SARS-CoV-2 Lurking in the Middle Ear

From the common rhinovirus to infamous coronavirus, respiratory viruses can trigger a cascade of ear complications, including acute otitis media (AOM). This roster includes syncytial virus, rhinovirus, adenovirus, coronavirus, bocavirus, influenza virus, parainfluenza virus, enterovirus, human metapneumovirus and SARS-Cov2. Moreover, Otitis media can often manifest as the initial sign of COVID-19 and be associated with hearing loss. Otitis media secretory is one of the most common ear complications after infection with the Omicron strain of SARS-CoV-2 virus, and the significantly higher incidence is associated with middle ear viral infection. Middle ear effusion SARS-CoV-2 virus antigen test detected the virus, which survived longer in the middle ear effusion than in the nasal cavity. The middle ear effusion test can detect SARS-CoV-2 virus antigen and determine whether the organism contains virus residue. 

Recent findings have unveiled a potentially alarming revelation - individuals diagnosed with otitis media with effusion (OME) post-COVID-19 may harbor traces of the virus within their middle ear. In this study, a striking 12.0% of middle ear effusion samples tested positive for SARS-CoV-2, hinting at the possibility of viral persistence and recurrence.

The study examined 23 patients, ranging from 32 to 84 years of age, who presented with OME following Omicron infection. 91.3% of these patients showcased unilateral symptoms, with fluid accumulation observed in 88.0% of ears. The median duration from infection to middle ear effusion sampling was 21 days, showcasing the potential for prolonged viral presence in this concealed reservoir.

Adding to the intrigue is the elusive nature of OME itself. Characterized by fluid accumulation in the middle ear sans acute infection, OME has long puzzled experts in otolaryngology and audiology. While bacterial infections and immunological responses have been implicated, the precise mechanisms remain veiled in mystery.

REFERENCES

Chengzhou Han, Huifang Wang, Ying Wang, Chao Hang, Yangyang Wang, Xiangming Meng, The silent reservoir? SARS-CoV-2 detection in the middle ear effusion of patients with Otitis media with effusion after omicron infection, American Journal of Otolaryngology, 2024, 104229, ISSN 0196-0709, https://doi.org/10.1016/j.amjoto.2024.104229. 

Zhang Y, Liu J, Yang F, He Y, Yan S, Bai Y, Zhang Z, Luan F. COVID-19-related secretory otitis media in the omicron era: a case series. Eur Arch Otorhinolaryngol. 2023 Oct;280(10):4697-4700. doi: 10.1007/s00405-023-08075-w. Epub 2023 Jun 21. PMID: 37341758.

Fan Y, Gao R, Shang Y, Tian X, Zhao Y, Chen X. Presence of SARS-CoV-2 in middle ear fluid and characterization of otitis media with effusion in patients with COVID-19. International Journal of Infectious Diseases. 2023 Nov 1;136:44-8.

Karimi-Galougahi M, Raad N, Ghorbani J, Mikaniki N, Haseli S. Otitis Media in COVID-19: A Case Series. Authorea Preprints. 2020 Jul 7.

Gene Therapy Rescues Childhood Deafness

Gene therapy, a revolutionary medical technique first conceptualized in the 1980s, has steadily advanced, offering new hope in treating various genetic disorders. This approach involves altering a person’s genetic makeup to combat diseases, representing a significant shift from traditional methods like drugs or surgery. 

Gene therapy faces challenges, including immune reactions, targeting errors, and the risk of new mutations. But in many cases benefits outweigh the risks.

A recent milestone in gene therapy has been its application in treating inherited hearing loss. The focus is on DFNB9, a form of deafness caused by mutations in the OTOF gene, responsible for producing otoferlin, a crucial protein in sound signal transmission. This leads to nonsyndromic Hearing Loss - a hearing loss that occurs with no other symptoms. A collaborative clinical trial between Chinese researchers and Mass Eye and Ear investigators has yielded remarkable results.

The trial involved six children with autosomal recessive deafness (DFNB9), all between one and seven years old. The gene therapy entailed injecting a functional OTOF gene using viral carriers into the inner ear. This process enabled the cells to produce otoferlin, thereby restoring hearing capabilities.

