Clonal hematopoiesis is associated with risk of severe Covid-19.
Clonal hematopoiesis is associated with risk of severe Covid-19.
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DOI：
10.1038/s41467-021-26138-6
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发表时间：
2021-10-13
影响因子：
16.6
通讯作者：
Zehir A
中科院分区：
文献类型：
--
作者：
Bolton KL;Koh Y;Foote MB;Im H;Jee J;Sun CH;Safonov A;Ptashkin R;Moon JH;Lee JY;Jung J;Kang CK;Song KH;Choe PG;Park WB;Kim HB;Oh MD;Song H;Kim S;Patel M;Derkach A;Gedvilaite E;Tkachuk KA;Wiley BJ;Chan IC;Braunstein LZ;Gao T;Papaemmanuil E;Esther Babady N;Pessin MS;Kamboj M;Diaz LA Jr;Ladanyi M;Rauh MJ;Natarajan P;Machiela MJ;Awadalla P;Joseph V;Offit K;Norton L;Berger MF;Levine RL;Kim ES;Kim NJ;Zehir A
造血干细胞和祖细胞的获得性体细胞突变(克隆性造血或CH)与高龄、心血管疾病和恶性疾病风险增加以及总存活率降低有关。这些不良后遗症可能是通过在CH患者中观察到的炎性改变而起作用的。促炎免疫学特征也与某些感染的较差预后有关，包括SARS-CoV-2及其相关疾病新冠肺炎。丙型肝炎是否易患严重的新冠肺炎或其他感染尚不清楚。在525例新冠肺炎患者中，我们发现CH与严重的新冠肺炎预后相关(OR = 1.85，95%=1.15-2.99，p = 0.01)，尤其是具有非癌症驱动突变特征的CH(OR = 2.01，95%CI = 1.15-3.5 0，p = 0.01)。我们进一步探讨了在MSK的14,211名实体肿瘤患者中CH与其他感染风险的关系。CH与艰难梭菌感染的危险性(HR = 2.0 1，95%CI：1.2 2~3.3 0，p = 6×10−3)和链球菌/肠球菌感染(HR = 1.5 6，95%CI = 1.15~2.13，p = 5×10−3)显著相关。这些发现表明CH与严重感染风险之间的关系值得进一步研究。克隆性造血(CH)与炎症特征的改变以及心血管疾病和恶性疾病的风险增加有关。在这里，作者分析了来自两个不同队列的患者数据，并表明CH与严重感染和严重Covid19有关。
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 = 6×10−3) and Streptococcus/Enterococcus infections (HR = 1.56, 95% CI = 1.15–2.13, p = 5×10−3). These findings suggest a relationship between CH and risk of severe infections that warrants further investigation. Clonal haematopoiesis (CH) has been associated with altered inflammatory profiles and increased risk of cardiovascular and malignant diseases. Here, the authors analyze patient data from two different cohorts and show that CH is associated with severe infections and severe Covid19.