Permanence of Cognitive Alterations in Post- and Long COVID Patients: Glia and Brain Alteration, Gender Differences and New Diabetes Diagnosis

Abstract

Background: COVID-19 has been associated with multisystemic sequelae, including persistent neurocognitive impairment and emerging metabolic alterations. Growing evidence suggests that glial dysfunction and inflammation may play a pivotal role in both cognitive decline and new-onset diabetes following SARS-CoV-2 infection. Objectives: This study aimed to assess the prevalence and characteristics of cognitive impairments in post-COVID-19 patients and to explore their correlation with new-onset diabetes, neuroanatomical changes, and psychological symptoms, with a specific focus on gender differences. Methods: A total of 245 patients (mean age 56.8 ± 12 years), previously diagnosed with COVID-19, were enrolled between April 2021 and August 2023. Participants underwent a comprehensive neuropsychological assessment (MMSE, Rey-Osterrieth Figure, FAB, Hamilton, STAI, IES-R), structured interviews, and, in a subset, brain MRI. Individuals with pre-existing neurological disorders were excluded. Data were analyzed for cognitive performance, neuroimaging abnormalities, and metabolic outcomes, including new-onset diabetes. Results: Cognitive dysfunction was identified in 87% of participants: mild in 47%, moderate in 21.6%, and severe in 10.8%. Glial alterations on MRI were observed in 51%, hippocampal atrophy in 9%, and temporal lobe reduction in 4%. Notably, 12% of patients developed new-onset diabetes post-COVID, of whom 80% exhibited mild to moderate cognitive deficits. Depressive symptoms were present in 80.9%, and anxiety in 93.5%, with significantly higher incidence in female patients. PTSD symptoms correlated with greater cognitive impairment. Ongoing research into the mechanisms underlying these persistent cognitive impairments in subjects with and without types 1 and 2 diabetes. This paper presents the final data of the research published in the previous article referenced in the bibliography. Conclusions: This study highlights a significant association between cognitive decline and new-onset diabetes in post-COVID patients, likely mediated by systemic inflammation and glial dysfunction. Particularly noteworthy are the findings of neuroanatomical alterations, including nonspecific glial signal changes, hippocampal atrophy, and temporal lobe volume reductions, suggesting post-infectious cerebral vulnerability with potential long-term consequences. These results support the need for integrating cognitive screening, brain neuroimaging, and metabolic monitoring into post-COVID care pathways—especially for women and individuals presenting with anxiety or depressive symptoms. An early and interdisciplinary approach is essential to address the neuro-metabolic and cerebral sequelae of long COVID.

1. Introduction

As the SARS-CoV-2 pandemic continues to evolve, so does our understanding of its extensive and long-term impacts on health, particularly in the realm of neurological functions. This study is an integral part of the ongoing effort to decode the long-term neurological effects of COVID-19, with a focus on cognitive impairments linked to alterations in glial cells, sex-specific manifestations, and their interrelation with new-onset diabetes. Employing advanced neuropsychological assessments, this research scrutinizes the extent of cognitive deficits among individuals recovering from post and long COVID, shedding light on the underlying mechanisms of glial dysfunction, gender-related differences in cognitive outcomes, and the incidence of diabetes as a comorbid condition [1,2,3].

Since the onset of the pandemic, SARS-CoV-2 has revolutionized scientific paradigms, compelling healthcare professionals to adopt a hybrid research–intervention model. The complexity of COVID-19—characterized by multifactorial and multidimensional symptoms—has challenged various specialties within medicine to adapt swiftly to emerging patient care needs. Recent studies from 2022 through 2023, by Mendez, Aminoff, Wilterdink, in 2021 and Johnson in 2022–2023, demonstrate that the psychophysical sequelae of SARS-CoV-2 are diverse, often mirroring symptoms across different syndromic presentations. Notably, impairments in cognitive functions are among the most debilitating consequences, leading to memory deficits, attention disorders, compromised language skills, and disrupted executive functions.

Other authors aiming to give more answers on these topics are as follows [4,5,6].

