43 results on '"Xu, Jiuyang"'
Search Results
2. 3-year outcomes of discharged survivors of COVID-19 following the SARS-CoV-2 omicron (B.1.1.529) wave in 2022 in China: a longitudinal cohort study
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Zhang, Hui, Huang, Chaolin, Gu, Xiaoying, Wang, Yeming, Li, Xia, Liu, Min, Wang, Qiongya, Xu, Jiuyang, Wang, Yimin, Dai, Huaping, Zhang, Dingyu, and Cao, Bin
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- 2024
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3. Mechanisms of long COVID: An updated review
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Liu, Yan, Gu, Xiaoying, Li, Haibo, Zhang, Hui, and Xu, Jiuyang
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- 2023
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4. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study
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Huang, Chaolin, Huang, Lixue, Wang, Yeming, Li, Xia, Ren, Lili, Gu, Xiaoying, Kang, Liang, Guo, Li, Liu, Min, Zhou, Xing, Luo, Jianfeng, Huang, Zhenghui, Tu, Shengjin, Zhao, Yue, Chen, Li, Xu, Decui, Li, Yanping, Li, Caihong, Peng, Lu, Li, Yong, Xie, Wuxiang, Cui, Dan, Shang, Lianhan, Fan, Guohui, Xu, Jiuyang, Wang, Geng, Wang, Ying, Zhong, Jingchuan, Wang, Chen, Wang, Jianwei, Zhang, Dingyu, and Cao, Bin
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- 2023
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5. 1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study
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Huang, Lixue, Yao, Qun, Gu, Xiaoying, Wang, Qiongya, Ren, Lili, Wang, Yeming, Hu, Ping, Guo, Li, Liu, Min, Xu, Jiuyang, Zhang, Xueyang, Qu, Yali, Fan, Yanqing, Li, Xia, Li, Caihong, Yu, Ting, Xia, Jiaan, Wei, Ming, Chen, Li, Li, Yanping, Xiao, Fan, Liu, Dan, Wang, Jianwei, Wang, Xianguang, and Cao, Bin
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- 2021
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6. Low-to-moderate dose corticosteroids treatment in hospitalized adults with COVID-19
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Liu, Zhibo, Li, Xia, Fan, Guohui, Zhou, Fei, Wang, Yeming, Huang, Lixue, Yu, Jiapei, Yang, Luning, Shang, Lianhan, Xie, Ke, Xu, Jiuyang, Huang, Zhisheng, Gu, Xiaoying, Li, Hui, Zhang, Yi, Wang, Yimin, Huang, Zhenghui, and Cao, Bin
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- 2021
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7. Use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in context of COVID-19 outbreak: a retrospective analysis
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Xu, Jiuyang, Huang, Chaolin, Fan, Guohui, Liu, Zhibo, Shang, Lianhan, Zhou, Fei, Wang, Yeming, Yu, Jiapei, Yang, Luning, Xie, Ke, Huang, Zhisheng, Huang, Lixue, Gu, Xiaoying, Li, Hui, Zhang, Yi, Wang, Yimin, Hayden, Frederick G., Horby, Peter W., Cao, Bin, and Wang, Chen
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- 2020
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8. Distinct roles for type I and type III interferons in virulent human metapneumovirus pathogenesis.
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Zhang, Yu, Xu, Jiuyang, Miranda-Katz, Margot, Sojati, Jorna, Tollefson, Sharon J., Manni, Michelle L., Alcorn, John F., Sarkar, Saumendra N., and Williams, John V.
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TYPE I interferons , *RESPIRATORY infections in children , *NEUTROPHILS , *PATHOGENESIS , *VIRAL replication , *WEIGHT loss - Abstract
Human metapneumovirus (HMPV) is an important cause of acute lower respiratory infection in children and adults worldwide. There are four genetic subgroups of HMPV and both neutralizing antibodies and T cells contribute to protection. However, little is known about mechanisms of pathogenesis and most published work is based on a few extensively passaged, laboratory-adapted strains of HMPV. In this study, we isolated and characterized a panel of low passage HMPV clinical isolates representing all four genetic subgroups. The clinical isolates exhibited lower levels of in vitro replication compared to a lab-adapted strain. We compared disease phenotypes using a well-established mouse model. Several virulent isolates caused severe weight loss, lung pathology, airway dysfunction, and fatal disease in mice, which was confirmed in three inbred mouse strains. Disease severity did not correlate with lung viral titer, as virulent strains exhibited restricted replication in the lower airway. Virulent HMPV isolates were associated with markedly increased proinflammatory cytokine production and neutrophil influx; however, depletion of neutrophils or genetic ablation of inflammasome components did not reverse disease. Virulent clinical isolates induced markedly increased type I and type III IFN (IFN) secretion in vitro and in vivo. STAT1/2-deficient mice lacking both type I and type III IFN signaling showed reduced disease severity and increased lung viral replication. Inhibition of type I IFN signaling using a blocking antibody or genetic ablation of the type I IFN receptor reduced pathology with minimal effect on viral replication. Conversely, blockade of type III IFN signaling with a neutralizing antibody or genetic ablation of the IFN-lambda receptor had no effect on pathogenesis but restored viral replication. Collectively, these results demonstrate distinct roles for type I and type III IFN in HMPV pathogenesis and immunity. Author summary: Human metapneumovirus (HMPV) is a leading cause of acute lower respiratory infection in children and adults worldwide. However, little is known about mechanisms of pathogenesis and most published studies use a few laboratory-adapted strains of HMPV. In this study, we isolated and characterized disease phenotypes of a panel of HMPV isolates. We identified several virulent isolates capable of causing severe and fatal disease in mice. Virulent HMPV isolates were associated with markedly increased proinflammatory cytokine production as well as increased type I and type III IFN (IFN) secretion in vitro and in vivo. Inhibition of type I IFN signaling reduced pathology with minimal effect on viral replication. Conversely, blockade or genetic ablation of type III IFN signaling had no effect on pathogenesis but restored viral replication. Collectively, these results demonstrate distinct roles for type I and type III IFN in HMPV defense and disease. [ABSTRACT FROM AUTHOR]
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- 2024
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9. Development and optimization of a direct plaque assay for trypsin-dependent human metapneumovirus strains
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Xu, Jiuyang, Zhang, Yu, and Williams, John V.
