Unraveling COVID-19 Relationship with Anxiety Disorders and Symptoms.

Background:While COVID-19 outcomes are associated with increased anxiety, individuals affected by anxiety disorders are more likely to develop severe COVID-19 outcomes. Methods:We 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. Results:We observed a strong genetic correlation of anxiety disorder with COVID-19 positive status (rg=0.35, p=2 × 10 -4 ) and COVID-19 hospitalization (rg=0.31, p=7.2 × 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" │gcp│=0.18, p=6.72 × 10 -17 ). Conversely, anxiety disorders appear to have a possible causal effect on COVID-19 (│gcp│=0.38, p=3.17 × 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. Conclusions:This 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.