This research uses a structured neuropsychological framework to systematically assess cognitive deficits detected in patients with post and long COVID. It is the final phase of research based on the initial protocols developed at Partinico Hospital (2021–2023) and refined through subsequent studies [7] with the aim of exploring the following:

• The potential presence of encephalic alterations—from the cortex to the brain stem—detected through state-of-the-art neuroimaging techniques as previously explored by Crunfli in 2022.
• The possible correlations between these neurological changes and neurocognitive deficits, with specific attention to alterations in diabetic patients (types 1 and 2).
• The hypothesis that neuroinflammation, a condition exacerbated by COVID-19 as confirmed by recent findings [2], may lead to severe executive dysfunctions, akin to a dysexecutive syndrome.

Furthermore, emerging data from 2022 and 2023 have begun to highlight the systemic impacts of the virus, particularly in relation to metabolic health, suggesting a bidirectional relationship between diabetes and cognitive impairments. These studies underscore the importance of integrating metabolic health management into post-COVID care protocols to mitigate the compounded risks associated with diabetes and cognitive decline.

The findings from this comprehensive study are expected to significantly enrich the global understanding of COVID-19’s neuropathological aftermath and to facilitate the development of targeted therapeutic approaches. By integrating the latest international research into our analysis, we aim to navigate the complex interplay between infectious disease and chronic neurological conditions effectively. This approach ensures that treatment strategies are not only responsive to the evolving landscape of COVID-19 but are also underpinned by a robust scientific foundation that prioritizes adaptability and precision in patient care. Through continued research and international collaboration, this study contributes to the critical discourse on managing and overcoming the long-term challenges posed by the pandemic [7,8,9,10].

2. Methods

2.1. Patients

Sample Size and Selection: This research involved 245 subjects (245 individuals (average age 56.8 ± 12 years, 39.60% (p < 0.05; 95%) female, 60.40 male) assessed on average at 150 ± 47.0 days after symptom onset.) who contracted COVID-19 between April 2021 and August 2023. The analysis focused on patients who were hospitalized and later reviewed at a post/long COVID clinic. The patients examined did not report any symptoms or diagnosis of diabetes.

Demographics and Conditions: These patients, consisting of 148 males and 97 females (average age 56.8 ± 12 years), underwent psychodiagnostics interviews and neurocognitive tests (subjects who had had brain or ischemic diseases before COVID were excluded from the sample).

2.2. Phases of the Research

Phase 1: Administration of a protocol that included various neurocognitive and psychological assessment tools such as the MMSE, Rey figure tests, FAB, Hamilton D, Stay X and Y, IES., corrected for gender, age, and education.

Phase 2: A correlation study between the test results and organic changes observed in neuroimaging, identifying the link between cognitive deficits and physical changes in the brain. Only a small percentage of patients had neuroimaging and neurocognitive tests prior to SARS-CoV-2 infection.

Phase 3: Structured cognitive rehabilitation for those with dysexecutive syndrome, incorporating new methods for rehabilitating executive functions, targeted at damaged domains. The effectiveness of the rehabilitation was assessed over a year, with retests at 6 and 12 months.

This methodology section outlines a comprehensive approach to assessing the neurocognitive impacts of COVID-19, employing a multi-phase strategy that progresses from broad screening to detailed examination and rehabilitation. The detailed description of each instrument and its purpose emphasizes the thoroughness of this research in identifying and addressing cognitive deficits arising from COVID-19, particularly focusing on executive functions, memory, spatial planning, and emotional wellbeing [11,12,13,14].

2.3. Instruments

MMSE: A comprehensive assessment of cognitive functions with a scoring system that categorizes the level of cognitive impairment. The total score ranges from a minimum of 0 to a maximum of 30 points. Cutoffs: 25–30 points: normal cognition; 21–24 points: mild dementia; 10–20 points: moderate dementia; 9 points or less: severe dementia.

Figure of Rey: Assesses visual spatial function and memory, with specific cutoffs for evaluation. Cutoffs: Copy > 28 recall > 6.2.

