Stellate Ganglion Block for COVID-19-Induced Olfactory Dysfunction
Condition: Anosmia; Hyposmia; Parosmia; Olfactory Disorder
MeSH terms: COVID-19; Anosmia; Olfaction Disorders
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Chronic olfactory dysfunction from the COVID-19 pandemic is a growing public health crisis
      with up to 1.2 million people in the Unites States affected. Olfactory dysfunction impacts
      one's quality of life significantly by decreasing the enjoyment of foods, creating
      environmental safety concerns, and affecting one's ability to perform certain jobs. Olfactory
      dysfunction is also an independent predictor of anxiety, depression, and even mortality.
      While the pandemic has increased the interest by the scientific community in combating the
      burgeoning health crisis, few effective treatments currently exist for olfactory dysfunction.
      Furthermore, patients impacted by "long COVID," or chronic symptoms after an acute COVID-19
      infection, experience impairments other than olfactory and gustatory dysfunction, such as
      chronic dyspnea, impaired memory and concentration, and severe fatigue. These symptoms have
      been hypothesized to be a result of sympathetic positive feedback loops and dysautonomia.
      Stellate ganglion blocks have been proposed to treat this hyper-sympathetic activation by
      blocking the sympathetic neuronal firing and resetting the balance of the autonomic nervous
      system. Studies prior to the COVID-19 pandemic have supported a beneficial effect of stellate
      ganglion blocks on olfactory dysfunction, and recent news reports and a published case series
      have described a dramatic benefit in both olfactory function and other long COVID symptoms in
      patients receiving stellate ganglion blocks. Therefore, we propose a single cohort
      prospective study to generate pilot data on the efficacy and safety of sequential stellate
      ganglion blocks for the treatment of COVID-19-induced olfactory dysfunction and other long
      COVID symptoms.
    

Detailed description: 
      One of the hallmark symptoms of infection with SARS-CoV-2 is olfactory dysfunction, and it is
      estimated that up to 1.2 million people in the United States will experience chronic
      olfactory dysfunction from the COVID-19 pandemic. While the majority of patients recover from
      COVID dysosmia, up to 15%-25% have long-term hyposmia. Olfactory impairment can take the form
      of hyposmia (diminished sense of smell), anosmia (absent sense of smell), or parosmia
      (distorted sense of smell). Etiologies of olfactory dysfunction include post-viral,
      traumatic, inflammatory (e.g., chronic rhinosinusitis), neurodegenerative (e.g., Parkinson's
      disease), and congenital, among others. Prior to the pandemic, post-viral anosmia was the
      most common cause of olfactory dysfunction, which has further increased as the dominant
      etiology as a result of COVID-19. The proposed pathophysiologic mechanisms of chronic
      COVID-19-induced olfactory dysfunction include inflammatory cytokine release, damage to the
      supporting environment of the olfactory epithelium, and retrograde propagation to higher
      order neurons. A unique feature of COVID-19-associated olfactory dysfunction is the high rate
      of persistent parosmia. In one study of 222 patients with COVID-19-associated olfactory
      dysfunction, 148 (67%) of these patients experienced parosmia at some point. Of the 148
      patients with parosmia at any point, 84 (57%) had persistent parosmia after a mean of 6.5
      months, distinguishing COVID-19-induced olfactory dysfunction from any other etiologies of
      olfactory dysfunction. Patients with olfactory dysfunction have decreased quality-of-life and
      describe their life as if "living in a box." These patients have concern for environmental
      safety, decreased enjoyment of their food, depression, anxiety, and even higher risk of
      mortality. The COVID-19 pandemic has highlighted the importance of the sense of olfaction,
      however, there is a scarcity of effective treatments for olfactory dysfunction. Furthermore,
      chronic olfactory dysfunction is just one of the constellation of symptoms included in "long
      COVID," or persistent symptoms after recovery from acute illness due to COVID-19. Other
      symptoms of long COVID include fatigue, dyspnea, cough, and impaired memory and
      concentration, among many others.These chronic symptoms are hypothesized to be, at least in
      part, a result of sympathetic hyperactivity resulting in positive feedback loops. Therefore,
      the stellate ganglion block, which inhibits the sympathetic nervous system, is hypothesized
      to reset the balance of the autonomic nervous system and provide relief for long COVID
      symptoms, including olfactory dysfunction.

