Cognitive difficulties are amongst the most frequently reported sequelae following COVID-19 infection, even in those experiencing mild to moderate illness (Matos et al., 2021). Recent research has identified patterns of diminished cognitive performance on tests of memory and executive functioning in COVID-19 cases; however, the etiology of neurocognitive difficulties remains unclear (Delgado-Alonso et al., 2022). Emerging evidence has identified moderate associations between decreased performance on neuropsychological tests of memory and elevated anxiety and depression symptom reporting in COVID-19 patients. Similar associations are well-established in the literature in persons with anxiety and depression disorders, warranting further investigation as to whether mental health variables such as internalizing symptom severity may moderate the association between COVID-19 illness and cognitive difficulties. This study examined how internalizing symptoms as indexed by depression and anxiety symptom scales may differentially influence performance on neuropsychological tests of memory between persons who have and have not had COVID-19.

In this cross-sectional study, 104 adults aged 19-80, were recruited in Ontario and British Columbia, Canada; 84 adults met inclusion criteria and participated in neuropsychological testing. There were 40 participants who tested positive for COVID-19 infection (N=44 with no suspected exposures or confirmed diagnosis of COVID-19). Participants had no history of dementia, mild cognitive impairment, or other known neurological disorder. Anxiety and depression symptoms were measured using the Generalized Anxiety Disorder-7 (GAD-7) and Center for Epidemiologic Studies Depression Scale (CES-D) via self-report on Qualtrics. Memory encoding and delayed recognition performance were assessed using the Hopkins Verbal Learning Test Revised (HVLT-R) and the Neuropsychological Assessment Battery Shape Learning subtest (NAB-SL). To test for potential moderating effects of anxiety and depression symptoms on the association between COVID-19 infection status and memory performance, a series of multiple linear regressions were conducted. Age and sex were included as covariates in all analyses.

Moderation analyses revealed that the interaction between COVID-19 infection and anxiety symptoms accounted for a significant portion of variance in both HVLT-R recognition (B= -0.78, SE= 0.34, p<0.05) and NAB-SL delayed recognition scores (B= -0.83, SE= 0.35, p<0.05). Simple slopes analyses revealed that among participants who tested positive for COVID-19 infection, higher GAD-7 scores were associated with lower verbal and visual recognition scores. A similar interaction was observed between COVID-19 and depressive symptoms in accounting for variance in NAB-SL delayed recognition scores, however, for that model the threshold of p=0.05 was not met in our small sample (p=0.07).

Findings demonstrate that anxiety symptom severity had a moderating effect on the impact of COVID-19 on delayed retrieval of verbal and visual information from memory. Future work in a larger sample is needed to further elucidate the potential moderating role of depression on memory in COVID-19 positive persons, as the current work suggests that depression symptoms could have a similar impact as anxiety. Further identifying the relationships between key modifiable psychological factors such as anxiety and memory following COVID-19 infection will provide insight into potential interventions to minimize the negative effects of internalizing symptoms on long-term cognitive outcomes.