Over 26 weeks, five of the six children showed significant hearing improvements, with abilities ranging from understanding speech to verbalizing words, even holding phone conversations. 

This success paves the way for addressing other genetic forms of deafness involving genes like GJB2, MYO15A, TMC1, or SLC26A4. These genes play various roles in the inner ear's development and function, and researchers are diligently working to develop targeted gene therapies for these conditions.

Gene therapy, once a concept, is now transforming lives. As research continues, it holds the promise of curing not just deafness but a spectrum of genetic disorders, marking a new era in medical science.

REFERENCE

Qi J, Tan F, Zhang L, Lu L, Zhang S, Zhai Y, Lu Y, Qian X, Dong W, Zhou Y, Zhang Z, Yang X, Jiang L, Yu C, Liu J, Chen T, Wu L, Tan C, Sun S, Song H, Shu Y, Xu L, Gao X, Li H, Chai R. AAV‐Mediated Gene Therapy Restores Hearing in Patients with DFNB9 Deafness. Adv Sci (Weinh). 2024 Jan 8:e2306788. doi: 10.1002/advs.202306788. Epub ahead of print. PMID: 38189623.

Music in the Streaming Age

In the grand tapestry of human evolution, our sense of hearing has played a pivotal role in our survival and cultural development. Over time, our hearing has evolved in response to environmental cues and the intricate dance of language and communication. This journey has left its imprint on the very structure of our inner ears and the regions of our brains responsible for language processing. 

As our societies grew in complexity, so did our music. It was evolving from simple and rhythmic, to intricate compositions of classical music and avant-garde, experimental, serialist, highly spatialized music. It was changing from danceable to complex and dissonant rhythms. Some complex music was very popular - such as psychedelic rock band Pink Floyd; other not so much - such as Karlheinz Stockhausen's compositions. Modern music was incorporating elements of many other genres - eg alternative rock: punk rock, heavy metal, and experimental music and even simpler Hip Hop: jazz, funk, and soul. The most popular music was not always simplest but was more accessible.

In the 2020s, the world of music experienced a seismic shift with the rise of streaming platforms like Spotify, Tencent, and Apple Music. The impact was profound, not only revitalizing the music industry's revenue but also redefining the very essence of music itself.

Traditionally, music was a patient storyteller, often taking its time to build up to a climactic chorus or hook. Yet, the economics of streaming introduced a new imperative – capturing the listener's attention within the first 30 seconds. Enter the "Pop Overture," a clever technique where a song hints at its chorus within the initial moments, engaging the listener and encouraging them to stay for the full musical journey. 

To keep the dreaded "skip rate" at bay, artists began to craft shorter songs. Lengthy instrumental intros were swapped for immediate engagement, resulting in a significant reduction in the average duration of hit songs. In 2021, nearly two-thirds of chart-toppers clocked in at under three minutes, a departure from the days when a four-minute+ song was the norm.

As individual songs shrank, albums expanded. Streaming listeners, keen to maximize their musical experience, embraced longer albums. More songs equaled more income, with Taylor Swift's "Midnights" dominating the Hot 100 chart by offering an extensive musical journey.

Streaming opened doors for genres that once struggled for visibility. Latin and K-Pop artists rose to prominence on Spotify's Global Top 100, fostering a rich tapestry of cross-genre collaborations. Remixes featuring artists from different backgrounds expanded a song's appeal and audience, exemplified by Justin Bieber's "Sorry (Latino Remix)" with J. Balvin.

While artistic creativity remains paramount, commercial considerations loom large. The streaming economy's dynamics, with its emphasis on plays, playlists, and recommendations, have compelled artists and labels to explore innovative strategies to maximize reach and revenue.

In this ever-evolving landscape of sound, music's essence has been reshaped by the streaming revolution. The emphasis on retaining listeners and optimizing plays has redefined how songs are crafted and albums are composed. With an emphasis on retaining listener engagement and maximizing plays, the industry has adapted to the evolving preferences and economics of the streaming era.

