Clinical Characteristics and Outcomes in Patients with COVID-19 Received Tocilizumab in Wuhan, China: A Multicentre Retrospective Cohort Study (preprint)

Background: Coronavirus Disease-2019 (COVID-19) has caused considerable morbidity and mortality. Hence, there is an urgency to find effective treatment. Tocilizumab, an inhibitor of IL-6, has been widely proposed as a treatment of severely ill patients without robust evidence supporting its use. Methods: In this multicentre, retrospective, cohort study, we included 5,235 adult patients who were admitted to 3 hospitals in Wuhan, China with confirmed COVID-19 from January 20 to March 18, 2020 . 65 patients in tocilizumab group and 130 patients in non-tocilizumab group were propensity score matched at a ratio of 2:1 based on age, sex, and comorbidities. Detailed demographic data, comorbidities, radiological and laboratory parameters, complications and treatments were compared between tocilizumab group and non-tocilizumab group. Furthermore, univariable and multivariable Logistic and Cox regression models were used to explore the risk of complications and in-hospital death associated with tocilizumab. Findings: During the follow-up, patients in non-tocilizumab group were more likely to develop into death (42 [32·31%] vs 14 [21·54%]). After adjusting for confounding, the detected risk for in-hospital death was lower in the tocilizumab group versus the non-tocilizumab group (HR=0·47; 95% CI=0·25-0·90; p=0·023). In the multivariable logistic regression model, use of tocilizumab was associated with a lower risk of ARDS (OR=0 · 23; 95% CI=0·11-0·45; p<0·0001). Before treatment the patients had heightened inflammation and more dysregulated immune cells, which might aggravate disease progression. However, abnormally elevated IL-6, CRP, fibrinogen and APTT decreased in COVID-19 patients after treatment. And the counts of lymphocytes and immune cells subset in peripheral blood, which decreased in patients, returned to normal after treatment. No obvious complications were observed. Interpretation: Tocilizumab may be of value in improving outcomes in severe patients of COVID-19, which provided a novel strategy for COVID-19-induced cytokine release syndrome (CRS). Our preliminary data could inform bedside decisions until more data from randomized, controlled clinical trials becomes available.Funding Statement: SARS-CoV-2 Pneumonia Emergency Technology Public Relations Project of Tongji Medical College, Huazhong University of Science and Technology (No. 2020kfyXGYJ043) and National Key Research and Development Plan for the Emergency Management of Novel Coronavi rus Pneumonia, China (No. 2020YFC0845100).Declaration of Interests: The authors report no conflicts of interest.Ethics Approval Statement: This study was approved by the Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (TJ-C20200108) and granted a waiver of informed consent from study participants.

Clinical Characteristics and Risk Factors of Disseminated Intravascular Coagulation in Patients with COVID-19 (preprint)

Background: Coronavirus disease 2019 (COVID-19) has spread globally. However, the association between COVID-19 and disseminated intravascular coagulation (DIC) has been scarcely addressed. We aimed to systematically characterize the clinical features and examine risk factors for DIC development in COVID-19 patients.Methods: In this single-centered, retrospective, and observational study, all patients with DIC (N=59) and 270 patients without DIC were matched by propensity score matching based on age, sex, and comorbidities. Demographic data, symptoms, radiological, laboratory examinations, and clinical outcomes were compared between patients with and without DIC. Furthermore, univariable and multivariable logistic regression were used to explore the risk factors associated with DIC development in COVID-19 patients.Results: Higher proportion of patients with DIC and COVID-19 (54 of 59 [91·53%]) developed into death than non DIC patients (58 of 270 [21·48%]). Patients with DIC presented aggravated inflammation responses, liver damage, and especially coagulation dysfunction. Moreover, in addition to previously reported coagulation-related markers, such as FDP, D-dimer, and platelet, we also identified several novel risk factors associated with DIC development, including decreased fibrinogen (OR=0·476, 95%CI=0·380-0·596, P<0·0001) and ALB (0·901, 0·845- 0·961, P=0·0015), and elevated IL-6 (1·010, 1·005-1·015, P=0·00017) and TNF-α (1·053, 1·016-1·091, P=0·0045).Conclusions: Patients with DIC and COVID-19 were predisposed to poor clinical outcomes. These risk factors identified may be helpful for early surveillance of disease progression and making standardized treatment strategies.

