Predictive values of immune indicators on respiratory failure in the early phase of COVID-19 due to Delta and precedent variants

BackgroundImmune response indicators in the early phase of COVID-19, including interferon and neutralizing responses against SARS-CoV-2, which predict hypoxemia remains unclear.MethodsThis prospective observational study recruited patients hospitalized with COVID-19 (before emergence of omicron vari...

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Main Authors: K. Nagaoka, H. Kawasuji, Y. Takegoshi, Y. Murai, M. Kaneda, K. Kimoto, S. Morimoto, H. Tani, H. Niimi, Y. Morinaga, Y. Yamamoto
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-09-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1197436/full
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author K. Nagaoka
H. Kawasuji
Y. Takegoshi
Y. Murai
M. Kaneda
K. Kimoto
S. Morimoto
H. Tani
H. Niimi
Y. Morinaga
Y. Yamamoto
author_facet K. Nagaoka
H. Kawasuji
Y. Takegoshi
Y. Murai
M. Kaneda
K. Kimoto
S. Morimoto
H. Tani
H. Niimi
Y. Morinaga
Y. Yamamoto
author_sort K. Nagaoka
collection DOAJ
description BackgroundImmune response indicators in the early phase of COVID-19, including interferon and neutralizing responses against SARS-CoV-2, which predict hypoxemia remains unclear.MethodsThis prospective observational study recruited patients hospitalized with COVID-19 (before emergence of omicron variant). As the immune indicators, we assessed the serum levels of IFN-I/III, IL-6, CXCL10 and VEGF, using an ELISA at within 5 days after the onset of symptoms, and serum neutralizing responses using a pseudovirus assay. We also assessed SARS-CoV-2 viral load by qPCR using nasal-swab specimens and serum, to assess the association of indicators and viral distribution.ResultsThe study enrolled 117 patients with COVID-19, of which 28 patients developed hypoxemia. None received vaccine before admission. Serum IFN-I levels (IFN-α and IFN-β), IL-6, CXCL10, LDH and CRP were significantly higher in patients who developed hypoxemia. A significant association with nasopharyngeal viral load was observed only for IFN-I. The serum levels of IFN-α, IL-6, CXCL10 were significantly associated with the presence of RNAemia. Multivariable analysis showed higher odds ratio of IFN-α, with cut-off value of 107 pg/ml, in regard to hypoxemia (Odds ratio [OR]=17.5; 95% confidence interval [CI], 4.7-85; p<0.001), compared to those of IL-6, >17.9 pg/ml (OR=10.5; 95% CI, 2.9-46; p<0.001).ConclusionsThis study demonstrated that serum IFN-α levels in the early phase of SARS-CoV-2 infection strongly predict hypoxemic respiratory failure in a manner different from that of the other indicators including IL-6 or humoral immune response, and instead sensitively reflect innate immune response against SARS-CoV-2 invasion.
