Amantadine in unvaccinated patients with early, mild to moderate COVID-19: A randomized, placebo-controlled, double-blind trial.

BACKGROUND AND PURPOSE: Adamantanes were listed as an interesting option as an early intervention against COVID-19. We aimed to evaluate the effectiveness of amantadine in preventing the progression of COVID-19 and its neurological sequelae. METHODS: Unvaccinated patients with confirmed SARS-CoV-2 infection within 5 days were enrolled. Subjects were randomized (50:50) to amantadine (AMD; 100 mg twice daily) or placebo (PLB) for 14 days. The Ordinal Scale for Clinical Improvement of the World Health Organization (OSCI-WHO) was the primary measure. Secondary endpoints included assessment for fatigue; depression, disorders of smell and taste, and sleepiness on Days 1 and 15. RESULTS: We enrolled 99 patients (49 AMD and 50 PLB). Disease progression (OSCI-WHO = 4) was observed in 6% (AMD) and 8% (PLB) patients (p > 0.05) with further deterioration (OSCI-WHO〉4) in 0% (AMD) and 8% (PLB) patients (p > 0.05). Complete recovery on Day 15 was 60% higher in the AMD compared with the PLB group (p = 0.025). There was improvement in taste (AMD: p = 0.003; PLB: p = 0.0001) and smell (AMD: p = 0.005; PLB: p = 0.0004) but not in fatigue in both groups. Improvement was observed in the AMD (p = 0.010) but not in the PLB group (p = 0.058) when assessing depression as well as sleepiness (AMD: p = 0.0002; PLB: p = 0.341). There was one death in the PLB group (2.0%) and none in the AMD group (p > 0.05) until Day 210. Overall, the drug was well tolerated. CONCLUSION: The central effects of amantadine on the nervous system with reduction of sleepiness and depression might have had a supportive effect on faster recovery in early COVID-19 patients.

Targeting pain in the long-term treatment of cervical dystonia with botulinum toxin A.

AIMS: Cervical pain is one of the most common non-motor symptoms of cervical dystonia (CD) and affects from 54.6% to 88.9% of patients. To date, minority of studies investigated the relevance of pain in a long-term botulinum toxin (BoNT) therapy of CD. The aim of the study was to define an impact of cervical pain on the disease severity and disability, as well as to assess antinociceptive BoNT efficacy in a long-term treatment of CD. MATERIALS AND METHODS: In this case-control study, CD patients who received stable doses of BoNT for at least 3 years were assessed with the use of validated scales. Participants were divided into two groups depending on the occurrence of CD-related pain. RESULTS: We examined 50 participants who received a mean of 24 injection cycles (6-51) of BoNT during a mean treatment period of 10.3 years (3.0-23.5). Participants with cervical pain (68.0%) were characterized by higher scores in all scales used in this study: TWSTRS severity (p = 0.030), disability (p < 0.001), total (p < 0.001) and TSUI score (p = 0.046). Pain reduction following BoNT injection lasted longer than muscle relaxation in 85.3% of patients. Pain improvement between first and last BoNT injection cycle was reported by 76.5% of patients with CD-related pain. CONCLUSIONS: The presence of cervical pain in CD may increase the severity of muscular symptoms and disease-related disability. BoNT has a noticeable antinociceptive effect in the long-term treatment of CD.

Cladribine suppresses disease activity in neuromyelitis optica spectrum disorder: a 2-year follow-up study.

BACKGROUND AND PURPOSE: Neuromyelitis optica spectrum disorder (NMOSD) is a difficult condition to treat. Cladribine selectively and transiently depletes B and T lymphocytes, leading to long-lasting immune reconstitution. This report describes observations from 24 months of follow-up after cladribine in NMOSD patients. METHODS: This is a retrospective analysis of a case series including 12 seropositive patients with NMOSD. Patients were given cladribine by subcutaneous injections in a series of several 2-day cycles of 20 mg administered at intervals of 4-6 weeks. Thus, the full treatment course delivered a cumulative bioavailable dose similar to that approved for treatment of multiple sclerosis. Annualized relapse rate (ARR), disability (Expanded Disability Status Scale [EDSS] score) and safety in the 24 months preceding and the 24 months following the initiation of cladribine treatment were assessed. RESULTS: The mean ARR in the 24 months preceding cladribine treatment was 1.04 (95% confidence interval [CI] 0.67-1.62). The mean ARR in the 24 months following initiation of cladribine treatment was 0.21 (95% CI 0.08-0.56). The ratio in the rate of events post versus prior cladribine initiation was 0.20 (95% CI 0.07-0.59) and highly significant (p = 0.0073). The EDSS score did not change over the follow-up period (2.5 ± 1.7; mean ± SD) compared to baseline (2.5 ± 1.5; mean ± SD). No serious adverse events considered to be linked to cladribine were observed during follow-up. CONCLUSIONS: Cladribine was safe in NMOSD patients over a 2-year observation period. Cladribine treatment was associated with clinical stabilization, as evidenced by significantly decreased ARR and no progression of EDSS score.

