Persistence of dysfunctional immune response 12 months after SARS-CoV-2 infection and their relationship with pulmonary sequelae and long COVID

Abstract Introduction Most patients recover fully after an acute infection by SARS-CoV-2. Some, however, may develop pulmonary sequelae (PS) and/or long COVID (LC). However, whether these two clinical conditions have similar or different pathogenic mechanisms is unknown. Methods The levels of autoan...

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Main Authors: Tamara Cruz, Núria Albacar, Estibaliz Ruiz, Gema M. Lledo, Lídia Perea, Alba Puebla, Alejandro Torvisco, Núria Mendoza, Pau Marrades, Jacobo Sellares, Alvar Agustí, Odette Viñas, Oriol Sibila, Rosa Faner
Format: Article
Language:English
Published: BMC 2025-04-01
Series:Respiratory Research
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Online Access:https://doi.org/10.1186/s12931-025-03200-1
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author Tamara Cruz
Núria Albacar
Estibaliz Ruiz
Gema M. Lledo
Lídia Perea
Alba Puebla
Alejandro Torvisco
Núria Mendoza
Pau Marrades
Jacobo Sellares
Alvar Agustí
Odette Viñas
Oriol Sibila
Rosa Faner
author_facet Tamara Cruz
Núria Albacar
Estibaliz Ruiz
Gema M. Lledo
Lídia Perea
Alba Puebla
Alejandro Torvisco
Núria Mendoza
Pau Marrades
Jacobo Sellares
Alvar Agustí
Odette Viñas
Oriol Sibila
Rosa Faner
author_sort Tamara Cruz
collection DOAJ
description Abstract Introduction Most patients recover fully after an acute infection by SARS-CoV-2. Some, however, may develop pulmonary sequelae (PS) and/or long COVID (LC). However, whether these two clinical conditions have similar or different pathogenic mechanisms is unknown. Methods The levels of autoantibodies and 184 inflammatory and organ damage associated proteins in plasma were determined (by immunofluorescence and Olink panels, respectively) 1 year after an acute infection by SARS-CoV-2 in 51 patients with PS (DLCO < 80% ref), 31 patients with LC and 31 patients fully recovered (Rec). PS was defined by the presence of reduced carbon monoxide diffusing capacity (DLCO) lower than 80% ref. LC was defined by the presence of chronic symptoms in the absence of an alternative diagnosis. Results We found that patients with PS or LC both showed increased levels than Rec of anti-microbial, immune cell activation and recruitment related proteins. Patients with PS showed higher levels of anti-nuclear autoantibodies, whereas LC patients had increased levels of organ-damage associated proteins. In patients with PS most of the elevated proteins correlate with the impairment of lung function (DLCO). Finally, in PS we additionally performed the determinations at an earlier time point (6 months) and showed that the expression of CCL20 and IFN-ɣ was already higher at 6 months, while CCL3 and CCL19 increase from 6 to 12 months, suggesting a pathogenic role in PS persistence. Conclusions Patients with PS or LC have abnormal but different persistent circulatory immune and organ damage biomarkers, suggesting different underlying biology of both post-COVID conditions.
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spelling doaj-art-3dc8d9e6a027426ca0bc6f618b904b1a2025-08-20T02:17:56ZengBMCRespiratory Research1465-993X2025-04-0126111110.1186/s12931-025-03200-1Persistence of dysfunctional immune response 12 months after SARS-CoV-2 infection and their relationship with pulmonary sequelae and long COVIDTamara Cruz0Núria Albacar1Estibaliz Ruiz2Gema M. Lledo3Lídia Perea4Alba Puebla5Alejandro Torvisco6Núria Mendoza7Pau Marrades8Jacobo Sellares9Alvar Agustí10Odette Viñas11Oriol Sibila12Rosa Faner13Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)Department of Autoimmune Diseases, Hospital ClínicInstitut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)Respiratory Institute, Hospital ClinicInstitut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)Abstract Introduction Most patients recover fully after an acute infection by SARS-CoV-2. Some, however, may develop pulmonary sequelae (PS) and/or long COVID (LC). However, whether these two clinical conditions have similar or different pathogenic mechanisms is unknown. Methods The levels of autoantibodies and 184 inflammatory and organ damage associated proteins in plasma were determined (by immunofluorescence and Olink panels, respectively) 1 year after an acute infection by SARS-CoV-2 in 51 patients with PS (DLCO < 80% ref), 31 patients with LC and 31 patients fully recovered (Rec). PS was defined by the presence of reduced carbon monoxide diffusing capacity (DLCO) lower than 80% ref. LC was defined by the presence of chronic symptoms in the absence of an alternative diagnosis. Results We found that patients with PS or LC both showed increased levels than Rec of anti-microbial, immune cell activation and recruitment related proteins. Patients with PS showed higher levels of anti-nuclear autoantibodies, whereas LC patients had increased levels of organ-damage associated proteins. In patients with PS most of the elevated proteins correlate with the impairment of lung function (DLCO). Finally, in PS we additionally performed the determinations at an earlier time point (6 months) and showed that the expression of CCL20 and IFN-ɣ was already higher at 6 months, while CCL3 and CCL19 increase from 6 to 12 months, suggesting a pathogenic role in PS persistence. Conclusions Patients with PS or LC have abnormal but different persistent circulatory immune and organ damage biomarkers, suggesting different underlying biology of both post-COVID conditions.https://doi.org/10.1186/s12931-025-03200-1COVID-19Pulmonary SequelaeLong COVIDPersistence of viral reservoirsAutoantibodiesOrgan-damage markers
spellingShingle Tamara Cruz
Núria Albacar
Estibaliz Ruiz
Gema M. Lledo
Lídia Perea
Alba Puebla
Alejandro Torvisco
Núria Mendoza
Pau Marrades
Jacobo Sellares
Alvar Agustí
Odette Viñas
Oriol Sibila
Rosa Faner
Persistence of dysfunctional immune response 12 months after SARS-CoV-2 infection and their relationship with pulmonary sequelae and long COVID
Respiratory Research
COVID-19
Pulmonary Sequelae
Long COVID
Persistence of viral reservoirs
Autoantibodies
Organ-damage markers
title Persistence of dysfunctional immune response 12 months after SARS-CoV-2 infection and their relationship with pulmonary sequelae and long COVID
title_full Persistence of dysfunctional immune response 12 months after SARS-CoV-2 infection and their relationship with pulmonary sequelae and long COVID
title_fullStr Persistence of dysfunctional immune response 12 months after SARS-CoV-2 infection and their relationship with pulmonary sequelae and long COVID
title_full_unstemmed Persistence of dysfunctional immune response 12 months after SARS-CoV-2 infection and their relationship with pulmonary sequelae and long COVID
title_short Persistence of dysfunctional immune response 12 months after SARS-CoV-2 infection and their relationship with pulmonary sequelae and long COVID
title_sort persistence of dysfunctional immune response 12 months after sars cov 2 infection and their relationship with pulmonary sequelae and long covid
topic COVID-19
Pulmonary Sequelae
Long COVID
Persistence of viral reservoirs
Autoantibodies
Organ-damage markers
url https://doi.org/10.1186/s12931-025-03200-1
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