Mood, Anxiety and Olfactory Dysfunction in <scp>COVID</scp>‐19: Evidence of Central Nervous System Involvement?

Speth, Marlene M.; Singer-Cornelius, Thirza; Oberle, Michael; Gengler, Isabelle; Brockmeier, Steffi Johanna; Sedaghat, Ahmad R.

doi:10.1002/lary.28964

Cited by 95 publications

(116 citation statements)

References 44 publications

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“…An Italian survey‐based study observed sleep impairment as the most commonly reported neurological symptom (94/103 patients) 73 . A prospective cross‐sectional study from the USA showed that impaired sense of smell was associated with anxiety and depressed mood 74 . Finally, a UK‐wide surveillance study recorded 23 patients with neuropsychiatric disorders, among them new‐onset psychosis (10 patients, 43%), neurocognitive syndrome (6 patients, 26%), and affective disorders (4 patients, 17%) 58 …”

Section: Resultsmentioning

confidence: 99%

Neurological manifestations of coronavirus infections – a systematic review

Almqvist

Granberg

Tzortzakakis

et al. 2020

Ann Clin Transl Neurol

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To optimize diagnostic workup of the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, we systematically reviewed neurological and neuroradiological manifestations of SARS-CoV-2 and all other known human coronavirus species (HCoV). Which lessons can we learn? We identified relevant publications (until 26 July 2020) using systematic searches in PubMed, Web of Science, and Ovid EMBASE with predefined search strings. A total of 4571 unique publications were retrieved, out of which 378 publications were selected for in-depth analysis by two raters, including a total of 17549 (out of which were 14418 SARS-CoV-2) patients. Neurological complications and associated neuroradiological manifestations are prevalent for all HCoVs (HCoV-229E, HKU1, NL63, OC43, Middle East respiratory syndrome (MERS)-CoV, SARS-CoV-1, and SARS-CoV-2). Moreover there are similarities in symptomatology across different HCoVs, particularly between SARS-CoV-1 and SARS-CoV-2. Common neurological manifestations include fatigue, headache, and smell/taste disorders. Additionally, clinicians need to be attentive for at least five classes of neurological complications: (1) Cerebrovascular disorders including ischemic stroke and macro/micro-hemorrhages, (2) encephalopathies, (3) para-/postinfectious immune-mediated complications such as Guillain-Barr e syndrome and acute disseminated encephalomyelitis, (4) (meningo-)encephalitis, potentially with concomitant seizures, and (5) neuropsychiatric complications such as psychosis and mood disorders. Our systematic review highlights the need for vigilance regarding neurological complications in patients infected by SARS-CoV-2 and other HCoVs, especially since some complications may result in chronic disability. Neuroimaging protocols should be designed to specifically screen for these complications. Therefore, we propose practical imaging guidelines to facilitate the diagnostic workup and monitoring of patients infected with HCoVs. additional HCoV species (HCoV-229E, HCoV-HKU1, HCoV-NL63, and HCoV-OC43) cause disease in humans, albeit typically with milder clinical courses. 3 While coronaviruses primarily target the human respiratory system, 4 they can also enter the central nervous system (CNS). This is evident from pre-clinical research, where murine coronaviruses have been used to model human encephalitis for decades. 5 HCoVs also show neurotropism. SARS-CoV-1 6 and SARS-CoV-2 7 both use the cell membrane-bound human angiotensin-converting enzyme 2 for cellular entry, which is, among other tissues, expressed on vascular endothelial cells in the brain. 8 Yet, SARS-CoV-2 seems to have an even higher affinity to bind to this receptor compared to SARS-CoV-1. 9 SARS-CoV-1 and SARS-CoV-2 are also most related genetically, with 79% genome homology. 10 Therefore, it is not surprising that several studies have described neurological symptomatology in both SARS-CoV-1 and SARS-CoV-2 infections. 3,11 Neurological complications have also been described in other HCoVs. 12 The aim of this study ...

