Otolaryngologists Have a Major Role to Play in Treating COVID-19 Long-Haulers

One year into the coronavirus pandemic, it’s clear that COVID-19 can cause lingering health problems.

Although the U.S. Centers for Disease Control and Prevention and other health agencies initially cast COVID-19 as an acute illness, we now know that some patients continue to suffer disturbing symptoms months after their initial infection. Persistent loss of taste and smell, continued shortness of breath, cough, fatigue, headaches, chest pain, mental fogginess, joint pain … the list of possible long-haul COVID-19 symptoms is nearly as long and diverse as the official list of acute COVID-19 symptoms.

According to an August 2020 article published in The Journal of Infection, approximately 30% of previously employed patients who were hospitalized in France with COVID-19 weren’t back to work after three months because their continuing symptoms interfered with their ability to function in daily life (J Infect. 2020;81:E4-E6).

Otolaryngologists may play an important role in helping COVID-19 long haulers regain function and quality of life. As medical professionals with extensive experience in managing conditions affecting the nose, mouth, and throat, otolaryngologists are uniquely positioned to help patients heal after COVID-19 infection.

Long-Haul COVID-19 Basics

At present, it seems that people with persistent symptoms post-COVID-19 infection can be roughly classified into two separate groups: those who have readily apparent organ damage and those who do not. Patients who experienced COVID-19-related heart damage, for instance, may develop cardiomyopathy, cardiac sarcoidosis, or heart failure. Exercise intolerance after an acute COVID-19 infection may be due to scarring of the lungs and damage to the alveoli.

Some patients with continuing symptoms don’t show any evidence of organ damage, however. They may feel short of breath, but their lung scans are normal. These patients are often “extremely frustrated” because their medical team can’t find any physical evidence of dysfunction and don’t know how to address or ease the patient’s symptoms, said Jonathan Aviv, MD, clinical director of the Voice and Swallowing Center‚ a division of ENT and Allergy Associates, Tarrytown, N.Y. Many of these patients can’t definitively prove a history of COVID-19 infection, as testing wasn’t widely available at the beginning of the pandemic.

It’s imperative that physicians listen to patients and take their complaints seriously. “We don’t know everything about this disease,” said Andrew Tassler, MD, assistant professor of otolaryngology–head and neck surgery at Weill Cornell Medical College in New York City. “So, if people report symptoms that aren’t known issues with COVID-19, I think you have to respect it and look into it.”

Olfactory Training

Loss of taste and smell are common with COVID-19 infection, and many people are finding that alterations in taste and smell can last well after the resolution of other COVID-19 symptoms. Otolaryngologists are less surprised by this finding than most people, as olfactory dysfunction has long been a known sequela of viral upper respiratory infections. SARS-CoV, the virus that caused the SARS pandemic of 2004-2005, has been linked with prolonged anosmia, so the current wave of patients reporting olfactory alterations after infection with SARS-CoV-2, the virus that causes COVID-19, seems predictable in hindsight (Int Forum Allergy Rhinol. 2020;10:814-820).

But COVID-19-related smell and taste alterations are different from previously known post-viral olfactory issues in a number of significant ways. First, “the incidence of olfactory loss in patients who become infected with COVID-19 is dramatically higher,” said Abtin Tabaee, MD, associate professor in the department of otolaryngology at Weill Cornell Medical College. “The percentage of patients diagnosed with COVID-19 who develop self-reported symptoms of olfactory dysfunction has been reported between 60% to 80% in multiple studies. That’s significantly higher than prior viral upper respiratory infections.”

The key question to ask patients is, ‘Does your shortness of breath or cough wake you up at night?’ If the answer is no, it’s almost always vagal. —Jonathan Aviv, MD

Secondly, “patients with olfactory dysfunction in the setting of COVID-19 typically do not present with other viral upper respiratory infection symptoms, even if other COVID-19 symptoms are present,” Dr. Tabaee said. “In fact, olfactory dysfunction may represent an isolated symptom without any other COVID-19 manifestations.”

