Prepandemic levels of cytokines and immunoglobulins and risk of SARS-CoV-2 infection and COVID-19 in the general population of Barcelona

BackgroundFrom a public health perspective it is remarkable that there are yet no longitudinal studies in the general population investigating the influence of the basal immune state, measured before the pandemic, on the risk of SARS-CoV-2 infection and COVID-19.ObjectiveTo investigate the specific...

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Main Authors: Miquel Porta, José Pumarega, Ruth Aguilar, David Prieto-Merino, Laura Campi, Cristina Rius, Judit Villar-García, Marta Vidal, Alfons Jimenez, Antonio Peña, Miguel-Ángel Muñoz, Leonardo Trasande, Francisco Bolúmar, Gemma Moncunill, Magda Gasull, Carlota Dobaño
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Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Public Health
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Online Access:https://www.frontiersin.org/articles/10.3389/fpubh.2025.1548456/full
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author Miquel Porta
Miquel Porta
Miquel Porta
Miquel Porta
Miquel Porta
Miquel Porta
José Pumarega
José Pumarega
José Pumarega
Ruth Aguilar
Ruth Aguilar
David Prieto-Merino
Laura Campi
Laura Campi
Cristina Rius
Cristina Rius
Cristina Rius
Judit Villar-García
Marta Vidal
Marta Vidal
Marta Vidal
Alfons Jimenez
Alfons Jimenez
Alfons Jimenez
Antonio Peña
Miguel-Ángel Muñoz
Miguel-Ángel Muñoz
Leonardo Trasande
Leonardo Trasande
Leonardo Trasande
Francisco Bolúmar
Francisco Bolúmar
Gemma Moncunill
Gemma Moncunill
Gemma Moncunill
Magda Gasull
Magda Gasull
Magda Gasull
Carlota Dobaño
Carlota Dobaño
Carlota Dobaño
author_facet Miquel Porta
Miquel Porta
Miquel Porta
Miquel Porta
Miquel Porta
Miquel Porta
José Pumarega
José Pumarega
José Pumarega
Ruth Aguilar
Ruth Aguilar
David Prieto-Merino
Laura Campi
Laura Campi
Cristina Rius
Cristina Rius
Cristina Rius
Judit Villar-García
Marta Vidal
Marta Vidal
Marta Vidal
Alfons Jimenez
Alfons Jimenez
Alfons Jimenez
Antonio Peña
Miguel-Ángel Muñoz
Miguel-Ángel Muñoz
Leonardo Trasande
Leonardo Trasande
Leonardo Trasande
Francisco Bolúmar
Francisco Bolúmar
Gemma Moncunill
Gemma Moncunill
Gemma Moncunill
Magda Gasull
Magda Gasull
Magda Gasull
Carlota Dobaño
Carlota Dobaño
Carlota Dobaño
author_sort Miquel Porta
collection DOAJ
description BackgroundFrom a public health perspective it is remarkable that there are yet no longitudinal studies in the general population investigating the influence of the basal immune state, measured before the pandemic, on the risk of SARS-CoV-2 infection and COVID-19.ObjectiveTo investigate the specific and combined effects of personal levels of cytokines and immunoglobulins—measured in individuals’ blood 4 years before the pandemic—on the risk of SARS-CoV-2 infection and COVID-19 in a general population.MethodsWe conducted a prospective cohort study in 240 individuals from the general population of Barcelona. Thirty cytokines and 31 immunoglobulins were quantified in prepandemic serum samples (collected in 2016–17) by high-throughput multiplex quantitative suspension array technology.ResultsHigher concentrations in 2016–17 of IL-8 and TNF-α significantly decreased the risk of SARS-CoV-2 seropositivity in 2020–21, whereas higher concentrations of MIP-1α were a risk factor for seropositivity. Most cytokines in mixtures with IL-8, MIP-1α, TNF-α or G-CSF were associated with SARS-CoV-2 seropositivity (all OR ≥2.0 or OR≤0.4 and p < 0.05). The five individual isotype-antigen pairs more clearly associated with seropositivity were: protectively, IgG to CMV pp150, IgG to CMV pp65, and IgG to N OC43; and, increasing risk of seropositivity, IgM to CMV pp65 and IgM to EBV EA-D. The four cytokines most consistently associated with the risk of COVID-19 were also G-CSF, IL-8, TNF-α, and MIP-1α. The four isotype-antigen pairs more strongly associated with risk of COVID-19 (all protective) were IgA to CMV pp65 and N 229E, and IgG to EBV EAD and VCAp18.ConclusionThe unique longitudinal design of this study, with measurements before and during the pandemic in a general population, provides novel knowledge on the protective and detrimental effects of specific individual cytokines and immunoglobulins, and their mixtures, on the risk of SARS-CoV-2 seropositivity and COVID-19. If confirmed, findings would be significantly relevant for medicine and public health.
