Researchers around the world are actively studying the prevalence, mechanism, duration, and severity of symptoms following acute SARS-CoV-2 infection. According to the CDC, as of mid-January 2022, over 65 million people in the United States had been diagnosed with COVID-19. A recent study reported that, of patients who had had COVID-19, 23% had at least one post-COVID condition (FAIR Health White Paper. Published June 15, 2021. www.bit.ly/3fF0AAF).
But how many of these individuals have COVID-19 manifestations that come under the purview of otolaryngologists? It has been well documented that the SARS-CoV-2 virus directly damages tissues in the upper respiratory system, inner ear, and the vagus nerve, causing loss of taste and smell, tinnitus, and swallowing issues. These symptoms can be acute (lasting up to four weeks), recurrent, and long lasting. Patients with long-lasting post-COVID conditions, also known as long-haul COVID-19, have conditions that last for more than four weeks.
Most of the long-haul COVID-19 patients seen by otolaryngologists in early 2020 were patients who presented with chemosensory loss. In a systematic review, the prevalence of smell loss from pooled COVID-19 studies was approximately 52% (Am J Med Sci. 2021;361:216-225). The rate of smell loss in patients who have COVID-19 after vaccination was about the same (62.3%) (Laryngoscope. 2022;132:419-421).
The prognosis for most of these patients is quite good, said Patricia Loftus, MD, an assistant professor in the rhinology and skull base surgery division in the department of otolaryngology–head and neck surgery at the University of California, San Francisco (UCSF). “The literature has reported that between 70% and 80% of people will regain their sense of smell within approximately three to four weeks after symptom onset, and by six months, 95% of people will have recovered their sense of smell,” she noted (Am J Otolaryngol. 2020;41:6:102639).
However, it should be noted that patients who experienced moderate to severe olfactory dysfunction were more likely to have persistent smell loss at six months when compared to patients with milder dysfunction at onset (Intern Med. 2021;290:451-461).
Because of the increase in awareness about loss of smell as an early harbinger of COVID-19, “we have seen more patients coming in with self-recognized smell loss or complete loss of smell,” said José Gurrola II, MD, an associate professor in the department of otolaryngology–head and neck surgery at UCSF.
“Depending on timing relative to their smell loss, we often discuss starting nasal steroids and olfactory training protocols. The sooner they present after the initial loss, the more optimistic we tend to be. We’re still working out the optimal treatment for those with long-term smell loss.” said Dr. Gurrola.
Because loss of smell is such a common symptom of COVID-19—more common than in other types of viral illnesses—it’s one of the ways Dr. Loftus may be able to differentiate COVID-19 patients from patients with other types of upper respiratory infections. Furthermore, COVID-19 smell loss presents more frequently without associated nasal symptoms such as congestion and rhinorrhea, whereas in other types of viral illnesses it’s usually the congestion that’s causing the associated smell loss. “If someone has loss of smell without associated nasal obstruction or congestion, we tell them to get tested and be evaluated.
We have seen a lot of downstream sequalae of COVID-19, such as voice, airway, and swallowing disorders caused by the Alpha and Delta variants, but I don’t know if we’ll see as many long-haul patients with Omicron—but it’s too early to say. —Diana Kirke, MBBS, MPhil
“We believe that the COVID-19 virus is directly attacking the sustentacular cells [or supporting cells] of the olfactory neurons but not the olfactory neurons themselves, since the sustentacular cells express the angiotensin-converting enzyme 2 [ACE2] receptor for the SARS-CoV-2 virus, but the olfactory neurons do not,” Dr. Loftus said. “Therefore, the neurons are damaged by not receiving the nutrition and structural support that the affected sustentacular cells provide, and in this way smell loss occurs even in the absence of nasal congestion or nasal drainage.”
