Vitamin A in resistance to and recovery from infection: relevance to SARS-CoV2

Abstract

SARS-CoV2 infects respiratory epithelial cells via its cellular receptor angiotensin-converting enzyme 2, causing a viral pneumonia with pronounced inflammation resulting in significant damage to the lungs and other organ systems, including the kidneys, though symptoms and disease severity are quite variable depending on the intensity of exposure and presence of underlying conditions that may affect the immune response. The resulting disease, coronavirus disease 2019 (COVID-19), can cause multi-organ system dysfunction in patients requiring hospitalisation and intensive care treatment. Serious infections like COVID-19 often negatively affect nutritional status, and the resulting nutritional deficiencies may increase disease severity and impair recovery. One example is the viral infection measles, where associated vitamin A (VA) deficiency increases disease severity and appropriately timed supplementation during recovery reduces mortality and hastens recovery. VA may play a similar role in COVID-19. First, VA is important in maintaining innate and adaptive immunity to promote clearance of a primary infection as well as minimise risks from secondary infections. Second, VA plays a unique role in the respiratory tract, minimising damaging inflammation, supporting repair of respiratory epithelium and preventing fibrosis. Third, VA deficiency may develop during COVID-19 due to specific effects on lung and liver stores caused by inflammation and impaired kidney function, suggesting that supplements may be needed to restore adequate status. Fourth, VA supplementation may counteract adverse effects of SARS-CoV2 on the angiotensin system as well as minimises adverse effects of some COVID-19 therapies. Evaluating interactions of SARS-CoV2 infection with VA metabolism may thus provide improved COVID-19 therapy.

Keywords: Angiotensin-converting enzyme 2 (ACE2); COVID-19; Immunity; Lipofibroblasts; Retinoic acid; SARS-CoV2; Vitamin A.

Graphical abstract

Fig. 1.

Overview of potential interactions between vitamin A and COVID-19. SARS-CoV2 uses angiotensin-converting enzyme 2 (ACE2) for receptor-mediated cell entry, leading to ACE2 down-regulation and a deregulation of the renin–angiotensin system. Viral RNA triggers the production of CD4⁺ T-helper type 1 cells and cytokines, including TNF-α, IL-1, IL-6 and IL-18. In the lung, SARS-CoV2 can lead to severe acute respiratory syndrome due to extensive pulmonary fibrosis promoted by enhanced lipofibroblast–myofibroblast transition. Since lipofibroblasts rely on retinoids to initiate, coordinate and regulate alveolar septal eruption and alveolo-genesis, the loss of retinoids during the virus-induced lipofibroblast–myofibroblast transition could impair the ability of the lung to repair damaged epithelial surfaces, potentially leading to long-lasting scarring, lung fibrosis and reduced pulmonary capacity, which could manifest into a ‘long COVID’ effect. Treatment of COVID-19 patients with dexamethasone could further increase localised vitamin A deficiency through the reduction of retinoid-binding proteins and receptors. On the other hand, SARS-CoV2 could also lead to systemic vitamin A deficiency through a combination of increased urinary losses, reduced intake and absorption and increased utilisation. The effects of local and systemic vitamin A deficiency have been shown to reduce the ability of the immune system to maintain healthy respiratory and intestinal epithelial barriers, activity and numbers of type 1 innate lymphoid cells and secretory IgA responses to virus infection. This vicious cycle of increased vitamin A deficiency and decreased regulatory and protective immunity impairs recovery and is likely to increase morbidity and mortality.