Association Between COVID-19 Pandemic and Serious Mental Illness: Systematic Review within Salutogenesis Model for Public Health Management

Background: The outbreak of the COVID-19 pandemic, the constant transformation of the SARS-COV-2 virus form, exposure to substantial psychosocial stress, environmental change, and isolation have led to the inference that the overall population's mental health could be affected, resulting in an increase in cases of psychosis. Objective(s): We initiated a systematic review to determine the impact of the SARS-COV-2 virus and its long-term effects-in both symptomatic and asymptomatic cases-on people with or without psychosis. We envisioned that this would give us an insight into effective clinical intervention methods for patients with psychosis during and after the pandemic. Method(s): We selected fifteen papers that met our inclusion criteria, i.e., those that considered participants with or without psychiatric illness and exposed to SARS-COV-2 infection, for this review and were retrieved via Google, Google Scholar, MEDLINE, PubMed, and PsychINFO Database. Key Gap: There is a dearth of research in understanding how COVID-19 affects people with or without a prior personal history of psychosis. Result(s): The systematic review summary provides insight into the state of knowledge. Insights from the systematic review have also been reviewed from the salutogenesis model's perspec-tive. There is moderate evidence of new-onset psychosis during the COVID-19 pandemic in which some antipsychotics treated the psychotic symptoms of patients while treating for COVID-19. Suggestions and recommendations are made for preventive and promotive public health strategies. Conclusion(s): The Salutogenesis model and Positive Psychology Interventions (PPI) provide another preventive and promotive public health management approach.Copyright © 2023 Bentham Science Publishers.

Cilta-Cel Efficacy and Safety in Patients with Progressive Multiple Myeloma after Exposure to Non-Cellular Anti-BCMA Immunotherapy

Introduction: CARTITUDE-2 (NCT04133636) is a phase 2, multicohort study evaluating cilta-cel, an anti-BCMA CAR-T therapy, in several multiple myeloma (MM) patient (pt) populations. Objective(s): To report updated results with longer follow-up on cohort C pts with previous exposure to a non-cellular anti- BCMA immunotherapy. Method(s): Cohort C pts had progressive MM after treatment (tx) with a proteasome inhibitor, immunomodulatory drug, anti-CD38 antibody, and non-cellular BCMA-targeting agent. A single cilta-cel infusion (target dose 0.75x106 CAR+ viable T cells/kg) was administered 5-7 days post lymphodepletion. Primary endpoint was minimal residual disease (MRD) negativity at 10-5. Secondary endpoints included overall response rate (ORR), duration of response (DOR), and adverse events (AEs). Result(s): As of June 1, 2022, 20 pts (13 ADC exposed;7 BsAb exposed) were treated with cilta-cel;4 pts did not receive cilta-cel due to either low cellular yield (n=2, 1 in each group) or death due to progressive disease (PD) prior to dosing (n=2, 1 in each group) and 6 pts received anti-BCMA tx as their last line of therapy (n=4 ADC, n=2 BsAb). During prior anti-BCMA tx, best responses included VGPR (ADC: 2 pts;BsAb: 1 pt), sCR (ADC: 1 pt), and CR (BsAb: 1 pt);the rest had best response of stable disease or PD (1 pt not evaluable). Baseline characteristics are presented in Figure 1A. Median time from last anti- BCMA agent to cilta-cel infusion was 195 d;median administered dose of cilta-cel was 0.65x106 CAR+ viable T cells/kg. At a median follow-up of 18.0 mo, 7/10 evaluable pts (70%) were MRD negative at 10-5 (ADC: 5/7 [71.4%], BsAb: 2/3 [66.7%]). ORR: full cohort, 60%;ADC, 61.5%;BsAb, 57.1% (Figure 1B). Median DOR: full cohort, 12.8 mo;ADC, 12.8 mo;BsAb, 8.2 mo. Median PFS: full cohort, 9.1 mo;ADC, 9.5 mo;BsAb, 5.3 mo. Cilta-cel responders had a shorter median duration of last anti- BCMA agent exposure (29.5 d) compared with non-responders (63.5 d). Responders also had a longer median time from last anti-BCMA tx exposure to apheresis (161.0 d) than non-responders (56.5 d). Most common AEs were hematologic. CRS: n=12 (60%;all Gr1/2), median time to onset 7.5 d, median duration 6.0 d. ICANS: n=4 (20%, 2 Gr3/4), median time to onset 9.0 d, median duration 7.0 d. No patient had movement or neurocognitive tx emergent AE/parkinsonism. There were 12 deaths (PD: 8;COVID-19 pneumonia: 2 [not tx related];subarachnoid hemorrhage: 1 [not tx related];C. difficile colitis: 1 [tx related]). (Figure Presented)(Figure Presented)Conclusions: Pts with heavily pretreated MM and previous exposure to a non-cellular anti-BCMA therapy had favorable responses to cilta-cel. However, depth and DOR appear lower than that seen in anti-BCMA-naive pts treated with cilta-cel (at 27.7 mo, median DOR was not reached in heavily pre-treated but anti-BCMA naive CARTITUDE-1 pts). These data may inform tx plans, including sequencing and washout period between BCMA-targeting agentsCopyright © 2023 American Society for Transplantation and Cellular Therapy

