Clonal Hematopoiesis and COVID-19 Severity in Cancer Patients
Clonal Hematopoiesis and COVID-19 Severity in Cancer Patients
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DOI：
10.1182/blood-2020-143041
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发表时间：
2021-08-03
期刊：
影响因子：
20.3
通讯作者：
Zehir A
中科院分区：
文献类型：
--
作者：
Bolton KL;Foote M;Jee J;Safonov A;Ptashkin R;Devlin S;Gedvilaite E;Gao T;Papaemmanuil E;Pessin MS;Kamboj M;Vijai J;Offit K;Awadalla P;Nataranjan P;Berger MF;Norton L;Levine RL;Zehir A
背景：高龄、医学共病和促炎免疫学特征与严重的COVID-19相关。造血干细胞的获得性体细胞突变（克隆造血或CH）在老年人中很常见。先前的研究表明CH与免疫系统和功能的改变有关。在这里，我们调查CH是否易患严重的COVID-19或其他感染。研究方法：我们对39，291名患有非血液学恶性肿瘤的成年癌症患者进行了回顾性队列研究，这些患者使用一组468个已知癌症驱动基因进行了肿瘤和血液测序。我们确定了2020年3月8日至2020年6月9日期间SARS-CoV-2检测呈阳性的个人。我们使用多变量逻辑回归模型确定CH与严重COVID-19（缺氧事件、住院或死亡）之间的关联。我们使用了一个已建立的ICD-CM代码聚集模式来识别不同的感染亚型。使用多变量考克斯回归确定CH和偶发感染风险之间的关系。结果：在研究队列中，436名患者为SARS-CoV-2阳性，165名患者发展为严重的COVID-19。与非重度相比，COVID-19合并CH的患者更有可能发展为重度疾病（OR=1.8; 95% CI：1.1-2.9; p=0.01）。与COVID-19阴性个体相比，CH在重度COVID-19患者中也更常见（OR=1.6，95% CI：1.2-2.4，p=0.01）。在62，891人年的随访中，4，059人发生感染。CH与脓毒症（HR=1.13; 95% CI 1.01-1.25，p=0.04）和细菌性肠炎（HR=1.8，95% CI 1.1-2.8，p=0.01）风险相关。结论：CH与严重的COVID-19和癌症患者其他感染的风险增加有关。博尔顿：圣杯：研究基金。Jee：MDSeq Inc.：专利和版税。Papaemmanuil：Celgene：咨询，酬金，研究基金; Prime Oncology：咨询，酬金; Illumina：咨询，酬金; Novartis：咨询，酬金; MSKCC：专利和特许权使用费; Kyowa Hakko Kirin：咨询，酬金; Isabl：私人公司的当前股权保持器持有人，实体董事会或咨询委员会成员。伯杰：Illumina：研究资金;圣杯：研究资金;罗氏：咨询。Levine：Prelude Therapeutics：研究经费; Qiagen：上市公司当前股权保持器持有人，实体董事会或咨询委员会成员; Loxo：私人公司当前股权保持器持有人，实体董事会或咨询委员会成员; Imago：私人公司当前股权保持器持有人，实体董事会或咨询委员会成员; C4 Therapeutics：私人公司的当前股权保持器持有人，实体董事会或咨询委员会成员; Isoplexis：私人公司的当前股权保持器持有人，实体董事会或咨询委员会成员; Celgene：咨询、酬金、研究基金; Roche：咨询，Honoraria，研究资金;礼来：咨询，Honoraria;杨森：咨询;安斯泰来：咨询; Morphosys：咨询;诺华：咨询;安进：Honoraria;吉利德：Honoraria。泽希尔：Illumina：酬金;纪念斯隆凯特琳癌症中心：目前的就业。
Background: Advanced age, medical co-morbidities and a pro-inflammatory immunologic profile are associated with severe COVID-19. Acquired somatic mutations in hematopoietic stem cells (clonal hematopoiesis or CH) are common in elderly individuals. Previous studies have shown CH is associated with alterations in immunologic repertoire and function. Here, we investigate whether CH predisposes to severe COVID-19 or other infections. Methods: We performed a retrospective cohort study of 39,291 adult cancer patients with non-hematologic malignancies who had their tumor and blood sequenced using a panel of 468 known cancer driver genes. We identified individuals who tested positive for SARS-CoV-2 between March 8, 2020 and June 9, 2020. We determined the association between CH and severe COVID-19 (hypoxic event, hospitalization or death) using multivariable logistic regression models. We used an established aggregation schema for ICD-CM codes to identify distinct infection subtypes. The relationship between CH and risk of incident infections was determined using multivariable Cox regression. Results: In the study cohort, 436 patients were positive for SARS-CoV-2 and 165 developed severe COVID-19. COVID-19 patients with CH were more likely to develop severe disease compared to non-severe (OR=1.8; 95% CI: 1.1-2.9; p=0.01). CH was also more common among patients with severe COVID-19 compared to COVID-19 negative individuals (OR=1.6, 95% CI: 1.2-2.4, p=0.01). In 62,891 person-years of follow-up, 4,059 individuals developed an infection. CH was associated with risk of sepsis (HR=1.13; 95% CI 1.01-1.25, p=0.04) and bacterial enteritis (HR=1.8, 95% CI 1.1-2.8, p=0.01). Conclusions: CH is associated with severe COVID-19 and an increased risk of other infections in cancer patients. Bolton:GRAIL: Research Funding. Jee:MDSeq Inc.: Patents & Royalties. Papaemmanuil:Celgene: Consultancy, Honoraria, Research Funding; Prime Oncology: Consultancy, Honoraria; Illumina: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; MSKCC: Patents & Royalties; Kyowa Hakko Kirin: Consultancy, Honoraria; Isabl: Current equity holder in private company, Membership on an entity’s Board of Directors or advisory committees. Berger:Illumina: Research Funding; Grail: Research Funding; Roche: Consultancy. Levine:Prelude Therapeutics: Research Funding; Qiagen: Current equity holder in publicly-traded company, Membership on an entity’s Board of Directors or advisory committees; Loxo: Current equity holder in private company, Membership on an entity’s Board of Directors or advisory committees; Imago: Current equity holder in private company, Membership on an entity’s Board of Directors or advisory committees; C4 Therapeutics: Current equity holder in private company, Membership on an entity’s Board of Directors or advisory committees; Isoplexis: Current equity holder in private company, Membership on an entity’s Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Lilly: Consultancy, Honoraria; Janssen: Consultancy; Astellas: Consultancy; Morphosys: Consultancy; Novartis: Consultancy; Amgen: Honoraria; Gilead: Honoraria. Zehir:Illumina: Honoraria; Memorial Sloan Kettering Cancer Center: Current Employment.