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Section: Resultsmentioning

confidence: 99%

Neurological manifestations of coronavirus infections – a systematic review

Almqvist

Granberg

Tzortzakakis

et al. 2020

Ann Clin Transl Neurol

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“…Some authors found significant associations between self-reported olfactory disorders and female gender [ 2 , 7 , 32 , 33 , 34 , 35 ], younger age [ 32 , 33 , 36 , 37 , 38 ], smoker [ 39 ] or no-smoker [ 33 ] habit, hypertension [ 15 ], diabetes [ 18 ], depression [ 40 ], or symptoms such as fever [ 2 ] and nasal obstruction [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Psychophysical Evaluation of the Olfactory Function: European Multicenter Study on 774 COVID-19 Patients

et al. 2021

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Background: The objective evaluation of the olfactory function of coronavirus disease 2019 patients is difficult because of logistical and operator-safety problems. For this reason, in the literature, the data obtained from psychophysical tests are few and based on small case series. Methods: A multicenter, cohort study conducted in seven European hospitals between March 22 and August 20, 2020. The Sniffin-Sticks test and the Connecticut Chemosensory Clinical Research Center orthonasal olfaction test were used to objectively evaluate the olfactory function. Results: This study included 774 patients, of these 481 (62.1%) presented olfactory dysfunction (OD): 280 were hyposmic and 201 were anosmic. There was a significant difference between self-reported anosmia/hyposmia and psychophysical test results (p = 0.006). Patients with gastroesophageal disorders reported a significantly higher probability of presenting hyposmia (OR 1.86; p = 0.015) and anosmia (OR 2.425; p < 0.001). Fever, chest pain, and phlegm significantly increased the likelihood of having hyposmia but not anosmia or an olfactory disturbance. In contrast, patients with dyspnea, dysphonia, and severe-to-critical COVID-19 were significantly more likely to have no anosmia, while these symptoms had no effect on the risk of developing hyposmia or an OD. Conclusions: Psychophysical assessment represents a significantly more accurate assessment tool for olfactory function than patient self-reported clinical outcomes. Olfactory disturbances appear to be largely independent from the epidemiological and clinical characteristics of the patients. The non-association with rhinitis symptoms and the high prevalence as a presenting symptom make olfactory disturbances an important symptom in the differential diagnosis between COVID-19 and common flu.

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“…Conversely, Meini et al reported that chemosensory dysfunction was more frequent in patients requiring hospitalization because of respiratory failure [ 18 ]. Speth et al noticed that the shortness of breath was more severe in patients experiencing olfactory dysfunction [ 29 ]. Although, in this study, there was no difference between patients with and without STD in Group P in terms of shortness of breath, ‘ground-glass appearance’ was significantly more frequent in the patients with STD.…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of smell and taste dysfunction and other related factors in COVID-19

Kavaz

Tahir

Bilek

et al. 2021

Eur Arch Otorhinolaryngol

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Purpose The objective of this study is to evaluate smell and taste dysfunction (STD) in coronavirus disease 2019 positive and negative patients, and to assess the factors associated with STD in COVID-19 positive patients. Methods Patients who had been tested with the real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for COVID-19 were identified, and according to the RT-PCR test results, patients were separated into Positive and Negative Groups. A telephone-based assessment was applied to both groups using the American Academy of Otolaryngology-Head and Neck Surgery Anosmia Reporting Tool. Patients in Positive Group were also asked to rate STD, nasal breathing, and anxiety in three different time periods (pre-/during-/post-COVID) using the visual analog scale (VAS). Results A total of 53 COVID-19 positive and 51 negative patients completed the surveys. STD was eightfold more frequent (OR 8.19; CI 95% 3.22-20.84) in the Positive Group. Of the 53 COVID-19 positive patients, 32 reported STD and 21 did not. 'Ground-glass appearance' on chest-computed tomography was more frequent and median lymphocyte count was significantly lower in COVID-19 positive patients with STD. During-COVID STD and nasal breathing VAS scores were significantly lower than the pre-and post-COVID scores. During-COVID STD scores were significantly correlated with anxiety scores (Spearman's rho-0.404, p = 0.022) but not correlated with nasal breathing scores. Conclusion STD may be related to increased inflammatory response as well as damage of olfactory neuronal pathway or non-neuronal olfactory mucosa. Understanding the exact cause of chemosensory impairment in COVID-19 can be helpful in explaining the pathophysiology of the disease.

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Mood, Anxiety and Olfactory Dysfunction in COVID‐19: Evidence of Central Nervous System Involvement?

Cited by 95 publications

References 44 publications

Neurological manifestations of coronavirus infections – a systematic review

Neurological manifestations of coronavirus infections – a systematic review

Psychophysical Evaluation of the Olfactory Function: European Multicenter Study on 774 COVID-19 Patients

Clinical significance of smell and taste dysfunction and other related factors in COVID-19

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