Nationwide longitudinal study reveals impact of both national restriction levels and genetic risk factors on loneliness during the COVID-19 pandemic.

The impact of social restrictions during the COVID-19 pandemic on social isolation and loneliness has been widely debated, yet little attention has been given to identifying particularly vulnerable groups. In this study, we analysed data from 8,042 participants of the Danish Blood Donor Study (DBDS) through a prospective design with multiple follow-ups, integrating genetic, health, and socioeconomic information to identify distinct loneliness trajectories during the pandemic. Using the 3-item UCLA Loneliness Scale (UCLA-3), we found that self-reported loneliness increased in parallel with social restriction index, with women being particularly affected. We identified three distinct loneliness trajectories: high loneliness, pandemic loneliness, and low loneliness. Individuals in the high and pandemic loneliness trajectories both had higher polygenic scores (PGS) for loneliness and for the personality trait neuroticism compared to the low loneliness trajectory. The high loneliness trajectory was additionally associated with high PGS for psychiatric disorders and low PGS for the personality trait extraversion in addition to a higher proportion of pre-pandemic psychiatric disorder diagnoses. In contrast, the pandemic loneliness trajectory was linked to low PGS for the personality traits agreeableness and conscientiousness, as well as higher PGS for religious participation. These findings highlight the need for tailored interventions targeting individuals with poor mental well-being.