Nuclear Factor Erythroid 2-Related Factor 2 and SARS-CoV-2 Infection Risk in COVID-19-Vaccinated Hospital Nurses

<b>Background/Objectives</b>: The COVID-19 pandemic has caused sickness and death among many health care workers. However, the apparent resistance of health care workers to SARS-CoV-2 infection despite their high-risk work environment remains unclear. To investigate if inflammation and c...

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Main Authors: Stefano Rizza, Luca Coppeta, Gianluigi Ferrazza, Alessandro Nucera, Maria Postorino, Andrea Quatrana, Cristiana Ferrari, Rossella Menghini, Susanna Longo, Andrea Magrini, Massimo Federici
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Language:English
Published: MDPI AG 2025-07-01
Series:Vaccines
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Online Access:https://www.mdpi.com/2076-393X/13/7/739
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author Stefano Rizza
Luca Coppeta
Gianluigi Ferrazza
Alessandro Nucera
Maria Postorino
Andrea Quatrana
Cristiana Ferrari
Rossella Menghini
Susanna Longo
Andrea Magrini
Massimo Federici
author_facet Stefano Rizza
Luca Coppeta
Gianluigi Ferrazza
Alessandro Nucera
Maria Postorino
Andrea Quatrana
Cristiana Ferrari
Rossella Menghini
Susanna Longo
Andrea Magrini
Massimo Federici
author_sort Stefano Rizza
collection DOAJ
description <b>Background/Objectives</b>: The COVID-19 pandemic has caused sickness and death among many health care workers. However, the apparent resistance of health care workers to SARS-CoV-2 infection despite their high-risk work environment remains unclear. To investigate if inflammation and circadian disruption contribute to resistance or diminished susceptibility to the SARS-CoV-2 virus, we retrospectively evaluated a cohort of volunteer hospital nurses (VHNs). <b>Methods</b>: A total of 246 apparently healthy VHNs (mean age 37.4 ± 5.9 years) who had received the BNT162b2 mRNA vaccine were asked to report their sleep quality, according to the Pittsburgh Sleep Quality Index, and number of SARS-CoV-2 infections during the observational study period (from the end of December 2020 to April 2025). The expression of inflammation-associated mediators and circadian transcription factors in peripheral blood mononuclear cells, as well as sleep quality, were examined. <b>Results</b>: Our findings revealed no anthropometric, biochemical, or inflammation-associated parameters but demonstrated significantly greater levels of NFE2L2, also known as nuclear factor erythroid-derived 2-like 2 (NFR2), gene expression in peripheral blood mononuclear cells among VHNs who had never been infected with SARS-CoV-2 (<i>n</i> = 97) than in VHNs with only one (<i>n</i> = 119) or with two or more (<i>n</i> = 35) prior SARS-CoV-2 infections (<i>p</i> < 0.01). This result was confirmed through one-to-one propensity score matching (<i>p</i> < 0.01). Moreover, NRF2 gene expression was not associated with the number of COVID-19 vaccinations (<i>p</i> = 0.598). Finally, NRF2 gene expression was higher among participants who reported better sleep quality (<i>p</i> < 0.01). <b>Conclusions</b>: Our findings suggest possible interactions among NRF2 gene expression, protection against SARS-CoV-2 infection, and the modulation of COVID-19 vaccination efficacy.
