Damian Sendler: Postviral anosmia accounts for up to 40% of all occurrences of adult olfactory impairment [1,2]. When the SARS-CoV-2 epidemic began, it was probably predictable to witness a rise in cases. Although olfactory impairment is common, it has been largely ignored until now because of its usefulness as a diagnostic marker and its great incidence. COVID-19-induced olfactory impairment, underlying pathophysiology, recovery rates, and treatment strategies are discussed here. 

OLFACTORY LOSS IN COVID-19: PREVALENCE AND PRESENCE 

Damian Jacob Sendler: In March 2020, olfactory loss appeared as a possible indicator of COVID-19 after early press reports in Germany, Korea, and Iran [3]. A meta-analysis of 3563 patients published in May 2020 revealed the mean prevalence of self-reported loss to be 47 percent (95 percent CI: 36 percent –59 percent) in, ranging from 11 percent to 84 percent in included case studies [4]. 

Only 35 percent of 60 hospitalized patients self-reported that they had lost their sense of taste or smell, but 98 percent of the patients tested positive for the condition on psychophysical tests [5]. It is possible to overstate the incidence of persistent olfactory loss due to COVID-19-related olfactory dysfunction if only psychophysical measures are used [6]. 

Damian Sendler

For individuals with COVID-19, loss of smell may be the sole presenting symptom [3]; additional symptoms predominate in 20% (95 percent CI: 13% –29%) of reported cases from May 2020 and appear concurrently in another 28% (95 percent CI: 22% –36%) of cases [4]. 7] of 114 patients with proven COVID-19 infection indicated that 47% of the patients suffered odor loss, while fewer than 5% of the patients reported additional sinonasal symptoms such rhinorrhoea and nasal congestion. [7]. Patients with COVID-19-related anosmia do not have the usual rhinitic symptoms of a cold, according to other research [8]. 

Olfactory impairment has been suggested as a possible predictor of the severity of COVID-19. Patients who were admitted to the hospital were substantially less likely to have anosmia or hyposmia (26.9% vs 66.7 percent, P 0.001), according to an early research by Yan et al.[9]. According to systematic studies, the incidence of self-reported scent loss in hospitalized patients was 31%, but it rose to 67% in mild to moderately symptomatic home-isolated patients [4]. While this is true for the first week after infection, another research of 106 individuals [10] revealed no link between olfactory function and illness severity. Researchers from the same group found no link between viral load and the degree of olfactory loss in a second investigation [11]. Another prospective research [12] found no statistical connection between baseline olfactory loss and the severity of chest CT results. Because of respiratory symptoms and anorexia, the authors believe that short-lived olfactory impairment may be ignored in more severe illness because of the overriding respiratory symptoms and the concomitant anorexia, which leads to lower nutritional intake. In Spain, an independent study group found the same results [13]. 

Damian Jacob Markiewicz Sendler: In one research, women were shown to be more likely than males to have anosmia (72.4% vs. 45.2% vs. 65.8%; P = 0.02) [14]. Angiotensin-converting enzyme 2 (ACE2) receptor expression in the olfactory epithelium decreases with age, according to a recent comprehensive study [15]. In addition, the prevalence of underlying OD may be growing. Varied virus variations are associated with different levels of olfactory impairment, and this seems to be true across geographic regions as well as temporal periods during the pandemic [17, 18]. 

Mechanisms of Olfactory Dysfunction in Covid-19 

It remains unclear what causes anosmia in COVID-19 even though there is a growing body of data. Due to the swelling of the nasal cavity, there may be olfactory conductivity loss as well as damage to the olfactory epithelium (OE). 

Damian Jacob Sendler

Even while nasal congestion is less common in COVID-19 than with other endemic coronaviruses, oedema inside the olfactory cleft may contribute to early OD impeding the supply of odorants to the OE [19,20]. However, MRI scans of individuals with COVID-19-related OD within 15 days after start showed a high incidence of total occlusion of the olfactory cleft, whereas other radiological examinations of patients with more chronic loss found this to be a rare finding. 

Postviral olfactory loss has been linked to olfactory epithelial damage [23]. Axonal injury to olfactory nerve fibers was found in postmortem examinations of COVID-19 patients who had anosmia and demonstrated localized atrophy of the OE [24]. Recovering olfactory epithelium was seen as early as day 4, but was still incomplete by day 14 in animal models of SARS-CoV-2 [25], which were infected via nasal injection. 

