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Single-cell multiomics revealed the dynamics of antigen presentation, immune response and T cell activation in the COVID-19 positive and recovered individuals

INTRODUCTION: Despite numerous efforts to describe COVID-19's immunological landscape, there is still a gap in our understanding of the virus's infections after-effects, especially in the recovered patients. This would be important to understand as we now have huge number of global populat...

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Autores principales: Chattopadhyay, Partha, Khare, Kriti, Kumar, Manish, Mishra, Pallavi, Anand, Alok, Maurya, Ranjeet, Gupta, Rohit, Sahni, Shweta, Gupta, Ayushi, Wadhwa, Saruchi, Yadav, Aanchal, Devi, Priti, Tardalkar, Kishore, Joshi, Meghnad, Sethi, Tavpritesh, Pandey, Rajesh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9755500/
https://www.ncbi.nlm.nih.gov/pubmed/36532041
http://dx.doi.org/10.3389/fimmu.2022.1034159
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author Chattopadhyay, Partha
Khare, Kriti
Kumar, Manish
Mishra, Pallavi
Anand, Alok
Maurya, Ranjeet
Gupta, Rohit
Sahni, Shweta
Gupta, Ayushi
Wadhwa, Saruchi
Yadav, Aanchal
Devi, Priti
Tardalkar, Kishore
Joshi, Meghnad
Sethi, Tavpritesh
Pandey, Rajesh
author_facet Chattopadhyay, Partha
Khare, Kriti
Kumar, Manish
Mishra, Pallavi
Anand, Alok
Maurya, Ranjeet
Gupta, Rohit
Sahni, Shweta
Gupta, Ayushi
Wadhwa, Saruchi
Yadav, Aanchal
Devi, Priti
Tardalkar, Kishore
Joshi, Meghnad
Sethi, Tavpritesh
Pandey, Rajesh
author_sort Chattopadhyay, Partha
collection PubMed
description INTRODUCTION: Despite numerous efforts to describe COVID-19's immunological landscape, there is still a gap in our understanding of the virus's infections after-effects, especially in the recovered patients. This would be important to understand as we now have huge number of global populations infected by the SARS-CoV-2 as well as variables inclusive of VOCs, reinfections, and vaccination breakthroughs. Furthermore, single-cell transcriptome alone is often insufficient to understand the complex human host immune landscape underlying differential disease severity and clinical outcome. METHODS: By combining single-cell multi-omics (Whole Transcriptome Analysis plus Antibody-seq) and machine learning-based analysis, we aim to better understand the functional aspects of cellular and immunological heterogeneity in the COVID-19 positive, recovered and the healthy individuals. RESULTS: Based on single-cell transcriptome and surface marker study of 163,197 cells (124,726 cells after data QC) from the 33 individuals (healthy=4, COVID-19 positive=16, and COVID-19 recovered=13), we observed a reduced MHC Class-I-mediated antigen presentation and dysregulated MHC Class-II-mediated antigen presentation in the COVID-19 patients, with restoration of the process in the recovered individuals. B-cell maturation process was also impaired in the positive and the recovered individuals. Importantly, we discovered that a subset of the naive T-cells from the healthy individuals were absent from the recovered individuals, suggesting a post-infection inflammatory stage. Both COVID-19 positive patients and the recovered individuals exhibited a CD40-CD40LG-mediated inflammatory response in the monocytes and T-cell subsets. T-cells, NK-cells, and monocyte-mediated elevation of immunological, stress and antiviral responses were also seen in the COVID-19 positive and the recovered individuals, along with an abnormal T-cell activation, inflammatory response, and faster cellular transition of T cell subtypes in the COVID-19 patients. Importantly, above immune findings were used for a Bayesian network model, which significantly revealed FOS, CXCL8, IL1β, CST3, PSAP, CD45 and CD74 as COVID-19 severity predictors. DISCUSSION: In conclusion, COVID-19 recovered individuals exhibited a hyper-activated inflammatory response with the loss of B cell maturation, suggesting an impeded post-infection stage, necessitating further research to delineate the dynamic immune response associated with the COVID-19. To our knowledge this is first multi-omic study trying to understand the differential and dynamic immune response underlying the sample subtypes.