Reversible parkinsonism post combined infection with COVID- 19 and typhoid

Objective: To describe a case of levo-dopa responsive parkinsonism secondary to combined COVID-19 and Enteric fever in a patient Background: The first link between viruses and parkinsonism comes from the possible relationship between lethargic encephalitis and the Spanish flu of 1918.In addition, other viruses, including West Nile virus, herpes viruses, influenza A virus, and human immunodeficiency virus (HIV), have been associated with parkinsonism Methods: A 31 years old presented with fever ,headache for 5 days followed by altered sensorium. At presentation he had neck rigidity ,was localizing to pain ,not fully oriented and not following verbal command but he had hypoxia and need nasal oxygen support.He had D-Dimer 12506,COVID-19 RTPCR positive and was treated with Remdesivir,ceftriaxone ,dexamethasone after which he had improvement in sensorium.At day 6 of illness he had generalized rigidity,bradykinesia with slow hypophonic speech and was needing support to sit and walk . A provisional diagnosis of infection related parkinsonism was considered and Cerebrospinal fluid study,MRI Brain and spine ,Blood culture were done .His Cerebrospinal fluid study has normal protein , glucose,cells, stains and culture and negative autoimmune and paraneoplastic plane . His urine culture,blood culture was positive for salmonella typhi and serum widal titre was 1:640.MRI Brain and spine does not show any new abnormalities except old trauma sequalae. He was treated with Levo-dopa carbidopa and titrated to a dose of 675 mg/day and had sustained improvement with levo-dopa carbidopa .There are 6 other case of COVID-19 associated parkinsonism in literature .There are also few case of typhoid associated case of parkinsonism described in literature . Our patient had combined infection of both COVID-19 and typhoid associated parkinsonism. Result(s): We report a case of Infection related parkinsonism secondary to combined COVID-19 plus typhoid infection Conclusion(s): Exploring the potential relationship of co-infection SARS-CoV-2 and Salmonella typhi infection with development of parkinsonism is essential because of the epidemiological implications,as well as to gain a better understanding of the pathophysiological aspects of these disorders.

Possible consequences of Covid-19 on the nervous system

OBJECTIVES: The aim of the survey was to find out what the possible consequences are of the COVID-19 disease on the nervous system and to propose a method of using artificial intelligence. MATERIAL AND METHODS: Recent research has shown that the risks to patients due to severe acute coronavirus 2 respiratory syndrome (SARS-COV-2) differ most significantly depending on age and the presence of underlying comorbidities such as: cardiovascular disease, hypertension, diabetes and others. The consequences of COVID-19 on the nervous system are especially important. We performed a detailed selection of articles describing the effects of COVID-19 on the nervous system. RESULT(S): We made a clear summary of the main consequences of COVID-19 on the nervous system and suggested a way to use artificial intelligence. CONCLUSION(S): We confirmed research that artificial intelligence methods have the potential to accelerate prediction, especially for the possible consequences of COVID-19 on the nervous system.Copyright © 2020 Neuroendocrinology Letters

Can google glass™ technology improve freezing of gait in parkinsonism? A pilot study.

