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Ke Shang

Bio: Ke Shang is an academic researcher from Huazhong University of Science and Technology. The author has contributed to research in topics: Medicine & Neuromyelitis optica. The author has an hindex of 7, co-authored 15 publications receiving 3255 citations.

Papers
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Journal ArticleDOI
TL;DR: Investigation of NLR and lymphocyte subsets is helpful in the early screening of critical illness, diagnosis and treatment of COVID-19 and shows the novel coronavirus might mainly act on lymphocytes, especially T lymphocytes.
Abstract: BACKGROUND: In December 2019, coronavirus 2019 (COVID-19) emerged in Wuhan and rapidly spread throughout China. METHODS: Demographic and clinical data of all confirmed cases with COVID-19 on admission at Tongji Hospital from 10 January to 12 February 2020 were collected and analyzed. The data on laboratory examinations, including peripheral lymphocyte subsets, were analyzed and compared between patients with severe and nonsevere infection. RESULTS: Of the 452 patients with COVID-19 recruited, 286 were diagnosed as having severe infection. The median age was 58 years and 235 were male. The most common symptoms were fever, shortness of breath, expectoration, fatigue, dry cough, and myalgia. Severe cases tend to have lower lymphocyte counts, higher leukocyte counts and neutrophil-lymphocyte ratio (NLR), as well as lower percentages of monocytes, eosinophils, and basophils. Most severe cases demonstrated elevated levels of infection-related biomarkers and inflammatory cytokines. The number of T cells significantly decreased, and were more impaired in severe cases. Both helper T (Th) cells and suppressor T cells in patients with COVID-19 were below normal levels, with lower levels of Th cells in the severe group. The percentage of naive Th cells increased and memory Th cells decreased in severe cases. Patients with COVID-19 also have lower levels of regulatory T cells, which are more obviously decreased in severe cases. CONCLUSIONS: The novel coronavirus might mainly act on lymphocytes, especially T lymphocytes. Surveillance of NLR and lymphocyte subsets is helpful in the early screening of critical illness, diagnosis, and treatment of COVID-19.

3,532 citations

Journal ArticleDOI
TL;DR: Patients with COVID-19 have lower level of regulatory T cells, and more obviously damaged in severe cases, compared with non-severe patients, which suggests surveillance of NLR and lymphocyte subsets is helpful in the early screening of critical illness, diagnosis and treatment of CO VID-19.
Abstract: Background: In December 2019, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan and rapidly spread throughout China. The immune response is likely to be highly involved in the pathological process of coronavirus disease 2019 (COVID-19). However, information on specific changes of immune response in COVID-19 are limited. Methods: Demographic and clinical data of all confirmed cases with COVID-19 on admission at Tongji Hospital from January 10 to February 12, 2020, were collected and analyzed. The expression of lymphocytes, lymphocyte subsets, infection related biomarkers and inflammatory cytokines were analyzed and compared between severe cases and non-severe patients. Findings: Of the 452 patients with COVID-19 recruited from January 10 to February 12, 2020, 286 were diagnosed as severe infection. The median age was 58 years and 235 were male. 201 patients had chronic diseases and a higher percentage in the severe cases. The most common symptoms were fever, shortness of breath, expectoration, and fatigue. Severe cases tend to have higher white blood cell and neutrophil lymphopenia ratio (NLR), as well as lower percentages of monocytes, eosinophils, and basophils. Most of severe cases demonstrated elevated levels of infection-related biomarkers, and inflammatory cytokines. The numbers of B cells, T cells and NK cells was significantly decreased in patients with COVID-19, and more severely decreased in the severe cases. T cells were shown to be most affected by SARS-CoV-2, and more hampered in severe cases. Both helper T cells and suppressor T cells in patients with COVID-19 were below normal levels. Helper T cells tend to be more affected in severe cases. The percentage of naive helper T cells increased and memory helper T cells decreased in severe cases. Patients with COVID-19 have lower level of regulatory T cells, and more obviously damaged in severe cases. Interpretation: SARS-CoV-2 might mainly act on lymphocytes, especially T lymphocytes, and induce a cytokine storm in the body, generate a series of immune responses. Surveillance of NLR and lymphocyte subsets is helpful in the early screening of critical illness, diagnosis and treatment of COVID-19. Funding Statement: None. Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: The study was performed in accordance with Tongji Hospital Ethics Committee (IRB ID: TJ-C20200121). Written informed consent was waived by the Ethics Commission of the designated hospital for emerging infectious disease.

