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Table of Contents
REVIEW ARTICLE
Year : 2020  |  Volume : 16  |  Issue : 4  |  Page : 159-163

Hearing loss: A neglected and morbid clinical entity in Corona Virus Disease 2019 pandemic


Department of Otorhinolaryngology, IMS and SUM Hospital, Siksha “O” Anusandhan University, Bhubaneswar, Odisha, India

Date of Submission16-Aug-2020
Date of Acceptance21-Oct-2020
Date of Web Publication23-Dec-2020

Correspondence Address:
Prof. Santosh Kumar Swain
Department of Otorhinolaryngology, IMS and SUM Hospital, Siksha “O” Anusandhan University Kalinga Nagar, Bhubaneswar - 751 003, Odisha
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AMJM.AMJM_57_20

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  Abstract 


Hearing loss may be caused by certain viral infections. The hearing loss due to viral infection can be congenital or acquired, bilateral or unilateral. The viral infections typically cause sensorineural hearing loss (SNHL), although conductive or mixed hearing loss can be found. The corona virus disease 2019 (COVID-19) infection has deleterious impact on the cochlear hair cells. The hearing loss will not improve even patient recovered from COVID-19 infections. This is probably a neuro-auditory involvement in COVID-19 infections. The current COVID-19 is caused by severe acute respiratory syndrome corona virus 2. The audiologic and radiologic investigations are helpful for evaluation of the hearing loss in COVID-19 patients. Hearing loss due to COVID-19 infections is rarely reported in medical literature so far. Hearing loss specifically SNHL is often challenging to the clinicians in this current pandemic. The mechanism for this deleterious effect on the cochlear hair cells requires further research. There is a large gap in the understanding of the etiopathogenesis, epidemiology, and clinical presentations such as hearing loss and human transmission of this disease. There should be a continuous monitoring of the hearing loss and tracing of this COVID-19 infection is needed to ensure the detail understanding of this inner ear pathogenesis. This review article provides an overview of COVID-19 infections and its impact on hearing loss.

Keywords: Cochlear hair cells, COID-19 infection, severe acute respiratory syndrome corona virus 2, sensorineural hearing loss


How to cite this article:
Swain SK, Pani SR. Hearing loss: A neglected and morbid clinical entity in Corona Virus Disease 2019 pandemic. Amrita J Med 2020;16:159-63

How to cite this URL:
Swain SK, Pani SR. Hearing loss: A neglected and morbid clinical entity in Corona Virus Disease 2019 pandemic. Amrita J Med [serial online] 2020 [cited 2021 May 11];16:159-63. Available from: https://www.ajmonline.org.in/text.asp?2020/16/4/159/304581




  Introduction Top


Corona virus disease 2019 (COVID-19) is a contagious infection of the respiratory airway caused by a novel virus called severe acute respiratory syndrome corona virus 2 (SARS-CoV-2).[1] COVID-19 pandemic was originated from China in December 2019.[2] The COVID-19 patients often present with cough, sore throat, headache, fever, muscle pain, diarrhea, loss of taste, loss of smell, and dyspnea.[1] The elderly persons or patients with comorbidity or with systemic diseases are susceptible to infections and serious outcome which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm.[3],[4] The neurological manifestations are found in certain viral infections such as anosmia, dysgeusia, facial nerve palsy, and sensorineural hearing loss (SNHL).[5] The link between the COVID-19 infection and hearing loss makes intuitive sense, given the neuropathic manifestations of the inner ear and auditory nerve leading to SNHL. The knowledge of the medical community regarding clinical manifestations of the COVID-19 infection is extremely dynamic as the behavior of this virus is still not established. During this pandemic, it is vital to find out every possible symptom of COVID-19 infection to break the chain of transmission. Hearing impairment is an uncommon and morbid clinical manifestation found among COVID-19 patients.[6] Hearing loss has an important role on communication and interaction, causing an invisible handicap of the affected person and psychological solitary confinement. Although certain viral infections cause hearing loss, there is still unknown whether COVID-19 infections lead to auditory dysfunction or not. Here this review article summarizes the etiopathology, clinical presentations, investigations, and current treatment of the hearing loss due to deleterious effect on the auditory system by the COVID-19 infections. It is hoped that this review article helps to health-care provides by enabling the early detection of these COVID-19 patients and their isolation, prevention of the transmission of the infection in early period of the disease, and targeted treatment to the patients.