[Orbital pseudotumor - current state of knowledge].

The orbital pseudo-tumor is an orbital inflammatory disease of unknown origin that can affect all the anatomical structures that make up the orbit. The diagnosis is based on the assessment of clinical symptoms, imaging tests and the exclusion of other possible causes. Glucocorticosteroids are used for treatment, but other immunosuppressants as well as biological treatments can be used. The aim of the study is to present, based on the literature review, the current state of knowledge about pathogenesis, symptoms, differential diagnosis, and treatment of the orbital pseudotumor.

[Stigmatisation of people with dementi].

The history of the concept of stigmatization dates back to ancient times, but the meaning of this term has changed over the years. Presently it is defined as the attitude of disapproval, negative perception, discrimination by a group due to certain features presented by it. This problem is also valid in medicine, affecting, among many others disorders, patients with dementia. Stigmatization carries a lot of negative consequences, causing feelings of shame that may lead to the exclusion from society. It also affects families and close relatives. The intensification of stigmatization depends on many factors, such as age, gender, education and ethnic structure of community. In this review paper we try to highlight the problem of stigmatization among people affected by dementia.

[ROLA I WARTOSC ROKOWNICZA MIKROKRWAWIEN MÓZGOWYCH W SCHORZENIACH NEUROLOGICZNYCH THE ROLE AND PROGNOSTIC VALUE OF CEREBRAL MICROBLEEDS IN NEUROLOGICAL DISORDERS 907].

Cerebral microbleeds (CMB) are small foci of low signal which are detected in neuroimaging. They correspond to hemosiderin and other blood breakdown products from brain vessels whose structure was affected by pathological processes. Their pathogenesis is closely related to angiopathy associated with hypertension and cerebral amyloid angiopathy. Microbleeds occur in a completely healthy population as well as in numerous neurological disorders. They are often present in people afflicted with dementia, in the course of neurodegenerative diseases and due to vascular causes. Their prevalence is also higher in people with ischemic stroke and in non-traumatic intracerebral bleeding. The presence of microbleeds is reflected in the prognosis of the patients, the presence of complications of treatment, and the occurrence of the disease entities in previously healthy people. They also affect the emotional state and quality of life of patients. We will try to summarize the current state of knowledge regarding the relationship between microbleeds and neurological disorders and present their potential predictive value.

[Brain microbleeds - definition, pathophysiology and the consequences].

Brain microbleeds are defined as small, circular hypointense changes in T2-sequensec of brain MRI, well demarcated from the surrounding tissue. They represent the phagocytized products of blood distribution extravasated from pathologically altered vessels. The echo-T2-dependent gradient (GRE) and magnetic susceptibility testing (SWI) sequences are usually used to visualize them. The pathogenesis of microbleeds very complex but angiopathy associated with arterial hypertension and cerebral amyloid angiopathy play a special role. Atherosclerotic lesions and inflammatory processes are also important. Microbleeds can be found in healthy people as well as in many disorders such as hypertension, Alzheimer's disease or other types of dementia. Their prevalence increases with age. Microbleeds may have a multidimensional effect on the surrounding brain tissue. It is suggested that they disrupt both the brain structure and the electrical function of neurons. In this review article we present current knowledge on the cerebral microbleeds.

[Dementia - diagnostic and therapeutic problems].

Deterioration of higher cortical functions in the course of dementia affects population of about 50 million people around the world. This clinical syndrome may be accompanied by diagnostic and therapeutic problems. Among them is the delayed diagnosis of dementia resulting from lack of knowledge of the disease, as well as the lack of good diagnostic tools used by general practitioners. Inadequate training of medical personnel may also be the problem, making it difficult to diagnose dementia at its early stage. The phenomenon of social stigmatization of people struggling with dementia is also very important. It affects both the patients themselves, making them look for help later, but also to the attitude of doctors, significantly hindering early diagnostics. Dementia is often accompanied by communication difficulties of the patient, resulting from cognitive impairment. In this study we discuss the main limitations of making early diagnostisc of dementia.

