TY - JOUR
T1 - Mass cytometry reveals a conserved immune trajectory of recovery in hospitalized COVID-19 patients
AU - The UCSF COMET Consortium
AU - Burnett, Cassandra E.
AU - Okholm, Trine Line Hauge
AU - Tenvooren, Iliana
AU - Marquez, Diana M.
AU - Tamaki, Stanley
AU - Munoz Sandoval, Priscila
AU - Willmore, Andrew
AU - Patel, Ravi
AU - Abe-Jones, Yumiko
AU - Asthana, Saurabh
AU - Beagle, Alexander
AU - Bhide, Sharvari
AU - Cai, Cathy
AU - Calvo, Maria
AU - Carrillo, Sidney A.
AU - Chak, Suzanna
AU - Collins, Zachary
AU - Darmanis, Spyros
AU - Fragiadakis, Gabriela K.
AU - Ghale, Rajani
AU - Giberson, Jeremy
AU - Glenn, Pat
AU - Gonzalez, Ana
AU - Hiam-Galvez, Kamir
AU - Jauregui, Alejandra
AU - Ke, Serena
AU - Lea, Tasha
AU - Lee, Deanna
AU - Lota, Raphael
AU - Lupin-Jimenez, Leonard
AU - Nguyen, Viet
AU - Nigam, Nishita
AU - Pierce, Logan
AU - Prasad, Priya
AU - Rao, Arjun
AU - Rashid, Sadeed
AU - Rodriguez, Nicklaus
AU - Samad, Bushra
AU - Shaw, Cole
AU - Sigman, Austin
AU - Sinha, Pratik
AU - Tang, Kevin
AU - Altamirano, Luz Torres
AU - Tumurbaatar, Erden
AU - Upadhyay, Vaibhav
AU - Ward, Alyssa
AU - Wong, Kristine
AU - Ye, Chun Jimmie
AU - Yee, Kimberly
AU - Zhou, Mingyue
AU - Hendrickson, Carolyn M.
AU - Kangelaris, Kirsten N.
AU - Langelier, Charles R.
AU - Krummel, Matthew F.
AU - Woodruff, Prescott G.
AU - Calfee, Carolyn S.
AU - Erle, David J.
AU - Ansel, K. Mark
AU - Spitzer, Matthew H.
N1 - Funding Information:
This work was supported by grants from The Carlsberg Foundation (T.L.H.O.); COVID-19 Fast Grants (M.H.S.); NCI 1F31CA260938-01 (C.E.B.); NSF GRFP (C.E.B.); UCSF Discovery Fellowship (C.E.B.); NIH NIAID Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) Network ( 3U19AI077439-13S1 and 3U19AI077439-13S2 ); Howard Hughes Medical Institute James H. Gilliam Fellowship (P.M.S.); NHLBI R35 HL140026 (C.S.C.); funding from NHLBI and NIAID to C.R.L.; NHLBI K23 and a DOD grants to C.M.H.; grant 2019-202665 from the Chan Zuckerberg Foundation and TSK-020586 from Genentech ; and NIH Grants P30DK063720 , S10OD018040 , S10OD018040 , and S10OD021822 to the UCSF Flow Cytometry CoLab. M.H.S. is an investigator of the Chan Zuckerberg Biohub and the Parker Institute for Cancer Immunotherapy.