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- 2018
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10. Airway-invasion-associated pulmonary computed tomography presentations characteristic of invasive pulmonary Aspergillosis in non-immunocompromised adults: a National Multicenter Retrospective Survey in China
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Liu, Zhibo, Li, Yuping, Tian, Xinlun, Liu, Qinghua, Li, Erran, Gu, Xiaoying, Liu, Min, Xu, Jiuyang, He, Zhiyi, Huang, Yi, Xu, Shuyun, Lai, Guoxiang, Chen, Yusheng, Zhang, Xiangyan, Zhang, Tiantuo, Xu, Jinfu, Zhu, Lanyan, Qu, Jieming, and Cao, Bin
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- 2020
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11. Risk Factors of Viral RNAaemia and Its Association With Clinical Prognosis Among Patients With Severe Coronavirus Disease 2019
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Li, Hui, Gu, Xiaoying, Xu, Jiuyang, Wang, Yeming, Li, Haibo, Cao, Bin, Li, Huadong, Gong, Fengyun, Ruan, Shunan, and Yang, Qingyu
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Research Letter - Published
- 2021
12. Antibody Responses and Clinical Outcomes in Adults Hospitalized with Severe COVID-19: A Post hoc Analysis of LOTUS China Trial
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Ren, Lili, Fan, Guohui, Wu, Wenjuan, Guo, Li, Wang, Yeming, Li, Xia, Wang, Conghui, Gu, Xiaoying, Li, Caihong, Wang, Ying, Wang, Geng, Zhou, Fei, Liu, Zhibo, Ge, Qing, Zhang, Yi, Li, Hui, Zhang, Lulu, Xu, Jiuyang, Wang, Chen, Wang, Jianwei, and Cao, Bin
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Adult ,China ,LOTUS China ,dynamic changes ,SARS-CoV-2 ,neutralizing antibody ,severe COVID-19 ,COVID-19 ,Antibodies, Viral ,clinical outcomes ,AcademicSubjects/MED00290 ,Immunoglobulin M ,Antibody Formation ,Major Article ,Humans ,humoral response - Abstract
The characteristics of neutralizing antibodies (NAbs) and antibody against major antigen proteins related to clinical outcomes in severe coronavirus disease 2019 (COVID-19) patients were still less known.NAbs and antibodies targeting nucleocapsid (N), spike protein (S), and the receptor-binding domain (RBD) in longitudinal plasma samples from the LOTUS China trial were measured by microneutralization assay and enzyme-linked immunosorbent assay (ELISA). Viral load was determined by real-time reverse transcription polymerase chain reaction (RT-PCR). A total of 576 plasma and 576 throat swabs were collected from 191 COVID-19 patients. Antibody titers related to adverse outcome and clinical improvement were analyzed. Multivariable adjusted generalized linear mixed model for random effects were developed.After day 28 post symptoms onset, the rate of antibody positivity reached 100% for RBD-immunoglobulin M (IgM), 97.8% for S-IgM, 100% for N-immunoglobulin G (IgG), 100% for RBD-IgG, 91.1% for N-IgM, and 91.1% for NAbs. The NAbs titers increased over time in both survivors and nonsurvivors and correlated to IgG antibodies against N, S, and RBD, whereas its presence showed no statistical correlation with death. N-IgG (slope -2.11, 95% confidence interval [CI] -3.04 to -1.18, P.0001), S-IgG (slope -2.44, 95% CI -3.35 to -1.54, P.0001), and RBD-IgG (slope -1.43, 95% CI -1.98 to -.88, P.0001) were negatively correlated with viral load. S-IgG titers were lower in nonsurvivors than survivors (P = .020) at week 4 after symptoms onset.IgM and IgG against N, S, and RBD and NAbs developed in most severe COVID-19 patients and do not correlate clearly with clinical outcomes. The levels of IgG antibodies against N, S, and RBD were related to viral clearance.
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- 2020
13. Appropriate use of antimicrobials in primary healthcare facility: a long way to go
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Xu, Jiuyang and Cao, Bin
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- 2023
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14. Cross-reactive antibody against human coronavirus OC43 spike protein correlates with disease severity in COVID-19 patients: a retrospective study.
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Guo, Li, Wang, Yeming, Kang, Liang, Hu, Yongfeng, Wang, Linghang, Zhong, Jingchuan, Chen, Hong, Ren, Lili, Gu, Xiaoying, Wang, Geng, Wang, Conghui, Dong, Xiaojing, Wu, Chao, Han, Lianlian, Wang, Ying, Fan, Guohui, Zou, Xiaohui, Li, Haibo, Xu, Jiuyang, and Jin, Qi
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- 2021
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15. The Effect of Prior Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Treatment on Coronavirus Disease 2019 (COVID-19) Susceptibility and Outcome: A Systematic Review and Meta-analysis.
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Xu, Jiuyang, Teng, Yaqun, Shang, Lianhan, Gu, Xiaoying, Fan, Guohui, Chen, Yijun, Tian, Ran, Zhang, Shuyang, and Cao, Bin
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COVID-19 , *META-analysis , *CONFIDENCE intervals , *SYSTEMATIC reviews , *ACE inhibitors , *SEVERITY of illness index , *RISK assessment , *TREATMENT effectiveness , *DISEASE susceptibility , *ANGIOTENSIN receptors - Abstract
There have been arguments on whether angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) treatment alters the risk of coronavirus disease 2019 (COVID-19) susceptibility and disease severity. We identified a total of 102 eligible studies for systematic review, in which 49 studies adjusting for confounders were included in the meta-analysis. We found no association between prior ACEI/ARB use and risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the general population (adjusted odds ratio [aOR], 1.00; 95% confidence interval [CI],.94–1.05). The risk of mortality (aOR,.87; 95% CI,.66–1.04) and severe outcomes (aOR,.95; 95% CI,.73–1.24) were also unchanged among COVID-19 patients taking ACEIs/ARBs. These findings remained consistent in subgroup analyses stratified by populations, drug exposures, and other secondary outcomes. This systematic review provides evidence-based support to current medical guidelines and position statements that ACEIs/ARBs should not be discontinued. Additionally, there has been no evidence for initiating ACEI/ARB regimen as prevention or treatment of COVID-19. [ABSTRACT FROM AUTHOR]
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- 2021
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16. Antibody Responses and Clinical Outcomes in Adults Hospitalized With Severe Coronavirus Disease 2019 (COVID-19): A Post hoc Analysis of LOTUS China Trial.
