Parkinson disease following COVID-19: Report of six cases.

BACKGROUND AND PURPOSE: Core clinical manifestations of COVID-19 include influenza-like and respiratory symptoms. However, it is now evident that neurological involvement may occur during SARS-CoV-2 infection, covering an extensive spectrum of phenotypical manifestations. A major challenge arising from this pandemic is represented by detecting emerging neurological complications following recovery from SARS-CoV-2 infection. To date, a few post-COVID-19-infected subjects diagnosed with Parkinson disease (PD) have been described, raising the possibility of a connection between the infection and neurodegenerative processes. Here, we describe a case series of six subjects who developed PD after COVID-19. METHODS: Patients were observed at Scientific Institute for Research and Health Care Mondino Foundation Hospital, Pavia (Italy), and San Paolo University Hospital of Milan (Italy) between March 2021 and June 2022. In all subjects, SARS-CoV-2 infection was confirmed by means of reverse transcriptase polymerase chain reaction from a nasopharyngeal swab. Subjects underwent an accurate neurological evaluation, and neuroimaging studies were performed. RESULTS: We describe six subjects who developed PD with an average time window after SARS-CoV-2 infection of 4-7 weeks. Apparently, no relationship with COVID-19 severity emerged, and no overt structural brain abnormalities were found. All subjects experienced unilateral resting tremor at onset and showed a satisfactory response to dopaminergic treatment. CONCLUSIONS: Immune responses to SARS-CoV-2 infection have been shown to shape the individual susceptibility to develop long-term consequences. We hypothesize that, in these subjects, COVID-19 has unmasked a latent neurodegenerative process. Characterization of the neuroinflammatory signatures in larger cohorts is warranted, which might provide novel insights into the pathogenesis of PD.

Not myopathic, but autonomic changes in patients with long-COVID syndrome: a case series.

INTRODUCTION: Neurological sequelae following SARS-CoV-2 infection still represent a serious concern both for neurologists and neuroscientists. In our paper, we investigated pain, myalgia, and fatigue as symptoms in long-COVID patients with an electrophysiological approach, comprising the evaluation of sympathetic skin responses (SSRs) and quantitative electromyography (qEMG). MATERIALS AND METHODS: Twelve patients were enrolled (mean age, 47.7 ± 11.6 years), referred to our attention because of myalgia, pain, or muscle cramps, which persisted about 6 months after the diagnosis of SARS-CoV-2 infection. They underwent conventional electroneurography (ENG), needle electromyography (EMG), and SSRs; moreover, qEMG was performed by sampling at least 20 motor unit potentials (20-30 MUPs) during weak voluntary contraction in deltoid and tibialis anterior muscles. The mean duration, amplitude, and percentage of polyphasic potentials were assessed and compared with healthy and age-matched volunteers. RESULTS: ENG did not disclose significant changes compared to healthy subjects; needle EMG did not reveal denervation activity. In addition, qEMG showed MUPs similar to those recorded in healthy volunteers in terms of polyphasia (deltoid: p = 0.24; TA: p = 0.35), MUP area (deltoid: p = 0.45; TA: p = 0.44), mean duration (deltoid: p = 0.06; TA: p = 0.45), and amplitude (deltoid: p = 0.27; TA: p = 0.63). SSRs were not recordable from lower limbs in seven patients (58%) and from the upper ones in three of them (25%). CONCLUSION: Our data suggest an involvement of the autonomic system, with a focus on cholinergic efferent sympathetic activity, without any evidence of myopathic changes.

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.

Behind the Scenes of COVID-19 Vaccine Hesitancy: Psychological Predictors in an Italian Community Sample.

Psychological variables may be crucial in favoring or discouraging health-related behaviors, including vaccine acceptance. This study aimed to extend the previous literature by outlining the psychological profile associated with COVID-19 vaccine hesitancy in a sample of Italian citizens. Between April and May 2021, 1122 Italian volunteers completed a web survey on COVID-19 vaccine acceptance, also including several self-reported psychological measures. A multiple hierarchical logistic regression analysis was performed to identify the psychological variables associated with vaccine hesitancy. Low confidence in COVID-19 vaccine efficacy and safety, low collective responsibility, high complacency, and high calculation (i.e., extensive information searching, and costs-benefit estimates) predicted higher hesitancy. Our results suggest that to be effective, vaccine-related communications should be as clear, understandable, and sound as possible, preventing the spreading of misunderstandings, or even fake information, that may foster people's insecurities and distrust. Furthermore, the advantages and necessity of vaccination, both at the individual and community-level, should be clearly emphasized. Efficacious vaccine-related communications may be crucial, not only to maintain an adequate immunity rate for COVID-19, but also to inform policymakers and public authorities in the case of possible future infectious outbreaks.

The Psychological Impact of COVID-19 among a Sample of Italian Adults with High-Functioning Autism Spectrum Disorder: A Follow-Up Study.

