Angulo-Aguado Mariana, Corredor-Orlandelli David, Carrillo-Martínez Juan Camilo, Gonzalez-Cornejo Mónica, Pineda-Mateus Eliana, Rojas Carolina, Triana-Fonseca Paula, Contreras Bravo Nora Constanza, Morel Adrien, Parra Abaunza Katherine, Restrepo Carlos M, Fonseca-Mendoza Dora Janeth, Ortega-Recalde Oscar
Center for Research in Genetics and Genomics - CIGGUR, GENIUROS Research Group, School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá, Colombia.
Department of Molecular Diagnosis, Genética Molecular de Colombia SAS, Bogotá, Colombia.
Front Med (Lausanne). 2022 Jun 20;9:910098. doi: 10.3389/fmed.2022.910098. eCollection 2022.
Genetic and non-genetic factors are responsible for the high interindividual variability in the response to SARS-CoV-2. Although numerous genetic polymorphisms have been identified as risk factors for severe COVID-19, these remain understudied in Latin-American populations. This study evaluated the association of non-genetic factors and three polymorphisms: rs4646994, rs2285666, and rs11385942, with COVID severity and long-term symptoms by using a case-control design. The control group was composed of asymptomatic/mild cases ( = 61) recruited from a private laboratory, while the case group was composed of severe/critical patients ( = 63) hospitalized in the Hospital Universitario Mayor-Méderi, both institutions located in Bogotá, Colombia. Clinical follow up and exhaustive revision of medical records allowed us to assess non-genetic factors. Genotypification of the polymorphism of interest was performed by amplicon size analysis and Sanger sequencing. In agreement with previous reports, we found a statistically significant association between age, male sex, and comorbidities, such as hypertension and type 2 diabetes mellitus (T2DM), and worst outcomes. We identified the polymorphism rs11385942 as an important risk factor for hospitalization ( < 0.01; OR = 5.73; 95% CI = 1.2-26.5, under the allelic test). Furthermore, long-term symptoms were common among the studied population and associated with disease severity. No association between the polymorphisms examined and long-term symptoms was found. Comparison of allelic frequencies with other populations revealed significant differences for the three polymorphisms investigated. Finally, we used the statistically significant genetic and non-genetic variables to develop a predictive logistic regression model, which was implemented in a Shiny web application. Model discrimination was assessed using the area under the receiver operating characteristic curve (AUC = 0.86; 95% confidence interval 0.79-0.93). These results suggest that rs11385942 may be a potential biomarker for COVID-19 severity in addition to conventional non-genetic risk factors. A better understanding of the impact of these genetic risk factors may be useful to prioritize high-risk individuals and decrease the morbimortality caused by SARS-CoV2 and future pandemics.
遗传因素和非遗传因素导致了个体对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）反应的高度个体差异。尽管众多基因多态性已被确定为重症冠状病毒病2019（COVID-19）的危险因素，但在拉丁裔人群中对这些因素的研究仍然不足。本研究采用病例对照设计，评估了非遗传因素以及三种多态性（rs4646994、rs2285666和rs11385942）与COVID严重程度和长期症状之间的关联。对照组由从一家私人实验室招募的无症状/轻症病例（n = 61）组成，而病例组由在哥伦比亚波哥大的梅德雷市长大学医院住院的重症/危重症患者（n = 63）组成。通过临床随访和对病历的详尽审查，我们得以评估非遗传因素。通过扩增子大小分析和桑格测序对感兴趣的多态性进行基因分型。与之前的报告一致，我们发现年龄、男性性别以及高血压和2型糖尿病（T2DM）等合并症与更差的预后之间存在统计学显著关联。我们确定多态性rs11385942是住院的一个重要危险因素（P < 0.01；比值比 = 5.73；95%置信区间 = 1.2 - 26.5，在等位基因检测下）。此外，长期症状在研究人群中很常见，并且与疾病严重程度相关。未发现所检测的多态性与长期症状之间存在关联。将等位基因频率与其他人群进行比较，发现所研究的三种多态性存在显著差异。最后，我们使用具有统计学显著性的遗传和非遗传变量建立了一个预测性逻辑回归模型，并在一个Shiny网络应用程序中实现。使用受试者操作特征曲线下面积评估模型判别能力（曲线下面积 = 0.86；95%置信区间0.79 - 0.93）。这些结果表明，除了传统的非遗传危险因素外，rs11385942可能是COVID-19严重程度的一个潜在生物标志物。更好地理解这些遗传危险因素的影响可能有助于对高危个体进行优先排序，并降低SARS-CoV-2及未来大流行所导致的病残率和死亡率。