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Ren, Lili, Fan, Guohui, Wu, Wenjuan, Guo, Li, Wang, Yeming, Li, Xia, Wang, Conghui, Gu, Xiaoying, Li, Caihong, Wang, Ying, Wang, Geng, Zhou, Fei, Liu, Zhibo, Ge, Qing, Zhang, Yi, Li, Hui, Zhang, Lulu, Xu, Jiuyang, Wang, Chen, and Wang, Jianwei
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REVERSE transcriptase polymerase chain reaction ,STATISTICS ,COVID-19 ,IMMUNOGLOBULINS ,VIRAL load ,TREATMENT effectiveness ,HOSPITAL care ,ENZYME-linked immunosorbent assay ,VIRAL antibodies ,POLYMERASE chain reaction ,DATA analysis - Abstract
Background The characteristics of neutralizing antibodies (NAbs) and antibody against major antigen proteins related to clinical outcomes in severe coronavirus disease 2019 (COVID-19) patients were still less known. Methods NAbs and antibodies targeting nucleocapsid (N), spike protein (S), and the receptor-binding domain (RBD) in longitudinal plasma samples from the LOTUS China trial were measured by microneutralization assay and enzyme-linked immunosorbent assay (ELISA). Viral load was determined by real-time reverse transcription polymerase chain reaction (RT-PCR). A total of 576 plasma and 576 throat swabs were collected from 191 COVID-19 patients. Antibody titers related to adverse outcome and clinical improvement were analyzed. Multivariable adjusted generalized linear mixed model for random effects were developed. Results After day 28 post symptoms onset, the rate of antibody positivity reached 100% for RBD-immunoglobulin M (IgM), 97.8% for S-IgM, 100% for N-immunoglobulin G (IgG), 100% for RBD-IgG, 91.1% for N-IgM, and 91.1% for NAbs. The NAbs titers increased over time in both survivors and nonsurvivors and correlated to IgG antibodies against N, S, and RBD, whereas its presence showed no statistical correlation with death. N-IgG (slope −2.11, 95% confidence interval [CI] −3.04 to −1.18, P <.0001), S-IgG (slope −2.44, 95% CI −3.35 to −1.54, P <.0001), and RBD-IgG (slope −1.43, 95% CI −1.98 to −.88, P <.0001) were negatively correlated with viral load. S-IgG titers were lower in nonsurvivors than survivors (P =.020) at week 4 after symptoms onset. Conclusions IgM and IgG against N, S, and RBD and NAbs developed in most severe COVID-19 patients and do not correlate clearly with clinical outcomes. The levels of IgG antibodies against N, S, and RBD were related to viral clearance. [ABSTRACT FROM AUTHOR]
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- 2021
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17. Risk Factors of Viral RNAaemia and Its Association With Clinical Prognosis Among Patients With Severe COVID-19.
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Li, Hui, Gu, Xiaoying, Li, Huadong, Gong, Fengyun, Xu, Jiuyang, Wang, Yeming, Li, Haibo, Ruan, Shunan, Yang, Qingyu, and Cao, Bin
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COVID-19 ,PROGNOSIS ,PATIENTS - Published
- 2021
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18. Influenza Virus in Community-Acquired Pneumonia: Current Understanding and Knowledge Gaps.
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Xu, Jiuyang, Yu, Jiapei, Yang, Luning, Zhou, Fei, Li, Hui, and Cao, Bin
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COMMUNITY-acquired pneumonia , *INFLUENZA A virus , *KNOWLEDGE gap theory , *COMMUNITY-acquired infections , *VIRUS diseases , *PATHOLOGY , *INFLUENZA , *INFLUENZA prevention , *VIRAL pneumonia , *INFLUENZA vaccines , *CLINICAL trials , *ANTIVIRAL agents , *DIFFERENTIAL diagnosis , *HEALTH attitudes , *EPIDEMICS , *MIXED infections - Abstract
Influenza virus infection poses a heavy burden on global health and economics. With the advancement in viral pathogen detection methods, the role of virus infection in community-acquired pneumonia has been increasingly recognized. The disease spectrum of influenza ranges from asymptomatic infection to severe or even fatal illness. Progress has been made in recent years to identify risk factors including lymphopenia and hypoxia for influenza mortality. Immunopathology plays an important role in influenza pathogenesis. The disturbed homeostasis after virus infection consists of both an excessive inflammatory phase and an immune suppression phase, collectively described as viral sepsis. Multiple antiviral therapies have been tested and some were advanced to late-phase clinical trials, including polymerase inhibitors, hemagglutinin inhibitors, host-acting antivirals, monoclonal antibodies, and adjunctive immunomodulatory therapies. Combination therapies have been shown to increase antiviral efficacy and genetic resistance barrier. In this review, we summarized the recent advances in our understanding of the disease pathogenesis, as well as the progress in antiviral therapy development. We also pointed out current key knowledge gaps in influenza research. Hopefully, experience gained from seasonal influenza research will prepare us for the next influenza pandemic and emerging respiratory pathogens. [ABSTRACT FROM AUTHOR]
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- 2020
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19. 2019 novel coronavirus outbreak: a quiz or final exam?
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Xu, Jiuyang, Chen, Yijun, Chen, Hao, and Cao, Bin
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The 2019 novel coronavirus (2019-nCoV) is an emerging pathogen and is threatening the global health. Strikingly, more than 28 000 cases and 550 deaths have been reported within two months from disease emergence. Armed with experience from previous epidemics in the last two decades, clinicians, scientists, officials, and citizens in China are all contributing to the prevention of further 2019-nCoV transmission. Efficient preliminary work has enabled us to understand the basic characteristics of 2019-nCoV, but there are still many unanswered questions. It is too early now to judge our performance in this outbreak. Continuous and strengthened efforts should be made not only during the epidemic, but also afterwards in order to prepare for any incoming challenges. [ABSTRACT FROM AUTHOR]
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- 2020
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20. Viral pneumonia in China: from surveillance to response
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Shang, Lianhan, Xu, Jiuyang, and Cao, Bin
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- 2020
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21. Guarding a city from the COVID-19 pandemic
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Xu, Jiuyang, Shang, Lianhan, and Cao, Bin
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- 2020
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22. A Novel Coronavirus (COVID-19) Outbreak: A Call for Action
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Zhang, Yi, Xu, Jiuyang, Li, Hui, and Cao, Bin
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- 2020
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23. Antibodies and vaccines against Middle East respiratory syndrome coronavirus.
