Efficacy of zinc as adjunctive pneumonia treatment in children aged 2 to 60 months in low-income and middle-income countries: a systematic review and meta-analysis

Brown, Nick; Kukka, Antti Juhani; Mårtensson, Andreas

doi:10.1136/bmjpo-2020-000662

Cited by 8 publications

(10 citation statements)

References 36 publications

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“…Zinc is required for a wide variety of immune functions ( 299 ) and those deficient in zinc, particularly children, are prone to increased diarrheal and respiratory infections. Zinc supplementation has been shown to significantly reduce the frequency and severity of both infections in children ( 300 ), although such findings are not universal [e.g., Howie et al ( 301 )], and a recent systematic review and meta-analysis found no evidence that adjunctive zinc treatment improves recovery from pneumonia in children in LMICs ( 302 ). Similar to vitamin C, zinc supplementation has also been suggested as a potential remedy for the treatment of the common cold (rhinovirus infection); a meta-analysis of 3 trials reporting on 199 patients supports a faster recovery time ( 303 ), although the small sample size ( n = 199) of included studies warrants caution.…”

Section: Resultsmentioning

confidence: 99%

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

James

Ali

Armitage

et al. 2021

The Journal of Nutrition

106

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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.

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Section: Resultsmentioning

confidence: 99%

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

James

Ali

Armitage

et al. 2021

The Journal of Nutrition

106

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“…A total of 32 studies were identified, including seven SRs and 25 RCTs. All SRs studied nutritional supplements as an adjunct treatment of pneumonia, with two evaluating zinc [ 17 , 18 ] and one each evaluating vitamin A [ 20 ], vitamin D [ 23 ], and vitamin C [ 22 ]. Two of these SRs examined the effectiveness of multiple adjunct therapies (zinc and vitamin A) [ 19 , 20 ].…”

Section: Resultsmentioning

confidence: 99%

Review of the role of additional treatments including oseltamivir, oral steroids, macrolides, and vitamin supplementation for children with severe pneumonia in low- and middle-income countries

et al. 2022

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Background Pneumonia is a major cause of death in children aged under five years. As children with severe pneumonia have the highest risk of morbidity and mortality, previous studies have evaluated the additional benefit of adjunctive treatments such as oseltamivir, oral steroids, macrolides, and vitamin supplementation that can be added to standard antibiotic management to improve clinical outcomes. The study reviewed the evidence for the role of these additional treatments for children with severe pneumonia in low- and middle-income countries (LMICs). Methods Four electronic databases were searched for English-language articles between 2000 to 2020. Systematic reviews (SRs) with meta-analyses, comparative cohort studies, and randomised controlled trials (RCTs) from LMICs that reported clinical outcomes for children with severe pneumonia aged between one month to 9 years who received adjunct treatment in addition to standard care were included. Risk of bias of included SRs was assessed using AMSTAR 2, and of individual studies using the Effective Public Health Practice Project (EPHPP) quality assessment tool for quantitative studies. Results Overall, the search identified 2147 articles, 32 of which were eligible, including 7 SRs and 25 RCTs. These studies evaluated zinc (4 SRs, 17 RCTs), Vitamin D (1 SR, 4 RCTs), Vitamin A (3 SRs, 1 RCT), Vitamin C (1 SR, 2 RCTs) and micronutrients (1 RCT). Most studies reported clinical outcomes of time to improvement, length of stay, and treatment failure (including mortality). No studies of oseltamivir, steroids, or macrolides fulfilling the inclusion criteria were identified. For zinc, pooled analyses from SRs showed no evidence of benefit. Similarly, a Cochrane review and one RCT found that Vitamin A did not improve clinical outcomes. For Vitamin D, an RCT evaluating a single high dose of 100 000 international units (IU) of vitamin D found a reduction in time to improvement, with 38%-40% documented vitamin D deficiency at baseline. However, two other studies of 1000 IU daily did not show any effect, but vitamin D status was not measured. For vitamin C, two studies found a reduction in time to symptom resolution in those with severe disease, with one reporting a shorter length of hospital stay. However, both studies were of weak quality. Most studies excluded malnourished children, and studies which included these children did not report specifically on the effect of micronutrients. Conclusions This review found that adjunctive zinc and vitamin A, in addition to standard care, does not improve clinical outcomes in children with severe pneumonia in LMICs (strong evidence). However, a reduction in time to symptom resolution was reported with high dose vitamin D supplementation in children with documented vitamin D deficiency (strong evidence from one study) and vitamin C (weak evidence), although further research is needed, especially in underweight children.

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“…Howie et al . 320 ) and a recent systematic review and meta-analysis found no evidence that adjunctive zinc treatment improves recovery from pneumonia in children in low- and middle-income countries 321 . Similar to vitamin C, zinc supplementation has also been suggested as a potential remedy for the treatment of the common cold (rhinovirus infection); a meta-analysis of 3 trials reporting on 199 patients supports a faster recovery time 322 although the small sample size (N=199) of included studies warrants caution.…”

Section: Zincmentioning

confidence: 98%

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

James

Ali

Armitage

et al. 2020

Preprint

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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.

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Efficacy of zinc as adjunctive pneumonia treatment in children aged 2 to 60 months in low-income and middle-income countries: a systematic review and meta-analysis

Cited by 8 publications

References 36 publications

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

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

Review of the role of additional treatments including oseltamivir, oral steroids, macrolides, and vitamin supplementation for children with severe pneumonia in low- and middle-income countries

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

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