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Abstract

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2, although largely affecting the respiratory system, commonly presents with numerous clinical symptoms from other systems. COVID-19 has been associated with both acute and persistent neurological abnormalities in a substantial proportion of patients. Notably, post-COVID-19 neuropsychological abnormalities have garnered attention, highlighting a high prevalence of neurocognitive issues in affected individuals. This narrative review synthesizes current knowledge on the neuropsychological impact of COVID-19, drawing insights from an extensive online search of published literature conducted in the PubMed (MEDLINE) and Scopus databases. The findings underscore significant neuropsychological effects of COVID-19 observed at both individual and societal levels during the ongoing pandemic. Neuropsychological deficits such as memory difficulties, attention problems, and executive dysfunction, alongside physical symptoms like headaches and fatigue were commonly reported. Additionally, psychological challenges, including fear, anxiety, and depression, emerged as prevalent issues arising from the uncertainties surrounding the situation, social isolation, and employment insecurities. The identified neuropsychological manifestations of COVID-19 can significantly impede normal cognitive and emotional functioning, potentially resulting in decreased productivity and an overall decline in mental health and quality of life. Early identification of signs indicative of neurological or psychological decline becomes imperative, offering a crucial opportunity to mitigate the risk of long-term neuropsychological dysfunction through the development of targeted interventions.

Keywords

brain cognition cognitive dysfunction COVID-19 depression mental health pandemics quality of life SARS-CoV-2

What do we already know about this topic?

The coronavirus disease 2019 (COVID-19), caused by the “severe acute respiratory syndrome coronavirus-2” (SARS-CoV-2), although largely affecting the respiratory system, commonly presents with numerous and persistent neurological abnormalities in a substantial proportion of patients.

How does your research contribute to the field?

This narrative review synthesizes current knowledge on the neuropsychological impact of COVID-19, drawing insights from an extensive online search of published literature and underscores significant neuropsychological effects observed at both individual and societal levels during the ongoing pandemic.

What are your research’s implications toward theory, practice, or policy?

Early identification of signs indicative of neurological or psychological decline becomes imperative, offering a crucial opportunity to mitigate the risk of long-term neuropsychological dysfunction through the development of targeted interventions.

Introduction

The global impact of the novel coronavirus (COVID-19) pandemic on public health has been profound, marked by unprecedented challenges and a substantial loss of human lives.¹ Concurrently, the virus has a notable impact on neuropsychological parameters, affecting the neuropsychological well-being of a significant proportion of COVID-19 survivors.^2,3 Individuals across all age groups are experiencing a wide range of neurological and psychological effects induced by the virus.^4
-6 These effects encompass memory loss, difficulty concentrating, executive dysfunction, physical and mental fatigue, as well as psychological challenges including depression, anxiety, fear and sleep disturbances. The spectrum also extends to more severe neurological or psychological conditions such as encephalitis, seizures, or even suicidal thoughts.

The “severe acute respiratory syndrome coronavirus-2” (SARS-CoV-2) that causes COVID-19, a condition that mainly affects the respiratory system, exhibits a wide range of clinical symptoms.^7
-9 It should be noted that a significant proportion of patients have both acute and long-term neurological abnormalities that have been linked to COVID-19 infection.^4
-6 According to a Wuhan-based study, approximately 36% of 214 hospitalized patients with laboratory-confirmed coronavirus disease demonstrated central nervous system (CNS) manifestations, including dizziness, headache, changed level of consciousness, seizure, ataxia, or acute cerebrovascular disease.⁵ Based on their respiratory condition, patients with more severe infections had a higher prevalence of these symptoms.⁵

In addition to neurological alterations, neuropsychological complications related to COVID-19 have also been investigated. Infection with COVID-19 has been linked to both the development of cognitive deficits and the worsening of pre-existing ones.⁴ Remarkably, findings suggest that cognitive decline does not appear only in the acute phase of severe cases.⁹ In the post-acute phase, neurocognitive alterations may continue to occur and form the “long-COVID” syndrome.¹⁰ In addition, some studies indicate probable COVID-19 impacts on cognition, even in mildly symptomatic individuals, 6 months following the infection.¹¹

With the emergence of COVID-19, there has been a noticeable gap in understanding its effects on cognition and behavior. While existing research predominantly focuses on the virological and clinical aspects of COVID-19, there remains a significant gap in understanding its neuropsychological consequences. This gap is critical as it overlooks the potential cognitive, emotional, and behavioral impacts of the virus, which are crucial for a comprehensive understanding of its overall impact on human health.