Clinical Characteristics and Risk Factors of Fatal Patients with COVID-19: a Retrospective Cohort Study in Wuhan, China (preprint)

Background The coronavirus disease 2019 (COVID-19) has caused global pandemic, resulting in considerable mortality. The risk factors, clinical treatments and especially comprehensive risk models for COVID-19 death are urgently warranted.Methods In this retrospective study, 281 non-survivors and 712 survivors with propensity score matching by age, sex and comorbidities were enrolled from January 13, 2020 to March 31, 2020.Results Higher SOFA, qSOFA, APACHE II and SIRS scores, hypoxia, elevated inflammatory cytokines, multi-organ dysfunction, decreased immune cells subsets and complications were significantly associated with the higher COVID-19 death risk. In addition to traditional predictors for death risk, including APACHE II (AUC = 0.83), SIRS (AUC = 0.75), SOFA (AUC = 0.70) and qSOFA scores (AUC = 0.61), another four prediction models that included immune cells subsets (AUC = 0.90), multiple organ damage biomarkers (AUC = 0.89), complications (AUC = 0.88) and inflammatory-related indexes (AUC = 0.75) were established. Additionally, the predictive accuracy of combining these risk factors (AUC = 0.950) was also significantly higher than that of each risk group alone, outperforming previous risk models, which was significant for early clinical management for COVID-19.Conclusions The potential risk factors could help to predict the clinical prognosis of COVID-19 patients at an early stage. The combined model might be more suitable for the death risk evaluation of COVID-19.

Risk factors related to acute respiratory distress syndrome and death in patients with COVID-19: a retrospective cohort study in Wuhan, China (preprint)

Background:The COVID-19 pandemic has been considered a great threat to global public health. We aimed to clarify the risk factors associated with the development of acute respiratory distress syndrome (ARDS) and progression from ARDS to death and construct a risk prediction model.Methods:In this single-centered, retrospective, and observational study, 796 COVID-19 patients developed ARDS and 735 COVID-19 patients without ARDS were matched by propensity score at an approximate ratio of 1:1 based on age, sex and comorbidities. Demographic data, symptoms, radiological findings, laboratory examinations, and clinical outcomes were compared between those with or without ARDS. Univariable and multivariable logistic regression models were applied to explore the risk factors for development of ARDS and progression from ARDS to death and establish a comprehensive risk model. Results:Higher SOFA, qSOFA, APACHE II and SIRS scores, elevated inflammatory cytokines, dysregulated multi-organ damage biomarkers, decreased immune cell subsets were associated with higher proportion of death (34.17% vs 1.22%; P<0.001) and increased risk odds of death (OR=57.216, 95%CI=28.373-115.378; P<0.001) in COVID-19 patients with ARDS. In addition to previous reported risk factors related to ARDS development and death, such as neutrophils, IL-6, D-Dimer, leukocytes and platelet, we identified elevated TNF-α (OR=1.146, 95%CI=1.100-1.194; P<0.001), CK-MB (OR=1.350, 95%CI=1.180-1.545; P<0.001), declined ALB (OR=0.834, 95%CI=0.799-0.872; P<0.001), CD8+ T cells (OR=0.983, 95%CI=0.976-0.990; P<0.001) and CD3-CD19+ B cells (OR=0.992, 95%CI=0.988-0.997; P=0.003) as novel risk factors. Most importantly, the predictive accuracy of the combined model integrating four score systems and these risk factors demonstrated highest among all models for the development of ARDS (AUC= 0.904) and the progression from ARDS to death (AUC= 0.959).Conclusion:COVID-19 patients with ARDS were more likely to develop into death. The potential risk factors and the comprehensive prediction model could be helpful to identify patients that are at risk of developing ARDS with poor prognosis at an early stage, which might help physicians to formulate a timely therapeutic strategy.