Although demographic information is still lacking, Dr. Gurrola has anecdotally noticed that, more often than not, most of the patients coming in with loss of taste will also have loss of smell, consistent with the COVID-19-era publications. The vast majority of studies into these COVID-19 comorbidities was published in 2020, prior to the release of the COVID-19 vaccines. “I am not aware if there are data demonstrating the vaccines’ impact on olfaction with the initial virus or the Delta variant, for instance. We’re looking forward to studies establishing whether the vaccines are olfaction protective and whether the newer variants have less of an inherent impact on olfaction.” Dr. Gurrola said.
“We also have data to show that loss of smell is more common in healthier, younger patients with mild COVID-19 infections—but even older patients with underlying conditions are now having milder symptoms when infected with COVID-19 after being vaccinated,” noted Dr. Loftus. “I haven’t seen many patients with reinfections, but it is absolutely possible that they could present with smell loss again.”
Unfortunately, that still leaves approximately 5% of COVID-19 patients who experience long-haul chemosensory symptoms, which is very significant—especially as more people are becoming infected with Delta and Omicron variants, noted Dr. Loftus.
In San Francisco, Dr. Gurrola hasn’t seen the groundswell in patients expected with Omicron, but he acknowledged that it may be too soon to tell. “I think that we have to wait for the data as to whether the vaccines are preventing chemosensory loss or whether the variants themselves are having different effects or sequelae.”
Vestibular Dysfunction, Tinnitus, and Hearing Loss
A meta-analysis of the impact of COVID-19 on tinnitus found that the associated stress and anxiety of the pandemic have contributed to patients developing or experiencing exacerbations of preexisting tinnitus cases. The authors reported that the pooled estimated prevalence of tinnitus post-COVID-19 was 8% (confidence interval [CI]: 5% to 13%) (J Clin Med. 2021;10:2763).
“I’m seeing a fair number of long-haul COVID-19 patients with tinnitus and dizziness, as well as a fair number of post-vaccine-tinnitus,” said Sarah Mowry, MD, a neurotologist and associate professor at Case Western Reserve University School of Medicine in Cleveland. “They are middle-aged and developed COVID-19 early in the pandemic, before vaccines were available. These patients have really bothersome and disabling tinnitus.”
Patients are also coming in with complaints of feeling off balance or a sense of disequilibrium and generalized dizziness, rather than a picture of episodic vertigo, noted Enrique Perez, MD, MBA, director of otology at Mount Sinai and an assistant professor at the New York Eye and Ear Infirmary of Mount Sinai in New York City. “Dizziness is the most challenging of all the inner ear complaints in these patients because it can be a vague symptom and can fall under other disease categories such as autonomic dysfunction. COVID-19-related chronic dizziness in long-haulers doesn’t always fit the picture of an inner ear disorder.”
Nevertheless, the increase in stress and anxiety that has occurred during the more than two-year-long pandemic has likely contributed to an increase in true vertiginous symptoms in Dr. Perez’ Ménière’s disease patients. “Many of my chronic Ménière’s patients have had new exacerbations of their vertigo in the last two years, after doing well prior to the pandemic,” he said. “This may be due to infections from COVID-19 or may be related to other stresses posed by the pandemic.”
When Dr. Perez takes a medical history, he now asks patients about stress and anxiety: Do they grind or clench their teeth? How are they sleeping? Such anecdotal experiences may well have mechanistic underpinnings, according to published research. A recent study by Konstantina Stakovic, MD, PhD, and her colleagues at Stanford University in Stanford, Calif., for example, demonstrated that human inner ear tissue expresses both the ACE2 receptor for SARS-CoV-2 virus as well as the cofactors required for virus entry. Hair cells and Schwann cells in explanted human vestibular tissue were also shown to be infected by SARS-CoV-2, as demonstrated by confocal microscopy (Commun Med. 2021;1:44).
We’re looking forward to studies establishing whether the vaccines are olfaction protective and whether the newer variants have less of an inherent impact on olfaction. —José Gurrola II, MD
“The study demonstrates that the virus doesn’t just cause neuroinflammation but also can directly infect hair cells in the inner ear,” noted Dr. Mowry.