Our initiative to investigate the neuropsychological impact of COVID-19 was motivated by the pressing global health crisis posed by the pandemic. In response to the critical need for understanding the broader implications of COVID-19 beyond its clinical aspects, we aim to provide insights into the cognitive, emotional, and behavioral consequences of the virus, as well as the mechanisms underlying them. By addressing these issues, we endeavor to contribute to a deeper comprehension of COVID-19’s overall impact on mental health and well-being.

The primary objective of this narrative review is to comprehensively investigate and analyze the neuropsychological impact of COVID-19, along with its underlying neuropathophysiological mechanisms, by conducting a thorough examination of the existing published literature.

Methods

Search Strategy

An online search of the existing published literature was conducted to identify studies examining the topic under investigation, covering the period from 2020 to 2023. The bibliographic search was carried out in PubMed (MEDLINE) and Scopus databases using the following search terms, which had to be part of the title, abstract or keywords:

(“2019-CoV” OR “SARS-CoV-2” OR “2019CoV” OR “severe acute respiratory syndrome coronavirus 2” OR “COVID-19” OR “COVID-2019” OR “coronavirus disease-2019”) AND (“neuropsychological effects” OR “neuropsychological sequelae” OR “neuropsychological impact” OR “neuropsychological deficits”).

Eligibility Criteria

To be considered eligible for inclusion in the review, studies had to meet specific criteria. Primarily, studies were expected to explicitly investigate and address the neuropsychological effects of the COVID-19 pandemic. Furthermore, they were required to have undergone a peer-review process to ensure the integrity and reliability of the research. Only articles written in English were considered for further analysis. Exclusions were made for studies exploring fields unrelated to neuropsychology within the context of COVID-19. Articles meeting the inclusion criteria underwent a comprehensive examination of their full text.

A Narrative Synthesis Approach: Selective Presentation of Key Studies Investigating COVID-19 Neuropsychological Impact

This narrative review focuses on presenting and analyzing a carefully curated selection of studies that are particularly relevant to the investigation of the neuropsychological impact of COVID-19. The decision to spotlight these particular studies was guided by a qualitative evaluation of their relevance to our specific aspects of interest and their contribution to our understanding of the topic. Through this approach, the review aims to provide a comprehensive narrative synthesis, offering insights into the key findings and the underlying neuropathophysiological mechanisms within the context of COVID-19 neuropsychological effects.

Results

The Neuropsychological Sequelae in Post-COVID-19 Patients: Exploring the Cognitive and Psychological Impacts

Studies examining post-COVID-19 neuropsychological abnormalities reveal the high frequency of neurocognitive problems among people who have contracted COVID-19.^10,12
-18 Table 1 presents a summary of the selected studies. Research findings suggest that individuals with a history of mild symptomatic SARS-CoV-2 infection are over 18 times more likely to exhibit cognitive impairment compared to those without a history of the virus.¹¹ While the long-term consequences of the virus are still unknown, emerging research suggests the possibility of persistent neuropsychological impairment, even after recovery.¹¹ Notably, this decline often goes unnoticed by the majority of affected individuals and their families.

Table 1.

Summary of the Included Studies Examining the Neuropsychological Impact of COVID-19 Infection. The Studies are Presented in Chronological Order.

