Could nutrition modulate COVID-19 susceptibility and severity of disease? A systematic review

Background: Many nutrients have powerful immunomodulatory actions with the potential to alter susceptibility to COVID-19 infection, progression to symptoms, likelihood of severe disease and survival. The pandemic has fostered many nutrition-related theories, sometimes backed by a biased interpretation of evidence. Objectives: To provide a systematic review of the latest evidence on how malnutrition across all its forms (under- and over-nutrition and micronutrient status) may influence both susceptibility to, and progression and severity of, COVID-19. Methods: We synthesised information on 13 nutrition-related components and their potential interactions with COVID-19: overweight, obesity and diabetes; protein-energy malnutrition; anaemia; vitamins A, C, D, and E; poly-unsaturated fatty acids; iron; selenium; zinc; anti-oxidants, and nutritional support. For each section we provide: a) a landscape review of pertinent material; b) a systematic search of the literature in PubMed and EMBASE databases, including a systematic search of a wide range of pre-print servers; and c) a screen of six clinical trial registries. Two reviewers were assigned per section for data extraction. All original research was considered, without restriction to study design, and included if it covered: 1) SARS-CoV-2, MERS-CoV or SARS-CoV viruses and 2) disease susceptibility or 3) disease progression, and 4) the nutritional component of interest. Searches took place between 16th May and 11th August, 2020. PROSPERO registration CRD42020186194. Results: Across the 13 searches, a total of 2732 articles from PubMed and EMBASE, 4164 articles from the pre-print servers, and 433 trials were returned. A total of 288 published articles and 278 pre-print articles were taken to full text screening. In the final narrative synthesis, we cover 22 published articles, 39 pre-print articles and 79 trials. The review highlights a range of mechanistic and observational evidence to highlight the role nutrition can play in susceptibility and progression of COVID-19. However, to date, there is limited evidence that high-dose supplements of micronutrients will either prevent severe disease or speed up recovery, although results of clinical trials are eagerly awaited. Conclusions: To date there is no conclusive evidence supporting adoption of novel nutritional therapies. However, given the known impacts of all forms of malnutrition on the immune system, public health strategies to reduce micronutrient deficiencies and undernutrition remain of critical importance. There is strong evidence that prevention of obesity, and its consequent type-2 diabetes, will reduce the risk of serious COVID-19 outcomes.