Cognitive and mental health trajectories of COVID-19: Role of hospitalisation and long-COVID symptoms

Background There is considerable evidence of cognitive impairment post COVID-19, especially in individuals with long-COVID symptoms, but limited research objectively evaluating whether such impairment attenuates or resolves over time, especially in young and middle-aged adults. Methods Follow-up assessments (T2) of cognitive function (processing speed, attention, working memory, executive function, memory) and mental health were conducted in 138 adults (18–69 years) who had been assessed 6 months earlier (T1). Of these, 88 had a confirmed history of COVID-19 at T1 assessment (≥20 days post-diagnosis) and were also followed-up on COVID-19-related symptoms (acute and long-COVID); 50 adults had no known COVID-19 history at any point up to their T2 assessment. Results From T1 to T2, a trend-level improvement occurred in intra-individual variability in processing speed in the COVID, relative to the non-COVID group. However, longer response/task completion times persisted in participants with COVID-19-related hospitalisation relative to those without COVID-19-related hospitalisation and non-COVID controls. There was a significant reduction in long-COVID symptom load, which correlated with improved executive function in non-hospitalised COVID-19 participants. The COVID group continued to self-report poorer mental health, irrespective of hospitalisation history, relative to non-COVID group. Conclusions Although some cognitive improvement has occurred over a 6-month period in young and middle-aged COVID-19 survivors, cognitive impairment persists in those with a history of COVID-19-related hospitalisation and/or long-COVID symptoms. Continuous follow-up assessments are required to determine whether cognitive function improves or possibly worsens, over time in hospitalised and long-COVID participants.


Introduction
Since the start of the coronavirus disease 2019 (COVID-19) pandemic, a vast amount of literature has acknowledged the psychological issues and cognitive disruption experienced by survivors [1][2][3][4][5][6].Living with COVID-19 has become the new normal, yet there is still uncertainty around the longer-term effects of COVID-19 on physical and mental well-being, given marked betweenstudy variability in the proportion of survivors reporting cognitive and mental health impairments post-acute infection [7].In a recent review [8], 21-65% of adults with long-COVID symptoms (≥12 weeks) were found to have some level of cognitive impairment, while another review [9] reported poor mental health for up to 6 months post a COVID-19 diagnosis.It is unclear at present whether COVID-19-related cognitive impairment and psychological symptoms attenuate or resolve over time and, if so, how long after a COVID-19 diagnosis an improvement can be seen, especially in young and middle-aged adults.
Previous studies have suggested some improvement in cognitive function [10][11][12][13][14][15] and psychological well-being [16], especially at longer (≥6 months) follow-ups, but these mostly examined older adults (mean age >50 years) [10,11,15,16] and focused on severely ill or hospitalised COVID-19 patients [12][13][14][15].As these groups are likely to need longer to recover from COVID-19 and its adverse cognitive and mental health impacts, with possible co-morbidities exacerbating and/or complicating post-COVID recovery, their findings may not generalise to working-age adults in the general population.A recent study [17] involving a large sample, though again with an over-representation of middle age adults (≥50 years), showed persistent cognitive deficits at about 2 years post-infection, especially in individuals who had experienced the symptoms for ≥12 weeks and/or a severe infection, or were experiencing ongoing symptoms.Encouragingly, the sub-group of adults who self-reported a full recovery showed no such deficits [17].There is clearly a need for further work to fully characterise the cognitive trajectory of COVID-19 in survivors with varying levels of symptoms and younger age groups.
In our recent study [18] investigating the impact of COVID-19 on cognitive function and mental health in a working-age sample (mean age: 38.70 ± 12.08), we had found a limited cognitive impact of COVID-19 diagnosis, with only intra-individual variability in processing speed being significantly increased in COVID-19 survivors, compared to non-COVID controls.There was, however, multifaceted cognitive impairment in association with long-COVID symptoms.Mental health and sleep quality were also worse in COVID-19 survivors, relative to non-COVID controls.Here, with a further assessment (6-month follow-up) of this previously assessed sample [18], we aimed to examine: (i) the longitudinal impact of COVID-19 on cognitive function, mental health, and sleep, first, on average, and then classified by COVID-19-related hospitalisation; and (ii) changes in long-COVID symptom load and their association with cognitive function, mental health and wellbeing at 6 months post the initial assessment.Based on previous findings [10-12, 14, 16, 19], we predicted: (i) a change towards normalisation of cognitive function, mental health, and sleep from study entry (T1) [18] to the 6-month follow-up (T2) assessments, on average, in the COVID group, relative to non-COVID group, and (ii) persistently impaired cognitive function, mental health, and sleep in participants with a history of COVID-19-related hospitalisation and/or ongoing long-COVID symptoms.
The study was approved by the College of Health, Medicine and Life Sciences Research Ethics Committee, Brunel University London (26518-A-Sep/2021-34167-1).All participants provided informed written consent and received £10 (Amazon voucher) for their time.

