Cited by 147COVID-19 Clinical Research StudiesNutrition and Health in AgingNutrition and Health Studies

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

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James, Philip T, Ali, Zakari, Armitage, Andrew E, Bonell, Ana, Cerami, Carla, Drakesmith, Hal, Jobe, Modou, Jones, Kerry S +10 more·2021·The Journal of Nutrition

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Abstract

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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  • Supplementing with micronutrients (including vitamins A, C, D, E, zinc, selenium, iron) and plant-based antioxidants (such as flavonoids and polyphenols) can reduce the risk of RTI by activating the immune system, reducing oxidative stress, providing anti-inflammatory effects, and maintaining respiratory tract barrier function.

    “Supplementing with micronutrients (including vitamins A, C, D, E, zinc, selenium, iron, etc.) and plant-based antioxidants (such as flavonoids and polyphenols) can reduce the risk of RTI by activating the immune system, reducing oxidative stress, providing anti-inflammatory effects, and maintaining respiratory tract barrier function.”

    From Comparative effectiveness of oral nutritional supplements in preventing respiratory tract infections among adults: a systematic review and network meta-analysis (2025) · cites this paper as [3]

    The Results (Vitamin D and Zinc; page not provided) report reduced respiratory-infection risk with some supplementation regimens, while the Discussion describes possible antioxidant mechanisms. But the Results (Antioxidants) say clinical evidence for benefits from dietary antioxidants is lacking, and the Discussion notes that vitamin E and iron supplementation may increase the risk of some respiratory infections. The paper therefore does not support the blanket claim that all the listed supplements reduce RTI risk through the stated mechanisms. (LLM, conf=0.90)

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  • In polymorbid medical inpatients exclusively fed orally, an adequate intake of micronutrients (vitamins and trace elements) to meet daily estimated requirements should be ensured.

    “In polymorbid medical inpatients exclusively fed orally, an adequate intake of micronutrients (vitamins and trace elements) to meet daily estimated requirements should be ensured.”

    From ESPEN guideline on nutritional support for polymorbid medical inpatients (2023) · cites this paper as [91]

    The Results, under “Nutritional support” (page unavailable), describe a protocol recommending multivitamin, multimineral, and trace-element supplements for hospitalized COVID-19 patients who may not meet nutritional needs through a normal diet. The passage does not specify polymorbid medical inpatients fed exclusively orally or say that supplementation should meet daily estimated micronutrient requirements. (LLM, conf=0.84)

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  1. [92]Zhang Y, Cui Y, Shen M, Zhang J, Liu B, Dai M, Chen L, Han D, Fan Y, Zeng Y et al. Comorbid diabetes mellitus was associated with poorer prognosis in patients with COVID-19: a retrospective cohort study, Available at: https://doi.org/10.1101/2020.03.24.20042358. medRxiv [Preprint]. Published online January 2020. doi: 10.1101/2020.03.24.20042358. [Accessed 2020 Jun 4]. · DOI
  2. [147]Hippchen T, Altamura S, Muckenthaler MU, Merle U. Hypoferremia predicts hospitalization and oxygen demand in COVID-19 patients. medRxiv [Preprint]. Published online 26 June 2020. doi: 10.1101/2020.06.26.20140525. PMC7665253 33205000 · DOI
  3. [167]WHO. Pocket book of hospital care for children: guidelines for the management of common childhood illnesses. Geneva (Switzerland): WHO; 2013. 24006557

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Authors
James, P. T., Ali, Z., Armitage, A. E., Bonell, A., Cerami, C., Drakesmith, H., Jobe, M., Jones, K. S., Liew, Z., Moore, S. E., Morales-Berstein, F., Nabwera, H. M., Nadjm, B., Pasricha, S.-R., Scheelbeek, P., Silver, M. J., Teh, M. R., & Prentice, A. M.
Affiliations
  • London School of Hygiene & Tropical Medicine (GB)
  • University of Oxford (GB)
  • University of Cambridge (GB)
  • King's College London (GB)
  • Liverpool School of Tropical Medicine (GB)
  • The University of Melbourne (AU)
Corresponding author
Prentice, Andrew M
Venue
The Journal of Nutrition
Publisher
Elsevier BV
Published
2021-07
Volume
151
Issue
7
Pages
1854-1878
ISSN
0022-3166 (ISSN-L)
OpenAlex
W3162385661
Cited by
147
References
392
Citations by year
2026: 4 · 2025: 10 · 2024: 27 · 2023: 39 · 2022: 41 · 2021: 24 · 2020: 2
FWCI
3.82
Type
journal article
Language
en
Open access
Locations
  • Journal of Nutrition (publishedVersion)
  • medRxiv (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
  • LSTM Online Archive (Liverpool School of Tropical Medicine) (acceptedVersion)
  • LSHTM Research Online (London School of Hygiene and Tropical Medicine) (submittedVersion)
  • Research Portal (King's College London) (submittedVersion, other-oa)
  • Bristol Research (University of Bristol) (submittedVersion)
Funders
  • Wellcome Trust (216021/Z/19/Z, 220225/Z/20/Z)
  • Wellcome (203905, 216451/Z/19/Z)
  • MRC (MC_UU_12010/10)
  • SEM
  • Medical Research Council (MR/P012019/1)
  • AMP
  • CC
  • Department for International Development (MC-A760-5QX00)
  • National Institute for Health Research (IS-BRC-1215- 20014)
  • NIHR
  • Cambridge University Hospitals
  • University of Cambridge
Topics
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
  • Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutrition and Health Studies
Keywords
COVID-19 pandemic, SARS-CoV-2, nutrition, malnutrition, micronutrient status, obesity, type 2 diabetes, protein-energy malnutrition, anemia, vitamins, polyunsaturated fatty acids, iron, selenium, zinc, antioxidants, dietary supplementation, disease severity, immunomodulation
MeSH terms
COVID-19, SARS-CoV-2, Anemia, Antioxidants, Diabetes Mellitus, Humans, Iron, Nutritional Status, Obesity, Protein-Energy Malnutrition, Selenium, Severity of Illness Index, Vitamins, Zinc, Fatty Acids, Omega-3, Comorbidity, Disease Progression, Nutritional Support, Dietary Supplements, Fatty Acids, Omega-6

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