907 citations

Journal ArticleDOI
01 May 2020
TL;DR: In this study, most infections among health care workers occurred during the early stage of the COVID-19 outbreak and in low-contagion areas; routine screening may be helpful in identifying asymptomatic carriers.
Abstract: Importance Health care workers (HCWs) have high infection risk owing to treating patients with coronavirus disease 2019 (COVID-19). However, research on their infection risk and clinical characteristics is limited. Objectives To explore infection risk and clinical characteristics of HCWs with COVID-19 and to discuss possible prevention measures. Design, Setting, and Participants This single-center case series included 9684 HCWs in Tongji Hospital, Wuhan, China. Data were collected from January 1 to February 9, 2020. Exposures Confirmed COVID-19. Main Outcomes and Measures Exposure, epidemiological, and demographic information was collected by a structured questionnaire. Clinical, laboratory, and radiologic information was collected from electronic medical records. A total of 335 medical staff were randomly sampled to estimate the prevalence of subclinical infection among a high-risk, asymptomatic population. Samples from surfaces in health care settings were also collected. Results Overall, 110 of 9684 HCWs in Tongji Hospital tested positive for COVID-19, with an infection rate of 1.1%. Of them, 70 (71.8%) were women, and they had a median (interquartile range) age of 36.5 (30.0-47.0) years. Seventeen (15.5%) worked in fever clinics or wards, indicating an infection rate of 0.5% (17 of 3110) among first-line HCWs. A total of 93 of 6574 non–first-line HCWs (1.4%) were infected. Non–first-line nurses younger than 45 years were more likely to be infected compared with first-line physicians aged 45 years or older (incident rate ratio, 16.1; 95% CI, 7.1-36.3;P Conclusions and Relevance In this case series, most infections among HCWs occurred during the early stage of disease outbreak. That non–first-line HCWs had a higher infection rate than first-line HCWs differed from observation of previous viral disease epidemics. Rapid identification of staff with potential infection and routine screening among asymptomatic staff could help protect HCWs.

354 citations

Journal ArticleDOI
01 Jan 2017-Stroke
TL;DR: Interestingly, FTY720 could reduce cognitive decline and ameliorate the disruption of WM integrity, a potential therapeutic drug targeting brain inflammation by skewing microglia toward M2 polarization after chronic cerebral hypoperfusion.
Abstract: Background and Purpose— White matter (WM) ischemic injury, a major neuropathological feature of cerebral small vessel diseases, is an important cause of vascular cognitive impairment in later life. The pathogenesis of demyelination after WM ischemic damage are often accompanied by microglial activation. Fingolimod (FTY720) was approved for the treatment of multiple sclerosis for its immunosuppression property. In this study, we evaluated the neuroprotective potential of FTY720 in a WM ischemia model. Methods— Chronic WM ischemic injury model was induced by bilateral carotid artery stenosis. Cognitive function, WM integrity, microglial activation, and potential pathway involved in microglial polarization were assessed after bilateral carotid artery stenosis. Results— Disruption of WM integrity was characterized by demyelination in the corpus callosum and disorganization of Ranvier nodes using Luxol fast blue staining, immunofluorescence staining, and electron microscopy. In addition, radial maze test demonstrated that working memory performance was decreased at 1-month post–bilateral carotid artery stenosis–induced injury. Interestingly, FTY720 could reduce cognitive decline and ameliorate the disruption of WM integrity. Mechanistically, cerebral hypoperfusion induced microglial activation, production of associated proinflammatory cytokines, and priming of microglial polarization toward the M1 phenotype, whereas FTY720 attenuated microglia-mediated neuroinflammation after WM ischemia and promoted oligodendrocytogenesis by shifting microglia toward M2 polarization. FTY720’s effect on microglial M2 polarization was largely suppressed by selective signal transducer and activator of transcription 3 (STAT3) blockade in vitro, revealing that FTY720-enabled shift of microglia from M1 to M2 polarization state was possibly mediated by STAT3 signaling. Conclusions— Our study suggested that FTY720 might be a potential therapeutic drug targeting brain inflammation by skewing microglia toward M2 polarization after chronic cerebral hypoperfusion.

