Department of Medicine, Washington University, St Louis, MO, USA.
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
Nat Commun. 2021 Oct 13;12(1):5975. doi: 10.1038/s41467-021-26138-6.
Acquired somatic mutations in hematopoietic stem and progenitor cells (clonal hematopoiesis or CH) are associated with advanced age, increased risk of cardiovascular and malignant diseases, and decreased overall survival. These adverse sequelae may be mediated by altered inflammatory profiles observed in patients with CH. A pro-inflammatory immunologic profile is also associated with worse outcomes of certain infections, including SARS-CoV-2 and its associated disease Covid-19. Whether CH predisposes to severe Covid-19 or other infections is unknown. Among 525 individuals with Covid-19 from Memorial Sloan Kettering (MSK) and the Korean Clonal Hematopoiesis (KoCH) consortia, we show that CH is associated with severe Covid-19 outcomes (OR = 1.85, 95%=1.15-2.99, p = 0.01), in particular CH characterized by non-cancer driver mutations (OR = 2.01, 95% CI = 1.15-3.50, p = 0.01). We further explore the relationship between CH and risk of other infections in 14,211 solid tumor patients at MSK. CH is significantly associated with risk of Clostridium Difficile (HR = 2.01, 95% CI: 1.22-3.30, p = 6×10) and Streptococcus/Enterococcus infections (HR = 1.56, 95% CI = 1.15-2.13, p = 5×10). These findings suggest a relationship between CH and risk of severe infections that warrants further investigation.
获得性造血干细胞和祖细胞（克隆性造血或 CH）中的体细胞突变与年龄增长、心血管疾病和恶性肿瘤风险增加以及总生存率降低相关。这些不良后果可能是由 CH 患者中观察到的改变的炎症特征介导的。促炎免疫特征也与某些感染（包括 SARS-CoV-2 和其相关疾病 COVID-19）的不良结局相关。CH 是否会导致 COVID-19 或其他感染加重尚不清楚。在 Memorial Sloan Kettering（MSK）和韩国克隆性造血（KoCH）联盟的 525 名 COVID-19 患者中，我们表明 CH 与 COVID-19 严重结局相关（OR=1.85，95%CI=1.15-2.99，p=0.01），特别是由非癌症驱动基因突变引起的 CH（OR=2.01，95%CI=1.15-3.50，p=0.01）。我们进一步在 MSK 的 14211 名实体瘤患者中探索了 CH 与其他感染风险的关系。CH 与艰难梭菌（HR=2.01，95%CI：1.22-3.30，p=6×10）和链球菌/肠球菌感染（HR=1.56，95%CI=1.15-2.13，p=5×10）的风险显著相关。这些发现提示 CH 与严重感染风险之间存在关联，值得进一步研究。
