Abstract
The IMPACC cohort, composed of >1,000 hospitalized COVID-19 participants, contains five illness trajectory groups (TGs) during acute infection (first 28 days), ranging from milder (TG1–3) to more severe disease course (TG4) and death (TG5). Here, we report deep immunophenotyping, profiling of >15,000 longitudinal blood and nasal samples from 540 participants of the IMPACC cohort, using 14 distinct assays. These unbiased analyses identify cellular and molecular signatures present within 72 h of hospital admission that distinguish moderate from severe and fatal COVID-19 disease. Importantly, cellular and molecular states also distinguish participants with more severe disease that recover or stabilize within 28 days from those that progress to fatal outcomes (TG4 vs. TG5). Furthermore, our longitudinal design reveals that these biologic states display distinct temporal patterns associated with clinical outcomes. Characterizing host immune responses in relation to heterogeneity in disease course may inform clinical prognosis and opportunities for intervention.
| Original language | English (US) |
|---|---|
| Article number | 101079 |
| Journal | Cell Reports Medicine |
| Volume | 4 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 20 2023 |
Keywords
- COVID-19
- SARS-CoV-2
- immunophenotyping
- longitudinal modeling
- multi-omics
- systems immunology
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
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In: Cell Reports Medicine, Vol. 4, No. 6, 101079, 20.06.2023.
Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Multi-omic longitudinal study reveals immune correlates of clinical course among hospitalized COVID-19 patients
AU - IMPACC Network
AU - Diray-Arce, Joann
AU - Fourati, Slim
AU - Doni Jayavelu, Naresh
AU - Patel, Ravi
AU - Maguire, Cole
AU - Chang, Ana C.
AU - Dandekar, Ravi
AU - Qi, Jingjing
AU - Lee, Brian H.
AU - van Zalm, Patrick
AU - Schroeder, Andrew
AU - Chen, Ernie
AU - Konstorum, Anna
AU - Brito, Anderson
AU - Gygi, Jeremy P.
AU - Kho, Alvin
AU - Chen, Jing
AU - Pawar, Shrikant
AU - Gonzalez-Reiche, Ana Silvia
AU - Hoch, Annmarie
AU - Milliren, Carly E.
AU - Overton, James A.
AU - Westendorf, Kerstin
AU - Abraham, James
AU - Adkisson, Michael
AU - Albert, Marisa
AU - Altamirano Torres, Luz
AU - Alvarenga, Bonny
AU - Anderson, Matthew L.
AU - Anderson, Evan J.
AU - Arnett, Azlann
AU - Asashima, Hiromitsu
AU - Atkinson, Mark A.
AU - Baden, Lindsey R.
AU - Barton, Brenda
AU - Beach, Katherine
AU - Beagle, Elizabeth
AU - Becker, Patrice M.
AU - Bell, Matthew R.
AU - Bernui, Mariana
AU - Bime, Chris
AU - Boddapati Kumar, Arun
AU - Booth, Leland J.
AU - Borresen, Brittney
AU - Brakenridge, Scott C.
AU - Bristow, Laurel
AU - Bryant, Robert
AU - Kimura, Hiroki
AU - Kraft, Monica
AU - Mosier, Jarrod
N1 - Funding Information: The authors thank Marianne Bernardo, Julia Boll, Jenny Brook, Omkar Chaudhary, Mitchell Cooney, Dimitri Duvilaire, John Fournier, Jennifer A. Fulcher, Tristan Horton, Laila Hussaini, Shannon Intluxay, Maxine Kuang, Megan Llamas, Clara E. Magyar, Aneesh K. Mehta, Elena Morrocchi, Catherine Muenker, Arash Naeim, Claudia Perdomo, Khadir Raddassi, Michael Rainone, Estefania Ramires-Sanchez, Shun Rao, William Ruff, Syim Salahuddin, Sarahmay Sanchez, Denise Shepherd, Christine Spainhour, Sanya Thomas, Sofia Vignolo, Haowei Wang, and the UCLA Center for Pathology Research Services and the Pathology Research Portal. The study was funded by the US National Institutes of Health National Institute of Allergy and Infectious Diseases through the following grants: R01AI135803 , U19AI118608 , U19AI128910 , U19AI090023 , U19AI090023 , P510D11132 , U19AI118610 , R01AI145835 , U19AI062629 , U19AI057229 , U19AI125357 , U19AI128913 , U19AI077439 , U54AI142766 , R01AI104870 , U19AI089992 , U19AI128913 , U19AI1289130, U19AI128913 and R01AI122220 . Funding Information: The Icahn School of Medicine at Mount Sinai has filed patent applications relating to SARS-CoV-2 serological assays and NDV-based SARS-CoV-2 vaccines, which list F.K. as co-inventor. Mount Sinai has spun out a company, Kantaro, to market serological tests for SARS-CoV-2. F.K. has consulted for Merck and Pfizer (before 2020) and is currently