[Paroxysmal dyskinesias - disorder categories, their causes and treatment].

Paroxysmal dyskinesias refer to category of abnormal involuntary movements, such as chorea, dystonia, athetosis, ballism or their various configurations. Depending on the type of seizure, sudden movement, stress, emotions, coffee or alcohol may be the trigger factors. Acute seizures are characterized by short duration and are self-limitated. Patients present correct portray of movements between seizures. Intact consciousness during seizure is the invariable characteristic of all paroxysmal dyskinesias. The intent of this work is to systematize knowledge about paroxysmal dyskinesias. This research includes synthetic information developed based on specialistic literature cencerned with paroxysmal movement disorders. The authors focused primarily on characteristics of the most important issues in this area, into which types of disorders, their causes and treament as well as psychopathology aspect having crucial influence on patients' life comfort were included. The essence of three categories of seizures were put across more extesively: paroxysmal kinesigenic dyskinesia, proxysmal non-kinesigenic dyskinesia and paroxysmal exercise-induced dyskinesia. Primary dyskinesias with genetic basis and secondary to other diseases, such as multiple sclerosis were distinguished. Modes of pharmacological treatment with antiepileptic drug and benzodiazepines were described. Special concern was put on holistic approach to problem of diagnosis and treatment of analyzed movement disorders.

[Review of diagnostic criteria for multiple sclerosis].

Multiple sclerosis (MS) is a chronic, autoimmune disease of the central nervous system, leading to inflammatory demyelination and damage to neurons and their axons. The essence of MS is the occurrence of neurological symptoms associated with the occurance of demyelinating lesions disseminated in time (DIT) and space (DIS) (i.e. occurring within various CNS structures, in particular: pyramidal and cerebellar pathways). The aim of the article was to present the evolution of diagnostic criteria of multiple sclerosis in the years 1965-2017. Analysis of the changing criteria reveal that over the last several years, the time necessary to diagnose the disease, previously associated with the anticipation of subsequent symptoms of MS, now is definitely shorter, and the diagnosis can be made before the next relapse of MS, including cerebrospinal fluid examination.

Anti-MAG autoantibodies are increased in Parkinson's disease but not in atypical parkinsonism.

There is emerging evidence that glial cells are involved in the neuropathological process in Parkinson's disease (PD) in addition to degeneration of neuronal structures. Recently, we confirmed the presence of an adaptive immune response against different glial-derived antigens in PD, with a possible role of anti-MAG, anti-MBP and anti-PLP antibodies in the disease progression. The aim of the present study was to assess humoral response against myelin-associated glycoprotein (MAG) in patients with parkinsonism (both idiopathic and atypical) to check whether these antibodies could serve as biomarkers of PD, its severity and progression. Anti-MAG autoantibodies were measured by an ELISA system in 99 PD patients, 33 atypical parkinsonism patients, and 36 control subjects. In PD patients, anti-MAG IgM autoantibodies were significantly higher in comparison to healthy control subjects (p = 0.038). IgM anti-MAG autoantibodies titers were also significantly higher in the whole group of patients with parkinsonism (either idiopathic or atypical) in comparison to healthy control subjects (1.88 ± 0.84 vs 1.70 ± 1.19, p = 0.017). This difference was mainly driven by the PD group, as the atypical parkinsonism group did not differ significantly from the control group in anti-MAG antibody levels (p = 0.51). A negative correlation between anti-MAG levels and disease duration was found in PD patients. Our study provides evidence for an increased production of autoantibodies against a protein of glial origin in PD. The negative correlation between anti-MAG antibodies and disease duration may suggest possible involvement of the immune system in disease progression. Increasing evidence that glia are involved in the neurodegenerative process to a greater extent than previously thought may turn out be useful in the search for biomarkers of the neurodegenerative process in PD.

Antibodies against small heat-shock proteins in Alzheimer's disease as a part of natural human immune repertoire or activation of humoral response?