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spelling doaj-art-e31f0f70ad944b188e07e2531483eede2025-08-20T05:32:58ZengFrontiers Media S.A.Frontiers in Public Health2296-25652025-08-011310.3389/fpubh.2025.15484561548456Prepandemic levels of cytokines and immunoglobulins and risk of SARS-CoV-2 infection and COVID-19 in the general population of BarcelonaMiquel Porta0Miquel Porta1Miquel Porta2Miquel Porta3Miquel Porta4Miquel Porta5José Pumarega6José Pumarega7José Pumarega8Ruth Aguilar9Ruth Aguilar10David Prieto-Merino11Laura Campi12Laura Campi13Cristina Rius14Cristina Rius15Cristina Rius16Judit Villar-García17Marta Vidal18Marta Vidal19Marta Vidal20Alfons Jimenez21Alfons Jimenez22Alfons Jimenez23Antonio Peña24Miguel-Ángel Muñoz25Miguel-Ángel Muñoz26Leonardo Trasande27Leonardo Trasande28Leonardo Trasande29Francisco Bolúmar30Francisco Bolúmar31Gemma Moncunill32Gemma Moncunill33Gemma Moncunill34Magda Gasull35Magda Gasull36Magda Gasull37Carlota Dobaño38Carlota Dobaño39Carlota Dobaño40School of Medicine, Universitat Autònoma de Barcelona, Barcelona, SpainHospital del Mar Research Institute (IMIM), Barcelona, SpainCIBER de Epidemiología y Salud Pública (CIBERESP), Barcelona, SpainDivision of Environmental Pediatrics, School of Medicine, New York University, New York, NY, United StatesDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesUniversitat Pompeu Fabra, Barcelona, SpainSchool of Medicine, Universitat Autònoma de Barcelona, Barcelona, SpainHospital del Mar Research Institute (IMIM), Barcelona, SpainCIBER de Epidemiología y Salud Pública (CIBERESP), Barcelona, SpainISGlobal, Barcelona, SpainFacultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, SpainUniversity of Alcalá de Henares, Madrid, SpainHospital del Mar Research Institute (IMIM), Barcelona, SpainCIBER de Epidemiología y Salud Pública (CIBERESP), Barcelona, SpainCIBER de Epidemiología y Salud Pública (CIBERESP), Barcelona, SpainUniversitat Pompeu Fabra, Barcelona, Spain0Agència de Salut Pública de Barcelona, Barcelona, SpainHospital del Mar Research Institute (IMIM), Barcelona, SpainISGlobal, Barcelona, SpainFacultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, Spain1CIBER de Enfermedades Infecciosas (CIBERINFEC), Barcelona, SpainISGlobal, Barcelona, SpainFacultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, Spain1CIBER de Enfermedades Infecciosas (CIBERINFEC), Barcelona, SpainUniversity of Alcalá de Henares, Madrid, SpainUniversitat Pompeu Fabra, Barcelona, Spain2Institut Universitari per a la Recerca a l’Atenció Primària de Salut Jordi Gol’, Catalan Institute of Health, Barcelona, SpainDivision of Environmental Pediatrics, School of Medicine, New York University, New York, NY, United States3Department of Population Health, New York University, New York, NY, United States4New York University Wagner School of Public Service, New York, NY, United StatesUniversity of Alcalá de Henares, Madrid, Spain5City University of New York, New York, NY, United StatesISGlobal, Barcelona, SpainFacultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, Spain1CIBER de Enfermedades Infecciosas (CIBERINFEC), Barcelona, SpainHospital del Mar Research Institute (IMIM), Barcelona, SpainCIBER de Epidemiología y Salud Pública (CIBERESP), Barcelona, SpainUniversitat Pompeu Fabra, Barcelona, SpainISGlobal, Barcelona, SpainFacultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, Spain1CIBER de Enfermedades Infecciosas (CIBERINFEC), Barcelona, SpainBackgroundFrom a public health perspective it is remarkable that there are yet no longitudinal studies in the general population investigating the influence of the basal immune state, measured before the pandemic, on the risk of SARS-CoV-2 infection and COVID-19.ObjectiveTo investigate the specific and combined effects of personal levels