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Inflammation characteristics and anti-inflammation treatment with tocilizumab of severe/critical COVID-19 patients: A retrospective cohort study.

ABSTRACT: The efficacy of tocilizumab on the prognosis of severe/critical COVID-19 patients is still controversial so far. We aimed to delineate the inflammation characteristics of severe/critical COVID-19 patients and determine the impact of tocilizumab on hospital mortality. Here, we performed a retrospective cohort study which enrolled 727 severe or critical inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Huoshenshan Hospital (Wuhan, China), among which 50 patients received tocilizumab. This study confirmed that most recovered patients manifested relatively normal inflammation levels at admission, whereas most of the deceased cases presented visibly severe inflammation at admission and even progressed into extremely aggravated inflammation before their deaths, proved by some extremely high concentrations of interleukin-6, procalcitonin, C-reactive protein and neutrophil count. Moreover, based on the Cox proportional-hazards models before or after propensity score matching, we demonstrated that tocilizumab treatment could lessen mortality by gradually alleviating excessive inflammation and meanwhile continuously enhancing the levels of lymphocytes within 14 days for severe/critical COVID-19 patients, indicating potential effectiveness for treating COVID-19.

SUBMITTER: Hu Q

PROVIDER: S-EPMC8193270 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Inflammation characteristics and anti-inflammation treatment with tocilizumab of severe/critical COVID-19 patients: A retrospective cohort study.

Hu Qin Q Xu Yu Y Xiang Ying Y Wang Bin B Yuan Zhiquan Z Shan Yifan Y Zhang Wenjing W Wu Na N Xia Tingting T Li Chengying C Xie Weijia W Jia Xiaoyue X Yu Zubin Z Bai Li L Li Yafei Y

International journal of biological sciences 20210517 8

The efficacy of tocilizumab on the prognosis of severe/critical COVID-19 patients is still controversial so far. We aimed to delineate the inflammation characteristics of severe/critical COVID-19 patients and determine the impact of tocilizumab on hospital mortality. Here, we performed a retrospective cohort study which enrolled 727 severe or critical inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Huoshenshan Hospital (Wuhan, China), among which 50 patients received tocilizum ...[more]

PMID: 34131411

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Project description:Background:No therapy is approved for COVID-19 pneumonia. The aim of this study was to assess the role of tocilizumab in reducing the risk of invasive mechanical ventilation and death in patients with severe COVID-19 pneumonia who received standard of care treatment. Methods:This retrospective, observational cohort study included adults (?18 years) with severe COVID-19 pneumonia who were admitted to tertiary care centres in Bologna and Reggio Emilia, Italy, between Feb 21 and March 24, 2020, and a tertiary care centre in Modena, Italy, between Feb 21 and April 30, 2020. All patients were treated with the standard of care (ie, supplemental oxygen, hydroxychloroquine, azithromycin, antiretrovirals, and low molecular weight heparin), and a non-randomly selected subset of patients also received tocilizumab. Tocilizumab was given either intravenously at 8 mg/kg bodyweight (up to a maximum of 800 mg) in two infusions, 12 h apart, or subcutaneously at 162 mg administered in two simultaneous doses, one in each thigh (ie, 324 mg in total), when the intravenous formulation was unavailable. The primary endpoint was a composite of invasive mechanical ventilation or death. Treatment groups were compared using Kaplan-Meier curves and Cox regression analysis after adjusting for sex, age, recruiting centre, duration of symptoms, and baseline Sequential Organ Failure Assessment (SOFA) score. Findings:Of 1351 patients admitted, 544 (40%) had severe COVID-19 pneumonia and were included in the study. 57 (16%) of 365 patients in the standard care group needed mechanical ventilation, compared with 33 (18%) of 179 patients treated with tocilizumab (p=0·41; 16 [18%] of 88 patients treated intravenously and 17 [19%] of 91 patients treated subcutaneously). 73 (20%) patients in the standard care group died, compared with 13 (7%; p<0·0001) patients treated with tocilizumab (six [7%] treated intravenously and seven [8%] treated subcutaneously). After adjustment for sex, age, recruiting centre, duration of symptoms, and SOFA score, tocilizumab treatment was associated with a reduced risk of invasive mechanical ventilation or death (adjusted hazard ratio 0·61, 95% CI 0·40-0·92; p=0·020). 24 (13%) of 179 patients treated with tocilizumab were diagnosed with new infections, versus 14 (4%) of 365 patients treated with standard of care alone (p<0·0001). Interpretation:Treatment with tocilizumab, whether administered intravenously or subcutaneously, might reduce the risk of invasive mechanical ventilation or death in patients with severe COVID-19 pneumonia. Funding:None.

