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The Role of Nutrition in COVID-19 Susceptibility and Severity of Disease: A Systematic Review
Open accessPublished version of a preprint
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, 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]
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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.”
From ESPEN guideline on nutritional support for polymorbid medical inpatients (2023) · cites this paper as [91]
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Micha, R., Mannar, V., Afshin, A., Allemandi, L., Baker, P., Battersby, J., Bhutta, Z. A., Chen, K. M., Corvalan, C., Cesare, M. D., et al. (2020) · Cited by 207
Zhang, Y., Li, H., Zhang, J., Cao, Y., Zhao, X., Yu, N., Gao, Y., Ma, J., Zhang, H., Zhang, J., et al. (2020) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14086 · Cited by 205
Obesity is Associated with Worse Outcomes in COVID‐19: Analysis of Early Data from New York City
Hajifathalian, K., Kumar, S. R., Newberry, C. A., Shah, S. L., Fortune, B. E., Krisko, T. I., Ortiz‐Pujols, S., Zhou, X. K., Dannenberg, A. J., Kumar, R. B., et al. (2020) · Obesity · doi:10.1002/oby.22923 · Cited by 205
Carlucci, P. M., Ahuja, T., Petrilli, C. M., Rajagopalan, H., Jones, S., & Rahimian, J. (2020) · Journal of Medical Microbiology · doi:10.1099/jmm.0.001250 · Cited by 204
Reactive Oxygen Species in TNFα-Induced Signaling and Cell Death
Morgan, M. J., & Liu, Z.-G. (2010) · Molecules and Cells · doi:10.1007/s10059-010-0105-0 · Cited by 203
Xie, Z., Wang, X., & Bikle, D. D. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00040 · Cited by 201
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Flagged first, then by citations
6 of the 392 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- Zhang Y, CuiY, ShenM, ZhangJ, LiuB, DaiM, ChenL, HanD, FanY, ZengYet 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
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Cited by
Sorted by citations
Probiotics-based foods and beverages as future foods and their overall safety and regulatory claims
Koirala, S., & Anal, A. K. (2021) · Future Foods · doi:10.1016/j.fufo.2021.100013 · Cited by 181
Alam, S., Sarker, M. M. R., Afrin, S., Richi, F. T., Zhao, C., Zhou, J., & Mohamed, I. N. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.671498 · Cited by 148
Dietary Supplements and Nutraceuticals under Investigation for COVID-19 Prevention and Treatment
Lordan, R., Rando, H. M., & Greene, C. S. (2021) · mSystems · doi:10.1128/msystems.00122-21 · Cited by 137
ESPEN guideline on nutritional support for polymorbid medical inpatients
Wunderle, C., Gomes, F., Schuetz, P., Stumpf, F., Austin, P., Ballesteros-Pomar, M. D., Cederholm, T., Fletcher, J., Laviano, A., Norman, K., et al. (2023) · Clinical Nutrition · doi:10.1016/j.clnu.2023.06.023 · Cited by 105
“Some studies suggest bene fi cial outcomes from supplementation of micronutrients: for example, a study relating micronutrients to COVID-19 infection by James et al. reported limited evidence that supplementation of certain micronutrients can prevent severe disease or shorten time to recovery [91].”
Scapaticci, S., Neri, C. R., Marseglia, G. L., Staiano, A., Chiarelli, F., & Verduci, E. (2022) · The Italian Journal of Pediatrics/Italian journal of pediatrics · doi:10.1186/s13052-022-01211-y · Cited by 105
Metadata
- 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
- ORCID
- Venue
- The Journal of Nutrition
- Publisher
- Elsevier BV
- Published
- 2021-07
- Volume
- 151
- Issue
- 7
- Pages
- 1854-1878
- ISSN
- 0022-3166 (ISSN-L)
- PMC
- PMC8194602
- OpenAlex
- W3162385661
- Cited by
- 147
- References
- 392
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 27 · 2023: 39 · 2022: 41 · 2021: 24
- FWCI
- 3.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- 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 (medical) › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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