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

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.