EFFECT OF DAILY WALNUT CONSUMPTION ON MEMORY IN SUBJECTS WITH LONG-COVID: A PILOT STUDY

Our proposed pilot study will include 60 adults (ages 50-80 years) with documented diagnosis of SARS-CoV2 infection presenting with long-COVID symptoms lasting longer than 12 weeks. They will be randomized 1:1 to usual care vs. an intervention group that will include 2 oz (57g) of walnuts daily into their habitual diet for 12 weeks. We will compare the improvement in symptoms of cognitive complains of "brain fog", fatigue and depression of the active intervention group vs. usual care. In this pilot study, we will assess all aspects of cognition, including Episodic Memory, Executive Function, Processing Speed, Working Memory, Attention, and Language, in order to determine the most sensitive outcome measures as well as to estimate the effect sizes for planning a future RO1 efficacy trial. Additionally, we will also test the methodology prior to application for a larger RO1 to assess recruitment feasibility, adherence, safety, and acceptability of the interventions in this population.Aim 1. To determine if daily consumption of walnuts for 12 weeks leads to improved cognition, fatigue and mood symptoms in subjects with long-COVID.Hypothesis 1a. Compared to the usual care group, subjects in the walnut group will show greater improvement in cognition (Memory and Executive Function) from baseline to the end of intervention. We will also explore the improvement in other cognitive domains (Processing Speed, Working Memory, Attention, and Language).Hypothesis 1b. Compared to the usual care group, subjects in the walnut group will show greater improvement in fatigue, and mood symptoms from baseline to the end of intervention.Between-group and within-group effect sizes for all outcome measures will be estimated to allow planning of a future RO1.Aim 2. To determine if daily consumption of walnuts for 12 weeks leads to benefits in clinical parameters, dietary quality and quality of life in subjects with long-COVID.Hypothesis 2a. Subjects in the walnut group will show improved clinical parameters (vital signs, body weight, body compositions) and improved dietary quality than those in the usual care group.Hypothesis 2b. Subjects in the active intervention arm will exhibit higher quality of life at the completion of the study compared to subjects in usual care.Aim 3. To examine feasibility, retention rates and adherence in this randomized trial of daily walnut consumption vs. usual care in subjects with long-COVID.Hypothesis 3. The current trial design will be feasible as assessed by retention rates (subjects complete at least 75% of post-randomization study visits). Compliance, as measured by blood fatty acids, urine ellagic acid and urolithin metabolites will be monitored in all subjectsExploratory Aim 4. To explore the mechanism of how walnut consumption affects brain fog, fatigue and mood symptoms.Hypothesis 4: Subjects in the walnut group will show decreased inflammation and increased beneficial bacterial tryptophan metabolites than those in the usual care group. The outcome of the investigation of the benefit of walnut consumption will provide important novel information on using dietary sources of polyunsaturated fatty acids and phytochemicals to mitigate the common symptoms of long-COVID.