Parosmia and phantosmia also seem to appear more commonly in patients affected by COVID-19 than other viral upper respiratory illnesses, said Zara Patel, MD, director of endoscopic skull base surgery and an associate professor of otolaryngology–head and neck surgery at Stanford University Medical Center in Stanford, Calif. Rather than perceiving the smell of coffee when sniffing a morning cup of joe, patients might smell paint thinner or the scent of burning chemicals. Some patients report smelling offensive scents, such as sulfur, although they aren’t near anything that emits that particular scent.

Physicians and researchers are still working to understand the pathophysiology underlying COVID-19-associated smell and taste alterations. Previous human and animal studies have revealed that there are multiple virus-specific potential sites of injury along the olfactory tract, and the site of injury may vary from virus to virus, Dr. Tabaee said. “In the case of COVID-19, we know that the SARS-CoV-2 virus attaches to the ACE-2 receptor and that these receptors are found primarily on the sustentacular cells of the olfactory epithelium, not on the olfactory nerve bodies,” Dr. Patel said. The fact that the virus affects the supporting cells rather than the body of the olfactory nerve likely explains why most people who experience COVID-19-related loss of smell eventually regain olfactory function.

A recently published meta-analysis of 27 studies found that estimated global pooled prevalence of loss of smell among COVID-19 patients was 48.47%; the estimated pooled prevalence for loss of taste was 41.47%. Approximately 35% of patients experienced combined loss of smell and taste (OTO Open. 2020;4(3)1-13). A Korean study of more than 3,000 people reported that most patients with COVID-19-related anosmia or ageusia fully recovered their senses within three weeks; interestingly, patients aged 20-39 were more likely to experience prolonged anosmia than older patients (J Korean Med Sci. 2020;35:e174). Dr. Patel estimates that “about 70 to 75 percent of patients regain their usual olfactory function.”

Although most patients will recover their sense of smell and taste without intervention, a significant number won’t, and persistent sensory alternations negatively impact quality of life and safety. Otolaryngologists can improve patients’ lives by educating their communities about evidence-based treatment options for olfactory dysfunction, including olfactory training.

Essentially, olfactory training is the process of recreating appropriate neural pathways (Int Forum Allergy Rhinol. 2020;10:814-820). Patients are instructed to sniff four different scents—rose, eucalyptus, lemon, and clove—twice a day, while focusing their thoughts on memories of those scents. Olfactory training should continue for at least six months.

“What we’re trying to do is spark nerve regeneration and recreate the correct synaptic pathway back to the olfactory cortex so aberrant pathways don’t form,” said Dr. Patel, noting that abnormal nerve signals can cause parosmia and phantosmia. Randomized controlled trials have found that olfactory training is effective in treating viral-associated olfactory loss, and that over-the-counter essential odors can be used in lieu of controlled concentrations of odorants (Int Forum Allergy Rhinol. 2020;10:814-820; Laryngoscope Investig Otolaryngol. 2017;2:53-56).

Although olfactory training can be initiated at any time—including years after loss of smell—earlier intervention typically leads to better outcomes. “I’d love it if I could see everyone a week after they got COVID-19,” Dr. Patel said. “The sooner we intervene, the larger the percentage of patients who’ll do well.” However, additional research is needed to demonstrate the effectiveness of early intervention in COVID-19 patients, Dr. Tabaee said.

Dr. Patel complements olfactory training with budesonide nasal irrigation, as a randomized controlled trial of 133 patients found that budesonide plus olfactory training may improve outcomes (Int Forum Allergy Rhinol. 2018;8:977-981). (Nearly 44% of patients who received combination treatment noted improvement, compared to 27% of the control group, who underwent olfactory training and saline irrigations). Another randomized controlled trial showed that omega-3 supplementation may improve olfactory function in patients suffering from smell dysfunction after endoscopic skull base surgery, so Dr. Patel tells her COVID-19 patients that they may want to consider omega-3 as well.

“It’s a complete extrapolation to use it to treat post-viral olfactory loss, but because the underlying basic science is sound, I do tell my patients about it, with the caveat that the evidence supporting its use is in a different patient group,” Dr. Patel said.

