1. Introduction

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first appeared in Wuhan, China in late 2019 and since has evolved into a global pandemic that has caused serious health threats and profoundly disrupted fundamental life activities. SARS-CoV-2 spreads through respiratory droplets via direct and close contact between infected, symptomatic and highly likely asymptomatic individuals. Transmission by indirect contact with contaminated surfaces or objects (fomite transmission) is also highly possible. SARS-CoV-2 can infect individuals of all ages; however, the elderly, individuals with weakened immunity, and those with underlying chronic pre-existing medical conditions such as chronic respiratory diseases, diabetes mellitus, hypertension, and cardiovascular diseases are more susceptible to contracting COVID-19 and more likely to experience serious illnesses due to COVID-19.

Since December 2019, the pandemic has evolved into several waves of infections linked to the emergence of various SARS-CoV-2 mutated variants known as the alpha (B.1.1.7), beta (B.1.351), delta (B.1.617.2) and omicron (B.1.1.529) variants. Comparisons of the variations in transmissibility, clinical characteristics, severity, and outcomes between patients infected with early and late variants were examined in a few previous studies. In particular, studies have shown that late variants are characterized by higher transmissibility (delta: 43–68% more transmissible than previously circulating variants [1], omicron: 36.5% more transmissible than delta [2]) compared to early variants (alpha and beta: 40–70% more transmissible compared to the original virus [3]). Although the transmissibility rate of COVID-19 late variants is considered to be higher than the original virus and early circulating variants, the severity of symptoms and clinical outcomes among variants has also changed slightly. For instance, the delta variant has been shown to be associated with more severe symptoms and about is twice as likely to require hospitalization than those infected with earlier circulating variants [4], whereas the omicron variant appears to be markedly less severe than early circulating variants [5] possibly due to the increased protection from COVID 19 vaccination status and cell-mediated immunity derived from previous infection. With regards to vaccination, the delta and omicron variants were predominant during the period of the widespread dissemination of COVID-19 vaccines, which began on mid-December 2020. Although the emergence of COVID-19 vaccines contributed to mitigate the severity and hospitalization posed by COVID-19, these COVID-19 variants are still considered very concerning due to the probable breakthrough infections.SARS-CoV-2 variants are generally characterized by a number of clinical manifestations, although slight differences in the proportion of some symptoms between variants also emerged. Since the beginning of the COVID-19 pandemic, variable degrees ranging from mild to severe self-reported symptoms have been reported and generally include cough, fever, difficulty breathing, and some digestive symptoms including diarrhea and vomiting [6]. Furthermore, the acute phase of COVID-19 may also be accompanied by some peripheral and central neurological manifestations such as memory or cognitive disturbances, disturbed consciousness, myalgia, headache, malaise or fatigue, and insomnia [7,8,9]. Additionally, sensory disturbances including anosmia, hyposmia, ageusia, hypogeusia, and audiovestibular complaints including dizziness, vertigo, tinnitus, and hearing loss were commonly reported COVID-19 manifestations [10]. Along with the evolution of COVID-19 variants, the proportion of some self-reported symptoms has also changed slightly. Although taste and smell disturbances were considered chief and distinctive symptoms of COVID-19, these symptoms became less common during the omicron variant compared to delta and earlier variants [11,12]. With regard to audiovestibular symptoms, several systematic reviews [13,14,15], case reports/series [16,17,18,19,20], self-report survey studies [10,21,22,23,24,25] and a few clinical testing studies [26,27,28], there were increased reports of hearing loss, tinnitus, dizziness, and vertigo among COVID-19 infected individuals. Nevertheless, the majority of these studies were performed during the predominant periods of the original virus and early circulating variants of the COVID-19 pandemic.

Considering the higher transmissibility of late COVID-19 variants, there is a need for studies that examine potential changes in audiovestibular symptomatology with changes in SARS-CoV-2 mutations, while also comparing the findings against uninfected control considering seasonal variations. Therefore, we aimed to compare whether audiovestibular symptoms of COVID-19 with the late variants (delta and omicron) differed from that of early circulating variants (alpha and beta).