REFERENCES

Streaming is changing the sound of music(https://www.wsj.com/arts-culture/music/streaming-is-changing-the-sound-of-music-182dc907)

https://news.ycombinator.com/item?id=37531602

https://www.reddit.com/r/dataisbeautiful/comments/e5htxy/are_songs_getting_shorter_or_just_our_attention/

Acknowledgements: ChatGPT, Bard and Bing image creator

A Leap Towards Curing Genetic Deafness

In recent years, gene therapy has surfaced as a beacon of hope for those grappling with genetic hearing loss, showcasing promising results in neonatal mice. However, when it comes to adults, the complex structure of the cochlea, nestled within the temporal bone, has made treatment significantly more challenging. A recent study reported results that could change this narrative, opening new avenues in auditory research with the potential to revolutionize treatment for progressive genetic-mediated hearing loss in adults.

The crux of this breakthrough lies in the innovative method of gene delivery through the cerebrospinal fluid (CSF), a channel that has not been explored extensively in previous research. This study illuminates the lymphatic-like characteristics exhibited by the cochlear aqueduct in mice, indicating a pathway for the diffusion of gene therapy to the inner ear. Leveraging in vivo time-lapse magnetic resonance imaging, computed tomography, and optical fluorescence microscopy, the research team traced the journey of large-particle tracers from the CSF to the inner ear, demonstrating a viable route for targeted gene delivery.

By utilizing a single intracisternal injection of an adeno-associated virus carrying the Slc17A8 gene, known for encoding the vesicular glutamate transporter-3 (VGLUT3), the researchers successfully restored hearing in adult deaf mice. This restoration was achieved without any discernible ectopic expression in the brain or the liver, emphasizing the precision of this approach.

This pivotal study marks a significant stride in auditory research, presenting a feasible and innovative method to treat genetic deafness in adults, a segment that was previously considered hard to reach due to the risks associated with potential damage to inner ear structures. The CSF administration through the cochlear aqueducts emerges as a promising route, promising not just advancements in rodent studies but potentially paving the way for human applications.

In essence, this research might herald a new era where genetic deafness in adults could be treated more effectively and safely. As the world of medical science stands on the brink of this significant advancement, it brings renewed hope and anticipation for individuals affected by progressive genetic-mediated hearing loss, inching us closer to a future where hearing restoration is within reach for all.

REFERENCE

Mathiesen BK, Miyakoshi LM, Cederroth CR, Tserga E, Versteegh C, Bork PA, Hauglund NL, Gomolka RS, Mori Y, Edvall NK, Rouse S. Delivery of gene therapy through a cerebrospinal fluid conduit to rescue hearing in adult mice. Science Translational Medicine. 2023 Jun 28;15(702):eabq3916.

The Promise of Bimodal Neuromodulation

Tinnitus, often described as a persistent ringing or buzzing in the ears leading to distress and discomfort, affects more than 10% of the population worldwide. For years, finding an effective treatment for this phantom auditory condition has been a challenge. One promising approach is bimodal neuromodulation. 

Extensive animal studies demonstrated the ability of bimodal neuromodulation to induce neural plasticity in the auditory brain. 

The TENT-A1 clinical trial (clinicaltrials.gov: NCT02669069) conducted in 2020 involved 326 participants and demonstrated the safety and effectiveness of bimodal neuromodulation using the Lenire device. This therapy combined sound and tongue stimulation and significantly reduced tinnitus symptom severity scores in over 80% of participants during the 12-week treatment period, with effects lasting up to 12 months after treatment. The trial used three different parameter settings (PS1, PS2, and PS3) involving synchronized sound and tongue stimulation, short interstimulus delays, and lower-frequency tones, respectively, along with background wideband noise. TENT-A2, which was statistically powered to evaluate the necessity of wideband noise, found that it was not required for therapeutic benefit in arm 2 (absent in parameter settings). Furthermore, TENT-A2 completed in 2022 (clinicaltrials.gov: NCT03530306) explored the impact of adjusting sound and tongue stimulus parameters, demonstrating significant findings in both arms (PS1-PS4 and PS6-PS10). These results represent significant progress in tinnitus treatment.

The study found that these therapeutic effects were sustained up to 12 months after the treatment ended. This long-term relief is a promising development for tinnitus sufferers.

