SARS-CoV-2 and the nervous system: current perspectives.

SARS-CoV-2 infection frequently causes neurological impairment in both adults and children. Recent publications have described significant aspects of the viral pathophysiology associated with neurological dysfunction. In theory, neurological manifestations following SARS-CoV-2 infection may be caused directly by the effects of the virus infecting the brain or indirectly by the local and systemic immune responses against the virus. Neurological manifestations can occur during the acute phase as well as in the post-acute phase of the infection. In this review, we discuss recent literature describing the association of nervous system disorders with COVID-19.

Bone marrow necrosis and fat embolism syndrome in sickle cell disease during COVID-19 infection treated successfully with sequential red cell and plasma exchange.

Fat embolism syndrome (FES) is a rare life-threatening condition that is particularly seen in milder forms of sickle cell disease (SCD). Widespread systemic fat emboli are generated in the context of extensive bone marrow necrosis. Multi-organ failure with a high morbidity and mortality may quickly develop. Infection with Parvovirus B19 is a common precipitant. Here, the authors report the case of a 35-year-old Afro-Caribbean man with HbSC disease who presented with FES having tested positive for SARS-COV-2. He rapidly became critically ill and required admission to the intensive care unit for organ support. He was treated with red cell exchange and plasma exchange and made a good recovery to leave hospital at week 7.

Effects of Varying Glucose Concentrations on ACE2's Hypothalamic Expression and Its Potential Relation to COVID-19-Associated Neurological Dysfunction.

The coronavirus disease 2019 (COVID-19) pandemic has negatively impacted millions of lives, despite several vaccine interventions and strict precautionary measures. The main causative organism of this disease is the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) which infects the host via two key players: the angiotensin-converting enzyme 2 (ACE2) and the transmembrane protease, serine 2 (TMPRSS2). Some reports revealed that patients with glycemic dysregulation could have increased susceptibility to developing COVID-19 and its related neurological complications. However, no previous studies have looked at the involvement of these key molecules within the hypothalamus, which is the central regulator of glucose in the brain. By exposing embryonic mouse hypothalamic neurons to varying glucose concentrations, we aimed to investigate the expression of ACE2 and TMPRSS2 using quantitative real time polymerase chain reaction and western blotting. A significant and time-dependent increase and decrease was observed on the viability of hypothalamic neurons with increasing and decreasing glucose concentrations, respectively (p < 0.01 and p < 0.001, respectively). Under the same increasing and decreasing glucose conditions, the expression of hypothalamic ACE2 also revealed a significant and time-dependent increase (p < 0.01). These findings suggest that SARS-CoV-2 invades the hypothalamic circuitry. In addition, it highlights the importance of strict glycemic control for COVID-19 in diabetic patients.

Neurological Manifestations of SARS-CoV2 Infection: A Narrative Review.

The COVID-19 virus frequently causes neurological complications. These have been described in various forms in adults and children. Headache, seizures, coma, and encephalitis are some of the manifestations of SARS-CoV-2-induced neurological impairment. Recent publications have revealed important aspects of viral pathophysiology and its involvement in nervous-system impairment in humans. We evaluated the latest literature describing the relationship between COVID-19 infection and the central nervous system. We searched three databases for observational and interventional studies in adults published between December 2019 and September 2022. We discussed in narrative form the neurological impairment associated with COVID-19, including clinical signs and symptoms, imaging abnormalities, and the pathophysiology of SARS-CoV2-induced neurological damage.

Lower Respiratory Tract Infections in Pediatric Patients with Severe Neurological Impairments: Clinical Observations and Perspectives in a Palliative Care Unit.

Pediatric palliative care (PPC) patients with a severe neurologic impairment (SNI) suffer considerable morbidity and increased mortality from lower respiratory tract infections (LRTIs). The indication and choice of antibiotic therapy for bacterial LRTIs are often challenging given the lack of evidence-based treatment recommendations for this vulnerable patient population. We conducted an observational study before the SARS-CoV-2 pandemic in an eight-bed pediatric palliative care inpatient unit. During two years of surveillance, we diagnosed and treated 33 cases of a bacterial LRTI in patients with an SNI; 5 patients were hospitalized with an LRTI more than once. Two patients died from complications due to LRTIs during hospitalization. Three patients (15%) were colonized with multidrug-resistant organisms. An initial antibiotic treatment failed in one-third of the cases; a successful therapy of the LRTI was achieved with broad-spectrum and extended-spectrum penicillins (n = 13; in combination with ß-lactamase inhibitors for n = 5 cases), cephalosporins (n = 13: n = 4 second-generation and n = 9 third-generation cephalosporins; in combination with other substances for n = 5 cases), ciprofloxacin (n = 3), and meropenem plus vancomycin (n = 2) or meropenem (n = 1). A respiratory specimen was obtained in 66.7% of cases with P. aeruginosa, E. coli, and K. pneumoniae accounting for the majority of the detected species. In most cases, there was no definite confirmation that the LRTI was caused by the species detected. The diagnostics and treatment of bacterial LRTIs in PPC patients with an SNI are challenging. The lack of controlled studies and the heterogeneity of this population often necessitate an individual approach. This lack of controlled studies may partly be compensated by a set of diagnostic and antibiotic stewardship criteria.

