The COVID-19 pandemic remains a significant public health concern despite the new vaccines and therapeutics. The clinical course of acute SARS-CoV-2 infection is highly variable and influenced by several factors related to the virus and the host. Numerous genetic studies, including candidate gene, exome, and genome sequencing studies, genome-wide association studies, and other omics efforts, have proposed various Mendelian and non-Mendelian associations with COVID-19 course. In this study, we conducted whole-exome sequencing on 90 unvaccinated patients from Turkey with no known comorbidities associated with severe COVID-19. Of these patients, 30 had severe, 30 had moderate, and 30 had mild/asymptomatic disease. We identified rare variants in genes associated with SARS-CoV-2 susceptibility and pathogenesis, with an emphasis on genes related to the regulation of inflammation, and discussed these in the context of the clinical course of the patients. In addition, we compared the frequencies of common variants between each group. Even though no variant remained statistically significant after correction for multiple testing, we observed that certain previously associated genes and variants showed significant associations before correction. Our study contributes to the existing literature regarding the genetic susceptibility to SARS-CoV-2. Future studies would be beneficial characterizing the host genetic properties in different populations.

尽管出现了新的疫苗和治疗方法，但 COVID-19 大流行仍然是一个重大的公共卫生问题。急性 SARS-CoV-2 感染的临床病程变化很大，并受到与病毒和宿主相关的多种因素的影响。许多遗传学研究，包括候选基因、外显子组和基因组测序研究、全基因组关联研究和其他组学工作，提出了与 COVID-19 课程的各种孟德尔和非孟德尔关联。在这项研究中，我们对来自土耳其的 90 名未接种疫苗的患者进行了全外显子组测序，这些患者没有与严重 COVID-19 相关的已知合并症。在这些患者中，30 名患有严重疾病，30 名患有中度疾病，30 名患有轻微/无症状疾病。我们鉴定了与 SARS-CoV-2 易感性和发病机制相关的基因的罕见变异，重点是与炎症调节相关的基因，并在患者的临床病程背景下讨论了这些变异。此外，我们还比较了每组之间常见变异的频率。尽管在多次测试校正后没有变异保持统计学显着性，但我们观察到某些先前相关的基因和变异在校正前显示出显着的关联。我们的研究对有关 SARS-CoV-2 遗传易感性的现有文献做出了贡献。未来的研究将有助于表征不同人群的宿主遗传特性。