The strict lockdowns imposed to contain the COVID-19 pandemic brought an increase in levels of stress, anxiety, and depression in the general population. However, in a previous study, our group found that individuals with High-Functioning Autism Spectrum Disorders (HF-ASD) reported an increase in their psychological wellbeing and a decrease in their daily tiredness, in relation to the social distancing measures imposed during the first Italian lockdown (between March and May 2020). In this follow-up study, conducted during the "second wave" of COVID-19, we included the same group of individuals with HF-ASD and evaluated their levels of stress, anxiety, depression, PTSD-related symptoms, tiredness, and perceived wellbeing; moreover, we compared our results to the ones we obtained during the first lockdown on the same population. We found that individuals with HF-ASD experienced higher levels of the aforementioned psychiatric symptoms during the second lockdown, with respect to the first one. These levels positively correlated with their scores at the Autism Quotient subscale Attention Switching: hence, we speculated that these symptoms might be due not only to the prolonging of the social distancing measures, but also to the uncertainty that HF-ASD participants started experiencing at the end of the first lockdown.

COVID-19 vaccination hesitancy among people with chronic neurological disorders: A position paper.

BACKGROUND AND PURPOSE: Health risks associated with SARS-CoV-2 infection are undisputed. Moreover, the capability of vaccination to prevent symptomatic, severe, and fatal COVID-19 is recognized. There is also early evidence that vaccination can reduce the chance for long COVID-19. Nonetheless, the willingness to get vaccinated and receive booster shots remains subpar among people with neurologic disorders. Vaccine scepticism not only jeopardizes collective efforts to end the COVID-19 pandemic but puts individual lives at risk, as some chronic neurologic diseases are associated with a higher risk for an unfavorable COVID-19 course. METHODS: In this position paper, the NeuroCOVID-19 Task Force of the European Academy of Neurology (EAN) summarizes the current knowledge on the prognosis of COVID-19 among patients with neurologic disease, elucidates potential barriers to vaccination coverage, and formulates strategies to overcome vaccination hesitancy. A survey among the Task Force members on the phenomenon of vaccination hesitancy among people with neurologic disease supports the lines of argumentation. RESULTS: The study revealed that people with multiple sclerosis and other nervous system autoimmune disorders are most skeptical of SARS-CoV-2 vaccination. The prevailing concerns included the chance of worsening the pre-existing neurological condition, vaccination-related adverse events, and drug interaction. CONCLUSIONS: The EAN NeuroCOVID-19 Task Force reinforces the key role of neurologists as advocates of COVID-19 vaccination. Neurologists need to argue in the interest of their patients about the overwhelming individual and global benefits of COVID-19 vaccination. Moreover, they need to keep on eye on this vulnerable patient group, its concerns, and the emergence of potential safety signals.

Evidence of SARS-CoV-2 in nasal brushings and olfactory mucosa biopsies of COVID-19 patients.

The aim of the present study is to detect the presence of SARS-CoV-2 of patients affected by COVID-19 in olfactory mucosa (OM), sampled with nasal brushing (NB) and biopsy, and to assess whether a non-invasive procedure, such as NB, might be used as a large-scale procedure for demonstrating SARS-CoV-2 presence in olfactory neuroepithelium. Nasal brushings obtained from all the COVID-19 patients resulted positive to SARS-CoV-2 immunocytochemistry while controls were negative. Double immunofluorescence showed that SARS-CoV-2 positive cells included supporting cells as well as olfactory neurons and basal cells. OM biopsies showed an uneven distribution of SARS-CoV-2 positivity along the olfactory neuroepithelium, while OM from controls were negative. SARS-CoV-2 was distinctively found in sustentacular cells, olfactory neurons, and basal cells, supporting what was observed in NB. Ultrastructural analysis of OM biopsies showed SARS-CoV-2 viral particles in the cytoplasm of sustentacular cells. This study shows the presence of SARS-CoV-2 at the level of the olfactory neuroepithelium in patients affected by COVID-19. For the first time, we used NB as a rapid non-invasive tool for assessing a potential neuroinvasion by SARS-CoV-2 infection.

Putative Role of the Lung-Brain Axis in the Pathogenesis of COVID-19-Associated Respiratory Failure: A Systematic Review.

The emergence of SARS-CoV-2 and its related disease caused by coronavirus (COVID-19) has posed a huge threat to the global population, with millions of deaths and the creation of enormous social and healthcare pressure. Several studies have shown that besides respiratory illness, other organs may be damaged as well, including the heart, kidneys, and brain. Current evidence reports a high frequency of neurological manifestations in COVID-19, with significant prognostic implications. Importantly, emerging literature is showing that the virus may spread to the central nervous system through neuronal routes, hitting the brainstem and cardiorespiratory centers, potentially exacerbating the respiratory illness. In this systematic review, we searched public databases for all available evidence and discuss current clinical and pre-clinical data on the relationship between the lung and brain during COVID-19. Acknowledging the involvement of these primordial brain areas in the pathogenesis of the disease may fuel research on the topic and allow the development of new therapeutic strategies.

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.

The Effect of Surgical Masks on the Featural and Configural Processing of Emotions.