Tinnitus treatments can be categorized into three main groups based on a recent scoping review:

Medical Technology Therapies: This category includes therapies that involve the use of medical devices or technology to manage tinnitus. Notably, the study highlighted the effectiveness of stimulation therapies, although evidence-based guidelines did not strongly recommend them. Stimulation therapies encompass approaches such as tinnitus masking, which uses external sounds to reduce the perception of tinnitus, and acoustic therapies.

Behavioral/Habituation Therapies: These therapies focus on behavioral interventions to help individuals habituate to the perception of tinnitus. Common approaches mentioned in the review include counseling, tinnitus retraining therapy (TRT), cognitive-behavioral therapy (CBT), relaxation techniques, and attention diversion strategies.

Pharmacological, Herbal, Complementary, and Alternative Medicine Therapies: This category encompasses treatments involving medications, herbal remedies, complementary therapies, and alternative medicine. However, the review noted a lack of significant findings and strong recommendations for these interventions, indicating the need for further research in this area.

Tinnitus research has predominantly focused on stimulation therapies and acoustic therapies. However. digital therapies, including internet-based interventions, are more cost-effective and are gaining traction in the treatment and management of tinnitus. They are showing promise in improving the effectiveness of interventions, particularly cognitive-behavioral therapy (CBT). They have the potential to improve patient outcomes and provide accessible options for individuals with tinnitus. However, their integration into healthcare systems requires careful consideration and the accumulation of strong evidence to support their effectiveness and long-term benefits.

REFERENCES

Conlon B, Hamilton C, Meade E, Leong SL, O Connor C, Langguth B, Vanneste S, Hall DA, Hughes S, Lim HH. Different bimodal neuromodulation settings reduce tinnitus symptoms in a large randomized trial. Sci Rep. 2022 Jun 30;12(1):10845. doi: 10.1038/s41598-022-13875-x. Erratum in: Sci Rep. 2023 Jul 10;13(1):11152. PMID: 35773272; PMCID: PMC9246951.

Chhaya, V., Patel, D., Shethia, F. et al. Current Therapeutic Trends for Tinnitus Cure and Control: A Scoping Review. Indian J Otolaryngol Head Neck Surg (2023). https://doi.org/10.1007/s12070-023-03910-2

Improving Accessibility and Affordability for Age-Related Hearing Loss

While hearing aids are the most common treatment for age-related hearing loss, low uptake of hearing aids is due to high cost, stigma, and a lack of perceived need. To increase accessibility and affordability, the U.S. Food and Drug Administration created a new OTC hearing aid category. Currently, there are various hearing devices available for individuals with and without hearing loss, including medical devices (prescription hearing aids, self-fitting OTC hearing aids, and pre-set OTC hearing aids) and non-medical devices (PSAPs, hearables, and consumer audio devices such as Apple's AirPods Pro and Live Listen feature, Samsung's Galaxy Buds and Hearing Aid feature, and Bose Hearphones). 

Regulated by the FDA, hearing aids have evolved rapidly in the last decade, with features, functionalities, and designs improving significantly. However, there is a lack of research on all aspects of OTC hearing aids currently on the market. High-quality independent research is necessary to supplement evidence provided by OTC hearing aid manufacturers for regulatory approval purposes. Recently published article has reviewed existing research on direct-to-consumer (DTC) hearing devices such as PSAPs and highlighted the need for immediate research on OTC hearing aids and service delivery models to inform policy and clinical care.

REFERENCE

Manchaiah V, Swanepoel W, Sharma A. Prioritizing research on over-the-counter (OTC) hearing aids for age-related hearing loss. Front Aging. 2023 Mar 23;4:1105879. doi: 10.3389/fragi.2023.1105879. PMID: 37033402; PMCID: PMC10078955.

The audio CAPTCHA

Audio CAPTCHAs are a type of CAPTCHA (Completely Automated Public Turing test to tell Computers and Humans Apart) used to determine if a user is a human or a bot. Audio CAPTCHAs are designed to be accessible to users with visual impairments, who may have difficulty reading visual CAPTCHAs. Hearing-based "I'm not a robot" quizzes play audio clips that read out the text or letters presented in the CAPTCHA. These recordings usually feature some form of background noise, which is intended to fool bots that try to interpret the audio. They used to be fairly effective since first generation bots struggled to properly interpret audio.  They even were used for shadow crowdsourcing, making people work for others without realizing it - eg, translate old newspapers and characters from street images for Google Maps. 

