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      Low dose of hydroxychloroquine reduces fatality of critically ill patients with COVID-19

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          Abstract

          Coronavirus disease 2019 (COVID-19) is a pandemic with no specific drugs and high fatality. The most urgent need is to find effective treatments. We sought to determine whether hydroxychloroquine (HCQ) application may reduce the death risk of critically ill COVID-19 patients. In this retrospective study, we included 550 critically ill COVID-19 patients who need mechanical ventilation in Tongji Hospital, Wuhan, from February 1, 2020 to April 4, 2020. All 550 patients received comparable basic treatments including antiviral drugs and antibiotics, and 48 of them were treated with oral HCQ treatment (200 mg twice a day for 7–10 days) in addition to the basic treatments. Primary endpoint is fatality of patients, and inflammatory cytokine levels were compared between HCQ and non-hydroxychloroquine (NHCQ) treatments. We found that fatalities are 18.8% (9/48) in HCQ group, which is significantly lower than 47.4% (238/502) in the NHCQ group ( P<0.001). The time of hospital stay before patient death is 15 (10–21) days and 8 (4–14) days for the HCQ and NHCQ groups, respectively ( P<0.05). The levels of inflammatory cytokine IL-6 were significantly reduced from 22.2 (8.3-118.9) pg mL –1 at the beginning of the treatment to 5.2 (3.0–23.4) pg mL –1 ( P<0.05) at the end of the treatment in the HCQ group but there is no change in the NHCQ group. These data demonstrate that addition of HCQ on top of the basic treatments is highly effective in reducing the fatality of critically ill patients of COVID-19 through attenuation of inflammatory cytokine storm. Therefore, HCQ should be prescribed as a part of treatment for critically ill COVID-19 patients, with possible outcome of saving lives. hydroxychloroquine, IL-6, mortalities, COVID-19

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          Most cited references10

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          Clinical Characteristics of Coronavirus Disease 2019 in China

          Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
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            COVID-19, cytokines and immunosuppression: what can we learn from severe acute respiratory syndrome?

            A severe outbreak of coronavirus disease 2019 (COVID-19) emerged in China in December 2019, and spread so rapidly that more than 200,000 cases have so far been reported worldwide; on January 30, 2020, the WHO declared it the sixth public health emergency of international concern. The two previously reported coronavirus epidemics (severe acute respiratory syndrome [SARS] and Middle East respiratory syndrome [MERS]) share similar pathogenetic, epidemiological and clinical features as COVID-19. As little is currently known about SARS-CoV-2, it is likely that lessons learned from these major epidemics can be applied to the new pandemic, including the use of novel immunosuppressive drugs.
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              Identification of a lysosomal pathway that modulates glucocorticoid signaling and the inflammatory response.

              The antimalaria drug chloroquine has been used as an anti-inflammatory agent for treating systemic lupus erythematosus and rheumatoid arthritis. We report that chloroquine promoted the transrepression of proinflammatory cytokines by the glucocorticoid receptor (GR). In a mouse collagen-induced arthritis model, chloroquine enhanced the therapeutic effects of glucocorticoid treatment. By inhibiting lysosome function, chloroquine synergistically activated glucocorticoid signaling. Lysosomal inhibition by either bafilomycin A1 (an inhibitor of the vacuolar adenosine triphosphatase) or knockdown of transcription factor EB (TFEB, a master activator of lysosomal biogenesis) mimicked the effects of chloroquine. The abundance of the GR, as well as that of the androgen receptor and estrogen receptor, correlated with changes in lysosomal biogenesis. Thus, we showed that glucocorticoid signaling is regulated by lysosomes, which provides a mechanistic basis for treating inflammation and autoimmune diseases with a combination of glucocorticoids and lysosomal inhibitors.
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                Author and article information

                Contributors
                dwwang@tjh.tjmu.edu.cn
                Journal
                Sci China Life Sci
                Sci China Life Sci
                Science China. Life Sciences
                Science China Press (Beijing )
                1674-7305
                1869-1889
                15 May 2020
                : 1-7
                Affiliations
                [1 ]GRID grid.33199.31, ISNI 0000 0004 0368 7223, Division of Cardiology, Department of Internal Medicine and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, , Huazhong University of Science and Technology, ; Wuhan, 430030 China
                [2 ]GRID grid.9227.e, ISNI 0000000119573309, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, , Chinese Academy of Sciences, ; Shanghai, 201203 China
                [3 ]GRID grid.440637.2, ISNI 0000 0004 4657 8879, Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, , Shanghai Tech University, ; Shanghai, 201210 China
                Article
                1732
                10.1007/s11427-020-1732-2
                7228868
                32418114
                4aed454a-d726-4f15-b999-e870c802f88d
                © Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 23 April 2020
                : 12 May 2020
                Categories
                Research Paper

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