4. DiscussionCOVID-19 variants have different transmission characteristics and clinical manifestations compared to the original coronavirus and early circulating variants. We conducted a comparative cross-sectional study to examine whether the evolving COVID-19 variants were associated with differences in reporting audiovestibular symptoms during the predominance periods for alpha/beta, delta, and omicron variants compared to non-COVID controls. Overall, our findings showed that COVID-19 infected individuals in all variant periods reported significantly more audiovestibular symptoms compared to non-COVID controls. However, our findings did not show significant changes in audiovestibular symptoms across COVID-19 variants. Furthermore, individuals infected when the delta variant was dominant reported audiovestibular symptoms at a higher rate, although not statistically significant, than other variants (See Table 2).Overall, about a quarter (24.02%) of all COVID-19 participants in all variants combined reported experiencing auditory symptoms; most commonly aural fullness (21%) followed by tinnitus (11.7%), and lastly hearing loss (8.7%). There were no significant differences in reporting auditory symptoms during the acute phase of all COVID-19 variants. Hearing loss estimates reported in our study were consistent with an earlier systematic review, conducted at the beginning of the pandemic, reporting a prevalence of about 7.6% [14]. Additionally, several studies revealed elevated hearing thresholds at high audiometric frequencies among COVID-19 patients [20,26,27,30,31]. In contrast, other studies comparing COVID-19 positive individuals with mild to moderate illness with asymptomatic individuals did not show significant differences in audiometric thresholds at any audiometric frequency. Two studies also reported a possible subclinical auditory dysfunction evidenced by reduced OAEs amplitudes [26,28,30] in conjunction with a lack of elevated audiometric thresholds [28]. Furthermore, COVID-19-related sudden sensorineural hearing loss was also reported in many case reports since the beginning of this pandemic [16,17,18,20,32,33]. Overall, these findings suggest that auditory symptoms are common during the acute phase of COVID-19, and comprehensive audiological testing is required to further elucidate the pathogenesis of the underlying auditory dysfunction.Tinnitus following positive COVID-19 test results was reported in a total of 94 (11.7%) participants, of which 10%, 13.7% and 12.5% were infected during the alpha/beta, delta, and omicron variants, respectively, and this was significantly higher than the non-COVID controls (1.7%). These estimates are consistent with previous studies reporting a prevalence of tinnitus ranging from 0.35% to as high as 35% [21,22,25,29,34,35]. The literature suggests that tinnitus is strongly associated with psychological disorders such as anxiety, stress, and depression [36,37,38]. These psychological disorders have been shown to be prevalent among infected and non-infected individuals during the COVID-19 pandemic [39,40] and among those with chronic tinnitus during the COVID-19 pandemic [41]. A previous study including non-COVID-19 participants with chronic tinnitus and COVID-19 infected individuals revealed that psychological disorders may possibly lead to the development of new tinnitus among COVID-19 infected individuals and the exacerbation of tinnitus during the COVID-19 pandemic among those with pre-existing tinnitus [29]. In the context of the COVID-19 pandemic, the onset of tinnitus can be in part explained by stressful and anxiety-related experiences of being diagnosed with COVID-19 or due to factors related to social isolation and lockdown in cases when lockdowns were implemented during the predominance periods of early variants. Regression analyses revealed that reports of experiencing tinnitus was associated with some neurological symptoms including changes of taste and smell and migraine.The increased odds of reporting auditory symptoms among those who reported changes of smell and taste as well as migraine following positive COVID-19 test results are consistent with our earlier report when the early variants were dominant [10]. It has been postulated that the causative agent of COVID-19 possibly infiltrates the central nervous system via the blood–brain barrier [42] or via the olfactory pathway [43]. The olfactory pathway entry point may in part explain the increased odds of experiencing changes of smell commonly reported by COVID-19 infected individuals as well as the increased odds of experiencing auditory symptoms found in our study. The pathogenesis of the manifestation of auditory symptoms following a positive COVID-19 test remains unclear. COVID-19 can cause inflammatory, vascular insult through coagulopathy and secondary immune mediated dysfunction. The severity or multitude of general symptoms could reflect the severity of the condition and be more likely to affect auditory and vestibular systems. Furthermore, COVID-19-related auditory symptoms can possibly be explained by the evidence that the cellular receptor for the SARS-CoV-2 (angiotensin-converting enzyme 2 [ACE-2] receptors) was confirmed to be present in multiple areas along the auditory pathway including the eustachian tube, middle ear tissues, hair cells, spiral ganglion cells, and in the stria vascularis [44,45]. Furthermore, findings from the original virus also suggested the presence of SARS-CoV-2 particles in the brainstem, a