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Xu, Jiuyang, Jia, Wenxu, Wang, Pengfei, Zhang, Senyan, Shi, Xuanling, Wang, Xinquan, and Zhang, Linqi
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- 2019
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24. Single intranasal immunization with chimpanzee adenovirus-based vaccine induces sustained and protective immunity against MERS-CoV infection.
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Jia, Wenxu, Channappanavar, Rudragouda, Zhang, Chao, Li, Mingxi, Zhou, Haixia, Zhang, Shuyuan, Zhou, Panpan, Xu, Jiuyang, Shan, Sisi, Shi, Xuanling, Wang, Xinquan, Zhao, Jincun, Zhou, Dongming, Perlman, Stanley, and Zhang, Linqi
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- 2019
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25. Letter from China: Managing the second‐wave COVID‐19 outbreak in Beijing.
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Xu, Jiuyang and Cao, Bin
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COVID-19 pandemic , *H7N9 Influenza , *COVID-19 - Abstract
Letter from China: Managing the second-wave COVID-19 outbreak in Beijing Keywords: China; coronavirus disease; COVID-19; SARS-CoV-2 EN China coronavirus disease COVID-19 SARS-CoV-2 275 276 2 02/20/21 20210301 NES 210301 The coronavirus 2019 (COVID-19) pandemic is circulating worldwide and threatening global health. Although COVID-19 community spread has been sporadic and remained low, the "war-time" for COVID-19 epidemic control in China seems to be continuing. [Extracted from the article]
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- 2021
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26. Response.
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Li, Hui, Xu, Jiuyang, and Cao, Bin
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- 2021
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27. 975. Roles of Type I and III Interferon in Severe Pathogenesis of Human Metapneumovirus.
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Williams, John V, Zhang, Yu, Xu, Jiuyang, Miranda-Katz, Margot, Rich, Helen, Manni, Michelle, Tollefson, Sharon, Sarkar, Saumendra, and Alcorn, John
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HUMAN metapneumovirus infection ,TYPE I interferons ,RESPIRATORY infections in children ,RESPIRATORY infections ,WEIGHT loss - Abstract
Background Human metapneumovirus (HMPV) is a leading cause of respiratory tract infection in children and adults. However, mechanisms of pathogenesis are not fully understood. Methods We tested HMPV clinical and laboratory isolates in an established C57BL/6 mouse model and measured weight loss, airway function, and viral titers. Immune responses were determined using cytokine quantitation and flow cytometry. Results HMPV clinical isolates induced variable disease severity ranging from mild to fatal disease. Laboratory strain TN/94-49 did not cause weight loss, but mice infected with clinical isolate C2-202 showed dramatic weight loss and 40% mortality within 5 days post-infection (Figure 1). These findings were confirmed in other inbred mouse strains. C2-202-infected mice also suffered from impaired pulmonary function post-recovery. Lung viral titer did not correlate with disease severity, suggesting immune-mediated pathogenesis. C2-202-infected mice exhibited increased production of type I and III interferons (IFN) and pro-inflammatory cytokines, and lung neutrophil infiltration. However, neutrophil depletion or inflammasome inactivation did not reduce disease. Stat1/Stat2 double knockout (KO) mice lacking type I and III IFN signaling exhibited reduced weight loss but increased lung viral titer after C2-202 infection (Figure 2). Type I IFN receptor (IFNAR) KO mice infected with C2-202 had reduced weight loss but unchanged lung viral titer (Figure 3), while the addition of type III IFN blockade to C2-202-infected IFNAR mice had no effect on disease but increased lung viral titer (Figure 4). Conclusion These results suggest that severe disease caused by virulent HMPV was due to exuberant IFN response. Moreover, type I IFN was primarily associated with disease, while type III IFN was associated with viral clearance. These data suggest that IFN signaling plays an important role in HMPV pathogenesis, and thus serves as a potential therapeutic target. Disclosures All Authors: No reported Disclosures. [ABSTRACT FROM AUTHOR]
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- 2019
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28. Development and optimization of a direct plaque assay for trypsin-dependent human metapneumovirus strains.
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Zhang, Yu, Williams, John V., and Xu, Jiuyang
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TRYPSIN , *HUMAN metapneumovirus infection , *RESPIRATORY infections , *PARAMYXOVIRUSES , *REVERSE transcriptase polymerase chain reaction , *RNA viruses - Abstract
Human metapneumovirus (HMPV) is a non-segmented, negative strand RNA virus belonging to the family Pneumoviridae , previously a subfamily of Paramyxoviridae . It is a leading cause of lower respiratory tract infection in infants, children, and adults with underlying medical conditions. HMPV grows poorly in cell culture and requires trypsin to cleave and mature the virus particles, which adds to the challenge of HMPV research. Currently, an indirect immuno-staining assay is commonly used to titrate HMPV, which is time-consuming and costly. In order to simplify virus quantification for HMPV, a direct plaque assay was developed. By optimizing trypsin concentration and other supplements in the agarose overlay, it was found that HMPV strains from all four subgroups formed clear and countable plaques 5–7 days post-infection. Animal tissue homogenate can also be directly titrated with this assay. Compared with the traditional assay, the direct plaque assay yields similar titer result, but saves time and eliminates the use of antibodies. Potentially, it can also be applied to plaque purification for HMPV clinical isolates. The direct plaque assay will be a valuable tool in HMPV research. [ABSTRACT FROM AUTHOR]
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- 2018
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29. Remdesivir and COVID-19 - Authors' reply.
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Wang, Yeming, Gu, Xiaoying, Xu, Jiuyang, Cao, Bin, and Wang, Chen
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- 2020
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30. SARS-CoV-2 and viral sepsis: observations and hypotheses.
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Li, Hui, Liu, Liang, Zhang, Dingyu, Xu, Jiuyang, Dai, Huaping, Tang, Nan, Su, Xiao, and Cao, Bin
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VIRAL pneumonia , *CYTOKINES , *ENDOTHELIUM , *LUNGS , *INFLAMMATION , *AUTOPSY , *COVID-19 , *SHOCK (Pathology) , *MACROPHAGES , *SEPSIS , *EPITHELIUM , *SEVERITY of illness index , *CATASTROPHIC illness , *EPIDEMICS , *BLOOD coagulation disorders , *DISEASE complications - Abstract
Since the outbreak of coronavirus disease 2019 (COVID-19), clinicians have tried every effort to understand the disease, and a brief portrait of its clinical features have been identified. In clinical practice, we noticed that many severe or critically ill COVID-19 patients developed typical clinical manifestations of shock, including cold extremities and weak peripheral pulses, even in the absence of overt hypotension. Understanding the mechanism of viral sepsis in COVID-19 is warranted for exploring better clinical care for these patients. With evidence collected from autopsy studies on COVID-19 and basic science research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV, we have put forward several hypotheses about SARS-CoV-2 pathogenesis after multiple rounds of discussion among basic science researchers, pathologists, and clinicians working on COVID-19. We hypothesise that a process called viral sepsis is crucial to the disease mechanism of COVID-19. Although these ideas might be proven imperfect or even wrong later, we believe they can provide inputs and guide directions for basic research at this moment. [ABSTRACT FROM AUTHOR]
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- 2020
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31. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.
