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

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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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          Most cited references338

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Clinical Characteristics of Coronavirus Disease 2019 in China

            Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
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              Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

              Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
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                Author and article information

                Contributors
                Journal
                J Nutr
                J Nutr
                jn
                The Journal of Nutrition
                Oxford University Press
                0022-3166
                1541-6100
                19 May 2021
                : nxab059
                Affiliations
                Department of Population Health, London School of Hygiene & Tropical Medicine , London, United Kingdom
                Medical Research Council (MRC) Unit The Gambia at the London School of Hygiene & Tropical Medicine , Fajara, The Gambia
                MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford , Oxford, United Kingdom
                Medical Research Council (MRC) Unit The Gambia at the London School of Hygiene & Tropical Medicine , Fajara, The Gambia
                Medical Research Council (MRC) Unit The Gambia at the London School of Hygiene & Tropical Medicine , Fajara, The Gambia
                MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford , Oxford, United Kingdom
                Medical Research Council (MRC) Unit The Gambia at the London School of Hygiene & Tropical Medicine , Fajara, The Gambia
                National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) Nutritional Biomarker Laboratory, MRC Epidemiology Unit, University of Cambridge , Cambridge, United Kingdom
                Department of Population Health, London School of Hygiene & Tropical Medicine , London, United Kingdom
                Medical Research Council (MRC) Unit The Gambia at the London School of Hygiene & Tropical Medicine , Fajara, The Gambia
                Department of Women and Children's Health, King's College London , London, United Kingdom
                Department of Population Health, London School of Hygiene & Tropical Medicine , London, United Kingdom
                Department of International Public Health, Liverpool School of Tropical Medicine , Liverpool, United Kingdom
                Medical Research Council (MRC) Unit The Gambia at the London School of Hygiene & Tropical Medicine , Fajara, The Gambia
                Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research , Parkville, Australia
                Department of Medical Biology, The University of Melbourne , Parkville, Australia
                Department of Population Health, London School of Hygiene & Tropical Medicine , London, United Kingdom
                Centre on Climate Change and Planetary Health, London School of Hygiene & Tropical Medicine , London, United Kingdom
                MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine , London, United Kingdom
                MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford , Oxford, United Kingdom
                Medical Research Council (MRC) Unit The Gambia at the London School of Hygiene & Tropical Medicine , Fajara, The Gambia
                Author notes
                Address correspondence to AMP (e-mail: andrew.prentice@ 123456lshtm.ac.uk ).
                Author information
                https://orcid.org/0000-0001-5448-8193
                https://orcid.org/0000-0002-8129-2230
                https://orcid.org/0000-0001-5977-6602
                https://orcid.org/0000-0001-5981-762X
                https://orcid.org/0000-0002-7634-0955
                https://orcid.org/0000-0002-8503-6103
                https://orcid.org/0000-0001-5309-5611
                https://orcid.org/0000-0002-7380-9797
                https://orcid.org/0000-0003-4362-0261
                https://orcid.org/0000-0003-1650-3238
                https://orcid.org/0000-0002-8237-2021
                https://orcid.org/0000-0003-1056-729X
                https://orcid.org/0000-0002-7704-3629
                https://orcid.org/0000-0002-5502-0434
                https://orcid.org/0000-0002-6209-2284
                https://orcid.org/0000-0002-3852-9677
                https://orcid.org/0000-0002-8095-9961
                https://orcid.org/0000-0001-5389-451X
                Article
                nxab059
                10.1093/jn/nxab059
                8194602
                33982105
                3aea7886-9df3-47d4-8142-e5517ca158c2
                © The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.

                This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

                This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model ( https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

                History
                : 03 November 2020
                : 22 December 2020
                : 17 February 2021
                Page count
                Pages: 25
                Funding
                Funded by: Wellcome Trust, DOI 10.13039/100010269;
                Award ID: 216021/Z/19/Z
                Award ID: 220225/Z/20/Z
                Funded by: Wellcome, DOI 10.13039/100010269;
                Award ID: 203905
                Award ID: 216451/Z/19/Z
                Funded by: MRC, DOI 10.13039/501100000265;
                Award ID: MC_UU_12010/10
                Funded by: SEM, DOI 10.13039/100014281;
                Funded by: Medical Research Council, DOI 10.13039/501100000265;
                Award ID: MR/P012019/1
                Funded by: AMP, DOI 10.13039/100005411;
                Funded by: CC, DOI 10.13039/100010309;
                Funded by: Department for International Development, DOI 10.13039/501100000278;
                Award ID: MC-A760-5QX00
                Funded by: National Institute for Health Research, DOI 10.13039/501100000272;
                Award ID: IS-BRC-1215- 20014
                Funded by: NIHR, DOI 10.13039/100006662;
                Funded by: Cambridge University Hospitals, DOI 10.13039/501100002926;
                Funded by: University of Cambridge, DOI 10.13039/501100000735;
                Categories
                Nutrition and Disease
                AcademicSubjects/MED00060
                AcademicSubjects/SCI00960
                Custom metadata
                PAP

                Nutrition & Dietetics
                sars-cov-2,covid-19,nutrition,disease risk,disease progression,micronutrients,systematic review

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