Measures and procedures
As described in Vakani et al. [18], data on demographics, mental health, and sleep were collected using self-report measures administered via Qualtrics (an online survey tool), taking ˜45 minutes in total to complete.Additionally, the COVID groups were asked to detail their COVID-19 diagnosis, acute symptoms at the time of infection, subjective psychological well-being and cognitive impairment, and chronic long-COVID symptoms at both T1 and T2.Cognitive data (T1 and T2) were collected using the selfadministered MyCognition [20] (MyCQ) PRO mobile application, taking ˜15 minutes to complete.

Cognitive function
The MyCQ mobile application tool (approved by the National Health Service in the UK) assesses processing speed, attention, working memory, executive function, and memory domains, using digital versions of commonly utilised neuropsychological tests validated against the Cambridge Neuropsychological Automated Test Battery [21][22][23].As described previously [18], Processing Speed was assessed using a simple reaction time (RT) task, Attention using a choice RT task, Working Memory using the 2-back task, Executive Function using the Trail-Making B task, and memory was assessed using a visual recognition memory task (for further details, see Table 1).

Mental health and sleep
The following two self-report scales were used: The Depression, Anxiety and Stress Scale-21 [24] assessed depression, anxiety, and stress with corresponding seven-item sub-scales.Each item is rated by participants on a four-point scale according to how often in the past week it applied to them.Higher scores indicate higher levels (severity) of symptoms.Internal consistency for all sub-scales was good-to-excellent (Cronbach's a ≥ 0.82) in this sample.

Statistical analysis
We first examined the demographic and other characteristics of study participants who provided both T1 and T2 data (n = 138) versus those with only T1 data (n = 84; not included in any further analysis), out of 222 participants from Vakani et al. [18], to  Vakani et al.
determine if there were any factors associated with nonvolunteering (especially in the COVID group) for T2 assessment.
Next, to examine possible changes from T1 to T2 in the COVID group (n = 88), relative to those in the non-COVID group (n = 50), we used a 2 (Group: COVID, non-COVID) × 2 (Time: T1, T2) repeated-measures analysis of variance (ANOVA), separately for each cognitive variable, with Group as a between-subjects factor and Time as a within-subjects factor.To examine possible differences in cognitive and mental health changes of hospitalised versus non-hospitalised COVID participants, we conducted 3 (Group Hos- pitalisation : Hospitalised COVID, Non-hospitalised COVID, non-COVID) × 2 (Time: T1, T2) repeated-measures ANOVAs; and confirmed any significant main or interaction effects after co-varying for age, given a trend-level age difference between hospitalised and nonhospitalised participants (see Results).To examine a change from T1 to T2 in total long-COVID symptom load (a sum of all symptom ratings), we ran a 2 (Hospitalisation: Hospitalised COVID, Non- hospitalised COVID) × 2 (Time: T1, T2) ANOVA with Hospitalisation as a between-subjects factor and Time as a within-subjects factor, co-varying for age.All ANOVAs were initially conducted with Sex entered as another between-subjects factor but Sex was then removed, as there were no main or interactive effects involving Sex, and the current sample has a relatively smaller number of males.Significant main effects and interactions from ANOVAs were followed up with the analysis of simple main effects and post hoc comparisons, as appropriate.Effect sizes, where reported, are partial eta squared (η p 2 ; the proportion of variance associated with a factor).Finally, the relationship between changes (T1 to T2) in total long-COVID symptom load and cognitive function was examined using Pearson correlations.
All analyses were performed using the Statistical Package for Social Sciences (version 28; IBM, New York, USA).The data distribution on all variables met the assumptions of parametric statistical procedures.Alpha level for testing the significance of effects was maintained at p ≤ 0.05.