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Zhou, Fei, Yu, Ting, Du, Ronghui, Fan, Guohui, Liu, Ying, Liu, Zhibo, Xiang, Jie, Wang, Yeming, Song, Bin, Gu, Xiaoying, Guan, Lulu, Wei, Yuan, Li, Hui, Wu, Xudong, Xu, Jiuyang, Tu, Shengjin, Zhang, Yi, Chen, Hua, and Cao, Bin
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COVID-19 , *AGE distribution , *CONFIDENCE intervals , *EPIDEMICS , *FISHER exact test , *LONGITUDINAL method , *MEDICAL cooperation , *MEDICAL records , *PROBABILITY theory , *RESEARCH , *RESEARCH funding , *COMORBIDITY , *LOGISTIC regression analysis , *RETROSPECTIVE studies , *DISEASE progression , *FIBRIN fibrinogen degradation products , *DESCRIPTIVE statistics , *HOSPITAL mortality , *LYMPHOCYTE count , *ACQUISITION of data methodology , *ODDS ratio , *MANN Whitney U Test - Abstract
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. [ABSTRACT FROM AUTHOR]- Published
- 2020
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32. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.
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Huang, Chaolin, Wang, Yeming, Li, Xingwang, Ren, Lili, Zhao, Jianping, Hu, Yi, Zhang, Li, Fan, Guohui, Xu, Jiuyang, Gu, Xiaoying, Cheng, Zhenshun, Yu, Ting, Xia, Jiaan, Wei, Yuan, Wu, Wenjuan, Xie, Xuelei, Yin, Wen, Li, Hui, Liu, Min, and Xiao, Yan
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SARS disease , *COVID-19 , *ADULT respiratory distress syndrome , *ELECTRONIC health records , *EMERGING infectious diseases , *MEDICAL sciences , *SEAFOOD markets , *CHEST X rays , *COMPARATIVE studies , *COMPUTED tomography , *COUGH , *DEMOGRAPHY , *FEVER , *HOSPITAL care , *INTENSIVE care units , *RESEARCH methodology , *MEDICAL cooperation , *MYALGIA , *PROGNOSIS , *RESEARCH , *TIME , *COMORBIDITY , *EVALUATION research - Abstract
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. [ABSTRACT FROM AUTHOR]- Published
- 2020
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33. Oral Simnotrelvir for Adult Patients with Mild-to-Moderate Covid-19.
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Cao B, Wang Y, Lu H, Huang C, Yang Y, Shang L, Chen Z, Jiang R, Liu Y, Lin L, Peng P, Wang F, Gong F, Hu H, Cheng C, Yao X, Ye X, Zhou H, Shen Y, Liu C, Wang C, Yi Z, Hu B, Xu J, Gu X, Shen J, Xu Y, Zhang L, Fan J, Tang R, and Wang C
- Subjects
- Adult, Humans, Administration, Oral, Antiviral Agents administration & dosage, Antiviral Agents adverse effects, Antiviral Agents pharmacology, Antiviral Agents therapeutic use, China, Coronavirus M Proteins antagonists & inhibitors, Coronavirus M Proteins metabolism, COVID-19 Drug Treatment methods, Double-Blind Method, Ritonavir administration & dosage, Ritonavir adverse effects, Ritonavir pharmacology, Ritonavir therapeutic use, SARS-CoV-2 drug effects, Time Factors, Drug Combinations, Coronavirus Protease Inhibitors administration & dosage, Coronavirus Protease Inhibitors adverse effects, Coronavirus Protease Inhibitors pharmacology, Coronavirus Protease Inhibitors therapeutic use, COVID-19 metabolism, COVID-19 therapy
- Abstract
Background: Simnotrelvir is an oral 3-chymotrypsin-like protease inhibitor that has been found to have in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and potential efficacy in a phase 1B trial., Methods: In this phase 2-3, double-blind, randomized, placebo-controlled trial, we assigned patients who had mild-to-moderate coronavirus disease 2019 (Covid-19) and onset of symptoms within the past 3 days in a 1:1 ratio to receive 750 mg of simnotrelvir plus 100 mg of ritonavir or placebo twice daily for 5 days. The primary efficacy end point was the time to sustained resolution of symptoms, defined as the absence of 11 Covid-19-related symptoms for 2 consecutive days. Safety and changes in viral load were also assessed., Results: A total of 1208 patients were enrolled at 35 sites in China; 603 were assigned to receive simnotrelvir and 605 to receive placebo. Among patients in the modified intention-to-treat population who received the first dose of trial drug or placebo within 72 hours after symptom onset, the time to sustained resolution of Covid-19 symptoms was significantly shorter in the simnotrelvir group than in the placebo group (180.1 hours [95% confidence interval {CI}, 162.1 to 201.6] vs. 216.0 hours [95% CI, 203.4 to 228.1]; median difference, -35.8 hours [95% CI, -60.1 to -12.4]; P = 0.006 by Peto-Prentice test). On day 5, the decrease in viral load from baseline was greater in the simnotrelvir group than in the placebo group (mean difference [±SE], -1.51±0.14 log
10 copies per milliliter; 95% CI, -1.79 to -1.24). The incidence of adverse events during treatment was higher in the simnotrelvir group than in the placebo group (29.0% vs. 21.6%). Most adverse events were mild or moderate., Conclusions: Early administration of simnotrelvir plus ritonavir shortened the time to the resolution of symptoms among adult patients with Covid-19, without evident safety concerns. (Funded by Jiangsu Simcere Pharmaceutical; ClinicalTrials.gov number, NCT05506176.)., (Copyright © 2024 Massachusetts Medical Society.)- Published
- 2024
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34. Pulmonary Mucormycosis with Rib Involvement in an Immunocompromised Patient.