221 citations

Journal ArticleDOI
TL;DR: TLR4-dependent autophagy regulates microglial polarization and induces ischemic white matter damage via STAT1/6 pathway, and TLR4 deficiency could mimic the phenomenon in microglia functional transformation, and exhibit a protective activity in chronic cerebral hypoperfusion.
Abstract: Rationale: Ischemic white matter damage frequently results in myelin loss, accompanied with microglial activation. We previously found that directing microglia towards an anti-inflammatory phenotype provided a beneficial microenvironment and helped maintain white matter integrity during chronic cerebral hypoperfusion. However, the molecular mechanisms underlying microglial polarization remain elusive. Methods: Hypoperfusion induced white matter damage mice model and lipopolysaccharide (LPS) induced primary cultured microglia were established. Autophagy activation in microglia was detected both in vivo and in vitro by immunofluorescence, Western blot and electron microscopy. Autophagy inhibitors/agonist were administrated to investigate the role of autophagic process in modulating microglial phenotypes. Quantitative real time-polymerase chain reaction and Western blot were carried out to investigate the possible pathway. Results: We identified rapid accumulation of autophagosomes in primary cultured microglia exposed to LPS and within activated microglia during white matter ischemic damage. Autophagy inhibitors switched microglial function from pro-inflammatory to anti-inflammatory phenotype. Furthermore, we found TLR4, one of the major receptors binding LPS, was most highly expressed on microglia in corpus callosum during white matter ischemic damage, and TLR4 deficiency could mimic the phenomenon in microglial functional transformation, and exhibit a protective activity in chronic cerebral hypoperfusion. Whereas, the anti-inflammatory phenotype of microglia in TLR4 deficiency group was largely abolished by the activation of autophagic process. Finally, our transcriptional analysis confirmed that the up-regulation of STAT1 and down-regulation of STAT6 in microglia exposure to LPS could be reversed by autophagy inhibition. Conclusion: These results indicated that TLR4-dependent autophagy regulates microglial polarization and induces ischemic white matter damage via STAT1/6 pathway.

67 citations


Cited by
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Book ChapterDOI
01 Jan 2010

5,842 citations

Journal ArticleDOI
28 May 2020-Cell
TL;DR: It is proposed that reduced innate antiviral defenses coupled with exuberant inflammatory cytokine production are the defining and driving features of COVID-19.

3,286 citations

Journal ArticleDOI
TL;DR: The interaction of SARS-CoV-2 with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression is described and the implications of these approaches for potential therapeutic interventions that target viral infection and/or immunoregulation are highlighted.
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Alongside investigations into the virology of SARS-CoV-2, understanding the fundamental physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies. Here, we provide an overview of the pathophysiology of SARS-CoV-2 infection. We describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression. From nascent reports describing SARS-CoV-2, we make inferences on the basis of the parallel pathophysiological and immunological features of the other human coronaviruses targeting the lower respiratory tract - severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Finally, we highlight the implications of these approaches for potential therapeutic interventions that target viral infection and/or immunoregulation.

3,236 citations

Journal ArticleDOI
TL;DR: The extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 are reviewed to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.
Abstract: Although COVID-19 is most well known for causing substantial respiratory pathology, it can also result in several extrapulmonary manifestations. These conditions include thrombotic complications, myocardial dysfunction and arrhythmia, acute coronary syndromes, acute kidney injury, gastrointestinal symptoms, hepatocellular injury, hyperglycemia and ketosis, neurologic illnesses, ocular symptoms, and dermatologic complications. Given that ACE2, the entry receptor for the causative coronavirus SARS-CoV-2, is expressed in multiple extrapulmonary tissues, direct viral tissue damage is a plausible mechanism of injury. In addition, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19. Here we review the extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.

2,113 citations

Journal ArticleDOI
TL;DR: Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents.
Abstract: Background Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19)...

1,887 citations