tetano
Editor, Senior Moderator
Front Immunol
. 2021 Oct 13;12:738073.
doi: 10.3389/fimmu.2021.738073. eCollection 2021.
Immune Response in Severe and Non-Severe Coronavirus Disease 2019 (COVID-19) Infection: A Mechanistic Landscape
Kavitha Mukund[SUP] 1 [/SUP], Priya Nayak[SUP] 1 [/SUP], Chethan Ashokkumar[SUP] 2 3 [/SUP], Sohail Rao[SUP] 4 [/SUP], Jose Almeda[SUP] 4 [/SUP], Monica M Betancourt-Garcia[SUP] 4 [/SUP], Rakesh Sindhi[SUP] 2 3 [/SUP], Shankar Subramaniam[SUP] 1 5 6 [/SUP]
Affiliations
Abstract
The mechanisms underlying the immune remodeling and severity response in coronavirus disease 2019 (COVID-19) are yet to be fully elucidated. Our comprehensive integrative analyses of single-cell RNA sequencing (scRNAseq) data from four published studies, in patients with mild/moderate and severe infections, indicate a robust expansion and mobilization of the innate immune response and highlight mechanisms by which low-density neutrophils and megakaryocytes play a crucial role in the cross talk between lymphoid and myeloid lineages. We also document a marked reduction of several lymphoid cell types, particularly natural killer cells, mucosal-associated invariant T (MAIT) cells, and gamma-delta T (γδT) cells, and a robust expansion and extensive heterogeneity within plasmablasts, especially in severe COVID-19 patients. We confirm the changes in cellular abundances for certain immune cell types within a new patient cohort. While the cellular heterogeneity in COVID-19 extends across cells in both lineages, we consistently observe certain subsets respond more potently to interferon type I (IFN-I) and display increased cellular abundances across the spectrum of severity, as compared with healthy subjects. However, we identify these expanded subsets to have a more muted response to IFN-I within severe disease compared to non-severe disease. Our analyses further highlight an increased aggregation potential of the myeloid subsets, particularly monocytes, in COVID-19. Finally, we provide detailed mechanistic insights into the interaction between lymphoid and myeloid lineages, which contributes to the multisystemic phenotype of COVID-19, distinguishing severe from non-severe responses.
Keywords: COVID-19; MDSC; aggregation; cDC2; immune-remodeling; low-density neutrophils; megakaryocyte; plasmablast.
. 2021 Oct 13;12:738073.
doi: 10.3389/fimmu.2021.738073. eCollection 2021.
Immune Response in Severe and Non-Severe Coronavirus Disease 2019 (COVID-19) Infection: A Mechanistic Landscape
Kavitha Mukund[SUP] 1 [/SUP], Priya Nayak[SUP] 1 [/SUP], Chethan Ashokkumar[SUP] 2 3 [/SUP], Sohail Rao[SUP] 4 [/SUP], Jose Almeda[SUP] 4 [/SUP], Monica M Betancourt-Garcia[SUP] 4 [/SUP], Rakesh Sindhi[SUP] 2 3 [/SUP], Shankar Subramaniam[SUP] 1 5 6 [/SUP]
Affiliations
- PMID: 34721400
- PMCID: PMC8548832
- DOI: 10.3389/fimmu.2021.738073
Abstract
The mechanisms underlying the immune remodeling and severity response in coronavirus disease 2019 (COVID-19) are yet to be fully elucidated. Our comprehensive integrative analyses of single-cell RNA sequencing (scRNAseq) data from four published studies, in patients with mild/moderate and severe infections, indicate a robust expansion and mobilization of the innate immune response and highlight mechanisms by which low-density neutrophils and megakaryocytes play a crucial role in the cross talk between lymphoid and myeloid lineages. We also document a marked reduction of several lymphoid cell types, particularly natural killer cells, mucosal-associated invariant T (MAIT) cells, and gamma-delta T (γδT) cells, and a robust expansion and extensive heterogeneity within plasmablasts, especially in severe COVID-19 patients. We confirm the changes in cellular abundances for certain immune cell types within a new patient cohort. While the cellular heterogeneity in COVID-19 extends across cells in both lineages, we consistently observe certain subsets respond more potently to interferon type I (IFN-I) and display increased cellular abundances across the spectrum of severity, as compared with healthy subjects. However, we identify these expanded subsets to have a more muted response to IFN-I within severe disease compared to non-severe disease. Our analyses further highlight an increased aggregation potential of the myeloid subsets, particularly monocytes, in COVID-19. Finally, we provide detailed mechanistic insights into the interaction between lymphoid and myeloid lineages, which contributes to the multisystemic phenotype of COVID-19, distinguishing severe from non-severe responses.
Keywords: COVID-19; MDSC; aggregation; cDC2; immune-remodeling; low-density neutrophils; megakaryocyte; plasmablast.