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Liu Y, Xu J, Wang C, Lu B, Liang C, Hou G, Cui X, and Cao B
- Subjects
- Humans, Immunocompromised Host, Tomography, X-Ray Computed, Ribs, Mucormycosis complications, Mucormycosis diagnosis
- Published
- 2023
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35. Improved response inhibition induced by attentional capture is associated with physical activity.
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Zhu H, Xu J, Zheng Y, Jiang G, Huang X, Tan X, and Wu X
- Subjects
- Humans, Reaction Time physiology, Psychomotor Performance physiology
- Abstract
The ability to stop a response promptly when a stop signal is presented is named response inhibition. It is generally accepted that the process of response inhibition requires a subject to pay attention to the stop instruction and then cancel the action. A wealth of converging evidence suggests that physical activity (PA) can promote response inhibition, but the potential contributions of attentional capture to the relationship between PA and response inhibition are currently unknown. In this study, the standard stop-signal task (SST) and two novel versions of the SST were used to solve this gap. A total of 58 college students were divided into a higher PA group and a lower PA group, respectively. In Experiment 1, the classical SST determined that the participants in the higher PA group displayed a significantly faster stop-signal reaction time (SSRT) than those in the lower PA group. Experiment 2 separated the attentional capture in the SST and revealed that the participants in the higher PA group could detect the signal faster than those in the lower PA group. Experiment 3 further added a stop signal to Experiment 2 and demonstrated that the participants in the higher PA group could more effectively deploy attentional resources to complete the task. Overall, these findings indicate that PA is positively associated with response inhibition and that the positive relationship is associated with effective allocation of attentional resources for faster attentional capture., Competing Interests: The authors declare that they have no competing interests., (© 2022 Zhu et al.)
- Published
- 2022
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36. Association of acute kidney injury with 1-year outcome of kidney function in hospital survivors with COVID-19: A cohort study.
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Gu X, Huang L, Cui D, Wang Y, Wang Y, Xu J, Shang L, Fan G, and Cao B
- Subjects
- Acute Kidney Injury etiology, Aged, COVID-19 complications, COVID-19 virology, Cohort Studies, Female, Follow-Up Studies, Glomerular Filtration Rate, Humans, Male, Middle Aged, Odds Ratio, Risk Factors, SARS-CoV-2 isolation & purification, Severity of Illness Index, Survivors, Acute Kidney Injury diagnosis, COVID-19 pathology, Kidney physiology
- Abstract
Background: Kidney damage in COVID-19 patients has been of special concern. The association of acute kidney injury (AKI) with post-acute kidney function among COVID-19 survivors was not sufficiently elucidated., Methods: An ambidirectional cohort study was conducted with enrollment of COVID-19 survivors discharged from hospital between Jan 7, and May 29, 2020. Study participants were invited to follow-up visits at 6 and 12 months after symptom onset. The primary outcome was percentage of estimated glomerular filtration rate (eGFR) decreased from acute phase (between symptom onset and hospital discharge) to follow-up, and secondary outcome was reduced renal function at follow-up., Findings: In total, 1,734 study participants were included in this study. Median follow-up duration was 342.0 days (IQR, 223.0-358.0) after symptom onset. After multivariable adjustment, percentage of eGFR decreased from acute phase to follow-up was 8.30% (95% CI, 5.99-10.61) higher among AKI participants than those without AKI at acute phase. Participants with AKI had an odds ratio (OR) of 4.60 (95% CI, 2.10-10.08) for reduced renal function at follow-up. The percentage of eGFR decreased for participants with AKI stage 1, stage 2, and stage 3 was 6.02% (95% CI, 3.48-8.57), 15.99% (95% CI, 10.77-21.22), and 17.79% (95% CI, 9.14-26.43) higher compared with those without AKI, respectively., Interpretation: AKI at acute phase of COVID-19 was closely related to the longitudinal decline and post-acute status of kidney function at nearly one-year after symptom onset. Earlier and more intense follow-up strategies on kidney function management could be beneficial to COVID-19 survivors., Funding: Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS 2020-I2M-CoV19-005, 2018-I2M-1-003, and 2020-I2M-2-013); National Natural Science Foundation of China (82041011); National Key Research and Development Program of China (2018YFC1200102); Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis (2020ZX09201001)., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2022
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37. The Efficacy and Safety of Janus Kinase Inhibitors for Patients With COVID-19: A Living Systematic Review and Meta-Analysis.
- Author
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Zhang X, Shang L, Fan G, Gu X, Xu J, Wang Y, Huang L, and Cao B
- Abstract
Background: Cytokine storm observed in patients with severe Coronavirus Disease 2019 (COVID-19) contributes to poor clinical outcomes and increased mortality. Janus kinases (JAKs) are important mediators in the cytokine storm. Therefore, we conduct a living systematic review and meta-analysis of the literature investigating efficacy and safety of JAK inhibitors for patients with COVID-19., Methods: Databases were searched up to December 1, 2021 for interventional and observational studies comparing JAK inhibitor treatment with concurrent control in patients with COVID-19. Efficacy and safety outcomes were evaluated by pooled risk ratio (RR)., Results: Of 3,170 records retrieved, 15 studies were eligible and 13 were evaluated in the meta-analysis ( n = 3,977). Based on data from three randomized controlled trials (RCTs), baricitinib treatment significantly decreased mortality by day 28 in hospitalized patients with COVID-19 (RR = 0.64, 95% CI 0.51-0.80) without increasing the incidence of adverse outcomes. In subgroup analysis, patients who required supplemental oxygen (RR = 0.62, 95% CI 0.41-0.95) or high-flow oxygen/non-invasive ventilation (RR = 0.59, 95% CI 0.42-0.85) at baseline benefited most. Pooled analysis of all eligible studies for JAK inhibitors (baricitinib, ruxolitinib, tofacitinib, and nezulcitinib) demonstrated a significant decrease in mortality (RR = 0.62, 95% CI 0.49-0.78) with no increase in the risk of adverse events., Conclusion: Baricitinib probably decreases mortality in hospitalized adult patients with COVID-19, especially for patients who required supplemental oxygen or high-flow oxygen/non-invasive ventilation at baseline. The efficacy and safety of other JAK inhibitors, such as ruxolitinib, tofacitinib, and nezulcitinib, await more evidence., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021261414, identifier: CRD42021261414., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Shang, Fan, Gu, Xu, Wang, Huang and Cao.)
- Published
- 2022
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38. Lessons learnt from hydroxychloroquine/azithromycin in treatment of COVID-19.
