@article{49bf71367fcf4f6ca22670cff2ec1c07,
title = "Clonal hematopoiesis is associated with risk of severe Covid-19",
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.",
author = "Bolton, {Kelly L.} and Youngil Koh and Foote, {Michael B.} and Hogune Im and Justin Jee and Sun, {Choong Hyun} and Anton Safonov and Ryan Ptashkin and Moon, {Joon Ho} and Lee, {Ji Yeon} and Jongtak Jung and Kang, {Chang Kyung} and Song, {Kyoung Ho} and Choe, {Pyoeng Gyun} and Park, {Wan Beom} and Kim, {Hong Bin} and Oh, {Myoung don} and Han Song and Sugyeong Kim and Minal Patel and Andriy Derkach and Erika Gedvilaite and Tkachuk, {Kaitlyn A.} and Wiley, {Brian J.} and Chan, {Ireaneus C.} and Braunstein, {Lior Z.} and Teng Gao and Elli Papaemmanuil and {Esther Babady}, N. and Pessin, {Melissa S.} and Mini Kamboj and Diaz, {Luis A.} and Marc Ladanyi and Rauh, {Michael J.} and Pradeep Natarajan and Machiela, {Mitchell J.} and Philip Awadalla and Vijai Joseph and Kenneth Offit and Larry Norton and Berger, {Michael F.} and Levine, {Ross L.} and Kim, {Eu Suk} and Kim, {Nam Joong} and Ahmet Zehir",
note = "Funding Information: This work was supported by the National Institute of Health (K08CA241318 to K.L.B, P50 CA172012 to L.B., T32-CA009207 to J.J.), American Society of Hematology (K.L.B.), EvansMDS Foundation (K.L.B.), European Hematology Association (E.P.), Gabrielle{\textquoteright}s Angels Foundation (E.P.), V Foundation (E.P.), Geoffrey Beene Foundation (E.P), Starr Cancer Consortium (to R.L., A.Z., M.B, R.P.), and the Cancer Colorectal Cancer Dream Team Translational Research Grant (SU2C-AACR-DT22-17 to L.D.). E.P. is a Josie Robertson Investigator. M.M. is supported by funds from the Intramural Research Program of the National Cancer Institute, National Institutes of Health. The KoCH cohort was supported through a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI14C1277). We thank the Global Science experimental Data hub Center (GSDC) and Korea Research Environment Open NETwork (KREONET) service for data computing and network provided by the Korea Institute of Science and Technology Information (KISTI). Work performed at Memorial Sloan Kettering Cancer Center was supported in part by the Cancer Center Support Grant (grant no. P30 CA008748), the Marie Josee and Henry R Kravis Center for Molecular Oncology, Cycle for Survival, and MSK Molecular Diagnostics Service. Funding Information: The authors declare the following competing interests: K.B. has received research funding from GRAIL and Bristol Myers Squibb; Y.K. is a co-founder in Genome Opinion. M.F.B. is on the advisory board for Roche and receives research support from Illumina. J.J. has a patent licensed by the company MDSeq Inc. R.L.L. is on the supervisory board of Qiagen and is a scientific advisor to Loxo, Imago, C4 Therapeutics, and Isoplexis, which include equity interest. He receives research support from and consulted for Celgene and Roche and has consulted for Lilly, Janssen, Astellas, Morphosys, and Novartis. He has received honoraria from Roche, Lilly, and Amgen for invited lectures and from Gilead for grant reviews. A.Z. received honoraria from Illumina. E.P. receives research funding from Celgene. D.G. and has received honoraria for speaking and scientific advisory engagements with Celgene, Prime Oncology, Novartis, Illumina, and Kyowa Hakko Kirin and is a co-founder in Isabl Technologies. M. Ladanyi has served on the advisory boards for AstraZeneca, Bristol Myers Squibb, Takeda, Bayer, BluePrint, Pfizer, Janssen, and Merck, and has received research support from Loxo Oncology and Helsinn Therapeutics, and Elevation Oncology. L.A.D. is a member of the board of directors of Personal Genome Diagnostics (PGDx) and Jounce Therapeutics; is a paid consultant to PGDx and Neophore; is an uncompensated consultant for Merck (with the exception of travel and research support for clinical trials); is an inventor of multiple licensed patents related to technology for circulating tumor DNA analyses and mismatch repair deficiency for diagnosis and therapy from Johns Hopkins University, some of which are associated with equity or royalty payments directly to Johns Hopkins and L.A.D.; and holds equity in PGDx, Jounce Therapeutics, Thrive Earlier Detection and Neophore; his wife holds equity in Amgen. The terms of all of these arrangements are being managed by Johns Hopkins and Memorial Sloan Kettering in accordance with their conflict of interest policies. H.I., C.H.S., H.S., S.K. are current employees of Genome Opinion and holds stock in the company. All other authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
day = "1",
doi = "10.1038/s41467-021-26138-6",
language = "English",
volume = "12",
journal = "Nature Communications",
issn = "2041-1723",
number = "1",
}