Thromboembolism is a frequent cause of severity and mortality in COVID-19. However, the etiology of this phenomenon is not well understood. A cohort of 1186 subjects, from the GEN-COVID consortium, infected by SARS-CoV-2 with different severity was stratified by sex and adjusted by age. Then, common coding variants from whole exome sequencing were mined by LASSO logistic regression. The homozygosity of the cell adhesion molecule P-selectin gene (SELP) rs6127 (c.1807G > A; p.Asp603Asn) which has been already associated with thrombotic risk is found to be associated with severity in the male subcohort of 513 subjects (odds ratio = 2.27, 95% Confidence Interval 1.54–3.36). As the SELP gene is downregulated by testosterone, the odd ratio is increased in males older than 50 (OR 2.42, 95% CI 1.53–3.82). Asn/Asn homozygotes have increased D-dimers values especially when associated with poly Q ≥ 23 in the androgen receptor (OR 3.26, 95% CI 1.41–7.52). These results provide a rationale for the repurposing of antibodies against P-selectin as adjuvant therapy in rs6127 male homozygotes especially if older than 50 or with an impaired androgen receptor.

中文翻译：

---

SELP Asp603Asn 和 COVID-19 男性的严重血栓形成

血栓栓塞是 COVID-19 严重程度和死亡率的常见原因。然而，这种现象的病因尚不清楚。来自 GEN-COVID 联盟的 1186 名受不同严重程度的 SARS-CoV-2 感染的受试者按性别分层并按年龄调整。然后，通过 LASSO 逻辑回归挖掘来自整个外显子组测序的常见编码变体。细胞粘附分子 P-选择素基因 (SELP) rs6127 (c.1807G > A; p.Asp603Asn) 的纯合性已经与血栓形成风险相关，被发现与 513 名受试者的男性亚组的严重程度相关（优势比率 = 2.27，95% 置信区间 1.54–3.36）。由于 SELP 基因被睾酮下调，因此 50 岁以上男性的奇数比增加 (OR 2.42, 95% CI 1.53–3.82)。Asn/Asn 纯合子具有增加的 D-二聚体值，尤其是当与雄激素受体中的 poly Q ≥ 23 相关时（OR 3.26，95% CI 1.41–7.52）。这些结果为重新利用抗 P-选择蛋白抗体作为 rs6127 男性纯合子的辅助治疗提供了依据，尤其是当年龄超过 50 岁或雄激素受体受损时。