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 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,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 +45 more
TLDR
In this paper, the authors show that acquired somatic mutations in hematopoietic stem and progenitor cells are associated with advanced age, increased risk of cardiovascular and malignant diseases, and decreased overall survival.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. 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.read more
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Journal ArticleDOI
Common and rare variant associations with clonal haematopoiesis phenotypes
Michael D. Kessler,Amy Damask,Sean O’Keeffe,Nilanjana Banerjee,Dadong Li,Kyoko Watanabe,Anthony Marketta,Michael Van Meter,Stefan Semrau,Julie Horowitz,Jing Tang,Jack A. Kosmicki,Veera M. Rajagopal,Yuxin Zou,Yariv Houvras,Arkopravo Ghosh,Christopher Gillies,Joelle Mbatchou,Ryan R. White,Niek Verweij,Jonas Bovijn,Neelroop N. Parikshak,Michelle G. LeBlanc,Marcus B. Jones,David J. Glass,Luca A. Lotta,Michael Cantor,Gurinder S. Atwal,Adam E. Locke,Manuel A. R. Ferreira,Raquel P. Deering,Charles Paulding,Alan R. Shuldiner,Gavin Thurston,Adolfo A. Ferrando,William J Salerno,Jeffrey G. Reid,John D. Overton,Jonathan Marchini,Hyun Min Kang,Aris Baras,Gonçalo R. Abecasis,Eric Jorgenson +42 more
TL;DR: In this paper , exome sequence data from 628,388 individuals was used to identify 24 risk loci in 40,208 carriers of clonal haematopoiesis of indeterminate potential and link them to other conditions including COVID-19, cardiovascular disease and cancer.
Journal ArticleDOI
Clonal hematopoiesis: Mutation-specific adaptation to environmental change.
Marcus A Florez,Brandon T. Tran,Trisha K. Wathan,James DeGregori,Eric M. Pietras,Katherine Y. King +5 more
TL;DR: In this article , the authors discuss how environmental contexts associated with CHIP, such as old age, infections, chemotherapy, or cigarette smoking, alter tissue microenvironments to facilitate the selection and expansion of specific CHIP mutant clones.
Journal ArticleDOI
Clonal hematopoiesis: Molecular and clinical implications.
TL;DR: Clonal hematopoiesis (CH) defines a population of cells with one or more mutations/copy number alterations that can expand with time and under positive clonal selection pressures as mentioned in this paper .
Journal ArticleDOI
Overall survival with circulating tumor DNA-guided therapy in advanced non-small-cell lung cancer
Posted ContentDOI
Exome sequencing of 628,388 individuals identifies common and rare variant associations with clonal hematopoiesis phenotypes
Michael D. Kessler,Amy Damask,Sean O'Keeffe,Nilanjana Banerjee,Sabine Semrau,D. Li,K. Watanabe,Julie Horowitz,Yariv Houvras,Christopher E. Gillies,Joelle Mbatchou,Rebekah R. White,Jack A. Kosmicki,Martha LeBlanc,David J. Glass,Luca A. Lotta,Mami Cantor,Gurinder S. Atwal,Adam E. Locke,Margaret A. Ferreira,Raquel P. Deering,Charles Paulding,Alan R. Shuldiner,Galloway Thurston,William J Salerno,Jim Reid,John D. Overton,Jonathan Marchini,H. Kang,Aris Baras,Gonaclo Abecasis,Eric Jorgenson +31 more
TL;DR: Using genome-wide and exome-wide association analyses, 27 loci are identified where germline genetic variation influences CH/CHIP predisposition, including missense variants in the DNA-repair gene PARP1 and the lymphocytic antigen coding gene LY75 that are associated with reduced incidence of CH/ CHIP.
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TL;DR: The presence of CHIP in peripheral‐blood cells was associated with nearly a doubling in the risk of coronary heart disease in humans and with accelerated atherosclerosis in mice.
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