Ruxolitinib as an Effective Treatment for Hemophagocytic Lymphohistiocytosis Secondary to SARS-Cov-2 Infection: A Case Report.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome. SARS-CoV-2 infection can induce secondary HLH, as described in previous case reports, but diagnosis and treatment are challenging. Case Study: We described an older male patient diagnosed with HLH related to previous SARS-CoV-2 infection. Fever was the only clinical manifestation initially but deterioration in clinical condition and laboratory parameters was observed during hospitalization. He responded poorly to classical therapy but was successfully treated with ruxolitinib. Conclusion: Clinicians should be aware of the possibility of HLH secondary to mild SARS-CoV-2 infection and take timely therapeutic measures to inhibit an inflammatory factor storm. Ruxolitinib is a potential choice for COVID-19 related HLH.

The Relationship between the Use of Non-Verbal Information in Communication and Student Connectedness and Engagement in Online Design Education

The COVID-19 pandemic poses a threat to the sustainability of higher education. Connectedness and engagement, two characteristics crucial to design education, have weakened significantly in online courses. However, limited research has been conducted on online design education than on STEM fields. Based on the dual coding theory, the purpose of this study was to use non-verbal tools to enhance design student connectedness and engagement in online class communication. In a quasi-experiment, 122 design students from a Chinese university were questioned and analyzed. They were randomly assigned to four different teaching situations and the effectiveness of two non-verbal tools was tested: emoticons and shared whiteboards. The ANOVA revealed a positive correlation between the use of non-verbal information in online class communication and the connectedness and engagement of design students. Moreover, the students in the group who used plentiful personified-form emoticons gave feedback and reported a stronger sense of connectedness and engagement. The whiteboard group's data did not significantly differ from the control group, unlike the STEM discipline. To better develop the sustainability of design education, we provide recommendations for the design of online-education software and the method of online design instruction.

Short-term effects of COVID-19 on the risk of traumatic fractures in China cities.

This study aimed to investigate the association between COVID-19 and fracture risk and provide a targeted reference for the world through China's experience. A nationally representative sample of COVID-19 prevalence areas selected using stratified random sampling was retrospectively analyzed. Age, sex, fracture site, mechanism of injury, and concurrent fractures of traumatic fracture patients in selected hospitals were collected from 10 January to 10 July 2020. The epidemiologic characteristics of traumatic fractures and the association between COVID-19 and fracture risk were explored using descriptive epidemiological methods and a distributed lag nonlinear model. A total of 67,249 patients (52.3% males, 49.4 ± 19.4 years old) with 68,989 fractures were included. The highest proportion of fractures were in the tibia and fibula (14.9%), followed by the femur (13.6%) and ulna and radius (12.5%). Low-energy fractures accounted for 23.3%. With the increase in newly confirmed COVID-19 cases, fracture risk decreased for children, young and middle-aged adults, elderly men, high-energy fractures, and residents in regions with < 1000 cumulative confirmed COVID-19 cases. Fracture risk decreased sharply in all residents except elderly women, for low-energy fractures, and in regions with > 1000 cumulative confirmed COVID-19 cases when newly confirmed COVID-19 cases increased in China. Primary (home) prevention measures are emphasized to prevent traumatic fractures.

SARS-CoV-2 ORF3a induces RETREG1/FAM134B-dependent reticulophagy and triggers sequential ER stress and inflammatory responses during SARS-CoV-2 infection.

SARS-CoV-2 infections have resulted in a very large number of severe cases of COVID-19 and deaths worldwide. However, knowledge of SARS-CoV-2 infection, pathogenesis and therapy remains limited, emphasizing the urgent need for fundamental studies and drug development. Studies have shown that induction of macroautophagy/autophagy and hijacking of the autophagic machinery are essential for the infection and replication of SARS-CoV-2; however, the mechanism of this manipulation and the function of autophagy during SARS-CoV-2 infection remain unclear. In the present study, we identified ORF3a as an inducer of autophagy (in particular reticulophagy) and revealed that ORF3a localizes to the ER and induces RETREG1/FAM134B-related reticulophagy through the HMGB1-BECN1 (beclin 1) pathway. As a consequence, ORF3a induces ER stress and inflammatory responses through reticulophagy and then sensitizes cells to the acquisition of an ER stress-related early apoptotic phenotype and facilitates SARS-CoV-2 infection, suggesting that SARS-CoV-2 ORF3a hijacks reticulophagy and then disrupts ER homeostasis to induce ER stress and inflammatory responses during SARS-CoV-2 infection. These findings reveal the sequential induction of reticulophagy, ER stress and acute inflammatory responses during SARS-CoV-2 infection and imply the therapeutic potential of reticulophagy and ER stress-related drugs for COVID-19.Abbreviations: CQ: chloroquine; DEGs: differentially expressed genes; ER: endoplasmic reticulum; GSEA: gene set enrichment analysis; HMGB1: high mobility group box 1; HMOX1: heme oxygenase 1; MERS-CoV: Middle East respiratory syndrome coronavirus; RETREG1/FAM134B: reticulophagy regulator 1; RTN4: reticulon 4; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TN: tunicamycin.

