[Mechanisms and Management of COVID-19-Associated Taste Disorders].

The taste buds in the human tongue contain specialized cells that generate taste signals when they are stimulated. These signals are then transmitted to the central nervous system, allowing the human body to distinguish nutritious substances from toxic or harmful ones. This process is critical to the survival of humans and other mammals. A number of studies have shown that dysgeusia, or taste disorder, is a common complication of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which can severely affect patients' nutritional intake and quality of life. Based on the physiological process of taste perception, the direct causes of dysgeusia include dysfunction of taste receptors and damage to the taste nervous system, while indirect causes include genetic factors, aging-related changes, bacterial and viral infections, and cancer treatments such as radiotherapy and chemotherapy. The pathogenic factors of dysgeusia are complicated, further research is needed to fully understand the underlying mechanisms, and some of the reported findings and conclusions still need further validation. All these form a great challenge for clinical diagnosis of the cause and targeted treatment of dysgeusia. Herein, we reviewed published research on the physiological process of taste perception, the potential mechanisms of taste disorders related to SARS-CoV-2 infection, and strategies for prevention and treatment, providing theoretical support for establishing and improving the comprehensive management of COVID-19 complicated by taste disorders.

Efficacy of pentasodium diethylenetriamine pentaacetate in ameliorating anosmia post COVID-19.

BACKGROUND: COVID-19 has been frequently demonstrated to be associated with anosmia. Calcium cations are a mainstay in the transmission of odor. One of their documented effects is feedback inhibition. Thus, it has been advocated that reducing the free intranasal calcium cations using topical chelators such as pentasodium diethylenetriamine pentaacetate (DTPA) could lead to restoration of the olfactory function in patients with post-COVID-19 anosmia. METHODOLOGY: This is a randomized controlled trial that investigated the effect of DTPA on post-COVID-19 anosmia. A total of 66 adult patients who had confirmed COVID-19 with associated anosmia that continued beyond three months of being negative for SARS-CoV-2 infection. The included patients were randomly allocated to the control group that received 0.9 % sodium chloride-containing nasal spray or the interventional group that received 2 % DTPA-containing nasal spray at a 1:1 ratio. Before treatment and 30 days post-treatment, the patients' olfactory function was evaluated using Sniffin' Sticks, and quantitative estimation of the calcium cations in the nasal mucus was done using a carbon paste ion-selective electrode test. RESULTS: Patients in the DTPA-treated group significantly improved compared to the control group in recovery from functional anosmia to hyposmia. Additionally, they showed a significant post-treatment reduction in the calcium concentration compared to the control group. CONCLUSION: This study confirmed the efficacy of DTPA in treating post-COVID-19 anosmia.

Comparison of prevalence and evolution of COVID-19 olfactory disorders in patients infected by D614 (wild) and B.1.1.7. Alpha variant: a brief report.

OBJECTIVES: To investigate the prevalence and the evolution of olfactory disorders (OD) related to coronavirus disease 2019 (COVID-19) in patients infected during the first and the second European waves. METHODS: From March 2020 to October 2020, COVID-19 patients with OD were recruited and followed over the 12-month post-infection. The following data were collected: demographic, treatments, vaccination status, and olfactory function. Olfaction was assessed with the Olfactory Disorder Questionnaire (ODQ), and threshold, discrimination, and identification (TDI) test. Outcomes were compared between patients of the first wave (group 1: wild/D614G virus) and the second wave (group 2: B.1.1.7. Alpha variant) at 1-, 3- and 12-month post-infection. RESULTS: Sixty patients completed the evaluations accounting for 33 and 27 patients in group 1 and 2, respectively. The 1-month TDI score (23.7 ± 5.3) was significantly lower in group 2 compared to group 1 (29.8 ± 8.7; p = 0.017). Proportion of normosmic patients at 1-month post-infection was significantly higher in group 1 compared to group 2 (p = 0.009). TDI scores only significantly increased from 1- to 3-month post-infection in anosmic and hyposmic patients. Focusing on There was a negative association between the 1-month ODQ and the 1-month TDI (rs = - 0.493; p = 0.012). ODQ was a significant predictor of TDI scores at 3- and 12-month post-infection. The 12-month prevalence of parosmia was 60.6% in group 1 and 42.4% in group 2, respectively. There was no significant influence of oral corticosteroid treatment, adherence to an olfactory training and vaccination status on the olfactory outcomes. CONCLUSIONS: Patients of the second wave (Alpha B.1.1.7. variant) reported significant higher proportion of psychophysical test abnormalities at 1-month post-infection than patients infected during the first wave (D614G virus).

