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Overlapping but Disparate Inflammatory and Immunosuppressive Responses to SARS-CoV-2 and Bacterial Sepsis: An Immunological Time Course Analysis

Both severe SARS-CoV-2 infections and bacterial sepsis exhibit an immunological dyscrasia and propensity for secondary infections. The nature of the immunological dyscrasias for these differing etiologies and their time course remain unclear. In this study, thirty hospitalized patients with SARS-CoV...

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Autores principales: Loftus, Tyler J., Ungaro, Ricardo, Dirain, Marvin, Efron, Philip A., Mazer, Monty B., Remy, Kenneth E., Hotchkiss, Richard S., Zhong, Luer, Bacher, Rhonda, Starostik, Petr, Moldawer, Lyle L., Brakenridge, Scott C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8696010/
https://www.ncbi.nlm.nih.gov/pubmed/34956225
http://dx.doi.org/10.3389/fimmu.2021.792448
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author Loftus, Tyler J.
Ungaro, Ricardo
Dirain, Marvin
Efron, Philip A.
Mazer, Monty B.
Remy, Kenneth E.
Hotchkiss, Richard S.
Zhong, Luer
Bacher, Rhonda
Starostik, Petr
Moldawer, Lyle L.
Brakenridge, Scott C.
author_facet Loftus, Tyler J.
Ungaro, Ricardo
Dirain, Marvin
Efron, Philip A.
Mazer, Monty B.
Remy, Kenneth E.
Hotchkiss, Richard S.
Zhong, Luer
Bacher, Rhonda
Starostik, Petr
Moldawer, Lyle L.
Brakenridge, Scott C.
author_sort Loftus, Tyler J.
collection PubMed
description Both severe SARS-CoV-2 infections and bacterial sepsis exhibit an immunological dyscrasia and propensity for secondary infections. The nature of the immunological dyscrasias for these differing etiologies and their time course remain unclear. In this study, thirty hospitalized patients with SARS-CoV-2 infection were compared with ten critically ill patients with bacterial sepsis over 21 days, as well as ten healthy control subjects. Blood was sampled between days 1 and 21 after admission for targeted plasma biomarker analysis, cellular phenotyping, and leukocyte functional analysis via enzyme-linked immunospot assay. We found that circulating inflammatory markers were significantly higher early after bacterial sepsis compared with SARS-CoV-2. Both cohorts exhibited profound immune suppression through 21 days (suppressed HLA-DR expression, reduced mononuclear cell IFN-gamma production), and expanded numbers of myeloid-derived suppressor cells (MDSCs). In addition, MDSC expansion and ex vivo production of IFN-gamma and TNF-alpha were resolving over time in bacterial sepsis, whereas in SARS-CoV-2, immunosuppression and inflammation were accelerating. Despite less severe initial physiologic derangement, SARS-CoV-2 patients had similar incidence of secondary infections (23% vs 30%) as bacterial sepsis patients. Finally, COVID patients who developed secondary bacterial infections exhibited profound immunosuppression evident by elevated sPD-L1 and depressed HLA-DR. Although both bacterial sepsis and SARS-CoV-2 are associated with inflammation and immune suppression, their immune dyscrasia temporal patterns and clinical outcomes are different. SARS-CoV-2 patients had less severe early inflammation and organ dysfunction but had persistent inflammation and immunosuppression and suffered worse clinical outcomes, especially when SARS-CoV-2 infection was followed by secondary bacterial infection.
