Omega-3 Oil Use in COVID-19 Patients in Qatar: a Randomized Controlled Trial

The outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) due to a novel coronavirus (COVID-19) has emerged from Wuhan, China in late December 2019 and spread rapidly worldwide. Until July 16, 2020, there has been more than 13 million confirmed cases worldwide and ~580,000 deaths attributed to the disease. With the fast evolution of this worldwide public-health emergency, the general public has demanded the urgent investigation of potentially beneficial drugs that may improve the outcome of those affected by SARS-CoV-2 infection. While new therapies and vaccines are urgently being investigated, they may take an inordinate time, or never be identified. In the world today, there is only one drug approved by the FDA for COVID-19 (Remdesivir), while the investigation of several other re-purposed drugs is potentially suggested for SARS-CoV-2 treatment. Many trials are taking place around the world, including some utilizing potentially dangerous drugs with considerable side effects and enormous costs. However, the clinical effectiveness and safety of all pharmacologic therapies so far have not been fully proven.

The preliminary findings about this disease indicates that patients with cardiovascular risk factors including diabetes, obesity and other pre-existing cardiovascular diseases have worse outcomes. Additionally, severe respiratory infection and hypoxia associate with severe COVID-19 might trigger many pathological pathways which leads to cardiovascular sequelae. In a cohort of 416 hospitalized patients with COVID-19, myocardial injury defined by an elevated high sensitivity troponin I level was associated with in-hospital mortality. Another study of 187 hospitalized patients with COVID-19 showed a similar association. Interestingly, the highest mortality rates were observed among patients with pre-existing cardiovascular disease. Importantly, none of the published experiences from anywhere in the world has explored omega-3 oil and its known protective cardiovascular benefits.

Omega-3 fatty acids are found in food such as fish and flaxseed as well as in dietary supplements labeled omega-3-oil.The beneficiary role of Omega-3 polyunsaturated fatty acids (PUFA), namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish, other marine sources, and supplements, have been shown to be anti-inflammatory through several cellular mechanisms including their incorporation into cellular membranes and resulting altered synthesis of eicosanoids. There is the potential that arachidonic acid (AA,) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and other dietary unsaturated fatty acids can inactivate enveloped viruses. It is thought that these fatty acids and others cause leakages or lysis of the viral envelopes by disrupting the membrane integrity, amongst other potential mechanisms. Indeed, the supplementation of EPA and DHA raises the level of these fatty acids in the phospholipids of cells involved in inflammation in a time and dose-dependent fashion at the expense of AA4. Li and colleagues reviewed 89 systematic reviews and meta-analyses investigating fish intake and all-cause mortality, concluding that fish intake at 2-4 servings per week is associated with the largest risk reduction.

In animal models despite these potential positive effects, there is conflicting evidence in relation to fish or fish oil consumption for some viral infections. In influenza models, fish oil-fed mice demonstrated impaired resistance to influenza infection due to their immunomodulatory and anti-inflammatory properties, which negatively dampened the immune response of the mice against the infection. In another mouse model, fish oil intake delayed influenza virus clearance and impaired the immune response in the lungs of mice by disrupting interferon-γ and immunoglobulin A. A further study indicated that it may be due to the impairment of virus-specific T lymphocyte cytotoxicity.

Despite the potential benefit, there are few human studies with omega 3 and immune and inflammatory response. The recent proposed benefit for omeg-3-oil is unique, EPA and DHA which are main fatty acids in omega-3-oils may act as substrates for the synthesis of specialized pro-resolving lipid mediators such as maresins, resolvins, and protectins, of which protectins may reduce the replication of influenza and potentially affect the inflammatory manifestations of respiratory viral diseases.