First author	Number of patients	Objective of interest	Results
Almeria et al²⁰	n = 35	To investigate the neuropsychological impact of COVID-19	Neuropsychological deficits, including difficulties in attention, memory, and executive functions, were frequent. The presence of neurological symptoms during COVID-19 infection elevated the risk of subsequent cognitive deficits. Symptoms such as oxygen therapy, headache, and diarrhea were associated with lower performance on neuropsychological tests. Cognitive complaints were correlated with symptoms of anxiety and depression in COVID-19 patients.
Woo²⁴	n = 18	To evaluate neurocognitive manifestations following COVID-19 recovery in predominantly young adults who experienced uncomplicated acute COVID-19	Significant neurocognitive deficits persisted after acute infection, including deficits in memory, attention, and concentration
Zhou et al¹⁸	n = 29	To assess the effects of COVID-19 on cognitive functions among recovered patients and explore its correlation with inflammatory profiles	Cognitive impairments exist even in patients recovered from COVID-19 and were linked to underlying inflammatory processes
Alemanno et al¹²	n = 87	To examine the neuropsychological effects of COVID-19 in patients admitted to a COVID-19 Rehabilitation Unit	More than80% of patients presented with cognitive deficits, as measured by the MoCA test
Bonizzato et al²²	n = 12	To validate the efficacy of an assessment model for COVID-19 patients	Over 50% of evaluated patients exhibited poor cognitive performance on screening tests
Di Pietro et al¹³	n = 294	To retrospectively assess the cognitive profile of post-acute COVID-19 patients in a neurorehabilitation unit and correlate neuropsychological findings with disability and functional recovery scores upon admission and discharge	Changes in verbal memory and executive functions were associated with the degree of functional impairment upon admission and with the subsequent functional improvement upon discharge
Del Bruto¹¹	n = 93	To longitudinally evaluate the prevalence of cognitive impairment in individuals with a past history of mild symptomatic SARS-CoV-2 infection	Evidence of cognitive impairment in mild COVID-19 cases; 18.1 times higher likelihood of cognitive decline compared to non-COVID controls
Ferrucci et al²¹	n = 38	To investigate the incidence of cognitive abnormalities 5 months following hospital discharge	Out of all patients, 42.1% exhibited deficits in processing speed, while 26.3% displayed impairments in delayed verbal recall
Graham et al¹⁰	n = 100	To examine the neuropsychological manifestations in non-hospitalized individuals with long-term COVID-19 symptoms	Non-hospitalized individuals with long-term COVID-19 symptoms experienced pronounced and persistent “brain fog” and fatigue with notable effects on their cognitive abilities and overall quality of life
Hosp et al¹⁴	n = 29	To thoroughly describe the neuropsychological consequences of COVID-19 in patients with severe illness necessitating hospitalization	Cognitive decline observed during subacute stage, as assessed through comprehensive neuropsychological testing. Underlying neocortical dysfunction.
Miskowiak et al¹⁵	n = 29	To examine the frequency, nature, and intensity of cognitive impairments 3 to 4 months post COVID-19 hospital discharge, their association with subjective cognitive complaints, quality of life, and illness-related factors	The majority of patients experienced cognitive impairment several months after hospitalization with COVID-19. These impairments were associated with subjective cognitive complaints and decreased quality of life. The severity of cognitive impairments was correlated with pulmonary dysfunction and d-dimer levels during the illness.
Negrini et al¹⁶	n = 9	To document the cognitive characteristics in post-acute COVID-19 patients and assess the impact of acute respiratory distress syndrome (ARDS) on cognitive deficits	A subset of patients exhibited general cognitive decline, which correlated with the duration of their ICU stay.
Poletti et al⁵²	n = 98	To examine cognitive functioning 6 months after being discharged from the hospital due to COVID-19 and assess implications for quality of life	COVID-19 sequelae encompass signs of persistent cognitive impairment that can endure for up to 6 months following hospital discharge, significantly impacting the quality of life. COVID-19 patients exhibited poorer performance in psychomotor coordination, information processing speed, verbal fluency, and executive functions, but similar working and verbal memory compared to healthy controls.
García-Sánchez²⁵	n = 63	To investigate the prevalence of cognitive impairment in post-COVID individuals with subjective cognitive complaints and examine whether such impairment is confined to a specific cognitive domain or spans across multiple domains	COVID-19 had a widespread impact on attention abilities, manifesting both as the primary affected cognitive domain and in conjunction with impairments in executive functions, learning, and long-term memory. These cognitive deficits were largely unrelated to clinical parameters such as hospitalization, disease duration, biomarkers, or affective measures
Mattioli et al²³	n = 215	To investigate cognitive impairment across varying severities of COVID-19 cases	Neurological deficits and cognitive impairment were more prevalent and severe in cases requiring ICU admission

