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 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

doi:10.1038/s41467-021-26138-6

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

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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. 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 language	English
Article number	5975
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-26138-6
State	Published - 1 Dec 2021

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Publisher Copyright:
© 2021, The Author(s).

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Bolton, K. L., Koh, Y., Foote, M. B., Im, H., Jee, J., Sun, C. H., Safonov, A., Ptashkin, R., Moon, J. H., Lee, J. Y., Jung, J., Kang, C. K., Song, K. H., Choe, P. G., Park, W. B., Kim, H. B., Oh, M. D., Song, H., Kim, S., ... Zehir, A. (2021). Clonal hematopoiesis is associated with risk of severe Covid-19. Nature Communications, 12(1), Article 5975. https://doi.org/10.1038/s41467-021-26138-6

@article{0b9e5b3571624c4c9489da1d3a6dc226,

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 = "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",

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Bolton, KL, Koh, Y, Foote, MB, Im, H, Jee, J, Sun, CH, Safonov, A, Ptashkin, R, Moon, JH, Lee, JY, Jung, J, Kang, CK , Song, KH , Choe, PG , Park, WB , Kim, HB, Oh, MD, Song, H, Kim, S, Patel, M, Derkach, A, Gedvilaite, E, Tkachuk, KA, Wiley, BJ, Chan, IC, Braunstein, LZ, Gao, T, Papaemmanuil, E, Esther Babady, N, Pessin, MS, Kamboj, M, Diaz, LA, Ladanyi, M, Rauh, MJ, Natarajan, P, Machiela, MJ, Awadalla, P, Joseph, V, Offit, K, Norton, L, Berger, MF, Levine, RL, Kim, ES , Kim, NJ & Zehir, A 2021, 'Clonal hematopoiesis is associated with risk of severe Covid-19', Nature Communications, vol. 12, no. 1, 5975. https://doi.org/10.1038/s41467-021-26138-6

TY - JOUR

T1 - Clonal hematopoiesis is associated with risk of severe Covid-19

AU - Bolton, Kelly L.

AU - Koh, Youngil

AU - Foote, Michael B.

AU - Im, Hogune

AU - Jee, Justin

AU - Sun, Choong Hyun

AU - Safonov, Anton

AU - Ptashkin, Ryan

AU - Moon, Joon Ho

AU - Lee, Ji Yeon

AU - Jung, Jongtak

AU - Kang, Chang Kyung

AU - Song, Kyoung Ho

AU - Choe, Pyoeng Gyun

AU - Park, Wan Beom

AU - Kim, Hong Bin

AU - Oh, Myoung don

AU - Song, Han

AU - Kim, Sugyeong

AU - Patel, Minal

AU - Derkach, Andriy

AU - Gedvilaite, Erika

AU - Tkachuk, Kaitlyn A.

AU - Wiley, Brian J.

AU - Chan, Ireaneus C.

AU - Braunstein, Lior Z.

AU - Gao, Teng

AU - Papaemmanuil, Elli

AU - Esther Babady, N.

AU - Pessin, Melissa S.

AU - Kamboj, Mini

AU - Diaz, Luis A.

AU - Ladanyi, Marc

AU - Rauh, Michael J.

AU - Natarajan, Pradeep

AU - Machiela, Mitchell J.

AU - Awadalla, Philip

AU - Joseph, Vijai

AU - Offit, Kenneth

AU - Norton, Larry

AU - Berger, Michael F.

AU - Levine, Ross L.

AU - Kim, Eu Suk

AU - Kim, Nam Joong

AU - Zehir, Ahmet

PY - 2021/12/1

Y1 - 2021/12/1

N2 - 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.

AB - 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.

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U2 - 10.1038/s41467-021-26138-6

DO - 10.1038/s41467-021-26138-6

M3 - Article

C2 - 34645798

AN - SCOPUS:85117421909

SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 5975

ER -

Clonal hematopoiesis is associated with risk of severe Covid-19

Abstract

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