PURPOSE: Freezing of gait (FOG) is a disabling phenomenon defined by the periodic absence or reduction of forward progression of the feet despite the intention to walk. We sought to understand whether Google Glass (GG), a lightweight wearable device that provides simultaneous visual-auditory cues, might improve FOG in parkinsonism. METHODS: Patients with parkinsonism and FOG utilized GG custom-made auditory-visual cue applications: "Walk With Me" and "Unfreeze Me" in a single session intervention. We recorded ambulation time with and without GG under multiple conditions including 25 feet straight walk, dual task of performing serial 7's while straight walking, 180 degree turn after walking 25 feet, and walking through a doorway. FOG and patient experience questionnaires were administered. RESULTS: Using the GG "Walk With Me" program, improvements were noted in the following: average 25 feet straight walk by 0.32 s (SD 2.12); average dual task of serial 7's and 25 feet straight walk by 1.79 s (SD 2.91); and average walk through doorway by 0.59 s (SD 0.81). Average 180 degree turn after 25 feet walk worsened by 1.89 s (SD 10.66). Using the "Unfreeze Me" program, only the average dual task of serial 7's and 25 feet straight walk improved (better by 0.82 s (SD 3.08 sec). All other tasks had worse performance in terms of speed of completion. CONCLUSION: This feasibility study provides preliminary data suggesting that some walking tasks may improve with GG, which uses various musical dance programs to provide visual and auditory cueing for patients with FOG.IMPLICATIONS FOR REHABILITATIONFreezing of gait in parkinsonian syndromes is a disabling motor block described by patients as having their feet stuck to the floor leading to difficulty in initiation of gait and increased risk for falls.Wearable assistive devices such as Google Glass™ use visual and auditory cueing that may improve gait pattern in patients with freezing of gait.Augmented reality programs using wearable assistive devices are a home-based therapy, with the potential for reinforcing physical therapy techniques; this is especially meaningful during the COVID-19 pandemic when access to both medical and rehabilitative care has been curtailed.

Steroid administration for post-COVID-19 Parkinsonism: A case report.

A 45-year-old man developed parkinsonism 3 weeks after being diagnosed with mild COVID-19. Levodopa and benserazide failed to improve his symptoms, necessitating ropinirole, and steroid treatment, which included a 5-day course of methylprednisolone followed by a 3-month oral prednisolone taper. One month after initiating steroid treatment, his symptoms improved significantly.

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.

COVID19-associated new-onset movement disorders: a follow-up study.

BACKGROUND: Neurological symptoms are common manifestation in acute COVID-19. This includes hyper- and hypokinetic movement disorders. Data on their outcome, however, is limited. METHODS: Cases with new-onset COVID-19-associated movement disorders were identified by searching the literature. Authors were contacted for outcome data which were reviewed and analyzed. RESULTS: Movement disorders began 12.6 days on average after the initial onset of COVID-19. 92% of patients required hospital admission (mean duration 23 days). In a fraction of patients (6 of 27; 22%; 4 males/2 females, mean age 66.8 years) the movement disorder (ataxia, myoclonus, tremor, parkinsonism) was still present after a follow-up period of 7.5 ± 3 weeks. Severe COVID-19 in general and development of encephalopathy were risk factors, albeit not strong predictors, for the persistence. CONCLUSIONS: The prognosis of new-onset COVID-19-associated movement disorder appears to be generally good. The majority recovered without residual symptoms within several weeks or months. Permanent cases may be due to unmasking of a previous subclinical movement disorder or due to vascular/demyelinating damage. Given the relatively low response rate of one third only and the heterogeneity of mechanisms firm conclusions on the (long-term) outome cannot, however, be drawn.

Are patients with Parkinson's disease at a lower risk of catching the common cold? Propensity score matching.

