The cognitive sequalae of COVID-19 and long COVID - the inconspicuous wound of the pandemic

Abstract

A novel disease named coronavirus disease 2019 (COVID-19) was discovered in the year 2019, and soon after declared a pandemic by the World Health Organization. Coronaviruses are neurotropic in nature and since the emergence of COVID-19 many studies have reported neuropsychological symptoms in infected individuals, including headaches, dizziness, seizures, depression, and also cognitive deficits. These symptoms can persist for many weeks to months and are commonly referred to as long COVID. This thesis, therefore, aimed to examine the neuropsychological impact of COVID-19, more specifically on cognitive function and psychological well-being cross-sectionally in a working-age sample, and in a sub-sample longitudinally. Furthermore, it explored the impact of long COVID on brain structures, again in a working-age sample. Three empirical studies were conducted, study one was a behavioural study investigating the effects of COVID-19 on cognitive function (processing speed, attention, working memory, executive function, and memory), and the associations of physical and mental health (specifically, depression, anxiety, stress, and sleep) with cognitive function in adults (N = 222) from the general population. Study two involved a follow-up of the sample investigated in study one to determine the longitudinal impact of COVID-19 and long-COVID symptoms on cognitive function, mental health, and sleep. Study three used whole brain magnetic resonance imaging to examine the association of persistent COVID-19 symptoms with grey matter, white matter, cerebral spinal fluid and various subcortical brain volumes (accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus), and its association with cognitive function, mental health, and sleep in a working-age, general population sample (N = 43) of COVID-19 survivors. The findings of study one showed significantly larger processing speed intra-individual variability, on average, in the COVID group, relative to the non-COVID group, with no significant difference observed in other cognitive variables. However, participants who required hospitalisation due to their diagnosis of COVID-19, relative to those who did not, showed poorer cognitive function in multiple domains, and total long-COVID symptom load was negatively associated with performance in all cognitive domains. In study two, a trend-level improvement at the six-month follow-up was observed in processing speed intra-individual variability in the COVID group with no significant change in the non-COVID group. A significant reduction in total long-COVID symptom load occurred at follow-up, and this correlated with an improvement in executive function, especially in the non-hospitalised COVID group. However, cognitive disruption persisted in COVID group participants with a history of hospitalisation and/or long-COVID symptoms. In study three, total persistent COVID-19 symptom load was significantly associated with smaller putamen volume, multiple cognitive domains, mental health, and sleep quality (medium-to-large effect sizes). Smaller putamen volume was also correlated with a disruption in multiple cognitive domains and poorer sleep quality, though only the relationship between lower executive function and persistent COVID-19 symptom load was mediated by smaller putamen volume. In conclusion, the findings showed a negative impact of COVID-19 on cognitive function, although to a lesser extent in this working-age sample than those reported earlier in older samples, and some improvement was visible after a six-month period. Hospitalisation history and long-COVID symptoms, however, were associated with wide-spread disruption in cognitive function and poor sleep quality. The disruption in cognitive function, in particular executive function, due to persistent COVID-19 symptoms seemed to be mediated by smaller putamen volume. These findings provide further insight into the relationship between COVID-19 and cognitive function, its effect on the brain, and the potential serious impact of hospitalisation history and long COVID on cognitive function and brain health. Overall, our findings suggest a need for longitudinal monitoring as well as remediation and support for those individuals who were hospitalised when acutely ill and/or have a diagnosis of long COVID.