the role of nutrition in covid 19 susceptibility and severity of disease a systematic CORD-Papers-2022-06-02 (Version 1)

Title: The Role of Nutrition in COVID-19 Susceptibility and Severity of Disease: A Systematic Review
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.
Published: 2021-05-19
Journal: J Nutr
DOI: 10.1093/jn/nxab059
DOI_URL: http://doi.org/10.1093/jn/nxab059
Author Name: James Philip T
Author link: https://covid19-data.nist.gov/pid/rest/local/author/james_philip_t
Author Name: Ali Zakari
Author link: https://covid19-data.nist.gov/pid/rest/local/author/ali_zakari
Author Name: Armitage Andrew E
Author link: https://covid19-data.nist.gov/pid/rest/local/author/armitage_andrew_e
Author Name: Bonell Ana
Author link: https://covid19-data.nist.gov/pid/rest/local/author/bonell_ana
Author Name: Cerami Carla
Author link: https://covid19-data.nist.gov/pid/rest/local/author/cerami_carla
Author Name: Drakesmith Hal
Author link: https://covid19-data.nist.gov/pid/rest/local/author/drakesmith_hal
Author Name: Jobe Modou
Author link: https://covid19-data.nist.gov/pid/rest/local/author/jobe_modou
Author Name: Jones Kerry S
Author link: https://covid19-data.nist.gov/pid/rest/local/author/jones_kerry_s
Author Name: Liew Zara
Author link: https://covid19-data.nist.gov/pid/rest/local/author/liew_zara
Author Name: Moore Sophie E
Author link: https://covid19-data.nist.gov/pid/rest/local/author/moore_sophie_e
Author Name: Morales Berstein Fernanda
Author link: https://covid19-data.nist.gov/pid/rest/local/author/morales_berstein_fernanda
Author Name: Nabwera Helen M
Author link: https://covid19-data.nist.gov/pid/rest/local/author/nabwera_helen_m
Author Name: Nadjm Behzad
Author link: https://covid19-data.nist.gov/pid/rest/local/author/nadjm_behzad
Author Name: Pasricha Sant Rayn
Author link: https://covid19-data.nist.gov/pid/rest/local/author/pasricha_sant_rayn
Author Name: Scheelbeek Pauline
Author link: https://covid19-data.nist.gov/pid/rest/local/author/scheelbeek_pauline
Author Name: Silver Matt J
Author link: https://covid19-data.nist.gov/pid/rest/local/author/silver_matt_j
Author Name: Teh Megan R
Author link: https://covid19-data.nist.gov/pid/rest/local/author/teh_megan_r
Author Name: Prentice Andrew M
Author link: https://covid19-data.nist.gov/pid/rest/local/author/prentice_andrew_m
sha: 8e363f91272244e15cda8322e2c7483ecf7a91af
license: no-cc
license_url: [no creative commons license associated]
source_x: Medline; PMC
source_x_url: https://www.medline.com/https://www.ncbi.nlm.nih.gov/pubmed/
pubmed_id: 33982105
pubmed_id_url: https://www.ncbi.nlm.nih.gov/pubmed/33982105
pmcid: PMC8194602
pmcid_url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194602
url: https://doi.org/10.1093/jn/nxab059 https://www.ncbi.nlm.nih.gov/pubmed/33982105/
has_full_text: TRUE
Keywords Extracted from Text Content: selenium human PUFAs high-dose supplements COVID-19 3 iron gastrointestinal coronavirus disease 2019 SARS-CoV-2 PubMed micronutrients COVID-19 vitamins A coronavirus SARS-CoV viruses and C, D prespecify lymphocyte organ hepatic acute-phase Roberton SARS-CoV parenteral human body; 2 protectins malariacontrol leukocyte enterocytes B IL-2 soils COVID-19 patients Micronutrients selenium-enriched fertilizers ARDS-type body patient Long-chain bone marrow polyphenols antigen jejunal epithelial cells iron-induced lung LC PUFAs fish-oil lipid emulsions cardiac Coxsackievirus B triceps plasma oxygen NG tube Vitamin C anti-inflammatory (258, 260) , a Tibet parvovirus B19 Coxsackievirus sections COVID-19 (113) TFRC HQ RBC H1N1 influenza oral chloroquine Congo patients nucleotide high-dose Plasma 25-hydroxyvitamin D ∼80 Guo intravenous sodium selenite E selenium blood glucose Enteral renal mouse rituximab (126)-and ≥50 y skeletal muscle green tea pulmonary tissue friends thrombomodulin (187) FOLEs resolvins epithelial hydrocortisone extract 30:70 SARS-CoV-2 papain-like protease 2774 participants Philippines zinc sulfate airways multivitamin-mineral Oral Parenteral hydrogen peroxide cardiovascular anorexia Coxsackievirus B3 minerals antioxidants COVID-19 (331) angiotensin-converting enzyme 2 human Wang UK Biobank 4 tocotrienols −0.44 host-viral metformin Transferrin Receptor vitamin A intestinal tracts cachexia Fatty acids glutathione human erythropoietin cathelicidins nasogastric (NG) tube. influenza A(H3N2) virus strain CD4 inflammatory-type eicosanoids cancers cell membranes LC PUFAs desaturase arachidonic acid measles (166) Selenium lipid Guatemala −2 z scores IgG1 poliovirus her mice CRP SARS-CoV-2 extracellular Vitamin D DHA maresins (257) hepcidin thioredoxin reductases macrophages ω-3 Vitamin C Landscape ribonucleotide reductase NRI-2002 25(OH)D serum vitamin A ≥200 vitamins C measles VDD CQ/HQ multiple-organ Parvovirus B19 C vitamins A endothelial COVID-19 risk factor (126 SARS-CoV2 virus SARS-CoV-2 (314) human selenoproteins lung steroids glutamine muscle mass/sarcopenia uric acid Liu (292) report a general systematic review of nutrition and IL-6 guinea pigs thiamin cellular iron Beck's extracellular zinc organ SPMs Iron vitamin D receptor ≥55 y B-cell epithelial tissue humans N-acetyl cysteine PubMed calcium acute-phase immune responses vitamins vitamin E hemoglobin transferrin receptor red wine transferrin 2-3 bottles Fat-to-carbohydrate omega-3 fatty acids high-dose vitamin A Vitamin E VDR IL-10 high-dose intravenous vitamin C sickle cell endosomal blood oxygen COVID-19 (214) coronavirus intravenously lymphoproliferative enveloped-virus glutathione reductases airway surface ∼750 cell membrane proinflammatory T-helper type 1 Vegetable oils intravenous vitamin C Wuhan cancer participants H3N2 viruses Nonmalarial · gut-barrier micronutrients individuals whey mucosal immune sulfur platelets COVID-19 severe/critical disease monocyte/macrophage aspirin human metapneumovirus rhEPO serum iron EPA-derived eicosanoids intravenous cells natural killer cells bowel children ferritin HbA1c feces taste olive oil gastrointestinal SARS-CoV viruses; Austria (123) COVID-19 CQ Human enteric CoV NF-κB (260) hepatitis A enteral vitamin People membrane PUFAs epithelial cells EPA LMICs CoV rotavirus COVID-19 patients ≥65 y in SARS-CoV-2 (313) paracetamol coronaviruses fish oils intracellular vegans/vegetarians COVID-19 (194) (195) (196) (197) ACE2 D'Avolio people [204] [205] [206] immune cells intravenous FOLE PubMed/EMBASE insulin Tsat Hydrocortisone post-gastroenteritis Beck Patient bronchial epithelium heart multivitamins macrophage gut Thiamine human viral infections ≥40 vitamin D liver erythroid 39.99 glucose-lowering oral human body hepatic disease Cancelled nonmalarial D ∼2000 Human retinol Iddir fetal −2 macrophage iron vegetables coronavirus disease 2019 iron (124) . muscle 1-3 neutrophils high-dose fish oil cell ascorbic acid PPE Vascular vitamin C/d intravenous high-dose HIV-1 high-dose vitamin C (183 IDA Lockdown villous Intravenous RBCs LC C The Author(s) 2021 iron quercetin MNA-sf blood ACE women men eicosanoids azithromycin PN SARS-CoV-2 virus tissues RTIs enteral Palaiodimos tracheal lymphocyte vitamin E-deficient mice Bone marrow PUFAs cheek serum retinol survivors vitamin B-12 supplementary vitamin E France DM nuts COVID-19 polymerase chain ∼6.5 heme lactose serum ferritin vaccine Coxsackie B3 C, D host-SARS-CoV-2 COVID- 19 7 B vitamins vitamin C tissue iron carotenoids nutrition-management hydrops fetalis intestinal lymphocyte hydroxychloroquine marrow cellular Metformin T cells Patients immunoglobulin thioredoxin ebselen intracellular lysosomes vitamin Vitamin A COVID- 19 13 intravenous immunoglobulin neutrophil follows-AMP
