COVID-19 Anosmia Study

Phase 2

Completed

Conditions: Anosmia
Covid19

Interventions: Drug: Omega-3 Fatty Acid Supplement
Drug: Placebo/Control

Registration Number: NCT04495816

Lead Sponsor: Icahn School of Medicine at Mount Sinai

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 139

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Omega-3	Omega-3 Fatty Acid Supplement	1,000 mg of omega-3 fatty acid (2 softgels per day for 6 weeks)
Placebo/Control	Placebo/Control	2 softgels per day for 6 weeks

Primary Outcome Measures

Name	Time	Method
Change in Brief Smell Identification Test (BSIT) in Participants With Laboratory-Confirmed COVID-19	Week 0 and Week 6	Mean change in BSIT in participants with severe olfactory dysfunction defined as BSIT ≤ 6. Brief Smell Identification Test (BSIT) is a 12-item instrument, full range score from 0 to 12, higher score indicates better olfactory performances.
Change in Brief Smell Identification Test (BSIT)	Week 0 and Week 6	Change in BSIT. Brief Smell Identification Test (BSIT) is a 12-item instrument, full range score from 0 to 12, higher score indicates better olfactory performances.
Change in Brief Smell Identification Test (BSIT) in Participants With Severe Olfactory Dysfunction	Week 0 and Week 6	Mean change in BSIT in participants with severe olfactory dysfunction defined as BSIT ≤ 7. Brief Smell Identification Test (BSIT) is a 12-item instrument, full range score from 0 to 12, higher score indicates better olfactory performances.
Change in Brief Smell Identification Test (BSIT) in Participants With Laboratory-Confirmed COVID-19 and Severe Olfactory Dysfunction	Week 0 and Week 6	Mean change in BSIT in participants with laboratory-confirmed COVID-19. Brief Smell Identification Test (BSIT) is a 12-item instrument, full range score from 0 to 12, higher score indicates better olfactory performances.

Secondary Outcome Measures

Name	Time	Method
Sinonasal Outcomes Test (SNOT-22)	baseline, weeks 1, 2, 4 and 6 after softgel initiation	Sino-Nasal Outcome Test (SNOT-22) is a 22-item instrument, total scale range from 0 to 110, higher score indicates more severe QOL impact.
Modified Brief Questionnaire of Olfactory Dysfunction (mQOD-NS)	baseline, weeks 1, 2, 4 and 6 after softgel initiation	The modified Brief Questionnaire of Olfactory Dysfunction - Negative Statements (QOD-NS) survey is a 17-item instrument, each item graded on a scale from 0 to 3, with total scale range from 0 to 51. Higher score indicates better olfactory-specific quality of life (QOL).