1 Introduction

The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has had an unprecedented global impact, affecting millions of people and overwhelming healthcare systems worldwide [1, 2]. Initially characterized primarily as a respiratory illness, it soon became evident that COVID-19 is a multisystem disease with significant neurological implications [3,4,5]. While respiratory symptoms such as cough, fever, and shortness of breath are commonly recognized, a growing body of evidence indicates that SARS-CoV-2 can also affect the nervous system, leading to various neurological complications [6, 7].

Neurological manifestations, including cognitive impairments, in COVID-19 patients, have been diverse, ranging from mild symptoms like headache and anosmia (loss of smell) to severe conditions such as encephalopathy, stroke, and Guillain-Barré syndrome [8,9,10]. These complications can occur during the acute phase of the infection or emerge as part of the post-acute sequelae, often referred to as "long COVID [11, 12]." Long COVID is a broad term encompassing persistent symptoms beyond 4 weeks after initial infection, affecting multiple organ systems [11]. The World Health Organization (WHO) defines Long COVID as a condition occurring in individuals with a history of SARS-CoV-2 infection, presenting with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis [13]. The mechanisms behind these cognitive effects are multifactorial, involving direct viral invasion, immune-mediated damage, and thromboembolic events [2].

The rationale for this study stems from the urgent need to understand the full spectrum of cognitive outcomes in COVID-19 patients. Despite the substantial number of reported cases, there remains a lack of comprehensive data on the consequences of cognitive complications associated with COVID-19 [10, 11]. This knowledge gap significantly affects patient management, rehabilitation, and resource allocation. Furthermore, as the pandemic evolves and the acute phase transitions into long-term management, the healthcare system must adapt to address the lingering effects of the virus. Understanding cognitive outcomes is crucial for developing targeted therapies and supportive measures to improve the quality of life and functional outcomes for COVID-19 survivors. Therefore, this paper aims to investigate the cognitive impairments in COVID-19 patients.

2 Methods

A literature search was conducted across PubMed, Scopus, Google Scholar, Web of Science, and the Cochrane Library. The search strategy utilized a combination of Medical Subject Headings (MeSH) terms and free-text keywords related to COVID-19 and cognitive impairment. The following Boolean search query was applied across databases where applicable ((COVID-19 OR SARS-CoV-2) AND (cognitive decline OR cognitive impairment OR brain fog OR memory OR attention OR executive function)). Additional filters were applied to limit studies to those published between January 2020 and March 2024. Reference lists of relevant articles were manually screened to identify additional studies.

2.1 Eligibility criteria

Inclusion criteria:

  • Peer-reviewed clinical trials, observational studies, and case reports focusing on COVID-19-related cognitive complications.

  • Studies assessing cognitive impairment through validated neuropsychological tests, imaging, or clinical assessments.

  • Studies involving adult and pediatric populations affected by COVID-19.

  • Studies where SARS-CoV-2 infection was confirmed through RT-PCR, antigen testing, or serology.

Exclusion criteria:

  • Non-English articles (due to translation constraints).

2.2 Study selection process

The study selection process followed PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The initial search retrieved [1903] articles. After removing duplicates ([1165]), title and abstract screening excluded [129] articles based on irrelevance. Full-text review of [27] articles led to the exclusion of [9] studies. Finally, [18] studies met all inclusion criteria and were included in this review. A PRISMA flowchart (Fig. 1) details the screening and selection process.

Fig. 1
figure 1

PRISMA flowchart

Full size image

2.3 Data extraction and synthesis

A data extraction form was used to collect information on study design, sample size, patient demographics, cognitive assessment tools, and key findings. A narrative synthesis approach was employed to integrate findings, identify common patterns, and discuss variations across studies.

