Unraveling COVID-19 Relationship with Anxiety Disorders and Symptoms

BackgroundWhile COVID-19 outcomes are associated with increased anxiety, individuals affected by anxiety disorders are more likely to develop severe COVID-19 outcomes. MethodsWe used genome-wide data from UK Biobank (up to 420,531 participants), FinnGen Project (up to 329,077 participants), Million Veteran Program (175,163 participants), and COVID-19 Host Genetics Initiative (up to 122,616 cases and 2,475,240 controls) to investigate possible causal effects and shared genetic mechanisms linking COVID-19 outcomes to anxiety disorders and symptoms. ResultsWe observed a strong genetic correlation of anxiety disorder with COVID-19 positive status (rg=0.35, p=2 x 10-4) and COVID-19 hospitalization (rg=0.31, p=7.2 x 10-4). Among anxiety symptoms, "Tense, sore, or aching muscles during worst period of anxiety" was genetically correlated with COVID-19 positive status (rg=0.33, p=0.001), while "Frequent trouble falling or staying asleep during worst period of anxiety" was genetically correlated with COVID-19 hospitalization (rg=0.24, p=0.004). Through a latent causal variable analysis, we observed that COVID-19 outcomes have statistically significant genetic causality proportion (gcp) on anxiety symptoms (e.g., COVID-19 positive status[->]"Recent easy annoyance or irritability" [boxv]gcp[boxv]=0.18, p=6.72 x 10-17). Conversely, anxiety disorders appear to have a possible causal effect on COVID-19 ([boxv]gcp[boxv]=0.38, p=3.17 x 10-9). Additionally, we also identified multiple loci with evidence of local genetic correlation between anxiety and COVID-19. These appear to be related to genetic effects shared with lung function, brain morphology, alcohol and tobacco use, and hematologic parameters. ConclusionsThis study provided important insights into the relationship between COVID-19 and mental health, differentiating the dynamics linking anxiety disorders to COVID-19 from the effect of COVID-19 on anxiety symptoms.