From the start of the COVID-19 pandemic, the use of surgical masks became widespread. However, they occlude an important part of the face and make it difficult to decode and interpret other people's emotions. To clarify the effect of surgical masks on configural and featural processing, participants completed a facial emotion recognition task to discriminate between happy, sad, angry, and neutral faces. Stimuli included fully visible faces, masked faces, and a cropped photo of the eyes or mouth region. Occlusion due to the surgical mask affects emotion recognition for sadness, anger, and neutral faces, although no significative differences were found in happiness recognition. Our findings suggest that happiness is recognized predominantly via featural processing.

A paradoxical psychological impact of COVID-19 among a sample of Italian adults with High Functioning Autism Spectrum Disorder.

BACKGROUND: Since February 2020, many governments of the world ordered strict social distancing rules to try to contain the COVID-19 pandemic, with a reported consequent increase in levels of stress, anxiety and depression in the general population. Aim of this study was to assess the prevalence of the aforementioned psychiatric symptoms across a sample of individuals with High Functioning Autism Spectrum Disorders (HF-ASDs) with respect to a group of neurotypical adults (NA), during the first two months of COVID-19 pandemic in Italy. METHOD: 45 adults with HF-ASDs and 45NA completed a structured online questionnaire, including; the Depression, Anxiety and Stress Scale - 21 items (DASS-21); the Impact of Event Scale-Revised (IES-R); the Perceived Stress Scale (PSS). We also explored some specific aspects of participants' psychological well-being through an ad-hoc questionnaire. RESULTS: Subjects with HF-ASDs scored significantly higher than NA at the DASS-21, the IES-R Total Score and the PSS; NA reported a higher perceived change of their lifestyle during the lockdown than individuals with HF-ASDs, and subjects with HF-ASDs reported to feel more comfortable and less tired during the lockdown period, in relation to the social distancing measures adopted by Italian authorities. CONCLUSIONS: Adults with HF-ASDs presented higher rates of depression, anxiety, stress and PTSD-related symptoms than NA during the first two months of COVID-19 pandemic. However, they also reported to feel subjectively more comfortable and less tired during the lockdown than before, in relation to the social distancing measures.

Critical illness neuropathy in severe COVID-19: a case series.

INTRODUCTION: Neurological complications of SARS-CoV-2 disease have received growing attention, but only few studies have described to date clinical and neurophysiological findings in COVID patients during their stay in intensive care units (ICUs). Here, we neurophysiologically assessed the presence of either critical illness neuropathy (CIP) or myopathy (CIM) in ICU patients. MATERIALS AND METHODS: Patients underwent a neurophysiological assessment, including bilateral examination of the median, ulnar, deep peroneal and tibial motor nerves and of the median, ulnar, radial and sural sensory nerves. Needle electromyography (EMG) was performed for both distal and proximal muscles of the lower and upper limbs. In order to differentiate CIP from CIM, Direct Muscle Stimulation (DMS) was applied either to the deltoid or tibialis anterior muscles. Peak to peak amplitudes and onset latencies of the responses evoked by DMS (DMSamp, DMSlat) or by motor nerve stimulation (MNSamp, MNSlat) were compared. The ratio MNSamp to DMSamp (NMR) and the MNSlat to DMSlat difference (NMD: MNSlat - DMSlat) were also evaluated. RESULTS: Nerve conduction studies showed a sensory-motor polyneuropathy with axonal neurogenic pattern, as confirmed by needle EMG. Both MNSamp and NMR were significantly reduced when compared to controls (p < 0.0001), whereas MNSlat and NMD were markedly increased (p = 0.0049). CONCLUSIONS: We have described COVID patients in the ICU with critical illness neuropathy (CIP). COVID-related CIP could have implications for the functional recovery and rehabilitation strategies.

Resilience, Psychological Well-Being and Daily Functioning Following Hospitalization for Respiratory Distress Due to SARS-CoV-2 Infection.

The ongoing COVID-19 pandemic has affected people's psychological well-being, and hospitalized patients could face an even greater risk of psychological distress. We aimed to study resilience in recovered COVID-19 patients after hospital discharge. We recruited 50 patients (38 males, aged 28-77) who were hospitalized for COVID-19 between March and April 2020. Participants underwent a psychological assessment 5 months after hospital discharge. We administered the Connor-Davidson Resilience Scale (CD-RISC-25), Beck's Depression inventory-II (BDI-II), and the State-Trait Anxiety Inventory Y-form (STAI). We also evaluated the impact of persisting physical, behavioral, and cognitive symptoms on resilience. Patients reported low resilience in the months following hospital discharge (CD-RISC-25 score [mean ± SD] = 55.82 ± 20.76), compared to data from studies on the general population. Lower resilience was associated with mood disturbances in the months following clinical recovery (p = 0.005), persisting fatigue (p = 0.015), sleep changes (p = 0.046), and subjective cognitive complaints (p < 0.05). Recovered COVID-19 patients exhibit low resilience following hospital discharge, which affects psychological well-being. The presence of persisting symptoms following hospital discharge affects psychological resilience. Interventions tailored to increase resilience should be considered to improve quality of life for recovered COVID-19 patients.