Platelet-rich plasma injection in the olfactory clefts of COVID-19 patients with long-term olfactory dysfunction.

OBJECTIVE: To investigate safety, feasibility, and effectiveness of platelet-rich plasma (PRP) injection into the olfactory clefts of COVID-19 patients with persistent olfactory dysfunction (OD). METHODS: From March 2022 to July 2022, COVID-19 patients with persistent OD were consecutively recruited to benefit from PRP injection into the olfactory clefts. Patient pain, annoyance, time of procedure, and adverse events were evaluated. Olfactory function was evaluated at baseline and 2-month post-injection with the olfactory disorder questionnaire (ODQ) and threshold, discrimination, and identification (TDI) test. RESULTS: Eighty-seven patients with anosmia (N = 30), hyposmia (N = 40), or parosmia (N = 17) with a mean OD duration of 15.7 months completed the evaluations. The PRP injection was successfully performed in all patients with a mean procedure time of 18.4 ± 3.4 min. The adverse events included transient epistaxis (N = 31), parosmia related to xylocaine spray (N = 10), and vasovagal episode (N = 2). The injection procedure was evaluated as somewhat or moderately painful by 41 (47%) and 22 (25%) patients, respectively. Thirty-seven patients were assessed after 2 months post-injection. The mean ODQ and TDI scores significantly improved from baseline to 2-month post-injection (p < 0.01). The olfactory improvement occurred after a mean of 3.6 ± 1.9 weeks. CONCLUSION: The injection of PRP into the olfactory clefts is safe and associated with adequate patient-reported outcomes. The findings of this preliminary study suggest possible efficacy on subjective and psychophysical evaluations, but future randomized controlled studies are needed to determine the superiority of PRP injection over placebo.

Phantosmia and psychogenic non-epileptic seizures in a patient with burning mouth syndrome suffering from severe depression.

Burning mouth syndrome (BMS) is a rare but serious medical condition with important psychiatric comorbidity and specific psychological correlates. Psychopathology related with BMS represents a real challenge for clinical decision-making. In this case, depression is the leading psychiatric diagnosis associated with patient's BMS somatic pain and is driven by anxiety and a dissociative functioning. Facing a complex psychosomatic symptomatology, we offer new clinical perspectives for the screening of psychological traits of BMS. Moreover, we highlight the need to foster interdisciplinarity to improve differential diagnosis and defining an optimal care path. This case report stimulates a reflection on management challenges for the consultation-liaison psychiatry and shows the importance of a person-centred approach when communicating the diagnosis.

Olfactory distortions in the general population.

Parosmia, distorted smell sensations, is a common consequence of respiratory virus infections. The phenomenon is not well understood in terms of its impact and long-term outcomes. We examined self-reported experiences of parosmia in a population-based sample from the Betula study that was conducted in Umeå in northern Sweden (baseline data collected in 1998-2000). We used a baseline sample of 2168 individuals aged 35-90 years and with no cognitive impairment at baseline. We investigated the prevalence of parosmia experiences and, using regression analyses, its relationship to other olfactory and cognitive variables and quality of life. Benefitting from the longitudinal study design, we also assessed the persistence of parosmia over 5 and 10 years prospectively. Parosmia experiences were prevalent in 4.8% of the population and it often co-occurred with phantosmia ("olfactory hallucinations"), but was not associated with lower self-rated overall quality of life or poor performance on olfactory or cognitive tests. For some individuals, parosmia was retained 5 years (17.0%) or even 10 years later (10.3%). Thus, parosmia experiences are commonly reported in the population, and can be persistent for some individuals, but might be mostly benign in nature. Our work complements research on clinical-level parosmia, which is typically more severe, and recent parosmia reports during the COVID-19 pandemic, where long-term outcomes are still unknown.

Photobiomodulation therapy for treatment olfactory and taste dysfunction COVID-19-related: A case report.