In the landscape of COVID-19-related neuropsychological outcomes, a wide range of psychometric instruments were utilized. While cognitive screening measures were more commonly employed, several studies incorporated comprehensive neuropsychological batteries for a more thorough evaluation. Studies that included brief assessment screening tests, such as the “Mini Mental State Examination” (MMSE) or the “Montreal Cognitive Assessment” (MoCA), showed that as compared to healthy controls, COVID-19 patients had a higher likelihood of exhibiting neuropsychological deficits.^12,14
-16 MoCA test stood out for its sensitivity in detecting cognitive dysfunction associated with COVID-19.¹² Subitem score analyses of these screening tools showed that the most impacted cognitive areas that contributed to the lower general score, were attentional processes, episodic memory, and executive functions.¹⁹

Studies that included more extensive neuropsychological tests can provide more detailed information on the profile of cognitive changes concerning each cognitive function, separately. With regards to memory abilities, some studies found impairment of long-term^13,14 and working memory,^10,14 but preservation of short-term memory.^14,18,20 Memory emerged as one of the cognitive functions most adversely impacted by COVID-19, with studies revealing an increased likelihood of memory loss and difficulty learning new material among individuals who have contracted the virus. In terms of attention, deficits were found in divided, sustained, and selective attention tasks, where compared to healthy controls, the COVID-19 group displayed longer reaction times and higher error rates.^10,17,18 Moreover, the virus appeared to have a negative impact on executive functioning. Among the executive functions, abstraction, inhibition and set shifting appeared as the most affected domains.^12,15,17 In addition, some studies detected processing speed deficits.²¹

Finally, mixed results have emerged regarding the impact of COVID-19 on language abilities and visuo-spatial skills.^{11,13,20,22
-24} While some studies found no significant changes after infection, others reported adverse effects on language and visuo-spatial processing. Specifically, certain studies highlighted the impact of COVID-19 on language abilities, resulting in difficulties in word selection, sentence construction, and comprehension of complex instructions.^20,24 Additionally, some studies suggest that the virus can impair visuo-spatial skills, affecting an individual’s ability to perform tasks such as reading maps, understanding schematics, and navigating.¹¹

Individuals with COVID-19 may encounter a spectrum of cognitive difficulties in various domains, ranging from mild to severe. In more severe cases, symptoms such as confusion, disorientation, memory loss, impaired problem-solving, and difficulty forming new memories have been documented.²⁵ These deficits might have enduring consequences, affecting one’s capacity to engage in social interactions, perform daily activities, and sustain employment. Even mild cognitive impairment can impact memory skills, executive functions, attention, and complex problem-solving abilities. Such difficulties may manifest as challenges in decision-making, quick information retrieval, multitasking, maintaining focus and organizing thoughts and information.²⁵ These cognitive changes can significantly hinder an individual’s functional abilities and social interactions.

