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      Vitamin D deficiency as a predictor of poor prognosis in patients with acute respiratory failure due to COVID-19

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          Abstract

          Purpose

          Hypovitaminosis D is a highly spread condition correlated with increased risk of respiratory tract infections. Nowadays, the world is in the grip of the Coronavirus disease 19 (COVID 19) pandemic. In these patients, cytokine storm is associated with disease severity. In consideration of the role of vitamin D in the immune system, aim of this study was to analyse vitamin D levels in patients with acute respiratory failure due to COVID-19 and to assess any correlations with disease severity and prognosis.

          Methods

          In this retrospective, observational study, we analysed demographic, clinical and laboratory data of 42 patients with acute respiratory failure due to COVID-19, treated in Respiratory Intermediate Care Unit (RICU) of the Policlinic of Bari from March, 11 to April 30, 2020.

          Results

          Eighty one percent of patients had hypovitaminosis D. Based on vitamin D levels, the population was stratified into four groups: no hypovitaminosis D, insufficiency, moderate deficiency, and severe deficiency. No differences regarding demographic and clinical characteristics were found. A survival analysis highlighted that, after 10 days of hospitalization, severe vitamin D deficiency patients had a 50% mortality probability, while those with vitamin D ≥ 10 ng/mL had a 5% mortality risk ( p = 0.019).

          Conclusions

          High prevalence of hypovitaminosis D was found in COVID-19 patients with acute respiratory failure, treated in a RICU. Patients with severe vitamin D deficiency had a significantly higher mortality risk. Severe vitamin D deficiency may be a marker of poor prognosis in these patients, suggesting that adjunctive treatment might improve disease outcomes.

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

          Chaolin Huang, Yeming Wang, Xingwang Li … (2020)
          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 course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study

            Xiaobo Yang, Yuan Yu, Jiqian Xu … (2020)
            Summary Background An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in December, 2019, in Wuhan, China. Information about critically ill patients with SARS-CoV-2 infection is scarce. We aimed to describe the clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia. Methods In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between survivors and non-survivors. The primary outcome was 28-day mortality, as of Feb 9, 2020. Secondary outcomes included incidence of SARS-CoV-2-related acute respiratory distress syndrome (ARDS) and the proportion of patients requiring mechanical ventilation. Findings Of 710 patients with SARS-CoV-2 pneumonia, 52 critically ill adult patients were included. The mean age of the 52 patients was 59·7 (SD 13·3) years, 35 (67%) were men, 21 (40%) had chronic illness, 51 (98%) had fever. 32 (61·5%) patients had died at 28 days, and the median duration from admission to the intensive care unit (ICU) to death was 7 (IQR 3–11) days for non-survivors. Compared with survivors, non-survivors were older (64·6 years [11·2] vs 51·9 years [12·9]), more likely to develop ARDS (26 [81%] patients vs 9 [45%] patients), and more likely to receive mechanical ventilation (30 [94%] patients vs 7 [35%] patients), either invasively or non-invasively. Most patients had organ function damage, including 35 (67%) with ARDS, 15 (29%) with acute kidney injury, 12 (23%) with cardiac injury, 15 (29%) with liver dysfunction, and one (2%) with pneumothorax. 37 (71%) patients required mechanical ventilation. Hospital-acquired infection occurred in seven (13·5%) patients. Interpretation The mortality of critically ill patients with SARS-CoV-2 pneumonia is considerable. The survival time of the non-survivors is likely to be within 1–2 weeks after ICU admission. Older patients (>65 years) with comorbidities and ARDS are at increased risk of death. The severity of SARS-CoV-2 pneumonia poses great strain on critical care resources in hospitals, especially if they are not adequately staffed or resourced. Funding None.
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              Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths

              William Grant, Henry Lahore, Sharon McDonnell … (2020)
              The world is in the grip of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing the risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increasing concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced the risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D (25(OH)D) concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome; and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce the risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/mL (100–150 nmol/L). For treatment of people who become infected with COVID-19, higher vitamin D3 doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.
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                Author and article information

                Contributors
                G. E. Carpagnano: elisiana.carpagnano@uniba.it
                V. Di Lecce: valentina.dilecce89@gmail.com
                V. N. Quaranta: vitalianonicola.40@gmail.com
                A. Zito: annapaolazito@yahoo.it
                E. Buonamico:
                ORCID: http://orcid.org/0000-0001-6348-1356
                enricobuonamico@gmail.com
                E. Capozza: elena.capozza@gmail.com
                A. Palumbo: alessandro.palumbo@policlinico.ba.it
                G. Di Gioia: giusdigioia@libero.it
                V. N. Valerio: vnvale@tiscali.it
                O. Resta: onofrio.resta@uniba.it
                Journal
                Journal ID (nlm-ta): J Endocrinol Invest
                Journal ID (iso-abbrev): J. Endocrinol. Invest
                Title: Journal of Endocrinological Investigation
                Publisher: Springer International Publishing (Cham )
                ISSN (Print): 0391-4097
                ISSN (Electronic): 1720-8386
                Publication date (Electronic): 9 August 2020
                Publication date PMC-release: 9 August 2020
                Pages: 1-7
                Affiliations
                [1 ]GRID grid.7644.1, ISNI 0000 0001 0120 3326, Institute of Respiratory Disease, Department of Basic Medical Science, Neuroscience, and Sense Organs, , University of Bari “Aldo Moro”, ; piazza Giulio Cesare 11, 70125 Bari, Italy
                [2 ]Pneumology Department, “Di Venere” Hospital Bari, Bari, Italy
                [3 ]Cardiology Department, “SS Annunziata” Hospital, Taranto, Italy
                Author information
                http://orcid.org/0000-0001-6348-1356
                Article
                Publisher ID: 1370
                DOI: 10.1007/s40618-020-01370-x
                PMC ID: 7415009
                PubMed ID: 32772324
                SO-VID: d132d3fe-e565-4e27-bf9a-b6d888729987
                Copyright © © The Author(s) 2020
                License:

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                Date received : 7 June 2020
                Date accepted : 18 July 2020
                Categories
                Subject: Original Article

                Keywords: covid-19,vitamin d deficiency,acute respiratory failure,mortality risk
                Data availability:
                Keywords: covid-19, vitamin d deficiency, acute respiratory failure, mortality risk

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