consulting for Pfizer, Seqirus, Third Rock Ventures, Merck, and Avimex. The Krammer laboratory is also collaborating with Pfizer on animal models of SARS-CoV-2. Viviana Simon is a co-inventor on a patent filed relating to SARS-CoV-2 serological assays (the “Serology Assays”). O.L. is a named inventor on patents held by Boston Children’s Hospital relating to vaccine adjuvants and human in vitro platforms that model vaccine action. His laboratory has received research support from GlaxoSmithKline (GSK). C.B.C. serves as a consultant to bioMerieux and is funded for a grant from the Bill & Melinda Gates Foundation. J.A.O. is a consultant at Knocean, Inc. J.L.-S. serves as a scientific advisor of Precion, Inc. S.R.H., G.M., and K.W. are employees of Metabolon, Inc. V.S.-M. is a current employee of MyOwnMed. N.R. reports contracts with Lilly and Sanofi for COVID-19 clinical trials and serves as a consultant for ICON EMMES for consulting on safety for COVID19 clinical trials. A. Rahman is a current employee of Immunai, Inc. S.H.K. is a consultant related to ImmPort data repository for Peraton. N.D.G. is a consultant for Tempus Labs and the National Basketball Association. Akiko Iwasaki is a consultant for 4BIO, Blue Willow Biologics, Revelar Biotherapeutics, RIGImmune, Xanadu Bio, and Paratus Sciences. M. Kraft receives research funds paid to her institution from NIH and ALA and from Sanofi and Astra-Zeneca for work in asthma; serves as a consultant for Astra-Zeneca, Sanofi, Chiesi, and GSK for severe asthma; and is a co-founder and CMO for RaeSedo, Inc., a company created to develop peptidomimetics for treatment of inflammatory lung disease. E. Melamed received research funding from Babson Diagnostics and honorarium from Multiple Sclerosis Association of America and has served on the advisory boards of Genentech, Horizon, Teva, and Viela Bio. Funding Information: The authors thank Marianne Bernardo, Julia Boll, Jenny Brook, Omkar Chaudhary, Mitchell Cooney, Dimitri Duvilaire, John Fournier, Jennifer A. Fulcher, Tristan Horton, Laila Hussaini, Shannon Intluxay, Maxine Kuang, Megan Llamas, Clara E. Magyar, Aneesh K. Mehta, Elena Morrocchi, Catherine Muenker, Arash Naeim, Claudia Perdomo, Khadir Raddassi, Michael Rainone, Estefania Ramires-Sanchez, Shun Rao, William Ruff, Syim Salahuddin, Sarahmay Sanchez, Denise Shepherd, Christine Spainhour, Sanya Thomas, Sofia Vignolo, Haowei Wang, and the UCLA Center for Pathology Research Services and the Pathology Research Portal. The study was funded by the US National Institutes of Health National Institute of Allergy and Infectious Diseases through the following grants: R01AI135803, U19AI118608, U19AI128910, U19AI090023, U19AI090023, P510D11132, U19AI118610, R01AI145835, U19AI062629, U19AI057229, U19AI125357, U19AI128913, U19AI077439, U54AI142766, R01AI104870, U19AI089992, U19AI128913, U19AI1289130, U19AI128913 and R01AI122220. Conceptualization, J.D.-A. S.F. IMPACC Network, C.B.C. N.R. M.C.A. H.M. R.R.M. E.K.H. R.P.S. D.E. A.O. P.M.B. A.D.A. L.G. B.P. and S.H.K.; formal analysis, J.D.-A. S.F. N.D.J. R.P. C.M. A.S.G.-R. R.D. J.Q. B.H.L. P.v.Z. A.S. E.C. A.K. A.B. and J.P.G.; data curation, J.D.-A. A.K. J.C. S.P. A.C.C. A.H. J.A.O. K.W. D.E. A.O. and B.P.; software, R.P. C.M. J.G. and L.G.; methodology, L.G. and S.H.K.; resources, S.E.B. S.K.-S. F.K. L.R. H.v.B. M.W. H.S. W.E. C.L. O.L. M.C.A. H.M. and R.R.M.; funding acquisition, IMPACC Network; supervision, N.D.G. H.v.B. M.W. J.R. H.S. W.E. C.C. C.L. O.L. M.C.A. H.M. L.G. B.P. and S.H.K. All authors wrote, edited, and reviewed the manuscript. The Icahn School of Medicine at Mount Sinai has filed patent applications relating to SARS-CoV-2 serological assays and NDV-based SARS-CoV-2 vaccines, which list F.K. as co-inventor. Mount Sinai has spun out a company, Kantaro, to market serological tests for SARS-CoV-2. F.K. has consulted for Merck and Pfizer (before 2020) and is currently consulting for Pfizer, Seqirus, Third Rock Ventures, Merck, and Avimex. The Krammer laboratory is also collaborating with Pfizer on animal models of SARS-CoV-2. Viviana Simon is a co-inventor on a patent filed relating to SARS-CoV-2 serological assays (the “Serology Assays”). O.L. is a named inventor on patents held by Boston Children's Hospital relating to vaccine adjuvants and human in vitro platforms that model vaccine action. His laboratory has received research support from GlaxoSmithKline (GSK). C.B.C. serves as a consultant to bioMerieux and is funded for a grant from the Bill & Melinda Gates Foundation. J.A.O. is a consultant at Knocean, Inc. J.L.