PMID- 35600330 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230206 IS - 2589-5370 (Electronic) IS - 2589-5370 (Linking) VI - 48 DP - 2022 Jun TI - Highly multiplexed immune repertoire sequencing links multiple lymphocyte classes with severity of response to COVID-19. PG - 101438 LID - 10.1016/j.eclinm.2022.101438 [doi] LID - 101438 AB - BACKGROUND: Disease progression of subjects with coronavirus disease 2019 (COVID-19) varies dramatically. Understanding the various types of immune response to SARS-CoV-2 is critical for better clinical management of coronavirus outbreaks and to potentially improve future therapies. Disease dynamics can be characterized by deciphering the adaptive immune response. METHODS: In this cross-sectional study we analyzed 117 peripheral blood immune repertoires from healthy controls and subjects with mild to severe COVID-19 disease to elucidate the interplay between B and T cells. We used an immune repertoire Primer Extension Target Enrichment method (immunoPETE) to sequence simultaneously human leukocyte antigen (HLA) restricted T cell receptor beta chain (TRB) and unrestricted T cell receptor delta chain (TRD) and immunoglobulin heavy chain (IgH) immune receptor repertoires. The distribution was analyzed of TRB, TRD and IgH clones between healthy and COVID-19 infected subjects. Using McFadden's Adjusted R2 variables were examined for a predictive model. The aim of this study is to analyze the influence of the adaptive immune repertoire on the severity of the disease (value on the World Health Organization Clinical Progression Scale) in COVID-19. FINDINGS: Combining clinical metadata with clonotypes of three immune receptor heavy chains (TRB, TRD, and IgH), we found significant associations between COVID-19 disease severity groups and immune receptor sequences of B and T cell compartments. Logistic regression showed an increase in shared IgH clonal types and decrease of TRD in subjects with severe COVID-19. The probability of finding shared clones of TRD clonal types was highest in healthy subjects (controls). Some specific TRB clones seems to be present in severe COVID-19 (Figure S7b). The most informative models (McFadden s Adjusted R2=0.141) linked disease severity with immune repertoire measures across all three cell types, as well as receptor-specific cell counts, highlighting the importance of multiple lymphocyte classes in disease progression. INTERPRETATION: Adaptive immune receptor peripheral blood repertoire measures are associated with COVID-19 disease severity. FUNDING: The study was funded with grants from the Berlin Institute of Health (BIH). CI - (c) 2022 The Authors. FAU - Dannebaum, Richard AU - Dannebaum R AD - Roche Sequencing Solutions Pleasanton, CA 94588, United States. FAU - Suwalski, Phillip AU - Suwalski P AD - Department of Cardiology, Charite Universitatsmedizin Berlin, Berlin, DE 10117, Germany. FAU - Asgharian, Hosseinali AU - Asgharian H AD - Roche Sequencing Solutions Pleasanton, CA 94588, United States. FAU - Du Zhipei, Gracie AU - Du Zhipei G AD - Roche Sequencing Solutions Pleasanton, CA 94588, United States. FAU - Lin, Hai AU - Lin H AD - Roche Sequencing Solutions Pleasanton, CA 94588, United States. FAU - Weiner, January AU - Weiner J AD - Core Unit Bioinformatics Berlin, Berlin Institute of Health at Charite-Universitatsmedizin Berlin, DE 10178, Germany. FAU - Holtgrewe, Manuel AU - Holtgrewe M AD - Core Unit Bioinformatics Berlin, Berlin Institute of Health at Charite-Universitatsmedizin Berlin, DE 10178, Germany. FAU - Thibeault, Charlotte AU - Thibeault C AD - Department of Infectious Diseases and Respiratory Medicine, Charite Universitatsmedizin Berlin, DE 12203, Germany. FAU - Muller, Melina AU - Muller M AD - Department of Cardiology, Charite Universitatsmedizin Berlin, Berlin, DE 10117, Germany. FAU - Wang, Xiaomin AU - Wang X AD - Department of Cardiology, Charite Universitatsmedizin Berlin, Berlin, DE 10117, Germany. FAU - Karadeniz, Zehra AU - Karadeniz Z AD - Department of Cardiology, Charite Universitatsmedizin Berlin, Berlin, DE 10117, Germany. FAU - Saccomanno, Jacopo AU - Saccomanno J AD - Department of Infectious Diseases and Respiratory Medicine, Charite Universitatsmedizin Berlin, DE 12203, Germany. FAU - Doehn, Jan-Moritz AU - Doehn JM AD - Department of Infectious Diseases and Respiratory Medicine, Charite Universitatsmedizin Berlin, DE 12203, Germany. FAU - Hubner, Ralf-Harto AU - Hubner RH AD - Department of Infectious Diseases and Respiratory Medicine, Charite Universitatsmedizin Berlin, DE 12203, Germany. FAU - Hinzmann, Bernd AU - Hinzmann B AD - Signature Diagnostics GmbH, DE 14473, Germany. FAU - Bluher, Anja AU - Bluher A AD - Signature Diagnostics GmbH, DE 14473, Germany. FAU - Siemann, Sandra AU - Siemann S AD - Signature Diagnostics GmbH, DE 14473, Germany. FAU - Telman, Dilduz AU - Telman D AD - Roche Sequencing Solutions Pleasanton, CA 94588, United States. FAU - Suttorp, Norbert AU - Suttorp N AD - Department of Infectious Diseases and Respiratory Medicine, Charite Universitatsmedizin Berlin, DE 12203, Germany. FAU - Witzenrath, Martin AU - Witzenrath M AD - Department of Infectious Diseases and Respiratory Medicine, Charite Universitatsmedizin Berlin, DE 12203, Germany. FAU - Hippenstiel, Stefan AU - Hippenstiel S AD - Department of Infectious Diseases and Respiratory Medicine, Charite Universitatsmedizin Berlin, DE 12203, Germany. FAU - Skurk, Carsten AU - Skurk C AD - Department of Cardiology, Charite Universitatsmedizin Berlin, Berlin, DE 10117, Germany. FAU - Poller, Wolfgang AU - Poller W AD - Department of Cardiology, Charite Universitatsmedizin Berlin, Berlin, DE 10117, Germany. FAU - Sander, Leif E AU - Sander LE AD - Department of Infectious Diseases and Respiratory Medicine, Charite Universitatsmedizin Berlin, DE 12203, Germany. FAU - Beule, Dieter AU - Beule D AD - Core Unit Bioinformatics Berlin, Berlin Institute of Health at Charite-Universitatsmedizin Berlin, DE 10178, Germany. FAU - Kurth, Florian AU - Kurth F AD - Department of Infectious Diseases and Respiratory Medicine, Charite Universitatsmedizin Berlin, DE 12203, Germany. FAU - Guettouche, Toumy AU - Guettouche T AD - Roche Sequencing Solutions Pleasanton, CA 94588, United States. FAU - Landmesser, Ulf AU - Landmesser U AD - Department of Cardiology, Charite Universitatsmedizin Berlin, Berlin, DE 10117, Germany. AD - Berlin Institute of Health at Charite-Universitatsmedizin Berlin, Germany. FAU - Berka, Jan AU - Berka J AD - Roche Sequencing Solutions Pleasanton, CA 94588, United States. FAU - Luong, Khai AU - Luong K AD - Roche Sequencing Solutions Pleasanton, CA 94588, United States. CN - Pa-COVID Study Group FAU - Rubelt, Florian AU - Rubelt F AD - Roche Sequencing Solutions Pleasanton, CA 94588, United States. FAU - Heidecker, Bettina AU - Heidecker B AD - Department of Cardiology, Charite Universitatsmedizin Berlin, Berlin, DE 10117, Germany. LA - eng PT - Journal Article DEP - 20220514 PL - England TA - EClinicalMedicine JT - EClinicalMedicine JID - 101733727 PMC - PMC9106482 OTO - NOTNLM OT - COVID-19 OT - Clinical course OT - Immune receptor OT - Immune repertoires COIS- Telman Dilduz, Dannenbaum Richard, Anja Bluher, Florian Rubelt, Gracie Du Zhipei, Luong Khai, Asgharin Hosseinali, Lin Hai and Berka Jan are employees of Roche Diagnostics and Dannenbaum Richard, Rubelt Forian, Lin Hai, Luong Khai, Berka Jan receive salary, stock and options as part of their employment compensation. EDAT- 2022/05/24 06:00 MHDA- 2022/05/24 06:01 PMCR- 2022/05/14 CRDT- 2022/05/23 03:52 PHST- 2021/11/02 00:00 [received] PHST- 2022/04/15 00:00 [revised] PHST- 2022/04/19 00:00 [accepted] PHST- 2022/05/23 03:52 [entrez] PHST- 2022/05/24 06:00 [pubmed] PHST- 2022/05/24 06:01 [medline] PHST- 2022/05/14 00:00 [pmc-release] AID - S2589-5370(22)00168-7 [pii] AID - 101438 [pii] AID - 10.1016/j.eclinm.2022.101438 [doi] PST - ppublish SO - EClinicalMedicine. 2022 Jun;48:101438. doi: 10.1016/j.eclinm.2022.101438. Epub 2022 May 14.