INTRODUCTION: Accumulating evidence indicating that inflammatory responses play crucial roles in Parkinson's disease (PD) development provided a hypothesis that physiological alpha-synuclein may contribute to inflammatory responses against infections during non-advanced stages of PD. Thus, we examined the risk of catching a common cold in patients with PD as compared to other common brain diseases. METHODS: We extracted PD (non-advanced; without dementia) and control (AD: Alzheimer's disease, migraine, epilepsy, and ischemic stroke) patient data from insurance claim data available between 2010 and 2021. After confirming the clinical PD diagnosis, we investigated factors associated with cold diagnoses and used propensity score matching to identify differences in the incidence of colds between PD and control patients. RESULTS: Diagnosis of colds in PD patients (n = 726) and controls (AD = 377, migraine = 1019, epilepsy = 3414, ischemic stroke = 6943) was found in 1186 (9.5%) patients, which was independently associated with being female (odds ratio: OR 1.59; 95%CI 1.41-1.79; P < 0.0001), follow-up by neurologists (OR 1.30; 95%CI 1.15-1.48; P < 0.0001), diagnosis of PD (OR 0.30; 95%CI 0.20-0.45; P < 0.0001) and COVID-19 pandemic period (OR 0.58; 95%CI 0.47-0.72; P < 0.0001). After propensity score matching, the incidence of colds was significantly lower in PD (3.4%) versus in controls; AD (9.8%; P < 0.0001), migraine (13.3%; P < 0.0001), epilepsy (11.0%; P < 0.0001), ischemic stroke (8.8%; P < 0.0001). CONCLUSIONS: Patients with PD were less likely to be diagnosed with colds. However, several confounding factors will need to be examined. Moreover, alpha-synuclein may provide protective resistance to viral infections by activating the immune system due to chronic inflammation in non-advanced PD patients.

Investigating neurological symptoms of infectious diseases like COVID-19 leading to a deeper understanding of neurodegenerative disorders such as Parkinson's disease.

Apart from common respiratory symptoms, neurological symptoms are prevalent among patients with COVID-19. Research has shown that infection with SARS-CoV-2 accelerated alpha-synuclein aggregation, induced Lewy-body-like pathology, caused dopaminergic neuron senescence, and worsened symptoms in patients with Parkinson's disease (PD). In addition, SARS-CoV-2 infection can induce neuroinflammation and facilitate subsequent neurodegeneration in long COVID, and increase individual vulnerability to PD or parkinsonism. These findings suggest that a post-COVID-19 parkinsonism might follow the COVID-19 pandemic. In order to prevent a possible post-COVID-19 parkinsonism, this paper reviewed neurological symptoms and related findings of COVID-19 and related infectious diseases (influenza and prion disease) and neurodegenerative disorders (Alzheimer's disease, PD and amyotrophic lateral sclerosis), and discussed potential mechanisms underlying the neurological symptoms and the relationship between the infectious diseases and the neurodegenerative disorders, as well as the therapeutic and preventive implications in the neurodegenerative disorders. Infections with a relay of microbes (SARS-CoV-2, influenza A viruses, gut bacteria, etc.) and prion-like alpha-synuclein proteins over time may synergize to induce PD. Therefore, a systematic approach that targets these pathogens and the pathogen-induced neuroinflammation and neurodegeneration may provide cures for neurodegenerative disorders. Further, antiviral/antimicrobial drugs, vaccines, immunotherapies and new therapies (e.g., stem cell therapy) need to work together to treat, manage or prevent these disorders. As medical science and technology advances, it is anticipated that better vaccines for SARS-CoV-2 variants, new antiviral/antimicrobial drugs, effective immunotherapies (alpha-synuclein antibodies, vaccines for PD or parkinsonism, etc.), as well as new therapies will be developed and made available in the near future, which will help prevent a possible post-COVID-19 parkinsonism in the 21st century.

Parkinsonism associated with viral infection

There are several known causes of secondary parkinsonism, the most common being head trauma, stroke, medications, or infections. A growing body of evidence suggests that viral agents may trigger parkinsonian symptoms, but the exact pathological mechanisms are still unknown. In some cases, lesions or inflammatory processes in the basal ganglia or substantia nigra have been found to cause reversible or permanent impairment of the dopaminergic pathway, leading to the occurrence of extrapyramidal symptoms. This chapter reviews current data regarding the viral agents commonly associated with parkinsonism, such as Epstein Barr virus (EBV), hepatitis viruses, human immunodeficiency virus (HIV), herpes viruses, influenza virus, coxsackie virus, and Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). We present possible risk factors, proposed pathophysiology mechanisms, published case reports, common associations, and prognosis in order to offer a concise overview of the viral spectrum involved in parkinsonism.

