Long-Term Effects of COVID-19 on Cognitive Function and Mental Health

The ongoing pandemic of COVID-19 continues to have a detrimental impact on society, even after the rapid development of safe and effective vaccines. The worst phases of the pandemic caused systemic and cultural shifts in education, work, commerce, social ties, and even the process of grieving. The SARS-CoV-2 virus has taken 6.5 million lives worldwide, over 1 million lives in the US, and nearly 23,000 Veterans receiving care in the VA system. The highly infectious Omicron variant has caused the largest surge of cases yet, with a peak in mid-January 2022. This variant causes milder symptoms but is more resistant to current vaccines. While the most severely affected COVID patients are rightfully the focus of many investigations, patients with milder disease may show lasting changes as well. An important study by Al-Aly, Xie, and Bowe (2021) identified all non-hospitalized Veterans who had at least one SARS-CoV-2 positive test and who survived 30 days after diagnosis. Six months later, those who had COVID had an excess burden of respiratory conditions, metabolic disorders, cardiovascular conditions, insomnia, fatigue, anxiety disorders, trauma-related disorders, and neurocognitive disorders. Follow-up studies found that many of these conditions can persist for at least one year (Xie et al., 2022a,b). In addition, the risk of adverse health outcomes increases in Veterans with multiple infections (Al-Aly et al., preprint). Although epidemiological studies have been helpful in identifying population-level trends, a key missing perspective can be provided by Veterans' ratings of their own mental and physical symptoms. This is critical because future interventions require a deeper understanding of the challenges faced by Veterans with post-COVID conditions. The unique needs of Veterans include higher rates of the comorbidities commonly associated with a greater risk of negative COVID outcomes (diabetes, hypertension, and cardiovascular conditions). Ongoing cognitive issues after a COVID infection can also have a negative impact on employment and daily functioning. Cognitive dysfunction was the third most commonly reported symptom in a survey of the Long Covid community (Davis et al., 2021), yet "brain fog" remains scantly investigated, especially in Veterans. The proposed observational study will have a two group, prospective, repeated measure (3 time points) design with a study group and a closely matched healthy comparator group. The study group will be Veterans (n=300) who had a positive test for SARS-CoV-2 within the last 3-24 months but were not hospitalized. This population comprises the majority of VA patients with positive tests for SARS-CoV-2 (approximately 85-90%). Their results will be compared to healthy Veteran controls matched on demographic variables, pre-existing psychiatric conditions, and major comorbidities (n=300). Follow-up tests will be conducted six months and 12 months later. The project will obtain objective measures of cognitive performance over time and explore their relationship to mental health (anxiety, depression, PTSD) and other persistent post-acute sequelae of SARS-CoV-2 (PASC) symptoms (insomnia, fatigue) in COVID-19 survivors. Covariates will adjust for baseline scores, number of vaccines, and time since diagnosis. We will also examine the impact of multiple infections on mental health and cognitive outcomes. A validated web-based testing platform will obtain objective and reliable measures of sustained attention, executive function, episodic memory, and working memory. A better understanding of specific weaknesses in cognitive function over time is necessary to identify future intervention targets in the Veteran population with persistent post- COVID conditions. Our study will also establish the importance of monitoring the mental health of Veterans who have recovered from COVID-19. Those with persistent symptoms can be referred to appropriate services to improve their quality of life.