It is postulated that the inflammatory process resulting from SARS-CoV-2 infection is the main cause of smell and taste dysfunctions in patients. In view of this, photobiomodulation, due to its anti-inflammatory and antioxidant effects, may be a promising therapeutic modality to treat these disorders. In the present case report, we observed clinical improvement in the symptoms of anosmia and ageusia related to COVID-19 after treatment with photobiomodulation. Due to the inflammatory nature of COVID-19 and the anti-inflammatory effects, photobiomodulation antioxidants already proven in the literature make it a promising therapeutic modality, especially sequela COVID-related, including olfactory (anosmia) and taste (ageusia) dysfunction. In the present case report, the patient's olfactory and gustatory functions were re-established after 10 treatment sessions with photobiomodulation.

Post-COVID-19 Impairment of the Senses of Smell, Taste, Hearing, and Balance.

BACKGROUND: Various symptoms have been associated with COVID-19, but little is known about the impacts of COVID-19 on the sensory system, risk factors, and the duration of symptoms. This study assesses olfactory, gustatory, hearing, and vestibular systems after COVID-19. METHODS: This cross-sectional, single-center study involved 50 patients one to six months after COVID-19 and reports their patient records and the extent, onset, and duration of olfactory, gustatory, hearing, and balance disorders using questionnaires during and after COVID-19. Sensory symptoms were objectively studied using the following clinical tests after COVID-19 Sniffin' Sticks, taste tests, tone/speech audiometry, and video head impulse test. RESULTS: Post-COVID-19-patients were suffering from olfactory and gustatory impairment for up to six months. According to the Dizziness Handicap Inventory, balance disorders were less noticed: Overall, about 40% of the patients during COVID-19 and nearly all patients recovered within six months. After COVID-19, clinical tests revealed that 75% were suffering from hyposomnia/anosmia, and 20% of all patients reported mild hypogeusia for up to six months. Vestibular disorders and hearing impairment rarely/did not occur. Females were significantly more affected by sensory impairments than males. CONCLUSIONS: COVID-19 particularly caused olfactory and gustatory impairment; balance disorders were present too; vestibular and auditory symptoms were negligible.

Metabolic correlates of olfactory dysfunction in COVID-19 and Parkinson's disease (PD) do not overlap.

PURPOSE: Hyposmia is a common feature of COVID-19 and Parkinson's disease (PD). As parkinsonism has been reported after COVID-19, a link has been hypothesized between SARS-CoV2 infection and PD. We aimed to evaluate brain metabolic correlates of isolated persistent hyposmia after mild-to-moderate COVID-19 and to compare them with metabolic signature of hyposmia in drug-naïve PD patients. METHODS: Forty-four patients who experienced hyposmia after SARS-COV2 infection underwent brain [18F]-FDG PET in the first 6 months after recovery. Olfaction was assessed by means of the 16-item "Sniffin' Sticks" test and patients were classified as with or without persistent hyposmia (COVID-hyposmia and COVID-no-hyposmia respectively). Brain [18F]-FDG PET of post-COVID subgroups were compared in SPM12. COVID-hyposmia patients were also compared with eighty-two drug-naïve PD patients with hyposmia. Multiple regression analysis was used to identify correlations between olfactory test scores and brain metabolism in patients' subgroups. RESULTS: COVID-hyposmia patients (n = 21) exhibited significant hypometabolism in the bilateral gyrus rectus and orbitofrontal cortex with respect to COVID-non-hyposmia (n = 23) (p < 0.002) and in middle and superior temporal gyri, medial/middle frontal gyri, and right insula with respect to PD-hyposmia (p < 0.012). With respect to COVID-hyposmia, PD-hyposmia patients showed hypometabolism in inferior/middle occipital gyri and cuneus bilaterally. Olfactory test scores were directly correlated with metabolism in bilateral rectus and medial frontal gyri and in the right middle temporal and anterior cingulate gyri in COVID-hyposmia patients (p < 0.006) and with bilateral cuneus/precuneus and left lateral occipital cortex in PD-hyposmia patients (p < 0.004). CONCLUSION: Metabolic signature of persistent hyposmia after COVID-19 encompasses cortical regions involved in olfactory perception and does not overlap metabolic correlates of hyposmia in PD.

Treatment of COVID-19-Related Olfactory Disorder Promoted by Kakkontokasenkyushin'i: A Case Series.