3 Results

Eighteen studies [13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30] were included in this review. Study characteristics are shown in Table 1. The sample sizes of these studies ranged from 12 to over 81,000 participants, with the age of participants spanning from 18 to 60 years. Various methods were employed to assess cognitive function, including standardized neuropsychological tests and batteries and self-reported cognitive symptom questionnaires. The most commonly affected cognitive domains identified were attention, memory, executive function, and processing speed. Hospitalization due to COVID-19 appeared to be associated with a higher risk of cognitive impairment. Additionally, some studies found associations between cognitive impairment and pre-existing conditions, mental health symptoms, and lung function. Among the included studies, 8 were prospective in design, meaning they measured cognitive function prior to COVID-19 infection and followed participants over time to assess post-infection cognitive changes.

Table 1 Study characteristics
Full size table

3.1 Prevalence of cognitive decline

The ongoing COVID-19 pandemic has not only presented significant challenges for physical health but has also raised concerns regarding its potential neurocognitive sequelae. Recent studies have demonstrated a concerning association between COVID-19 infection and cognitive decline, with reported prevalence rates varying widely from 17.5% to 68.5% [16, 22, 24]. An observational cohort study by Birberg et al. [13] found that 37% of individuals who recovered from COVID-19 exhibited some form of cognitive impairment, while a study conducted by Largent et al. [14] indicated a 25.9% prevalence of cognitive deficits in a cohort of hospitalized patients.

This variability in prevalence is attributed to several methodological differences across studies, including variations in cognitive assessment tools (Mini-Mental et al. [MMSE], Montreal Cognitive Assessment [MoCA]) and diagnostic criteria for cognitive impairment, as well as potential disparities in the severity of initial COVID-19 infection among participants [17, 25,26,27]. Studies utilizing more comprehensive neuropsychological testing, such as the Cambridge Neuropsychological Test Automated Battery (CANTAB), tend to report higher rates of cognitive decline than those relying on more straightforward screening tools [22]. Furthermore, self-reported studies often reveal discrepancies in prevalence rates compared to clinical assessments [14]. A study by Largent et al. found that 42% of participants reported cognitive difficulties, but when subjected to standardized cognitive assessments, only 28% met the criteria for cognitive impairment [14, 19].

A particularly concerning aspect of this emerging body of evidence is the persistence of cognitive deficits. Research indicates that these impairments are not transient and can endure for several months following the initial infection [19, 22]. A longitudinal study by Krishnan et al. demonstrated that 25% of patients experienced persistent cognitive difficulties, particularly in attention and memory, even 6 months post-infection [18]. These cognitive impairments have significant implications for daily functioning; for example, a study highlighted that 30% of participants reported difficulties completing daily tasks, while 20% faced challenges in their work performance [21].

The severity of the initial COVID-19 infection is a relevant factor, with hospitalized patients exhibiting a greater degree of cognitive decline compared to those with milder cases. A study by Ollila et al. found that cognitive decline was observed in 75% of patients admitted to intensive care, compared to only 40% among those treated in outpatient settings [19]. Additionally, pre-existing health conditions, such as depression, anxiety, and other comorbidities, may elevate the risk and severity of post-COVID-19 cognitive decline. Patients with a history of depression were found to have a 1.5 to twofold increased risk of cognitive impairment post-infection [15, 29].

3.2 Areas of cognitive impairment

Numerous studies have identified specific cognitive domains significantly impaired following COVID-19 infection, highlighting widespread deficits in attention, memory, executive function, and processing speed.

3.2.1 Attention

Birberg et al. [13] reported a mean RBANS Global Cognition Score of 83.4, with 37% of participants scoring below the established cut-off for cognitive impairment. Notably, 30% of the cohort demonstrated significant deficits in attention, characterized by difficulty maintaining focus during conversations, increased distractibility during tasks, and challenges sustaining attention over prolonged periods. Furthermore, this study highlighted a positive correlation between neurocognitive performance and the length of hospital stay. In addition, the study by Krishnan et al. [18] examined cognitive profiles in individuals with persistent symptoms post-COVID-19. Among their sample of 200 participants, attention deficits were prevalent, with 45% reporting difficulties in maintaining focus, which correlated with higher levels of anxiety and fatigue. Another study by Becker et al. [27] revealed that attention deficits were prevalent in 65% of participants hospitalized due to severe COVID-19. Furthermore, Hampshire et al. [23] analyzed data from over 81,000 participants. They found significant cognitive deficits in attention among those who had recovered from COVID-19, with a notable reduction in attentional capacity compared to non-infected controls. Specifically, approximately 20% of individuals reported difficulties in tasks requiring sustained attention, indicating that attention-related cognitive impairments may be a widespread consequence of COVID-19, affecting various demographic groups.