However, the effectiveness of audio CAPTCHAs has been challenged by the improving accuracy of automated speech recognition (ASR) systems, which are able to solve audio CAPTCHAs even in the presence of background noise. As a result, researchers have focused on developing new audio CAPTCHA designs that are more resistant to ASR attacks, as well as evaluating the performance of different audio CAPTCHA designs under various conditions.

Some of the audio CAPTCHA papers have explored the use of different types of audio signals, such as noise and music, to create audio CAPTCHAs that are more difficult for ASR systems to solve. Other papers have examined the use of multiple audio CAPTCHAs in sequence, or the use of visual and audio CAPTCHAs in combination, in an effort to increase the overall security of the CAPTCHA system.

Both text and image-based CAPTCHAs are becoming difficult for humans to resolve. Bruce Schneier, an internationally renowned security technologist, offered this humorous example on his blog: "select all images where if you were to add a decrescendo it would add to the musicality of the piece without being interpreted as an overly heavy-handed metaphor within the context of the thematic material "

ChatGPT answered to this challenge by writing lyrics to short musical pieces incorporating a decrescendo: 

 Verse 1: (Moderately fast tempo, 8th note = 120 bpm) 

The sun is shining bright, 

The birds are singing sweet, 

My heart is filled with joy, 

As I dance down the street. 

Chorus: (8th note = 120 bpm) 

Life is good, life is grand, 

I am free to roam this land. 

Verse 2: (Moderately fast tempo, 8th note = 120 bpm) 

But as the day wears on, The clouds start to roll in. My steps slow down, As the rain begins. 

Chorus: (8th note = 120 bpm) Life is good, life is grand, But sometimes it's hard to understand. 

Bridge:(Moderately slow tempo, 8th note = 60 bpm) The rain falls heavy now, My mood starts to change. I feel a sense of sadness, As I contemplate the pain. 

Outro: (Moderately slow tempo, 8th note = 60 bpm) But even in the darkest times, There is always a way. The rain will eventually stop, And a brighter day will come my way. (Decrescendo from 8th note = 60 bpm to pianissimo) 

In this musical piece, the decrescendo at the end helps to convey a sense of resolution and hopefulness, as the music gradually fades out to a pianissimo dynamic. The use of a decrescendo in this context adds to the musicality of the piece without being overly heavy-handed or interpreting the thematic material in a specific way.

It's a challenge to develop effective CAPTCHAs that are able to differentiate between humans and bots, while also being accessible to all users.

REFERENCES

Alqarni M, Yu F, Raavi R, Sukhai M. An Accessible Web CAPTCHA Design for Visually Impaired Users.

Solanki S, Krishnan G, Sampath V, Polakis J. In (cyber) space bots can hear you speak: Breaking audio captchas using bots speech recognition. InProceedings of the 10th ACM Workshop on Artificial Intelligence and Security 2017 Nov 3 (pp. 69-80).

Reinheimer BM, Islam F, Shumailov I. Audio CAPTCHA with a Few Cocktails: It’s so Noisy I Can’t Hear You. InCambridge International Workshop on Security Protocols 2019 Apr 10 (pp. 20-40). Springer, Cham.

Shirali-Shahreza S, Penn G, Balakrishnan R, Ganjali Y. Seesay and hearsay captcha for mobile interaction. InProceedings of the SIGCHI Conference on Human Factors in Computing Systems 2013 Apr 27 (pp. 2147-2156).

Huang CH, Wu PH, Liu YW, Wu SH. Attacking and Defending Behind A Psychoacoustics-Based Captcha. InICASSP 2021-2021 IEEE International Conference on Acoustics, Speech and Signal Processing (ICASSP) 2021 Jun 6 (pp. 895-899). IEEE.

IG: Special thanks to OpenAI's Assistant for their help with writing this article.