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spelling pubmed-86960102021-12-24 Overlapping but Disparate Inflammatory and Immunosuppressive Responses to SARS-CoV-2 and Bacterial Sepsis: An Immunological Time Course Analysis Loftus, Tyler J. Ungaro, Ricardo Dirain, Marvin Efron, Philip A. Mazer, Monty B. Remy, Kenneth E. Hotchkiss, Richard S. Zhong, Luer Bacher, Rhonda Starostik, Petr Moldawer, Lyle L. Brakenridge, Scott C. Front Immunol Immunology Both severe SARS-CoV-2 infections and bacterial sepsis exhibit an immunological dyscrasia and propensity for secondary infections. The nature of the immunological dyscrasias for these differing etiologies and their time course remain unclear. In this study, thirty hospitalized patients with SARS-CoV-2 infection were compared with ten critically ill patients with bacterial sepsis over 21 days, as well as ten healthy control subjects. Blood was sampled between days 1 and 21 after admission for targeted plasma biomarker analysis, cellular phenotyping, and leukocyte functional analysis via enzyme-linked immunospot assay. We found that circulating inflammatory markers were significantly higher early after bacterial sepsis compared with SARS-CoV-2. Both cohorts exhibited profound immune suppression through 21 days (suppressed HLA-DR expression, reduced mononuclear cell IFN-gamma production), and expanded numbers of myeloid-derived suppressor cells (MDSCs). In addition, MDSC expansion and ex vivo production of IFN-gamma and TNF-alpha were resolving over time in bacterial sepsis, whereas in SARS-CoV-2, immunosuppression and inflammation were accelerating. Despite less severe initial physiologic derangement, SARS-CoV-2 patients had similar incidence of secondary infections (23% vs 30%) as bacterial sepsis patients. Finally, COVID patients who developed secondary bacterial infections exhibited profound immunosuppression evident by elevated sPD-L1 and depressed HLA-DR. Although both bacterial sepsis and SARS-CoV-2 are associated with inflammation and immune suppression, their immune dyscrasia temporal patterns and clinical outcomes are different. SARS-CoV-2 patients had less severe early inflammation and organ dysfunction but had persistent inflammation and immunosuppression and suffered worse clinical outcomes, especially when SARS-CoV-2 infection was followed by secondary bacterial infection. Frontiers Media S.A. 2021-12-09 /pmc/articles/PMC8696010/ /pubmed/34956225 http://dx.doi.org/10.3389/fimmu.2021.792448 Text en Copyright © 2021 Loftus, Ungaro, Dirain, Efron, Mazer, Remy, Hotchkiss, Zhong, Bacher, Starostik, Moldawer and Brakenridge 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
Loftus, Tyler J.
Ungaro, Ricardo
Dirain, Marvin
Efron, Philip A.
Mazer, Monty B.
Remy, Kenneth E.
Hotchkiss, Richard S.
Zhong, Luer
Bacher, Rhonda
Starostik, Petr
Moldawer, Lyle L.
Brakenridge, Scott C.
Overlapping but Disparate Inflammatory and Immunosuppressive Responses to SARS-CoV-2 and Bacterial Sepsis: An Immunological Time Course Analysis
title Overlapping but Disparate Inflammatory and Immunosuppressive Responses to SARS-CoV-2 and Bacterial Sepsis: An Immunological Time Course Analysis
title_full Overlapping but Disparate Inflammatory and Immunosuppressive Responses to SARS-CoV-2 and Bacterial Sepsis: An Immunological Time Course Analysis
title_fullStr Overlapping but Disparate Inflammatory and Immunosuppressive Responses to SARS-CoV-2 and Bacterial Sepsis: An Immunological Time Course Analysis
title_full_unstemmed Overlapping but Disparate Inflammatory and Immunosuppressive Responses to SARS-CoV-2 and Bacterial Sepsis: An Immunological Time Course Analysis
title_short Overlapping but Disparate Inflammatory and Immunosuppressive Responses to SARS-CoV-2 and Bacterial Sepsis: An Immunological Time Course Analysis
title_sort overlapping but disparate inflammatory and immunosuppressive responses to sars-cov-2 and bacterial sepsis: an immunological time course analysis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8696010/
https://www.ncbi.nlm.nih.gov/pubmed/34956225
http://dx.doi.org/10.3389/fimmu.2021.792448
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