Characterization of autoantibodies specific for some disease-related proteins, would allow to better assess their role as diagnostic and prognostic markers. In the light of increasing evidence for both humoral and cellular adaptive immune responses in the pathophysiology of Alzheimer's disease (AD), and data on the increased small heat-shock proteins (sHSP) expression in this disease, it seemed justified to assess humoral response against sHSP in AD patients. The aim of the study was to check whether AD has the ability to elicit immune response against small HSP, which could also serve as disease biomarkers. IgG and IgM autoantibodies against alpha B-crystallin and anti-HSP 60 IgG autoantibodies were assessed in 59 AD patients and 59 healthy subjects. Both IgM and IgG autoantibodies against alpha B-crystallin in AD patients were significantly higher compared to healthy controls (p < 0.05). No statistically significant differences were found between AD patients and healthy subjects were found in anti-HSP60 IgG autoantibody titers (p = 0.29). Anti-HSP60 antibodies present in AD patients may indeed belong to natural human immune repertoire, and chronic neurodegenerative process does not have significant inducing effect on the systemic immunoreactivity against HSP60. Increased titers of IgM and IgG autoantibodies against alpha B-crystallin in AD patients may reflect activation of humoral immune response in the course of this chronic disease, probably secondary to its increased expression. Further prospective studies, on larger group of AD patients and measuring a change in antibodies titers with disease progression are necessary to assess the exact role of these antibodies in AD.

Chitinase 3-like 1: prognostic biomarker in clinically isolated syndromes.

Chitinase 3-like 1 (CHI3L1) has been proposed as a biomarker associated with the conversion to clinically definite multiple sclerosis in patients with clinically isolated syndromes, based on the finding of increased cerebrospinal fluid CHI3L1 levels in clinically isolated syndrome patients who later converted to multiple sclerosis compared to those who remained as clinically isolated syndrome. Here, we aimed to validate CHI3L1 as a prognostic biomarker in a large cohort of patients with clinically isolated syndrome. This is a longitudinal cohort study of clinically isolated syndrome patients with clinical, magnetic resonance imaging, and cerebrospinal fluid data prospectively acquired. A total of 813 cerebrospinal fluid samples from patients with clinically isolated syndrome were recruited from 15 European multiple sclerosis centres. Cerebrospinal fluid CHI3L1 levels were measured by enzyme-linked immunosorbent assay. Multivariable Cox regression models were used to investigate the association between cerebrospinal fluid CHI3L1 levels and time to conversion to multiple sclerosis and time to reach Expanded Disability Status Scale 3.0. CHI3L1 levels were higher in patients who converted to clinically definite multiple sclerosis compared to patients who continued as clinically isolated syndrome (P = 8.1 × 10(-11)). In the Cox regression analysis, CHI3L1 levels were a risk factor for conversion to multiple sclerosis (hazard ratio = 1.7; P = 1.1 × 10(-5) using Poser criteria; hazard ratio = 1.6; P = 3.7 × 10(-6) for McDonald criteria) independent of other covariates such as brain magnetic resonance imaging abnormalities and presence of cerebrospinal fluid oligoclonal bands, and were the only significant independent risk factor associated with the development of disability (hazard ratio = 3.8; P = 2.5 × 10(-8)). High CHI3L1 levels were associated with shorter time to multiple sclerosis (P = 3.2 × 10(-9) using Poser criteria; P = 5.6 × 10(-11) for McDonald criteria) and more rapid development of disability (P = 1.8 × 10(-10)). These findings validate cerebrospinal fluid CHI3L1 as a biomarker associated with the conversion to multiple sclerosis and development of disability and reinforce the prognostic role of CHI3L1 in patients with clinically isolated syndrome. We propose that determining cerebrospinal fluid chitinase 3-like 1 levels at the time of a clinically isolated syndrome event will help identify those patients with worse disease prognosis.

Aggressive behavior as a rare side effect of subthalamic stimulation in Parkinson's disease.

Although deep brain stimulation (DBS) has a well-established position in the treatment of Parkinson's disease (PD), it may be accompanied by different side effects including behavioral changes. We present a patient with advanced PD after bilateral stimulation of the subthalamic nucleus (STN) who developed attacks of aggressive behavior. The patient with a 12 year history of PD underwent the procedure of DBS with one-stage bilateral stereotactic approach using the Leksel G stereotactic frame. For STN identification microrecording technique was applied (5 microelectrodes). Four weeks after surgery STN stimulation was switched on. With increasing the amplitude of stimulation on the right (active contacts 1 and 2) the patient experienced transient episodes of aggression. Change of stimulation mode led to withdrawal of all side effects. We hypothesize that aggression episodes in the patient were caused by stimulation of limbic circuit probable within STN although we cannot exclude simultaneous stimulation of neighboring structures. Aggression episodes are rare side effect of STN-DBS, nevertheless they may be expected in more posteromedial placement of the electrode within STN. The presented case extends the evidence for non-motor functions of STN and highlights its role as an integrating structure within the basal ganglia system.