Extracted Text Content in Record: First 5000 Characters:Background: Many nutrients have powerful immunomodulatory actions with the potential to alter susceptibility to coronavirus disease 2019 infection, progression to symptoms, likelihood of severe disease, and survival. 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. 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. 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. J Nutr 2021;00:1-25. We considered all populations of any sex, age, or nutritional status, with no specific geographic boundaries. We restricted the systematic searches to human populations and studies in English. All original research was considered, without restriction to study design. Systematic reviews were included to search bibliographies. We excluded comments, letters, opinions, and nonsystematic reviews. Main outcomes for disease susceptibility were related to key concepts such as immunosuppression, inflammation, lymphocyte regulation, oxidative stress, and all forms of immune dysfunction. Main outcomes for disease progression related to viral load, viral replication, viral mutation, and transmission; worsening of respiratory tract and gastrointestinal infections; multiple organ failure; and other pathological features on disease progression to death. As the potential role of nutrition in disease susceptibility and progression is broad, we did not prespecify the measures of effect to consider. Instead, we report the measures of effect that the authors have used in the eligible studies. A lead and co-author were assigned to each of the 13 nutrition-related sections of the review. The 2 researchers then performed the PubMed and EMBASE searches for their section. After abstract screening, full texts were retrieved for the potentially eligible studies. The lead author then reviewed these studies and used a standardized template to extract 2 James et al. Landscape review. Protein-energy malnutrition (PEM), also called protein-energy undernutrition or simply "undernutrition," is a state of nutritional insufficiency attributable to inadequate energy and/or protein intake and is often associated with multiple A systematic review of nutrition and COVID-19 3 The astonishing spread of severe acute respiratory syndrome coronavirus (CoV) 2 (SARS-CoV-2) since late 2019 has resulted in a global pandemic of the coronavirus disease 2019 . Alongside the worldwide effort to deliver a vaccine, there has been a surge of interest in the epidemiological factors that underlie susceptibility to COVID-19, and its progression, in an attempt to explore the most effective preventative and curative options (1) (2) (3) (4) . Potential interactions between nutritional status and immune function have been widely documented (5) (6) (7) . As the pandemic unfolds, it exacerbates the C The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com Manuscript received November 3, 2020. Initial review completed December 22, 2020. Revision accepted February 17, 2021. First published online 0, 2021; doi: https://doi.org/10.1093/jn/nxab059. 1 risk factors for malnutrition in all its forms (8, 9) . Disrup
Keywords Extracted from PMC Text: survivors SARS-CoV coronavirus thrombomodulin (187) women 39.99 cathelicidins H3N2 viruses intracellular Coxsackievirus B3 vitamins Coxsackie B3 vitamin D receptor hemoglobin Human enteric CoV Thiamine intravenous her IL-10 selenium-enriched fertilizers lactose Bone marrow B-cell tissues 2774 participants RTIs hydrocortisone thioredoxin reductases tracheal Palaiodimos E B thiamin neutrophil COVID-19 (331) human vegans/vegetarians COVID-19 patients CQ/HQ whey insulin lung CRP moderate-dose vitamin C coronaviruses measles (166) nutrition-management muscle mass/sarcopenia Nonmalarial humans supplementary vitamin E ω-3 PUFA liver CQ 4 tocotrienols −0.44 gut 23–60 vitamin C PubMed/EMBASE anti-inflammatory (258, 260), a Coxsackievirus B " vitamin D vegetables People SPMs oral VDR parvovirus B19 human viral infections Parenteral Guo HIV-1 SARS-CoV2 virus Tibet high-dose vitamin C (183 Philippines glucose N-acetyl ferritin extract PubMed SARS-CoV-2 (313) vitamin E immune cells intracellular lysosomes vitamins C SARS-CoV viruses; blood hydrops fetalis COVID-19 (214) cellular high-dose Beck intravenous sodium selenite " extracellular azithromycin Vitamin C Cancelled ACE Enteral feces multivitamins cardiac lymphoproliferative lymphocyte serum ferritin human metapneumovirus COVID-19 risk factor (126 renal France Coxsackievirus resolvins lipid −5.40 Langlois macrophages poliovirus cancers epithelial tissue ∼750 25(OH)D Iron MNA-sf intestinal lymphocyte influenza A(H3N2) virus strain