FAB: Examines global executive functioning. It includes the conceptualization of similarities and abstraction, mental flexibility, and the use of self-organizational strategies, programming, planning and organization of behaviors, sensitivity to interference, inhibitory control, and ability to manage impulsiveness and environmental autonomy. The cut-off is >12.

Hamilton D Test: Evaluates the severity of depressive symptoms. The HAM-D items are graded, some at the 3 level (0–2) and others at the 5 level (0–4) of severity, and each level is associated with a precise and comprehensive definition. The cut-offs are as follows: <7 normal/absence, 8–17 mild depression, 18–24 moderate depression, <25 severe depression.

STAI: Measures both state and trait anxiety with a scoring system to classify the level of anxiety. The X and Y forms are composed of 40 items each, where 20 items measure state anxiety and the other 20 measure trait anxiety. State anxiety refers to an emotional state at a given time, while trait anxiety refers to a personality trait that characterizes different people. The cut-offs are classified as follows: <40 normal/absence, 40–50 mild anxiety, 50–60 moderate anxiety, <60 severe anxiety.

IES-R: Assesses the presence of post-traumatic stress disorder (PTSD) symptoms, with cut-offs for avoidance, intrusion, and hyperarousal. The cut-offs for avoidance are as follows: 0–0.5 normal, 0.5–1.00 mild, 1.01–2.49 moderate, 2.5–4 severe. The cut-offs for intrusion are as follows: 0–0.5 normal, 0.5–1.00 mild, 1.01–2.49 moderate, 2.5–4 severe. The cut-offs for hyperarousal are as follows: 0–0.5 normal, 0.5–1.00 mild, 1.01–2.49 moderate, 2.5–4 severe.

3. Multivariate Analysis

A multivariate analysis (MANOVA—multivariate analysis of variance) was conducted to identify patterns and associations that explain the variability of cognitive and psychological impacts post-COVID: Assessment of Gender’s Role in Cognitive Alterations and Psychological Symptoms Post-COVID-19: As shown in Figure 1, women appear to be more affected by cognitive alterations than men. This finding suggests sex-specific vulnerabilities that may be due to biological, social, or behavioral factors that differentiate the impact of COVID-19 on men and women.

Influence of New-Onset Diabetes on the Severity of Cognitive Deficits: Patients with new-onset diabetes (12% (p < 0.05; 95%) of the sample) showed significant cognitive impairments. Specifically, 42% (p < 0.05; 95%) had mild cognitive disorder, 31% (p < 0.05; 95%) had moderate cognitive disorder, and 7% (p < 0.05; 95%) had severe cognitive disorder. A total of 80% (p < 0.05; 95%) of the new-onset diabetic group experienced some form of cognitive deficit, equivalent to 9.6% (p < 0.05; 95%) of the total study population. This substantial fraction underscores the severe impact of new-onset diabetes on cognitive health post-COVID.

Interactions Between PTSD Symptoms and Cognitive Alterations: This analysis aimed to determine if psychological stress contributes to worsening cognitive outcomes. The results indicate that PTSD is present in 78% (p < 0.05; 95%) of patients with mild cognitive deficits and 56% (p < 0.05; 95%) of those with severe disorders. This suggests a significant relationship between PTSD and cognitive impairments, where psychological distress potentially exacerbates cognitive decline.

Note: All data presented in the paper are statistically significant with a p-value of p < 0.05. Where results are not statistically significant, this has been clearly indicated.

4. Results and Discussion

4.1. Cognitive Alteration

The preliminary findings indicated that cognitive impairments were present in 87% (p < 0.05; 95%) of the sample. Specifics are as follows:

