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Blood Interferon-α Levels and Severity, Outcomes, and Inflammatory Profiles in Hospitalized COVID-19 Patients

Background: Deficient interferon responses have been proposed as one of the relevant mechanisms prompting severe manifestations of COVID-19. Objective: To evaluate the interferon (IFN)-α levels in a cohort of COVID-19 patients in relation to severity, evolution of the clinical manifestations and imm...

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Autores principales: Contoli, Marco, Papi, Alberto, Tomassetti, Luca, Rizzo, Paola, Vieceli Dalla Sega, Francesco, Fortini, Francesca, Torsani, Francesca, Morandi, Luca, Ronzoni, Luca, Zucchetti, Ottavio, Pavasini, Rita, Fogagnolo, Alberto, Volta, Carlo Alberto, Bartlett, Nathan W., Johnston, Sebastian L., Spadaro, Savino, Campo, Gianluca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985458/
https://www.ncbi.nlm.nih.gov/pubmed/33767713
http://dx.doi.org/10.3389/fimmu.2021.648004
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author Contoli, Marco
Papi, Alberto
Tomassetti, Luca
Rizzo, Paola
Vieceli Dalla Sega, Francesco
Fortini, Francesca
Torsani, Francesca
Morandi, Luca
Ronzoni, Luca
Zucchetti, Ottavio
Pavasini, Rita
Fogagnolo, Alberto
Volta, Carlo Alberto
Bartlett, Nathan W.
Johnston, Sebastian L.
Spadaro, Savino
Campo, Gianluca
author_facet Contoli, Marco
Papi, Alberto
Tomassetti, Luca
Rizzo, Paola
Vieceli Dalla Sega, Francesco
Fortini, Francesca
Torsani, Francesca
Morandi, Luca
Ronzoni, Luca
Zucchetti, Ottavio
Pavasini, Rita
Fogagnolo, Alberto
Volta, Carlo Alberto
Bartlett, Nathan W.
Johnston, Sebastian L.
Spadaro, Savino
Campo, Gianluca
author_sort Contoli, Marco
collection PubMed
description Background: Deficient interferon responses have been proposed as one of the relevant mechanisms prompting severe manifestations of COVID-19. Objective: To evaluate the interferon (IFN)-α levels in a cohort of COVID-19 patients in relation to severity, evolution of the clinical manifestations and immune/inflammatory profile. Methods: This is prospective study recruiting consecutive hospitalized patients with respiratory failure associated with SARS-COV-2 infection and matched controls. After enrollment, patients were assessed every 7 ± 2 days for additional 2 consecutive visits, for a total of 21 days. The severity of the clinical condition was ranked based on the level of respiratory support required. At each time-point blood samples were obtained to assess immune cells and mediators by multiplex immunoassay. Results: Fifty-four COVD-19 and 11 control patients matched for severity were enrolled. At recruitment, lower levels of blood IFN-α were found in COVID-19 patients compared to controls (3.8-fold difference, p < 0.01). Improvements in COVID-19 severity were paralleled by a significant increase of blood IFN-α levels. A significant increase in blood IFN-α was found over the study period in survivors (70% of the study population). A similar trend was found for blood IFN-β with IFN-β levels below the threshold of detectability in a substantial proportion of subjects. Significantly higher values of blood lymphocytes and lower levels of IL-10 were found at each time point in patients who survived compared to patients who died. In patients who clinically improved and survived during the study, we found an inverse association between IL-10 and IFN-α levels. Conclusion: The study identifies a blood immune profile defined by deficient IFN-α levels associated with increased IL-10 expression in patients progressing to severe/life threatening COVID-19 conditions, suggesting the involvement of immunological pathways that could be target of pharmacological intervention. Clinical Trial Registration: ClinicalTrials.gov identifier NCT04343053.