Covid-19, nervous system pathology, and Parkinson's disease: Bench to bedside.

Coronavirus disease 2019 (Covid-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is primarily regarded as a respiratory disease; however, multisystemic involvement accompanied by a variety of clinical manifestations, including neurological symptoms, are commonly observed. There is, however, little evidence supporting SARS-CoV-2 infection of central nervous system cells, and neurological symptoms for the most part appear to be due to damage mediated by hypoxic/ischemic and/or inflammatory insults. In this chapter, we report evidence on candidate neuropathological mechanisms underlying neurological manifestations in Covid-19, suggesting that while there is mostly evidence against SARS-CoV-2 entry into brain parenchymal cells as a mechanism that may trigger Parkinson's disease and parkinsonism, that there are multiple means by which the virus may cause neurological symptoms.

Covid-19 and Parkinson's disease: Acute clinical implications, long-COVID and post-COVID-19 parkinsonism.

The Coronavirus Disease 2019 (Covid-19), caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has led to unprecedented challenges for the delivery of healthcare and has had a clear impact on people with chronic neurological conditions such as Parkinson's disease (PD). Acute worsening of motor and non-motor symptoms and long-term sequalae have been described during and after SARS-CoV-2 infections in people with Parkinson's (PwP), which are likely to be multifactorial in their origin. On the one hand, it is likely that worsening of symptoms has been related to the viral infection itself, whereas social restrictions imposed over the course of the Covid-19 pandemic might also have had such an effect. Twenty cases of post-Covid-19 para-infectious or post-infectious parkinsonism have been described so far where a variety of pathophysiological mechanisms seem to be involved; however, a Covid-19-induced wave of post-viral parkinsonism seems rather unlikely at the moment. Here, we describe the interaction between SARS-CoV-2 and PD in the short- and long-term and summarize the clinical features of post-Covid-19 cases of parkinsonism observed so far.

[Post COVID-19 disorders: is the epidemic of parkinsonism threatening the world?] / Postkovidnye narusheniya: grozit li miru epidemiya parkinsonizma?

During the pandemic caused by SARS-CoV-2, the ability of this virus to infect the structures of the peripheral and central nervous system becomes increasingly clear. Damage to the nervous system is noted in almost 85% of patients who have had COVID-19, both those who have had this disease in severe form, and in patients with mild or asymptomatic course. COVID-19 worsens symptoms in patients with Parkinson's disease (PD), which potentially increases the risk of death due to pneumonia and respiratory disorders in patients with severe stages of PD. There is a concern that the COVID-19 pandemic may lead to a sharp increase in the incidence of parkinsonism, while the ability of the SARS-CoV-2 virus to cause PD is assumed. The following ways of virus penetration, including the SARS-CoV-2 virus, into the structures of the central nervous system are considered - viremia and endothelial cell damage, as well as retrograde axonal transport. The direct penetration of the COVID-19 virus into the structures of the brain may be due to a disturbance of the blood-brain barrier due to a «cytokine storm¼ and activation of lymphocytes, which is due to the processes of neuroinflammation. According to some of its manifestations, the extrapyramidal syndrome observed in patients with COVID-19 resembles lethargic encephalitis von Economo. However, the question of the possibility of COVID-19 causing the development of PD is extremely complex and ambiguous. The latency period between viral encephalitis and the onset of parkinsonism can reach 5 years. It is possible that the basis for the development of neurological disorders, including parkinsonism, in this category of patients is an energy deficit that leads to disruption of the functioning of neural networks (human connectome) of the human brain. Based on the currently very limited data concerning the penetration of the COVID-19 virus into the structures of the central nervous system, there is no convincing evidence of this virus causing parkinsonism. The final clarity on this issue will be provided by the results of observations on the condition of patients who have undergone COVID-19.