3.2.2 Memory

COVID-19 infection appears to disrupt both short-term and long-term memory processes. Méndez et al. [24] reported that among a cohort of COVID-19 survivors, a substantial number exhibited difficulties in remembering new verbal information, such as names of colleagues or recently added grocery items. Their findings noted that approximately 40% of participants struggled with verbal memory tasks, which are essential for effective communication and daily task completion. In addition, a study by Herman et al. [15], which utilized the Cognitive Failures Questionnaire to assess cognitive functioning in a population in Indonesia, found that 55% of respondents reported significant memory lapses, particularly in recalling recent events and new information. Furthermore, Miskowiak et al. [22] found that 44–53% of patients exhibited clinically significant impairments in working memory and executive functions. This decline in working memory was associated with poorer daily functioning and overall quality of life. Notably, older patients and those hospitalized during their COVID-19 infection showed more pronounced memory deficits, indicating that demographic and clinical factors may play a role in the severity of memory impairments. Becker et al. [27] also highlighted the vulnerability of verbal memory in post-COVID-19 patients, noting that participants reported difficulties recalling names, tasks, and appointments. These impairments were prevalent in 60% of the cohort and were linked to factors such as age, pre-existing health conditions, and the severity of the COVID-19 infection.

3.2.3 Executive function

Executive function is another critical area significantly impacted by COVID-19. Ollila et al. [19] conducted a prospective controlled cohort study involving 213 patients, comparing cognitive performance between ICU-treated COVID-19 patients, home-isolated patients, and non-COVID controls. The study found that ICU patients exhibited significant long-term cognitive impairments, mainly executive functions. Cognitive performance scores were markedly lower in ICU patients compared to home-isolated and non-COVID controls. Specifically, 45% of ICU patients demonstrated deficits in planning, organization, and problem-solving abilities, which are vital for effective daily functioning. Further supporting these findings, Birberg et al. [13] highlighted that executive function deficits were prevalent among their cohort of COVID-19 survivors, with 30% of participants reporting challenges in tasks requiring higher cognitive processes. The study noted that issues with executive function led to difficulties in multitasking and managing daily responsibilities, underscoring the real-world implications of these cognitive impairments. Moreover, Krishnan et al. [19] observed mild cognitive deficits in executive function among patients with persistent post-COVID-19 symptoms. Their findings indicated that approximately 37% of participants reported significant struggles with executive tasks, such as initiating and organizing tasks, which are essential for professional and personal responsibilities. The study also noted a high prevalence of mood disorders and fatigue, suggesting that emotional and psychological factors may exacerbate executive dysfunction. Hampshire et al. [25] conducted a more extensive analysis of over 81,000 participants and found that individuals who had recovered from COVID-19 exhibited significant impairments in multiple cognitive domains, including executive function. They reported that the cognitive deficits affected the ability to plan and execute tasks, with nearly 50% of participants indicating difficulties in these areas.

3.2.4 Processing speed

Processing speed has also been adversely affected by COVID-19. Largent et al. [14] conducted a longitudinal observational study involving 3908 COVID-19-positive individuals, revealing that 25.9% reported cognitive symptoms. Among these individuals, a considerable proportion experienced difficulties with processing speed, which manifested as challenges in keeping up with fast-paced conversations and prolonged response times in everyday tasks. The study indicated that individuals experiencing cognitive symptoms had a 2.5-fold increased likelihood of encountering significant processing speed deficits, particularly among those aged 40–49 years and those with pre-existing health conditions. Complementing these findings, Herman et al. [15] assessed cognitive failures within a longitudinal framework and found that cognitive speed was notably impaired among participants, with an average Cognitive Failures Questionnaire score of 45.6. Participants reported frequent issues in daily life, such as losing track of conversations and difficulty managing multiple tasks simultaneously, further underscoring the challenges posed by slowed processing speed. In a study conducted by Abramoff et al. [16], 324 COVID-19 survivors were evaluated, revealing that 38% experienced severe anxiety and 31.8% reported severe depression, both of which were correlated with impaired processing speed. The authors noted that emotional distress appeared to exacerbate cognitive symptoms, complicating the recovery process.

