The landscape of potential health benefits of carotenoids as natural supportive therapeutics in protecting against Coronavirus infection

Abstract

The Coronavirus Disease-2019 (COVID-19) pandemic urges researching possibilities for prevention and management of the effects of the virus. Carotenoids are natural phytochemicals of anti-oxidant, anti-inflammatory and immunomodulatory properties and may exert potential in aiding in combatting the pandemic. This review presents the direct and indirect evidence of the health benefits of carotenoids and derivatives based on in vitro and in vivo studies, human clinical trials and epidemiological studies and proposes possible mechanisms of action via which carotenoids may have the capacity to protect against COVID-19 effects. The current evidence provides a rationale for considering carotenoids as natural supportive nutrients via antioxidant activities, including scavenging lipid-soluble radicals, reducing hypoxia-associated superoxide by activating antioxidant enzymes, or suppressing enzymes that produce reactive oxygen species (ROS). Carotenoids may regulate COVID-19 induced over-production of pro-inflammatory cytokines, chemokines, pro-inflammatory enzymes and adhesion molecules by nuclear factor kappa B (NF-κB), renin-angiotensin-aldosterone system (RAS) and interleukins-6- Janus kinase-signal transducer and activator of transcription (IL-6-JAK/STAT) pathways and suppress the polarization of pro-inflammatory M1 macrophage. Moreover, carotenoids may modulate the peroxisome proliferator-activated receptors γ by acting as agonists to alleviate COVID-19 symptoms. They also may potentially block the cellular receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human angiotensin-converting enzyme 2 (ACE2). These activities may reduce the severity of COVID-19 and flu-like diseases. Thus, carotenoid supplementation may aid in combatting the pandemic, as well as seasonal flu. However, further in vitro, in vivo and in particular long-term clinical trials in COVID-19 patients are needed to evaluate this hypothesis.

Keywords: Anti-inflammation; COVID-19; Carotenoids; Immunity; Natural supportive therapeutics; SARS-CoV-2.

Graphical abstract

Fig. 1

Structures of common carotenoids.

Fig. 2

Structure and pathogenesis of Coronavirus Disease-2019 (COVID-19).

Fig. 3

Putative mechanisms contributing to increased susceptibility for severe Coronavirus Disease-2019 (COVID-19) illness and the hypothetical protective mechanisms of dietary carotenoids. We presume that following viral entry of SARS-CoV-2 into the respiratory epithelial cell and other target cells via binding the cell surface angiotensin converting enzyme 2 (ACE2), the patient experiences oxidative stress and reactive oxygen species (ROS)-mediated inflammation and dysregulated innate and adaptive immune response. The accumulation of a series of complications may lead to severe illness, multi-organ damage, acute lung injury (ALI), and acute respiratory distress syndrome (ARDS). Carotenoids can inhibit these main signalling pathways to suppress the excess oxidative stress and overproduction of pro-inflammatory cytokines.