Genetic Variation, Diet, Inflammation, and the Risk for COVID-19

Abstract

COVID-19, which is caused by SARS-CoV-2, is characterized by various symptoms, ranging from mild fatigue to life-threatening pneumonia, "cytokine storm," and multiorgan failure. The manifestation of COVID-19 may lead to a cytokine storm, i.e., it facilitates viral replication that triggers a strong release of cytokines, which then modulates the immune system and results in hyperinflammation. Today's diet is high in omega-6 fatty acids and deficient in omega-3 fatty acids; this, along with a high fructose intake, leads to obesity, which is a chronic state of low-grade inflammation. Omega-6 fatty acids are proinflammatory and prothrombotic whereas omega-3 fatty acids are less proinflammatory and thrombotic. Furthermore, omega-3 fatty acids make specialized lipid mediators, namely resolvins, protectins, and maresins, that are potent anti-inflammatory agents. Throughout evolution there was a balance between omega-6 and omega-3 fatty acids with a ratio of 1-2/1 omega-6/omega-3, but today this ratio is 16-20/1 omega-6/omega-3, leading to a proinflammatory state. In addition, genetic variants in FADS1, FADS2, ELOV-2, and ELOV-5 lead to a more efficient biosynthesis of long-chain polyunsaturated fatty acids (PUFAs), e.g., of linoleic acid (LA) to arachidonic acid (ARA), and (alpha-linolenic acid) (ALA) to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), leading to higher ARA levels. Because the US diet is already high in omega-6 fatty acids, the increased biosynthesis of ARA in people with the derived FADS haplotype (haplotype D) leads to an increased production of leukotrienes, thromboxanes, C-reactive protein (CRP), and eventually elevated levels of cytokines, like interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF), which may increase susceptibility to COVID-19. About 80% of African Americans, 50% of Hispanics, and 45% of European Americans have the FADS haplotype D and are thus efficient metabolizers, which could account for the higher vulnerability of these populations to COVID-19. Therefore, another reason that African Americans and Hispanics are more susceptible to COVID-19 is that they have a higher frequency of haplotype D, which is no longer beneficial in today's environment and diet. Genetic variation must be considered in all studies of disease development and therapy because it is important to the practice of precision nutrition by physicians and other health professionals. The objective of this commentary is to emphasize the importance of genetic variation within populations and its interaction with diet in the development of disease. Differences in the frequency of genes and their interactions with nutrients in various population groups must be considered among the factors contributing to health disparities in the development of COVID-19. A balanced omega-6/omega-3 ratio is essential to health. Physicians should measure their patients' fatty acids and recommend decreasing the intake of foods rich in omega-6 fatty acids and increasing the intake of omega-3 fatty acids along with fruits and vegetables.

Keywords: COVID-19 risk; Diet; Genetic variation; Inflammation; Obesity; Omega-6 and omega-3 fatty acid balance.