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Xu J and Cao B
- Subjects
- Azithromycin, Drug Therapy, Combination, Humans, SARS-CoV-2, Hydroxychloroquine, COVID-19 Drug Treatment
- Abstract
Competing Interests: Conflict of interest: J. Xu has nothing to disclose. Conflict of interest: B. Cao has nothing to disclose.
- Published
- 2022
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39. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study.
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Huang C, Huang L, Wang Y, Li X, Ren L, Gu X, Kang L, Guo L, Liu M, Zhou X, Luo J, Huang Z, Tu S, Zhao Y, Chen L, Xu D, Li Y, Li C, Peng L, Li Y, Xie W, Cui D, Shang L, Fan G, Xu J, Wang G, Wang Y, Zhong J, Wang C, Wang J, Zhang D, and Cao B
- Subjects
- Aged, COVID-19 epidemiology, COVID-19 psychology, COVID-19 Serological Testing statistics & numerical data, China epidemiology, Cohort Studies, Comorbidity, Fatigue epidemiology, Fatigue etiology, Female, Humans, Length of Stay statistics & numerical data, Male, Middle Aged, Muscle Weakness epidemiology, Muscle Weakness etiology, Pandemics, SARS-CoV-2, Severity of Illness Index, Sleep Wake Disorders epidemiology, Sleep Wake Disorders etiology, Surveys and Questionnaires, Post-Acute COVID-19 Syndrome, COVID-19 complications, Quality of Life
- Abstract
Background: The long-term health consequences of COVID-19 remain largely unclear. The aim of this study was to describe the long-term health consequences of patients with COVID-19 who have been discharged from hospital and investigate the associated risk factors, in particular disease severity., Methods: We did an ambidirectional cohort study of patients with confirmed COVID-19 who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7, 2020, and May 29, 2020. Patients who died before follow-up, patients for whom follow-up would be difficult because of psychotic disorders, dementia, or re-admission to hospital, those who were unable to move freely due to concomitant osteoarthropathy or immobile before or after discharge due to diseases such as stroke or pulmonary embolism, those who declined to participate, those who could not be contacted, and those living outside of Wuhan or in nursing or welfare homes were all excluded. All patients were interviewed with a series of questionnaires for evaluation of symptoms and health-related quality of life, underwent physical examinations and a 6-min walking test, and received blood tests. A stratified sampling procedure was used to sample patients according to their highest seven-category scale during their hospital stay as 3, 4, and 5-6, to receive pulmonary function test, high resolution CT of the chest, and ultrasonography. Enrolled patients who had participated in the Lopinavir Trial for Suppression of SARS-CoV-2 in China received severe acute respiratory syndrome coronavirus 2 antibody tests. Multivariable adjusted linear or logistic regression models were used to evaluate the association between disease severity and long-term health consequences., Findings: In total, 1733 of 2469 discharged patients with COVID-19 were enrolled after 736 were excluded. Patients had a median age of 57·0 (IQR 47·0-65·0) years and 897 (52%) were men. The follow-up study was done from June 16, to Sept 3, 2020, and the median follow-up time after symptom onset was 186·0 (175·0-199·0) days. Fatigue or muscle weakness (63%, 1038 of 1655) and sleep difficulties (26%, 437 of 1655) were the most common symptoms. Anxiety or depression was reported among 23% (367 of 1617) of patients. The proportions of median 6-min walking distance less than the lower limit of the normal range were 24% for those at severity scale 3, 22% for severity scale 4, and 29% for severity scale 5-6. The corresponding proportions of patients with diffusion impairment were 22% for severity scale 3, 29% for scale 4, and 56% for scale 5-6, and median CT scores were 3·0 (IQR 2·0-5·0) for severity scale 3, 4·0 (3·0-5·0) for scale 4, and 5·0 (4·0-6·0) for scale 5-6. After multivariable adjustment, patients showed an odds ratio (OR) 1·61 (95% CI 0·80-3·25) for scale 4 versus scale 3 and 4·60 (1·85-11·48) for scale 5-6 versus scale 3 for diffusion impairment; OR 0·88 (0·66-1·17) for scale 4 versus scale 3 and OR 1·77 (1·05-2·97) for scale 5-6 versus scale 3 for anxiety or depression, and OR 0·74 (0·58-0·96) for scale 4 versus scale 3 and 2·69 (1·46-4·96) for scale 5-6 versus scale 3 for fatigue or muscle weakness. Of 94 patients with blood antibodies tested at follow-up, the seropositivity (96·2% vs 58·5%) and median titres (19·0 vs 10·0) of the neutralising antibodies were significantly lower compared with at the acute phase. 107 of 822 participants without acute kidney injury and with estimated glomerular filtration rate (eGFR) 90 mL/min per 1·73 m
2 or more at acute phase had eGFR less than 90 mL/min per 1·73 m2 at follow-up., Interpretation: At 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations, and are the main target population for intervention of long-term recovery., Funding: National Natural Science Foundation of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, and Peking Union Medical College Foundation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)- Published
- 2021
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40. Comparison of severity scores for COVID-19 patients with pneumonia: a retrospective study.
- Author
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Fan G, Tu C, Zhou F, Liu Z, Wang Y, Song B, Gu X, Wang Y, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Wu W, and Cao B
- Subjects
- Betacoronavirus isolation & purification, COVID-19, China epidemiology, Female, Hospitalization statistics & numerical data, Humans, Male, Middle Aged, Organ Dysfunction Scores, Predictive Value of Tests, Prognosis, Retrospective Studies, Risk Factors, SARS-CoV-2, Severity of Illness Index, Clinical Decision Rules, Coronavirus Infections diagnosis, Coronavirus Infections epidemiology, Coronavirus Infections physiopathology, Pandemics, Pneumonia, Viral diagnosis, Pneumonia, Viral epidemiology, Pneumonia, Viral etiology, Pneumonia, Viral mortality, Pneumonia, Viral physiopathology, Risk Assessment methods
- Abstract
Competing Interests: Conflict of interest: C. Tu has nothing to disclose. Conflict of interest: F. Zhou has nothing to disclose. Conflict of interest: Z. Liu has nothing to disclose. Conflict of interest: Y. Wang has nothing to disclose. Conflict of interest: B. Song has nothing to disclose. Conflict of interest: X. Gu has nothing to disclose. Conflict of interest: Y. Wang has nothing to disclose. Conflict of interest: Y. Wei has nothing to disclose. Conflict of interest: H. Li has nothing to disclose. Conflict of interest: X. Wu has nothing to disclose. Conflict of interest: J. Xu has nothing to disclose. Conflict of interest: S. Tu has nothing to disclose. Conflict of interest: Y. Zhang has nothing to disclose. Conflict of interest: W. Wu has nothing to disclose. Conflict of interest: B. Cao has nothing to disclose. Conflict of interest: G. Fan has nothing to disclose.
