Discussion

This mixed-methods study aimed to explore the extent and lived experiences of cognitive symptoms in LC. The majority of participants in this study reported a decline in cognitive ability and concern about this change. Cognitive symptoms were among the most common symptoms reported alongside low energy, immobility and breathlessness. The experiences of subjective cognitive impairments included difficulties with memory, attention, language, executive function and processing speed. Cognitive symptoms had profound negative effects on participants’ ability to work, complete ADL, their psychological well-being and self-image, in some cases for >2 years after the initial infection. Participants attempted to manage their cognitive symptoms using strategies to reduce decision-making and mental load, facilitate memory and improve energy levels. However, the strategies were described as tedious and frustrating to implement, with mixed effectiveness. By combining quantitative and qualitative methods, this study found that cognitive symptoms are among the most prevalent symptoms in LC with considerable negative impacts on the well-being, functioning and daily lives of people with LC.

The findings of this study are consistent with previous research on both objective measures of cognitive impairment5 6 and the lived experiences of LC.17 18 Our findings strongly align with those of Callan et al,18 showing the experiences of subjective cognitive impairments, altered self-identity and the challenges of managing ongoing symptoms. Similar to previous studies, we found cognitive impairment in LC impacted occupational status, including reducing working hours, changing job roles and loss of pre-COVID-19 employment.25 Additionally, participants reported difficulties in completing ADL, which reflects previous research highlighting the functional limitations caused by cognitive decline in LC.26 High rates of mood disorders, such as anxiety and depression, were also prevalent among participants, reinforcing existing evidence that emotional and mental health challenges often accompany cognitive dysfunction in LC.27 Furthermore, many participants described living an altered lifestyle, consistent with prior findings that LC can affect individuals’ ability to engage in social, professional and personal activities.28 These results contribute to the growing literature documenting the far-reaching impact of ongoing cognitive impairment in LC. The novel findings of this study are the interactions found between the experiences of cognitive impairment, physical and psychological functioning and self-management of cognitive symptoms. Poor memory, attention and executive functioning affected many areas of daily functioning and contributed to a loss of self-worth and identity and reduced psychological well-being. Strategies used for self-management of cognitive symptoms involved living an altered lifestyle by reducing daily demands, activities, exercise and decision-making and implementing ‘reminders’ for tasks and regular rest, most of which added further distraction and frustration to daily life. This may reflect a vicious cycle of withdrawal from daily life, low mood and poor self-coping strategies that essentially exacerbate cognitive impairment.

Building on the findings of this study and prior research, we propose a new framework to conceptualise the factors contributing to cognitive impairment in LC, which appear to reflect an interacting symptom network.29 The Long-COVID Interacting Network of factors affecting Cognitive Symptoms (LINCS) framework integrates the findings of this study and previous research showing the neural, lifestyle and individual factors shaping actual and self-perceived cognitive dysfunction in LC (see figure 4). The possible interplay between psychological, physical and social factors, and the contribution of this to ongoing cognitive dysfunction following COVID-19, has previously been suggested by Callan et al.18 The need for this framework stems from the lack of evidence-based recommendations for clinicians regarding LC treatment.30 Furthermore, patients with LC have reported the challenging experiences of accessing primary care such as receiving inconsistent advice from healthcare professionals, difficulty accessing and navigating services and a lack of treatment options.31 32 This model provides a comprehensive framework for understanding the complexity of cognitive dysfunction in LC patients, which emphasises the multifaceted nature of the condition and may inform a more holistic approach to treatment by considering biological mechanisms and internal and external factors. The aim of presenting the LINCS framework is to guide future research and clinical practice towards more personalised, integrated and multidisciplinary care strategies for managing cognitive symptoms in LC, in line with previously published recommendations.31–33

• Download figure
• Open in new tab
• Download powerpoint

Figure 4

A conceptual framework of the Long-COVID Interacting Network of factors affecting Cognitive Symptoms.

