February 21, 2024

Insights into the relationship between COVID-19 and mental health

In a recent study posted to the medRxiv* preprint server, researchers investigated the likely causal consequences and common genetic mechanisms that link the results of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to anxiety disorders and symptoms.

Study: Unraveling COVID-19 Relationship with Anxiety Disorders and Symptoms. Image Credit: tadamichi/Shutterstock.com

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.


The pandemic of the coronavirus disease 2019 (COVID-19) has significantly impacted mental health, increasing anxiety disorders and symptoms. This increase has been primarily observed among hospitalized COVID-19 individuals and those with a history of mental illness.

Conversely, anxiety disorders increase the likelihood of severe COVID-19 outcomes, and the relationship between anxiety and COVID-19 can impact the immune system, increasing the risk of infections and compromised host defense systems.

A comprehensive analysis of comorbidity with anxiety disorders can help develop targeted interventions and improve mental health outcomes.

About the study

In the present study, researchers explored the link between COVID-19 and anxiety disorders and characteristics, investigating potential pleiotropic pathways that may be responsible for the reported comorbidity.

The researchers drew on large-scale genome-wide association studies (GWAS) datasets from the United Kingdom Biobank (UKBB, 420,531 individuals), the FinnGen Project (329,077 individuals), the Million Veteran Program (MVP, 175,163 individuals), and the SARS-CoV-2 infection Host Genetics Initiative (HGI, 122,616 and 2,475,240 cases and controls, respectively) of 2021.

The genome-wide association study was carried out using regression modeling. Anxiety characteristics were chosen based on single nucleotide polymorphism (SNP) heritability.

The two-item generalized anxiety disorder (GAD-2) scale assessed anxiety symptoms. Individuals of European heritage were excluded from the study.

The latent causal variable (LCV) technique was utilized to determine if the observed genetic association is due to potential causal effects. The local analysis of [co]variant association (LAVA) technique was used to discover the genomic areas contributing to pathogenic pathways shared by COVID-19 and anxiety-related symptoms.

To identify specific loci that may be related to COVID-19 outcomes and anxiety-related phenotypes via tissue-specific transcriptomic regulation, hypothesis prioritization in multi-trait Colocalization (HyPrColoc) analysis was performed concerning the regions that showed significant local genetic correlation.

The Genotype-Tissue Expression (GTEx) method was utilized to determine the expression of quantitative trait loci (eQTL) in the LAVA-identified areas.

COVID-19-anxiety colocalized loci having a posterior probability greater than 70% were recognized as such by the HyPrColoc developers.


Anxiety disorders with COVID-19 positive status and COVID-19 hospitalization were shown to have a high genetic link. COVID-19 positivity was genetically associated with tight, hurting, or stiff muscles at the worst times of worry.

COVID-19 hospitalization was genetically linked to difficulty falling or keeping asleep during the most anxious phase. According to the LCV study, COVID-19 results have a substantial genetic causality percentage (gcp) on anxiety symptoms.

Anxiety disorders, on the other hand, appear to have a probable causal influence on COVID-19 (gcp, 0.4).

Furthermore, the researchers discovered multiple loci with evidence of local genetic correlations between anxiety and COVID-19, which appeared to be related to genetic effects shared with lung function, brain morphology (grey matter volume in vermis crus II of the cerebellum, which is associated with social mentalizing and emotional self-experiences), level of education, tobacco and alcohol consumption, and hematologic parameters such as mean corpuscular volume (MCV), platelet count, and platelet count.

SARS-CoV-2 infections and accompanying hospitalizations were genetically connected with several anxiety traits, while general practitioner visits for tension, sadness, or anxiety were genetically correlated with COVID-19-associated severe respiratory disease.

Four anxiety phenotypes might influence the COVID-19 outcome, three of which were connected to UKBB case-control criteria, with anxiety disorder being the most influential.

The local genetic correlation analysis found distinct loci contributing to pleiotropic pathways relating COVID-19 results to anxiety disorders and symptoms. Within the 7:130,418,705-131,856,481″ locus, 508 genome-wide correlations were found, with the greatest ones being high-density lipoprotein cholesterol (HDL-C) and insulin-like growth factor 1 (IGF-1) values.

The colocalization study showed that the observed local genetic connections were not the result of a single variation.


Overall, the study findings showed a consistent overlap of COVID-19 outcomes with anxiety disorders and symptoms, supporting the association across the anxiety spectrum. The results provided valuable insights into the relationship between COVID-19 and mental health, highlighting the potential contribution of multiple pleiotropic pathways.

Anxiety disorders may increase susceptibility to COVID-19, while COVID-19 outcomes may contribute to anxiety-related behavioral symptoms.

Genetic effects shared with risk factors may also be critical in the association between COVID-19 and anxiety. The findings indicated that anxiety disorders and physical symptoms might have a causal effect on COVID-19, while COVID-19 may play a causal role in anxiety-related behavioral symptoms.

Additionally, worse COVID-19 outcomes, including hospitalization and severe respiratory disease, may affect anxiety severity. The local genetic correlations observed may be due to multiple variants within each locus.

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

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