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Clonal hematopoiesis is associated with risk of severe Covid-19

Author

Listed:
  • Kelly L. Bolton

    (Washington University)

  • Youngil Koh

    (Seoul National University Hospital
    Genome Opinion Inc.
    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
    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
    Brigham and Women’s Hospital, Harvard Medical School)

  • 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
    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)

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.

Suggested Citation

  • 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 S, 2021. "Clonal hematopoiesis is associated with risk of severe Covid-19," Nature Communications, Nature, vol. 12(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26138-6
    DOI: 10.1038/s41467-021-26138-6
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    References listed on IDEAS

    as
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