Cognitive and Motor Decline in Dementia with Lewy Bodies and Parkinson's Disease Dementia.

Background: There is a need to better understand the rate of cognitive and motor decline of Dementia with Lewy bodies (DLB) and Parkinson's disease Dementia (PDD). Objectives: To compare the rate of cognitive and motor decline in patients with DLB and PDD from the E-DLB Consortium and the Parkinson's Incidence Cohorts Collaboration (PICC) Cohorts. Methods: The annual change in MMSE and MDS-UPDRS part III was estimated using linear mixed regression models in patients with at least one follow-up (DLB n = 837 and PDD n = 157). Results: When adjusting for confounders, we found no difference in the annual change in MMSE between DLB and PDD (-1.8 [95% CI -2.3, -1.3] vs. -1.9 [95% CI -2.6, -1.2] [P = 0.74]). MDS-UPDRS part III showed nearly identical annual changes (DLB 4.8 [95% CI 2.1, 7.5]) (PDD 4.8 [95% CI 2.7, 6.9], [P = 0.98]). Conclusions: DLB and PDD showed similar rates of cognitive and motor decline. This is relevant for future clinical trial designs.

Neurofilament heavy chain and heat shock protein 70 as markers of seizure-related brain injury.

PURPOSE: Status epilepticus (SE) has deleterious effects on brain tissue, but whether brief recurrent seizures may also damage neurons represents a matter of controversy. Therefore, it remains a central area of epilepsy research to identify individuals at risk where disease progression can be potentially prevented. Biomarkers may serve as tools for such identification. Thus the present study aimed at analyzing the levels of heat shock protein 70 (HSP-70, also designated as HSPA1A) and neurofilament heavy chain protein (NfH(SMI35) ) in cerebrospinal fluid (CSF) of patients with seizures of different severity. METHODS: Forty-one patients were included, of whom 20 patients had a single generalized tonic-clonic seizure (GTCS) episode (SS), 11 had repetitive GTCS (RS), and 10 experienced convulsive SE. The control group consisted of 18 subjects. HSP-70 levels were measured using a conventional enzyme-linked immunosorbent assay (ELISA), whereas the NfH(SMI35) protein levels were detected by an electrochemiluminescence (ECL) immunoassay. KEY FINDINGS: Patients with SE (p < 0.001) and RS (p < 0.05) had significantly higher NfH(SMI35) levels than controls, and SE was associated with increased concentrations when compared with SS (p < 0.001). NfH(SMI35) levels in SS did not differ from controls. Patients with SE had significantly raised HSP-70 levels compared to RS (p < 0.05), SS (p < 0.05), and controls (p < 0.001). SS and RS did not differ from each or from controls. Levels of NfH(SMI35) and HSP-70 showed a significant correlation (r = 0.34; p = 0.007) in the group of all study subjects, which was not apparent when controls and patients with seizures were considered separately. The correlation between NfH(SMI35) and HSP-70 tended to be inverse in patients with SE, but it did not reach statistical significance (r = -0.3; p > 0.05). SIGNIFICANCE: Studying biochemical markers as additional quantitative tools for the measurement of neuronal damage (especially subclinical), complementary to available techniques of imaging, and clinical assessment might prove useful for identifying patients at risk of accumulating neuronal injury resulting from uncontrolled seizures. NfH(SMI35) and HSP-70 are of potential value as sensitive and specific biomarkers of seizure-related pathologic events. Future longitudinal studies are needed to monitor such patients by correlating biochemical, neuroimaging, and clinical methods of assessment.

Bilateral paramedian thalamic infarction with hypothalamic dysfunction.

Unilateral thalamic lesions cause transient or permanent behavioral, sensory and oculomotor disturbances; bilateral lesions of thalamus result in more severe and longer lasting symptoms. We present an atypical case of bilateral paramedian thalamic infarct with concomitant hypothalamic dysfunction. The only risk factor of ischaemic stroke found in the patient was a short lasting episode of atrial fibrillation. Bilateral paramedian thalamic infarcts may result from occlusion of one paramedian thalamic artery, which arises from the posterior cerebral artery, either with separated or with a common trunk, thus supplying the thalamus bilaterally. Independently of anatomical variants of thalamus blood supply, the most probable cause of infarct in our patient was unilateral or bilateral occlusion of the posterior cerebral artery by cardioembolism, probably in the course of basilar artery occlusion. Hypothalamic dysfunction may accompany thalamic infarcts; thus hypothalamo-pituitary function should be routinely assessed in bithalamic infarcts.

