Patients with COVID-19-associated olfactory impairment also show impaired trigeminal function

Otte, Martin Sylvester; Bork, Marie-Luise; Zimmermann, Philipp; Klußmann, Jens Peter; Lüers, Jan-Christoffer

doi:10.1016/j.anl.2021.07.012

Cited by 12 publications

(12 citation statements)

References 31 publications

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“…Indeed, there is evidence of the involvement of the trigeminal nerve function in COVID-19 patients. 29,34 Notably, viral load measured by different techniques (genomic and subgenomic qPCR, and infectious virus titration) unequivocally followed the same pattern described by the IHC in terms of viral antigen detected in brain histological sections. Infectious virus in the brain was detected from 4 dpi onwards in an increasing trend, with the highest loads detected by 6 and 7 dpi, as expected.…”

Section: Discussionmentioning

confidence: 54%

Chronological brain lesions after SARS-CoV-2 infection in hACE2-transgenic mice

et al. 2021

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory disease, but it can also affect other organs including the central nervous system. Several animal models have been developed to address different key questions related to Coronavirus Disease 2019 (COVID-19). Wild-type mice are minimally susceptible to certain SARS-CoV-2 lineages (beta and gamma variants), whereas hACE2-transgenic mice succumb to SARS-CoV-2 and develop a fatal neurological disease. In this article, we aimed to chronologically characterize SARS-CoV-2 neuroinvasion and neuropathology. Necropsies were performed at different time points, and the brain and olfactory mucosa were processed for histopathological analysis. SARS-CoV-2 virological assays including immunohistochemistry were performed along with a panel of antibodies to assess neuroinflammation. At 6 to 7 days post inoculation (dpi), brain lesions were characterized by nonsuppurative meningoencephalitis and diffuse astrogliosis and microgliosis. Vasculitis and thrombosis were also present and associated with occasional microhemorrhages and spongiosis. Moreover, there was vacuolar degeneration of virus-infected neurons. At 2 dpi, SARS-CoV-2 immunolabeling was only found in the olfactory mucosa, but at 4 dpi intraneuronal virus immunolabeling had already reached most of the brain areas. Maximal distribution of the virus was observed throughout the brain at 6 to 7 dpi except for the cerebellum, which was mostly spared. Our results suggest an early entry of the virus through the olfactory mucosa and a rapid interneuronal spread of the virus leading to acute encephalitis and neuronal damage in this mouse model.

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Section: Discussionmentioning

confidence: 54%

Chronological brain lesions after SARS-CoV-2 infection in hACE2-transgenic mice

et al. 2021

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“…These findings may suggest a potential route of penetration of SARS-CoV-2 through the intranasal trigeminal nerve endings. Spread of the virus from nasal epithelial cells to the olfactory bulb has also been suggested [53,54]. There are reports of the suppression of the olfactory system by the massive calcitonin gene-related peptide (CGRP) release from the overactive trigeminal afferent system.…”

Section: Discussionmentioning

confidence: 99%

Facial Diplegia—Complication or Manifestation of SARS-CoV-2 Infection? A Case Report and Systemic Literature Review

et al. 2021

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Since the outbreak of the new coronavirus, healthcare systems around the world have witnessed not only COVID-19 symptoms but also long-term complications of the aforementioned, including neurological problems. We report a clinical case of an adult patient with bilateral facial nerve palsy and progressive ascending paresis of the limbs after contracting the novel coronavirus (COVID-19). Additionally, the systematic review aimed to identify and summarize specific clinical features, outcomes and complications of the studies focusing on bilateral facial diplegia as a sequela of COVID-19 infection. The total number of analyzed patients was 15. Only one patient was diagnosed with isolated bilateral palsy; the rest had Guillain-Barré Syndrome (GBS). With one exception, all the presented cases had favorable outcomes, with facial palsy recovery from slight to almost complete. In patients with a confirmed COVID-19 diagnosis, bilateral facial palsy may be an isolated symptom as well as a variant of GBS. Symptoms of cranial nerve damage during a COVID-19 infection may explain the appearance of facial nerve damage. In order to clarify the spectrum of neurological manifestations and a causal relation between SARS-CoV-2, COVID-19 vaccination and neurological symptoms, direct attention towards the study of this virus is crucial. It seems reasonable to recognize human coronavirus as another potential GBS trigger.

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“…However, numerous nerve endings of the fifth cranial nerve, the trigeminal nerve, are also present in the nasal cavity. Since various studies have identified the presence of a huge viral load in the trigeminal ganglion [ 27 , 48 , 49 ] and its role in the perception and differentiation of certain odors [ 27 , 28 ], we decided to test this hypothesis of trigeminal nerve involvement by examining the sensitivity of the olfactory and the trigeminal nerve using clove and camphor fragrances. The rationale for choosing these specific fragrances was also based on various scientific studies, which suggested that the fragrances of cloves are primarily recognized by the olfactory nerve and the fragrances of camphor are primarily recognized by the trigeminal nerve [ 3 , 30 , 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

Assessment of Smell and Taste Disturbances among COVID-19 Convalescent Patients: A Cross-Sectional Study in Armenia

Melkumyan

Shingala

Simonyan

et al. 2022

JCM

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Background and Objectives: Neurological manifestations of Coronavirus Disease 2019 (COVID-19) such as olfactory and gustatory disturbance have been reported among convalescent COVID-19 patients. However, scientific data on the prevalence of smell and taste disturbance are lacking. Therefore, we present findings on the degree of smell and taste disturbances among the Armenian population. Methods: Study participants were randomly recruited and then categorized into two groups based on their course of the disease. A cross-sectional study was performed to assess participants’ sensitivity to smell triggered by the olfactory and the trigeminal nerves; their ability to differentiate between various odors; and to evaluate their gustatory perception. Results: The smell test revealed that the degree of olfactory nerve disturbance was different by 30.7% in those participants of the early group as compared to those of the late group, and the degree of trigeminal nerve disturbance was different by 71.3% in the early group as compared to the late group. A variation of the differentiating ability among the participants of the early and late groups was detected. Gustatory disturbances for all flavors were also found to be different in both the groups. A moderate positive correlation (0.51) was found between the overall sensitivity of smell and the ability to differentiate between various odors as cumulatively stimulated by both the olfactory and trigeminal nerves. Also, a moderate positive correlation (0.33) was found between headache and smell sensitivity through the olfactory nerve and a high negative correlation (−0.71) was found between headache and smell sensitivity through the trigeminal nerve. Conclusion: Pathological changes in the olfactory and trigeminal perceptive abilities caused disturbances in smell sensation, with the trigeminal nerve being more affected. The capacity to differentiate fragrances did not improve with time and the disturbance severity of bitter taste perception was higher among the study participants.

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Patients with COVID-19-associated olfactory impairment also show impaired trigeminal function

Cited by 12 publications

References 31 publications

Chronological brain lesions after SARS-CoV-2 infection in hACE2-transgenic mice

Chronological brain lesions after SARS-CoV-2 infection in hACE2-transgenic mice

Facial Diplegia—Complication or Manifestation of SARS-CoV-2 Infection? A Case Report and Systemic Literature Review

Assessment of Smell and Taste Disturbances among COVID-19 Convalescent Patients: A Cross-Sectional Study in Armenia

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