3.2.5 Age-associated cognitive domains

Age is a significant factor influencing cognitive performance post-COVID-19. Studies indicate that older adults, particularly those over the age of 65, are particularly susceptible to cognitive decline, experiencing more severe cognitive deficits following infection [18, 23]. Herman et al. [15] reported that older participants reported higher average Cognitive Failures Questionnaire scores. The study demonstrated that cognitive failure was linked to age, with older adults (over 60) reporting an 18% increase in cognitive complaints compared to younger adults. Furthermore, Largent et al. [14] identified that cognitive symptoms were particularly pronounced in individuals aged 40–49 years, but this age group still had lower cognitive deficits than those over 65. Among the older population, they noted that 54% of older adults reported moderate to severe cognitive symptoms.

3.3 Risk factors for cognitive decline

While the link between COVID-19 infection and cognitive decline is established, it is crucial to identify the factors elevating the risk of experiencing these impairments.

3.3.1 Severity of initial COVID-19 infection

A growing body of studies suggests a correlation between the severity of the initial COVID-19 infection and the degree of subsequent cognitive decline. Birberg et al. [13] highlighted that hospitalized patients exhibited a significantly higher risk for developing cognitive impairments, with their study showing that 37% of participants scored below the cognitive impairment cut-off on the RBANS Global Cognition Score. Furthermore, those with more extended hospital stays were more likely to experience deficits in attention and memory, suggesting a direct link between the severity of illness and cognitive outcomes. Similarly, Ollila et al. [19] found that 45% of ICU patients showed long-term cognitive impairments in executive function compared to home-isolated patients. This finding supports the notion that the biological processes associated with a robust immune response to the virus might contribute to neurological dysfunction.

3.3.2 Pre-existing health conditions

The presence of certain pre-existing health conditions heightens the risk and severity of cognitive decline following COVID-19 infection. Conditions that compromise vascular health or increase inflammation, such as diabetes and cardiovascular disease, could exacerbate the neurological effects of COVID-19. For instance, Largent et al. [14] identified that individuals with pre-existing health conditions had a 2.5-fold increased likelihood of experiencing significant cognitive deficits post-infection, with older adults being particularly vulnerable. Abramoff et al. [16] also noted that cognitive outcomes were poorer among Black and low-income patients, indicating that socioeconomic factors may intersect with health conditions to influence cognitive decline.

3.3.3 Pre-existing mental health conditions

Emerging evidence suggests a potential link between pre-existing mental health conditions, such as depression and anxiety, and post-COVID-19 cognitive decline. Krishnan et al. [18] found that individuals with confirmed COVID-19 and persistent cognitive complaints exhibited high prevalence rates of mood disorders and fatigue. The study highlighted that 31.8% of participants experienced severe anxiety, suggesting that mental health conditions could exacerbate the subjective experience of cognitive difficulties.

3.4 Potential contributing factors

Emerging evidence suggests that several factors beyond COVID-19 infection itself may contribute to cognitive decline in survivors. A multifaceted approach is necessary to understand how various biological, psychological, and social determinants interplay in the context of post-COVID cognitive outcomes.

3.4.1 Neuroinflammation and hypoxia

Neuroinflammation, characterized by a state of chronic low-grade inflammation in the brain, has been proposed as a critical contributor to post-COVID-19 cognitive decline [26, 29]. This inflammatory response can damage neural tissue and disrupt normal cognitive functions. Hypoxia, a potential consequence of severe COVID-19 infection, particularly among hospitalized patients, is also crucial to consider. Herman et al. and Chen et al. suggest that hypoxia may contribute to cognitive decline by impairing cerebral blood flow, thereby hindering the delivery of oxygen and nutrients to neurons. This impaired perfusion can result in significant deficits in cognitive functions, particularly in attention and memory [15, 20].