Funding Information:
This work was supported by grants from The Carlsberg Foundation (T.L.H.O.); COVID-19 Fast Grants (M.H.S.); NCI 1F31CA260938-01 (C.E.B.); NSF GRFP (C.E.B.); UCSF Discovery Fellowship (C.E.B.); NIH NIAID Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) Network (3U19AI077439-13S1 and 3U19AI077439-13S2); Howard Hughes Medical Institute James H. Gilliam Fellowship (P.M.S.); NHLBI R35 HL140026 (C.S.C.); funding from NHLBI and NIAID to C.R.L.; NHLBI K23 and a DOD grants to C.M.H.; grant 2019-202665 from the Chan Zuckerberg Foundation and TSK-020586 from Genentech; and NIH Grants P30DK063720, S10OD018040, S10OD018040, and S10OD021822 to the UCSF Flow Cytometry CoLab. M.H.S. is an investigator of the Chan Zuckerberg Biohub and the Parker Institute for Cancer Immunotherapy. C.E.B. I.T. P.M.S. K.M.A. D.J.E. and M.H.S. conceived the project and designed CyTOF experiments. C.E.B. T.L.H.O. and M.H.S. conceptualized the study. C.E.B. I.T. D.M.M. and S.T. performed CyTOF experiments. T.L.H.O. and C.E.B. performed data analysis and generated all figures. A.W. provided clinical information. C.E.B. T.L.H.O. and M.H.S. wrote and revised the manuscript. M.H.S. supervised the study. C.S.C. C.M.H. C.R.L. M.F.K. P.G.W. and D.J.E. founded and led the COMET Consortium. All authors read and approved the final manuscript. M.H.S. is a board member and equity holder in Teiko.bio and has received research support from Roche/Genentech, Bristol Myers Squibb, Pfizer, and Valitor. C.S.C. has received funding from NHLBI, FDA, DOD, Genentech, and Quantum Leap Healthcare Collaborative and is on consulting/advisory boards for Vasomune, Gen1e Life Sciences, Janssen, and Cellenkos. C.M.H. has been consulting for Spring Discovery. P.G.W. has a contract from Genentech to study COVID-19. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science. The author list of this paper includes contributors from the location where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.
Funding Information:
M.H.S. is a board member and equity holder in Teiko.bio and has received research support from Roche/Genentech, Bristol Myers Squibb, Pfizer, and Valitor. C.S.C. has received funding from NHLBI, FDA, DOD, Genentech, and Quantum Leap Healthcare Collaborative and is on consulting/advisory boards for Vasomune, Gen1e Life Sciences, Janssen, and Cellenkos. C.M.H. has been consulting for Spring Discovery. P.G.W. has a contract from Genentech to study COVID-19.
Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/7/12
Y1 - 2022/7/12
N2 - While studies have elucidated many pathophysiological elements of COVID-19, little is known about immunological changes during COVID-19 resolution. We analyzed immune cells and phosphorylated signaling states at single-cell resolution from longitudinal blood samples of patients hospitalized with COVID-19, pneumonia and/or sepsis, and healthy individuals by mass cytometry. COVID-19 patients showed distinct immune compositions and an early, coordinated, and elevated immune cell signaling profile associated with early hospital discharge. Intra-patient longitudinal analysis revealed changes in myeloid and T cell frequencies and a reduction in immune cell signaling across cell types that accompanied disease resolution and discharge. These changes, together with increases in regulatory T cells and reduced signaling in basophils, also accompanied recovery from respiratory failure and were associated with better outcomes at time of admission. Therefore, although patients have heterogeneous immunological baselines and highly variable disease courses, a core immunological trajectory exists that defines recovery from severe SARS-CoV-2 infection.
AB - While studies have elucidated many pathophysiological elements of COVID-19, little is known about immunological changes during COVID-19 resolution. We analyzed immune cells and phosphorylated signaling states at single-cell resolution from longitudinal blood samples of patients hospitalized with COVID-19, pneumonia and/or sepsis, and healthy individuals by mass cytometry. COVID-19 patients showed distinct immune compositions and an early, coordinated, and elevated immune cell signaling profile associated with early hospital discharge. Intra-patient longitudinal analysis revealed changes in myeloid and T cell frequencies and a reduction in immune cell signaling across cell types that accompanied disease resolution and discharge. These changes, together with increases in regulatory T cells and reduced signaling in basophils, also accompanied recovery from respiratory failure and were associated with better outcomes at time of admission. Therefore, although patients have heterogeneous immunological baselines and highly variable disease courses, a core immunological trajectory exists that defines recovery from severe SARS-CoV-2 infection.
KW - COVID-19
KW - disease resolution
KW - immune cell signaling
KW - immune response
KW - recovery
UR - http://www.scopus.com/inward/record.url?scp=85133353992&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2022.06.004
DO - 10.1016/j.immuni.2022.06.004
M3 - Article
C2 - 35779527
AN - SCOPUS:85133353992
VL - 55
SP - 1284-1298.e3
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 7
ER -