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spelling pubmed-79854582021-03-24 Blood Interferon-α Levels and Severity, Outcomes, and Inflammatory Profiles in Hospitalized COVID-19 Patients Contoli, Marco Papi, Alberto Tomassetti, Luca Rizzo, Paola Vieceli Dalla Sega, Francesco Fortini, Francesca Torsani, Francesca Morandi, Luca Ronzoni, Luca Zucchetti, Ottavio Pavasini, Rita Fogagnolo, Alberto Volta, Carlo Alberto Bartlett, Nathan W. Johnston, Sebastian L. Spadaro, Savino Campo, Gianluca Front Immunol Immunology Background: Deficient interferon responses have been proposed as one of the relevant mechanisms prompting severe manifestations of COVID-19. Objective: To evaluate the interferon (IFN)-α levels in a cohort of COVID-19 patients in relation to severity, evolution of the clinical manifestations and immune/inflammatory profile. Methods: This is prospective study recruiting consecutive hospitalized patients with respiratory failure associated with SARS-COV-2 infection and matched controls. After enrollment, patients were assessed every 7 ± 2 days for additional 2 consecutive visits, for a total of 21 days. The severity of the clinical condition was ranked based on the level of respiratory support required. At each time-point blood samples were obtained to assess immune cells and mediators by multiplex immunoassay. Results: Fifty-four COVD-19 and 11 control patients matched for severity were enrolled. At recruitment, lower levels of blood IFN-α were found in COVID-19 patients compared to controls (3.8-fold difference, p < 0.01). Improvements in COVID-19 severity were paralleled by a significant increase of blood IFN-α levels. A significant increase in blood IFN-α was found over the study period in survivors (70% of the study population). A similar trend was found for blood IFN-β with IFN-β levels below the threshold of detectability in a substantial proportion of subjects. Significantly higher values of blood lymphocytes and lower levels of IL-10 were found at each time point in patients who survived compared to patients who died. In patients who clinically improved and survived during the study, we found an inverse association between IL-10 and IFN-α levels. Conclusion: The study identifies a blood immune profile defined by deficient IFN-α levels associated with increased IL-10 expression in patients progressing to severe/life threatening COVID-19 conditions, suggesting the involvement of immunological pathways that could be target of pharmacological intervention. Clinical Trial Registration: ClinicalTrials.gov identifier NCT04343053. Frontiers Media S.A. 2021-03-09 /pmc/articles/PMC7985458/ /pubmed/33767713 http://dx.doi.org/10.3389/fimmu.2021.648004 Text en Copyright © 2021 Contoli, Papi, Tomassetti, Rizzo, Vieceli Dalla Sega, Fortini, Torsani, Morandi, Ronzoni, Zucchetti, Pavasini, Fogagnolo, Volta, Bartlett, Johnston, Spadaro and Campo. http://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
Contoli, Marco
Papi, Alberto
Tomassetti, Luca
Rizzo, Paola
Vieceli Dalla Sega, Francesco
Fortini, Francesca
Torsani, Francesca
Morandi, Luca
Ronzoni, Luca
Zucchetti, Ottavio
Pavasini, Rita
Fogagnolo, Alberto
Volta, Carlo Alberto
Bartlett, Nathan W.
Johnston, Sebastian L.
Spadaro, Savino
Campo, Gianluca
Blood Interferon-α Levels and Severity, Outcomes, and Inflammatory Profiles in Hospitalized COVID-19 Patients
title Blood Interferon-α Levels and Severity, Outcomes, and Inflammatory Profiles in Hospitalized COVID-19 Patients
title_full Blood Interferon-α Levels and Severity, Outcomes, and Inflammatory Profiles in Hospitalized COVID-19 Patients
title_fullStr Blood Interferon-α Levels and Severity, Outcomes, and Inflammatory Profiles in Hospitalized COVID-19 Patients
title_full_unstemmed Blood Interferon-α Levels and Severity, Outcomes, and Inflammatory Profiles in Hospitalized COVID-19 Patients
title_short Blood Interferon-α Levels and Severity, Outcomes, and Inflammatory Profiles in Hospitalized COVID-19 Patients
title_sort blood interferon-α levels and severity, outcomes, and inflammatory profiles in hospitalized covid-19 patients
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985458/
https://www.ncbi.nlm.nih.gov/pubmed/33767713
http://dx.doi.org/10.3389/fimmu.2021.648004
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