What Is Different in COVID-19-Associated Olfactory Loss from Classical Postinfectious Olfactory Impairment?

The Smell and Taste Corner, the first section in an ENT specialty journal dedicated exclusively to chemosensory issues, was initiated in the summer of 2019 by the conviction that human smell and taste were underestimated [1]. Meanwhile, a bit more than 3 years after the onset of the SARS-CoV-2 pandemic, that is not the case anymore, and the world has a different view on olfactory disorders (OD).

The small community of specialists dealing with smell and taste disorders has rapidly grown, and the literature on OD related to COVID-19 has exploded. Within the flood of published papers, sorting through the multitude of new studies to determine relevant, non-biased, and properly performed epidemiologic studies has been difficult even for experts in the field.

The authors of this editorial have vast experience in evaluating patients through specialized smell and taste outpatient clinics for more than a decade and regularly exchange ongoing clinical patient experiences. As we gain more experience observing patient symptoms and progress, our cumulative sense is that COVID-19-related OD shows many common features [2, 3] but also distinct differences [4] from the formerly known “classic” postinfectious olfactory dysfunction (PIOD) [5]. Several characteristics of COVID-19-related OD appear to deviate from what we have observed with classic postinfectious or post-viral OD.

• 1.Little or no concomitant nasal symptoms. Common nasal symptoms such as obstruction and rhinorrhea are typically reported to co-occur with classic post-viral OD but have been absent or minimally present in COVID-19-related OD, at least for early variants of the virus [6]. With the sudden onset of olfactory loss [7], many patients would probably never have associated it with an infection if not for the current high public awareness of the relationship between COVID-19 and OD prompting testing for SARS-CoV-2 infection. The common absence of typical upper respiratory infection symptoms with OD related to COVID-19 induces us to reconsider how we previously categorized patients as having an idiopathic cause for OD [8], which may also be related to other viral infections with a similar mode of action.
• 2.Younger age of onset. We observe persisting OD in young patients with COVID-19, even within the pediatric population [9]. Classic PIOD is more common in women and occurs, on average, after the fourth decade. It was rarely seen or described in young adults and children [8, 10].
• 3.High prevalence of olfactory distortions. Parosmia and/or phantosmia are common and very pronounced complaints in patients with prolonged OD after COVID-19. The real incidence of olfactory distortions, a very characteristic symptom accompanying or following PIOD, is estimated to be present in roughly 30–50% of cases seen in specialized clinics [8]. In most cases, it spontaneously resolves after one and a half years [11]. At present, our clinical observation would suggest that a much higher prevalence of parosmia and phantosmia occurs and remains in patients with long-standing post-COVID-19 OD. It is currently difficult to state if this is an observer bias due to increased awareness of these symptoms, a reflection of previous underreporting, or a greater intolerance of these distortions in a younger population of patients. In light of a growing number of reports suggesting cognitive difficulties in long-standing COVID-19 patients [12, 13] and possible prolonged effects on intracranial vascular structures [14], it is not clear if the distortions result from a central process rather than a peripheral cause [15, 16].

In conclusion, most of us wonder if COVID-19 OD resembles what we have known to be PIOD (formerly termed post-upper respiratory tract infection-related OD), or reflects a different pathophysiology resulting from the sequelae of a unique viral infection where the olfactory epithelium and related structures are predilection sites for invasion. Little was known on PIOD before as much has been learned with the COVID-19 pandemics, about how the olfactory epithelium is affected [17]. It remains a yet open question if subsequent peripheral and possible (long-term) central modifications will occur via the trans-olfactory route as this has been described with herpetic meningoencephalitis [18] and hypothesized for neurodegenerative diseases [19]. Many aspects of post-COVID OD remain to be understood, and long-term follow-up of persisting COVID-19 OD cases [20, 21] will help shed more light onto these open questions. It is hence clear that the story of the Smell and Taste Corner is to be continued, since many unknown questions in the field of chemosensory disorders wait to be explored.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

None of the authors has any funding relevant to this study.

Author Contributions

Authors B.N.L., J.W.H., I.K., E.H.H., C.H., E.M., and T.H. contributed equally to the writing and critical correction of this editorial.