guinea pigs albumin SARS-CoV-2 inpatients arterial oxygen COVID-19 LC children inflammatory-type eicosanoids SARS-CoV-2 (314) jejunal epithelial cells HbA1c ≥200 villous airways gut-barrier enterocytes PN Congo acute-phase immune responses fish-oil plasma Dushianthan bone marrow red wine HQ soils transferrin intravenous vitamin C neutrophils VDD Wang non–COVID-19 vitamin A host–virus C RBCs Vascular triceps platelets hepcidin Parvovirus B19 hepatitis A carotenoids enteral vitamin enveloped-virus human body; 2 organ high-dose intravenous vitamin C −2 COVID-19 (113) glucose-lowering ACE2 IgG1 cachexia intravenous immunoglobulin COVID‐19 CoV blood glucose fish oils TFRC IL-6 ribonucleotide reductase ≥50 y COVID-19 polymerase chain green tea Tsat" COVID-19–positive SARS-CoV-2 papain-like protease Vitamin D enteral Human rituximab anorexia CD4 uric acid cell membranes LC PUFAs transferrin receptor men immunoglobulin hydrogen peroxide membrane PUFAs human erythropoietin glutathione post-gastroenteritis individuals COVID-19–induced gastrointestinal antigen human body epithelial cells ARDS-type bowel sections vitamin D– taste participants ≥55 y T cells glutathione reductases PaO2-to-FiO2 sickle cell rotavirus hepatic disease pulmonary tissue iron Vitamin A Beck's LC PUFAs cellular iron Liu (292) report a general systematic review of nutrition and 5–7 73–81 micronutrients olive oil nuts cancer 194–197 EPA endosomal macrophage iron Selenium DM hepatic acute-phase serum iron erythroid prespecify Fatty acids coronavirus disease 2019 metformin vitamin C/d fetal Austria (123) heart intravenously enteral ω-3 heme cell 895.5 FOLEs aspirin marrow eicosanoids fish-oil lipid emulsions leukocyte iron airway surface gastrointestinal people 276–278 Lockdown COVID-19 severe/critical disease Hydrocortisone monocyte/macrophage paracetamol high-dose fish oil nonmalarial maresins (257) Patients PPE skeletal muscle human selenoproteins proinflammatory T-helper type 1 patient rhEPO COVID-19 patients ≥65 y in intestinal tracts multivitamin-mineral epithelial Plasma 25-hydroxyvitamin D B vitamins cell membrane desaturase cells Intravenous serum retinol bronchial epithelium sulfur preprint sections iron— measles protectins extracellular zinc NRI-2002 intravenous high-dose oral chloroquine cardiovascular measles mortality—20 NG tube UK Biobank quercetin acute-phase Wuhan selenium Vegetable oils retinol mice ω-3 macrophage vitamin D–metabolizing ≥40 PUFAs Metformin steroids DHA muscle mouse EPA-derived eicosanoids angiotensin-converting enzyme 2 ∼80 high-dose vitamin A cheek friends ascorbic acid thioredoxin −5.91 oxygen vitamin B-12 ebselen ∼2000 body calcium arachidonic acid Patient tissue glutamine patients hydroxychloroquine Guatemala RBC nucleotide IDA H1N1 influenza omega-3 fatty acids ∼6.5 iron (124). blood oxygen D'Avolio NF-κB (260) Vitamin E serum vitamin A Long-chain −2 z scores IL-2 very-high-dose supplements N-acetyl cysteine multiple-organ 348,598 minerals vitamins A natural killer cells Transferrin Receptor gene(TFRC LMICs endothelial parenteral intravenous FOLE vitamin D
Extracted PMC Text Content in Record: First 5000 Characters:The astonishing spread of severe acute respiratory syndrome coronavirus (CoV) 2 (SARS-CoV-2) since late 2019 has resulted in a global pandemic of the coronavirus disease 2019 (COVID-19). Alongside the worldwide effort to deliver a vaccine, there has been a surge of interest in the epidemiological factors that underlie susceptibility to COVID-19, and its progression, in an attempt to explore the most effective preventative and curative options (1–4). Potential interactions between nutritional status and immune function have been widely documented (5–7). As the pandemic unfolds, it exacerbates the risk factors for malnutrition in all its forms (8, 9). Disruption to agricultural production, market linkages, and seasonal labor movements contribute to food price increases (10, 11), making nutritious food even more expensive for those most at risk of micronutrient deficiencies and undernutrition. Cancelled and delayed nutrition