3.4.2 Psychological factors

The psychological impact of COVID-19 infection—including stress, anxiety, and depression—should not be overlooked as a potential contributor to cognitive decline [15, 23]. These psychological factors can independently affect critical cognitive domains such as attention, memory, and executive function. Furthermore, they exacerbate the subjective experience of cognitive difficulties among individuals experiencing post-COVID-19 cognitive decline. For example, Krishnan et al. identified a high prevalence of mood disorders among COVID-19 survivors, indicating that mental health status plays a significant role in cognitive outcomes. Longitudinal studies are necessary to disentangle the independent and interactive effects of psychological factors and biological mechanisms on post-COVID-19 cognitive decline. It is essential to recognize that while the cognitive impairments observed may be attributed to neurobiological changes due to the virus, the psychological distress experienced during and after infection can significantly impact patients' cognitive experiences.

3.4.3 Socioeconomic and racial disparities

Socioeconomic status (SES) and race are additional factors that may influence cognitive outcomes following COVID-19 infection [25,26,27,28]. Social determinants of health—such as access to quality healthcare, nutrition, and education—play a critical role in shaping health outcomes. For instance, individuals from lower socioeconomic backgrounds may have a higher prevalence of pre-existing health conditions, such as cardiovascular disease or diabetes, which could exacerbate the neurological effects of COVID-19. The intersectionality of race and SES may also lead to disparities in cognitive decline post-COVID-19, underscoring the need for targeted interventions in high-risk populations.

3.4.4 The role of vaccination

The impact of COVID-19 vaccination on cognitive outcomes is an evolving area of investigation. While some studies suggest that vaccination may offer a protective effect against cognitive decline [29], the evidence is still inconclusive. For example, Miskowiak et al. found that vaccinated individuals exhibited lower cognitive impairments rates than unvaccinated counterparts. However, more research is needed to confirm these findings and understand how vaccination may influence cognitive recovery following infection [28, 29].

3.4.5 Limitations and considerations

Acknowledging the limitations of existing studies regarding cognitive decline post-COVID-19 is crucial. Factors such as hypoxia, psychological distress, and other medical disorders must be emphasized when interpreting cognitive outcomes. A comprehensive understanding of the cognitive profiles of COVID-19 survivors requires consideration of these variables. The presence of other medical disorders may complicate the relationship between COVID-19 and cognitive decline, and future studies should focus on disentangling these complex interactions.

4 Discussion

The reviewed studies showed a significant association between COVID-19 infection and cognitive decline in survivors. The most commonly affected cognitive domains in COVID-19 survivors include attention, memory, executive function (planning and organization), and processing speed. Notably, verbal memory appears particularly vulnerable. These impairments can significantly impact daily life, making it difficult to focus, retain information, plan tasks effectively, and react quickly.

4.1 Underlying mechanisms

Although the connection between COVID-19 and cognitive decline has been established, the precise biological mechanisms remain under investigation. Emerging evidence suggests that different processes contribute to cognitive impairment depending on whether the individual is in the acute phase of infection or experiencing persistent symptoms in long COVID [31, 32].

4.1.1 Mechanisms in the acute phase of COVID-19

During the acute phase, cognitive impairment is primarily driven by a combination of direct viral invasion, systemic inflammation, hypoxia, and cerebrovascular dysfunction [33].

One of the major contributors to cognitive decline in acute COVID-19 is the ability of SARS-CoV-2 to invade the central nervous system (CNS). The virus gains entry through the angiotensin-converting enzyme 2 (ACE2) receptor, which is expressed in neurons and glial cells [34]. Post-mortem studies have detected viral RNA in brain tissue, supporting the hypothesis of direct neuroinvasion [35]. Once inside the CNS, the virus triggers an intense inflammatory response, leading to activation of microglia and infiltration of peripheral immune cells. This neuroinflammatory cascade results in excessive production of pro-inflammatory cytokines, oxidative stress, mitochondrial dysfunction, and excitotoxicity, all of which contribute to neuronal injury and synaptic dysfunction [36]. Additionally, the disruption of neurotransmitter homeostasis—particularly involving glutamate, acetylcholine, and dopamine—further exacerbates deficits in attention, memory, and executive function [37].

