The Feasibility of Omega-3 Supplementation Compared to Placebo in the Management of Long COVID Symptoms Among Healthcare Workers: A Randomized Controlled Trial.

Background:  COVID-19 is known to cause significant multisystem inflammatory responses, leading to symptoms beyond the acute phase of illness. These "long COVID" symptoms affect quality of life and interfere with daily activities. This pilot study looks at the feasibility, tolerability, and safety of omega-3 (docosahexaenoic acid+eicosapentaenoic acid, EPA) among healthcare workers with long COVID symptoms in New Jersey.

Methods:  This double-blind, randomized-controlled pilot trial used self-administered omega-3 vs. placebo for 12 weeks in healthcare workers. The enrollment period was from October 2021 to March 2023. Participants were monitored weekly for compliance and adverse effects. They completed the Symptoms and Quality of Life survey biweekly. Baseline and week-12 blood test for omega-3 levels and arachidonic acid (AA):EPA ratio was also measured and analyzed. Descriptive statistics were calculated for all variables at 12 weeks. An independent sample t-test was conducted to compare the ages of the treatment groups. Fisher's exact tests were conducted on each outcome by the treatment arm. No adjustments for multiple testing were included; therefore, significance was set at p ≤ 0.05. Analyses were conducted using R version 4.3.3 (R Core Team, Vienna, Austria).

Results:  Thirty-two healthcare workers were recruited, and 18 completed the study. Feasibility was assessed based on enrollment and compliance with the study protocol. There was no significant difference in age between the placebo and treatment groups. The intervention group did not show significant improvement in the long COVID symptoms: shortness of breath (p = 0.39), cough (p = 0.76), fatigue (p = 0.57), lack of taste (p = 0.10), and lack of smell (p = 0.10). In the placebo group, baseline average omega-3 and AA:EPA ratio were 4.09 (standard deviation, SD = 0.85) and 23.9 (SD = 13.4), respectively, and week-12 omega-3 and AA:EPA ratio were 4.46 (SD = 0.95) and 20.8 (SD = 6.0), respectively. For the supplement group, baseline average omega 3 and AA:EPA ratio were 3.75 (SD = 0.48) and 23.1 (SD = 8.3), respectively, and week-12 omega-3 and AA:EPA ratio were 5.97 (SD = 1.93) and 11.8 (SD = 14.0), respectively. One supplement-treated participant and five placebo-treated participants experienced adverse events. No serious adverse events were reported.

Conclusions:  This pilot study successfully demonstrated the feasibility, safety, and tolerability of using omega-3 supplements for the treatment of long COVID syndrome. The study results did not show statistically significant improvement in the long COVID symptoms. The mean difference in the AA:EPA ratio in the placebo vs. supplement group showed a pronounced decline in inflammatory markers in the supplement group. However, our study did not show a connection between the decreased inflammatory markers and clinical symptoms. We may need a longer follow-up to understand the possible clinical benefits of the decreased AA:EPA ratio.