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spelling doaj-art-6dca98e3f4274d0b8b2cd6aadb0af4542025-08-20T03:13:54ZengMDPI AGVaccines2076-393X2025-07-0113773910.3390/vaccines13070739Nuclear Factor Erythroid 2-Related Factor 2 and SARS-CoV-2 Infection Risk in COVID-19-Vaccinated Hospital NursesStefano Rizza0Luca Coppeta1Gianluigi Ferrazza2Alessandro Nucera3Maria Postorino4Andrea Quatrana5Cristiana Ferrari6Rossella Menghini7Susanna Longo8Andrea Magrini9Massimo Federici10Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Occupational Medicine, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Occupational Medicine, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Occupational Medicine, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy<b>Background/Objectives</b>: The COVID-19 pandemic has caused sickness and death among many health care workers. However, the apparent resistance of health care workers to SARS-CoV-2 infection despite their high-risk work environment remains unclear. To investigate if inflammation and circadian disruption contribute to resistance or diminished susceptibility to the SARS-CoV-2 virus, we retrospectively evaluated a cohort of volunteer hospital nurses (VHNs). <b>Methods</b>: A total of 246 apparently healthy VHNs (mean age 37.4 ± 5.9 years) who had received the BNT162b2 mRNA vaccine were asked to report their sleep quality, according to the Pittsburgh Sleep Quality Index, and number of SARS-CoV-2 infections during the observational study period (from the end of December 2020 to April 2025). The expression of inflammation-associated mediators and circadian transcription factors in peripheral blood mononuclear cells, as well as sleep quality, were examined. <b>Results</b>: Our findings revealed no anthropometric, biochemical, or inflammation-associated parameters but demonstrated significantly greater levels of NFE2L2, also known as nuclear factor erythroid-derived 2-like 2 (NFR2), gene expression in peripheral blood mononuclear cells among VHNs who had never been infected with SARS-CoV-2 (<i>n</i> = 97) than in VHNs with only one (<i>n</i> = 119) or with two or more (<i>n</i> = 35) prior SARS-CoV-2 infections (<i>p</i> < 0.01). This result was confirmed through one-to-one propensity score matching (<i>p</i> < 0.01). Moreover, NRF2 gene expression was not associated with the number of COVID-19 vaccinations (<i>p</i> = 0.598). Finally, NRF2 gene expression was higher among participants who reported better sleep quality (<i>p</i> < 0.01). <b>Conclusions</b>: Our findings suggest possible interactions among NRF2 gene expression, protection against SARS-CoV-2 infection, and the modulation of COVID-19 vaccination efficacy.https://www.mdpi.com/2076-393X/13/7/739COVID-19SARS-CoV-2healthcare workersvaccineBNT162b2 mRNA vaccineanti-S-RBD IgG antibody
spellingShingle Stefano Rizza
Luca Coppeta
Gianluigi Ferrazza
Alessandro Nucera
Maria Postorino
Andrea Quatrana
Cristiana Ferrari
Rossella Menghini
Susanna Longo
Andrea Magrini
Massimo Federici
Nuclear Factor Erythroid 2-Related Factor 2 and SARS-CoV-2 Infection Risk in COVID-19-Vaccinated Hospital Nurses
Vaccines
COVID-19
SARS-CoV-2
healthcare workers
vaccine
BNT162b2 mRNA vaccine
anti-S-RBD IgG antibody
title Nuclear Factor Erythroid 2-Related Factor 2 and SARS-CoV-2 Infection Risk in COVID-19-Vaccinated Hospital Nurses
title_full Nuclear Factor Erythroid 2-Related Factor 2 and SARS-CoV-2 Infection Risk in COVID-19-Vaccinated Hospital Nurses
title_fullStr Nuclear Factor Erythroid 2-Related Factor 2 and SARS-CoV-2 Infection Risk in COVID-19-Vaccinated Hospital Nurses
title_full_unstemmed Nuclear Factor Erythroid 2-Related Factor 2 and SARS-CoV-2 Infection Risk in COVID-19-Vaccinated Hospital Nurses
title_short Nuclear Factor Erythroid 2-Related Factor 2 and SARS-CoV-2 Infection Risk in COVID-19-Vaccinated Hospital Nurses
title_sort nuclear factor erythroid 2 related factor 2 and sars cov 2 infection risk in covid 19 vaccinated hospital nurses
topic COVID-19
SARS-CoV-2
healthcare workers
vaccine
BNT162b2 mRNA vaccine
anti-S-RBD IgG antibody
url https://www.mdpi.com/2076-393X/13/7/739
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