Omega-3s Tame Inflammation in Elderly COVID-19 Patients

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In frail elderly adults with COVID-19 infections, treatment with omega-3 fatty acids may improve lipid responses and decrease levels of proinflammatory lipid mediators, results of a small randomized controlled trial suggest.

Results of the study, which included 22 patients with multiple comorbidities, were presented during a session of the European Geriatric Medicine Society (EuGMS) annual congress, held in a hybrid format in Athens, Greece, and online.

The patients, who had a median age of 81 years, were randomized to receive an intravenous infusion of an omega-3 polyunsaturated fatty acid (PUFA) emulsion containing 10 g of fish oil per 100 mL or a saline placebo.

Those who received the intravenous infusion had significant decreases from baseline to end of treatment in the neutrophil-to-lymphocyte ratio (NLR), indicating marked reductions in systemic inflammation.

In contrast, patients randomized to a saline placebo had no significant improvements in NLR, reported Magnus Bäck, MD, PhD, from the Karolinska Institute in Stockholm, Sweden, at the meeting.

"Our lipidomic analysis also showed that omega-3 treatment skewed the lipid response, with reduced levels of pro-inflammatory lipid mediators, and increased levels of pro-resolving mediators," according to a late-breaking abstract, which Bäck presented during the session.

Omega-3 treatment was not significantly associated with reduction in either C-reactive protein (CRP) or the proinflammatory cytokine interleukin-6, however.

"Eicosanoid Storm"

In a review article published in January 2021 in the open-access journal Frontiers in Physiology, Bäck and colleagues outlined the rationale for their randomized trial.

"Excessive inflammation has been reported in severe cases with respiratory failure and cardiovascular complications," they write. "In addition to the release of cytokines, referred to as cytokine release syndrome or 'cytokine storm,' increased pro-inflammatory lipid mediators derived from the omega-6 polyunsaturated fatty acid (PUFA) arachidonic acid may cause an 'eicosanoid storm,' which contributes to the uncontrolled systemic inflammation."

Omega-3 PUFA contains proresolving mediators that can limit inflammatory reactions, suggesting the possibility of an inflammation-resolving benefit in patients with COVID-19 without concerns about immunosuppression, the authors hypothesize.

Trial Details

In the trial, COVID-Omega-F, they enrolled patients with a COVID-19 diagnosis requiring hospitalization. Patients with an allergy to fish oil or who had contraindications to intravenous PUFA administration (eg, risk for bleeding, shock, or emboli) were excluded.

Ten patients were randomly assigned to receive infusions of the omega-3 PUFA and 12 were assigned to receive infusions of the placebo, once daily for 5 days.

The primary outcome measure was change in inflammatory biomarkers, including white blood cell counts, CRP, cytokines, and lipid mediators.

Baseline demographic and clinical characteristics were similar between the two study arms, with a median of about 7 days since the onset of symptoms, and 3.5 days since a diagnosis of COVID-19.

All patients had low lymphocyte responses reflected by a high NLR, a prognostic measure for worse outcomes in patients with COVID-19 infections, Bäck said.

Inflammation was moderate, with a CRP of 65 mg/L in the placebo group and 62 mg/L in the omega-3 group.

Seven patients in each study arm received concomitant corticoid treatment. Two patients in each arm died in hospital, but there were no serious treatment-related adverse events.

Inflammatory Markers Improve

As noted before, there was a significant decline in NLR from baseline among patients randomized to omega-3 (P = .02) but no corresponding decrease in patients assigned to placebo infusions.

"The significant decrease was largely driven by an increase in the lymphocyte count in the omega-3 treated group (P = .004), whereas lymphocytes did not significantly change," Bäck said.

As expected, patients in the omega-3 group had pronounced increases in omega-3 fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

The metabolism of fatty acids also differed markedly between the groups, with a significant decrease in the omega-3 group but not the placebo group in proinflammatory mediators, and an increase in precursors to proresolving mediators, Bäck noted.

AF Concerns

In a question-and-answer part of the session, a physician who identified herself as "Senya from Russia" questioned the safety of omega-3 treatment in this population, "because recently there was a meta-analysis which showed that omega-3 fatty acids will increase the risk of atrial fibrillation in older adults especially."

The systematic review and meta-analysis she referred to, published in Circulation and reported on by theheart.org / Medscape Cardiology, showed that among 81,210 patients with a mean age of 65 enrolled in seven randomized controlled trials, omega-3 fatty acid supplementation was associated with a 25% increase in risk for atrial fibrillation. This risk appeared to be higher in trials testing doses greater than 1 gram per day, according to the paper.

"This was not monitored in this study," Bäck replied. "It is true that the meta-analysis showed an increased incidence of atrial fibrillation, so it would be something to monitor in case this trial would be expanded to a larger population."

EuGMS 2021. Late-breaking abstract. Presented October 12, 2021.

The study was supported by the Karolinska Institute. Bäck disclosed no relevant financial relationships, and disclosure information for Senya was not available.

Neil Osterweil, an award-winning medical journalist, is a long-standing and frequent contributor to Medscape.

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