Molecular insights into the bidirectional link between anxiety and COVID-19: a combined clinical and bioinformatics approach

IntroductionNumerous studies have reported an increased incidence of anxiety in individuals affected by COVID-19; however, the specific molecular mechanisms underlying this association remain poorly understood.MethodsIn this study, we employed the Zung Self-Rating Anxiety Scale (SAS) to assess anxie...

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Main Authors: Wenjie Huang, Biao Hu, Chengyu Gu, Hao Wu, Yize Huang, Dexiang Yang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Psychiatry
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Online Access:https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1643355/full
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author Wenjie Huang
Biao Hu
Chengyu Gu
Hao Wu
Yize Huang
Dexiang Yang
author_facet Wenjie Huang
Biao Hu
Chengyu Gu
Hao Wu
Yize Huang
Dexiang Yang
author_sort Wenjie Huang
collection DOAJ
description IntroductionNumerous studies have reported an increased incidence of anxiety in individuals affected by COVID-19; however, the specific molecular mechanisms underlying this association remain poorly understood.MethodsIn this study, we employed the Zung Self-Rating Anxiety Scale (SAS) to assess anxiety levels in 36 asymptomatic COVID-19 patients. In parallel, we conducted a comprehensive literature-based data mining analysis to reconstruct the functional and molecular pathways linking COVID-19 and anxiety. Additionally, we performed a meta-analysis using eight independent COVID-19 case–control gene expression datasets to examine expression alterations in the literature-derived pathways.ResultsOur findings revealed that even among asymptomatic individuals, approximately 25% exhibited mild anxiety symptoms, which negatively correlated with age. The reconstructed pathways suggested that COVID-19 may contribute to cognitive decline through multisystem dysfunction and structural or functional brain abnormalities—hallmarks of anxiety disorders. The meta-analysis confirmed increased expression of four anxiety-related molecular mediators in response to COVID-19 infection: CALCA, TNF, PLAT, and PPARG, with the latter three associated with neurocognitive decline.ConclusionThese results provide molecular-level evidence for a bidirectional association between COVID-19 and anxiety, potentially mediated by dysregulated inflammatory cytokines and other secreted proteins. Furthermore, impaired cognitive function may serve as a critical link connecting these two conditions.
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spelling doaj-art-24703f9f5ea34e58bea9e53377abec6c2025-08-20T03:51:48ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402025-07-011610.3389/fpsyt.2025.16433551643355Molecular insights into the bidirectional link between anxiety and COVID-19: a combined clinical and bioinformatics approachWenjie Huang0Biao Hu1Chengyu Gu2Hao Wu3Yize Huang4Dexiang Yang5Department of Pulmonary and Critical Care Medicine, Tongling Hospital Affiliated to Bengbu Medical University, Tongling, Anhui, ChinaDepartment of Pulmonary and Critical Care Medicine, Tongling Hospital Affiliated to Bengbu Medical University, Tongling, Anhui, ChinaDepartment of Psychiatry, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, ChinaDepartment of Pulmonary and Critical Care Medicine, Tongling Hospital Affiliated to Bengbu Medical University, Tongling, Anhui, ChinaDepartment of Infectious Diseases, Tongling People’s Hospital Affiliated to Bengbu Medical University, Tongling, Anhui, ChinaDepartment of Pulmonary and Critical Care Medicine, Tongling Hospital Affiliated to Bengbu Medical University, Tongling, Anhui, ChinaIntroductionNumerous studies have reported an increased incidence of anxiety in individuals affected by COVID-19; however, the specific molecular mechanisms underlying this association remain poorly understood.MethodsIn this study, we employed the Zung Self-Rating Anxiety Scale (SAS) to assess anxiety levels in 36 asymptomatic COVID-19 patients. In parallel, we conducted a comprehensive literature-based data mining analysis to reconstruct the functional and molecular pathways linking COVID-19 and anxiety. Additionally, we performed a meta-analysis using eight independent COVID-19 case–control gene expression datasets to examine expression alterations in the literature-derived pathways.ResultsOur findings revealed that even among asymptomatic individuals, approximately 25% exhibited mild anxiety symptoms, which negatively correlated with age. The reconstructed pathways suggested that COVID-19 may contribute to cognitive decline through multisystem dysfunction and structural or functional brain abnormalities—hallmarks of anxiety disorders. The meta-analysis confirmed increased expression of four anxiety-related molecular mediators in response to COVID-19 infection: CALCA, TNF, PLAT, and PPARG, with the latter three associated with neurocognitive decline.ConclusionThese results provide molecular-level evidence for a bidirectional association between COVID-19 and anxiety, potentially mediated by dysregulated inflammatory cytokines and other secreted proteins. Furthermore, impaired cognitive function may serve as a critical link connecting these two conditions.https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1643355/fullCOVID-19anxietysignal pathwaygene expressionSAS
spellingShingle Wenjie Huang
Biao Hu
Chengyu Gu
Hao Wu
Yize Huang
Dexiang Yang
Molecular insights into the bidirectional link between anxiety and COVID-19: a combined clinical and bioinformatics approach
Frontiers in Psychiatry
COVID-19
anxiety
signal pathway
gene expression
SAS
title Molecular insights into the bidirectional link between anxiety and COVID-19: a combined clinical and bioinformatics approach
title_full Molecular insights into the bidirectional link between anxiety and COVID-19: a combined clinical and bioinformatics approach
title_fullStr Molecular insights into the bidirectional link between anxiety and COVID-19: a combined clinical and bioinformatics approach
title_full_unstemmed Molecular insights into the bidirectional link between anxiety and COVID-19: a combined clinical and bioinformatics approach
title_short Molecular insights into the bidirectional link between anxiety and COVID-19: a combined clinical and bioinformatics approach
title_sort molecular insights into the bidirectional link between anxiety and covid 19 a combined clinical and bioinformatics approach
topic COVID-19
anxiety
signal pathway
gene expression
SAS
url https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1643355/full
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