site where the primary afferent innervation of cochleovestibular nerves arises [46]. Additionally, the predominant report of aural fullness in all analyzed COVID-19 variants can also be explained by the fact that ACE-2 was also predominantly present in the eustachian tube [44,45], indicating that that the eustachian tube is likely susceptible to SARS-CoV-2 infection and consequently leads to reports of aural fullness.Vestibular symptoms among COVID-19 infected individuals were reported more frequently in all COVID-19 analyzed variants compared to auditory symptoms. Specifically, vestibular symptoms were reported by 34.9%, 36.3%, and 35.3% of individuals, respectively, when the alpha/beat, delta, and omicron variants were dominant. A previous study performed comprehensive vestibular examinations on COVID-19 positive individuals and revealed significant abnormalities in video head impulse testing (vHIT), cervical and ocular vestibular evoked myogenic potentials compared to non-COVID controls [31], suggesting possible COVID-19 effects on the vestibular system. Our analysis also showed that anemia was significantly associated with self-reports of dizziness and vertigo. Previous studies indicated that anemia is a risk factor associated with severe COVID-19 disease and severe inflammatory responses as well as more organ damage [47]. The exact mechanism of anemia leading to inner ear manifestations such as auditory or vestibular disorders is still unclear. However, it is reasonable to speculate that the underlying mechanism of anemia-induced vestibular symptoms is related to inflammatory, metabolic, and vaso-occlusion of the blood supply to the inner ear. The inner ear vasculature is sensitive and thus vulnerable to insults that disrupt blood flow to the inner ear [48], in addition to them being end organs supplied by labyrinthine arteries with no collateral circulation. This compromised circulation to the inner ear structures may lead to increased susceptibility to developing thrombosis or hypoxia and therefore leads to vestibular disorders among COVID-19 patients with anemia.A logistic regression analysis in the current study also showed that female participants are more likely to report vestibular symptoms compared to males. Gender differences with regards to vestibular disorders were reported in the literature demonstrating a significant female predominance with respect to developing vestibular disorders [49,50] such as vestibular neuritis, Meniere’s disease, benign paroxysmal positional vertigo (BPPV) [51], vestibular migraine [52], and mal de debarquement syndrome [53]. These gender differences have been hypothesized to be related to the hormonal influence, however, the exact mechanism as to why women develop vestibular disorders more frequently than men remains unclear [50].Although participants were provided with the operational definition and description of each vestibular symptom analyzed, there may still be some overlap between reports of experienced symptoms. Moreover, it is still unclear whether the reports of vestibular symptoms following COVID-19 are of a central or peripheral nature. It is difficult to clearly differentiate between the multitude of causes of vestibular problems and whether it is of central or peripheral vestibular origin for the onset of dizziness and vertigo following positive COVID-19 test solely on the basis of self-report questionnaire without further history taking and vestibular testing. For instance, logistic regression analyses of the current study revealed that individuals with shortness of breath as a COVID-19 symptom are more likely to experience vestibular problems. Shortness of breath might reflect severity of the condition and the possible involvement of different body systems. Hypoxia and coagulopathy-related vascular insults could cause both central and peripheral vestibular disorders. Moreover, vestibular symptoms were also associated with headache and fatigue as COVID-19 symptoms. Angiopathic, hypoxic or immune mediated insults to the brain might cause headache and vestibular center insults. Additionally, COVID-19-related stress could trigger migraines, which can cause both central and peripheral vestibular manifestations. With regard to fatigue, diffuse macroangiopathic thrombi or cardiomyositis associated with COVID-19 could cause cardiac related fatigue and possible vascular vestibular insult. Furthermore, COVID-19 could cause myositis [54], possibly indicating that fatigue might be associated with the weakness of postural control muscles [55]. Fatigue may also lead to recumbency and decreased mobility which subsequently could cause orthostatic dizziness/hypotension. Taken together, there is overlap between the origin of vestibular symptoms and disorders and, therefore, careful history taking in addition to physical and vestibular examinations is required to unravel the etiopathology of vestibular manifestations as a result of COVID-19.

The current study has some limitations. First, data concerning gene sequencing for the analyzed COVID-19 variants were not available to the researcher. However, personal communication with the Saudi surveillance center revealed that selected samples of positive RT-PCR tests of late variants accounted for the majority of cases when these variants were dominant. Second, the cross-sectional survey design of our study does not substitute comprehensive audiological and vestibular testing to elucidate the nature of auditory and vestibular dysfunction caused by COVID-19.