Post-viral effects of COVID-19 in the olfactory system and their implications

Abstract

Background The mechanisms by which any upper respiratory virus, including SARS-CoV-2, impairs chemosensory function are not known. COVID-19 is frequently associated with olfactory dysfunction after viral infection, which provides a research opportunity to evaluate the natural course of this neurological finding. Clinical trials and prospective and histological studies of new-onset post-viral olfactory dysfunction have been limited by small sample sizes and a paucity of advanced neuroimaging data and neuropathological samples. Although data from neuropathological specimens are now available, neuroimaging of the olfactory system during the acute phase of infection is still rare due to infection control concerns and critical illness and represents a substantial gap in knowledge. Recent developments The active replication of SARS-CoV-2 within the brain parenchyma (ie, in neurons and glia) has not been proven. Nevertheless, post-viral olfactory dysfunction can be viewed as a focal neurological deficit in patients with COVID-19. Evidence is also sparse for a direct causal relation between SARS-CoV-2 infection and abnormal brain findings at autopsy, and for trans-synaptic spread of the virus from the olfactory epithelium to the olfactory bulb. Taken together, clinical, radiological, histological, ultrastructural, and molecular data implicate inflammation, with or without infection, in either the olfactory epithelium, the olfactory bulb, or both. This inflammation leads to persistent olfactory deficits in a subset of people who have recovered from COVID-19. Neuroimaging has revealed localised inflammation in intracranial olfactory structures. To date, histopathological, ultrastructural, and molecular evidence does not suggest that SARS-CoV-2 is an obligate neuropathogen. Where next? The prevalence of CNS and olfactory bulb pathosis in patients with COVID-19 is not known. We postulate that, in people who have recovered from COVID-19, a chronic, recrudescent, or permanent olfactory deficit could be prognostic for an increased likelihood of neurological sequelae or neurodegenerative disorders in the long term. An inflammatory stimulus from the nasal olfactory epithelium to the olfactory bulbs and connected brain regions might accelerate pathological processes and symptomatic progression of neurodegenerative disease. Persistent olfactory impairment with or without perceptual distortions (ie, parosmias or phantosmias) after SARS-CoV-2 infection could, therefore, serve as a marker to identify people with an increased long-term risk of neurological disease.

Olfactory Disorders in Post-Acute COVID-19 Syndrome

“…Hyposmia was reported in a study in Padua as an isolated or more prominent symptom of SARS-CoV-2 infection, often associated with hypogeusia [25]. Hyposmia and parosmia can be persistent olfactory dysfunctions in PACS [28].…”

“…In contrast to common upper airways infection, rhinorrhea or nasal congestion are less associated with anosmia in COVID -19; however, it can affect the central nervous system, as observed in an 18-FDG PET/CT study, in which a reduction in metabolic activity was reported in the left orbitofrontal cortex, and it can be associated with edema of the olfactory bulb in MRI [26][27][28]. Anosmia can lead to suspicion of COVID-19 diagnosis, as it can be the only clinical feature present [29].…”

Precocious Puberty and Covid-19 Into Perspective: Potential Increased Frequency, Possible Causes, and a Potential Emergency to Be Addressed

“…Sars-Cov2 binds ACE-II receptors that are particularly abundant in the central nervous system, with subsequent neuronal transport, haematogenous and nasal route dissemination via the olfactory bulb, thus explaining one of the typical symptoms of covid-19 that is anosmia ( 3 ). The olfactory bulb is of great importance for chemical communication between the environment and the brain, and studies have shown inflammation of the olphactory bulb and epithelium related with covid-19 ( 4 ). Interestingly, an increased volume of the olphactory bulb has been described to be strongly correlated with precocious puberty onset ( 5 ).…”

Olfactory evaluation in hospitalised and self-isolated patients with COVID-19: a single-centre experience on 55 cases

“…The absence of correlation between self-rated nasal obstruction and subjective or semiobjective smell assessment suggests that olfactory dysfunction in patients with COVID-19 was not due to nasal obstruction but was rather a consequence of the inflammation in olfactory epithelium. 18 …”