As for Omicron’s impact on patients with tinnitus and vertigo, it may be too early to tell. “I haven’t seen as much of an uptick of [tinnitus or dizziness] complaints as would be expected with such a highly transmissible variant if it led to inner ear dysfunction. I initially suspected we would see a lot more patients showing up,” said Dr. Perez.
Diana Kirke, MBBS, MPhil, is seeing two types of long-haul COVID-19 patients with voice/airway and swallowing symptoms. The first are those with the inflammatory sequalae of intubation: glottic stenosis, posterior stenosis, and postglottic stenosis. “I have never operated on so many airways or performed as many open airway surgeries as I have during the last two years,” said Dr. Kirke, who is an assistant professor in the department of otolaryngology–head and neck surgery at the Icahn School of Medicine at Mount Sinai in New York City.
“We have a paper in process looking at the rise in intubation-related airway issues and examining whether it’s a result of the SARS-CoV-2 virus or from just the sheer number of intubations that occurred during the pandemic,” she said. “My suspicion is that our histopathological study of the tracheas will show a big inflammatory response as a result of the virus itself.”
In terms of the second type of patient with non-intubation complications, “we are seeing mostly voice changes, dysphonia, and changes in swallowing or dysphagia, likely secondary to a motor or sensory vagal neuropathy,” Dr. Kirke said. “This is essentially the voice, airway, and swallowing version of the commonly reported anosmia and parosmia. Our histopathological study will also look at the nerves as well as the degree of inflammation around the nerve,” she said.
Practice protocols have changed dramatically with the arrival of Omicron because of the infectious nature of the new variant. Omicron has an oropharyngeal presentation compared with earlier iterations of the virus.
“Starting in early December, there were a lot of people coming into the office with acute sore throats,” said Dr. Kirke. “We are triaging patients differently now. If they don’t require acute intervention, we now see these presentations via telemedicine, unless of course the patients have a negative COVID-19 test. For any significant office procedure where there is a lot of airway exposure or aerosolization risk, the patient needs to have a negative PCR test. This is something we weren’t doing with previous iterations of the virus.”
Working with Multidisciplinary Groups
Many of the long-term COVID-19 patients have multiple issues. Therefore, getting patients evaluated by the right specialist is very important. Clinics for long-haul COVID-19 conditions are being established at larger medical centers across the United States, bringing together multidisciplinary teams to provide a comprehensive and coordinated treatment approach for COVID-19 patients.
“We’re lucky to have a long-haul institution affiliated with our practice,” Dr. Kirke said. “We have seen a lot of downstream sequalae of COVID-19, such as voice, airway, and swallowing disorders caused by the Alpha and Delta variants, but I don’t know if we’ll see as many long-haul patients with Omicron—but it’s too early to say.”
“I think it’s important for our tinnitus patients to have a multidisciplinary approach to managing these post-COVID-19 symptoms,” Dr. Perez added. “We have a post-COVID-19 clinic that helps to manage some of the rehabilitation issues for patients; the team is organized under physical medicine and rehabilitation, with neurologists and psychologists involved.”
With regard to tinnitus in particular, “these patients can’t sleep, are anxious, and are exhausted,” Dr. Mowry said. Having patients work on good sleep hygiene and stress management, as well as providing cognitive behavior therapy, is the standard treatment for tinnitus, she noted. “Prescribing a sleep aid may also be necessary. There are really no data regarding starting anti-inflammatory therapy for COVID-19-associated tinnitus or balance disorder in patients who present weeks or months after infection.”
“It has been a strange privilege to have experienced this pandemic firsthand as a physician,” Dr. Kirke added. “It has been an honor to look after these long-haul patients and guide them through it—many have felt quite lost or thought they were going crazy.”
Nikki Kean is a freelance medical writer based in New Jersey