• Mild Cognitive Impairment: Detected in 47% (p < 0.05; 95%) of participants and higher in females (31% (p < 0.05; 95%) female, 16% (p < 0.05; 95%) male). This is the largest category. It indicates that nearly half of the post-COVID patients have experienced mild cognitive alterations. This reflects how the virus can impact cognitive functions, albeit not severely, and underscores the importance of monitoring even subtle changes over time.
• Moderate to Severe Impairment: Noted in 21.6% (p < 0.05; 95%) of the male and 12% (p < 0.05; 95%) of the female patients, respectively, with a significant prevalence in males. This category demonstrates that a significant segment of the population experiences cognitive impacts that extend beyond mild. These patients may require more intensive supportive interventions to address these challenges.
• Severe Deficits: 10.8% (p < 0.05; 95%) of the study population showed severe deficits, signaling that this group of individuals may face substantial daily life challenges due to their post-COVID neurological conditions.
• Individual Domain Alterations: At 26.4% (p < 0.05; 95%), this suggests there is a considerable percentage of individuals with disorders manifesting in specific cognitive domains, such as memory, attention, or other executive functions.
• Absence of Decline: Although it represents a small slice of the chart at 5.0% (p < 0.05; 95%), this category is important to acknowledge because it shows that a portion of the patients has not exhibited any detectable cognitive decrease based on the tests used. However, it is noteworthy that the sum of the percentages exceeds 100% (p < 0.05; 95%), which might indicate an overlap of categories (for instance, some individuals may have more than one type of deficit) [7,15,16].

4.2. PTSD Symptoms

PTSD symptoms were reported in 24% (p < 0.05; 95%) of the sample, without significant gender differences. The analysis aimed to determine if psychological stress, particularly PTSD (Post-Traumatic Stress Disorder), contributes to worsening cognitive outcomes in post-COVID patients [17]. The findings revealed a significant presence of PTSD among patients with cognitive impairments, indicating a strong relationship between these conditions.

• Mild Cognitive Deficits: 33.6% (p < 0.05; 95%) of patients who exhibited mild cognitive impairments also showed symptoms of PTSD. This high percentage suggests that a substantial majority of those experiencing less severe cognitive issues are also dealing with significant psychological stress.
• Severe Cognitive Disorders: 20.4% (p < 0.05; 95%) of patients with severe cognitive impairments had PTSD symptoms. While lower than the percentage for mild cognitive deficits, this still represents more than half of the patients with severe cognitive issues, indicating a considerable overlap between severe cognitive decline and PTSD.

These results, shown in Figure 2, suggest that PTSD is commonly found among patients with both mild and severe cognitive impairments, implying that psychological distress may play a role in exacerbating cognitive decline. PTSD can affect brain regions that are critical for memory, attention, and executive function, which are areas also impacted by COVID-19. Therefore, the psychological stress from PTSD could potentially worsen cognitive impairments. Overall, the data also suggest that while a substantial number of PTSD patients experience various levels of cognitive impairment, a majority still do not face cognitive issues. This information could be vital for developing targeted interventions and support mechanisms for those affected.

This significant association underscores the need for a comprehensive approach to post-COVID care that includes mental health support. Addressing PTSD symptoms through targeted psychological interventions may help mitigate cognitive decline and improve overall recovery outcomes for patients. Integrating mental health care with cognitive rehabilitation could be crucial in managing the complex interplay between psychological stress and cognitive impairments in post-COVID patients.

4.3. New-Onset Diabetes

Influence of New-Onset Diabetes on the Severity of Cognitive Deficits:

The findings of this study highlight a significant correlation between new-onset diabetes and cognitive impairments in post-COVID patients. Among the 12% (p < 0.05; 95%) of participants diagnosed with new-onset diabetes, a substantial 80% (p < 0.05; 95%) exhibited some form of cognitive deficit. Within this group, minimal cognitive differences were observed between type 1 and type 2 diabetics. The composition of the sample was as follows: 7% (p < 0.05; 95%) had type 2 diabetes, 5% (p < 0.05; 95%) had type 1, and no cases of LADA diabetes were identified.

This group was further categorized as follows:

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Mild Cognitive Disorder: 42% (p < 0.05; 95%) of new-onset diabetic patients.

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Moderate Cognitive Disorder: 31% (p < 0.05; 95%) of new-onset diabetic patients.

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Severe Cognitive Disorder: 7% (p < 0.05; 95%) of new-onset diabetic patients.

