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      Funktionelle und morphologische Geschmacks- und Geruchsstörungen bei COVID-19-Patienten Translated title: Functional and morphological disorders of taste and olfaction in COVID-19 patients

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          Abstract

          Ziele

          Testen der Prävalenz und Entwicklung akuter olfaktorischer und gustatorischer Funktionsstörungen und ihrer morphologischen Korrelate bei COVID-19-Patienten, die aufgrund von COVID-19-bedingten Atemwegserkrankungen einen Krankenhausaufenthalt benötigen.

          Methoden

          Eingeschlossen wurden 53 Krankenhauspatienten (23 Männer, 30 Frauen, Alter 42,54 ± 10,95 Jahre) mit RT-PCR-bestätigter COVID-19-Diagnose. Die Patienten wurden zweimal untersucht: direkt nach der Entlassung aus dem Krankenhaus und 4–6 Wochen später. Elektrogustometrische (EGM-)Schwellen im von der Chorda tympani versorgten Zungenbereich, am weichen Gaumen und im Bereich der Papillae vallatae wurden beidseitig erfasst. Der Geruchssinn wurde mit Riechstäbchen untersucht (Sniffin’ Sticks, Burghart GmbH, Wedel, Deutschland). Mittels Kontaktendoskopie wurden die Nasen- und Mundschleimhäute (fungiforme Papillen, fPap) der Patienten untersucht. Die Ergebnisse wurden mit denen von 53 gesunden Personen verglichen (23 Männer, 30 Frauen, Alter 42,90 ± 10,64 Jahre).

          Ergebnisse

          Die EGM-Schwellenwerte der Patienten waren in beiden Fällen signifikant höher als die der gesunden Probanden. Die EGM-Schwellenwerte bei der 2. Messung waren signifikant niedriger als bei der 1. Messung. Dementsprechend waren die vom Patienten berichteten gustatorischen Ergebnisse bei der 2. Messung verbessert. Dasselbe Muster wurde bei der Verwendung von Sniffin’ Sticks gefunden. Signifikante Veränderungen in Form und Vaskularisierung von fPap wurden bei Patienten festgestellt, insbesondere beim 1. Mal. Bemerkenswert ist, dass keine signifikanten Unterschiede in der Vaskularisation der Nasenschleimhaut der Patienten beobachtet wurden.

          Schlussfolgerung

          COVID-19 beeinträchtigt sowohl die Geschmacks- als auch die Geruchsfunktion. Es beeinflusst auch parallel die Struktur und Vaskularisierung der Mundschleimhaut, wenn auch die Nasenschleimhaut in einem viel geringeren, nicht signifikanten Ausmaß. Unsere Ergebnisse deuten darauf hin, dass COVID-19 eine leichte bis schwere Neuropathie mehrerer Hirnnerven verursachen kann.

          Translated abstract

          Objective

          This study aimed to test the prevalence and evolution of acute olfactory and gustatory functional impairment and their morphologic correlates in COVID-19 patients who require hospitalization due to COVID-19-related respiratory conditions.

          Methods

          Included were 53 consecutive hospitalized patients (23 males, 30 females; age 42.54 ± 10.95 years) with an RT-PCR-confirmed COVID-19 diagnosis. Patients were examined twice: just after hospital discharge and 4–6 weeks later. Electrogustometric (EGM) thresholds at the tongue area supplied by the chorda tympani, at the soft palate, and in the region of the vallate papillae were recorded bilaterally. Olfaction was examined by Sniffin’ sticks (Burghardt GmbH, Wedel, Germany). The patients’ nasal and oral mucosa (fungiform papillae, fpap) were examined by contact endoscopy. Findings were compared to those of 53 healthy individuals matched for sex and age (23 males, 30 females; age 42.90 ± 10.64 years).

          Results

          EGM thresholds in patients were significantly higher than those of healthy subjects at both timepoints. EGM thresholds at the second measurement were significantly lower than those at the first measurement. Accordingly, patient-reported gustatory outcomes were improved at the second measurement. The same pattern was found using Sniffin’ sticks. Significant alterations in form and vascularization of fPap were detected in patients, especially at the first instance. Interestingly we did not observe any significant changes in the morphology and vascularization of nasal mucosa.

          Conclusion

          COVID-19 affects both gustatory and olfactory functions. In parallel, it also affects the structure and vascularization of both nasal and oral mucosa, albeit the nasal mucosa to a much lesser, non-significant extent. Our findings suggest that COVID-19 may cause a mild to profound neuropathy of multiple cranial nerves.

