受严重形式的COVID-19。KIRBx基因型，以及KIR2DL2，KIR2DS2，KIR2DS3和KIR3DS1被鉴定为重症COVID-19的生物标志物。我们的逻辑回归模型，其中包括临床和KIR/HLA变量，将我们的患者队列分类为具有高灵敏度和特异性的严重COVID-19疾病的高/低风险(Se=94.29%，95%CI[80.84-99.30]；Sp=84.55%，95%CI[79.26-88.94]；OR=47.58，95CI[11.73-193.12]，p<0.0001)。这些结果说明了KIR/HLA配体多态性与不同COVID-19结果之间的关联，并指出了在未来可能的传染病暴发中使用它们作为替代生物标志物来检测重症患者的可能性。