New-onset Parkinsonism as a Covid-19 infection sequela: A systematic review and meta-analysis.

Background: There remains a scarcity of literature regarding COVID-19 and its neurological sequelae. This study highlights Parkinsonism as a post-COVID-19 sequela and helps us understand a possible link between the two. Methods: A literature search covering relevant databases was conducted for studies reporting the development of Parkinsonism in patients recovering from COVID-19 infection. A quality assessment tool developed by The Joanna Briggs Institute Critical Appraisal tools for the assessment of case reports was utilized. Fisher's exact test was used to explore the factors associated with COVID-19 and Parkinsonism as its complication. Results: Ten studies were included in our study. The median age of patients was 60.0, with an interquartile range of 42.5-72.0. There were 8 males (61.5%) patients, and 53.8% of cases were reported to have at least one comorbidity. Cogwheel rigidity was the most common symptom of Parkinsonism in 11 patients. While the most standard treatment modality used was Levodopa in 76.9% of cases. Using the Fisher's Exact test, it was identified that 10 patients (76.9%) with bradykinesia made a full recovery. Conclusion: Despite presumed "recovery" from COVID-19, patients still face a wide range of neurological complications. One of these complications presenting as Parkinsonism requires health care professionals to be on the lookout for the long-term effects of COVID-19. Hence, our study provides information on the possible likely hood of a link between COVID-19 and the development of Parkinsonism as post-COVID neurological sequelae.

Impact of the COVID-19 pandemic on patients with Parkinson's disease and other movement disorders

Introduction: The coronavirus disease-19 (COVID-19) pandemic is a global health crisis that has directly and indirectly impacted almost all populations globally. In this study, we aimed to study the impact of the COVID-19 pandemic on motor and nonmotor symptoms in patients with various movement disorders who visited our outpatient department. Materials and Methods: We conducted a prospective study using a structured questionnaire involving patients who visited our outpatient department during the COVID-19 pandemic from May 2020 to April 2021. The study was conducted at the Department of Neurology at the National Institute of Mental Health and Neuro Sciences, Bangalore. Results: A total of 208 patients with the following disorders were assessed: Parkinson's disease (n = 141), atypical parkinsonism (n = 31), dystonia (n = 15), Wilson's disease (n = 5), and other disorders (n = 16). Approximately, 3.5% of the patients had acquired the COVID-19 infection. Almost 80% of the patients had missed scheduled appointments with their physicians during this study period due to travel restrictions or the fear of traveling. Approximately, 50% of the patients experienced worsening of their motor and nonmotor symptoms. Approximately, 25% of patients availed teleconsultation facilities, and majority of them found it to be equivalent to or better than in-person consultation. Almost 80% of the patients were eager to receive the COVID-19 vaccination. Conclusion: The COVID-19 pandemic resulted in worsening of both motor and nonmotor symptoms in patients with movement disorders. Teleconsultation is a helpful option in managing the patients' symptoms during the pandemic. © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

Smell deficits in COVID-19 and possible links with Parkinson's disease.

Olfactory impairment is a common symptom in Coronavirus Disease 2019 (COVID-19), the disease caused by Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) infection. While other viruses, such as influenza viruses, may affect the ability to smell, loss of olfactory function is often smoother and associated to various degrees of nasal symptoms. In COVID-19, smell loss may appear also in absence of other symptoms, frequently with a sudden onset. However, despite great clinical interest in COVID-19 olfactory alterations, very little is known concerning the mechanisms underlying these phenomena. Moreover, olfactory dysfunction is observed in neurological conditions like Parkinson's disease (PD) and can precede motor onset by many years, suggesting that viral infections, like COVID-19, and regional inflammatory responses may trigger defective protein aggregation and subsequent neurodegeneration, potentially linking COVID-19 olfactory impairment to neurodegeneration. In the following chapter, we report the neurobiological and neuropathological underpinnings of olfactory impairments encountered in COVID-19 and discuss the implications of these findings in the context of neurodegenerative disorders, with particular regard to PD and alpha-synuclein pathology.