Brain positron emission tomography (PET) and cognitive abnormalities one year after COVID-19.

Emerging evidence indicates that the etiologic agent responsible for coronavirus disease 2019 (COVID-19), can cause neurological complications. COVID-19 may induce cognitive impairment through multiple mechanisms. The aim of the present study was to describe the possible neuropsychological and metabolic neuroimaging consequences of COVID-19 12 months after patients' hospital discharge. We retrospectively recruited 7 patients (age [mean ± SD] = 56 years ± 12.39, 4 men) who had been hospitalized for COVID-19 with persistent neuropsychological deficits 12 months after hospital discharge. All patients underwent cognitive assessment and brain (18F-FDG) PET/CT, and one also underwent 18F-amyloid PET/CT. Of the seven patients studied, four had normal glucose metabolism in the brain. Three patients showed various brain hypometabolism patterns: (1) unilateral left temporal mesial area hypometabolism; (2) pontine involvement; and (3) bilateral prefrontal area abnormalities with asymmetric parietal impairment. The patient who showed the most widespread glucose hypometabolism in the brain underwent an 18F-amyloid PET/CT to assess the presence of Aß plaques. This examination showed significant Aß deposition in the superior and middle frontal cortex, and in the posterior cingulate cortex extending mildly in the rostral and caudal anterior cingulate areas. Although some other reports have already suggested that brain hypometabolism may be associated with cognitive impairment at shorter intervals from SarsCov-2 infection, our study is the first to assess cognitive functions, brain metabolic activity and in a patient also amyloid PET one year after COVID-19, demonstrating that cerebral effects of COVID-19 can largely outlast the acute phase of the disease and even be followed by amyloid deposition.

Relationship between Reaction Times and Post-COVID-19 Symptoms Assessed by a Web-Based Visual Detection Task.

Long-COVID is a clinical condition in which patients affected by SARS-CoV-2 usually report a wide range of physical and cognitive symptoms from 3 to 6 months after the infection recovery. The aim of the current study was to assess the link between self-reported long-COVID symptoms and reaction times (RTs) in a self-administered Visual Detection Task (VDT) in order to identify the predictor symptoms of the slowing in reaction times to determine attention impairment. In total, 362 participants (age (mean ± S.D.: 38.56 ± 13.14); sex (female-male: 73.76-26.24%)) responded to a web-based self-report questionnaire consisting of four sections: demographics, disease-related characteristics, and medical history questions. The final section consisted of a 23 item 5-point Likert-scale questionnaire related to long-term COVID-19 symptoms. After completing the questionnaire, subjects performed a VDT on a tablet screen to assess reaction times (RTs). An exploratory factorial analysis (EFA) was performed on the 23 long-COVID symptom questions, identifying 4 factors (cognition, behavior, physical condition, presence of anosmia and/or ageusia). The most important predictors of RTs were cognition and physical factors. By dissecting the cognitive and physical factors, learning, visual impairment, and headache were the top predictors of subjects' performance in the VDT. Long-COVID subjects showed higher RTs in the VDT after a considerable time post-disease, suggesting the presence of an attention deficit disorder. Attention impairment due to COVID-19 can be due to the presence of headaches, visual impairments, and the presence of cognitive problems related to the difficulty in learning new activities. The link between the slowing of reaction times and physical and cognitive symptoms post-COVID-19 suggests that attention deficit disorder is caused by a complex interaction between physical and cognitive symptoms. In addition, the study provides evidence that RTs in a VDT represent a reliable measure to detect the presence of long-COVID neurological sequelae.

Serum neurofilament light chain levels in Covid-19 patients without major neurological manifestations.

BACKGROUND: Increased serum levels of neurofilament light chain (sNFL), a biomarker of neuroaxonal damage, have been reported in patients with Covid-19. We aimed at investigating whether sNFL is increased in Covid-19 patients without major neurological manifestations, is associated with disease severity, respiratory and routine blood parameters, and changes longitudinally in the short term. METHODS: sNFL levels were measured with single molecule array (Simoa) technology in 57 hospitalized Covid-19 patients without major neurological manifestations and in 30 neurologically healthy controls. Patients were evaluated for PaO2/FiO2 ratio on arterial blood gas, Brescia Respiratory Covid Severity Scale (BRCSS), white blood cell counts, serum C-reactive protein (CRP), plasma D-dimer, plasma fibrinogen, and serum creatinine at admission. In 20 patients, NFL was also measured on serum samples obtained at a later timepoint during the hospital stay. RESULTS: Covid-19 patients had higher baseline sNFL levels compared to controls, regardless of disease severity. Baseline sNFL correlated with serum CRP and plasma D-dimer in patients with mild disease, but was not associated with measures of respiratory impairment. Longitudinal sNFL levels tended to be higher than baseline ones, albeit not significantly, and correlated with serum CRP and plasma D-dimer. The PaO2/FiO2 ratio was not associated with longitudinal sNFL, whereas BRCSS only correlated with longitudinal sNFL variation. CONCLUSIONS: We provide neurochemical evidence of subclinical axonal damage in Covid-19 also in the absence of major neurological manifestations. This is apparently not fully explained by hypoxic injury; rather, systemic inflammation might promote this damage. However, a direct neurotoxic effect of SARS-CoV-2 cannot be excluded.