The atlas of ACE2 expression in fetal and adult human hearts reveals the potential mechanism of heart-injured patients infected with SARS-CoV-2.

Numerous studies have shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect host cells through binding to angiotensin I converting enzyme 2 (ACE2) expressing in various tissues and organs. In this study, we deeply analyzed the single-cell expression profiles of ACE2 in fetal and adult human hearts to explore the potential mechanism of SARS-CoV-2 harming the heart. The molecular docking software was used to simulate the binding of SARS-CoV-2 and its variant spike protein with ACE2. The genes closely related to ACE2 in renin-angiotensin system (RAS) were identified by constructing a protein-protein interaction network. Through the analysis of single-cell transcription profiles at different stages of human embryos, we found that the expression level of ACE2 in ventricular myocytes was increased with embryonic development. The results of single-cell sequencing analysis showed that the expression of ACE2 in ventricular myocytes was upregulated in heart failure induced by dilated cardiomyopathy compared with normal hearts. The upregulation of ACE2 increases the risk of infection with SARS-CoV-2 in fetal and adult human hearts. We also further confirmed the expression of ACE2 and ACE2-related genes in normal and SARS-CoV-2-infected human pluripotent stem cell-derived cardiomyocytes. In addition, the pathway analysis revealed that ACE2 may regulate the differently expressed genes in heart failure through calcium signaling pathway and Wnt signaling pathway.

Analysis of pathogens and risk factors of secondary pulmonary infection in patients with COVID-19.

To investigate the distribution and risk factors of pathogens in secondary pulmonary infection in patients with COVID-19.142 patients with confirmed COVID-19 from Shanghai Public Health Clinical Center were collected, and 32 patients with pulmonary infection were taken as the infection group. The distribution of pathogens in the sputum specimens was applied for retrospective analysis. Meanwhile, 110 patients diagnosed with COVID-19, but without pulmonary infection were regarded as the asymptomatic group. The risk factors of pulmonary infection were analyzed with generalized linear models and logistic regression. The pathogens in the lung infection group were mainly gram-negative bacteria (22, 68.8%), especially Klebsiella pneumoniae. Gram-positive bacteria and fungi accounted for 13 (40.6%), mainly Staphylococcus aureus, and 11 (34.4%), mainly Candida albicans. There were 14 cases (43.8%) infected with two or more pathogens. The comparison between the two groups found that, patients with elder age, underlying diseases, more lung lesions and low protein contents, were more likely to develop lung infections. At last, univariate analysis showed that 6 factors, including indwelling gastric catheter, the number of deep vein catheters, tracheal intubation tracheotomy, invasive mechanical ventilation, hormonal application, and the use of more than three antibacterial drugs, are risk factors for COVID-19 secondary pulmonary infection. Generalized linear models and logistic regression analysis showed antimicrobial use as an independent risk factor for COVID-19 secondary lung infection. There are many risk factors for secondary lung infection in severe COVID-19 patients, and it is recommended to use antibiotics reasonably.

Coagulopathy in patients with COVID-19: a systematic review and meta-analysis.

COVID-19 patients frequently exhibit coagulation abnormalities and thrombotic events. In this meta-analysis, we investigated the association between coagulopathy and the severity of COVID-19 illness. Using PubMed, Embase, Cochrane, WanFang Database, CNKI, and medRxiv, a systematic literature search was conducted for studies published between December 1, 2019 and May 1, 2020. We then analyzed coagulation parameters in COVID-19 patients exhibiting less severe and more severe symptoms. All statistical analyses were performed using Stata14.0 software. A total of 3,952 confirmed COVID-19 patients from 25 studies were included in the meta-analysis. Patients with severe symptoms exhibited higher levels of D-dimer, prothrombin time (PT), and fibrinogen (FIB) than patients with less severe symptoms (SMD 0.83, 95% CI: 0.70-0.97, I2 56.9%; SMD 0.39, 95% CI: 0.14-0.64, I2 79.4%; and SMD 0.35, 95% CI: 0.17-0.53, I2 42.4%, respectively). However, platelet and activated partial thromboplastin times did not differ (SMD -0.26, 95% CI: -0.56-0.05, I2 82.2%; and SMD -0.14, 95% CI: -0.45-0.18, I2 75.7%, respectively). These findings demonstrate that hypercoagulable coagulopathy is associated with the severity of COVID-19 symptoms and that D-dimer, PT, and FIB values are the main parameters that should be considered when evaluating coagulopathy in COVID-19 patients.

Anticoagulation Management in Severe Coronavirus Disease 2019 Patients on Extracorporeal Membrane Oxygenation.

