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      Altered Lipid Metabolism in Recovered SARS Patients Twelve Years after Infection

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          Abstract

          Severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-like coronavirus are a potential threat to global health. However, reviews of the long-term effects of clinical treatments in SARS patients are lacking. Here a total of 25 recovered SARS patients were recruited 12 years after infection. Clinical questionnaire responses and examination findings indicated that the patients had experienced various diseases, including lung susceptibility to infections, tumors, cardiovascular disorders, and abnormal glucose metabolism. As compared to healthy controls, metabolomic analyses identified significant differences in the serum metabolomes of SARS survivors. The most significant metabolic disruptions were the comprehensive increase of phosphatidylinositol and lysophospha tidylinositol levels in recovered SARS patients, which coincided with the effect of methylprednisolone administration investigated further in the steroid treated non-SARS patients with severe pneumonia. These results suggested that high-dose pulses of methylprednisolone might cause long-term systemic damage associated with serum metabolic alterations. The present study provided information for an improved understanding of coronavirus-associated pathologies, which might permit further optimization of clinical treatments.

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          Characterization and complete genome sequence of a novel coronavirus, coronavirus HKU1, from patients with pneumonia.

          Despite extensive laboratory investigations in patients with respiratory tract infections, no microbiological cause can be identified in a significant proportion of patients. In the past 3 years, several novel respiratory viruses, including human metapneumovirus, severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), and human coronavirus NL63, were discovered. Here we report the discovery of another novel coronavirus, coronavirus HKU1 (CoV-HKU1), from a 71-year-old man with pneumonia who had just returned from Shenzhen, China. Quantitative reverse transcription-PCR showed that the amount of CoV-HKU1 RNA was 8.5 to 9.6 x 10(6) copies per ml in his nasopharyngeal aspirates (NPAs) during the first week of the illness and dropped progressively to undetectable levels in subsequent weeks. He developed increasing serum levels of specific antibodies against the recombinant nucleocapsid protein of CoV-HKU1, with immunoglobulin M (IgM) titers of 1:20, 1:40, and 1:80 and IgG titers of <1:1,000, 1:2,000, and 1:8,000 in the first, second and fourth weeks of the illness, respectively. Isolation of the virus by using various cell lines, mixed neuron-glia culture, and intracerebral inoculation of suckling mice was unsuccessful. The complete genome sequence of CoV-HKU1 is a 29,926-nucleotide, polyadenylated RNA, with G+C content of 32%, the lowest among all known coronaviruses with available genome sequence. Phylogenetic analysis reveals that CoV-HKU1 is a new group 2 coronavirus. Screening of 400 NPAs, negative for SARS-CoV, from patients with respiratory illness during the SARS period identified the presence of CoV-HKU1 RNA in an additional specimen, with a viral load of 1.13 x 10(6) copies per ml, from a 35-year-old woman with pneumonia. Our data support the existence of a novel group 2 coronavirus associated with pneumonia in humans.
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            Osteonecrosis of hip and knee in patients with severe acute respiratory syndrome treated with steroids.

            To evaluate whether there is a relationship between steroid treatment and risk for osteonecrosis of the hip and knee in patients with severe acute respiratory syndrome (SARS). The hospital ethics committee approved the study, and all patients provided written informed consent. A total of 254 patients with confirmed SARS treated with steroids underwent evaluation with magnetic resonance (MR) imaging for osteonecrosis. Clinical profiles, joint symptoms, relevant past medical and drug history, steroid dose, and radiographic and MR imaging evidence of osteonecrosis and other bone abnormalities were evaluated. Mann-Whitney, Kruskal-Wallis, and Pearson exact chi(2) tests were performed, and univariate and multivariate logistic regression analyses were applied. One hundred thirty-four (53%) of 254 patients had recent onset of large joint pain, but 211 (80%) of 264 painful joints were not associated with abnormality on MR images. MR images in 12 (5%) of 254 patients showed evidence of subchondral osteonecrosis in the proximal femur (n = 9), distal femur (n = 2), and proximal and distal femora and proximal tibiae (n = 1). Additional nonspecific subchondral and intramedullary bone marrow abnormalities were present in 77 (30%) of 254 patients. Results of multiple logistic regression analysis confirmed cumulative prednisolone-equivalent dose to be the most important risk factor for osteonecrosis. The risk of osteonecrosis was 0.6% for patients receiving less than 3 g and 13% for patients receiving more than 3 g prednisolone-equivalent dose. No relationship was found between additional nonspecific bone marrow abnormalities and steroid dose. An appreciable dose-related risk was found for osteonecrosis in patients receiving steroid therapy for SARS. Additional nonspecific bone marrow abnormalities were frequent. Joint pain was common after SARS infection and was not a useful clinical indicator of osteonecrosis. (c) RSNA, 2005.
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              Identification of New Respiratory Viruses in the New Millennium

              The rapid advancement of molecular tools in the past 15 years has allowed for the retrospective discovery of several new respiratory viruses as well as the characterization of novel emergent strains. The inability to characterize the etiological origins of respiratory conditions, particularly in children, led several researchers to pursue the discovery of the underlying etiology of disease. In 2001, this led to the discovery of human metapneumovirus (hMPV) and soon following that the outbreak of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) promoted an increased interest in coronavirology and the latter discovery of human coronavirus (HCoV) NL63 and HCoV-HKU1. Human bocavirus, with its four separate lineages, discovered in 2005, has been linked to acute respiratory tract infections and gastrointestinal complications. Middle East Respiratory Syndrome coronavirus (MERS-CoV) represents the most recent outbreak of a completely novel respiratory virus, which occurred in Saudi Arabia in 2012 and presents a significant threat to human health. This review will detail the most current clinical and epidemiological findings to all respiratory viruses discovered since 2001.
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                Author and article information

                Contributors
                xugw@dicp.ac.cn
                huaiyong.chen@foxmail.com
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                22 August 2017
                22 August 2017
                2017
                : 7
                : 9110
                Affiliations
                [1 ]ISNI 0000 0000 9792 1228, GRID grid.265021.2, Key Research Laboratory for Infectious Disease Prevention for State Administration of Traditional Chinese Medicine, , Tianjin Institute of Respiratory Diseases, Haihe Clinical College of Tianjin Medical University, ; Tianjin, China
                [2 ]ISNI 0000 0004 1793 300X, GRID grid.423905.9, CAS Key Laboratory of Separation Sciences for Analytical Chemistry, , Dalian Institute of Chemical Physics, Chinese Academy of Sciences, ; Dalian, 116023 China
                [3 ]GRID grid.417026.6, Department of Respiratory Medicine, , Tianjin Haihe Hospital, ; Tianjin, China
                [4 ]GRID grid.417026.6, Department of Nutrition, , Tianjin Haihe Hospital, ; Tianjin, China
                [5 ]GRID grid.417026.6, Department of Basic Medicine, , Tianjin Haihe Hospital, ; Tianjin, China
                [6 ]GRID grid.417026.6, Department of Gastroenterology, , Tianjin Haihe Hospital, ; Tianjin, China
                Author information
                http://orcid.org/0000-0003-4298-3554
                Article
                9536
                10.1038/s41598-017-09536-z
                5567209
                28831119
                ac87a529-7d05-483a-9aea-4e5ddaad5b7c
                © The Author(s) 2017

                Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 23 September 2016
                : 24 July 2017
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