When considering the clinical parameters associated with the neuropsychological impact of COVID-19, several studies have indicated that individuals hospitalized for COVID-19 tend to experience more pronounced neuropsychological impairments compared to those who receive outpatient care.²⁶ Furthermore, data from various research projects suggests that intensive care unit (ICU) hospitalization is associated with even more severe cognitive decline.¹⁶ Interestingly, certain studies have found no significant correlation between cognitive deficits associated with COVID-19 and clinical parameters, such as hospitalization, illness severity, and pathological biomarkers.^25,27

COVID-19 has also been linked to a greater chance of developing mild or major neurocognitive disorders, such as mild cognitive impairment (MCI) or dementia, respectively.⁴ Remarkably, patients with pre-existing dementia have an increased likelihood of developing severe forms of illness when contracting COVID-19, experiencing deterioration of their symptoms, and requiring hospitalization.²⁸

In addition to neurocognitive deficits, post-COVID-19 syndrome is also linked to elevated levels of psychosocial distress, underscoring the critical importance of addressing mental health in the context of the pandemic.²⁹ The most common psychological issues after infection appear to be depression and anxiety.^12,20,22,30 The anxiety and depressive disorders observed in COVID-19 patients could be linked to the psychological trauma associated with the illness and the experience of possible hospitalization. Moreover, additional mediating factors, such as fear of infection, social isolation, employment insecurities, and the loss of loved ones, can exacerbate psychological distress, further intensifying symptoms of anxiety and depression. In addition, changes in behavior such as increased irritability, aggression and distractibility may also serve as signs of post-COVID-19 neuropsychiatric issues. These difficulties might be more pronounced in those who have experienced more severe forms of COVID-19 infection. Such neuropsychiatric symptoms may at least partially explain the cognitive difficulties observed in patients who had previously contracted the virus.¹⁹ However, it is an issue that needs further investigation.

Another particularly alarming aspect of COVID-19’s impact is its potential link to increased rates of drug abuse and suicidal thoughts.³¹ The psychological effects of the virus may persist, leading to enduring disorders, such as post-traumatic stress disorder (PTSD). Consequently, it becomes imperative not only to address immediate mental health concerns, but also to maintain a focus on the long-term well-being of COVID-19 survivors.

Unraveling the Neurobiological Landscape: Mechanisms Underlying COVID-19 Impact on Cognitive Functions

The mechanisms underlying the impact of COVID-19 on cognitive performances are still being investigated. It is possible that different neurobiological mechanisms lead to different neurocognitive manifestations.¹⁹ These mechanisms may involve the direct impact of cellular damage due to SARS-CoV-2, secondary inflammatory disease, reduced activity of “angiotensin converting enzyme 2” (ACE-2) which normally has the function of protecting the nervous system, decreased oxygen delivery to the brain (hypoxia), metabolic abnormalities, cerebral vascular disease, stroke, sepsis, oxidative stress, and/or multi-organ damage caused by severe infection.^8,32

The results from studies on post-COVID-19 syndrome have sparked debate. Some authors identified extensive limbic and subcortical hypometabolism in patients reporting multiple symptoms (such as fatigue and memory loss), while other researchers found no metabolic changes on positron emission tomography (PET) and only minor cognitive impairments, if any, in these patients.³³ However, critical evaluation of these studies is essential, considering common methodological problems. Moreover, it appears that there is potential utility for PET and single-photon emission computed tomography (SPECT) in the clinical investigation of diagnostic issues related to COVID-19.³³ These imaging techniques could offer valuable insights into the neurobiological mechanisms underlying the virus’s impact on cognitive functions, providing a more comprehensive understanding of its neuropsychological consequences.

Additionally, COVID-19 has been associated with inflammatory changes that might contribute to the development of neurological and neuropsychological symptoms. Recent studies suggest that SARS-CoV-2 hinders the body’s efforts to control its spread, establishing a positive feedback loop of continued viral replication and cytokine/chemokine release, ultimately resulting in the cytokine storm that is a hallmark of the illness.^34,35 Some cytokines may penetrate the blood-brain barrier, activate microglia, and induce inflammatory changes in the CNS, which may result in excitotoxicity and neuronal degeneration. These changes, experienced by COVID-19 patients, may cause, exacerbate, and/or prolong cognitive deficits.³⁶

