TY - JOUR
T1 - Immune phenotypes that are associated with subsequent COVID-19 severity inferred from post-recovery samples
AU - Liechti, Thomas
AU - Iftikhar, Yaser
AU - Mangino, Massimo
AU - Beddall, Margaret
AU - Goss, Charles W.
AU - O’Halloran, Jane A.
AU - Mudd, Philip A.
AU - Roederer, Mario
N1 - Funding Information:
This work was supported by the intramural research program of the Vaccine Research Center (NIAID. NIH) to M.R. This study utilized samples obtained from the Washington University School of Medicine’s COVID-19 biorepository, which is supported by: the Barnes-Jewish Hospital Foundation; the Siteman Cancer Center grant P30 CA091842 from the National Cancer Institute of the National Institutes of Health; and the Washington University Institute of Clinical and Translational Sciences grant UL1TR002345 from the National Center for Advancing Translational Sciences of the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the view of the NIH. M.M. is supported by the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London. T.L. is supported by the International Society for Advancement of Cytometry (ISAC) Marylou Ingram Scholar Program. We thank the Flow Cytometry Facility at the Vaccine Research Center including Erica Smit, Esther Thang, Richard Nguyen and Steve Perfetto. In addition, we thank Ingelise Gordon, Charla Andrews, Maria Burgos Florez, Laura Novik, Britta Flach, Emily Coates, Nina Berkowitz and Martin Gaudinski from the VRC Clinical Trials Program and Obrimpong Amoa-Awua and Adrian McDermott from the Vaccine Immunology Program for their support regarding PBMC samples from the NIH and Evergreen cohort. Furthermore, we thank all donors from the VRC and the Washington University cohorts.
Funding Information:
This work was supported by the intramural research program of the Vaccine Research Center (NIAID. NIH) to M.R. This study utilized samples obtained from the Washington University School of Medicine’s COVID-19 biorepository, which is supported by: the Barnes-Jewish Hospital Foundation; the Siteman Cancer Center grant P30 CA091842 from the National Cancer Institute of the National Institutes of Health; and the Washington University Institute of Clinical and Translational Sciences grant UL1TR002345 from the National Center for Advancing Translational Sciences of the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the view of the NIH. M.M. is supported by the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London. T.L. is supported by the International Society for Advancement of Cytometry (ISAC) Marylou Ingram Scholar Program. We thank the Flow Cytometry Facility at the Vaccine Research Center including Erica Smit, Esther Thang, Richard Nguyen and Steve Perfetto. In addition, we thank Ingelise Gordon, Charla Andrews, Maria Burgos Florez, Laura Novik, Britta Flach, Emily Coates, Nina Berkowitz and Martin Gaudinski from the VRC Clinical Trials Program and Obrimpong Amoa-Awua and Adrian McDermott from the Vaccine Immunology Program for their support regarding PBMC samples from the NIH and Evergreen cohort. Furthermore, we thank all donors from the VRC and the Washington University cohorts.
Publisher Copyright:
© 2022, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
PY - 2022/12
Y1 - 2022/12
N2 - Severe COVID-19 causes profound immune perturbations, but pre-infection immune signatures contributing to severe COVID-19 remain unknown. Genome-wide association studies (GWAS) identified strong associations between severe disease and several chemokine receptors and molecules from the type I interferon pathway. Here, we define immune signatures associated with severe COVID-19 using high-dimensional flow cytometry. We measure the cells of the peripheral immune system from individuals who recovered from mild, moderate, severe or critical COVID-19 and focused only on those immune signatures returning to steady-state. Individuals that suffered from severe COVID-19 show reduced frequencies of T cell, mucosal-associated invariant T cell (MAIT) and dendritic cell (DC) subsets and altered chemokine receptor expression on several subsets, such as reduced levels of CCR1 and CCR2 on monocyte subsets. Furthermore, we find reduced frequencies of type I interferon-producing plasmacytoid DCs and altered IFNAR2 expression on several myeloid cells in individuals recovered from severe COVID-19. Thus, these data identify potential immune mechanisms contributing to severe COVID-19.
AB - Severe COVID-19 causes profound immune perturbations, but pre-infection immune signatures contributing to severe COVID-19 remain unknown. Genome-wide association studies (GWAS) identified strong associations between severe disease and several chemokine receptors and molecules from the type I interferon pathway. Here, we define immune signatures associated with severe COVID-19 using high-dimensional flow cytometry. We measure the cells of the peripheral immune system from individuals who recovered from mild, moderate, severe or critical COVID-19 and focused only on those immune signatures returning to steady-state. Individuals that suffered from severe COVID-19 show reduced frequencies of T cell, mucosal-associated invariant T cell (MAIT) and dendritic cell (DC) subsets and altered chemokine receptor expression on several subsets, such as reduced levels of CCR1 and CCR2 on monocyte subsets. Furthermore, we find reduced frequencies of type I interferon-producing plasmacytoid DCs and altered IFNAR2 expression on several myeloid cells in individuals recovered from severe COVID-19. Thus, these data identify potential immune mechanisms contributing to severe COVID-19.
UR - http://www.scopus.com/inward/record.url?scp=85142479966&partnerID=8YFLogxK
U2 - 10.1038/s41467-022-34638-2
DO - 10.1038/s41467-022-34638-2
M3 - Article
C2 - 36433939
AN - SCOPUS:85142479966
SN - 2041-1723
VL - 13
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 7255
ER -