Identifying risk factors and predicting long COVID in a Spanish cohort

Abstract Many studies have investigated symptoms, comorbidities, demographic factors, and vaccine effects in relation to long COVID (LC-19) across global populations. However, a number of these studies have shortcomings, such as inadequate LC-19 categorisation, lack of sex disaggregation, or a narro...

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Main Authors: Antonio Guillén-Teruel, Jose L. Mellina-Andreu, Gabriel Reina, Enrique González-Billalabeitia, Ramón Rodriguez-Iborra, José Palma, Juan A. Botía, Alejandro Cisterna-García
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Language:English
Published: Nature Portfolio 2025-03-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-94765-w
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author Antonio Guillén-Teruel
Jose L. Mellina-Andreu
Gabriel Reina
Enrique González-Billalabeitia
Ramón Rodriguez-Iborra
José Palma
Juan A. Botía
Alejandro Cisterna-García
author_facet Antonio Guillén-Teruel
Jose L. Mellina-Andreu
Gabriel Reina
Enrique González-Billalabeitia
Ramón Rodriguez-Iborra
José Palma
Juan A. Botía
Alejandro Cisterna-García
author_sort Antonio Guillén-Teruel
collection DOAJ
description Abstract Many studies have investigated symptoms, comorbidities, demographic factors, and vaccine effects in relation to long COVID (LC-19) across global populations. However, a number of these studies have shortcomings, such as inadequate LC-19 categorisation, lack of sex disaggregation, or a narrow focus on certain risk factors like symptoms or comorbidities alone. We address these gaps by investigating the demographic factors, comorbidities, and symptoms present during the acute phase of primary COVID-19 infection among patients with LC-19 and comparing them to typical non-Long COVID-19 patients. Additionally, we assess the impact of COVID-19 vaccination on these patients. Drawing on data from the Regional Health System of the Region of Murcia in southeastern Spain, our analysis includes comprehensive information from clinical and hospitalisation records, symptoms, and vaccination details of over 675126 patients across 10 hospitals. We calculated age and sex-adjusted odds ratios (AOR) to identify protective and risk factors for LC-19. Our findings reveal distinct symptomatology, comorbidity patterns, and demographic characteristics among patients with LC-19 versus those with typical non-Long COVID-19. Factors such as age, female sex (AOR = 1.39, adjusted p < 0.001), and symptoms like chest pain (AOR > 1.55, adjusted p < 0.001) or hyposmia (AOR > 1.5, adjusted p < 0.001) significantly increase the risk of developing LC-19. However, vaccination demonstrates a strong protective effect, with vaccinated individuals having a markedly lower risk (AOR = 0.10, adjusted p < 0.001), highlighting the importance of vaccination in reducing LC-19 susceptibility. Interestingly, symptoms and comorbidities show no significant differences when disaggregated by type of LC-19 patient. Vaccination before infection is the most important factor and notably decreases the likelihood of long COVID. Particularly, mRNA vaccines offer more protection against developing LC-19 than viral vector-based vaccines (AOR = 0.48). Additionally, we have developed a model to predict LC-19 that incorporates all studied risk factors, achieving a balanced accuracy of 73% and ROC-AUC of 0.80. This model is available as a free online LC-19 calculator, accessible at ( LC-19 Calculator ).
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spelling doaj-art-29a8029dbcc841d5b2b8f5504cda949b2025-08-20T02:49:26ZengNature PortfolioScientific Reports2045-23222025-03-0115111510.1038/s41598-025-94765-wIdentifying risk factors and predicting long COVID in a Spanish cohortAntonio Guillén-Teruel0Jose L. Mellina-Andreu1Gabriel Reina2Enrique González-Billalabeitia3Ramón Rodriguez-Iborra4José Palma5Juan A. Botía6Alejandro Cisterna-García7Department of Information and Communication Engineering, University of MurciaDepartment of Information and Communication Engineering, University of MurciaServicio de Microbiología, Clínica, Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra (IdiSNA)Department of Medical Oncology, Hospital UniversitarioSubdirección General de Tecnologías de la Información, Servicio Murciano de SaludDepartment of Information and Communication Engineering, University of MurciaDepartment of Information and Communication Engineering, University of MurciaDepartment of Information and Communication Engineering, University of MurciaAbstract Many studies have investigated symptoms, comorbidities, demographic factors, and vaccine effects in relation to long COVID (LC-19) across global populations. However, a number of these studies have shortcomings, such as inadequate LC-19 categorisation, lack of sex disaggregation, or a narrow focus on certain risk factors like symptoms or comorbidities alone. We address these gaps by investigating the demographic factors, comorbidities, and symptoms present during the acute phase of primary COVID-19 infection among patients with LC-19 and comparing them to typical non-Long COVID-19 patients. Additionally, we assess the impact of COVID-19 vaccination on these patients. Drawing on data from the Regional Health System of the Region of Murcia in southeastern Spain, our analysis includes comprehensive information from clinical and hospitalisation records, symptoms, and vaccination details of over 675126 patients across 10 hospitals. We calculated age and sex-adjusted odds ratios (AOR) to identify protective and risk factors for LC-19. Our findings reveal distinct symptomatology, comorbidity patterns, and demographic characteristics among patients with LC-19 versus those with typical non-Long COVID-19. Factors such as age, female sex (AOR = 1.39, adjusted p < 0.001), and symptoms like chest pain (AOR > 1.55, adjusted p < 0.001) or hyposmia (AOR > 1.5, adjusted p < 0.001) significantly increase the risk of developing LC-19. However, vaccination demonstrates a strong protective effect, with vaccinated individuals having a markedly lower risk (AOR = 0.10, adjusted p < 0.001), highlighting the importance of vaccination in reducing LC-19 susceptibility. Interestingly, symptoms and comorbidities show no significant differences when disaggregated by type of LC-19 patient. Vaccination before infection is the most important factor and notably decreases the likelihood of long COVID. Particularly, mRNA vaccines offer more protection against developing LC-19 than viral vector-based vaccines (AOR = 0.48). Additionally, we have developed a model to predict LC-19 that incorporates all studied risk factors, achieving a balanced accuracy of 73% and ROC-AUC of 0.80. This model is available as a free online LC-19 calculator, accessible at ( LC-19 Calculator ).https://doi.org/10.1038/s41598-025-94765-wCOVID-19SARS-CoV-2VaccinesLong COVIDLC-19
spellingShingle Antonio Guillén-Teruel
Jose L. Mellina-Andreu
Gabriel Reina
Enrique González-Billalabeitia
Ramón Rodriguez-Iborra
José Palma
Juan A. Botía
Alejandro Cisterna-García
Identifying risk factors and predicting long COVID in a Spanish cohort
Scientific Reports
COVID-19
SARS-CoV-2
Vaccines
Long COVID
LC-19
title Identifying risk factors and predicting long COVID in a Spanish cohort
title_full Identifying risk factors and predicting long COVID in a Spanish cohort
title_fullStr Identifying risk factors and predicting long COVID in a Spanish cohort
title_full_unstemmed Identifying risk factors and predicting long COVID in a Spanish cohort
title_short Identifying risk factors and predicting long COVID in a Spanish cohort
title_sort identifying risk factors and predicting long covid in a spanish cohort
topic COVID-19
SARS-CoV-2
Vaccines
Long COVID
LC-19
url https://doi.org/10.1038/s41598-025-94765-w
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