Inflammation appears to be an important characteristic of COVID-19 that may underlie both acute and persistent cognitive changes.⁴ It’s noteworthy that inflammatory features are also observed in patients with neurocognitive disorders, such as Alzheimer’s disease (AD). Thus, the investigation of the common molecular substrates between these 2 diseases may provide valuable information and elucidate the mechanisms underlying the neuropsychological sequelae shown in a proportion of COVID-19 survivors.⁴ Additionally, it has been stated that patients with apolipoprotein E (APOE) e4 allele are more likely to demonstrate more severe neurological alterations after COVID-19 infection.³⁷ It is noteworthy that the same allele is also connected to an increased likelihood of developing AD.³⁸

SARS-CoV-2 may also contribute to neuropsychological changes due to its association with cerebrovascular dysfunction. ACE-2 is a receptor that is concentrated in endothelial cells, including cerebral blood vessels, and serves as the specific binding site for SARS-CoV-2. The depletion of ACE-2 due to this binding might lead to endothelial dysfunction and an increased tendency for blood clotting, known as hypercoagulability, potentially resulting in strokes.³⁹ Research indicates that strokes in COVID-19 patients are often associated with severe illness stages, including multiple organ failure and severe pneumonia, and are more prevalent in individuals with pre-existing cerebrovascular conditions and other risk factors.⁴⁰ Ischemic strokes are the most observed type among COVID-19 patients who experience strokes, followed by hemorrhagic strokes.⁴⁰

Finally, delirium, which is an acute disorder accompanied by sudden change in mental status and confusion, constitutes a common symptom seen in COVID-19-infected individuals transferred to ICU.⁴¹ Older age, the male gender, high blood pressure, severe respiratory symptoms, and dementia are all key risk factors for the syndrome.^32,41,42 Of note, over 50% of COVID-19 patients hospitalized in ICU demonstrate this clinical syndrome.⁴³ Delirium, through an acute biological process at both structural and functional levels of the brain, may be associated with the development of neuropsychological deficits in COVID-19-infected individuals.³² Therefore, close monitoring of patients in terms of delirium may prevent the appearance of subsequent cognitive impairment.⁴¹

Ongoing research continues to explore and shed light on the complexities of these mechanisms. It is crucial to elucidate the specific neurobiological pathways of SARS-CoV-2 for a deeper understanding of its potential neurological and cognitive effects.

Insights From Post-Mortem Neuropathological Studies

SARS-CoV-2 is considered to have neuroinvasive potential, possibly leading to acute brain disorders or exacerbating respiratory distress in COVID-19 patients.⁴⁴ Numerous studies have investigated the neuropathological consequences of COVID-19 using postmortem brain samples from autopsies.^45
-51 These studies examined brain tissue from fatal COVID-19 cases to assess glial responses, inflammatory changes, and the presence of SARS-CoV-2 in the CNS and they consistently identified acute hypoxic injury, hemorrhage, vascular changes, and mild-to-moderate non-specific inflammation as the most prevalent neuropathological features in COVID-19.^45,47,50 Pronounced neuroinflammatory changes, including activation of microglia and astrocytes, were notably observed, particularly in the brainstem.^46,47 Furthermore, brain autopsies have also revealed the presence of low levels of viral SARS-CoV-2 RNA.^45,46 Viral proteins of SARS-CoV-2 have been detected in cranial nerves that originate from the lower brainstem, as well as in isolated cells within the brainstem.⁴⁶ Interestingly, the presence of SARS-CoV-2 in the CNS did not correlate with the severity of neuropathological changes.⁴⁶ However, other studies have not detected evidence of CNS involvement, such as signs of encephalitis or vasculitis, in postmortem evaluations of COVID-19 patients.⁵¹

Although cerebrovascular pathology and microglial-predominant inflammation are consistently observed as the main neuropathological features associated with COVID-19, there is still uncertainty regarding the specific mechanisms underlying the neurological and neuropsychological symptoms during acute infection or in the post-acute phase.⁵⁰ Despite this lack of consensus, studies that incorporate microscopic and molecular findings from post-mortem brain tissues undoubtedly offer valuable insights into the occurrence and persistence of neurocognitive manifestations among a notable proportion of individuals affected by COVID-19, thereby enriching our understanding.