      Treatment No standard of care treatment for post-viral olfactory dysfunction exists. The most
      commonly used treatment for post-viral olfactory dysfunction is olfactory training; however,
      a large proportion of patients do not receive benefit and continue to have persistent
      symptoms. A multitude of other therapies have been tried with minimal success, including
      theophylline, vitamin A, sodium citrate, and intranasal insulin. As a result, there is a
      critical need for the development of a novel intervention to address the large volume of
      patients with olfactory dysfunction as a result of the COVID-19 pandemic.

      The stellate ganglion block (SGB) involves an ultrasound-guided injection of a local
      anesthetic to inhibit the stellate ganglion. The SGB is proposed to inhibit the sympathetic
      neural connections within the head, neck, and upper extremity, improve regional blood flow,
      reduce adrenal hormone concentration, and even reestablish circadian rhythms through
      modulation of melatonin. The SGB has been used successfully in a multitude of disorders,
      including post-traumatic stress disorder, cluster headache, complex regional pain syndrome,
      and peripheral vascular disease.

      The SGB was first proposed to treat olfactory dysfunction by Lee et al in 2003, where 38
      post-viral olfactory dysfunction participants were treated with SGB and 13 participants
      remained untreated as controls. Subjective olfactory function improved in 27 (71%) of the
      treated participants compared to zero (0%) of the controls. Olfactory perception was improved
      significantly in the SGB group assessed both by the butanol threshold test and odor
      identification test. There were no complications of SGB in the 38 treated participants.
      Another study in 2007 by Moon et al found that in 13 participants with various etiologies of
      olfactory dysfunction, seven (54%) demonstrated improvement with repeated SGBs. The same
      group conducted a study published in 2013 looking at the long-term results of SGB in treating
      olfactory dysfunction from various etiologies. Of 37 participants with olfactory dysfunction
      unresponsive to oral or intranasal steroids who underwent SGB, 15 (41%) were determined to be
      responsive and 22 (59%) unresponsive to the treatment. Importantly, the responsive group had
      a mean duration of olfactory dysfunction of 1.6 years vs. a mean duration of olfactory
      dysfunction of 4 years in the unresponsive group. The study found that in those who respond
      to SGB, the beneficial effects on olfaction last at least 5 years. Of the 37 treated
      participants there was only 1 who experienced a complication, which was a temporary brachial
      plexus block.

      Most recently, anecdotal news reports and a published case series point to a possible
      beneficial effect of SGB on both chronic COVID-19-induced olfactory dysfunction and various
      other long COVID symptoms. A published case series by Liu et al describes two patients who
      underwent SGB for long COVID symptoms, including olfactory dysfunction. SGB was performed on
      the right side then either one or two days later to the left side. Both patients reported
      significant and durable improvement in symptoms, including fatigue, "brain fog," and
      olfactory and gustatory dysfunction that persisted at 60-day follow-up. Nearly all other long
      COVID symptoms, including cough, chest pain, heart palpitations, and orthostatic dizziness,
      also improved at the one week and two-month follow-up time points. The authors concluded that
      although the sample size is limited, SGB may have a significant impact on the dysautonomia
      caused by COVID-19 and improve long COVID symptoms, giving rationale to conduct a larger
      study. Therefore, we propose a single cohort prospective study to generate pilot data on the
      effectiveness and safety of sequential stellate ganglion blocks for the treatment of
      COVID-19-induced olfactory dysfunction and other long COVID symptoms.
    

Intervention name(s): Stellate Ganglion Block
Intervention type(s): Drug
Intervention description(s): The stellate ganglion will be identified using ultrasound guidance, and after a test does of 1% lidocaine, 1% mepivacaine will be injected near the stellate ganglion.
Other intervention name(s): mepivacaine
Intervention MeSH terms: Mepivacaine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: COVID-19