NMOSD-Diagnostic Dilemmas Leading towards Final Diagnosis.

(1) Background: The emergence of white matter lesions in the central nervous system (CNS) can lead to diagnostic dilemmas. They are a common radiological symptom and their patterns may overlap CNS or systemic diseases and provoke underdiagnosis or misdiagnosis. The aim of the study was to assess factors influencing the underdiagnosis of neuromyelitis optica spectrum disorder (NMOSD) as well as to estimate NMOSD epidemiology in Lubelskie voivodeship, Poland. (2) Methods: This retrospective study included 1112 patients, who were made a tentative or an established diagnosis of acute or subacute onset of neurological deficits. The evaluation was based on medical history, neurological examination, laboratory and radiographic results and fulfilment of diagnosis criteria. (3) Results: Up to 1.62 percent of patients diagnosed with white matter lesions and up to 2.2% of the patients previously diagnosed with MS may suffer from NMOSD. The duration of delayed diagnosis is longer for males, despite the earlier age of onset. Seropositive cases for antibodies against aquaporin-4 have worse prognosis for degree of disability. (4) Conclusions: Underdiagnosis or misdiagnosis in NMOSD still remains a problem in clinical practice and has important implications for patients. The incorrect diagnosis is caused by atypical presentation or NMOSD-mimics; however, covariates such as gender, onset and diagnosis age may also have an influence.

The Usefulness of Optical Coherence Tomography in Disease Progression Monitoring in Younger Patients with Relapsing-Remitting Multiple Sclerosis: A Single-Centre Study.

The purpose of the study was to assess the usefulness of optical coherence tomography (OCT) in the detection of the neurodegenerative process in younger patients with multiple sclerosis (MS). The study group consisted of 61 patients with a relapsing remitting course of MS (mean age 36.4 ± 6.7 years) divided into two groups: short (≤5 years) and long (>10 years) disease duration. OCT, P300 evoked potential, Montreal Cognitive Assessment, and performance subtests (Picture Completion and Digit Symbol) of the Wechsler Adult Intelligence Scale were performed in all patients. Mean values of most parameters assessed in OCT (pRNFL Total, pRNFL Inferior, pRNFL Superior, pRNFL Temporalis, mRNFL, GCIPL, mRNFL+GCIPL) were significantly lower in MS patients in comparison to controls. And in patients with longer disease duration in comparison to those with shorter. Most OCT parameters negatively correlated with the EDSS score (p < 0.05). No significant correlation was found between OCT results and both P300 latency and the results of psychometric tests. OCT, as a simple, non-invasive, quick, and inexpensive method, could be useful for monitoring the progression of disease in MS patients.

The use of amantadine in the prevention of progression and treatment of COVID-19 symptoms in patients infected with the SARS-CoV-2 virus (COV-PREVENT): Study rationale and design.

BACKGROUND: COVID-19, a disease caused by infection with the SARS-CoV-2 virus, is asymptomatic or mildly symptomatic in most cases. Some patients, usually burdened with risk factors develop acute respiratory failure and other organ dysfunction. In such cases, the mortality rate is very high despite the use of intensive therapy. Amantadine has complex activity including antiviral, antiinflammatory and dopaminergic effects. This clinical trial will assess the efficacy and safety of amantadine in the prevention of COVID-19 progression toward acute respiratory failure and neurological complications. METHODS AND RESULTS: The trial will enroll 200 patients who are positive for SARS-CoV-2 infection and have one or more risk factors for worsening the disease. These patients will be included as hospitalized or ambulatory subjects for early treatment of illness. The recruitment will take place in 8 centers covering different regions of Poland. For 14 days they will be given either 200 mg of amantadine a day or placebo. Our hypothesis is a considerable reduction in the number of patients with progression toward respiratory insufficiency or neurological complications thanks to the treatment of amantadine. CONCLUSIONS: Demonstrating the efficacy and safety of amantadine treatment in improving the clinical condition of patients diagnosed with COVID-19 is of great importance in combating the effects of the pandemic. It has potential to influence on the severity and course of neurological complications, which are very common and persist long after the infection as long-COVID syndrome. CLINICAL TRIAL REGISTRATION: www. CLINICALTRIALS: gov identification no. NCT04854759; Eudra CT number: 2021-001144-98 (dated 27 February 2021).