Sample characteristics
About two-thirds (62%) of the sample with T1 assessments (n = 222) [18] provided T2 data (n = 138) (Figure 1).Fifteen (75%) of 20 participants with a history of hospitalisation at T1 also provided T2 data.There was no age difference [t(206) = 0.36, p = 0.72] between the groups with both T1 and T2 assessments and only T1 assessment.Other characteristics were also comparable for these (T1 and T2, T1 only) groups (Supplementary Table S1).COVID participants who completed both assessments versus those with only T1 assessment also had comparable demographics, COVID-related symptoms (Supplementary Tables S1 and S2), as well as cognitive and mental health characteristics (Supplementary Table S3).
For attention, there was only a main effect of Group in RTs [F(1,123) = 4.67, p = 0.03, η p 2 = 0.04], showing slower RTs on both occasions in the COVID group, relative to the non-COVID group (Table 3).
For working memory, executive function, and memory tasks, no significant main effects or interactions were found.
For working memory (RA, %), there was only a marginally significant main effect of Time [F(1,131) = 3.98, p = 0.05, η p 2 = 0.03; higher RA at T2 than T1], which became non-significant after co-varying for age [F(1,130) = 3.09, p = 0.08, η p 2 = 0.02] (Table 4).For executive function, there was a main effect of Group Hospita- lisation    the non-COVID group.Additionally, there was a main effect of Time for depression [F(1,136) = 4.73, p = 0.03, η p 2 = 0.03] explained by lower depression at T2 relative to T1 in both groups (Table 5).No significant effects (only trends) were found for stress.The Group Effect was present on all PSQI sub-components, indicating poorer sleep quality in the COVID compared to the non-COVID group.

