To capture the natural history of COVID-19 associated olfactory dysfunction as measured by two patient reported outcome measures (SNOT-22, QOD-NS) and a 6-week BSIT with a comparison to an intervention arm receiving daily omega-3 supplements.
Infection with the novel coronavirus (COVID-19) has been linked to new-onset olfactory
dysfunction, often as the only presenting symptom. In one multicenter European study, 85.6%
of patients with mild to moderate symptoms reported hyposmia or anosmia with early recovery
of olfactory function in just under half of patients. However, the pathogenesis and natural
history of COVID-19 related olfactory dysfunction is poorly understood.
Anosmia most commonly arises in association with sinonasal disease or post-infectious or
post-traumatic disorders. Notably, olfactory loss has been associated with impaired quality
of life, higher rates of depression, and even increased mortality risk. Spontaneous recovery
has been observed in patients with post- infectious olfactory dysfunction, typically over a
period of months to years, with an estimated one-third of patients demonstrating meaningful
improvement after one year.
Smell retraining therapy appears to be an effective therapeutic option for patients with
post-infectious olfactory dysfunction, particularly for patients who initiate treatment
within one year from onset of symptoms, but requires an intervention period of at least three
to four months. Various pharmacotherapies have been investigated in the treatment of
post-infectious anosmia but none have clearly demonstrated utility with the exception of a
possible benefit for nasal steroid irrigations in combination with smell retraining therapy.
More recently, omega-3 polyunsaturated fat supplementation has emerged as a promising
pharmacotherapy for olfactory dysfunction in patients without sinonasal disease. Omega-3
fatty acid deficient mice demonstrate evidence of olfactory dysfunction and mice receiving
omega-3 fatty acids have improved recovery after peripheral nerve injury, which has been
linked to neuroprotective effects mediated through anti-oxidant and anti-inflammatory
pathways. In humans, a large cross-sectional study found that older adults with higher
dietary fat intake had lower incidence of olfactory impairment. From a clinical perspective,
patients without sinonasal disease receiving postoperative omega-3 fatty acid supplementation
after endoscopic endonasal skull base surgery in a randomized control trial demonstrated a
significantly greater rate of return of normal olfactory dysfunction.
Little is known about either the natural history of olfactory dysfunction associated with
COVID-19 infection or about the therapeutic efficacy of omega-3 fatty acid supplementation in
patients with post-viral anosmia. The study team hopes to gain a better understanding of each
through a randomized double-blind placebo control study that assesses both objective and
subjective perception of olfactory dysfunction over a period of 6 weeks after infection.
Drug: Omega-3 Fatty Acid Supplement
Participants randomized to this arm will be instructed to take two of the softgels they received per day for 6 weeks. They will receive softgels containing 1,000 mg of omega-3 fatty acid. 1000 mg of omega-3 fatty acid blend including 683 mg Eicosapentaenoic Acid and 252 mg Docosahexaenoic Acid
Drug: Placebo/Control
Patients randomized to this arm will also be instructed to take two of the softgels they received per day for 6 weeks. They will receive placebo softgels that are indistinguishable from those containing fish oil.
Inclusion Criteria:
- Adults (18 years of age or older) with self-reported new-onset olfactory dysfunction
- Positive COVID-19 diagnosis will be deemed eligible for inclusion.
Exclusion Criteria:
- Patients <18 years of age
- Patients who are unable to provide informed consent
- Patients without a positive COVID-19 PCR result obtained through nasopharyngeal swab -
Patients with a COVID-19 diagnosis but without self-reported anosmia
- Patients with severe COVID-19 disease as defined by the Mouth Sinai Health System
Treatment Guidelines for SARS-COV-2 (requiring high flow nasal cannula,
non-rebreather, CPAP/BIPAP, or mechanical ventilation OR patients requiring pressor
medication OR patients with evidence of end organ damage)
- Patients with pre-existing self-reported olfactory dysfunction
- Patients with a history of chronic nasal/sinus infections (rhinosinusitis) or history
of endoscopic sinus surgery
- Patients using nasal steroid sprays or irrigations for any reason
- Patients who are prisoners of the state
- Patients who have psychiatric or developmental disorder conditions that may impair
ability to provide informed consent
- Patients will also be excluded if they have an allergy to fish or an omega-3
supplement, or do not eat fish or fish- containing substances for any reason
Mount Sinai Hospital
New York, New York, United States
Alfred-Marc Iloreta, MD, Principal Investigator
Icahn School of Medicine at Mount Sinai