Abstract
Objectives
The audio-vestibular equivalent of neurological symptoms secondary to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been discussed; however, it has not been fully clarified. Although it has been reported that the vestibulocochlear system is affected in adult coronavirus disease-2019 (COVID-19) patients, there is no study in the literature in which the pediatric patient group with COVID-19 was evaluated comprehensively with auditory and vestibular tests. In this study, the short-term damage caused by SARS-CoV-2 in the vestibulocochlear system in pediatric patients was examined.
Methods
This study aimed to evaluate the vestibulocochlear system of pediatric patients (aged 9–15 years) with a recent history of COVID-19. The study included 35 individuals with a recent history of COVID-19 and 35 age-gender-matched healthy individuals (control group). Pure tone audiometry, suppressed otoacoustic emission (OAE), video head impulse test (VHIT), and cervical and ocular vestibular evoked myogenic potentials (c/o-VEMP) tests were administered to all participants following their otoscopic examinations, and the obtained data were compared between the two groups.
Results
When the data obtained with pure tone audiometry were compared, statistically significant differences were found between the groups at four different frequencies (1000, 2000, 4000, and 8000 Hz) in favor of the control group. There was a statistically significant difference between the groups in the signal-to-noise ratio (SNR) values obtained before noise at 2800 Hz and before and after noise at 4000 Hz. VHIT lateral gain, LARP gain, and RALP gain were statistically significantly lower in the COVID-19 group than in the control group (p < 0.05). VHIT lateral asymmetry parameter was measured higher in the COVID-19 group than in the control group, and this difference was statistically significant (p < 0.05). In the VHIT test, the asymmetry parameter was significantly higher in the COVID-19 group (p < 0.05). In the o-VEMP test, n10 latency, p15 latency, n10-p15 interlatency, n10-p15 interpeak amplitude, and asymmetry parameters were measured, and no statistically significant difference was found between the COVID-19 group and the control group (p > 0.05).
Conclusion
Evidence was obtained that the cochleovestibular system was damaged in pediatric patients in the early post-COVID-19 period.
Keywords: Cochleovestibular system, COVID-19, Pediatric, Vertigo
1. Introduction
A new type of coronavirus emerged in the city of Wuhan in China in 2019, spreading worldwide and creating a pandemic. This new type of coronavirus was defined as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and named coronavirus disease-2019 (COVID-19) by the World Health Organization [1].
COVID-19 may be asymptomatic or present with a wide range of clinical complaints such as respiratory distress, fever, myalgia, sore throat, cough, and smell and taste disorders. In addition to these classical complaints, other symptoms such as facial paralysis, sudden hearing loss, and dizziness and tinnitus, which alert otolaryngologists, were frequently observed during the pandemic process.
In studies, it has been shown that many viral pathogens (Rubella, measles, mumps, herpes simplex virus, human immunodeficiency virus, varicella zoster virus), especially cytomegalovirus (CMV), cause congenital or acquired hearing loss by damaging labyrinth structures [2]. Viral pathogens are thought to damage the labyrinth structures directly (stria vascularis, organ of Corti, Reissner's membrane, cochlear and central neuronal structures) or indirectly (decreased immunity and secondary infection, host immune response to viral antigen) [2]. In temporal bone studies, it has been shown histopathologically that viruses pass through the stria vascularis and endolymph, cause cochlear duct and saccule hydrops, can be cultured from the perilymph fluid, and cause viral antigen production in spiral ganglion cells in the organ of Corti [[3], [4], [5]]. Since the neurotropic and neuroinvasive characteristics of SARS-CoV-2 were defined, its neurological effects have been discussed [6]. In studies published so far, it has been reported that SARS-CoV-2 causes neurological symptoms in approximately 30% of the patients [7]. It is discussed whether the neurological symptoms secondary to SARS-CoV-2 are the direct or indirect effects of the virus. Various authors have reported that the vestibulocochlear system is affected in patients with COVID-19 [8,9]; however, there is no study in the literature in which pediatric COVID-19 patients were evaluated comprehensively with auditory and vestibular tests. As this is the first study in the literature to examine the audio-vestibular findings in this group, it is of great importance.