Transforming curry extract-spice to liposome-based curcumin

Despite the devastating impact of COVID-19 on all domains of health, very few studies focus on epigenetics-based approaches to target both the viral-host immune responses and central nervous system involvement in COVID-19. Hospitalized COVID-19 patients experience a wide array of neurological symptoms ranging from convulsions to strokelike syndrome and anosmia. None of the pipeline antiviral drugs has been shown to penetrate the blood-brain barrier to exert neurotrophic actions to counteract the COVID-19 damage to the brain. We have identified curcumin extracted from Turmeric (Curcuma longa) exhibiting dual properties: to disrupt viral attachment and hijacking host-viral immune response and to target epigenetics pathway regulating oxidative stress and inflammation responses underlying COVID-19 syndrome. We recruit nanotechnology to formulate liposome-based curcumin: Lipocurc, and completed Phase I study showing very favorable safety and efficacy in Parkinson disease model. We propose to translate the findings to COVID-19 syndrome and exploit the antidepressant and cognitive enhancing properties to accelerate recovery from COVID-19 through navigating brain pathways regulating mood, behavioral control, and cognition within the context of acute and postacute COVID-19 syndrome. © 2021 Elsevier Inc.

Multidisciplinary outpatient rehabilitation of physical and neurological sequelae and persistent symptoms of covid-19: a prospective, observational cohort study.

PURPOSE: This prospective, observational cohort study investigated the effects of multidisciplinary rehabilitation of post Covid-19 sequelae and persistent symptoms and their impact on patients' functioning and quality of life. METHODS: From 58 patients referred for neurorehabilitation, 43 were eligible for and participated in the present study. Before and after 8 weeks of rehabilitation, patients underwent physical, neuropsychological and respiratory evaluations and assessment of functional independence, impact of fatigue and quality of life. RESULTS: Forty of 43 individuals (52 ± 11.4 years, 24 male) completed the rehabilitation program. Fatigue (87.5%), dyspnea and/or shortness of breath (62.5%), and cognitive impairment (37.5%) were reported by both previously hospitalized and home-confined patients. Neurological sequelae (35.5%) were present only in hospitalized patients. After 8 weeks of rehabilitation, patients reported significant improvements in motor functional independence, upper and lower limb functionality, impact of fatigue on daily activities, respiratory muscle strength, cognitive performance, and quality of life. CONCLUSIONS: Post Covid-19 patients present with heterogeneous neurological, physical, and respiratory impairments requiring a multidisciplinary rehabilitation approach to reduce disability and improve functionality and quality of life. A comprehensive assessment of clinical profiles and responses to rehabilitation may facilitate the identification of rehabilitation candidates and help to design effective rehabilitation interventions.Implication for rehabilitationPost Covid-19 patients present multiple, heterogeneous neurological, physical and respiratory impairments that are observed in both previously hospitalized and home-confined patients.Eight weeks of multidisciplinary rehabilitation may significantly reduce disability and improve functionality and quality of life.A comprehensive assessment of their clinical profile and response to rehabilitation may facilitate the identification of rehabilitation candidates and help to design more effective rehabilitation interventions.

What's going on following acute covid-19? Clinical characteristics of patients in an out-patient rehabilitation program.

BACKGROUND: Coronavirus disease 2019 (COVID-19) patients present long-lasting physical and neuropsychological impairment, which may require rehabilitation. OBJECTIVES: The current cross-sectional study characterizes post COVID-19 sequelae and persistent symptoms in patients in an outpatient rehabilitation program. METHODS: Thirty patients [16 post-ICU and 14 non-ICU; median age = 54(43.8-62) years; 19 men] presenting sequelae and/or persistent symptoms (>3 months after acute COVID-19) were selected of 41 patients referred for neurorehabilitation. Patients underwent physical, neuropsychological and respiratory evaluation and assessment of impact of fatigue and quality of life. RESULTS: The main reasons for referral to rehabilitation were: fatigue (86.6%), dyspnea (66.7%), subjective cognitive impairment (46.7%) and neurological sequelae (33.3%). Post-ICU patient presented sequelae of critical illness myopathy and polyneuropathy, stroke and encephalopathy and lower forced vital capacity compared to non-ICU patients. Cognitive impairment was found in 63.3% of patients, with a similar profile in both sub-groups. Increased physical fatigue, anxiety and depression and low quality of life were prevalent irrespective of acute COVID-19 severity. CONCLUSIONS: The variability of post COVID-19 physical and neuropsychological impairment requires a complex screening process both in ICU and non-ICU patients. The high impact of persistent symptoms on daily life activities and quality of life, regardless of acute infection severity, indicate need for rehabilitation.

[SARS-CoV-2 and neurological disorders: the revelance of biomarkers?] / SARS-CoV-2 et atteintes neurologiques : quelle est la place des biomarqueurs ?

Soon after the pandemic, numerous publications described cases of neurological disorders associated with the SARS-CoV-2 infection. The range of neurological symptoms is becoming increasingly more extensive as the pandemic progresses. However, it is not yet well established whether the manifestations are due to direct viral damage to the nervous system or indirect consequences of the infection. This review presents an inventory of the biochemical markers studied in the context of neurological disorders related to SARS-CoV-2. By reflecting various physiopathological mechanisms, these biomarkers allow both a better understanding of the pathophysiology of Covid-19 and a contribution to the diagnosis of neurologic troubles; they could participate in the prognostic evaluation of patients.