  Methods of the Literature Search Top


For searching the published research articles, we conducted an electronic survey of the SCOPUS, Medline, Google Scholar, and PubMed database. The search terms in the database included hearing loss, sensorineural hearing loss, sudden sensorineural hearing loss, and COVID-19 infection. The abstracts of the published articles were identified by this search method and other articles were identified manually from citations. This manuscript reviews the etiology, epidemiology, clinical presentations, diagnosis, and current treatment of the hearing loss in COVID-19 patients. This review article presents a baseline from where further prospective trials for hearing loss in COVID-19 patients could be designed and helps as a spur for further research in this rarely encountered morbid clinical entity.


  Epidemiology Top


COVID-19 infection is a highly contagious and found in the respiratory system due to novel virus SARS-CoV-2. The first case was reported in Wuhan, China, in late December 2019 where the outbreak of the novel CoV now called as SARS-CoV-2 spread worldwide.[2] World Health Organization (WHO) pronounced this disease caused by this virus as COVID-19 on February 11, 2020. WHO has declared COVID-19 as pandemic disease on March 11, 2020, and COVID-19 spread to around 199 countries by March 26, 2020 with more than 462,680 positive cases and approximately 20834 deaths.[7] The pandemic of the COVID-19 is showing a grim and tragic situation worldwide in current days. It is affecting on the global economy along with clinical practice for routine patient care. The association between the COVID-19 infections cause a challenge to the hearing health-care provides as it has impact on hearing. The WHO has estimated that approximately 360 million people with disabling hearing loss in the world which proved that more than half of the persons with hearing loss can be prevented by early diagnosis and prompt treatment.[1] The widespread transmission and infectivity of the COVID-19 lead to an unrestricted health threat to the planet.[8] COVID-19 infections and its impact on auditory system are not reported much in literature and are very little mentioned in the medical literature. Brainstem involvement by CoV and the damaging effect of the virus leading to neuro-auditory dysfunction cause hearing loss.[9] There is a study revealing effect of COVID-19 infections on the cochlear hair cells and leading to hearing loss even in asymptomatic patients.[10]


  Corona Virus Disease 2019 Virus Top


The etiologic agent for COVID-19 infection is a novel CoV called as SARS-CoV-2.[11] This disease is called COVID-19 by WHO.[11] This virus [Figure 1] was formerly known as 2019 novel CoV (2019-nCoV), positive-sense, single-stranded RNA virus with diameter of 60–140 nm.[11] It is a new variety of the CoV which belongs to the genus of beta CoV.[12] So far, 2019-nCoV is the 7th member of the CoV family which can infect human being. The incubation period of COVID-19 ranges from 1 to 14 days with a median of 5–6 days although recent study document that the incubation period may extend to 24 days.[13] A longer incubation has implication in quarantine policies and prevention of the spread of the disease. This virus primarily transmitted via respiratory droplets but also it is found in blood and stool, so raising question regarding mode of transmission.[14] The viral infection typically damages the auditory system especially to the cochlear hair cells; however few viruses can damage the auditory brain stem as well. The mechanism for damage to the peripheral auditory system is through injury to the organ of Corti, stria vascularis or spiral ganglion. Sometimes, the auditory damage is mediated through the patient's immune system against the proteins expressed by the virus as in Cytomegalovirus and the low immunity cause secondary bacterial infections of the inner ear as in Human Immune deficiency virus and measles.[15]
Figure 1: Structure of the corona virus disease 2019 virus (Black arrow is spike protein over lipid membrane, Green arrow indicates RNA)

