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 PatelAndriy 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, Ahmet Zehir

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish
Article number5975
JournalNature communications
Volume12
Issue number1
DOIs
StatePublished - Dec 1 2021

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