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          Most cited references31

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          Neurological associations of COVID-19

          Summary Background The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is of a scale not seen since the 1918 influenza pandemic. Although the predominant clinical presentation is with respiratory disease, neurological manifestations are being recognised increasingly. On the basis of knowledge of other coronaviruses, especially those that caused the severe acute respiratory syndrome and Middle East respiratory syndrome epidemics, cases of CNS and peripheral nervous system disease caused by SARS-CoV-2 might be expected to be rare. Recent developments A growing number of case reports and series describe a wide array of neurological manifestations in 901 patients, but many have insufficient detail, reflecting the challenge of studying such patients. Encephalopathy has been reported for 93 patients in total, including 16 (7%) of 214 hospitalised patients with COVID-19 in Wuhan, China, and 40 (69%) of 58 patients in intensive care with COVID-19 in France. Encephalitis has been described in eight patients to date, and Guillain-Barré syndrome in 19 patients. SARS-CoV-2 has been detected in the CSF of some patients. Anosmia and ageusia are common, and can occur in the absence of other clinical features. Unexpectedly, acute cerebrovascular disease is also emerging as an important complication, with cohort studies reporting stroke in 2–6% of patients hospitalised with COVID-19. So far, 96 patients with stroke have been described, who frequently had vascular events in the context of a pro-inflammatory hypercoagulable state with elevated C-reactive protein, D-dimer, and ferritin. Where next? Careful clinical, diagnostic, and epidemiological studies are needed to help define the manifestations and burden of neurological disease caused by SARS-CoV-2. Precise case definitions must be used to distinguish non-specific complications of severe disease (eg, hypoxic encephalopathy and critical care neuropathy) from those caused directly or indirectly by the virus, including infectious, para-infectious, and post-infectious encephalitis, hypercoagulable states leading to stroke, and acute neuropathies such as Guillain-Barré syndrome. Recognition of neurological disease associated with SARS-CoV-2 in patients whose respiratory infection is mild or asymptomatic might prove challenging, especially if the primary COVID-19 illness occurred weeks earlier. The proportion of infections leading to neurological disease will probably remain small. However, these patients might be left with severe neurological sequelae. With so many people infected, the overall number of neurological patients, and their associated health burden and social and economic costs might be large. Health-care planners and policy makers must prepare for this eventuality, while the many ongoing studies investigating neurological associations increase our knowledge base.
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            Neuropathology of patients with COVID-19 in Germany: a post-mortem case series

            Background Prominent clinical symptoms of COVID-19 include CNS manifestations. However, it is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, gains access to the CNS and whether it causes neuropathological changes. We investigated the brain tissue of patients who died from COVID-19 for glial responses, inflammatory changes, and the presence of SARS-CoV-2 in the CNS. Methods In this post-mortem case series, we investigated the neuropathological features in the brains of patients who died between March 13 and April 24, 2020, in Hamburg, Germany. Inclusion criteria comprised a positive test for SARS-CoV-2 by quantitative RT-PCR (qRT-PCR) and availability of adequate samples. We did a neuropathological workup including histological staining and immunohistochemical staining for activated astrocytes, activated microglia, and cytotoxic T lymphocytes in the olfactory bulb, basal ganglia, brainstem, and cerebellum. Additionally, we investigated the presence and localisation of SARS-CoV-2 by qRT-PCR and by immunohistochemistry in selected patients and brain regions. Findings 43 patients were included in our study. Patients died in hospitals, nursing homes, or at home, and were aged between 51 years and 94 years (median 76 years [IQR 70–86]). We detected fresh territorial ischaemic lesions in six (14%) patients. 37 (86%) patients had astrogliosis in all assessed regions. Activation of microglia and infiltration by cytotoxic T lymphocytes was most pronounced in the brainstem and cerebellum, and meningeal cytotoxic T lymphocyte infiltration was seen in 34 (79%) patients. SARS-CoV-2 could be detected in the brains of 21 (53%) of 40 examined patients, with SARS-CoV-2 viral proteins found in cranial nerves originating from the lower brainstem and in isolated cells of the brainstem. The presence of SARS-CoV-2 in the CNS was not associated with the severity of neuropathological changes. Interpretation In general, neuropathological changes in patients with COVID-19 seem to be mild, with pronounced neuroinflammatory changes in the brainstem being the most common finding. There was no evidence for CNS damage directly caused by SARS-CoV-2. The generalisability of these findings needs to be validated in future studies as the number of cases and availability of clinical data were low and no age-matched and sex-matched controls were included. Funding German Research Foundation, Federal State of Hamburg, EU (eRARE), German Center for Infection Research (DZIF).
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              Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study

