Clonal hematopoiesis is associated with risk of severe Covid-19

Kelly L. Bolton (), Youngil Koh, Michael B. Foote, Hogune Im, Justin Jee, Choong Hyun Sun, Anton Safonov, Ryan Ptashkin, Joon Ho Moon, Ji Yeon Lee, Jongtak Jung, Chang Kyung Kang, Kyoung-Ho Song, Pyoeng Gyun Choe, Wan Beom Park, Hong Bin Kim, Myoung-don Oh, Han Song, Sugyeong Kim, Minal Patel, Andriy Derkach, Erika Gedvilaite, Kaitlyn A. Tkachuk, Brian J. Wiley, Ireaneus C. Chan, Lior Z. Braunstein, Teng Gao, Elli Papaemmanuil, N. Esther Babady, Melissa S. Pessin, Mini Kamboj, Luis A. Diaz, Marc Ladanyi, Michael J. Rauh, Pradeep Natarajan, Mitchell J. Machiela, Philip Awadalla, Vijai Joseph, Kenneth Offit, Larry Norton, Michael F. Berger, Ross L. Levine, Eu Suk Kim (), Nam Joong Kim () and Ahmet Zehir ()
Additional contact information
Kelly L. Bolton: Washington University
Youngil Koh: Seoul National University Hospital
Michael B. Foote: Memorial Sloan Kettering Cancer Center
Hogune Im: Genome Opinion Inc.
Justin Jee: Memorial Sloan Kettering Cancer Center
Choong Hyun Sun: Genome Opinion Inc.
Anton Safonov: Memorial Sloan Kettering Cancer Center
Ryan Ptashkin: Memorial Sloan Kettering Cancer Center
Joon Ho Moon: Kyungpook National University Hospital, School of Medicine, Kyungpook National University
Ji Yeon Lee: National Medical Center
Jongtak Jung: Seoul National University Bundang Hospital
Chang Kyung Kang: Seoul National University Hospital
Kyoung-Ho Song: Seoul National University Bundang Hospital
Pyoeng Gyun Choe: Seoul National University Hospital
Wan Beom Park: Seoul National University Hospital
Hong Bin Kim: Seoul National University Bundang Hospital
Myoung-don Oh: Seoul National University Hospital
Han Song: Genome Opinion Inc.
Sugyeong Kim: Genome Opinion Inc.
Minal Patel: Memorial Sloan Kettering Cancer Center
Andriy Derkach: Memorial Sloan Kettering Cancer Center
Erika Gedvilaite: Memorial Sloan Kettering Cancer Center
Kaitlyn A. Tkachuk: Memorial Sloan Kettering Cancer Center
Brian J. Wiley: Washington University
Ireaneus C. Chan: Washington University
Lior Z. Braunstein: Memorial Sloan Kettering Cancer Center
Teng Gao: Memorial Sloan Kettering Cancer Center
Elli Papaemmanuil: Memorial Sloan Kettering Cancer Center
N. Esther Babady: Memorial Sloan Kettering Cancer Center
Melissa S. Pessin: Memorial Sloan Kettering Cancer Center
Mini Kamboj: Memorial Sloan Kettering Cancer Center
Luis A. Diaz: Memorial Sloan Kettering Cancer Center
Marc Ladanyi: Memorial Sloan Kettering Cancer Center
Michael J. Rauh: Queen’s University
Pradeep Natarajan: Massachusetts General Hospital
Mitchell J. Machiela: National Cancer Institute
Philip Awadalla: Ontario Institute for Cancer Research
Vijai Joseph: Memorial Sloan Kettering Cancer Center
Kenneth Offit: Memorial Sloan Kettering Cancer Center
Larry Norton: Memorial Sloan Kettering Cancer Center
Michael F. Berger: Memorial Sloan Kettering Cancer Center
Ross L. Levine: Memorial Sloan Kettering Cancer Center
Eu Suk Kim: Seoul National University Bundang Hospital
Nam Joong Kim: Seoul National University Hospital
Ahmet Zehir: Memorial Sloan Kettering Cancer Center

Nature Communications, 2021, vol. 12, issue 1, 1-8

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-26138-6

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