Efficacy of Thymosin Alpha 1 in the Treatment of COVID-19: A Multicenter Cohort Study.

Background: Thymosin alpha 1 (Tα1) is widely used to treat patients with COVID-19 in China; however, its efficacy remains unclear. This study aimed to explore the efficacy of Tα1 as a COVID-19 therapy. Methods: We performed a multicenter cohort study in five tertiary hospitals in the Hubei province of China between December 2019 and March 2020. The patient non-recovery rate was used as the primary outcome. Results: All crude outcomes, including non-recovery rate (65/306 vs. 290/1,976, p = 0.003), in-hospital mortality rate (62/306 vs. 271/1,976, p = 0.003), intubation rate (31/306 vs. 106/1,976, p = 0.001), acute respiratory distress syndrome (ARDS) incidence (104/306 vs. 499/1,976, p = 0.001), acute kidney injury (AKI) incidence (26/306 vs. 66/1,976, p < 0.001), and length of intensive care unit (ICU) stay (14.9 ± 12.7 vs. 8.7 ± 8.2 days, p < 0.001), were significantly higher in the Tα1 treatment group. After adjusting for confounding factors, Tα1 use was found to be significantly associated with a higher non-recovery rate than non-Tα1 use (OR 1.5, 95% CI 1.1-2.1, p = 0.028). An increased risk of non-recovery rate associated with Tα1 use was observed in the patient subgroups with maximum sequential organ failure assessment (SOFA) scores ≥2 (OR 2.0, 95%CI 1.4-2.9, p = 0.024), a record of ICU admission (OR 5.4, 95%CI 2.1-14.0, p < 0.001), and lower PaO2/FiO2 values (OR 1.9, 95%CI 1.1-3.4, p = 0.046). Furthermore, later initiation of Tα1 use was associated with a higher non-recovery rate. Conclusion: Tα1 use in COVID-19 patients was associated with an increased non-recovery rate, especially in those with greater disease severity.

Intravenous immunoglobulin treatment for patients with severe COVID-19: a retrospective multicentre study.

OBJECTIVES: Intravenous immunoglobulin (IVIG) is commonly used to treat severe COVID-19, although the clinical outcome of such treatment remains unclear. This study evaluated the effectiveness of IVIG treatment in severe COVID-19 patients. METHODS: This retrospective multicentre study evaluated 28-day mortality in severe COVID-19 patients with or without IVIG treatment. Each patient treated with IVIG was matched with one untreated patient. Logistic regression and inverse probability weighting (IPW) were used to control confounding factors. RESULTS: The study included 850 patients (421 IVIG-treated patients and 429 non-IVIG-treated patients). After matching, 406 patients per group remained. No significant difference in 28-day mortality was observed after IPW analysis (average treatment effect (ATE) = 0.008, 95% CI -0.081 to 0.097, p 0.863). There were no significant differences between the IVIG group and non-IVIG group for acute respiratory distress syndrome, diffuse intravascular coagulation, myocardial injury, acute hepatic injury, shock, acute kidney injury, non-invasive mechanical ventilation, invasive mechanical ventilation, continuous renal replacement therapy and extracorporeal membrane oxygenation except for prone position ventilation (ATE = -0.022, 95% CI -0.041 to -0.002, p 0.028). DISCUSSION: IVIG treatment was not associated with significant changes in 28-day mortality in severe COVID-19 patients. The effectiveness of IVIG in treating patients with severe COVID-19 needs to be further investigated through future studies.

Novel phenotypes of coronavirus disease: a temperature-based trajectory model.

BACKGROUND: Coronavirus disease has heterogeneous clinical features; however, the reasons for the heterogeneity are poorly understood. This study aimed to identify clinical phenotypes according to patients' temperature trajectory. METHOD: A retrospective review was conducted in five tertiary hospitals in Hubei Province from November 2019 to March 2020. We explored potential temperature-based trajectory phenotypes and assessed patients' clinical outcomes, inflammatory response, and response to immunotherapy according to phenotypes. RESULTS: A total of 1580 patients were included. Four temperature-based trajectory phenotypes were identified: normothermic (Phenotype 1); fever, rapid defervescence (Phenotype 2); gradual fever onset (Phenotype 3); and fever, slow defervescence (Phenotype 4). Compared with Phenotypes 1 and 2, Phenotypes 3 and 4 had a significantly higher C-reactive protein level and neutrophil count and a significantly lower lymphocyte count. After adjusting for confounders, Phenotypes 3 and 4 had higher in-hospital mortality (adjusted odds ratio and 95% confidence interval 2.1, 1.1-4.0; and 3.3, 1.4-8.2, respectively), while Phenotype 2 had similar mortality, compared with Phenotype 1. Corticosteroid use was associated with significantly higher in-hospital mortality in Phenotypes 1 and 2, but not in Phenotypes 3 or 4 (p for interaction < 0.01). A similar trend was observed for gamma-globulin. CONCLUSIONS: Patients with different temperature-trajectory phenotypes had different inflammatory responses, clinical outcomes, and responses to corticosteroid therapy.

Corticosteroid treatment in severe COVID-19 patients with acute respiratory distress syndrome.

BACKGROUNDCorticosteroids are widely used in patients with COVID 19, although their benefit-to-risk ratio remains controversial.METHODSPatients with severe COVID-19-related acute respiratory distress syndrome (ARDS) were included from December 29, 2019 to March 16, 2020 in 5 tertiary Chinese hospitals. Cox proportional hazards and competing risks analyses were conducted to analyze the impact of corticosteroids on mortality and SARS-CoV-2 RNA clearance, respectively. We performed a propensity score (PS) matching analysis to control confounding factors.RESULTSOf 774 eligible patients, 409 patients received corticosteroids, with a median time from hospitalization to starting corticosteroids of 1.0 day (IQR 0.0-3.0 days) . As compared with usual care, treatment with corticosteroids was associated with increased rate of myocardial (15.6% vs. 10.4%, P = 0.041) and liver injury (18.3% vs. 9.9%, P = 0.001), of shock (22.0% vs. 12.6%, P < 0.001), of need for mechanical ventilation (38.1% vs. 19.5%, P < 0.001), and increased rate of 28-day all-cause mortality (44.3% vs. 31.0%, P < 0.001). After PS matching, corticosteroid therapy was associated with 28-day mortality (adjusted HR 1.46, 95% CI 1.01-2.13, P = 0.045). High dose (>200 mg) and early initiation (≤3 days from hospitalization) of corticosteroid therapy were associated with a higher 28-day mortality rate. Corticosteroid use was also associated with a delay in SARS-CoV-2 coronavirus RNA clearance in the competing risk analysis (subhazard ratio 1.59, 95% CI 1.17-2.15, P = 0.003).CONCLUSIONAdministration of corticosteroids in severe COVID-19-related ARDS is associated with increased 28-day mortality and delayed SARS-CoV-2 coronavirus RNA clearance after adjustment for time-varying confounders.FUNDINGNone.