- Published
- 2020
- Full Text
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41. Mendelian randomization in COVID-19: Applications for cardiovascular comorbidities and beyond.
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Teng Y, Xu J, Zhang Y, Liu Z, and Zhang S
- Subjects
- Betacoronavirus, COVID-19, Comorbidity, Genetic Variation genetics, Humans, Pandemics, Risk Factors, SARS-CoV-2, Cardiovascular Diseases complications, Coronary Artery Disease complications, Coronavirus Infections epidemiology, Diabetes Mellitus pathology, Genetic Predisposition to Disease genetics, Mendelian Randomization Analysis, Pneumonia, Viral epidemiology
- Abstract
Competing Interests: Declaration of Competing Interest The authors declare there is no conflict of interest.
- Published
- 2020
- Full Text
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42. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial.
- Author
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Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y, Fu S, Gao L, Cheng Z, Lu Q, Hu Y, Luo G, Wang K, Lu Y, Li H, Wang S, Ruan S, Yang C, Mei C, Wang Y, Ding D, Wu F, Tang X, Ye X, Ye Y, Liu B, Yang J, Yin W, Wang A, Fan G, Zhou F, Liu Z, Gu X, Xu J, Shang L, Zhang Y, Cao L, Guo T, Wan Y, Qin H, Jiang Y, Jaki T, Hayden FG, Horby PW, Cao B, and Wang C
- Subjects
- Adenosine Monophosphate adverse effects, Adenosine Monophosphate therapeutic use, Aged, Alanine adverse effects, Alanine therapeutic use, Antiviral Agents adverse effects, Betacoronavirus, COVID-19, China, Double-Blind Method, Female, Humans, Infusions, Intravenous, Male, Middle Aged, Negative Results, Pandemics, SARS-CoV-2, COVID-19 Drug Treatment, Adenosine Monophosphate analogs & derivatives, Alanine analogs & derivatives, Antiviral Agents therapeutic use, Coronavirus Infections drug therapy, Pneumonia, Viral drug therapy
- Abstract
Background: No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). Remdesivir (GS-5734), a nucleoside analogue prodrug, has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models., Methods: We did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2-10 in single daily infusions) or the same volume of placebo infusions for 10 days. Patients were permitted concomitant use of lopinavir-ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomisation to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. Primary analysis was done in the intention-to-treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04257656., Findings: Between Feb 6, 2020, and March 12, 2020, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group who withdrew after randomisation was not included in the ITT population. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1·23 [95% CI 0·87-1·75]). Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1·52 [0·95-2·43]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early., Interpretation: In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies., Funding: Chinese Academy of Medical Sciences Emergency Project of COVID-19, National Key Research and Development Program of China, the Beijing Science and Technology Project., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2020
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43. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19.
- Author
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Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, Li X, Xia J, Chen N, Xiang J, Yu T, Bai T, Xie X, Zhang L, Li C, Yuan Y, Chen H, Li H, Huang H, Tu S, Gong F, Liu Y, Wei Y, Dong C, Zhou F, Gu X, Xu J, Liu Z, Zhang Y, Li H, Shang L, Wang K, Li K, Zhou X, Dong X, Qu Z, Lu S, Hu X, Ruan S, Luo S, Wu J, Peng L, Cheng F, Pan L, Zou J, Jia C, Wang J, Liu X, Wang S, Wu X, Ge Q, He J, Zhan H, Qiu F, Guo L, Huang C, Jaki T, Hayden FG, Horby PW, Zhang D, and Wang C
- Subjects
- Adult, Aged, Antiviral Agents adverse effects, Betacoronavirus genetics, COVID-19, COVID-19 Testing, Clinical Laboratory Techniques, Coronavirus Infections diagnosis, Coronavirus Infections mortality, Coronavirus Infections virology, Cytochrome P-450 CYP3A Inhibitors adverse effects, Drug Therapy, Combination, Female, Hospital Mortality, Humans, Intention to Treat Analysis, Lopinavir adverse effects, Male, Middle Aged, Pandemics, Patient Acuity, Pneumonia, Viral mortality, Pneumonia, Viral virology, Proportional Hazards Models, Reverse Transcriptase Polymerase Chain Reaction, Ritonavir adverse effects, SARS-CoV-2, Time-to-Treatment, Treatment Failure, Viral Load, Antiviral Agents therapeutic use, Betacoronavirus isolation & purification, Coronavirus Infections drug therapy, Cytochrome P-450 CYP3A Inhibitors therapeutic use, Lopinavir therapeutic use, Pneumonia, Viral drug therapy, Ritonavir therapeutic use
- Abstract
Background: No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2., Methods: We conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao
2 ) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao2 ) to the fraction of inspired oxygen (Fio2 ) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir-ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone. The primary end point was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first., Results: A total of 199 patients with laboratory-confirmed SARS-CoV-2 infection underwent randomization; 99 were assigned to the lopinavir-ritonavir group, and 100 to the standard-care group. Treatment with lopinavir-ritonavir was not associated with a difference from standard care in the time to clinical improvement (hazard ratio for clinical improvement, 1.31; 95% confidence interval [CI], 0.95 to 1.80). Mortality at 28 days was similar in the lopinavir-ritonavir group and the standard-care group (19.2% vs. 25.0%; difference, -5.8 percentage points; 95% CI, -17.3 to 5.7). The percentages of patients with detectable viral RNA at various time points were similar. In a modified intention-to-treat analysis, lopinavir-ritonavir led to a median time to clinical improvement that was shorter by 1 day than that observed with standard care (hazard ratio, 1.39; 95% CI, 1.00 to 1.91). Gastrointestinal adverse events were more common in the lopinavir-ritonavir group, but serious adverse events were more common in the standard-care group. Lopinavir-ritonavir treatment was stopped early in 13 patients (13.8%) because of adverse events., Conclusions: In hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir-ritonavir treatment beyond standard care. Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit. (Funded by Major Projects of National Science and Technology on New Drug Creation and Development and others; Chinese Clinical Trial Register number, ChiCTR2000029308.)., (Copyright © 2020 Massachusetts Medical Society.)- Published
- 2020
- Full Text
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