Discussion

The unprecedented global impact of COVID-19 pandemic has triggered a profound crisis with notable effects on the health and well-being of individuals worldwide. One of the less-explored but potentially severe consequences of the virus is the neuropsychological decline observed in individuals following COVID-19. This narrative review offered a thorough examination of the neuropsychological impact of COVID-19, uncovering the cognitive impairments and psychological implications for a significant proportion of affected individuals. The articles investigated the neuropsychological effects of COVID-19 across diverse groups of individuals, considering populations from various nationalities.

The analysis of research findings highlights a broad range of neuropsychological effects associated with COVID-19, spanning from mild to severe cognitive deficits. Various studies utilized cognitive screening tools, such as the MMSE and MoCA, while others employed comprehensive neuropsychological batteries to provide detailed insights into specific cognitive domains.^11
-24 According to the results of the included studies, difficulties in memory and learning, attentional processes, executive functions, and processing speed emerged as the most prominent post-COVID-19 neuropsychological deficits. These deficits may persist post-recovery and tend to be more severe in hospitalized patients,²⁷ particularly those admitted to the ICU.¹⁶ However, it is essential to approach the interpretation of cognitive deficits following COVID-19 with caution, taking into consideration potential confounding factors, as well as the risk of overinterpretation due to possible gaps in assessing individuals’ premorbid functioning.

A critical examination of the association between COVID-19 infection and neuropsychological deficits reveals several underlying mechanisms, encompassing both neuropathological and psychological factors. The neuropathological mechanisms include hypoxia, neuroinflammatory changes, metabolic abnormalities, and cerebrovascular pathology, such as strokes and thrombotic events,^45
-51 which can contribute to the development of neuropsychological difficulties following infection. Moreover, the heightened levels of neuropsychiatric symptoms and psychological distress associated with COVID-19, characterized by depression, anxiety, emotional lability, fear, irritability, and sleep disturbances,^12,20,22,30 probably stemming from the underlying neuropathological mechanisms, the trauma of infection and potential hospitalization, can further exacerbate cognitive difficulties. It is also notable that cognitive deficits can deteriorate psychological symptoms, establishing a bidirectional relationship between the 2 domains. Figure 1 depicts a schematic illustration of the relationship between neuropathological mechanisms, neurocognitive deficits, and neuropsychiatric symptoms following COVID-19 infection.

Figure 1.

The dynamic interplay of neuropathological mechanisms, neurocognitive deficits, and neuropsychiatric symptoms in post-COVID-19 pathology.

Furthermore, emerging evidence suggests that certain individuals may be at an increased risk of developing neurocognitive disorders such as MCI or dementia, following COVID-19 infection.⁴ The virus can induce structural and functional alterations in the brain, precipitating processes like neuroinflammation and neurodegeneration. Additionally, individuals with pre-existing neurological or psychiatric conditions may be particularly vulnerable to the consequences of the pandemic, experiencing deterioration of their symptoms.²⁸

All these neuropsychological manifestations following COVID-19 infection undoubtedly exhibit a negative impact on individuals, families, and communities, potentially resulting in decreased productivity and an overall decline in mental health and well-being. COVID-19 can significantly diminish an individual’s perceived quality of life,^10,52 affecting multiple aspects across various domains of daily living. Quality of life encompasses functional abilities, role functioning, the quality and quantity of social interactions, psychological well-being, somatic sensations, happiness, life situations, life satisfaction, and the sense of fulfillment.⁵³ It is evident that COVID-19 sequelae, including cognitive impairment and psychological distress, can profoundly impact individuals’ quality of life.^10,52