Project description:BackgroundTocilizumab was approved for chimeric antigen receptor T-cell therapy induced cytokine release syndrome and it may provide clinical benefit for selected COVID-19 patients.MethodsIn this retrospective cohort study, we analyzed hypoxic COVID-19 patients who were consecutively admitted between March 13, 2020 and April 19, 2020. Patients with lung infiltrates and elevated inflammatory markers received a single dose of tocilizumab if no contraindication was present. Systemic steroid, hydroxychloroquine, and azithromycin were concomitantly used for majority of the patients.FindingsOf the 51 patients included for analysis, 28 (55%) received tocilizumab and 23 (45%) did not receive tocilizumab. Tocilizumab cohort required more invasive ventilation (68% vs. 22%) at baseline and during entire hospitalization (75% vs. 48%). The median time to clinical improvement in tocilizumab vs. no tocilizumab cohorts was 8 days (Interquartile range [IQR]: 6·25 - 9·75 days) vs. 13 days (IQR: 9·75 - 15·25 days) among patients who required mechanical ventilation at any time (Hazard ratio for clinical improvement: 1·83, 95% confidence interval [CI]: 0·57 - 5·84) and 6·5 days vs. 7 days among all patients (Hazard ratio for clinical improvement: 1·14, 95% CI: 0·55 - 2·38), respectively. The median duration of vasopressor support and invasive mechanical ventilation were 2 days (IQR: 1·75 - 4·25 days) vs. 5 days (IQR: 4 - 8 days), p = 0.039, and 7 days (IQR: 4 - 14 days) vs. 10 days (IQR: 5 - 15 days) in tocilizumab vs. no tocilizumab cohorts, p = 0.11, respectively. Similar rates of hospital-acquired infections occurred in both cohorts (18% in tocilizumab and 22% in no tocilizumab cohort).InterpretationIn patients with severe COVID-19, tocilizumab was associated with significantly shorter duration of vasopressor support. Although not statistically significant, tocilizumab also resulted in shorter median time to clinical improvement and shorter duration of invasive ventilation. These findings require validation from ongoing clinical trials of Tocilizumab in COVID-19 patients.

Project description:IntroductionThis retrospective, single-center study was performed to systemically describe the characteristics and outcomes of patients with severe and critical coronavirus disease 2019 (COVID-19) in Wuhan, analyze the risk factors, and propose suggestions for clinical diagnosis and treatment to guide the subsequent clinical practice.MethodsA total of 753 consecutive patients with COVID-19 admitted to the West Campus of Wuhan Union Hospital from January 22, 2020 to May 7, 2020 were enrolled in this study. Demographic, clinical, laboratory, and outcome data were extracted from the electronic medical records of Wuhan Union Hospital and were exhaustively analyzed using R (version 3.6.1).ResultsA total of 493 severe and 228 critical cases out of 753 COVID-19 cases were considered in this study. Among the critical cases, the death rate was 79.4%, and age was a risk factor for death. Compared to the severe disease group, the critical disease group had higher white blood cell (WBC) and neutrophil counts and a decreased lymphocyte count at admission. Compared to early death cases (death within 1 week after admission), a more prolonged course of the disease was associated with a higher risk of hypoproteinemia, liver injury, thrombocytopenia, anemia, disseminated intravascular coagulation (DIC), coagulation disorders, acute kidney injury (AKI), and infection. Higher creatine kinase (CK) and lactate dehydrogenase (LDH) levels were related to early death events, but univariate and multivariate analyses confirmed only LDH as an independent predictor of early death. Notably, anticoagulation therapy was associated with an improved prognosis of critical cases in this cohort.ConclusionOur results showed large differences between patients with severe and critical COVID-19. During the course of COVID-19 in the critical disease group, the incidence of hypoproteinemia, anemia, thrombocytopenia, and coagulation disorders increased significantly, which highlighted the importance of medical care in the first week after admission. LDH could act as an independent predictor of early death in critical cases, and anticoagulation therapy was correlated with an improved prognosis of patients with critical COVID-19.

Dataset Information

Inflammation characteristics and anti-inflammation treatment with tocilizumab of severe/critical COVID-19 patients: A retrospective cohort study.

Publications

Inflammation characteristics and anti-inflammation treatment with tocilizumab of severe/critical COVID-19 patients: A retrospective cohort study.

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