of cytokines and immunoglobulins—measured in individuals’ blood 4 years before the pandemic—on the risk of SARS-CoV-2 infection and COVID-19 in a general population.MethodsWe conducted a prospective cohort study in 240 individuals from the general population of Barcelona. Thirty cytokines and 31 immunoglobulins were quantified in prepandemic serum samples (collected in 2016–17) by high-throughput multiplex quantitative suspension array technology.ResultsHigher concentrations in 2016–17 of IL-8 and TNF-α significantly decreased the risk of SARS-CoV-2 seropositivity in 2020–21, whereas higher concentrations of MIP-1α were a risk factor for seropositivity. Most cytokines in mixtures with IL-8, MIP-1α, TNF-α or G-CSF were associated with SARS-CoV-2 seropositivity (all OR ≥2.0 or OR≤0.4 and p < 0.05). The five individual isotype-antigen pairs more clearly associated with seropositivity were: protectively, IgG to CMV pp150, IgG to CMV pp65, and IgG to N OC43; and, increasing risk of seropositivity, IgM to CMV pp65 and IgM to EBV EA-D. The four cytokines most consistently associated with the risk of COVID-19 were also G-CSF, IL-8, TNF-α, and MIP-1α. The four isotype-antigen pairs more strongly associated with risk of COVID-19 (all protective) were IgA to CMV pp65 and N 229E, and IgG to EBV EAD and VCAp18.ConclusionThe unique longitudinal design of this study, with measurements before and during the pandemic in a general population, provides novel knowledge on the protective and detrimental effects of specific individual cytokines and immunoglobulins, and their mixtures, on the risk of SARS-CoV-2 seropositivity and COVID-19. If confirmed, findings would be significantly relevant for medicine and public health.https://www.frontiersin.org/articles/10.3389/fpubh.2025.1548456/fullcytokinesimmunoglobulinsetiologyrisk factorsSARS-CoV-2COVID-19
spellingShingle Miquel Porta
Miquel Porta
Miquel Porta
Miquel Porta
Miquel Porta
Miquel Porta
José Pumarega
José Pumarega
José Pumarega
Ruth Aguilar
Ruth Aguilar
David Prieto-Merino
Laura Campi
Laura Campi
Cristina Rius
Cristina Rius
Cristina Rius
Judit Villar-García
Marta Vidal
Marta Vidal
Marta Vidal
Alfons Jimenez
Alfons Jimenez
Alfons Jimenez
Antonio Peña
Miguel-Ángel Muñoz
Miguel-Ángel Muñoz
Leonardo Trasande
Leonardo Trasande
Leonardo Trasande
Francisco Bolúmar
Francisco Bolúmar
Gemma Moncunill
Gemma Moncunill
Gemma Moncunill
Magda Gasull
Magda Gasull
Magda Gasull
Carlota Dobaño
Carlota Dobaño
Carlota Dobaño
Prepandemic levels of cytokines and immunoglobulins and risk of SARS-CoV-2 infection and COVID-19 in the general population of Barcelona
Frontiers in Public Health
cytokines
immunoglobulins
etiology
risk factors
SARS-CoV-2
COVID-19
title Prepandemic levels of cytokines and immunoglobulins and risk of SARS-CoV-2 infection and COVID-19 in the general population of Barcelona
title_full Prepandemic levels of cytokines and immunoglobulins and risk of SARS-CoV-2 infection and COVID-19 in the general population of Barcelona
title_fullStr Prepandemic levels of cytokines and immunoglobulins and risk of SARS-CoV-2 infection and COVID-19 in the general population of Barcelona
title_full_unstemmed Prepandemic levels of cytokines and immunoglobulins and risk of SARS-CoV-2 infection and COVID-19 in the general population of Barcelona
title_short Prepandemic levels of cytokines and immunoglobulins and risk of SARS-CoV-2 infection and COVID-19 in the general population of Barcelona
title_sort prepandemic levels of cytokines and immunoglobulins and risk of sars cov 2 infection and covid 19 in the general population of barcelona
topic cytokines
immunoglobulins
etiology
risk factors
SARS-CoV-2
COVID-19
url https://www.frontiersin.org/articles/10.3389/fpubh.2025.1548456/full
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