Heightened Circulating Interferon-Inducible Chemokines, and Activated Pro-Cytolytic Th1-Cell Phenotype Features Covid-19 Aggravation in the Second Week of Illness

Covid-19 features a delayed onset of critical illness occurring approximately one week from the beginning of symptoms, which corresponds to the bridging of innate and adaptive immunity. We reasoned that the immune events occurring at the turning point of disease might mark the direction toward patho...

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Published in:Frontiers in immunology Vol. 11; p. 580987
Main Authors: Tincati, Camilla, Cannizzo, E. Stefania, Giacomelli, Mauro, Badolato, Raffaele, d’Arminio Monforte, Antonella, Marchetti, Giulia
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 20.10.2020
Subjects:
Aged
Chemokines - blood
Covid-19
COVID-19 - blood
COVID-19 - immunology
COVID-19 - virology
Female
Humans
immunity
Immunology
immunopathology
Interferons - blood
Leukocytes, Mononuclear - immunology
Male
Middle Aged
Phenotype
S/M/N protein-reactive T-cells
SARS-CoV-2
SARS-CoV-2 - genetics
SARS-CoV-2 - physiology
Th1 Cells - immunology
SARS-CoV-2
immunopathology
immunity
Covid-19
S/M/N protein-reactive T-cells
ISSN:1664-3224, 1664-3224
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Summary:Covid-19 features a delayed onset of critical illness occurring approximately one week from the beginning of symptoms, which corresponds to the bridging of innate and adaptive immunity. We reasoned that the immune events occurring at the turning point of disease might mark the direction toward pathogenic protective inflammatory responses. Subjects with either severe (s; PaO2/FiO2 ratio <200) or mild (m; PaO2/FiO2 ratio>300) Covid-19 were enrolled. A range of chemokines and cytokines as well as reactive oxygen species (ROS) were measured in plasma. Dendritic and NK cell frequency, monocyte and B-/T-cell phenotype and SARS-CoV-2-specific T-cell responses were assessed in PBMC. Twenty mCovid-19 and 20 sCovid-19 individuals were studied. sCovid-19 patients displayed higher non-classical monocytes, plasma chemokines (CXCL8, CXCL9, CXCL10), cytokines (IL-6, IL-10), and ROS mCovid-19. sCovid-19 also showed significantly increased activated CD38+HLA-DR+ T-lymphocyte, and granzyme-B+/perforin+ pro-cytolytic T-cells. All Covid-19 patients showed SARS-CoV-2 specific-T-cell response with a predominance of Th1 bi- or trifunctional IFN- /IL-2/TNF- -expressing CD4+, while no difference according to disease severity was observed. Severe Covid-19 features heightened circulating IFN-inducible chemokines and activated pro-cytolytic Th1 cell phenotype in the second week of illness, yet SARS-CoV-2-specific responses are similar to that of mild illness. Altogether, our observations suggest Th1 polarization coupled to higher cytolytic profile in sCovid-19 as correlate of disease pathogenesis and as potential targets to be investigated in the roadmap to therapy and vaccine development.
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Edited by: Marcus Thelen, Institute for Research in Biomedicine (IRB), Switzerland
This article was submitted to Cytokines and Soluble Mediators in Immunity, a section of the journal Frontiers in Immunology
Reviewed by: Daniele Lilleri, Fondazione Ospedale San Matteo (IRCCS), Italy; Piergiuseppe De Berardinis, Consiglio Nazionale delle Ricerche (Bologna), Italy; Giovanni Bernardini, Sapienza University of Rome, Italy
These authors have contributed equally to this work
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2020.580987