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No Cognitive Deficits: Surprisingly, 20% (p < 0.05; 95%) of the patients exhibited no cognitive deficits, suggesting that a portion of new-onset diabetic patients maintain normal cognitive functions. In Italy, the percentage of people with diabetes stands at 6% (p < 0.05; 95%), with 1.8% (p < 0.05; 95%) having type 1 diabetes. Analyzing the age groups of individuals with diabetes revealed that almost 65% (p < 0.05; 95%) (63.5% (p < 0.05; 95%)) are aged 65 or older, and 20% (p < 0.05; 95%) of Italian diabetics are 80 years old or more. Working-age individuals between 20 and 64 years old represent a significant portion, accounting for 35% (p < 0.05; 95%) (precisely 34.6% (p < 0.05; 95%), approximately one million people). Among these, the largest share belongs to the higher age bracket (50–64 years), comprising 23.7% (p < 0.05; 95%) of all Italian diabetics. Younger individuals, under 20 years of age, make up about 2% (p < 0.05; 95%) of the total.

The age-based classification also reflects the starkly different prevalences of type 1 and type 2 diabetes. Type 2 diabetes accounts for over 90% (p < 0.05; 95%) of diabetic patients, and the likelihood of its onset increases with age.

These findings contextualize this study’s results, underlining the broader demographic trends in the prevalence of different diabetes types and their potential implications for the cognitive impairments observed in post-COVID patients with new-onset diabetes. The high prevalence of cognitive deficits, especially in individuals with type 2 diabetes, aligns with the increasing risk of diabetes-related complications with advancing age.

The data in Figure 3 suggest that new-onset diabetes is associated with varying degrees of cognitive impairment, with a considerable number of patients experiencing mild to moderate deficits. This information is crucial for healthcare providers in customizing interventions and providing support mechanisms for diabetic patients at risk of cognitive decline.

These results indicate that new-onset diabetes post-COVID is strongly associated with cognitive impairments, affecting 9.6% (p < 0.05; 95%) of the total study population [10]. This substantial fraction underscores the severe impact of new-onset diabetes on cognitive health post-COVID and suggests several important considerations [7,17,18]:

Metabolic syndrome and Neurological Interactions: The high prevalence of cognitive impairments in new-onset diabetic patients may be due to complex interactions between metabolic dysregulation and neurological functions. Hyperglycemia, insulin resistance, and inflammation—common in type 2 diabetes—can adversely affect brain health, leading to cognitive decline.

Systemic Impact of COVID-19: These findings highlight the systemic impact of COVID-19, which extends beyond respiratory issues to encompass significant metabolic and neurological disturbances. The virus may trigger or exacerbate metabolic conditions such as diabetes, which in turn contribute to cognitive impairments [19].

Need for Integrated Care: The strong association between new-onset diabetes and cognitive deficits emphasizes the need for integrated care approaches. Post-COVID care should include regular monitoring and management of metabolic health alongside cognitive assessments. The early identification and treatment of diabetes may help mitigate its impact on cognitive functions.

Targeted Interventions: Given the severity of cognitive impairments observed, targeted interventions are necessary. Cognitive rehabilitation programs tailored to the needs of diabetic patients recovering from COVID-19 could help improve cognitive outcomes. Additionally, managing blood sugar levels effectively might reduce the risk of cognitive decline.

4.4. Mood Disorders: Anxiety and Affective Disorders in Diabetes

Mood and affective disorders exhibit a significant prevalence among participants, with the adjusted findings revealing the following:

Overall Mood Disorders: 80.9% (p < 0.05; 95%) of the total sample exhibited mood disorders, highlighting a broader impact of COVID-19 on mental health than initially estimated. This figure is significantly higher than the Italian national average, which reports a prevalence of depression around 5.5% (p < 0.05; 95%) in the general population, according to the latest epidemiological data [20,21,22,23,24,25,26].

Depression: A large segment of the study population is affected by depression, categorized into mild, moderate, and severe levels (Mezzatesta C. et al. in Neurocognitive Disorders in Post and Long COVID Patients: Preliminary Data, Gender Differences and New Diabetes Diagnosis). Among the participants with depression, 12% (p < 0.05; 95%) were newly diagnosed diabetics. Within this group, 7% (p < 0.05; 95%) had type 2 diabetes, and 5% (p < 0.05; 95%) had type 1 diabetes. Among those with type 2 diabetes, 70% (p < 0.05; 95%) experienced depressive symptoms, while the incidence of depression among individuals with type 1 diabetes was 87% (p < 0.05; 95%).

