Integrating SARS-CoV-2-specific interferon-? release assay testing in the evaluation of patients hospitalized with COVID-19

T cell-mediated immunity is crucial for protection against severe COVID-19. The performance of SARS-CoV-2-specific IFN-gamma release assays (IGRAs) to measure T cell responses during severe acute infection is unknown. We conducted a prospective, longitudinal analysis of patients hospitalized for con...

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Detalhes bibliográficos
Autores: Masia, M, de la Rica, A, Fernández-González, M, Garcia, JA, Padilla, S, Garcia-Abellán, J, Botella, A, Mascarell, P, Gutiérrez, F
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Recursos:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
Repositorio:r-FISABIO. Repositorio Institucional de Producción Científica
OAI Identifier:oai:fisabio.fundanetsuite.com:p15843
Acesso em linha:https://fisabio.portalinvestigacion.com/publicaciones/15843
Access Level:acceso abierto
Palavra-chave:interferon-gamma release
IGRA
T cell immunity
COVID-19
SARS-CoV-2
mitogen
Omicron
outcomes
mortality
Delta
performance
accuracy
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spelling Integrating SARS-CoV-2-specific interferon-? release assay testing in the evaluation of patients hospitalized with COVID-19Masia, Mde la Rica, AFernández-González, MGarcia, JAPadilla, SGarcia-Abellán, JBotella, AMascarell, PGutiérrez, Finterferon-gamma releaseIGRAT cell immunityCOVID-19SARS-CoV-2mitogenOmicronoutcomesmortalityDeltaperformanceaccuracyT cell-mediated immunity is crucial for protection against severe COVID-19. The performance of SARS-CoV-2-specific IFN-gamma release assays (IGRAs) to measure T cell responses during severe acute infection is unknown. We conducted a prospective, longitudinal analysis of patients hospitalized for confirmed COVID-19. A standardized SARS-CoV-2-specific quantitative IGRA was measured on admission. Follow-up lasted 90 days. Two hundred forty-eight patients were included; 181 (73%) were vaccinated, 142 (57.3%) were infected with the Omicron variant, and 106 (42.7%) were infected with the Delta variant. The SARS-CoV-2-IGRA result was positive (>200 mIU/mL) in 125 (50.5%) patients, with 44 (35.2%) showing concomitant mitogen-induced IFN-gamma response. Compared with patients with negative and borderline results, those with positive SARS-CoV-2 IGRA were younger and showed lower frequency of co-existing comorbidities, lower median Charlson comorbidity index, lower frequency of World Health Organization (WHO) severity score > 4, higher peripheral arterial oxygen saturation to inspired fraction of oxygen (SpO2/FiO2) ratio on admission, higher S-IgG and N-IgG antibody responses, and lower mortality at 28/60/90 days. These findings were consistent for both the Omicron and Delta variants. Similar patterns to those described above were observed in the subset of patients with positive SARS-CoV-2-IGRA and indeterminate mitogen-induced responses, as well as in those exhibiting both positive SARS-CoV-2-specific and mitogen responses. Twenty-eight (11.3%) patients had borderline (100-200 mIU/mL) SARS-CoV-2-IGRA results and shared several similarities with patients with negative SARS-CoV-2 IGRA. In an adjusted Cox model, a negative SARS-CoV-2-IGRA result was found to be an independent predictor of mortality. Using a receiver operating characteristics curve analysis, we found that an IFN-gamma value of 150 mIU/mL was identified as the optimal cut-off point for predicting mortality, with 79% [95% confidence interval (CI) 61-93] sensitivity, 61% (95% CI 55-68) specificity, 18% (95% CI 15-22) positive predictive value, 96% (95% CI 93-98) negative predictive value, and an area under the curve (AUC) of 70%. The assay's performance remained consistent regardless of mitogen results or the presence of the Delta or Omicron variants. IMPORTANCE The cellular immune response is essential in the protection against severe disease in patients with established SARS-CoV-2 infection. The novelty of this study lies in the evaluation of the overall performance of a standardized assay to measure cellular immune response, the SARS-CoV-2-specific interferon-gamma release assay (IGRA), in hospitalized patients with severe COVID-19. The SARS-CoV-2 IGRA was shown to accurately classify patients based on disease severity and prognosis, and the study revealed that test performance was not affected by the SARS-CoV-2 variant or control tube results. We identified an assay cut-off point with a high negative predictive value against mortality. The SARS-CoV-2 IGRA in patients hospitalized for COVID-19 may be a useful tool to assess cellular immunity and adopt targeted therapeutic and preventive measures.AMER SOC MICROBIOLOGY2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fisabio.portalinvestigacion.com/publicaciones/15843Microbiology SpectrumISSN: 21650497reponame:r-FISABIO. Repositorio Institucional de Producción Científicainstname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)Inglésinfo:eu-repo/semantics/openAccessoai:fisabio.fundanetsuite.com:p158432026-06-11T12:45:17Z
dc.title.none.fl_str_mv Integrating SARS-CoV-2-specific interferon-? release assay testing in the evaluation of patients hospitalized with COVID-19
title Integrating SARS-CoV-2-specific interferon-? release assay testing in the evaluation of patients hospitalized with COVID-19
spellingShingle Integrating SARS-CoV-2-specific interferon-? release assay testing in the evaluation of patients hospitalized with COVID-19
Masia, M
interferon-gamma release