-S. serves as a scientific advisor of Precion, Inc. S.R.H. G.M. and K.W. are employees of Metabolon, Inc. V.S.-M. is a current employee of MyOwnMed. N.R. reports contracts with Lilly and Sanofi for COVID-19 clinical trials and serves as a consultant for ICON EMMES for consulting on safety for COVID19 clinical trials. A. Rahman is a current employee of Immunai, Inc. S.H.K. is a consultant related to ImmPort data repository for Peraton. N.D.G. is a consultant for Tempus Labs and the National Basketball Association. Akiko Iwasaki is a consultant for 4BIO, Blue Willow Biologics, Revelar Biotherapeutics, RIGImmune, Xanadu Bio, and Paratus Sciences. M. Kraft receives research funds paid to her institution from NIH and ALA and from Sanofi and Astra-Zeneca for work in asthma; serves as a consultant for Astra-Zeneca, Sanofi, Chiesi, and GSK for severe asthma; and is a co-founder and CMO for RaeSedo, Inc. a company created to develop peptidomimetics for treatment of inflammatory lung disease. E. Melamed received research funding from Babson Diagnostics and honorarium from Multiple Sclerosis Association of America and has served on the advisory boards of Genentech, Horizon, Teva, and Viela Bio. Publisher Copyright: © 2023 The Authors
PY - 2023/6/20
Y1 - 2023/6/20
N2 - The IMPACC cohort, composed of >1,000 hospitalized COVID-19 participants, contains five illness trajectory groups (TGs) during acute infection (first 28 days), ranging from milder (TG1–3) to more severe disease course (TG4) and death (TG5). Here, we report deep immunophenotyping, profiling of >15,000 longitudinal blood and nasal samples from 540 participants of the IMPACC cohort, using 14 distinct assays. These unbiased analyses identify cellular and molecular signatures present within 72 h of hospital admission that distinguish moderate from severe and fatal COVID-19 disease. Importantly, cellular and molecular states also distinguish participants with more severe disease that recover or stabilize within 28 days from those that progress to fatal outcomes (TG4 vs. TG5). Furthermore, our longitudinal design reveals that these biologic states display distinct temporal patterns associated with clinical outcomes. Characterizing host immune responses in relation to heterogeneity in disease course may inform clinical prognosis and opportunities for intervention.
AB - The IMPACC cohort, composed of >1,000 hospitalized COVID-19 participants, contains five illness trajectory groups (TGs) during acute infection (first 28 days), ranging from milder (TG1–3) to more severe disease course (TG4) and death (TG5). Here, we report deep immunophenotyping, profiling of >15,000 longitudinal blood and nasal samples from 540 participants of the IMPACC cohort, using 14 distinct assays. These unbiased analyses identify cellular and molecular signatures present within 72 h of hospital admission that distinguish moderate from severe and fatal COVID-19 disease. Importantly, cellular and molecular states also distinguish participants with more severe disease that recover or stabilize within 28 days from those that progress to fatal outcomes (TG4 vs. TG5). Furthermore, our longitudinal design reveals that these biologic states display distinct temporal patterns associated with clinical outcomes. Characterizing host immune responses in relation to heterogeneity in disease course may inform clinical prognosis and opportunities for intervention.
KW - COVID-19
KW - SARS-CoV-2
KW - immunophenotyping
KW - longitudinal modeling
KW - multi-omics
KW - systems immunology
UR - http://www.scopus.com/inward/record.url?scp=85162133285&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85162133285&partnerID=8YFLogxK
U2 - 10.1016/j.xcrm.2023.101079
DO - 10.1016/j.xcrm.2023.101079
M3 - Article
C2 - 37327781
AN - SCOPUS:85162133285
SN - 2666-3791
VL - 4
JO - Cell Reports Medicine
JF - Cell Reports Medicine
IS - 6
M1 - 101079
ER -