The LINCS framework also highlights neuroinflammatory processes and brain structural changes as primary biological drivers of cognitive impairment in LC. Previous reviews have reported on the current understanding of the neurobiology of LC.12 34 The COVID-19 infection triggers an inflammatory response in the respiratory system, which can spread to the central nervous system (CNS). Within the CNS, cytokines, chemokines and activated microglial cells disrupt various neural cell types. This disruption interferes with the maintenance of myelin, impairs neuroplasticity and hinders hippocampal neurogenesis. It can also initiate neurotoxic responses in astrocytes, leading to a breakdown in neural circuits and cognitive impairment.13 COVID-19 infection can trigger antineural autoantibodies and T cells to provoke an autoimmune response, potentially leading to autoimmune encephalitis and contributing to continued neural damage.35 In more severe cases of COVID-19, nervous system injury can also result from hypoxia, further aggravating neuroinflammation.14 15 Structural changes to the brain following COVID-19 infection include reduced global brain size and grey matter thickness in the orbitofrontal cortex and parahippocampal gyrus.9 Several studies have highlighted the risks of developing abnormal tau pathology and cytotoxic amyloid protein aggregation in LC,10 11 which may indicate a future trajectory toward neurodegeneration.

Lifestyle factors also play a significant role in the cognitive impairment associated with LC. In a previous publication, we reported on the experiences and needs of individuals with LC and found that many participants experienced symptoms that significantly impacted their daily lives.24 Participants commonly reported challenges such as impaired physical mobility, cognitive dysfunction and social withdrawal. These difficulties often led to changes in employment, including reduced working hours, adjusting their role or being unable to return to work. Additionally, social withdrawal was frequently driven by a lack of understanding and support from family, friends and society, which contributed to feelings of shame and isolation. These changes in an individual’s engagement with their surroundings may reduce mental stimulation, further accelerating cognitive decline. Notably, both physical and social withdrawal, along with increased sedentary behaviour, are well-documented risk factors for the development of Dementia,36 37 highlighting the need to address these lifestyle factors when considering interventions for cognitive symptoms in LC patients.

The findings of the current study, in line with existing research, enhance our understanding of the individual factors that exacerbate cognitive symptoms in LC. Participants reported their efforts to recover by implementing coping strategies and managing fatigue and energy levels, while also dealing with the high prevalence of mood disorders. Prior evidence highlights the interconnectedness of these factors, suggesting they may collectively contribute to cognitive impairment in LC. For instance, fatigue and depression have been shown to impair cognition in conditions such as chronic fatigue syndrome and multiple sclerosis,38 39 and major depressive disorder is associated with reduced brain grey matter volume.40 Participants also described withdrawing from ADL as a way to manage symptoms. However, reduced cognitive, physical and social engagement, along with prolonged absence from work, have been associated with accelerated cognitive decline in mid to later adulthood.41–43 These findings emphasise the importance of addressing both the physical and psychological components in managing cognitive dysfunction in LC.

Given the evidence of accelerated cognitive ageing and dementia risk in LC,9 10 16 this clinical population of an estimated 2 million people in the UK2 may be the next generation at risk of developing age-related neurodegenerative diseases, fuelling a future epidemic of dementia in the UK. Currently, there is no approved treatment for LC,44 and the findings of this study highlight the vital need for an intervention to tackle the cognitive symptoms in LC, with aims to improve quality of life and reduce possible dementia risk. A recent scoping review evaluated treatments for cognitive impairment in LC and provided key recommendations for primary care management.30 The authors emphasised that a multidisciplinary, patient-centred approach is appropriate for addressing the cognitive symptoms. One of the main recommendations was for patients to adopt a healthy lifestyle, incorporating a balanced diet including key vitamins, micronutrients and probiotics, sufficient sleep, stress-reduction techniques, and appropriate physical activity. The WHO self-management booklet on LC provides a comprehensive strategy for returning to physical activity using a cautious pacing approach to mitigate overexertion.33 This approach contrasts with graded exercise therapy, which has been shown to potentially cause harm and worsen postexertional malaise in various chronic health conditions, including LC.31 Behavioural interventions were also identified, including cognitive training, mind–body interventions, music therapy and meditation.30 Overall, this scoping review underscored the importance of tailoring care plans to each individual, combining lifestyle modifications with medical and psychological interventions to create a comprehensive and adaptive treatment strategy for cognitive impairment.30 These recommendations align with the LINCS framework by advocating for a multidisciplinary and individualised approach to addressing the various factors which appear to exacerbate cognitive symptoms in LC. LC is a relatively new condition, and as such, the underlying pathology of cognitive impairment remains poorly understood and there is a current lack of high-quality evidence supporting targeted interventions for managing cognitive deficits in LC patients.30 Future research should prioritise identifying the precise mechanisms driving cognitive impairment in LC, including neuroinflammatory processes, neural dysregulation and neurovascular dysfunction.34 Additionally, there is a need for large-scale, high-quality, longitudinal studies to evaluate the effectiveness of both pharmacological and non-pharmacological interventions, such as cognitive rehabilitation and lifestyle modifications, in improving cognitive function. Developing standardised assessment tools and outcome measures will also be crucial to ensure consistency across studies and provide clearer guidance for clinical practice.30