Numerous subjective and objective tests have been described to evaluate the vestibulocochlear system. An otoacoustic emission (OAE) is used for measuring outer hair cells and the function of the cochlea [10]. It gives precious information to evaluate the early damage in the cochlea and outer hair cells that cannot be assessed in pure tone audiometry [11]. Suppressed OAE is used to evaluate whether the efferents originating from the Medial Olivary Complex (MOC) are functioning. Vestibular-evoked myogenic potentials (VEMP) is an objective test defined to measure saccule and utricle functions [12]. The video head impulse test (VHIT) is an objective test battery that assesses the semicircular canals and the superior and inferior vestibular nerves via the vestibule-ocular reflex.
Studies evaluating the cochleovestibular system in the literature are mostly on adult patients. Studies examining the vestibulocochlear system in detail in pediatric patients are scarce and have a narrow scope [13]. In this study, the vestibulocochlear system was discussed with objective and subjective tests in pediatric patients in the early-post-COVID-19 period, and it was investigated whether SARS-CoV-2 damaged the vestibulocochlear system in this period.
2. Materials end methods
In this study, we aimed to evaluate the vestibulocochlear involvement of pediatric patients (aged 9–15 years) in the early period of post-COVID-19. The research was carried out in the Audiology Unit and Otolaryngology Clinic of the Inonu University Turgut Ozal Medical Center between December 2021 and March 2022. Thirty-five patients in the early post-COVID-19 period (COVID-19 group) and 35 age- and gender-matched healthy individuals (control group) were included in the study. All patients in the COVID-19 group were evaluated after their first COVID-19 infection and none of them had been vaccinated before. In the COVID-19 group, patients who survived the COVID-19 disease as an outpatient and did not need oxygen support during the recovery period were included (which can be classified as a mild disease). The diagnosis of COVID-19 was made in all patients by real-time Polymerase Chain Reaction (PCR) via the oro-nasopharyngeal swab sample. Those who had complaints of dizziness and imbalance, conductive hearing loss, and otologic and neurological diseases in both control group and COVID-19 group (before COVID-19) were excluded from the study. Ethical approval was obtained from the Inonu University Health Sciences Institute Non-Interventional Clinical Research Ethics Committee (Decision number: 2021/2558), and written and verbal informed consent was obtained from the parents of all children participating in the study. While conducting the research, all principles of the Declaration of Helsinki were adhered to and followed. Pure tone audiometry, suppressed OAE, VHIT, and c/o-VEMP tests were applied to all participants included in the study after their otoscopic examinations.
2.1. Sociodemographic data form
The parents filled out a form containing information such as age, gender, symptoms during the disease process, date of diagnosis, and duration of disease.
2.2. Otoacoustic emission (OAE) and pure tone audiometry
Audiological evaluations were made by the same audiologist, accompanied by an otolaryngologist. Pure tone audiometry consisting of 8 frequencies (125, 250, 500, 1000, 2000, 4000, 6000, and 8000 Hz) was performed in all patients with the Interacoustics-Clinical Audiometer AC40 (Middelfart, Denmark) device in a quiet cabin. During the statistical analysis, each frequency was compared between the two groups.
Transient evoked OAE (TE-OAE) tests and contralateral suppression (CLS) application were performed using an Otodynamics-ILO 292 USB II (Herts, United Kingdom) device. A test probe was placed in both ears and 260 linear instantaneous stimuli with 80 ± 3 dB sound-pressure level (dB SPL) intensity were recorded in the ipsilateral ear, and a 60 dB wideband noise was sent to the contralateral ear in linear stimulus mode, then TEOAE measurements were made in the ipsilateral ear with and without noise [14]. Immediate evoked otoacoustic emission responses were recorded at frequencies of 1000, 1400, 2000, 2800, and 4000 Hz. Signal-to-noise ratio (SNR) values of both tests were analyzed as operating parameters.
2.3. Video head impulse test (VHIT)
The Video Head Impulse Test (VHIT) is a vestibular test battery used to evaluate the functions of the semicircular canals (SCC). This test battery provides information about the vestibulo-ocular reflex (VOR) at high frequencies by evaluating the harmony between rapid head movement and eye movement. The test was performed with a Micromedical Technologies-EyeSeeCam (Illınois, US) device. At the end of the test, the VOR gain graph was obtained according to the head and eye movement speeds. The speed ratio of head and eye movement should be 1.0 in healthy individuals. In our clinic, the standard deviations of this value were calculated and evaluated between 0.8 and 1.1. A VOR gain of less than 0.8 and a percentage of asymmetry greater than 6.9 were considered a pathological VHIT response [15].
