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.

Skin‐Inspired High‐Performance Active‐matrix Circuitry for Multimodal User‐Interaction

Artificial electronic skin (e‐skin), a network of mechanically flexible sensors which can wrap irregular surfaces conformally and quantify various stimuli sensitively, is potentially useful in healthcare monitoring and human‐machine interaction (HMI). Although various approaches have mimicked the structures and functions of the human skin, challenges remain with high‐density integration, super sensitivity, and multi‐functionality. A multimodal and comfortable skin‐inspired active‐matrix circuitry is reported here with high pixel density (>100 cm–2) based on all 2D materials, which exhibits excellent performance to detect both mechanical interactions and humidity variations. The ultra‐high sensitivity (>400 and ≈ 104 for strain and humidity sensing, respectively), long‐term stability (>1000 cycles), and rapid response time for every pixel can fulfill simultaneous multi‐stimulus sensing. Accordingly, a respiratory monitor is constructed to realize healthcare monitoring through observing the human breath frequency, intensity, and humidity in real‐time. Moreover, the multimodal e‐skin breaks through shackles of the contact sensor medium for HMI. 3D strain and humidity spatial mapping can reflect object location information even without contact, avoiding cross‐infection of viruses effectively between users during the COVID‐19 pandemic. The reported e‐skin will broaden applications for future healthcare and human–machine interactive devices. [ABSTRACT FROM AUTHOR] Copyright of Advanced Functional Materials is the property of John Wiley & Sons, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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.

Corticosteroid therapy in critically ill patients with COVID-19: a multicenter, retrospective study.

BACKGROUND: Corticoid therapy has been recommended in the treatment of critically ill patients with COVID-19, yet its efficacy is currently still under evaluation. We investigated the effect of corticosteroid treatment on 90-day mortality and SARS-CoV-2 RNA clearance in severe patients with COVID-19. METHODS: 294 critically ill patients with COVID-19 were recruited between December 30, 2019 and February 19, 2020. Logistic regression, Cox proportional-hazards model and marginal structural modeling (MSM) were applied to evaluate the associations between corticosteroid use and corresponding outcome variables. RESULTS: Out of the 294 critically ill patients affected by COVID-19, 183 (62.2%) received corticosteroids, with methylprednisolone as the most frequently administered corticosteroid (175 accounting for 96%). Of those treated with corticosteroids, 69.4% received corticosteroid prior to ICU admission. When adjustments and subgroup analysis were not performed, no significant associations between corticosteroids use and 90-day mortality or SARS-CoV-2 RNA clearance were found. However, when stratified analysis based on corticosteroid initiation time was performed, there was a significant correlation between corticosteroid use (≤ 3 day after ICU admission) and 90-day mortality (logistic regression adjusted for baseline: OR 4.49, 95% CI 1.17-17.25, p = 0.025; Cox adjusted for baseline and time varying variables: HR 3.89, 95% CI 1.94-7.82, p < 0.001; MSM adjusted for baseline and time-dependent variants: OR 2.32, 95% CI 1.16-4.65, p = 0.017). No association was found between corticosteroid use and SARS-CoV-2 RNA clearance even after stratification by initiation time of corticosteroids and adjustments for confounding factors (corticosteroids use ≤ 3 days initiation vs no corticosteroids use) using MSM were performed. CONCLUSIONS: Early initiation of corticosteroid use (≤ 3 days after ICU admission) was associated with an increased 90-day mortality. Early use of methylprednisolone in the ICU is therefore not recommended in patients with severe COVID-19.

A Pattern Categorization of CT Findings to Predict Outcome of COVID-19 Pneumonia.

Background: As global healthcare system is overwhelmed by novel coronavirus disease (COVID-19), early identification of risks of adverse outcomes becomes the key to optimize management and improve survival. This study aimed to provide a CT-based pattern categorization to predict outcome of COVID-19 pneumonia. Methods: One hundred and sixty-five patients with COVID-19 (91 men, 4-89 years) underwent chest CT were retrospectively enrolled. CT findings were categorized as Pattern 0 (negative), Pattern 1 (bronchopneumonia pattern), Pattern 2 (organizing pneumonia pattern), Pattern 3 (progressive organizing pneumonia pattern), and Pattern 4 (diffuse alveolar damage pattern). Clinical findings were compared across different categories. Time-dependent progression of CT patterns and correlations with clinical outcomes, i.e." discharge or adverse outcome (admission to ICU, requiring mechanical ventilation, or death), with pulmonary sequelae (complete absorption or residuals) on CT after discharge were analyzed. Results: Of 94 patients with outcome, 81 (86.2%) were discharged, 3 (3.2%) were admitted to ICU, 4 (4.3%) required mechanical ventilation, 6 (6.4%) died. 31 (38.3%) had complete absorption at median day 37 after symptom onset. Significant differences between pattern-categories were found in age, disease severity, comorbidity and laboratory results (all P < 0.05). Remarkable evolution was observed in Pattern 0-2 and Pattern 3-4 within 3 and 2 weeks after symptom-onset, respectively; most of patterns remained thereafter. After controlling for age, CT pattern significantly correlated with adverse outcomes [Pattern 4 vs. Pattern 0-3 [reference]; hazard-ratio [95% CI], 18.90 [1.91-186.60], P = 0.012]. CT pattern [Pattern 3-4 vs. Pattern 0-2 [reference]; 0.26 [0.08-0.88], P = 0.030] and C-reactive protein [>10 vs. ≤ 10 mg/L [reference]; 0.31 [0.13-0.72], P = 0.006] were risk factors associated with pulmonary residuals. Conclusion: CT pattern categorization allied with clinical characteristics within 2 weeks after symptom onset would facilitate early prognostic stratification in COVID-19 pneumonia.

Improved Epidemic Dynamics Model and Its Prediction for COVID-19 in Italy

The outbreak of coronavirus disease 2019 (COVID-19) has become a global public health crisis due to its high contagious characteristics. In this article, we propose a new epidemic-dynamics model combining the transmission characteristics of COVID-19 and then use the reported epidemic data from 15 February to 30 June to simulate the spread of the Italian epidemic. Numerical simulations showed that (1) there was a remarkable amount of asymptomatic individuals;(2) the lockdown measures implemented by Italy effectively controlled the spread of the outbreak;(3) the Italian epidemic has been effectively controlled, but SARS-CoV-2 will still exist for a long time;and (4) the intervention of the government is an important factor that affects the spread of the epidemic.