Although the changes in neuropsychological functioning following COVID-19 may initially appear temporary, if left untreated, they could have long-term implications for overall functioning. Therefore, it is evident that long-term monitoring after COVID-19 infection is crucial to timely detect any possible signs of neuropsychological decline. Timely diagnosis and intervention are vital to minimize the risk of persistent neuropsychological impairment. Clinicians and healthcare professionals can play a pivotal role in addressing the multifaceted effects of COVID-19 on cognitive and psychological well-being. It is important that they are aware of these effects so that they can provide appropriate support and interventions to individuals who are struggling with such difficulties. By addressing immediate concerns while sustaining a focus on long-term status, clinicians can facilitate the prompt identification of signs indicating neurological or psychological decline, enabling targeted interventions.

Moreover, it is highly recommended that clinicians inform affected individuals about the potential neuropsychological effects of the virus, prompting them to be proactive in seeking medical advice, undergoing regular medical check-ups, accessing mental health counseling, and prioritizing self-care practices to safeguard personal and familial well-being. With appropriate care, many individuals can overcome these challenges, increasing the likelihood of returning to their previous level of everyday functioning.

In conclusion, research findings highlight the need for thorough neuropsychological evaluations and interventions for all post-COVID patients reporting cognitive complaints, extending beyond those with severe symptoms or hospitalizations.²⁵ Recognizing that individuals with various disease trajectories may exhibit neurocognitive difficulties emphasize the importance of timely assessment and tailored interventions to address their unique challenges. Further research is imperative to gain a comprehensive understanding of the multifaceted effects of COVID-19 on cognition. It is recommended that future research endeavors explore the longitudinal improvement of cognitive abilities over time, potentially employing neuroimaging techniques to understand the neural contributory factors.²⁵ These efforts will not only enhance our understanding of the intricacies of post-COVID-19 neuropsychological effects, but will also inform refined treatment strategies, ultimately leading to improved clinical outcomes for the affected individuals.²⁵

Conclusions

The narrative review underscores the profound neuropsychological impact of COVID-19, emphasizing its effects beyond respiratory symptoms. Cognitive functioning and mental health are significantly impacted in a substantial proportion of the affected individuals, necessitating a comprehensive approach to address these challenges. Managing the neuropsychological consequences of COVID-19 demands a multidisciplinary approach that integrates clinical care, comprehensive neuropsychological evaluations, and psychological support. It also requires a collaborative effort involving healthcare professionals, researchers, and policymakers. This holistic approach is essential for accurately assessing and effectively managing the cognitive and emotional manifestations associated with the virus. Ongoing research efforts in the field hold significant promise to further advance our understanding of the intricacies of COVID-19’s neuropsychological effects and their underlying mechanisms.

Footnotes

Author Contribution Declaration

Conceptualization, K.M. and E.T.; methodology, K.M. & ET; software, E.C.; validation, K.M, E.C., and E.T.; formal analysis, K.M.; investigation, K.M..; resources, E.T.; data curation, E.C..; writing—original draft preparation, K.M. & E.C.; writing—review and editing, K.M., E.C. & E.T.; visualization, K.M..; supervision, K.M.; project administration, K.M.

Data Availability Statement

N/A.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Kalliopi Megari

Ethical Statement

N/A.

Informed Consent/Patient Consent

N/A.

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Highlighting the Neuropsychological Consequences of COVID-19: Evidence From a Narrative Review

Abstract

Keywords

Introduction

Methods

Search Strategy

Eligibility Criteria

A Narrative Synthesis Approach: Selective Presentation of Key Studies Investigating COVID-19 Neuropsychological Impact

Results

The Neuropsychological Sequelae in Post-COVID-19 Patients: Exploring the Cognitive and Psychological Impacts

Unraveling the Neurobiological Landscape: Mechanisms Underlying COVID-19 Impact on Cognitive Functions

Insights From Post-Mortem Neuropathological Studies

Discussion

Conclusions

Footnotes

Author Contribution Declaration

Data Availability Statement

Declaration of Conflicting Interests

Funding

ORCID iD

Ethical Statement

Informed Consent/Patient Consent

References