Anxiety: 93.5% (p < 0.05; 95%) of participants reported clinically significant levels of anxiety. Of these, 15% (p < 0.05; 95%) were individuals with new-onset diabetes, with 9% (p < 0.05; 95%) having type 2 diabetes and 6% (p < 0.05; 95%) having type 1 diabetes. This considerable figure underscores the widespread anxiety among participants, including symptoms such as insomnia, irritability, and tension [27,28].

As shown in Figure 4, the data underscore the substantial impact of both depression and anxiety on the participants, highlighting the need for targeted mental health interventions and support.

Gender Differences: Women exhibited higher levels of both anxiety and depression as compared with men, highlighting the critical role of gender in the psychological aftermath of COVID-19.

• These findings underscore the necessity for a comprehensive and integrated approach to post-COVID care, addressing both cognitive and psychological health. Tailored therapeutic strategies, informed by ongoing research and international collaboration, are essential for managing the diverse and interconnected sequelae of COVID-19. Continued research and targeted interventions will be pivotal in navigating the long-term health implications of the pandemic and ensuring effective patient care.

4.5. MRI Findings in Post- and Long COVID

• Our study revealed significant alterations in the MRIs of post- and long COVID patients, highlighting a range of brain changes, which are in agreement with the findings of researchers Marius Schwabenland and Henrike Salié as published in the journal Immunology. Their work underscores the neuroinflammatory processes and immune responses triggered by SARS-CoV-2, which may contribute to the observed structural and functional changes in the brain [29,30].

These changes were observed in 64% (p < 0.05; 95%) of the examined patients, indicating a concerning prevalence of brain alterations among COVID-19 survivors [2,3,7].

Glial Alterations in the Frontal and Prefrontal Lobes (51% (p < 0.05; 95%)):

Glial alterations represent more than half of the cases, with profound implications for cognitive function and behavior. Glial cells, including astrocytes and microglia, play crucial roles in maintaining neural homeostasis, protecting against infections, and supporting synaptic transmission.

Temporal Lobe Atrophy (4% (p < 0.05; 95%)):

Temporal lobe atrophy, though less common, is associated with brain volume loss in a region crucial for memory and facial recognition. This condition can predispose individuals to memory disorders and recognition deficits.

Reduced Hippocampal Size (9% (p < 0.05; 95%)):

The reduction in hippocampal size is significant, as this region is essential for memory formation and retrieval. Reduced hippocampal volume is linked to learning difficulties and long-term memory deficits. The neurological effects of COVID-19 are an emerging area of research, and our findings align with recent studies documenting similar brain changes in post- and long COVID patients [31].

4.5.1. Glial Alterations

Recent studies suggest that COVID-19 can induce neuroinflammation, with microglial and astrocytic activation in the brain. These alterations may contribute to the cognitive and behavioral dysfunctions observed in post-COVID-19 patients. For example, in 2022, Douaud reported significant changes in grey matter and signs of neuroinflammation in COVID-19 patients.

4.5.2. Temporal Lobe Atrophy

The literature indicates that viral infections can accelerate neurodegeneration and brain atrophy. In COVID-19 patients, studies such as [31,32] have shown temporal atrophy in a minority of cases, correlated with cognitive and memory deficits.

4.5.3. Reduced Hippocampal Size

Reduced hippocampal volume has been documented in various studies and is linked to persistent cognitive symptoms in post-COVID-19 patients. For instance [9], observed a correlation between the severity of COVID-19 symptoms and a reduction in hippocampal volume, suggesting a direct impact of the virus on hippocampal neurogenesis [33,34].

4.6. Limitations and Strengths of This Study

This study offers a unique contribution to the existing literature by combining neuropsychological assessments and MRI data to explore the cognitive impacts of COVID-19, particularly related to new-onset diabetes. It builds upon previously published data to provide an integrated view of post-COVID cognitive decline.