Beyond direct neural damage, hypoxia plays a crucial role in acute cognitive impairment. Severe COVID-19 can result in respiratory failure, leading to reduced oxygen delivery to the brain [38]. Hypoxic injury impairs neuronal metabolism, induces endothelial dysfunction, and promotes neurovascular damage [39]. Compounding this, COVID-19 is associated with a hypercoagulable state, increasing the risk of thrombotic events such as stroke and microvascular thrombosis [40]. These cerebrovascular complications can cause focal or diffuse brain injury, leading to deficits in processing speed, memory, and executive function [41].

4.1.2 Mechanisms in long COVID (post-acute sequelae of COVID-19)

For many individuals, cognitive symptoms persist long after the resolution of the acute infection. The mechanisms driving cognitive dysfunction in long COVID differ from those in the acute phase and are characterized by chronic neuroinflammation, persistent cerebrovascular dysfunction, immune dysregulation, and psychological factors [42].

One of the primary contributors to long COVID cognitive impairment is sustained neuroinflammation. Even after viral clearance, microglia and astrocytes may remain in a state of chronic activation, releasing inflammatory mediators that disrupt synaptic function and impair neuronal repair [43]. This prolonged inflammatory response is thought to contribute to brain fog, memory deficits, and executive dysfunction in long COVID [44]. Additionally, autoimmune dysregulation has been implicated, with studies suggesting that SARS-CoV-2 may trigger the production of autoantibodies that target neural structures, leading to further cognitive deterioration [45].

Cerebrovascular dysfunction may also play a key role in long-term cognitive impairment. Some individuals with long COVID experience dysautonomia, a condition in which autonomic nervous system regulation is disrupted, leading to cerebral hypoperfusion and symptoms such as dizziness, fatigue, and cognitive slowing [46]. Persistent endothelial dysfunction and microvascular abnormalities may further compromise blood flow to critical brain regions, resulting in long-term neurovascular impairment [47].

Psychological factors also contribute to cognitive deficits in long COVID. Anxiety, depression, and chronic stress following COVID-19 can lead to dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, resulting in prolonged elevation of cortisol levels [48]. Excess cortisol is known to have neurotoxic effects, particularly on the hippocampus, a key brain region involved in memory formation [29]. The combination of stress-related neurotransmitter imbalances and structural brain changes in long COVID may therefore exacerbate cognitive symptoms [30].

Neuroimaging studies of long COVID patients have provided further insight into the neural correlates of persistent cognitive dysfunction. MRI studies have revealed volume loss in brain regions associated with memory and executive function, including the prefrontal cortex, hippocampus, and amygdala [31]. Functional imaging has also shown alterations in connectivity patterns between brain networks responsible for attention and cognition, suggesting that long COVID may be associated with long-term neural remodeling and neurodegeneration [32].

While both acute and long COVID involve neuroinflammatory and vascular mechanisms, their relative contributions differ across disease phases [33]. In the acute phase, direct viral invasion, systemic inflammation, hypoxia, and thrombotic events play dominant roles in driving cognitive impairment [34]. In contrast, long COVID is characterized by persistent neuroinflammation, microvascular dysfunction, autoimmune dysregulation, and psychological sequelae [35].

The acute phase of COVID-19 is marked by a rapid-onset inflammatory response that results in widespread neuronal damage and cerebrovascular complications [36]. In some cases, these acute insults resolve with time, leading to cognitive recovery. However, for individuals with long COVID, prolonged neuroinflammatory activity, persistent endothelial dysfunction, and sustained HPA axis dysregulation contribute to chronic cognitive impairment [37]. These distinct pathophysiological pathways highlight the need for different therapeutic strategies depending on the stage of the disease.