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  Etiopathology Top


There are several viral infections associated with hearing loss. SNHL is a known complication of certain viral infections. There is a plausible mechanism which may cause virus associated hearing loss. A current study of 58 patients with COVID-19 infections is associated with encephalopathy where majority showed leptomeningeal contrast enhancement.[16] SNHL is a possible complication due to bacterial or viral meningitis and found in approximately 7% of the cases.[17] The hearing loss due to viral infections can be congenital or acquired in nature and unilateral or bilateral. Certain virus can directly make injury to the inner ear or can increase the susceptibility of the bacterial or fungal infections of the labyrinth leading to hearing loss. Virus causing hearing loss is often sensorineural in nature although mixed and conductive hearing loss may be found after certain virus infection. In some cases, the hearing loss can recover spontaneously.[18],[19] Although viral infections typically manifest SNHL, a virus is associated with otosclerosis with conductive hearing loss and human immunodeficiency virus (HIV) infections leads to conductive hearing loss through fungal and bacterial infections after making immunosuppression of the host by the virus.[20] The mechanism of the hearing loss by viral infections vary greatly and ranges from direct injury to the inner ear structures like organ of Corti and hair cells as documented in measles infections to the induction of the host related damage.[21] Although there are several viral infections causing hearing loss, it is still unknown for the exact cause of the hearing loss by COVID-19 by affecting the auditory system or not. One study showed that COVID-19 infections cause deleterious effects on the outer hair cells of the cochlea.[10] Even in the absence of the major respiratory symptoms of the COVID-19 patients, there is no guarantee for the healthy cochlear functions. The damage to the outer hair cells can be documented by transient evoked oto-acoustic emission (TEOAE).[22] Viral damage to the auditory system is often intra-cochlear; however certain virus can damage the auditory brainstem as well. The mechanism behind the injury of the auditory system may include direct damage by the virus to the organ of Corti, stria vascularis or to the spiral ganglion. The viral damage may also be mediated by the immune system of the patient against the virus expressed proteins as in cytomegalovirus and low immunity of the host leads to bacterial infections of the ear as in measles and HIV infections.[15] The entry point of the SARS CoV-2 is the respiratory airway and then enters the cell by penetrating to angiotensin-converting enzyme 2 (ACE2) inside the lungs. Once the cytosolic pH reduces, the ACE2 binds easily to the virus. As the cytosolic pH reduces with increase of the age, the virus leads to severe infections in the elderly age group.[23] The virus often attaches to the hemoglobin and enters into the red blood cell (RBC). Then the virus moved with RBC or vascular endothelium, possible infects the tissues with ACE2 in its tissue. There is high concentration of the ACE2 in the brain and medulla oblongata. There is also high concentration of the ACE2 auditory center such as temporal lobe of the brain.[24] It increases the viral load at the auditory center. The virus leads to release of the excess of the cytokines at the hearing center or at its surroundings and cause permanent hearing loss by damage through oxidative damage. If virus infects the RBC, it deoxygenates the RBC. If there is activation of the virus at the auditory center, leads to hypoxic hearing center and permanent SNHL.[10]


  Clinical Presentations Top


The symptoms of the COVID-19 patients may appear 2–14 days after exposure to the viral infections as per the incubation period of the SARS CoV-2 virus. The clinical presentations of the COVID-19 patients include cough, fatigue, fever, loss of smell, loss of taste (dysgeusia), gastrointestinal symptoms and dyspnea. The COVID-19 patients mainly presents with lower respiratory tract related clinical manifestations such as cough, dyspnea, chest tightness, fever, and cough, which can progress to ARDS.[25] It also presents some upper respiratory manifestations such as sore throat, nasal congestions, rhinorrhea, and olfactory dysfunction.[26] The old age person infected with COVID-19 infections is susceptible to ARDS and cytokine storm.[27] Due to infections at the nose and nasopharynx, the  Eustachian tube More Details may be blocked and lead to eustachian tube dysfunction. The eustachian tube dysfunction leads to fullness of the ear and otalgia. The eustachian tube dysfunction further leads to acute suppurative otitis media which manifests as severe ear pain, ear discharge, and hearing loss.[28] The hearing loss due to viral infections varies from mild to profound degree and unilateral or bilateral. The hearing loss is typically high frequency SNHL.[10] The patients also present with SSNHL. The SSNHL is defined as a hearing loss of more than 30 decibel at three consecutive frequencies at least during the period of <3 days. Patient may present with tinnitus and vertigo along with SNHL. This may be attributed to the damage of the outer hair cells by the virus but the exact mechanism is still not known. Absence of the major respiratory symptoms may hide the impact of the viral infections of the cochlea and hide the deafness as a symptom due to COVID-19 infections. There are also several reports regarding the neurological manifestations in the COVID-19 infections. The nonspecific neurological manifestations like ataxia, dizziness, neuralgia because of the peripheral nerve involvement are documented in the COVID-19 infections.[22] In the past outbreak with SARS-CoV and Middle East respiratory syndrome CoV, cerebrospinal fluid analysis had shown the presence of the viral nucleic acid and also autopsy study revealed neurological involvement.[29] Another study with autopsy result of COVID-19 patients had shown edematous and hyperemic brain tissue with degeneration of the neuronal fibers.[30] One current study on the COVID-19 infections, approximately 20% cases presented with SNHL without prior risk factors for hearing loss.[6]


