systemic corticosteroids show no benefit in severe and critical covid 19 patients CORD-Papers-2021-10-25 (Version 1)

Title: Systemic corticosteroids show no benefit in severe and critical COVID-19 patients in Wuhan, China: A retrospective cohort study
Abstract: Background: Systemic corticosteroids are recommended by some treatment guidelines and used in severe and critical COVID-19 patients, though evidence supporting such use is limited. Methods: From December 26, 2019 to March 15, 2020, 1514 severe and 249 critical hospitalized COVID-19 patients were collected from two medical centers in Wuhan, China. We performed multivariable Cox models, Cox model with time-varying exposure and propensity score analysis (both inverse-probability-of-treatment-weighting (IPTW) and propensity score matching (PSM)) to estimate the association of corticosteroid use with the risk of in-hospital mortality among severe and critical cases. Results: Corticosteroids were administered in 531 (35.1%) severe and 159 (63.9%) critical patients. Compared to no corticosteroid use group, systemic corticosteroid use showed no benefit in reducing in-hospital mortality in both severe cases (HR=1.77, 95% CI: 1.08-2.89, p=0.023), and critical cases (HR=2.07, 95% CI: 1.08-3.98, p=0.028). In the time-varying Cox analysis that with time varying exposure, systemic corticosteroid use still showed no benefit in either population (for severe patients, HR=2.83, 95% CI: 1.72-4.64, p< 0.001; for critical patients, HR=3.02, 95% CI: 1.59-5.73, p=0.001). Baseline characteristics were matched after IPTW and PSM analysis. For severe COVID-19 patients at admission, corticosteroid use was not associated with improved outcome in either the IPTW analysis. For critical COVID-19 patients at admission, results were consistent with former analysis that corticosteroid use did not reduce in-hospital mortality. Conclusions: Corticosteroid use showed no benefit in reducing in-hospital mortality for severe or critical cases. The routine use of systemic corticosteroids among severe and critical COVID-19 patients was not recommended.
Published: 5/14/2020
DOI: 10.1101/2020.05.11.20097709
DOI_URL: http://doi.org/10.1101/2020.05.11.20097709
Author Name: Wu, J
Author link: https://covid19-data.nist.gov/pid/rest/local/author/wu_j
Author Name: Huang, J
Author link: https://covid19-data.nist.gov/pid/rest/local/author/huang_j
Author Name: Zhu, G
Author link: https://covid19-data.nist.gov/pid/rest/local/author/zhu_g
Author Name: Liu, Y
Author link: https://covid19-data.nist.gov/pid/rest/local/author/liu_y
Author Name: Xiao, H
Author link: https://covid19-data.nist.gov/pid/rest/local/author/xiao_h
Author Name: Zhou, Q
Author link: https://covid19-data.nist.gov/pid/rest/local/author/zhou_q
Author Name: Si, X
Author link: https://covid19-data.nist.gov/pid/rest/local/author/si_x
Author Name: Yi, H
Author link: https://covid19-data.nist.gov/pid/rest/local/author/yi_h
Author Name: Wang, C
Author link: https://covid19-data.nist.gov/pid/rest/local/author/wang_c
Author Name: Yang, D
Author link: https://covid19-data.nist.gov/pid/rest/local/author/yang_d
Author Name: Chen, S
Author link: https://covid19-data.nist.gov/pid/rest/local/author/chen_s
Author Name: Liu, X
Author link: https://covid19-data.nist.gov/pid/rest/local/author/liu_x
Author Name: Liu, Z
Author link: https://covid19-data.nist.gov/pid/rest/local/author/liu_z
Author Name: Wang, Q
Author link: https://covid19-data.nist.gov/pid/rest/local/author/wang_q
Author Name: Lv, Q
Author link: https://covid19-data.nist.gov/pid/rest/local/author/lv_q
Author Name: Huang, Y
Author link: https://covid19-data.nist.gov/pid/rest/local/author/huang_y
Author Name: Yu, Y
Author link: https://covid19-data.nist.gov/pid/rest/local/author/yu_y
Author Name: Guan, X
Author link: https://covid19-data.nist.gov/pid/rest/local/author/guan_x
Author Name: Li, Y
Author link: https://covid19-data.nist.gov/pid/rest/local/author/li_y
Author Name: Nirantharakumar, K
Author link: https://covid19-data.nist.gov/pid/rest/local/author/nirantharakumar_k
Author Name: Cheng, K
Author link: https://covid19-data.nist.gov/pid/rest/local/author/cheng_k
Author Name: Peng, S
Author link: https://covid19-data.nist.gov/pid/rest/local/author/peng_s
sha: b33f2c1101ee38e656cd832ef6f6be31d61f4e0d
license: medrxiv
source_x: MedRxiv; WHO
source_x_url: https://www.who.int/
url: http://medrxiv.org/cgi/content/short/2020.05.11.20097709v1?rss=1 https://doi.org/10.1101/2020.05.11.20097709
has_full_text: TRUE
Keywords Extracted from Text Content: Corticosteroids corticosteroid Corticosteroid patients COVID-19 patients Wuhan corticosteroids HR=2.83 creatinine LDH H1N1 p<0.05 1D Figure 1C medRxiv pulmonary AST CIs dexamethasone medRxiv preprint 1514/1763 H1N1 viral pneumonia non-corticosteroid methylprednisolone organs corticosteroid neutrophil granulocyte platelet, haemoglobin COVID-19 [23] lymphocyte alanine aminotransferase line BUN COVID-19 patients corticosteroids Wuhan, COVID-19 hydrocortisone glucose oxygen low-dose blood glucose n=198 https://doi.org/10.1101/2020.05.11.20097709 doi Wuhan. CKD PSM Wuhan patients Corticosteroid coronavirus Supplementary Table 7 Corticosteroids lactate dehydrogenase CRP kidney K-M ALT blood urea nitrogen inpatients aspartate aminotransferase lymphocytes cancer
