Post-viral olfactory loss and parosmia

Abstract

The emergence of SARS-CoV-2 has brought olfactory dysfunction to the forefront of public awareness, because up to half of infected individuals could develop olfactory dysfunction. Loss of smell-which can be partial or total-in itself is debilitating, but the distortion of sense of smell (parosmia) that can occur as a consequence of a viral upper respiratory tract infection (either alongside a reduction in sense of smell or as a solo symptom) can be very distressing for patients. Incidence of olfactory loss after SARS-CoV-2 infection has been estimated by meta-analysis to be around 50%, with more than one in three who will subsequently report parosmia. While early loss of sense of smell is thought to be due to infection of the supporting cells of the olfactory epithelium, the underlying mechanisms of persistant loss and parosmia remain less clear. Depletion of olfactory sensory neurones, chronic inflammatory infiltrates, and downregulation of receptor expression are thought to contribute. There are few effective therapeutic options, so support and olfactory training are essential. Further research is required before strong recommendations can be made to support treatment with steroids, supplements, or interventions applied topically or injected into the olfactory epithelium in terms of improving recovery of quantitative olfactory function. It is not yet known whether these treatments will also achieve comparable improvements in parosmia. This article aims to contextualise parosmia in the setting of post-viral olfactory dysfunction, explore some of the putative molecular mechanisms, and review some of the treatment options available.

Keywords: epidemiology; pathology, surgical; pharmacology, clinical; physiology.

Figure 1

Putative mechanisms of post-viral olfactory dysfunction. CSF=cerebrospinal fluid

Figure 2

Potential mechanisms of parosmia. (A) Normal arrangement of olfactory neuroepithelium and its central projections; this image shows the bipolar olfactory sensory neurons, supported by sustenacular cells, and basal cells. (B) Viral induced disruption of the neuroepithelium, with loss of olfactory sensory neurons, sustenacular cells, and basal cells. (C) In the so-called miswiring hypothesis of parosmia, aberrant neural regeneration leads to formation of random and incorrect axonal connection. (D) In the hypothesis of incomplete neural regeneration of parosmia, whereby correct axonal regeneration occurs but only for selected receptor types, leading to incomplete characterisation and misclassification of an odour owing to failure to detect all odour molecular components