              Summary Background Concerns regarding potential neurological complications of COVID-19 are being increasingly reported, primarily in small series. Larger studies have been limited by both geography and specialty. Comprehensive characterisation of clinical syndromes is crucial to allow rational selection and evaluation of potential therapies. The aim of this study was to investigate the breadth of complications of COVID-19 across the UK that affected the brain. Methods During the exponential phase of the pandemic, we developed an online network of secure rapid-response case report notification portals across the spectrum of major UK neuroscience bodies, comprising the Association of British Neurologists (ABN), the British Association of Stroke Physicians (BASP), and the Royal College of Psychiatrists (RCPsych), and representing neurology, stroke, psychiatry, and intensive care. Broad clinical syndromes associated with COVID-19 were classified as a cerebrovascular event (defined as an acute ischaemic, haemorrhagic, or thrombotic vascular event involving the brain parenchyma or subarachnoid space), altered mental status (defined as an acute alteration in personality, behaviour, cognition, or consciousness), peripheral neurology (defined as involving nerve roots, peripheral nerves, neuromuscular junction, or muscle), or other (with free text boxes for those not meeting these syndromic presentations). Physicians were encouraged to report cases prospectively and we permitted recent cases to be notified retrospectively when assigned a confirmed date of admission or initial clinical assessment, allowing identification of cases that occurred before notification portals were available. Data collected were compared with the geographical, demographic, and temporal presentation of overall cases of COVID-19 as reported by UK Government public health bodies. Findings The ABN portal was launched on April 2, 2020, the BASP portal on April 3, 2020, and the RCPsych portal on April 21, 2020. Data lock for this report was on April 26, 2020. During this period, the platforms received notification of 153 unique cases that met the clinical case definitions by clinicians in the UK, with an exponential growth in reported cases that was similar to overall COVID-19 data from UK Government public health bodies. Median patient age was 71 years (range 23–94; IQR 58–79). Complete clinical datasets were available for 125 (82%) of 153 patients. 77 (62%) of 125 patients presented with a cerebrovascular event, of whom 57 (74%) had an ischaemic stroke, nine (12%) an intracerebral haemorrhage, and one (1%) CNS vasculitis. 39 (31%) of 125 patients presented with altered mental status, comprising nine (23%) patients with unspecified encephalopathy and seven (18%) patients with encephalitis. The remaining 23 (59%) patients with altered mental status fulfilled the clinical case definitions for psychiatric diagnoses as classified by the notifying psychiatrist or neuropsychiatrist, and 21 (92%) of these were new diagnoses. Ten (43%) of 23 patients with neuropsychiatric disorders had new-onset psychosis, six (26%) had a neurocognitive (dementia-like) syndrome, and four (17%) had an affective disorder. 18 (49%) of 37 patients with altered mental status were younger than 60 years and 19 (51%) were older than 60 years, whereas 13 (18%) of 74 patients with cerebrovascular events were younger than 60 years versus 61 (82%) patients older than 60 years. Interpretation To our knowledge, this is the first nationwide, cross-specialty surveillance study of acute neurological and psychiatric complications of COVID-19. Altered mental status was the second most common presentation, comprising encephalopathy or encephalitis and primary psychiatric diagnoses, often occurring in younger patients. This study provides valuable and timely data that are urgently needed by clinicians, researchers, and funders to inform immediate steps in COVID-19 neuroscience research and health policy. Funding None.
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                Author and article information

                Contributors
                papavlid@googlemail.com
                Journal
                HNO
                HNO
                Hno
                Springer Medizin (Heidelberg )
                0017-6192
                1433-0458
                30 August 2022
                : 1-9
                Affiliations
                [1 ]GRID grid.410607.4, HNO-Klinik, , Universitätsklinikikum, ; Mainz, Deutschland
                [2 ]GRID grid.5110.5, ISNI 0000000121539003, Klinik für Anästhesiologie und Intensivmedizin, , Universitätsmedizin Graz, ; Graz, Österreich
                [3 ]GRID grid.4793.9, ISNI 0000000109457005, Klinik für Pulmologie, , Aristotle Universität Thessaloniki, ; Thessaloniki, Griechenland
                [4 ]Klinik für Innere Medizin, Klinikum Veria, Veria, Griechenland
                [5 ]GRID grid.410607.4, HNO Klinik, , Universitätsklinikum Mainz, ; Mainz, Deutschland
                [6 ]Badralexistr. 3, 59132 Veria, Griechenland
                Article
                1218
                10.1007/s00106-022-01218-1
                9425785
                36040511
                db303d6b-a8b5-45ea-9f85-14f394a4069e
                © The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2022

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 3 August 2022
                Categories
                Originalien

                covid-19,geschmack,geruchssinn,elektrogustometrie,kontaktendoskopie,taste,olfaction,electrogustometry,contact endoscopy

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