Geographical Variations in Host Predisposition to COVID-19 Related Anosmia, Ageusia, and Neurological Syndromes

Abstract

The novel coronavirus disease (COVID-19), has become the most critical global health challenge in recent history. With SARS-CoV-2 infection, there was an unexpectedly high and specific prevalence of olfactory and taste disorders (OTDs). These high rates of hyposmia and hypogeusia, initially reported as up to 89% in European case series, led to the global inclusion of loss of taste and/or smell as a distinctive feature of COVID-19. However, there is emerging evidence that there are striking differences in the rates of OTDs in East Asian countries where the disease first emerged, as compared to Western countries (15.8 vs. 60.9%, p-value < 0.01). This may be driven by either variations in SARS-CoV-2 subtypes presenting to different global populations or genotypic differences in hosts which alter the predisposition of these different populations to the neuroinvasiveness of SARS-CoV-2. We also found that rates of OTDs were significantly higher in objective testing for OTDs as compared to subjective testing (73.6 vs. 60.8%, p-value = 0.03), which is the methodology employed by most studies. Concurrently, it has also become evident that racial minorities across geographically disparate world populations suffer from disproportionately higher rates of COVID-19 infection and mortality. In this mini review, we aim to delineate and explore the varying rates of olfactory and taste disorders amongst COVID-19 patients, by focusing on their underlying geographical, testing, ethnic and socioeconomic differences. We examine the current literature for evidence of differences in the olfactory and gustatory manifestations of COVID-19 and discuss current pathophysiological hypotheses for such differences.

Increasing incidence of parosmia and phantosmia in patients recovering from COVID-19 smell loss

“…While some studies suggest self-reports may underestimate smell loss prevalence relative to direct assessment 18,30,31 , others found correlations between self-reporting and direct assessments 32 . Furthermore, although direct assessments have been proposed very recently 33 , self-report remains the current standard of care for assessment of parosmia and phantosmia 34 , at least until newly proposed methods can be further validated.…”

The D614G virus mutation enhances anosmia in COVID-19 patients: Evidence from a systematic review and meta-analysis of studies from South Asia

“…This is unlikely to be a decisive factor for two reasons. Careful analyses of East Asians for chemosensory dysfunction revealed low prevalence, 5,89,90 even with objective olfactory testing, 91 and when the olfactory dysfunction was reexamined in Chinese populations at a later date, the anosmia prevalence still was significantly lower in Chinese patients than in Caucasian patients. 92 Second, we show here for South Asians that even studies conducted later in the pandemic, when the media had widely publicized and revealed anosmia/hyposmia as a cardinal symptom of COVID-19, reported a low prevalence when they examined cohorts in a region (e.g.…”

“…3,4,10,114,115 An emerging consensus favors a crucial role of the sustentacular support cells in the olfactory epithelium as the primary mechanism of COVID-induced anosmia. 5,8,114,[116][117][118][119][120] Since the SARS-CoV-2 entry protein (ACE2) is not or only minimally expressed in olfactory receptor neurons, the virus rarely infects the neurons, 121 but rather enters the olfactory epithelium through sustentacular support cells and secretory cells in Bowman glands and primarily damages these cell types (Fig. 5A).…”

“…1,2,[4][5][6][7] Such differences may be due to multiple factors, but two reasons are currently considered to be most relevant: differences at the level of the human host (variants in the virus entry proteins, angiotensin-converting enzyme 2, ACE2, and/or in the protease TMPRSS2), and differences at the level of the virus (mutations of the spike protein resulting in an altered efficiency of entry to the host cell, and therefore higher infectivity), or a combination of these host and virus factors. 1,2,4,5,[8][9][10][11][12][13] For historical reasons of how the pandemic unfolded, it has been difficult to define the relative contributions of host and virus factors for anosmia. The pandemic started in East Asia with the less infectious D614 virus strain, but when COVID-19 reached Europe and North America and the rest of the world, the virus with a D614G mutation in the spike protein rapidly replaced the original D614 virus.…”

“…Some studies reported the prevalence of anosmia or hyposmia to be lower than 1%, while others reported a prevalence of over 70%. 1,2,[4][5][6][7] Such differences may be due to multiple factors, but two reasons are currently considered to be most relevant: differences at the level of the human host (variants in the virus entry proteins, angiotensin-converting enzyme 2, ACE2, and/or in the protease TMPRSS2), and differences at the level of the virus (mutations of the spike protein resulting in an altered efficiency of entry to the host cell, and therefore higher infectivity), or a combination of these host and virus factors. 1,2,4,5,[8][9][10][11][12][13] For historical reasons of how the pandemic unfolded, it has been difficult to define the relative contributions of host and virus factors for anosmia.…”