Persistent Shortness of Breath

Although it seems reasonable to assume that post-COVID shortness of breath and cough are likely due to pulmonary injury, recent research and experience suggest that isn’t always the case. Beginning in July 2020, Dr. Aviv and his colleagues noticed that they were seeing patients who had likely had COVID-19 in the spring and were still experiencing disruptive shortness of breath during conversations, despite normal chest X-rays and lung CTs. The only apparent abnormality, from a pulmonary perspective, was a flattened inspiratory flow loop on spirometry. Otolaryngologist examination of the larynx revealed paradoxical vocal fold movement disorder, a treatable condition that can be caused by inflammation of the vagus nerve and has been previously noted after upper respiratory infection (Int J Respir Pulm Med. 2020;4:0073-0074; Ann Otol Rhinol Laryngol. 2009;118:247-252).

Patients who experience persistent shortness of breath after COVID-19 should be referred to an otolaryngologist if no pulmonary abnormalities are noted. “The key question to ask patients is, ‘Does your shortness of breath or cough wake you up at night?’” Dr. Aviv said. “If the answer is no, it’s almost always vagal.” If a laryngoscopy reveals paradoxical motion of the vocal cords during breathing, initiating respiratory retraining and a low-acid diet may ease patient symptoms. All 18 patients of the initial cohort treated by Dr. Aviv and his colleagues experienced resolution of shortness of breath with treatment (Int J Pulm & Res Sci. 2020;4:0073-0074).

The percentage of patients diagnosed with COVID-19 who develop self-reported symptoms of olfactory dysfunction has been reported between 60% to 80% in multiple studies. That’s significantly higher than prior viral upper respiratory infections. —Abtin Tabaee, MD

Respiratory retraining involves increased resistance breathing exercises and is usually administered by a speech-language pathologist (SLP). However, not all SLPs are familiar with or trained to conduct respiratory retraining. Your nearest academic medical center may be able to point you toward SLPs who offer respiratory retraining, which can be delivered virtually.

A low-acid diet, or one that avoids foods with a pH less than 4, does not aggravate the vagus nerve, Dr. Aviv said, and may allow it to heal. Foods to avoid include flavored sodas, bottled iced teas, citrus fruits, tomato sauce, vinegar, and wine.

Otolaryngologists should inform their pulmonary colleagues that shortness of breath and cough after likely COVID-19 infection may be caused by vagal neuropathy. A collaborative approach is necessary to ensure that patients access effective treatment.

Laryngotracheal Stenosis

Some severely ill COVID-19 patients require prolonged mechanical ventilation. If mechanical support is needed beyond a week or so, a tracheotomy may be performed to facilitate ventilation. Long-term endotracheal intubation and tracheostomy are known to increase the risk of laryngotracheal stenosis (LTS), granulomas, and tracheo-esophageal fistulae. In the summer of 2020, European otolaryngologists warned that “it is highly probable that in the future months and years, otolaryngologists will be called to manage an increasing number of LTS due to the worldwide emerging issues related to the COVID-19 pandemic” (Eur Arch Otorhinolaryngol [published online ahead of print June 6, 2020] doi: 10.1007/s00405-020-06112-6).

To date, U.S. physicians have yet to notice a surge of patients with LTS. “We’re not yet seeing a lot of stenoses at the site of the trach or as a result of intubation,” said Dr. Tassler. “That doesn’t mean it won’t come.”

The European Laryngological Society recommended in July that “every patient with a history of a COVID-19-related ICU stay should be followed after discharge by an otolaryngologist or other airway specialist to proactively diagnose early complications at the level of the larynx and trachea” (ibid). Given what otolaryngologists have since learned about smell and taste alterations and persistent shortness of breath and cough after COVID-19 infection, it seems prudent that all patients experiencing continued symptoms consult an otolaryngologist.

Otolaryngologists will have to educate the public (as well as their colleagues in other disciplines) about the essential role they can play in the diagnosis and management of post-COVID-19 complications.

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Jennifer Fink is a freelance medical writer based in Wisconsin.