ORIGINAL RESEARCH article
Front. Psychiatry
Sec. Behavioral and Psychiatric Genetics
Volume 16 - 2025 | doi: 10.3389/fpsyt.2025.1643355
This article is part of the Research TopicThe Genetic Intersection of Mental and Physical Health: Unraveling Shared Heritable Risk FactorsView all articles
Molecular Insights into the Bidirectional Link Between Anxiety and COVID-19: A Combined Clinical and Bioinformatics Approach
Provisionally accepted
- 1Department of Pulmonary and Critical Care Medicine,Tongling People's Hospital affiliated to Bengbu Medical University, Tongling, China
- 2Department of Psychiatry, Tongde Hospital of Zhejiang Province, Hangzhou, China
- 3Department of Infectious Diseases,Tongling People's Hospital affiliated to Bengbu Medical University, Tongling, China
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Introduction: Numerous 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.In 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.Results: Our 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 abnormalitieshallmarks 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.These 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.
Keywords: COVID-19, Anxiety, Signal pathway, Gene Expression, SAS
Received: 08 Jun 2025; Accepted: 01 Jul 2025.
Copyright: © 2025 Huang, Hu, Gu, Wu, Huang and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dexiang Yang, Department of Pulmonary and Critical Care Medicine,Tongling People's Hospital affiliated to Bengbu Medical University, Tongling, China
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