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spelling doaj.art-11fb25ed98624e819e06a2e6995836a82023-09-04T08:10:11ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-09-011410.3389/fimmu.2023.11974361197436Predictive values of immune indicators on respiratory failure in the early phase of COVID-19 due to Delta and precedent variantsK. Nagaoka0H. Kawasuji1Y. Takegoshi2Y. Murai3M. Kaneda4K. Kimoto5S. Morimoto6H. Tani7H. Niimi8Y. Morinaga9Y. Yamamoto10Department of Clinical Infectious Diseases, Toyama University Graduate School of Medicine and Pharmaceutical Sciences, Toyama, JapanDepartment of Clinical Infectious Diseases, Toyama University Graduate School of Medicine and Pharmaceutical Sciences, Toyama, JapanDepartment of Clinical Infectious Diseases, Toyama University Graduate School of Medicine and Pharmaceutical Sciences, Toyama, JapanDepartment of Clinical Infectious Diseases, Toyama University Graduate School of Medicine and Pharmaceutical Sciences, Toyama, JapanDepartment of Clinical Infectious Diseases, Toyama University Graduate School of Medicine and Pharmaceutical Sciences, Toyama, JapanDepartment of Clinical Infectious Diseases, Toyama University Graduate School of Medicine and Pharmaceutical Sciences, Toyama, JapanInnovation Platform & Office for Precision Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanDepartment of Virology, Toyama Institute of Health, Toyama, JapanClinical Research Center for Infectious Diseases, Toyama University Graduate School of Medicine and Pharmaceutical Sciences, Toyama, JapanDepartment of Microbiology, Toyama University Graduate School of Medicine and Pharmaceutical Sciences, Toyama, JapanDepartment of Clinical Infectious Diseases, Toyama University Graduate School of Medicine and Pharmaceutical Sciences, Toyama, JapanBackgroundImmune response indicators in the early phase of COVID-19, including interferon and neutralizing responses against SARS-CoV-2, which predict hypoxemia remains unclear.MethodsThis prospective observational study recruited patients hospitalized with COVID-19 (before emergence of omicron variant). As the immune indicators, we assessed the serum levels of IFN-I/III, IL-6, CXCL10 and VEGF, using an ELISA at within 5 days after the onset of symptoms, and serum neutralizing responses using a pseudovirus assay. We also assessed SARS-CoV-2 viral load by qPCR using nasal-swab specimens and serum, to assess the association of indicators and viral distribution.ResultsThe study enrolled 117 patients with COVID-19, of which 28 patients developed hypoxemia. None received vaccine before admission. Serum IFN-I levels (IFN-α and IFN-β), IL-6, CXCL10, LDH and CRP were significantly higher in patients who developed hypoxemia. A significant association with nasopharyngeal viral load was observed only for IFN-I. The serum levels of IFN-α, IL-6, CXCL10 were significantly associated with the presence of RNAemia. Multivariable analysis showed higher odds ratio of IFN-α, with cut-off value of 107 pg/ml, in regard to hypoxemia (Odds ratio [OR]=17.5; 95% confidence interval [CI], 4.7-85; p<0.001), compared to those of IL-6, >17.9 pg/ml (OR=10.5; 95% CI, 2.9-46; p<0.001).ConclusionsThis study demonstrated that serum IFN-α levels in the early phase of SARS-CoV-2 infection strongly predict hypoxemic respiratory failure in a manner different from that of the other indicators including IL-6 or humoral immune response, and instead sensitively reflect innate immune response against SARS-CoV-2 invasion.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1197436/fullCOVID-19type I interferonpneumoniahypoxemiainterleukin-6CXCL-10
spellingShingle K. Nagaoka
H. Kawasuji
Y. Takegoshi
Y. Murai
M. Kaneda
K. Kimoto
S. Morimoto
H. Tani
H. Niimi
Y. Morinaga
Y. Yamamoto
Predictive values of immune indicators on respiratory failure in the early phase of COVID-19 due to Delta and precedent variants
Frontiers in Immunology
COVID-19
type I interferon
pneumonia
hypoxemia
interleukin-6
CXCL-10
title Predictive values of immune indicators on respiratory failure in the early phase of COVID-19 due to Delta and precedent variants
title_full Predictive values of immune indicators on respiratory failure in the early phase of COVID-19 due to Delta and precedent variants
title_fullStr Predictive values of immune indicators on respiratory failure in the early phase of COVID-19 due to Delta and precedent variants
title_full_unstemmed Predictive values of immune indicators on respiratory failure in the early phase of COVID-19 due to Delta and precedent variants
title_short Predictive values of immune indicators on respiratory failure in the early phase of COVID-19 due to Delta and precedent variants
title_sort predictive values of immune indicators on respiratory failure in the early phase of covid 19 due to delta and precedent variants
topic COVID-19
type I interferon
pneumonia
hypoxemia
interleukin-6
CXCL-10
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1197436/full
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