Clonal hematopoiesis is associated with risk of severe Covid-19

被引：49

作者：

Bolton, Kelly L. ^{[1
]}

Koh, Youngil ^{[2
,3
,4
]}

Foote, Michael B. ^{[5
]}

Im, Hogune ^{[3
]}

Jee, Justin ^{[4
]}

Sun, Choong Hyun ^{[3
]}

Safonov, Anton ^{[5
]}

Ptashkin, Ryan ^{[6
]}

Moon, Joon Ho ^{[7
]}

Lee, Ji Yeon ^{[8
]}

Jung, Jongtak ^{[9
]}

Kang, Chang Kyung ^{[2
]}

Song, Kyoung-Ho ^{[9
]}

Choe, Pyoeng Gyun ^{[2
]}

Park, Wan Beom ^{[2
]}

Kim, Hong Bin ^{[9
]}

Oh, Myoung-don ^{[2
]}

Song, Han ^{[3
]}

Kim, Sugyeong ^{[3
]}

Patel, Minal ^{[10
]}

Derkach, Andriy ^{[11
]}

Gedvilaite, Erika ^{[6
]}

Tkachuk, Kaitlyn A. ^{[5
]}

Wiley, Brian J. ^{[1
]}

Chan, Ireaneus C. ^{[1
]}

Braunstein, Lior Z. ^{[12
]}

Gao, Teng ^{[13
]}

Papaemmanuil, Elli ^{[13
]}

Babady, N. Esther ^{[5
,14
]}

Pessin, Melissa S. ^{[14
]}

Kamboj, Mini ^{[5
]}

Diaz, Luis A., Jr. ^{[5
]}

Ladanyi, Marc ^{[6
]}

Rauh, Michael J. ^{[15
]}

Natarajan, Pradeep ^{[16
,17
]}

Machiela, Mitchell J. ^{[18
]}

Awadalla, Philip ^{[19
]}

Joseph, Vijai ^{[20
]}

Offit, Kenneth ^{[20
]}

Norton, Larry ^{[5
]}

Berger, Michael F. ^{[6
,13
]}

Levine, Ross L. ^{[5
]}

Kim, Eu Suk ^{[9
]}

Kim, Nam Joong ^{[2
]}

Zehir, Ahmet ^{[6
]}

机构：

[1] Washington Univ, Dept Med, St Louis, MO 63130 USA

[2] Seoul Natl Univ Hosp, Dept Internal Med, Seoul, South Korea

[3] Genome Opin Inc, Seoul, South Korea

[4] Seoul Natl Univ Hosp, Ctr Precis Med, Seoul, South Korea

[5] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA

[6] Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA

[7] Kyungpook Natl Univ, Kyungpook Natl Univ Hosp, Sch Med, Dept Internal Med, Daegu, South Korea

[8] Natl Med Ctr, Dept Internal Med, Seoul, South Korea

[9] Seoul Natl Univ, Dept Internal Med, Bundang Hosp, Seongnam, South Korea

[10] Mem Sloan Kettering Canc Ctr, Ctr Hematol Malignancies, New York, NY USA

[11] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA

[12] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, 1275 York Ave, New York, NY 10021 USA

[13] Mem Sloan Kettering Canc Ctr, Ctr Computat Oncol, Dept Epidemiol & Biostat, Computat Oncol Serv, New York, NY USA

[14] Mem Sloan Kettering Canc Ctr, Dept Lab Med, New York, NY USA

[15] Queens Univ, Dept Pathol & Mol Med, Kingston, ON, Canada

[16] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA USA

[17] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA USA

[18] NCI, Div Canc Epidemiol & Genet, Bethesda, MD USA

[19] Ontario Inst Canc Res, Toronto, ON, Canada

[20] Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Res Lab, New York, NY USA

来源：

NATURE COMMUNICATIONS | 2021年 / 12卷 / 01期

基金：

美国国家卫生研究院;

关键词：

MUTATIONS;

D O I：

10.1038/s41467-021-26138-6

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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. 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 = 6x10(-3)) and Streptococcus/Enterococcus infections (HR = 1.56, 95% CI = 1.15-2.13, p = 5x10(-3)). These findings suggest a relationship between CH and risk of severe infections that warrants further investigation.

引用

页数：8

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