There is growing awareness that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, even in its mild or moderate respiratory forms, can include long-term neuropsychological deficits. Standardized neuropsychological, psychiatric, neurological, and olfactory tests were administered to 45 patients 236.51 ± 22.54 days after hospital discharge following severe, moderate, or mild respiratory severity from SARS-CoV-2 infection (severe = intensive care unit hospitalization, moderate = conventional hospitalization, mild = no hospitalization). Deficits were found in all domains of cognition, and the prevalence of psychiatric symptoms was relatively high in the three groups. The severe infection group performed more poorly on long-term episodic memory tests and exhibited greater anosognosia than did the other two groups. Those with moderate infection had poorer emotion recognition, which was positively correlated with persistent olfactory dysfunction. Individuals with mild infection were more stressed, anxious, and depressed. The data support the hypothesis that the virus targets the central nervous system (notably the limbic system) and the notion that there are different neuropsychological phenotypes.

Objective: Several studies have reported poor long-term neuropsychological performances in patients following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but none has yet considered the effect of administering multiple intercorrelated neuropsychological tests and assessed the frequency of cognitive deficits in a normative population. Our aim was therefore to assess the presence of cumulative neuropsychological deficits in an actual post-coronavirus disease of 2019 (COVID-19) comparison group versus one simulated using Monte-Carlo methods. Method: Validated neuropsychological Monte-Carlo simulation methods were applied to scores from a battery of neuropsychological tests (memory, executive, attentional, perceptual, logical reasoning, language, and ideomotor praxis) administered to 121 patients who had had mild, moderate, or severe COVID-19 (mean age: 56.70 years; 32% women), 222 ± 43 days post-infection. The cumulative percentages of the three severity subgroups were compared with the results of a false discovery rate-corrected probability analysis based on normative data. Results: The cumulative percentages of deficits in memory and executive functions among the severe and moderate patients were significantly higher than those estimated for the normative population. Moderate patients also had significantly more deficits in perception and logical reasoning. In contrast, the mild group did not have significantly more cumulative deficits. Conclusions: Moderate and severe forms of COVID-19 cause greater long-term neuropsychological deficits than those that would be found in a normative population, reinforcing the hypothesis of long-term effects of SARS-CoV-2 on cognitive function, independent of the severity of the initial infection.

This meta-analysis was conducted to quantify the risk of patients exhibiting cognitive deficits in the acute phase of COVID-19 at the time of the first variants (i.e., before the vaccine) and quantify the potential vulnerability of older patients and those who experienced more severe respiratory symptoms. To this end, we searched the LitCovid and EMBASE platforms for articles, including preprints, and included all studies (n = 48) that featured a measurement of cognition, which encompassed 2233 cases of COVID-19. Of these, 28 studies reported scores on global cognitive efficiency scales administered in the acute phase of COVID-19 (up to 3 months after infection). We were able to perform a meta-analysis of proportions on 24 articles (N_patients = 943), and a logistic regression on 18 articles (N_patients = 518). The meta-analysis for proportion indicated that 52.31% of patients with COVID-19 exhibited cognitive deficits in the acute phase. This high percentage, however, has to be interpreted taking in consideration the fact that the majority of patients were hospitalized, and some presented neurological complications, such as encephalopathy. A bootstrap procedure with random resampling revealed that an age of 59 was the threshold at which one would be more prone to present cognitive deficits. However, the severity of respiratory symptoms did not influence the scores on a global cognitive efficiency scale. Overall, our results indicated that neuropsychological deficits were a major consequence of the acute phase of the first forms of COVID-19.

The biological mechanisms underlying objective and subjective fatigue in post-COVID syndrome remain unclear. This study investigates whether immune responses during the acute phase of SARS-CoV-2 infection predict fatigue dimensions 6–9 months post-infection. We analyzed serum immune markers from 54 hospitalized patients (mean age: 58.69 ± 10.90 yrs; female: 31 %) and assessed their association with chronic fatigue using general linear mixed models. Elevated levels of IL-1RA, IFNγ, TNFα, and monocyte percentage during acute infection predicted increased physical and total fatigue. Additionally, higher TNFα levels (r = −0.40, p = .019) correlated with reduced awareness of cognitive fatigue. These findings highlight the role of acute inflammation in the persistence of post-COVID fatigue.

Background: Parkinson's disease (PD) is characterized by heterogeneous clinical phenotypes that may be influenced by the asymmetry of striatal denervation. The alpha-Synuclein Origin site and Connectome (SOC) model proposes that different disease onset patterns—“body first” versus “brain first”—affect symptom development and cognitive decline. Objective: This study aims to explore the relationship between striatal denervation asymmetry, ceramide metabolism, and cognitive performance in early-stage PD. Methods: We analyzed data from 329 patients with PD at baseline, categorized by the type of putamen denervation asymmetry predominance at baseline, along with data from 167 healthy controls. We performed generalized linear mixed models introducing ceramides levels and cognitive performance as discriminating factors. Spearman correlations were used to highlight the relationship between cognition and ceramides. Results: Our findings revealed that patients with asymmetric striatal denervation exhibited higher concentrations of C18:0 ceramides compared to both symmetric patients and healthy controls. Moreover, patients with symmetric denervation demonstrated greater cognitive impairment than those with right or left asymmetry. Conclusions: The study highlights the importance of striatal denervation asymmetry in influencing ceramide metabolism and cognitive function in early-stage PD. These findings suggest that specific ceramide profiles may serve as metabolic markers to distinguish clinical phenotypes, providing insights into disease progression.

The emergence of SARS-CoV-2 has renewed interest in the relationship between immunity and cognition. Despite decades of work, the impact of viral exposure, mainly in the field of HIV, herpes and hepatitis infections, on distinct cognitive processes remains unclear, as most studies use global screening tools (e.g., MoCA) in isolation in each infectious context. This systematic narrative review adopts a transnosological approach, summarizing previously reported immune-cognition relationships across viral infections. Of 931 studies, 32 met inclusion criteria (N = 25,325) spanning SARS-CoV-2, HIV, herpes, hepatitis, Epstein-Barr virus, and multiple infections. Reported studies on immuno-cognitive relationships reveal several consistent findings. Elevated circulating CD14⁺CD16⁺ intermediate monocytes correlated with slower processing speed, reduced episodic memory and mental flexibility. Higher CD4⁺ T cells were associated with better processing speed, while reduced T cells and B cells levels together with elevated IgG predicted deficits in memory and attention. Most proinflammatory cytokines (e.g., IL-6, TNF-α, IFN-γ) were associated with impairments in overlapping cognitive domains (e.g., memory), whereas IL-10, an anti-inflammatory cytokine, consistently supported executive and memory performance.