2.4. Vestibular evoked myogenic potentials test (c-VEMP/o-VEMP)
c-VEMP and o-VEMP tests were performed with the Neurosoft Neuro-Audio (Ivanovo-Russia) device. When myogenic potentials could not be obtained, it was considered a pathological finding. The proportion of patients in whom myogenic potentials could not be obtained in both the o-VEMP test and the c-VEMP test were statistically compared between groups. The electromyographic signals were amplified and bandpass-filtered between 30 and 2000 Hz. Short-tone burst stimulations (105 dB HL, 500 Hz, each with a 2-ms rise fall time and a 0-ms plateau time) were delivered to each ear. The peak latencies of waves p13 and n23, p13-n23 interpeak latencies, and peak-to-peak amplitudes (p13–n23) were recorded for each ear. The asymmetry ratio was calculated to compare the right and left ears using the formula described by Murofushi et al. [16].
The Ocular VEMP (o-VEMP) test was performed while the participants were in a sitting position. The peaks of the first waveform formed after the stimulus were determined as n10 and p15. The electromyographic signals were amplified and bandpass-filtered between 1 and 1000 Hz. Sound stimuli were delivered to the contralateral side of the active electrode with an intensity of 105 dB HL. The peak latencies of waves n10 and p15 and peak-to-peak amplitudes (n10–p15) were recorded for each ear. The asymmetry ratio was calculated to compare the right and left ears using the formula described by Murofushi et al. [16].
2.5. Statistical analysis
Data analysis was carried out with the SPSS 25 (New York, US) program. Whether the data included in the study conformed to the normal distribution was checked with the Kolmogorov-Smirnov Test [17]. The significance level (p) for comparison tests was taken as 0.05.
Since the variables did not have a normal distribution (p > 0.05), the analysis was continued with non-parametric test methods. Comparisons in independent pairs were made with the Mann-Whitney U test because the assumption of normality was not provided. In the analysis of categorical data, cross tables were created and the Chi-square (ꭓ2) analysis was performed.
3. Results
Demographic data are presented in Table 1 . The mean age of the participants included in the study was 12.66 ± 2.11 years (min: 9-max: 15) in the COVID-19 group and 11.71 ± 2.23 years (min: 9-max: 15) in the control group. There was no statistically significant difference between the groups in terms of mean age (p = 0.070). The gender distribution of the groups was similar and there was no statistically significant difference (p = 0.810).
Table 1.
Comparison of demographic data between groups.
| Groups |
p-value | |||||
|---|---|---|---|---|---|---|
| COVID-19 Group |
Control Group |
|||||
| Mean ± SD | Min-Max | Mean ± SD | Min-Max | |||
| Age | 12,66 ± 2,11 | 9–15 | 11,71 ± 2,23 | 9–15 | 0,070b | |
| Count | Percent (%) | Count | Percent (%) | |||
| Gender | Female | 15 | 42,9% | 16 | 45,7% | 0,810a |
| Male | 20 | 57,1% | 19 | 54,3% | ||
SD; standard deviation pa; Chi-square test value (ꭓ2), pb; Mann Whitney U test value, *p-values in bold indicate statistically significance.
The parameters related to the disease process of COVID-19 were analyzed, and none of the patients with COVID-19 were hospitalized and received oxygen therapy. The most common symptom was evaluated as fever (68.6%). Apart from fever, the symptoms recorded in the patients were shortness of breath, arthralgia, weakness, headache, dizziness and vertigo, and loss of taste and loss of smell, in order of frequency. When patients were retrospectively screened for audiovestibular complaints during the COVID-19 period, six patients had complaints of vertigo/dizziness, fullness in the ear, and tinnitus. There were only vertigo/dizziness and hearing loss in three patients, only tinnitus in two patients, and fullness in the ear only in two patients. Tinnitus and vertiginous complaints were present in only two patients at time of study. In the further examinations of these two patients, mild sensorineural hearing loss affecting advanced frequencies (4000 Hz and above) was observed in both, and vestibular tests were considered normal. The mean duration of COVID-19 was 11.31 ± 2.79 days. The mean time from one negative COVID-19 PCR test to audio-vestibular evaluation was 51.75 ± 18.82 days.
Pure tone audiometry was measured at eight different frequencies. When the groups were compared, statistically significant differences were noted between the groups at four different frequencies (1000, 2000, 4000, and 8000 Hz). The hearing thresholds of the control group were determined better than the COVID-19 group in all four frequencies. In Table 2 , mean values of 8 frequencies and comparisons of both groups are presented.