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spelling pubmed-97555002022-12-17 Single-cell multiomics revealed the dynamics of antigen presentation, immune response and T cell activation in the COVID-19 positive and recovered individuals Chattopadhyay, Partha Khare, Kriti Kumar, Manish Mishra, Pallavi Anand, Alok Maurya, Ranjeet Gupta, Rohit Sahni, Shweta Gupta, Ayushi Wadhwa, Saruchi Yadav, Aanchal Devi, Priti Tardalkar, Kishore Joshi, Meghnad Sethi, Tavpritesh Pandey, Rajesh Front Immunol Immunology INTRODUCTION: Despite numerous efforts to describe COVID-19's immunological landscape, there is still a gap in our understanding of the virus's infections after-effects, especially in the recovered patients. This would be important to understand as we now have huge number of global populations infected by the SARS-CoV-2 as well as variables inclusive of VOCs, reinfections, and vaccination breakthroughs. Furthermore, single-cell transcriptome alone is often insufficient to understand the complex human host immune landscape underlying differential disease severity and clinical outcome. METHODS: By combining single-cell multi-omics (Whole Transcriptome Analysis plus Antibody-seq) and machine learning-based analysis, we aim to better understand the functional aspects of cellular and immunological heterogeneity in the COVID-19 positive, recovered and the healthy individuals. RESULTS: Based on single-cell transcriptome and surface marker study of 163,197 cells (124,726 cells after data QC) from the 33 individuals (healthy=4, COVID-19 positive=16, and COVID-19 recovered=13), we observed a reduced MHC Class-I-mediated antigen presentation and dysregulated MHC Class-II-mediated antigen presentation in the COVID-19 patients, with restoration of the process in the recovered individuals. B-cell maturation process was also impaired in the positive and the recovered individuals. Importantly, we discovered that a subset of the naive T-cells from the healthy individuals were absent from the recovered individuals, suggesting a post-infection inflammatory stage. Both COVID-19 positive patients and the recovered individuals exhibited a CD40-CD40LG-mediated inflammatory response in the monocytes and T-cell subsets. T-cells, NK-cells, and monocyte-mediated elevation of immunological, stress and antiviral responses were also seen in the COVID-19 positive and the recovered individuals, along with an abnormal T-cell activation, inflammatory response, and faster cellular transition of T cell subtypes in the COVID-19 patients. Importantly, above immune findings were used for a Bayesian network model, which significantly revealed FOS, CXCL8, IL1β, CST3, PSAP, CD45 and CD74 as COVID-19 severity predictors. DISCUSSION: In conclusion, COVID-19 recovered individuals exhibited a hyper-activated inflammatory response with the loss of B cell maturation, suggesting an impeded post-infection stage, necessitating further research to delineate the dynamic immune response associated with the COVID-19. To our knowledge this is first multi-omic study trying to understand the differential and dynamic immune response underlying the sample subtypes. Frontiers Media S.A. 2022-12-02 /pmc/articles/PMC9755500/ /pubmed/36532041 http://dx.doi.org/10.3389/fimmu.2022.1034159 Text en Copyright © 2022 Chattopadhyay, Khare, Kumar, Mishra, Anand, Maurya, Gupta, Sahni, Gupta, Wadhwa, Yadav, Devi, Tardalkar, Joshi, Sethi and Pandey https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Chattopadhyay, Partha
Khare, Kriti
Kumar, Manish
Mishra, Pallavi
Anand, Alok
Maurya, Ranjeet
Gupta, Rohit
Sahni, Shweta
Gupta, Ayushi
Wadhwa, Saruchi
Yadav, Aanchal
Devi, Priti
Tardalkar, Kishore
Joshi, Meghnad
Sethi, Tavpritesh
Pandey, Rajesh
Single-cell multiomics revealed the dynamics of antigen presentation, immune response and T cell activation in the COVID-19 positive and recovered individuals
title Single-cell multiomics revealed the dynamics of antigen presentation, immune response and T cell activation in the COVID-19 positive and recovered individuals
title_full Single-cell multiomics revealed the dynamics of antigen presentation, immune response and T cell activation in the COVID-19 positive and recovered individuals
title_fullStr Single-cell multiomics revealed the dynamics of antigen presentation, immune response and T cell activation in the COVID-19 positive and recovered individuals
title_full_unstemmed Single-cell multiomics revealed the dynamics of antigen presentation, immune response and T cell activation in the COVID-19 positive and recovered individuals
title_short Single-cell multiomics revealed the dynamics of antigen presentation, immune response and T cell activation in the COVID-19 positive and recovered individuals
title_sort single-cell multiomics revealed the dynamics of antigen presentation, immune response and t cell activation in the covid-19 positive and recovered individuals
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9755500/
https://www.ncbi.nlm.nih.gov/pubmed/36532041
http://dx.doi.org/10.3389/fimmu.2022.1034159
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