Clonal hematopoiesis is associated with risk of severe Covid-19

  1. Kelly L. Bolton
  2. Youngil Koh
  3. Michael B. Foote
  4. Hogune Im
  5. Justin Jee
  6. Choong Hyun Sun
  7. Anton Safonov
  8. Ryan Ptashkin
  9. Joon Ho Moon
  10. Ji Yeon Lee
  11. Jongtak Jung
  12. Chang Kyung Kang
  13. Kyoung-Ho Song
  14. Pyeong Gyun Choe
  15. Wan Beom Park
  16. Hong Bin Kim
  17. Myoung-don Oh
  18. Han Song
  19. Sugyeong Kim
  20. Minal Patel
  21. Andriy Derkach
  22. Erika Gedvilaite
  23. Kaitlyn A. Tkachuk
  24. Lior Z. Braunstein
  25. Teng Gao
  26. Elli Papaemmanuil
  27. N. Esther Babady
  28. Melissa S. Pessin
  29. Mini Kamboj
  30. Luis A. Diaz
  31. Marc Ladanyi
  32. Michael J. Rauh
  33. Pradeep Natarajan
  34. Mitchell J. Machiela
  35. Philip Awadalla
  36. Vijai Joseph
  37. Kenneth Offit
  38. Larry Norton
  39. Michael F Berger
  40. Ross L Levine
  41. Eu Suk Kim
  42. Nam Joong Kim
  43. Ahmet Zehir
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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. 1–4 These adverse sequelae may be mediated by altered inflammatory profiles observed in patients with CH. 2,5,6 A pro-inflammatory immunologic profile is also associated with worse outcomes of certain infections, including SARS-CoV-2 and its associated disease Covid-19. 7,8 Whether CH predisposes to severe Covid-19 or other infections is unknown. Among 515 individuals with Covid-19 from Memorial Sloan Kettering (MSK) and the Korean Clonal Hematopoiesis (KoCH) consortia, we found that CH was associated with severe Covid-19 outcomes (OR=1.9, 95%=1.2-2.9, p=0.01). We further explored the relationship between CH and risk of other infections in 14,211 solid tumor patients at MSK. CH was significantly associated with risk of Clostridium Difficile (HR=2.0, 95% CI: 1.2-3.3, p=6×10 −3 ) and Streptococcus/Enterococcus infections (HR=1.5, 95% CI=1.1-2.1, p=5×10 −3 ). These findings suggest a relationship between CH and risk of severe infections that warrants further investigation.

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