Olfactory disorders are one of the characteristic symptoms of the coronavirus disease of 2019 (COVID-19), which causes infection and inflammation of the upper and lower respiratory tract. To our knowledge, there are no treatments for COVID-19-related olfactory disorder. Here, we report five olfactory disorder cases in COVID-19, treated using the Japanese traditional (Kampo) medicine, kakkontokasenkyushin'i. We treated five patients with mild COVID-19 at an isolation facility using Kampo medicine, depending on their symptoms. Patients with the olfactory disorder presented with a blocked nose, nasal discharge or taste impairment. Physical examination using Kampo medicine showed similar findings, such as a red tongue with red spots and sublingual vein congestion, which presented as blood stasis and inflammation; thus, we prescribed the Kampo medicine, kakkontokasenkyushin'i. After administration, the numeric rating scale scores of the smell impairment improved within 3 days from 9 to 3 in case 1, from 10 to 0 in case 2, from 9 to 0 in case 3, from 5 to 0 in case 4, and from 9 to 0 within 5 days in case 5. Following the treatment, other common cold symptoms were also alleviated. Kakkontokasenkyushin'i can be used for treating nasal congestion, rhinitis, and inflammation in the nasal mucosa. The olfactory disorder in COVID-19 has been reportedly associated with inflammation and congestion, especially in the olfactory bulb and olfactory cleft. Kakkontokasenkyushin'i may be one of the treatment alternatives for the olfactory disorder with rhinitis in patients with COVID-19.

Association Between Olfactory Dysfunction and Critical Illness and Mortality in COVID-19: A Meta-analysis.

LEVEL OF EVIDENCE: 4.

Olfactory Training and Visual Stimulation Assisted by a Web Application for Patients With Persistent Olfactory Dysfunction After SARS-CoV-2 Infection: Observational Study.

BACKGROUND: Persistent olfactory dysfunction is a significant complication of SARS-CoV-2 infection. Olfactory training involving aromatic oils has been recommended to improve olfactory recovery, but quantitative data are missing. OBJECTIVE: We aimed to quantify the benefit of olfactory training and visual stimulation assisted by a dedicated web application for patients who experienced olfactory dysfunction for ≥1 month. METHODS: We performed an observational, real-life, data-based study on a cohort of patients who experienced at least 1 month of persistent olfactory dysfunction between January 30 and March 26, 2021. An analysis was performed after a mean olfactory training time of 4 weeks, and at least 500 patients were assessable for primary outcome assessment. Participants exposed themselves twice daily to odors from 4 high-concentration oils and visual stimulation assisted by a dedicated web application. Improvement was defined as a 2-point increase on a 10-point, self-assessed olfactory visual analogue scale. RESULTS: In total, 548 patients were assessable for primary outcome assessment. The mean baseline, self-assessed olfactory score was 1.9 (SD 1.7), and this increased to 4.6 (SD 2.8) after a mean olfactory training time of 27.7 days (SD 17.2). Olfactory training was associated with at least a 2-point increase in 64.2% (352/548) of patients. The rate of patients' olfactory improvement was higher for patients who trained for more than 28 days than that rate for patients who trained for less than 28 days (73.3% vs 59%; P=.002). The time to olfactory improvement was 8 days faster for patients with hyposmia compared to the time to improvement for patients with anosmia (P<.001). This benefit was observed regardless of the duration of the olfactory dysfunction. CONCLUSIONS: Olfactory training and visual stimulation assisted by a dedicated web application was associated with significant improvement in olfaction, especially after 28 days of olfactory training.

Quality of life and safety impact of COVID-19 associated smell and taste disturbances.

OBJECTIVE: The association between COVID-19 and chemosensory loss has garnered substantial attention, however to date little is known about the real-life consequences of impairment in this unique patient population. The aim of this study is to evaluate the quality of life (QOL) and personal safety deficits experienced by patients with COVID-19 infection. STUDY DESIGN: Prospective, longitudinal questionnaires. SETTING: National survey. METHODS: A longitudinal web-based nationwide survey of adults with COVID-19 and/or a sudden change in smell and taste was launched April 10, 2020. Previously published questions on chemosensory-related QOL and safety events were asked at the 6-month follow-up survey. RESULTS: As of February 10, 2021, 480 eligible respondents took the 6-month questionnaire, of whom 322 were COVID-19 positive. Impact on QOL was substantial with 96% of subjects reporting at least one of the defined deficits, and over 75% reporting at least 3 of these. "Reduced enjoyment of food" was the most common complaint (87%), while 43% of subjects self-reported depression. The prevalence of safety-related issues was common in this population, with over 57% reporting at least one, and 36% reporting 2 or more events. Of the events asked, the inability to smell smoke that others could perceive was the most common at 45%. CONCLUSIONS: COVID-19 associated chemosensory losses have a real and substantial impact on both quality of life and safety, beyond mere inconvenience. The high prevalence of these issues despite a relatively short period of olfactory deficit should alert clinicians to the serious risks to an already vulnerable patient population.

