Chloroquine-induced hearing loss: ototoxicity monitoring in COVID-19 patients

Over the past few decades, audiological ototoxicity monitoring has proven to be effective in early detection, identification, and as a resultant, the prevention of ototoxicity or medication-induced hearing loss. Ototoxicity is an adverse pharmacological reaction affecting the inner ear and is characterized by cochlear and/or vestibular dysfunction. Medication-induced ototoxicity may result in temporary or permanent hearing and balance dysfunction.

COVID-19, a novel or new pandemic, is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Common symptoms in infected individuals include a fever, cough, headache, sore throat and shortness of breath. This disease has been declared a Public Health Emergency of International Concern and a pandemic causing many countries to go into lockdown in order to prevent and control the disease. 

In the wake of the COVID-19 pandemic, recommended measures to prevent infection are hand hygiene, respiratory hygiene, social distancing and not touching your face (eyes, nose and mouth) with unwashed hands. Treatment of the COVID-19 disease is normally symptomatic management and general support of the infected individual. In patients with a severe manifestation of COVID-19, recent reports suggest that chloroquine may be beneficial in inhibiting the replication of the virus in such patients. These benefits, however, have been observed in small studies and observations that need to be verified by large scale formal clinical studies. 

Besides the established consequences of using chloroquine being retinal toxicity, there’s literature suggesting that chloroquine may be associated with ototoxicity. Case reports suggest tinnitus, balance dysfunction and sensorineural hearing loss as manifestations.

There is a growing debate regarding the reversibility of chloroquine-induced hearing loss. While some studies showed recovery of hearing impairment after discontinuation of the drug, others showed irreversibility. However, various studies suggest that treatment-related complications can be corrected if the medication is stopped and therapy such as steroids is administered

In addition, though hydroxychloroquine has been shown to have minimal risk of toxicity compared to chloroquine, multiple case reports and case series implicate hydroxychloroquine as potentially causing ototoxicity. The onset of hearing loss in individuals treated with the medication varies from a few months to years after the initial administration of the drug.

Other ototoxic medication that might be used in the treatment of COVID-19

Medical professionals may introduce alternate types of ototoxic medication during the acute treatment phase of COVID-19, for example, aminoglycosides for the treatment of secondary bacterial infections in pneumonia. Medications like kanamycin and in rare cases, vancomycin are examples of antibiotics that are used for the treatment of pneumonia.

Thus, it is important that medical professionals are aware of the ototoxic nature of the treatments used and to implement necessary cautionary measures. 

Ototoxicity monitoring in COVID-19 patients

Unfortunately, ototoxic hearing loss often goes unnoticed in the early stages, until it adversely affects the patient’s communication abilities. The World Health Organization has identified ototoxicity as one of the preventable causes of hearing impairment. Undoubtedly, by the time a patient complains about hearing impairment and balance-related problems, permanent damage may already have occurred. 

Unlike other forms of toxicities (i.e. nephrotoxicity), symptoms related to ototoxic hearing loss are poorly correlated to drug dosage; thus, the only way to detect ototoxicity is through timely and regular audiometric assessments. 

Ototoxicity monitoring in COVID-19 patients who are on such drugs is paramount in order to prevent further hearing deteriorations. This continued monitoring allows for changes in therapeutic management and to prepare the patient for possible side effects. This also provides the healthcare practitioner with concrete evidence of the impact the medication has on the hearing status of the patient. We all know the effects of hearing loss in individuals of all age-groups. In a busy in- and out-patient facility, saving lives, hearing loss of patients may go unnoticed. It is important that both physicians, nurses, audiologists and other healthcare professionals are aware of the effects of such drugs, to ensure appropriate measurements in place for our population. 

What should we do now?

It is key to note that prevention is the best form of rehabilitation. Effective ototoxicity monitoring programs have been established. The need to modify and contextualize these programs for the current pandemic is paramount. The overriding problem is there are very little to no audiologists in most countries, making the provision of audiological care difficult. 

The good news is that new technologies like tele-audiology and portable, booth-free, and automated audiological equipment are meeting the challenges that traditional technology cannot. 

What is tele-audiology? Tele-audiology is the use of technology to evaluate and manage patients over the internet using video conferencing as a platform. This provides patients with access to audiological care even in environments without audiologists. 

There are three different ways in which telemedicine, in this case, tele-audiology, is applied to analyze, interpret and provide recommendations to patients. Below are the three principles of telemedicine which can be applied:

  • Synchronous: This audiovisual happens in real-time by having a computer at the patient’s site and at the clinician’s site connected to the internet. The clinician remotely controls the computer at the patient’s site to monitor the status of the patient’s hearing. The clinician will then analyze and interpret the patient data in real-time, and provide recommendations. This can be done by using standard desktop sharing applications like TeamViewer
  • Asynchronous: The trained healthcare worker assesses the patient’s hearing, then forwards the patient’s data to an audiologist once the healthcare worker has access to the internet (read up on task shifting). The audiologist then interprets the patient data and sends back recommendations (i.e. ‘ototoxicity detected, please reduce drug dosage or frequency’) to the patient site.  This can be as simple as taking a picture of the audiogram with one’s phone and sending it over WhatsApp for interpretation. 
  • Hybrid: This is the use of both synchronous and asynchronous methods

However, on its own, tele-audiology is not enough. We need to have connected devices that enable the process to work efficiently. That is where we, eMoyo and the KUDUwave audiometer, come in.

KUDUwave™ is a portable solution which can be used to provide audiology services or test extended high frequencies in the field without a traditional soundproofed/treated booth.

The KUDUwave has been used to successfully monitor for ototoxicity in almost all individuals in MDR-TB programs. Because of this success record, it can be used today as cross-contamination is a problem with COVID-19 and also the suggested treatment may be ototoxic. 

The KUDUwave is a sound booth, headset and audiometer combined in a single lightweight headset device, enabling the required mobility and functionality to solve many of the issues related to drug-related ototoxicity mentioned above.

  1. KUDUwave is portable – this allows hearing healthcare professionals to deliver audiological services to clinics in and around their area,  ensuring that as many patients are seen as possible This is essential during times like these, as patients on this drug may increase drastically. 
  2. All KUDUwaves have Extended high-frequency capability (>8kHz)  – This is the key to early detection and helping  to avoid permanent hearing loss. The KUDUwave is capable of testing up to 16 kHz, making the portable audiometer ideal for drug-related hearing loss monitoring. The KUDUwave is able to detect ultra-high frequency hearing losses, therefore, detecting hearing loss prior to speech frequencies being affected.

Conclusions

The 1948 WHO definition of health is “A state of complete physical, mental and social well-being and not merely the absence of disease or infirmity”. Let us remind ourselves of this definition of health during our war against this pandemic. Hearing impairment, no matter the cause or the age of onset, has mental, social, psychological and economical implications.

 

Disclaimer: 

There is no intention to deter the population from using medications that could possibly save their lives. If people elect to use the treatment, healthcare professionals need to recognise the symptoms and implement measures to minimize or eliminate the risks associated with ototoxic medication.