BACKGROUND: Many nutrients have powerful immunomodulatory actions with the potential to alter susceptibility to coronavirus disease 2019 (COVID-19) infection, progression to symptoms, likelihood of severe disease, and survival. OBJECTIVE: The aim was to review the latest evidence on how malnutrition across all its forms (under- and overnutrition and micronutrient status) may influence both susceptibility to, and progression of, COVID-19. METHODS: We synthesized information on 13 nutrition-related components and their potential interactions with COVID-19: overweight, obesity, and diabetes; protein-energy malnutrition; anemia; vitamins A, C, D, and E; PUFAs; iron; selenium; zinc; antioxidants; and nutritional support. For each section we provide: 1) a landscape review of pertinent material; 2) a systematic search of the literature in PubMed and EMBASE databases, including a wide range of preprint servers; and 3) a screen of 6 clinical trial registries. All original research was considered, without restriction to study design, and included if it covered: 1) severe acute respiratory syndrome coronavirus (CoV) 2 (SARS-CoV-2), Middle East respiratory syndrome CoV (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 16 May and 11 August 2020. RESULTS: Across the 13 searches, 2732 articles from PubMed and EMBASE, 4164 articles from the preprint servers, and 433 trials were returned. In the final narrative synthesis, we include 22 published articles, 38 preprint articles, and 79 trials. CONCLUSIONS: Currently there is limited evidence that high-dose supplements of micronutrients will either prevent severe disease or speed up recovery. However, results of clinical trials are eagerly awaited. 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. Furthermore, there is strong evidence that prevention of obesity and type 2 diabetes will reduce the risk of serious COVID-19 outcomes. This review is registered at PROSPERO as CRD42020186194.

The Role of Nutrition in COVID-19 Susceptibility and Severity of Disease: A Systematic Review.

Objective:  To compare three low-lactose milk formulas differing in osmolality and degree of protein hydrolysis in the treatment of diarrhoea and malnutrition in subjects with high rates of lactose intolerance, osmotic diarrhoea and a tropical/environmental enteropathy.

Methods:  A randomized double-blind trial of 180 Aboriginal children under 3 years of age admitted with acute diarrhoea and/or malnutrition was carried out. The intervention milk formulas were: (i) De-Lact, a low-osmolality lactose-free formula; (ii) O-Lac, a lactose-free formula; and (iii) Alfare, a partially hydrolysed formula. Outcome measures were diarrhoeal severity, weight gain, formula palatability and changes in intestinal permeability (L/R ratios).

Results:  The duration of diarrhoea in days (mean; 95% confidence interval) was significantly longer on Alfare (8.5; 7.0−10.0) compared to De-Lact (6.1; 5.0−7.2) and O-Lac (6.9; 5.6−8.1; P = 0.04). There were no differences in mean intake between formulas, but palatability of Alfare was significantly worse (P < 0.01) than the other formulas. Over the trial 5 days, improvement in L/R ratios was significantly greater (P = 0.05) for De-Lact (18.6; 10.6−26.6) than for Alfare (8.5; 2.1−14.9). Weight gain was not significantly different between the three formulas, except in a malnourished subgroup who had better weight gain on De-Lact (P = 0.05).

Conclusions:  In these Aboriginal children with diarrhoea and growth failure, a low osmolality milk was associated with better outcomes and a partially hydrolysed formula with less improvement in mucosal recovery, suggesting that cow's milk protein intolerance is not contributing to greater diarrhoeal severity or enteropathy in Aboriginal children.

Milk formulas in acute gastroenteritis and malnutrition: A randomized trial

Infectious diarrhoea has been recognised as a serious public health problem for Aboriginal Australians, particularly infants and young children, for more than two decades. These diseases are caused by bacterial, viral and parasitic infections which are spread mainly by the faecal-oral route and which must be interrupted if prevention is to be effective. This paper reviews published reports on this subject and interventions which have been used elsewhere to reduce the incidence of infectious diarrhoea. These reports have important implications for Aboriginal health but interventions and strategies to overcome this problem must recognise the unique circumstances of Aboriginal people in Australia.

Diarrhoea in Australian Aborigines.

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 16 th May and 11 th 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.

https://www.medrxiv.org/content/medrxiv/early/2020/10/21/2020.10.19.20214395.1.full.pdf

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

Impact of gastric endoscopic submucosal dissection in elderly patients: The latest single center large cohort study with a review of the literature.

The prevalence and duration of lactose malabsorption was studied in 64 Central Australian Aboriginal children requiring hospitalization for acute enteritis. Lactose malabsorption was determined by the breath-hydrogen test. Sixty-nine per cent were shown to malabsorb lactose, a figure similar to that for well nourished urban European children, hospitalized for acute enteritis. Whereas 90 per cent of the European children became lactose-tolerant 1 month later, only three of 32 aboriginal children were lactose-tolerant after 3 months. Lactose malabsorption was also associated with more frequent hospitalizations in affected children.



Coronavirus-like particles were the commonest agent isolated from Aboriginal children. The majority of the Aboriginal children were malnourished (< 80% standard weight for age) which may have been contributed to by their lactose malabsorption and explain why this failed to recover in the same way as European children. The possibility of lactose malabsorption must be taken into consideration when managing Aboriginal children with acute diarrhoeal disease and undernutrition. The use of the breath-hydrogen test allows an accurate diagnosis of lactose malabsorption to be made in Aboriginal children with diarrhoea so that appropriate dietary management can be instituted.

Graeme R. Edgeley

Papers

Lactose malabsorption in Central Australian Aboriginal children hospitalized with acute enteritis