Extracted Text Content in Record: First 5000 Characters:Background: Systemic corticosteroids are recommended by some treatment guidelines and used in severe and critical COVID-19 patients, though evidence supporting such use is limited. : From December 26, 2019 to March 15, 2020, 1514 severe and 249 critical hospitalized COVID-19 patients were collected from two medical centers in Wuhan, China. We performed multivariable Cox models, Cox model with time-varying exposure and propensity score analysis (both inverse-probability-of-treatment-weighting (IPTW) and propensity score matching (PSM)) to estimate the association of corticosteroid use with the risk of in-hospital mortality among severe and critical cases. Results: Corticosteroids were administered in 531 (35.1%) severe and 159 (63.9%) critical patients. Compared to no corticosteroid use group, systemic corticosteroid use showed no benefit in reducing in-hospital mortality in both severe cases (HR=1.77, 95% CI: 1.08-2.89, p=0.023), and critical cases (HR=2.07, 95% CI: 1.08-3.98, p=0.028). In the time-varying Cox analysis that with time varying exposure, systemic corticosteroid use still showed no benefit in either population (for severe patients, HR=2.83, 95% CI: 1.72-4.64, p<0.001; for critical patients, HR=3.02, 95% CI: 1.59-5.73, p=0.001). Baseline characteristics were matched after IPTW and PSM analysis. For severe COVID-19 patients at admission, corticosteroid use was not associated with improved outcome in either the IPTW analysis. For critical COVID-19 patients at admission, results were consistent with former analysis that corticosteroid use did not reduce in-hospital mortality. Conclusions: Corticosteroid use showed no benefit in reducing in-hospital mortality for severe or critical cases. The routine use of systemic corticosteroids among severe and critical COVID-19 patients was not recommended. The current pandemic of coronavirus disease-19 has become the most severe global health crisis [1] . At present, the cumulative number of confirmed COVID-19 cases worldwide has exceeded 3 million and is still rising rapidly [2] . Although most of COVID-19 patients reportedly had mild symptoms and good prognosis, the mortality of hospitalized severe and critical cases was 18.2% and 49%, respectively [3, 4] . Due to the lack of specific therapies for COVID-19, one of the biggest challenges faced by clinicians in all countries is the clinical management of severe and critical cases with the goal of reducing mortality. Systemic corticosteroids have been studied extensively with variable and inconsistent results in the treatment of acute respiratory distress syndrome (ARDS) caused by viral pneumonia [5] [6] [7] . During the outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), systemic corticosteroids were used in 79.6% and 48.9% of critical cases, respectively [5, 8] . Two studies of patients with SARS and influenza A (H1N1) viral pneumonia showed that the use of systemic corticosteroids was associated with reduced mortality in critical patients [6, 8] . However, several other studies of patients with SARS and one study of patients with MERS all indicated that its use could be harmful [5, [9] [10] [11] [12] . A meta-analysis published in 2019 also showed a significant increase in mortality in influenza pneumonia patients treated with systemic corticosteroids [13] . The is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 14, 2020. . https://doi.org/10.1101/2020.05. 11.20097709 doi: medRxiv preprint harm or benefit for the use of systemic corticosteroids in severe and critical COVID-19 patients. In the current study, we analysed the clinical data of 1514 severe and 249 critical COVID-19 cases from two medical centres in Wuhan city and investigated the effects of systemic corticosteroids in severe and critical COVID-19 patients. Consecutive inpatients with laboratory confirmed or clinically diagnosed COVID-19 We collected the patients' clinical data, including demographic information, medical history, laboratory indexes, corticosteroid use and prognosis. The admission . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 14, 2020. . https://doi.org/10.1101/2020.05.11.20097709 doi: medRxiv preprint laboratory indexes were defined as the first records of laboratory indexes since admission. Corticosteroid use was defined as the use of intravenous systemic corticosteroids, including hydrocortisone, methylprednisolone, and dexamethasone. The dose of corticosteroids was converted to methylprednisolone-equivalent doses (1mg methylprednisolone = 0.1875mg dexamethasone = 5mg hydrocortisone). We evaluated whether using corticosteroids could affect the in-hospital morta
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