Table 2.
Comparisons of pure tone averages between groups.
| Frequency | Control |
COVID-19 |
p value | ||
|---|---|---|---|---|---|
| Mean ± SD | Median (Min-Max) | Mean ± SD | Median (Min-Max) | ||
| 125 Hz | 5,36 ± 2,46 | 5 (0–10) | 5,29 ± 2,68 | 5 (0–10) | 0,884 |
| 250 Hz | 6,71 ± 3,8 | 5 (0–15) | 7,64 ± 3,97 | 5 (0–20) | 0,291 |
| 500 Hz | 7,07 ± 3,76 | 5 (0–15) | 7,5 ± 3,48 | 5 (5–20) | 0,821 |
| 1000 Hz | 5,29 ± 3,98 | 5 (0–15) | 7,71 ± 3,48 | 10 (0–15) | <0,001* |
| 2000 Hz | 5,14 ± 4,08 | 5 (0–15) | 7,29 ± 3,68 | 5 (0–15) | 0,001* |
| 4000 Hz | 5,5 ± 4,67 | 5 (0–20) | 7,71 ± 3,58 | 5 (0–20) | 0,001* |
| 6000 Hz | 9,36 ± 6,19 | 10 (0–30) | 7,57 ± 3,78 | 5 (0–20) | 0,078 |
| 8000 Hz | 8,79 ± 8,53 | 5 (0–50) | 7,43 ± 3,38 | 7,5 (0–15) | 0,945 |
SD; standard deviation, Hz; Hertz, *p-values in bold indicate statistically significance.
Statistical analysis of whether suppression occurred in suppressed transient otoacoustic emission is presented in Table 3 . Suppression at five different frequencies was obtained almost completely in the control group (not observed in 1 participant at 1000 Hz and 2 participants at 1400 Hz). In contrast, there were patients in whom suppression was not obtained at every frequency in the COVID-19 group. The inability to obtain suppression in the COVID-19 group at all frequencies was higher and statistically significant compared to the control group.
Table 3.
Comparison of the presence of suppression in the otoacoustic emission test between groups.
| Frequencies | Suppression (dB SPL) | Groups |
p value | |
|---|---|---|---|---|
| COVID-19 | Control | |||
| 1000 Hz | <1 | 14 (20,0%) | 1 (1,4%) | 0,001* |
| >1 | 56 (80,0%) | 69 (98,6%) | ||
| 1400 Hz | <1 | 14 (20,0%) | 2 (2,9%) | 0,003* |
| >1 | 56 (80,0%) | 68 (97,1%) | ||
| 2000 Hz | <1 | 5 (7,1%) | 0 (0,0%) | 0,008* |
| >1 | 65 (92,9%) | 70 (100,0%) | ||
| 2800 Hz | <1 | 16 (22,9%) | 0 (0,0%) | 0,001* |
| >1 | 54 (77,1%) | 70 (100,0%) | ||
| 4000 Hz | <1 | 17 (24,3%) | 0 (0,0%) | 0,001* |
| >1 | 53 (75,7%) | 70 (100,0%) | ||
dB SPL: decibel Sound Pressure Level, *p-values in bold indicate statistically significance.
Suppressed otoacoustic emission data were analyzed by comparing the signal-noise ratio (SNR) values obtained from the ipsilateral ear before and after the noise was introduced into the contralateral ear (Table 4 ). There was a statistically significant difference between the groups in terms of the SNR values obtained before the noise at 2800 Hz and before and after the noise at 4000 Hz.
Table 4.
Comparison of SNR values obtained during OAE and Suppressed OAE between groups.