One-year cognitive follow-up of COVID-19 hospitalized patients.

BACKGROUND AND PURPOSE: Cognitive dysfunction has been observed following recovery from COVID-19. To the best of our knowledge, however, no study has assessed the progression of cognitive impairment after 1 year. The aim was to assess cognitive functioning at 1 year from hospital discharge, and eventual associations with specific clinical variables. METHODS: Seventy-six patients (aged 22-74 years) who had been hospitalized for COVID-19 were recruited. Patients received neuropsychological assessments at 5 (n = 76) and 12 months (n = 53) from hospital discharge. RESULTS: Over half (63.2%) of the patients had deficits in at least one test at 5 months. Compared to the assessment at 5 months, verbal memory, attention and processing speed improved significantly after 1 year (all p < 0.05), whereas visuospatial memory did not (all p > 0.500). The most affected domains after 1 year were processing speed (28.3%) and long-term visuospatial (18.1%) and verbal (15.1%) memory. Lower PaO2 /FiO2 ratios in the acute phase were associated with worse verbal long-term memory (p = 0.029) and visuospatial learning (p = 0.041) at 5 months. Worse visuospatial long-term memory at 5 months was associated with hyposmia (p = 0.020) and dysgeusia (p = 0.037). CONCLUSION: Our study expands the results from previous studies showing that cognitive impairment can still be observed after 1 year. Patients with severe COVID-19 should receive periodic cognitive follow-up evaluations, as cognitive deficits in recovered patients could have social and occupational implications.

Attachment, Personality and Locus of Control: Psychological Determinants of Risk Perception and Preventive Behaviors for COVID-19.

Background: The understanding of factors that shape risk perception is crucial to modulate the perceived threat and, in turn, to promote optimal engagement in preventive actions. Methods: An on-line, cross-sectional, survey was conducted in Italy between May and July 2020 to investigate risk perception for COVID-19 and the adoption of preventive measures. A total of 964 volunteers participated in the study. Possible predictors of risk perception were identified through a hierarchical multiple linear regression analysis, including sociodemographic, epidemiological and, most of all, psychological factors. A path analysis was adopted to probe the possible mediating role of risk perception on the relationship between the independent variables considered and the adoption of preventive measures. Results: Focusing on the psychological predictors of risk perception, high levels of anxiety, an anxious attachment, and an external locus of control predicted higher perceived risk. Conversely, high levels of openness personality and of avoidant attachment predicted a lower perception of risk. In turn, the higher was the perceived risk the higher was the adoption of precautionary measures. Furthermore, psychological factors influenced the adoption of preventive behaviors both directly and indirectly through their effect on risk perception. Conclusions: Our findings might be taken into high consideration by stakeholders, who are responsible for promoting a truthful perception of risk and proper compliance with precautionary measures.

Testing olfactory dysfunction in acute and recovered COVID-19 patients: a single center study in Italy.

BACKGROUND: Olfactory dysfunction in coronavirus disease 2019 (COVID-19) is common during acute illness and appears to last longer than other symptoms. The aim of this study was to objectively investigate olfactory dysfunction in two cohorts of patients at two different stages: during acute illness and after a median recovery of 4 months. METHODS: Twenty-five acutely ill patients and 26 recovered subjects were investigated. Acute patients had a molecular diagnosis of COVID-19; recovered subjects had a positive antibody assay and a negative molecular test. A 33-item psychophysical olfactory identification test tailored for the Italian population was performed. RESULTS: Median time from symptoms onset to olfactory test was 33 days in acute patients and 122 days in recovered subjects. The former scored a significantly higher number of errors at psychophysical testing (median [IQR]: 8 [13] vs 3 [2], p < 0.001) and were more frequently hyposmic (64% vs 19%, p = 0.002). Recovered subjects reported a variable time to subjective olfactory recovery, from days up to 4 months. Participants included in the study reported no significant nasal symptoms at olfactory testing. Among recovered subject who reported olfactory loss during acute COVID-19, four (27%) were still hyposmic. Demographic and clinical characteristics did not show significant associations with olfactory dysfunction. CONCLUSION: Moderate-to-severe hospitalized patients showed a high level and frequency of olfactory dysfunction compared to recovered subjects. In the latter group, subjects who reported persisting olfactory dysfunction showed abnormal scores on psychophysical testing, indicating that, at least in some subjects, persistent hyposmia may represent a long-term sequela of COVID-19.