Discussion
This investigation focused on charting the cognitive and mental health trajectories of COVID-19 in a UK adult sample (≤69 years) that had been assessed 6 months earlier (T1) [18].The findings showed: (i) a trend-level improvement (from T1 to T2) in processing speed RT variability but a continued slowing on the attention task (longer RTs) in the COVID, relative to the non-COVID group; (ii) within the COVID group, poorer cognitive function (processing speed, attention, executive function) in previously hospitalised, relative to non-hospitalised, participants on both occasions of testing (T1, T2); (iii) higher depression and anxiety, and reduced sleep quality in the COVID group, relative to the non-COVID group, at both T1 and T2, though an improvement in depression was visible in non-hospitalised COVID participants; (iv) reduced overall long-COVID symptom load at T2 compared to T1, particularly in non-hospitalised COVID participants (only a nonsignificant reduction in hospitalised COVID participants); (v) association between higher long-COVID symptom load and poorer performance on most cognitive indices; (vi) an association between reduced long-COVID symptom load and improved executive function at T2, again observed only in non-hospitalised COVID participants; and (vii) medium-sized associations between reduced long-COVID symptom load and improved mental health and well-being.
Regarding the impact of COVID-19 on cognitive function, in our previous study involving this working-age sample [18] the only cognitive variable to show a robust adverse impact of COVID-19 (regardless of hospitalisation history) was intra-individual variability in processing speed RTs, with larger RT variability in COVID-19 survivors compared to both non-COVID controls and their own pre-pandemic level (sub-sample for whom such data were available).The present investigation, encouragingly, demonstrated a trend towards normalisation (from T1 to T2) in this measure and thus suggested, on average, only a limited and possibly reversible adverse cognitive effects of COVID-19 in a working-age population.However, participants who had required COVID-19 hospitalisation showed continued cognitive impairment, a finding which is well documented in the literature, with hospitalisation status significantly impacting cognitive function and the speed of any possible recovery months after initial infection and hospitalisation [13,[26][27][28][29][30][31].Our findings are also consistent with earlier findings of Del Brutto et al. [11] who observed an improvement towards normalisation in Montreal Cognitive Assessment scores at 18 months post-infection in older adults (mean age: 62.7 years) who had a history of mild COVID-19 and no hospitalisation and had shown a significant impairment when assessed earlier at 6 months post-infection.Their findings, taken together with ours, suggest cognitive improvement towards normalisation in COVID-19 survivors, especially without COVID-19-related hospitalisation, and that this recovery may occur relatively earlier (6-12 months post-COVID-19) in younger/working-age samples.Hospitalised COVID participants in our and other samples may show persistent cognitive impairment as a consequence of COVID-19-related structural and/or functional changes in the brain [32,33], which needs to be explored further.
Regarding total long-COVID symptom load, a significant reduction was observed from T1 to T2, which significantly correlated with improved executive function only in non-hospitalised COVID participants, again suggesting a stronger/faster recovery in those without a hospitalisation history.However, for the majority of the sample, regardless of hospitalisation history, various self-Table 6. Descriptive statistics (non-COVID group presented in Table 5) and results of the repeated-measures Group Hospitalisation  reported long-COVID symptoms were still present at T2, with sizeable associations between long-COVID symptom load and cognitive function, in line with previous findings [34,35].Mental health and sleep were still impacted at T2 in COVID-19 survivors, irrespective of hospitalisation history, though depression was lower at T2 than T1 in those without COVID-19-related hospitalisation.Notably, sleep appeared to be the most impacted.Interestingly, recent findings show that people with a COVID-19 history are more likely to be a late/evening chronotype, compared to those with no known history of COVID-19 [36], and late chronotype itself has been associated with poor quality of sleep [37][38][39].There are also suggestions that the lockdowns resulted in delayed chronotype due to the altered social schedule, such as, reduced exposure to sunlight coupled together with longer and later sleeping patterns, which can all contribute to reduced quality of sleep [37,40,41].It is possible that those with a history of COVID-19 were more impacted by subsequent lockdowns and shifted more towards eveningness and consequently poor sleep quality.
The strengths of this follow-up study include: (i) the response rate was reasonable with about two-thirds of the original sample [18] available for this investigation, and (ii) the current sample was representative of the original sample.Nonetheless, the limitation of relying on self-report for COVID-19-related information inherent to our earlier study [18] also applies to this study.Despite this limitation, the findings may have important implications.For example, consistently poor(er) performance observed in hospitalised COVID participants on tasks which emphasise speed could   European Psychiatry negatively impact daily activities such as driving [42] and may present as a bio-marker for accelerated aging [13].Given this, frequent follow-ups of COVID-    Vakani et al.
(Pearson's r) of total long-COVID symptom load (at T1 and T2, and the change from T1 to T2) with cognitive function and mental health (at T1 and T2, and the change from T1 to T2) Correlations of total long-COVID symptom load with cognitive function, mental health, and sleep Correlations between decrease in total long-COVID symptom load from T1 to T2 a Abbreviations: ms, milliseconds; RT, reaction time.a Long-COVID data not available for 6 participants (1 hospitalised, 5 non-hospitalised).

Table 1 .
Cognitive domains, tests, and indices examined through MyCognition's mobile application

Table 5 .
Descriptive statistics and results of the repeated-measures Group (COVID, non-COVID) × Time (T1, T2) analysis of variance (ANOVA) on mental health and sleep measures DASS-21, The Depression, Anxiety and Stress Scale-21; PSQI, Pittsburgh Sleep Quality Index.Higher scores indicate higher levels of depression, anxiety and stress.Higher scores indicate poor sleep quality.a

Table 7 .
19 survivors, especially those with COVID-19-related hospitalisation and/or long-COVID symptoms, are needed to assess any potential worsening and/or improvement in cognitive function over time.Moreover, remedial interventions, such as mindfulness training, may help reduce cognitive slowing [43] in diverse samples impacted by COVID-19.However, those participants who had required hospitalisation due to COVID-19, compared to those who did not, continued to display multifaceted cognitive impairment.Continuous follow-up assessments are required to determine whether cognitive improvement continues over time in COVID-19 survivors, particularly in hospitalised/long-COVID participants or whether cognitive function in this sub-group worsens further unless addressed by suitable interventions.material.The supplementary material for this article can be found at https://doi.org/10.1192/j.eurpsy.2024.7.Associations