| Frequency | Groups |
p-value* | |||
|---|---|---|---|---|---|
| COVID-19 Group |
Control Group |
||||
| Mean ± SD | Median (Min-Max) | Mean ± SD | Median (Min-Max) | ||
| 1 kHz | 14,39 ± 5,16 | 13,65 (5,2–25,20) | 14,24 ± 4,65 | 13,90 (7,5–25,6) | 0,833 |
| 1 kHz with suppression | 11,17 ± 5,23 | 10,15 (3,1–24,8) | 9,86 ± 4,02 | 9,1 (5,1–20,9) | 0,212 |
| 1.4 kHz | 14,13 ± 5,01 | 12,65 (7,1–27,1) | 13,82 ± 4,91 | 14,35 (6,3–25)9 | 0,698 |
| 1.4 kHz with suppression | 11,45 ± 5,08 | 11,1 (5,1–26,4) | 10,36 ± 4,67 | 10,15 (4,2–23)9 | 0,157 |
| 2 kHz | 14,35 ± 4,49 | 14,55 (6,8–25,9) | 15,36 ± 5,65 | 15 (6,2–27,1) | 0,498 |
| 2 kHz with suppression | 11,19 ± 4,07 | 11,45 (5,1–23,7) | 10,97 ± 4,98 | 10,5 (4,5–22,9) | 0,486 |
| 2.8 kHz | 13,12 ± 4,51 | 12,2 (7,1–25,5) | 15,39 ± 6,1 | 14,55 (6,1–28,6) | 0,042* |
| 2.8 kHz with suppression | 10,59 ± 4,51 | 10,75 (3,7–25,4) | 11,59 ± 5,28 | 10,95 (4,5–22,9) | 0,381 |
| 4 kHz | 11,63 ± 4,24 | 10,1 (4,2–21,5) | 15,36 ± 5,34 | 15,45 (6,1–27,5) | <0,001* |
| 4 kHz with suppression | 9,22 ± 4,08 | 7,85 (4,1–19,8) | 11,44 ± 4,46 | 11,35 (5–21,8) | 0,003* |
SNR: The signal-to-noise ratio, OAE: otoacoustic emission, kHz: kilohertz, SD: Standard deviation, *p-values in bold indicate statistically significance.
The VHIT lateral gain, left anterior right posterior (LARP) gain, right anterior left posterior (RALP) gain, lateral asymmetry, LARP asymmetry, and RALP asymmetry values of the participants included in the study were compared between the groups, and the data are presented in Table 5 . VHIT lateral gain, LARP gain, and RALP gain were statistically significantly lower in the COVID-19 group than in the control group (p < 0.001, p = 0.049, p = 0.044, respectively). The VHIT lateral asymmetry parameter was statistically higher in the COVID-19 group than in the control group (p = 0.036). In addition, there was no statistically significant difference between patients with and without COVID-19 according to LARP asymmetry and RALP asymmetry values (p > 0.05, Table 5).
Table 5.
Comparison of the v-HIT parameters between groups.
| Groups |
p-value* | ||||
|---|---|---|---|---|---|
| COVID-19 Group |
Control Group |
||||
| Mean ± SD | Median (Min-Max) | Mean ± SD | Median (Min-Max) | ||
| v-HIT lateral gain | 0,91 ± 0,07 | 0,9 (0,76–1,12) | 0,97 ± 0,06 | 0,98 (0,8–1,08) | <0,001* |
| v-HIT LARP gain | 0,84 ± 0,1 | 0,85 (0,62–1,06) | 0,88 ± 0,12 | 0,9 (0,63–1,07) | 0,049* |
| v-HIT RALP gain | 0,84 ± 0,12 | 0,85 (0,6–1,03) | 0,88 ± 0,11 | 0,9 (0,67–1,08) | 0,044* |
| v-HIT lateral asymmetry | 3,14 ± 1,54 | 3,1 (0,8–6,7) | 2,39 ± 1,59 | 2 (0,4–7) | 0,036* |
| v-HIT LARP asymmetry | 4,49 ± 2,94 | 3,3 (0,9–12,7) | 3,93 ± 2,84 | 3 (0,5–10,5) | 0,344 |
| v-HIT RALP asymmetry | 4,51 ± 3 | 3,6 (0,1–15,2) | 3,55 ± 2,36 | 2,5 (1–9,7) | 0,075 |
v-HIT: Video Head Impulse Test, LARP: Left Anterior, Right Posterior, RALP: Right Anterior, Left Posterior SD: Standard deviation, *p-values in bold indicate statistically significance.
The participants also received the c-VEMP and o-VEMP tests. In the c-VEMP test, p13 latency, n23 latency, p13-n23 interlatency, and p13-n23 interpeak amplitude and asymmetry parameters were measured and compared between groups. Except for the asymmetry value, there was no statistically significant difference between the groups (p > 0.05). The asymmetry parameter was statistically higher in the COVID-19 group (p = 0.008). In the o-VEMP test, n10 latency, p15 latency, n10-p15 interlatency, and n10-p15 interpeak amplitude and asymmetry parameters were measured and no statistically significant difference was found between the groups (p > 0.05, Table 6 ). The presence of waves in the c-VEMP and o-VEMP tests were compared between the groups. In the COVID-19 group, c-VEMP could not be obtained in 10 patients, whereas it could not be obtained in 4 patients in the control group. In the COVID-19 group, the o-VEMP test could not be obtained in 6 patients, whereas it could not be obtained in 4 patients in the control group. When the number of patients in whom waves could not be obtained in both o-VEMP and c-VEMP were compared, there was no statistical difference (p > 0.05).
