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      Selenium Deficiency Is Associated with Mortality Risk from COVID-19

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          Abstract

          SARS-CoV-2 infections underlie the current coronavirus disease (COVID-19) pandemic and are causative for a high death toll particularly among elderly subjects and those with comorbidities. Selenium (Se) is an essential trace element of high importance for human health and particularly for a well-balanced immune response. The mortality risk from a severe disease like sepsis or polytrauma is inversely related to Se status. We hypothesized that this relation also applies to COVID-19. Serum samples ( n = 166) from COVID-19 patients ( n = 33) were collected consecutively and analyzed for total Se by X-ray fluorescence and selenoprotein P (SELENOP) by a validated ELISA. Both biomarkers showed the expected strong correlation ( r = 0.7758, p < 0.001), pointing to an insufficient Se availability for optimal selenoprotein expression. In comparison with reference data from a European cross-sectional analysis (EPIC, n = 1915), the patients showed a pronounced deficit in total serum Se (mean ± SD, 50.8 ± 15.7 vs. 84.4 ± 23.4 µg/L) and SELENOP (3.0 ± 1.4 vs. 4.3 ± 1.0 mg/L) concentrations. A Se status below the 2.5th percentile of the reference population, i.e., [Se] < 45.7 µg/L and [SELENOP] < 2.56 mg/L, was present in 43.4% and 39.2% of COVID samples, respectively. The Se status was significantly higher in samples from surviving COVID patients as compared with non-survivors (Se; 53.3 ± 16.2 vs. 40.8 ± 8.1 µg/L, SELENOP; 3.3 ± 1.3 vs. 2.1 ± 0.9 mg/L), recovering with time in survivors while remaining low or even declining in non-survivors. We conclude that Se status analysis in COVID patients provides diagnostic information. However, causality remains unknown due to the observational nature of this study. Nevertheless, the findings strengthen the notion of a relevant role of Se for COVID convalescence and support the discussion on adjuvant Se supplementation in severely diseased and Se-deficient patients.

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          Most cited references35

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          Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR

          Background The ongoing outbreak of the recently emerged novel coronavirus (2019-nCoV) poses a challenge for public health laboratories as virus isolates are unavailable while there is growing evidence that the outbreak is more widespread than initially thought, and international spread through travellers does already occur. Aim We aimed to develop and deploy robust diagnostic methodology for use in public health laboratory settings without having virus material available. Methods Here we present a validated diagnostic workflow for 2019-nCoV, its design relying on close genetic relatedness of 2019-nCoV with SARS coronavirus, making use of synthetic nucleic acid technology. Results The workflow reliably detects 2019-nCoV, and further discriminates 2019-nCoV from SARS-CoV. Through coordination between academic and public laboratories, we confirmed assay exclusivity based on 297 original clinical specimens containing a full spectrum of human respiratory viruses. Control material is made available through European Virus Archive – Global (EVAg), a European Union infrastructure project. Conclusion The present study demonstrates the enormous response capacity achieved through coordination of academic and public laboratories in national and European research networks.
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            Structure of Mpro from COVID-19 virus and discovery of its inhibitors

            A new coronavirus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the aetiological agent responsible for the 2019-2020 viral pneumonia outbreak of coronavirus disease 2019 (COVID-19)1-4. Currently, there are no targeted therapeutic agents for the treatment of this disease, and effective treatment options remain very limited. Here we describe the results of a programme that aimed to rapidly discover lead compounds for clinical use, by combining structure-assisted drug design, virtual drug screening and high-throughput screening. This programme focused on identifying drug leads that target main protease (Mpro) of SARS-CoV-2: Mpro is a key enzyme of coronaviruses and has a pivotal role in mediating viral replication and transcription, making it an attractive drug target for SARS-CoV-25,6. We identified a mechanism-based inhibitor (N3) by computer-aided drug design, and then determined the crystal structure of Mpro of SARS-CoV-2 in complex with this compound. Through a combination of structure-based virtual and high-throughput screening, we assayed more than 10,000 compounds-including approved drugs, drug candidates in clinical trials and other pharmacologically active compounds-as inhibitors of Mpro. Six of these compounds inhibited Mpro, showing half-maximal inhibitory concentration values that ranged from 0.67 to 21.4 μM. One of these compounds (ebselen) also exhibited promising antiviral activity in cell-based assays. Our results demonstrate the efficacy of our screening strategy, which can lead to the rapid discovery of drug leads with clinical potential in response to new infectious diseases for which no specific drugs or vaccines are available.
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              Comorbidity and its impact on 1590 patients with Covid-19 in China: A Nationwide Analysis