OBJECTIVE: To explore special coagulation characteristics and anticoagulation management in extracorporeal membrane oxygenation (ECMO)-assisted patients with coronavirus disease 2019 (COVID-19). DESIGN: Single-center, retrospective observation of a series of patients. PARTICIPANTS: Laboratory-confirmed severe COVID-19 patients who received venovenous ECMO support from January 20-May 20, 2020. INTERVENTIONS: This study analyzed the anticoagulation management and monitoring strategies, bleeding complications, and thrombotic events during ECMO support. MEASUREMENTS AND MAIN RESULTS: Eight of 667 confirmed COVID-19 patients received venovenous ECMO and had an elevated D-dimer level before and during ECMO support. An ECMO circuit pack (oxygenator and tubing) was replaced a total of 13 times in all 8 patients, and coagulation-related complications included oxygenator thrombosis (7/8), tracheal hemorrhage (5/8), oronasal hemorrhage (3/8), thoracic hemorrhage (3/8), bleeding at puncture sites (4/8), and cannulation site hemorrhage (2/8). CONCLUSIONS: Hypercoagulability and secondary hyperfibrinolysis during ECMO support in COVID-19 patients are common and possibly increase the propensity for thrombotic events and failure of the oxygenator. Currently, there is not enough evidence to support a more aggressive anticoagulation strategy.

Efficacy and safety of Lianhua Qingwen combined with conventional antiviral Western Medicine in the treatment of coronavirus disease (covid-19) in 2019: Protocol for a systematic review and meta-analysis.

BACKGROUND: The novel coronavirus pneumonia (COVID-19) has spread to >200 countries and regions. There is no effective antiviral drug for COVID-19. Traditional Chinese medicine, such as Lianhua Qingwen, has achieved some curative effect in many countries, but its effect is not clear. We aim to assess the efficacy and safety of Lianhua Qingwen combined with Conventional antiviral Western Medicine in Clinical treatment of COVID-19 or asymptomatic infection. METHODS: The following electronic bibliographic databases will be searched to identify relevant studies: CNKI, CBM, VIP and Wanfang databases, PubMed, EMBASE, MEDLINE, Cochrane central, and clinical trial registration centers, such as China Clinical Trial Registration Center (ChiCTR), Netherlands National Trial Registration Center (NTR) and clinical trials.gov. In addition, Manual retrieval of articles, conference papers, ongoing experiments, internal reports, among others, to supplement electronic retrieval. Select all eligible studies published before May 8, 2020.According to the Cochrane Handbook "bias risk" assessment tool, bias risk is independently assessed. The independent Newcastle Ottawa scale was used to conduct methodological quality assessment of nonrandomized trials. STATA15.1 and RevMan5.3 software were used to analyze meta outcomes of different intervention measures for the treatment of new crown pneumonia and the control group (conventional antiviral western medicine treatment) clinical efficacy. RESULTS: This study will provide a relatively high-quality synthesis of current evidence of Lianhua Qingwen combined with Conventional antiviral Western Medicine in the treatment of COVID-19 from several aspects including the Clinical effective rate, CT improvement rate, severe conversion rate, antipyretic time, disappearance rate of fever symptoms, disappearance rate of cough symptoms, disappearance rate of asthenia symptoms, and adverse drug events. CONCLUSION: The conclusion of this review will provide evidence to judge whether Lianhua Qingwen combined with Conventional antiviral Western Medicine is an effective and safe intervention for COVID-19. ETHICS AND DISSEMINATION: This systemic review will evaluate the efficacy and safety of Lianhua Qingwen combined with Conventional antiviral Western Medicine in the treatment of COVID-19. Since all the data included are published, the systematic review does not need ethical approval. INPLASY REGISTRATION NUMBER: INPLASY202060067.

Extracorporeal Membrane Oxygenation for Coronavirus Disease 2019 in Shanghai, China.

Severe cases of coronavirus disease 2019 (COVID-19) cannot be adequately managed with mechanical ventilation alone. The role and outcome of extracorporeal membrane oxygenation (ECMO) in the management of COVID-19 is currently unclear. Eight COVID-19 patients have received ECMO support in Shanghai with seven with venovenous (VV) ECMO support and one veno arterial (VA) ECMO during cardiopulmonary resuscitation. As of March 25, 2020, four patients died (50% mortality), three patients (37.5%) were successfully weaned off ECMO after 22, 40, and 47 days support, respectively, but remain on mechanical ventilation. One patient is still on VV ECMO with mechanical ventilation. The partial pressure of oxygen/fractional of inspired oxygen ratio before ECMO initiation was between 54 and 76, and all were well below 100. The duration of mechanical ventilation before ECMO ranged from 4 to 21 days. Except the one emergent VA ECMO during cardiopulmonary resuscitation, other patients were on ECMO support for between 18 and 47 days. In conclusion, ensuring effective, timely, and safe ECMO support in COVID-19 is key to improving clinical outcomes. Extracorporeal membrane oxygenation support might be an integral part of the critical care provided for COVID-19 patients in centers with advanced ECMO expertise.