counseling, micronutrient distributions, vaccine rounds, and school meal programs accentuate the vulnerability (12–14). Lockdown measures in many countries have increased physical and psychological barriers to healthy eating and exercising, creating an obesogenic environment for many (15, 16). Understanding the relation between nutritional status and risk of COVID-19 is therefore of critical importance to generate evidence-based recommendations. There may be a potential for nutritional interventions to reduce an individual's susceptibility to infection, progression to symptoms, and likelihood of severe disease (including the use of high- or very-high-dose supplements enterally or intravenously as nutraceuticals). However, nutrition information has long been miscommunicated to the public (17–19), and nutrition-related myths on COVID-19 protection and treatment are widely prevalent in this pandemic (20). To this end, we have conducted a comprehensive systematic review of journal articles, preprints, and clinical trial registries to provide a robust evidence base of what is currently known and what gaps remain. We adopted 3 key approaches for compiling information for each of the 13 sections listed above, as follows: For the PubMed and EMBASE database searches, a search string was designed to encompass terms related to the following: 1) SARS-CoV-2, Middle East respiratory syndrome CoV (MERS-CoV), or SARS-CoV viruses; 2) disease susceptibility; 3) disease progression; and 4) the nutritional component of interest. The search string was then built combining the terms for 1 AND (2 OR 3) AND 4. The search string corresponding to components 1–3 was kept consistent between all sections, with component 4 being adapted to the relevant exposure of interest. The clinical trial registry and preprint server searches were restricted to COVID-19. Full search string terms for the PubMed, EMBASE, preprint server, and clinical trial registry searches are provided in Supplemental Material 2. In the landscape reviews we summarized the insights learned from other viral diseases, where relevant, and included other coronaviruses (MERS-CoV and SARS-CoV) in the systematic searches. From the outset we acknowledge that COVID-19 is behaving differently to other viral diseases, and therefore cautiously extrapolate risk throughout the review. We considered all populations of any sex, age, or nutritional status, with no specific geographic boundaries. We restricted the systematic searches to human populations and studies in English. All original research was considered, without restriction to study design. Systematic reviews were included to search bibliographies. We excluded comments, letters, opinions, and nonsystematic reviews. Main outcomes for disease susceptibility were related to key concepts such as immunosuppression, inflammation, lymphocyte regulation, oxidative stress, and all forms of immune dysfunction. Main outcomes for disease progression related to viral load, viral replication, viral mutation, and transmission; worsening of respiratory tract and gastrointestinal infections; multiple organ failure; and other pathological features on disease progression to death. As the potential role of nutrition in disease susceptibility and progression is broad, we did not prespecify the measures of effect to consider. Instead, we report the measures of effect that the authors have used in the eligible studies. A lead and co-author were assigned to each of the 13 nutrition-related sections of the review. The 2 researchers then performed the PubMed and EMBASE searches for their section. After abstract screening, full texts were retrieved for the potentially eligible studies. The lead author then reviewed these studies and used a standardized template to extract data on the eligible studies. A team of 2 researchers searched and abstract-screened all the preprint servers listed in Supplemental Material 1 for all 13 sections. They exported potentially eligible matches to the lead author of the relevant section for the full sc
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