@article{f554be0d2ccc4308a2e07f57b4e4e4aa,
title = "Combinatorial analysis reveals highly coordinated early-stage immune reactions that predict later antiviral immunity in mild COVID-19 patients",
abstract = "While immunopathology has been widely studied in patients with severe COVID-19, immune responses in non-hospitalized patients have remained largely elusive. We systematically analyze 484 peripheral cellular or soluble immune features in a longitudinal cohort of 63 mild and 15 hospitalized patients versus 14 asymptomatic and 26 household controls. We observe a transient increase of IP10/CXCL10 and interferon-β levels, coordinated responses of dominant SARS-CoV-2-specific CD4 and fewer CD8 T cells, and various antigen-presenting and antibody-secreting cells in mild patients within 3 days of PCR diagnosis. The frequency of key innate immune cells and their functional marker expression are impaired in hospitalized patients at day 1 of inclusion. T cell and dendritic cell responses at day 1 are highly predictive for SARS-CoV-2-specific antibody responses after 3 weeks in mild but not hospitalized patients. Our systematic analysis reveals a combinatorial picture and trajectory of various arms of the highly coordinated early-stage immune responses in mild COVID-19 patients.",
keywords = "combinatorial analysis, COVID-19, early-stage response, immunology, mild patients, non-hospitalized, predict antibody levels, SARS-CoV-2, systems immunology, transient cytokine response",
author = "Capelle, \{Christophe M.\} and S{\'e}verine Cir{\'e} and Olivia Domingues and Isabelle Ernens and Fanny Hedin and Aur{\'e}lie Fischer and Snoeck, \{Chantal J.\} and Wim Ammerlaan and Maria Konstantinou and Kamil Grzyb and Alexander Skupin and Carty, \{Cara L.\} and Christiane Hilger and Georges Gilson and Aljosa Celebic and Paul Wilmes and \{Del Sol\}, Antonio and Kaplan, \{Ian M.\} and Fay Betsou and Tamir Abdelrahman and Antonio Cosma and Michel Vaillant and Guy Fagherazzi and Markus Ollert and Hefeng, \{Feng Q.\}",
note = "Funding Information: We acknowledge the active involvement of all the participants in the Predi-COVID cohort. We are also thankful for the support of the cohort recruitment team from CIEC of LIH and of the IBBL processing and biorepository teams. We also acknowledge Prof. Laetitia Huiart for her efforts in initiating the Predi-COVID cohort and Aur{\'e}lie Sausy, Sophie M{\'e}riaux, and Jean-Yves Servais for their technical help. The Predi-COVID study is supported by the Luxembourg National Research Fund (FNR) ( 14716273 ), the Fondation Andr{\'e} Losch , and the European Regional Development Fund (FEDER, no. 2018-04-026-21 ). F.Q.H. was partially supported by FNR AFR-RIKEN bilateral program (TregBAR, 11228353 , F.Q.H. and M.O.) and PRIDE programme ( 11012546/NEXTIMMUNE and 10907093/CRITICS ). C.H. was partially supported by the FNR COVID-19/2020-1/14703957/COV-Immun. P.W. acknowledges funding from the European Research Council under the European Union{\textquoteright}s Horizon 2020 research and innovation program (no. 863664 ). Funding Information: We acknowledge the active involvement of all the participants in the Predi-COVID cohort. We are also thankful for the support of the cohort recruitment team from CIEC of LIH and of the IBBL processing and biorepository teams. We also acknowledge Prof. Laetitia Huiart for her efforts in initiating the Predi-COVID cohort and Aur?lie Sausy, Sophie M?riaux, and Jean-Yves Servais for their technical help. The Predi-COVID study is supported by the Luxembourg National Research Fund (FNR) (14716273), the Fondation Andr? Losch, and the European Regional Development Fund (FEDER, no. 2018-04-026-21). F.Q.H. was partially supported by FNR AFR-RIKEN bilateral program (TregBAR, 11228353, F.Q.H. and M.O.) and PRIDE programme (11012546/NEXTIMMUNE and 10907093/CRITICS). C.H. was partially supported by the FNR COVID-19/2020-1/14703957/COV-Immun. P.W. acknowledges funding from the European Research Council under the European Union's Horizon 2020 research and innovation program (no. 863664). C.M.C. designed and performed the experiments, performed data analysis, and drafted the manuscript. S.C. O.D. F.H. M.K. and W.A. performed parts of experiments. I.E. and A.F. coordinated the recruitment. C.J.S. C.H. G.G. T.A. and K.G. collected samples and performed parts of experiments. A.C. and M.V. collected clinical data, quality control, and data management. C.L.C. and I.M.K. analyzed the TCR repertoire data. A.S. A.D.S. P.W. A.C. F.B. and G.F. provided substantial supervision and insights into the project. F.Q.H. and M.O. conceived and oversaw the whole project and finalized the manuscript. The authors declare no competing interests. We worked to ensure gender balance in the recruitment of human subjects. We worked to ensure ethnic or other types of diversity in the recruitment of human subjects. We worked to ensure that the study questionnaires were prepared in an inclusive way. The author list of this article includes contributors from the location where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = apr,
day = "19",
doi = "10.1016/j.xcrm.2022.100600",
language = "English",
volume = "3",
journal = "Cell Reports Medicine",
issn = "2666-3791",
publisher = "Cell Press",
number = "4",
}