  Investigations Top


Tuning fork tests, pure tone audiometry, tympanometry, and otoacoustic emissions (OAE) are useful tests to evaluate the hearing loss in patients with COVID-19. The type and degree of hearing loss are easily assessed by the tuning fork test and pure tone audiometry. Tympanometry is done to assess the middle ear pathology. Type-A tympanogram is usually found in SNHL and type-C tympanogram seen in hearing loss with eustachian tube dysfunction. OAE represent a form of energy produced from the outer hair cells of the cochlea. The outer hair cell functions of the cochlea are easily known through the OAE. There is damage of the outer hair cells in certain viral infections. OAE can be spontaneous OAEs, evoked by transient stimuli like clicks or tone bursts (TEOAEs).TEOAEs are not invasive and can be easily performed. For performing TEOAEs, the time is short, low cost, and high sensitivity.[31] In all the cases of SNHL, TEOAEs picked up the subtle deterioration in the outer hair cell functions of the cochlea. The high frequencies tones are also lower than normal in COVID-19 patients with SNHL. TEOAE is also useful to assess the cochlear hearing loss in COVID-19 infections. It can pick up the subtle deterioration in the outer hair cell functions of the cochlea. The injury to the outer hair cells is easily evidenced by the decreased amplitude of the TEOAEs in the COVID-19 patients. These outcomes may be attributed to the damaging effects of the SARS CoV-2 virus infection on the outer hair cells but the exact mechanism is still not clear.[10] Magnetic resonance imaging (MRI) detects the signs of the inflammation in the meninges and the cochlea [Figure 2] in COVID-19 patients with SNHL. The primary goal of the MRI in case of SSNHL is to exclude pathology at the cerebellopontine angle, brain lesions, and cochlear lesions or labyrinthitis. However, ability to elicit viral labyrinthitis in COVID-19 patients with SSNHL is controversial. Gadolinium enhanced MRI of the brain often shows pathology of the cochlea, cochlear, and vestibular nerve on the side of the hearing loss. SARS-CoV-2 trigger immune mediated inflammation which suggests severe case of the infection associated with dysregulation of the immune system. In this severe inflammatory conditions, neutrophils to lymphocyte ratio and inflammatory cytokines like interleukin-6 are raised.[32]
Figure 2: Magnetic resonance imaging with gadolinium contrast showing high signal of the right cochlea

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  Treatment Top


The effective treatment for the COVID-19 infections is currently under the urgent investigation. Presently there is no evidence of the randomized clinical trials regarding the specific treatment which improves the patient outcome in COVID-19 infection.[33] Corticosteroids play a vital role for treating the SSNHL due to COVID-19 infections as in other etiology. However, in the infections with this novel CoV, corticosteroids may enhance the chance of the severe infections and lead to delayed clearance of the virus.[34] Chloroquine and hydroxychloroquine are promising drugs for COVID-19 patient; however their side effect is ototoxicity leading to SNHL and tinnitus. The use of the corticosteroids in SSNHL is well proven although certain side effects are associated with it. Intratympanic steroid injection may be preferred. One study shows the systemic administrations of the corticosteroids is superior to the intratympanic injections.[35] The systemic administration of the corticosteroid is also safer than intratympanic injection. All the patients with SNHL are usually treated with oral prednisolone 1 mg/kg/day in tapering dose for 3 weeks along with vitamin B-complex and proton pump inhibitor daily. In current COVID-19 pandemic, the treatment of the SSNHL with corticosteroids is often limited to the unilateral hearing loss of more than 60 decibel, particularly in single normal ear and in the absence of any symptoms of the COVID-19.[36] The few vasoactive and hemodilution therapies can be tried in SSNHL and these medications include pentoxifyline, Ginko biloba, dextran, nifedipine, and combination thereof.[37] The antiviral medication and hyperbaric oxygen therapy are also tried to improve the sudden hearing loss in COVID-19 infections but the outcome still need further research. The eustachian dysfunction is treated as usual with antihistamines, nasal decongestants, and Valsalva. If the hearing loss in the COVID-19 patients is not adequately treated, the patient may be recovered from the COVID-19 infection but the hearing loss does not improve. Once the COVID-19 infection diagnosed, early isolation of the patient and prompt initiation of the COVID-19 targeted treatment along with administration of the corticosteroids is done if clinical anticipate or at initial stage of the SNHL. Some recent studies showed the benefits of chloroquine and hydroxychloroquine in COVID-19 infections. It should be remembered that there are possibility of the ototoxicity of these drugs and patients with COVID-19 infections those survived showed sign of ototoxic effect of chloroquine and hydroxychloroquine such as hearing loss, tinnitus and imbalance.[38]


  Conclusion Top


There is a deleterious effect of the COVID-19 infection on the hair cells of the cochlea. The exact mechanism of the cochlear damage by SARS-CoV-2 still requires further research. Although the otological symptom such as hearing loss is not common like cough and fever in COVID-19 infections but it has high impact on patients hearing and communication which make life miserable. If any COVID-19 patient presented with hearing loss, immediately require audiological and radiological tests along with prompt treatment. Clinician should keep in mind regarding this nonspecific and morbid clinical entity such as SNHL in COVID-19 patients. Awareness of such clinical symptom in COVID-19 patients is often crucial in present pandemic because hearing loss could be the only presentation for recognizing the COVID-19 patients.

Financial support and sponsorship

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Conflicts of interest

There are no conflicts of interest.



 
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