The term ‘brain fog’ was used by some participants in this study to describe their cognitive symptoms, however previous evidence suggests the term lacks specificity and may not capture the severity of cognitive symptoms experienced in LC.18 The term ‘fog’ implies a perceptual deficit or ‘clouding’ of cognitive processes, whereas in this study, participants reported reduced processing speed, increased cognitive effort and a feeling of disconnection in the brain. Without the development of appropriate terminology to define these symptoms and a lack of recognition of the specific impairments to cognitive functioning, there is a barrier to medical diagnosis and the development of targeted cognitive interventions. An alternative code name has been proposed to describe the accelerated process of cognitive decline in pre-existing dementia following COVID-19, termed FADE-IN-MEMORY, that is, Fatigue, decreased Fluency, Attention deficit, Depression, Executive dysfunction, slowed INformation processing speed, and subcortical MEMORY impairment.45 The findings of this study show that FADE-IN-MEMORY might also be an appropriate term to describe the experience of cognitive symptoms in LC.

The strengths of this study include the rigorous and well-established methods to analyse the focus group data. The Framework Analysis23 is a data analysis technique that provides a structured yet flexible approach to processing qualitative data. By organising, coding, and conducting thematic analysis in a systematic manner, this method allows for efficient analysis of qualitative research while strengthening the credibility of the research process.46 The Framework Analysis is increasingly used in the analysis of qualitative data in multidisciplinary health research.46 The use of quantitative data collection to supplement the qualitative responses in this study allowed us to quantify the self-perceived change in cognitive abilities following LC and compare the severity of cognitive symptoms with other symptoms. However, the questionnaire rating scales were arbitrary, and the self-report nature of the questionnaire may not reflect an objective measure of cognitive functioning. Having said that, the extent of memory deficits following COVID-19 infection has been found to increase with the severity of self-reported ongoing symptoms,7 demonstrating the link between objective and subjective cognitive measures. One possibility for related future research would be to administer a brief test of global cognitive function, such as the Montreal Cognitive Assessment,47 to measure participants’ individual global cognitive function on the day of the focus group discussions. However, tests of global cognitive function primarily measure working memory and, therefore, may not capture the impairments in other cognitive domains participants reported in this study. There are also concerns that global screening tools, developed for identifying dementia and mild cognitive impairment, may lack sensitivity in reliability detecting cognitive deficits in LC.48 Furthermore, in this study, the self-report nature of the questionnaire complemented the qualitative data in which the overall aim was to investigate the lived experience of cognitive symptoms from the participants’ perspective, rather than to obtain an objective measurement of cognitive functioning. This study may be limited by the biased sample of mostly female and middle-aged participants, which prevented the comparison of possible age and gender differences in the experience of LC symptoms.

This mixed-methods study found that cognitive dysfunction was commonly reported by participants and had a significant impact on daily life and overall functioning. Participants were concerned about their cognitive decline and the limited options available for symptom management and treatment. There is a clear need for interventions that address the complex, multifactorial nature of cognitive impairment in LC. Without such targeted strategies, individuals with LC face an increased risk of accelerated cognitive ageing and the potential onset of dementia. This study introduced the LINCS framework and designed to provide a structured approach for clinicians to assess and manage the array of factors contributing to cognitive dysfunction in LC. By integrating multiple dimensions of cognitive health, the LINCS framework offers a valuable tool for both clinical practice and future research, which could be used to inform the development of interventions that are tailored to the needs of LC patients. Future high-quality, large-scale intervention studies are essential to identify effective treatments for cognitive dysfunction in individuals affected by LC.