Chemosensory Dysfunction in Patients with COVID-19: What Do We Learn from the Global Outbreak?

PURPOSE OF REVIEW: Chemosensory dysfunction in the patients with COVID-19 has been reported frequently in the studies from different regions of the world. However, the prevalence of smell and/or taste disorders presents significant ethnic and geographic variability. In addition, the pathogenesis of chemosensory dysfunction remains unclarified. RECENT FINDINGS: This is a narrative review on the recent state of the prevalence, mechanism, and diagnostic and therapeutic strategy of chemosensory dysfunction in COVID-19 patients during the global pandemic. The chemosensory dysfunction was analysis based on recent studies, which either used questionnaires, Likert scales (0-10), or smell tests to estimate the smell and taste dysfunction. The ethnic and geographic difference of the prevalence of smell and/or taste disorders and the potential underlying mechanisms have been discussed. Several suggestions on the diagnosis and treatment of COVID-19 patients with smell and taste disorders were summarized for the physicians. This review provides a comprehensive overview of the current studies regarding the chemosensory dysfunction during the COVID-19 worldwide outbreak.

The relationship between positivity for COVID-19 RT-PCR and symptoms, clinical findings, and mortality in Turkey.

Introduction: This study aimed to assess the correlation between nucleic acid amplification test (real-time reverse transcription-polymerase chain reaction, RT-PCR) positivity of patients presenting with suspected COVID-19 and pneumonic infiltration consistent with COVID-19-specific pneumonia diagnosis on thoracic computed tomography (CT), with symptoms, laboratory findings, and clinical progression.Methods: The study included 286 patients (female:male 131:155; mean age, 53.3 ± 17.9 years) who were divided into two groups according to their RT-PCR test results. The symptoms, laboratory examinations, clinical findings, and thoracic CT imaging of the patients were evaluated.Results: While the physical examination, comorbidities, and total CT scores were similar between the groups, taste/smell abnormalities were observed more frequently in the PCR-positive group. The use of moxifloxacin, lopinavir/ritonavir, and tocilizumab was higher in the PCR-positive group (p = 0.016, p < 0.001, and p = 0.002, respectively). The duration of hospitalization, intensive care requirement, and mortality rate of the studied groups did not differ between the groups.Conclusions: Among patients presenting with suspected COVID-19 and pneumonic infiltration consistent with COVID-19 on thoracic CT, the symptoms, physical examination, total CT scores, duration of hospitalization, intensive care requirement, and mortality rate were similar between RT-PCR-positive and RT-PCR-negative patients. However, PCR-positive patients appeared to require more specific treatments.

Could COVID-19 anosmia and olfactory dysfunction trigger an increased risk of future dementia in patients with ApoE4?

The association of the coronavirus disease 2019 (COVID-19) with significant neurological and neuropsychiatric complications has been increasingly reported, both during the acute illness and in its aftermath. However, due to the short duration of patient follow up until now, it is not clear whether this infection will be associated with longer-term neurological and/or neuropsychiatric sequelae. In particular, the question of whether COVID-19 will be associated with an increased risk and rate of future dementia remains open and subject to speculation. During the course of the COVID-19 pandemic, an increasing number of patients have reported sudden anosmia or other olfactory dysfunction as concurrent symptoms. The possibility that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may reach the brain via the olfactory nerve or an upper nasal trancribrial route is an interesting working hypothesis. Among the identified genetic risk factors for Late-onset Alzheimer's disease (LOAD), Apo E4 is one of the strongest and most frequent. People carrying one or two copies of the e4 allele of Apo E4 have significant odor recognition deficits in comparison to those not carrying this haplotype. The hypothesis invoked in this paper is that anosmia/olfactory dysfunctions induced by SARS-CoV-2 may cause an increased a risk of future neurodegenerative dementia in ApoE4 carriers, and that this risk would be higher than in Apo E4 carriers affected by anosmia not induced by SARS-CoV-2. This would be associated with virus-induced chronic modifications in the central nervous system. It is proposed that COVID-19 patients with anosmia and no other serious symptoms should be followed up as part of specifically designed and approved studies in order to identify the early stages of dementia (especially LOAD and Dementia with Lewy Bodies), thereby improving our knowledge of the mechanisms involved in pre-cognitive stages of neurodegenerative dementia and making best use of any available therapies. This latter opportunity is unique and should not be lost.

