TY - JOUR
T1 - Overlapping but Disparate Inflammatory and Immunosuppressive Responses to SARS-CoV-2 and Bacterial Sepsis
T2 - An Immunological Time Course Analysis
AU - Loftus, Tyler J.
AU - Ungaro, Ricardo
AU - Dirain, Marvin
AU - Efron, Philip A.
AU - Mazer, Monty B.
AU - Remy, Kenneth E.
AU - Hotchkiss, Richard S.
AU - Zhong, Luer
AU - Bacher, Rhonda
AU - Starostik, Petr
AU - Moldawer, Lyle L.
AU - Brakenridge, Scott C.
N1 - Funding Information:
Research reported in this publication was supported by the University of Florida Clinical and Translational Science Institute, which is supported in part by the NIH National Center for Advancing Translational Sciences under award number UL1 TR001427. T.J.L. was supported by the National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health under Award Number K23 GM140268. Infrastructure support was also provided by grants RM1 GM139690-01 and R01 GM132364-01 from NIGMS. Funding sources had no role in study design, in the collection, analysis, and interpretation of data, in the writing of the report, or in the decision to submit the paper for publication.
Publisher Copyright:
Copyright © 2021 Loftus, Ungaro, Dirain, Efron, Mazer, Remy, Hotchkiss, Zhong, Bacher, Starostik, Moldawer and Brakenridge.
PY - 2021/12/9
Y1 - 2021/12/9
N2 - 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.
AB - 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.
KW - ELISpot
KW - MDSC
KW - immune response
KW - immune suppression
KW - inflammation
UR - http://www.scopus.com/inward/record.url?scp=85121719374&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2021.792448
DO - 10.3389/fimmu.2021.792448
M3 - Article
C2 - 34956225
AN - SCOPUS:85121719374
SN - 1664-3224
VL - 12
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 792448
ER -