              Background The coronavirus disease 2019 (Covid-19) outbreak is evolving rapidly worldwide. Objective To evaluate the risk of serious adverse outcomes in patients with coronavirus disease 2019 (Covid-19) by stratifying the comorbidity status. Methods We analysed the data from 1590 laboratory-confirmed hospitalised patients 575 hospitals in 31 province/autonomous regions/provincial municipalities across mainland China between December 11th, 2019 and January 31st, 2020. We analyse the composite endpoints, which consisted of admission to intensive care unit, or invasive ventilation, or death. The risk of reaching to the composite endpoints was compared according to the presence and number of comorbidities. Results The mean age was 48.9 years. 686 patients (42.7%) were females. Severe cases accounted for 16.0% of the study population. 131 (8.2%) patients reached to the composite endpoints. 399 (25.1%) reported having at least one comorbidity. The most prevalent comorbidity was hypertension (16.9%), followed by diabetes (8.2%). 130 (8.2%) patients reported having two or more comorbidities. After adjusting for age and smoking status, COPD [hazards ratio (HR) 2.681, 95% confidence interval (95%CI) 1.424–5.048], diabetes (HR 1.59, 95%CI 1.03–2.45), hypertension (HR 1.58, 95%CI 1.07–2.32) and malignancy (HR 3.50, 95%CI 1.60–7.64) were risk factors of reaching to the composite endpoints. The HR was 1.79 (95%CI 1.16–2.77) among patients with at least one comorbidity and 2.59 (95%CI 1.61–4.17) among patients with two or more comorbidities. Conclusion Among laboratory-confirmed cases of Covid-19, patients with any comorbidity yielded poorer clinical outcomes than those without. A greater number of comorbidities also correlated with poorer clinical outcomes.

                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                16 July 2020
                July 2020
                : 12
                : 7
                : 2098
                Affiliations
                [1 ]ATORG, Aschaffenburg Trauma and Orthopedic Research Group, Center for Orthopedics, Trauma Surgery and Sports Medicine, Hospital Aschaffenburg-Alzenau, D-63739 Aschaffenburg, Germany; arash.moghaddam-alvandi@ 123456klinikum-ab-alz.de (A.M.); asan.cherkezov@ 123456stud-mail.uni-wuerzburg.de (A.C.); linda-glaab@ 123456t-online.de (L.S.); Joachim.Diegmann@ 123456klinikum-ab-alz.de (J.D.); manuel.bachmann.md@ 123456gmail.com (M.B.)
                [2 ]HTRG, Heidelberg Trauma Research Group, Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Heidelberg University Hospital, D-69118 Heidelberg, Germany; raban.heller@ 123456charite.de
                [3 ]Institute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, D-13353 Berlin, Germany; qian.sun@ 123456charite.de (Q.S.); julian.seelig@ 123456charite.de (J.S.); julian.hackler@ 123456charite.de (J.H.); petra.seemann@ 123456charite.de (P.S.); waldemar.minich@ 123456charite.de (W.B.M.)
                [4 ]Institute of Medical Biometry and Informatics, Heidelberg University Hospital, Im Neuenheimer Feld 130.3, D-69120 Heidelberg, Germany; pilz@ 123456imbi.uni-heidelberg.de
                Author notes
                [* ]Correspondence: lutz.schomburg@ 123456charite.de ; Tel.: +49-30-450524289; Fax: +49-30-450524922
                Author information
                https://orcid.org/0000-0001-8006-9742
                https://orcid.org/0000-0001-6081-2316
                https://orcid.org/0000-0002-9685-1613
                https://orcid.org/0000-0001-9445-1555
                Article
                nutrients-12-02098
                10.3390/nu12072098
                7400921
                32708526
                b9959cc3-e53a-4534-a37f-b8690bbacdff
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 05 July 2020
                : 12 July 2020
                Categories
                Article

                Nutrition & Dietetics
                trace element,inflammation,selenoprotein p,micronutrient,covid-19
                Nutrition & Dietetics
                trace element, inflammation, selenoprotein p, micronutrient, covid-19

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