Table 6.
Comparison of the c-VEMP and o-VEMP parameters between groups.
| Groups |
p-value* | ||||
|---|---|---|---|---|---|
| COVID-19 Group |
Control Group |
||||
| Mean ± SD | Median (Min-Max) | Mean ± SD | Median (Min-Max) | ||
| c-VEMP p13 (ms) | 13,11 ± 1,47 | 13,1 (10,5–17,2) | 13,16 ± 1,35 | 13 (10,5–16,2) | 0,904 |
| c-VEMP n23 (ms) | 21,23 ± 1,61 | 21,6 (17,1–24,5) | 20,95 ± 1,61 | 20,95 (17,8–24,5) | 0,213 |
| p13-n23 interlatency (ms) | 8,09 ± 1,93 | 8,1 (4,2–11,5) | 7,72 ± 1,12 | 7,9 (5,1–9,9) | 0,234 |
| p13-n23amplitude (mV) | 86,6 ± 38,42 | 84,15 (24,3–176,9) | 90,81 ± 51 | 78,4 (35,3–267,1) | 0,880 |
| c-VEMP asymmetry | 13,91 ± 6,69 | 13,9 (1,8–26,8) | 10,08 ± 5,2 | 10 (0,6–27,3) | 0,008 |
| o-VEMP n10 (ms) | 10,21 ± 1,37 | 10,05 (8,4–15,7) | 10,26 ± 1,08 | 10 (8,4–12,8) | 0,513 |
| o-VEMP p15 (ms) | 15,73 ± 1,56 | 15,3 (13,4–19,5) | 15,91 ± 1,64 | 15,95 (12,7–19,1) | 0,449 |
| n10-p15 interlatency (ms) | 5,53 ± 1 | 5,65 (3,2–7,4) | 5,66 ± 1,09 | 5,45 (3,6–8,4) | 0,462 |
| n10-p15 amplitude (mV) | 8,5 ± 5,6 | 7,3 (3,1–28,3) | 9,82 ± 5,95 | 7,95 (2,8–29,5) | 0,746 |
| o-VEMP asymmetry | 15,88 ± 10 | 15,9 (0,7–35,6) | 10,95 ± 6,39 | 11,2 (0,4–24,4) | 0,067 |
c-VEMP: Cervical vestibular-evoked myogenic potential, o-VMEP: Ocular vestibular-evoked myogenic potential, SD: Standard deviation,ms:millisecond, mV:millivolt, *p-values in bold indicate statistically significance.
4. Discussion
The effects of SARS-CoV-2 on the cochleovestibular system have been widely discussed in adult patients, and most studies show that it damages the system [8,18,19]. On the other hand, some studies claim that SARS-CoV-2 does not cause any damage to the cochleovestibular system [20]. Although there are a few studies that evaluate cochlear functions in the pediatric patient group, no study evaluating the vestibular system has been reported [13,21,22]. It has been reported that not only SARS-CoV-2 but also other viral infections can damage the cochleovestibular system by causing inflammation directly or through mediators [23,24]. Since the neurotropic and neuroinvasive characteristic of SARS-CoV-2 has been described [6], its effects on the vestibulocochlear system in pediatric patients are intriguing. In this study, it was aimed to evaluate the cochleovestibular system with objective and subjective test batteries in pediatric patients with COVID-19.
In our study, hearing thresholds obtained at 1000, 2000, 4000, and 8000 Hz in pure tone audiometry were statistically significantly worse in the COVID-19 group (p < 0.001, p = 0.001, p = 0.001, p = 0.014, respectively) compared to the control group. In studies conducted with pure tone audiometry in adult patients, it was stated that SARS-CoV-2 might play a role in the etiopathogenesis of hearing loss [18]. Swain et al. conducted a study in which they evaluated 192 cases of COVID-19, and reported hearing loss in 24 (12.5%) patients [25]. COVID-19 patients presenting with sudden hearing loss have also been reported. In our study, similar to the literature, hearing thresholds in pediatric patients with COVID-19 were worse at 4 frequencies, which may indicate a possible cochlear damage. Viral infections can adversely affect the auditory system. This involvement is usually intracochlear. Organ of Corti, stria vascularis, or spiral ganglion may be affected in peripheral involvement [26]. The negative impact of hearing thresholds in pediatric patients with COVID-19 in our study supports this relationship. The data were obtained in the early period after COVID-19. Although there were statistically significant data, the clinical effect on patients was minimal. It seems very likely that they will improve over time.