However, some limitations must be noted:

No control group could mean that a lack of a non-COVID comparison group limits causal inference.

Overlap of symptoms: Cognitive and psychiatric symptoms (e.g., PTSD, anxiety) may intersect, complicating interpretation.

Selection bias: Patients were all recruited from post-COVID clinics, possibly overrepresenting severe cases.

Few pre-COVID MRIs: Most participants lacked baseline imaging, limiting longitudinal analysis.

Despite these constraints, this study remains one of the few to correlate cognitive impairment and MRI changes in post-COVID patients, underscoring the importance of integrated neurological and metabolic follow-up.

5. Conclusions

Integrating these new insights and international research findings, the conclusions of our study are significantly enriched, underscoring the profound and varied impacts of COVID-19 on cognitive health and the necessity of a nuanced approach to post-recovery care.

Our findings, which indicated cognitive impairments in 87% (p < 0.05; 95%) of the participants, are now contextualized within a global framework of research, illustrating a clearer picture of the pandemic’s neurological aftermath. The heightened prevalence of mild cognitive impairment in females and more severe impairments in males reflects broader biologically and socially mediated vulnerabilities to COVID-19’s neuropsychological effects [34,35].

5.1. Psychological Sequelae

The reported PTSD symptoms in 24% (p < 0.05; 95%) of the sample, without significant gender differences, highlight the psychological toll of the COVID-19 experience. This aligns with global observations of COVID-19’s psychiatric impacts, necessitating integrated mental health support for survivors to address the spectrum of stress-related disorders.

5.2. Intersection with Metabolic Health

The association between new-onset diabetes and cognitive deficits further complicates the post-COVID landscape. This connection emphasizes the virus’s systemic impact, affecting both metabolic processes and cognitive function. International studies suggest that COVID-19’s role in metabolic dysregulation may be a critical factor in understanding and addressing the long-term cognitive sequelae of the infection.

5.3. Neuroanatomy Sequela

The MRI findings in our sample of post- and long COVID patients underscore the need for further research to fully understand the mechanisms underlying these brain changes. Glial alterations, temporal atrophy, and hippocampal reduction suggest significant neuroinflammatory and neurodegenerative impacts of COVID-19. It is crucial to integrate these findings with targeted therapeutic approaches that address both the cognitive and neuropsychiatric consequences of the disease based on emerging evidence from the international literature.

5.4. Conclusions Enhanced by Global Research

The integration of international scientific research into our study’s conclusions offers a more comprehensive understanding of the long-term effects of COVID-19 on cognitive health. It underscores the complexity of these impacts across different populations, marked by gender differences, the severity of cognitive impairments, psychological conditions like PTSD, and the emergence of metabolic issues like diabetes.

This enriched perspective calls for a multidisciplinary approach to post-COVID care, incorporating neurocognitive assessments, psychological support, and metabolic health monitoring. Tailored therapeutic strategies, informed by an expanding body of global research, are essential for addressing the diverse and interconnected sequelae of COVID-19. Ongoing research and international collaboration will be pivotal in navigating the pandemic’s long-term health implications, ensuring that interventions are informed by a broad spectrum of scientific insights and are responsive to the evolving needs of COVID-19 survivors.

The significant data observed in patients with new-onset diabetes post-COVID highlight the critical need for comprehensive and integrated healthcare strategies. Addressing both metabolic and cognitive health is essential for improving long-term outcomes for these patients.

This study highlights the widespread cognitive impairments in post- and long COVID patients, emphasizing the critical role of glial cell dysfunction. Notably, the research reveals significant gender differences in cognitive outcomes and establishes a link between new-onset diabetes and the worsening of cognitive deficits. These findings support the need for targeted interventions to address the neurological sequelae of COVID-19, underscoring the importance of ongoing research into the mechanisms underlying these persistent cognitive impairments.

Moreover, the chronic and progressive nature of these deficits over time may constitute a distinct form of “COVID Dementia,” an emerging condition that warrants close clinical monitoring, regular neuropsychological assessments, and dedicated therapeutic strategies to prevent further cognitive decline and improve the quality of life for affected patients.