Frequency and Clinical Utility of Olfactory Dysfunction in COVID-19: a Systematic Review and Meta-analysis.

BACKGROUND: Olfactory dysfunction (OD) has been gaining recognition as a symptom of COVID-19, but its clinical utility has not been well defined. OBJECTIVES: To quantify the clinical utility of identifying OD in the diagnosis of COVID-19 and determine an estimate of the frequency of OD amongst these patients. METHODS: PubMed was searched up to 1 August 2020. Meta-analysis A included studies if they compared the frequency of OD in COVID-19 positive patients (proven by reverse transcription polymerase chain reaction) to COVID-19 negative controls. Meta-analysis B included studies if they described the frequency of OD in COVID-19 positive patients and if OD symptoms were explicitly asked in questionnaires or interviews or if smell tests were performed. RESULTS: The pooled frequency of OD in COVID-19 positive patients (17,401 patients, 60 studies) was 0.56 (0.47-0.64) but differs between detection via smell testing (0.76 [0.51-0.91]) and survey/questionnaire report (0.53 [0.45-0.62]), although not reaching statistical significance (p = 0.089). Patients with reported OD were more likely to test positive for COVID-19 (diagnostic odds ratio 11.5 [8.01-16.5], sensitivity 0.48 (0.40 to 0.56), specificity 0.93 (0.90 to 0.96), positive likelihood ratio 6.10 (4.47-8.32) and negative likelihood ratio 0.58 (0.52-0.64)). There was significant heterogeneity amongst studies with possible publication bias. CONCLUSION: Frequency of OD in COVID-19 differs greatly across studies. Nevertheless, patients with reported OD were significantly more likely to test positive for COVID-19. Patient-reported OD is a highly specific symptom of COVID-19 which should be included as part of the pre-test screening of suspect patients.

Neurological injuries in COVID-19 patients: direct viral invasion or a bystander injury after infection of epithelial/endothelial cells.

A subset of patients with coronavirus 2 disease (COVID-19) experience neurological complications. These complications include loss of sense of taste and smell, stroke, delirium, and neuromuscular signs and symptoms. The etiological agent of COVID-19 is SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), an RNA virus with a glycoprotein-studded viral envelope that uses ACE2 (angiotensin-converting enzyme 2) as a functional receptor for infecting the host cells. Thus, the interaction of the envelope spike proteins with ACE2 on host cells determines the tropism and virulence of SARS-CoV-2. Loss of sense of taste and smell is an initial symptom of COVID-19 because the virus enters the nasal and oral cavities first and the epithelial cells are the receptors for these senses. Stroke in COVID-19 patients is likely a consequence of coagulopathy and injury to cerebral vascular endothelial cells that cause thrombo-embolism and stroke. Delirium and encephalopathy in acute and post COVID-19 patients are likely multifactorial and secondary to hypoxia, metabolic abnormalities, and immunological abnormalities. Thus far, there is no clear evidence that coronaviruses cause inflammatory neuromuscular diseases via direct invasion of peripheral nerves or muscles or via molecular mimicry. It appears that most of neurologic complications in COVID-19 patients are indirect and as a result of a bystander injury to neurons.

Neurological manifestations of COVID-19: available evidences and a new paradigm.

The recent pandemic outbreak of coronavirus is pathogenic and a highly transmittable viral infection caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2). In this time of ongoing pandemic, many emerging reports suggested that the SARS-CoV-2 has inimical effects on neurological functions, and even causes serious neurological damage. The neurological symptoms associated with COVID-19 include headache, dizziness, depression, anosmia, encephalitis, stroke, epileptic seizures, and Guillain-Barre syndrome along with many others. The involvement of the CNS may be related with poor prognosis and disease worsening. Here, we review the evidence of nervous system involvement and currently known neurological manifestations in COVID-19 infections caused by SARS-CoV-2. We prioritize the 332 human targets of SARS-CoV-2 according to their association with brain-related disease and identified 73 candidate genes. We prioritize these 73 genes according to their spatio-temporal expression in the different regions of brain and also through evolutionary intolerance analysis. The prioritized genes could be considered potential indicators of COVID-19-associated neurological symptoms and thus act as a possible therapeutic target for the prevention and treatment of CNS manifestations associated with COVID-19 patients.