The OE’s sustentacular supporting and basal cells contain ACE2 receptors, which are critical for SARS-CoV-2 viral entrance [27,28]. Even if the ORNs do not express ACE2 or get infected directly, damage to these cells may lead to decreased sensitivity and cilia loss, leading in OD. As direct ORN damage would need a longer length of time to resolve OD, this explanation is compatible with the early recovery trend. Both mature sensory neurones and sustentacular cells have been detected in the ORNs in recent in vivo experiments utilizing mucosa brush sampling [26], demonstrating entrance into the ORNs itself and evidence of cell death in both groups. 

Damien Sendler: According to animal models and olfactory epithelial biopsies obtained after the death of COVID-19 patients, there is evidence to suggest that the loss of odorant receptor expression on otherwise intact ORNs is caused by an inflammatory process. Golden Syrian hamsters with SARS-CoV-2 showed that the local immune response increased macrophage expression, which may hinder healing of the OE and restoration of ORNs [25]. Viral persistence has been found in the olfactory epithelium of individuals with persistent loss, along with ongoing inflammation, increased IL6, and apoptosis. [26▪]. Basal stem cells’ regeneration ability has been demonstrated to be greatly reduced by inflammation, and this process may possibly explain for long-term olfactory impairment [29] Anecdotal claims of improved recovery after vaccination may be a result of more efficient virus clearance. 

The retrograde axonal transfer of viruses to the OB and CNS has been extensively shown [31,32]. Coronavirus particles have been detected inside the OB three days after inoculation, and within the cortex seven days later [33]. A comparable route of viral entry via the OB and fast invasion of the CNS was seen in ACE2 transgenic mice infected with SARS-CoV-1 [34]; equally high viral RNA loads were identified throughout the whole pathway from the olfactory endothelium to the bulb [26]. Hyperintensity in the olfactory bulb has been recorded in a number of studies [35,36,37], however it was only seen in 19% of individuals in a neuroimaging cohort [38]. Patients with long-term COVID-19-induced OD may benefit from baseline imaging that shows severe OB atrophy two months after symptoms first appear on MRI scans obtained before to infection [39]. Two individuals with chronic COVID-19 OD were discovered to have hypometabolism on PET imaging in the rectus gyrus [40]. There is no clear indication that SARS-CoV-2 was transported backwards into the OB from the OE, but these investigations have shown signs of neurotropism, atrophy, and hypometabolism as a result of this loss of function. 

There needs to be more study into the mechanism of olfactory loss since it will help us develop new treatments. 

Recovering OLFACTORY LOSS FROM COVID-19 

For many years, researchers have used questionnaires or objective olfactory tests to assess recovery rates and risk factors for persistence. A large percentage of patients reported full olfactory recovery in as little as 10 days, according to early data [41]. Self-reported studies [43,44,45,46] show that recovery rates range from 31.7 percent to 89 percent. 

Self-reporting, on the other hand, seems to overstate the extent of recovery (in contrast to under-estimating the initial prevalence of olfactory loss.) Boscolo-Rizzo et al.[46] showed a considerable discrepancy between self-reported olfactory function and psychophysical assessment; surprisingly, only 41% of 112 patients with self-reported normal sense of smell at 6 months demonstrated normosmia with UPSIT testing. [46] 

Six-month and longer-term results are now available in a growing number of research studies. According to Leedman et al.[47], 64 percent of patients with verified COVID-19 were normosmic at 6 months, 3.5 percent were anosmic, and the rest were hyposmic as determined by UPSIT testing, as reported by Leedman et al.[47]. The results of a case-control research conducted by Dr. Boscolo-Rizzo [48] showed that 46% of patients and 10% of controls had olfactory impairment, with 7% of COVID-19 cases being anosmic on average, 401 days after infection. Even with the greatest recorded recovery rates with COVID-19, a large percentage of individuals globally will still suffer from severe olfactory impairment. 

PAROSIS AND PHANTOSMIA IN THE QUALITATIVE OLFACTORY DISESFUNCTION 

According to many patients, the development of parosmia often occurs within two or three months after the onset of symptoms [49]. Parosmia may occur in certain people even if they have not previously reported losing their sense of smell. “COVID scent” has a noxious burnt-chemical-like aroma, and is typically considered unpleasant. Coffee, onions, garlic, pork, citrus fruits, and toothpaste are all common irritants [50]. 

We do not know what causes parasmia and phantomia. As shown by results of lower ORN numbers and the prevalence of immature neurones in histological investigation of the olfactory epithelium, one explanation holds that there are fewer working olfactory neurones, resulting in an inadequate odorant characterisation [51]. As an alternative, it has been posited that parosmia may be the result of aberrant activity on positron emission tomography (PET) and functional magnetic resonance imaging (MRI). 

Although anecdotal evidence exists for the use of anticonvulsants, such as gabapentin, to decrease distortions in severe instances, there is little data to support therapeutic recommendations.

Dr. Damian Jacob Sendler and his media team provided the content for this article.