IGRA
T cell immunity
COVID-19
SARS-CoV-2
mitogen
Omicron
outcomes
mortality
Delta
performance
accuracy
title_short Integrating SARS-CoV-2-specific interferon-? release assay testing in the evaluation of patients hospitalized with COVID-19
title_full Integrating SARS-CoV-2-specific interferon-? release assay testing in the evaluation of patients hospitalized with COVID-19
title_fullStr Integrating SARS-CoV-2-specific interferon-? release assay testing in the evaluation of patients hospitalized with COVID-19
title_full_unstemmed Integrating SARS-CoV-2-specific interferon-? release assay testing in the evaluation of patients hospitalized with COVID-19
title_sort Integrating SARS-CoV-2-specific interferon-? release assay testing in the evaluation of patients hospitalized with COVID-19
dc.creator.none.fl_str_mv Masia, M
de la Rica, A
Fernández-González, M
Garcia, JA
Padilla, S
Garcia-Abellán, J
Botella, A
Mascarell, P
Gutiérrez, F
author Masia, M
author_facet Masia, M
de la Rica, A
Fernández-González, M
Garcia, JA
Padilla, S
Garcia-Abellán, J
Botella, A
Mascarell, P
Gutiérrez, F
author_role author
author2 de la Rica, A
Fernández-González, M
Garcia, JA
Padilla, S
Garcia-Abellán, J
Botella, A
Mascarell, P
Gutiérrez, F
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv interferon-gamma release
IGRA
T cell immunity
COVID-19
SARS-CoV-2
mitogen
Omicron
outcomes
mortality
Delta
performance
accuracy
topic interferon-gamma release
IGRA
T cell immunity
COVID-19
SARS-CoV-2
mitogen
Omicron
outcomes
mortality
Delta
performance
accuracy
description T cell-mediated immunity is crucial for protection against severe COVID-19. The performance of SARS-CoV-2-specific IFN-gamma release assays (IGRAs) to measure T cell responses during severe acute infection is unknown. We conducted a prospective, longitudinal analysis of patients hospitalized for confirmed COVID-19. A standardized SARS-CoV-2-specific quantitative IGRA was measured on admission. Follow-up lasted 90 days. Two hundred forty-eight patients were included; 181 (73%) were vaccinated, 142 (57.3%) were infected with the Omicron variant, and 106 (42.7%) were infected with the Delta variant. The SARS-CoV-2-IGRA result was positive (>200 mIU/mL) in 125 (50.5%) patients, with 44 (35.2%) showing concomitant mitogen-induced IFN-gamma response. Compared with patients with negative and borderline results, those with positive SARS-CoV-2 IGRA were younger and showed lower frequency of co-existing comorbidities, lower median Charlson comorbidity index, lower frequency of World Health Organization (WHO) severity score > 4, higher peripheral arterial oxygen saturation to inspired fraction of oxygen (SpO2/FiO2) ratio on admission, higher S-IgG and N-IgG antibody responses, and lower mortality at 28/60/90 days. These findings were consistent for both the Omicron and Delta variants. Similar patterns to those described above were observed in the subset of patients with positive SARS-CoV-2-IGRA and indeterminate mitogen-induced responses, as well as in those exhibiting both positive SARS-CoV-2-specific and mitogen responses. Twenty-eight (11.3%) patients had borderline (100-200 mIU/mL) SARS-CoV-2-IGRA results and shared several similarities with patients with negative SARS-CoV-2 IGRA. In an adjusted Cox model, a negative SARS-CoV-2-IGRA result was found to be an independent predictor of mortality. Using a receiver operating characteristics curve analysis, we found that an IFN-gamma value of 150 mIU/mL was identified as the optimal cut-off point for predicting mortality, with 79% [95% confidence interval (CI) 61-93] sensitivity, 61% (95% CI 55-68) specificity, 18% (95% CI 15-22) positive predictive value, 96% (95% CI 93-98) negative predictive value, and an area under the curve (AUC) of 70%. The assay's performance remained consistent regardless of mitogen results or the presence of the Delta or Omicron variants. IMPORTANCE The cellular immune response is essential in the protection against severe disease in patients with established SARS-CoV-2 infection. The novelty of this study lies in the evaluation of the overall performance of a standardized assay to measure cellular immune response, the SARS-CoV-2-specific interferon-gamma release assay (IGRA), in hospitalized patients with severe COVID-19. The SARS-CoV-2 IGRA was shown to accurately classify patients based on disease severity and prognosis, and the study revealed that test performance was not affected by the SARS-CoV-2 variant or control tube results. We identified an assay cut-off point with a high negative predictive value against mortality. The SARS-CoV-2 IGRA in patients hospitalized for COVID-19 may be a useful tool to assess cellular immunity and adopt targeted therapeutic and preventive measures.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fisabio.portalinvestigacion.com/publicaciones/15843
url https://fisabio.portalinvestigacion.com/publicaciones/15843
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv AMER SOC MICROBIOLOGY
publisher.none.fl_str_mv AMER SOC MICROBIOLOGY
dc.source.none.fl_str_mv Microbiology Spectrum
ISSN: 21650497
reponame:r-FISABIO. Repositorio Institucional de Producción Científica
instname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
instname_str Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
reponame_str r-FISABIO. Repositorio Institucional de Producción Científica
collection r-FISABIO. Repositorio Institucional de Producción Científica
repository.name.fl_str_mv
repository.mail.fl_str_mv
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