4.2 Long-term cognitive sequelae and rehabilitation needs

The persistence of cognitive decline observed in COVID-19 survivors necessitates a deeper understanding of its long-term trajectory. These impairments in attention, memory, executive function, and processing speed can significantly impact an individual's ability to perform daily activities, manage finances, and maintain employment (refer to previous sections for references on affected domains). The potential for long-term cognitive decline shows the urgent need for the development and implementation of effective rehabilitation programs. These programs ideally employ a multidisciplinary approach, incorporating cognitive retraining strategies, memory enhancement techniques, and executive function interventions tailored to address the specific needs of COVID-19 survivors. Additionally, exploring the potential benefits of cognitive rehabilitation for mitigating the long-term effects of COVID-19 on vocational functioning and overall quality of life is crucial.

4.3 Support systems for survivors and caregivers

Beyond rehabilitation programs, establishing robust support systems for both COVID-19 survivors and their caregivers is paramount. Individuals experiencing cognitive decline require assistance with daily tasks, medication management, and financial planning. Support groups for survivors and caregivers can provide a platform for shared experiences, emotional support, and the exchange of coping strategies. Furthermore, healthcare professionals should be equipped with the knowledge and resources necessary to manage and support survivors with cognitive impairments effectively.

4.4 Vaccination and potential protective effects

The potential protective effects of COVID-19 vaccination on cognitive outcomes warrant further investigations. If vaccination can be demonstrated to mitigate the risk or severity of cognitive decline, it would solidify its importance as a crucial public health intervention. Future research should prioritize elucidating the potential mechanisms by which vaccination might protect cognitive function. This knowledge would inform public health recommendations regarding vaccination and guide the development of targeted preventive strategies.

The growing body of evidence linking COVID-19 infection to cognitive decline demands a multifaceted public health response. Understanding the long-term effects of this complication necessitates continued research to inform the development of effective rehabilitation programs, robust support systems, and potentially protective interventions like vaccination.

5 Limitations

While this systematic review provides valuable insights into the cognitive consequences of COVID-19 and their underlying mechanisms, it is important to acknowledge its inherent limitations. These limitations stem from both the reviewed studies and the methodology of this review itself. Another limitation is the difficulty in controlling for confounding variables such as pre-existing neurological disorders, psychiatric conditions, or socioeconomic factors. Many individuals who developed cognitive impairment after COVID-19 may have had undiagnosed cognitive vulnerabilities prior to infection. Additionally, the psychological impact of the pandemic itself—such as social isolation, stress, and anxiety—could contribute to cognitive symptoms, complicating the attribution of deficits solely to viral pathology. This review was restricted to studies published in English, which may have led to the exclusion of relevant research conducted in other languages. Important findings from non-English studies, particularly those from regions heavily affected by COVID-19, may have been overlooked. This language bias could limit the comprehensiveness and global applicability of the findings.

6 Conclusion

The association between COVID-19 infection and cognitive impairment constitutes a significant public health concern. While emerging evidence supports this relationship, the underlying mechanisms still need to be understood. However, the complexity of this relationship necessitates further investigation to elucidate underlying mechanisms and inform effective interventions. Future studies should prioritize prospective cohort studies with rigorous neurocognitive assessments to establish causal relationships and track the long-term trajectory of cognitive decline. Longitudinal studies incorporating multimodal imaging techniques, including structural and functional MRI, will enhance the understanding of brain structural and functional changes associated with COVID-19. Additionally, exploring the role of genetic factors and comorbidities in modulating vulnerability to cognitive decline is imperative. Moreover, future studies should employ standardized neuropsychological assessment batteries and incorporate validated measures of psychological distress. This knowledge can inform the development of effective rehabilitation strategies and robust support systems for COVID-19 survivors. Exploring the potential protective effects of vaccination on cognitive outcomes holds significant promise for mitigating the long-term public health burden associated with COVID-19. The link between COVID-19 and impairment presents a formidable challenge, yet it also offers a unique opportunity for scientific advancement and the optimization of public health initiatives.