Efferents from the MOC originate from the medial part of the Superior Olivary Complex and terminate in the outer hair cells. The activation of MOC efferents causes a decrease in signals from outer hair cells (as obtained via OAE), which is called suppression [[27], [28], [29]]. MOC efferents have critical functions in hearing. They support auditory perception in noisy environments through anti-masking, and this mechanism maintains enhanced tone and intensity determination and speech discrimination. They regulate selective attention by regulating the functions of outer hair cells in the ear where the stimulus is targeted. In addition, MOC protects the inner ear from acoustic damage [30]. In a study conducted by Koca et al. MOC functions of pediatric COVID-19 patients were measured with suppressed OAE and they reported that some frequencies of patients with COVID-19 were affected [21]. In this study, SNR measurements were performed in the suppressed OAE test to evaluate the efferent pathways. In all frequencies (1000, 1400, 2000, 2800, and 4000 Hz), suppression was obtained in more patients in the control group than in the COVID-19 group (p < 0.001, p = 0.003, p = 0.008, p < 0.001, p < 0.001 for each frequency, respectively). The SNR values obtained without suppression at 2800 Hz and the SNR values with and without suppression obtained at 4000 Hz were statistically significantly lower in the COVID-19 group (p = 0.042, p < 0.001, p = 0.003, respectively). Data from our study and previously reported studies suggest that the MOC efferent system may be damaged in patients with COVID-19. The clinical response of this damage shown by the data in the MOC system is not fully known. It should be noted that it may be temporary and these data may become similar to the data from the control group over time. In the future, it will be possible to clarify whether a problem will occur later in critical tasks such as speech discrimination and tonal discrimination with studies examining the longer period.
The v-HIT is an objective test developed to evaluate the functions of the semicircular canals and superior/inferior vestibular nerves via the vestibulo-ocular reflex [31,32]. In a study conducted by Bozdemir et al. in adult patients, caloric and v-HIT tests were performed in patients with COVID-19, and they found a decrease in lateral canal gains compared to the control group [33]. In the data obtained in our study, lateral gains and RALP and LARP gains were lower in the COVID-19 group. In addition, lateral asymmetry was higher in the COVID-19 group than in the control group. These results show that the vestibular systems of pediatric patients may be more affected by COVID-19 than adult patients.
c-VEMP measures the functions of the inferior vestibular nerve and saccule over the vestibulo-collic reflex, and o-VEMP is an objective test battery that can measure the functions of the superior vestibular nerve and utricle. Longer latency of VEMP waves, longer interpeak latency, lower amplitude of the waves, or no waves are considered pathological in the VEMP test [12]. In our previous study with VEMP in patients with COVID-19, the amplitude of p13-n23 was significantly lower in adult patients with COVID-19, and longer latency of n23 was detected [9]. In this study, only the c-VEMP asymmetry value was higher in the COVID-19 group than that in the control group. When the patients in whom c-VEMP and o-VEMP waves could not be obtained were compared between the groups, no significant difference was observed. Based on the data obtained with the VEMP test battery, it can be said that COVID-19 does not cause a possible sequela in the c-VEMP and o-VEMP arc in pediatric patients.
The lack of caloric testing in this study can be considered a limitation. Another limitation is the lack of pre-study patient data. The data obtained are short-term data after COVID-19. Long-term follow-ups are required to reach a conclusion more clearly. Since no imaging was performed on the temporal bones of the patients included in the study, middle and inner ear anomalies could not be excluded.
In conclusion, the effects of COVID-19 on the cochleovestibular system are still a topic of research interest. Studies on pediatric patients are limited and this is the first study in terms of vestibular assessment. Evidence was obtained that COVID-19 causes damage to the cochlea-vestibular system in pediatric patients in the early post-COVID-19 period; however, it is certain that prospective studies with longer follow-up of these patients are needed.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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