One of the hallmark symptoms of infection with SARS-CoV-2 is olfactory dysfunction (OD).
While the majority of patients recover from COVID dysosmia, up to 15%-25% have long-term
hyposmia and it is estimated that up to 1.2 million people in the United States will
experience chronic OD from the COVID-19 pandemic. A unique feature of COVID-19-associated
OD is the high rate of persistent parosmia. In one study of 222 patients with
COVID-19-associated olfactory dysfunction by Lerner et al, 148 (67%) of these patients
experienced parosmia at some point, and estimates of persistent parosmia 6 months after
COVID-19 infection range from 25% to 57%.Patients with OD have decreased quality-of-life
and have described their lives as if "living in a box." These patients have concerns for
environmental safety, decreased enjoyment of their food, depression, anxiety, and even a
higher risk of mortality. Unpublished work by our group has demonstrated a relationship
between parosmia and increased risk of screening positive for anxiety, depression, and
suicidality.
The COVID-19 pandemic has highlighted the importance of the sense of olfaction, but no
standard of care treatment for post-viral OD exists. The most commonly used treatment for
post-viral OD 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 in randomized clinical trials 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 number of
patients with OD due to the COVID-19 pandemic.
The stellate ganglion block (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, migraine, and complex regional pain syndrome. A
meta-analysis of 12 clinical trials found that SGB was superior to placebo in reducing
pain scores among patients with various sympathetic hyperactivity-associated disorders.
Many "long COVID" symptoms, those that persist after recovery from acute COVID-19
infection, are hypothesized to be, at least in part, a result of sympathetic
hyperactivity resulting in positive feedback loops. Therefore, the stellate ganglion
block (SGB) is hypothesized to reset the balance of the autonomic nervous system and
provide relief for long COVID symptoms, including OD.
The SGB was first proposed to treat OD by Lee et al in 2003, where 38 post-viral OD
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.
Additional studies by Moon et al noted improvement in OD of various etiologies after
repeated SGBs. However, each of these studies were limited by their use of unvalidated
outcome measures in a heterogeneous OD population in the pre-COVID era, limiting their
external validity to the present day.
A multitude of anecdotal news reports and published case series point to a possible
beneficial effect of the SGB on both chronic COVID-19-induced OD and various other long
COVID symptoms. Numerous pain management clinics across the country are offering the SGB
for long COVID with thousands of dollars of out-of-pocket costs to patients without
adequate evidence to justify its use. One case series of 195 parosmic patients noted up
to a 75% response rate after SGB.
Recently, our study team completed a prospective, pilot single-arm trial of 20
participants with persistent COVID-19-associated OD who underwent bilateral stellate
ganglion blocks and were followed for 1 month post-procedure. At 1-month, 10 (50%)
participants experienced at least slight subjective improvement in their OD, 11 (55%)
attained a clinically meaningful improvement in smell identification using the UPSIT, and
7 (35%) achieved a clinically meaningful improvement in olfactory-specific QOL.
Therefore, we propose a double-blinded, placebo-controlled randomized clinical trial
assessing the efficacy of a stellate ganglion block versus saline injection in a total of
140 participants with persistent COVID-19-associated parosmia.