Phone No: +86 18071093208 Word count of abstract: 215 Word count of text: 2483 Highlights  The immune status is significantly different between severe and non-severe COVID-19  The decrease of T lymphocyte correlated with the course of patients with COVID-19  The level of T lymphocyte is an indicator for severity and prognosis of COVID-19Abstract: Objectives: To explore the clinical course and its dynamic features of immune status in COVID-19 patients and find predictors correlated with severity and prognosis of COVID-19. Methods: The electronic medical records of 204 patients with COVID-19 pneumonia confirmed by nucleic acid testing were retrospectively collected and analyzed. Results: All Patients were divided into severe (69) and non-severe group (135). Lymphocyte subsets count, including CD3+ T cell, CD4+ T cell, CD8+ T cell, B cell (CD19+) and NK J o u r n a l P r e -p r o o f cell (CD16+56+), were significantly lower in severe group (P＜0.001). The dynamic levels of T lymphocytes in severe group were significantly lower from disease onset, but in the improved subgroup the value of T lymphocyte began to increase after about 15-day treatment and finally returned to the normal level. The cut-off value of the counts of CD3+ (576), CD4+ (391) and CD8+ (214) T cell were calculated and indicated significantly high sensitivity and specificity for severity of COVID-19. Conclusion: Our results shown that the decrease of CD3+, CD4+ and CD8+ T lymphocyte correlated with the course of patients with COVID-19 pneumonia, especially in severe cases. The level of T lymphocyte could be used as an indicator for prediction of severity and prognosis of patients with COVID-19 pneumonia. The application of glucocorticoid should be cautious in severe cases. IgE, IU/mL <100 23.5 (17.3-80.8) 21.9 (17.3-84.3) 30.85 (17.3-68.9) 0.707J o u r n a l P r e -p r o o f

Aimed to characterize the CT imaging and clinical course of asymptomatic cases with COVID-19 pneumonia. Methods: Asymptomatic cases with COVID-19 pneumonia confirmed by SARS-COV-2 nucleic acid testing in Renmin Hospital of Wuhan University were retrospectively enrolled. The characteristics of CT imaging and clinical feature were collected and analyzed. Results: 58 asymptomatic cases with COVID-19 pneumonia admitted to our hospital between Jan 1, 2020 and Feb 23, 2020 were enrolled. All patients had history of exposure to SARS-CoV-2. On admission, patients had no symptoms and laboratory findings were normal. The predominant feature of CT findings in this cohort was ground glass opacity (GGO) (55, 94.8%) with peripheral (44, 75.9%) distribution, unilateral location (34, 58.6%) and mostly involving one or two lobes (38, 65.5%), often accompanied by characteristic signs. After short-term follow-up, 16 patients (27.6%) presented symptoms with lower lymphocyte count and higher CRP, mainly including fever, cough and fatigue. The evolution of lesions on CT imaging were observed in 10 patients (17.2%). The average days of hospitalization was19.80 ±10.82 days, and was significantly longer in progression patients (28.60 ±7.55 day). Conclusion: CT imaging of asymptomatic cases with COVID-19 pneumonia has definite characteristics. Since asymptomatic infections as "covert transmitter", and some patients can progress rapidly in the short term. It is essential to pay attention to the surveillance of asymptomatic patients with COVID-19. CT scan has great value in screening and detecting patients with COVID-19 pneumonia, especially in the highly suspicious, asymptomatic cases with negative nucleic acid testing.

Itaconate, a metabolite produced during inflammatory macrophage activation, has been extensively described to be involved in immunoregulation, oxidative stress, and lipid peroxidation. As a form of iron and lipid hydroperoxide-dependent regulated cell death, ferroptosis plays a critical role in sepsis-induced acute lung injury (ALI). However, the relationship between itaconate and ferroptosis remains unclear. This study aims to explore the regulatory role of itaconate on ferroptosis in sepsis-induced ALI. In in vivo experiments, mice were injected with LPS (10 mg/kg) for 12 h to generate experimental sepsis models. Differential gene expression analysis indicated that genes associated with ferroptosis existed significant differences after itaconate pretreatment. 4-octyl itaconate (4-OI), a cell-permeable derivative of endogenous itaconate, can significantly alleviate lung injury, increase LPS-induced levels of glutathione peroxidase 4 (GPX4) and reduce prostaglandin-endoperoxide synthase 2 (PTGS2), malonaldehyde (MDA), and lipid ROS. In vitro experiments showed that both 4-OI and ferrostatin-1 inhibited LPS-induced lipid peroxidation and injury of THP-1 macrophage. Mechanistically, we identified that 4-OI inhibited the GPX4-dependent lipid peroxidation through increased accumulation and activation of Nrf2. The silence of Nrf2 abolished the inhibition of ferroptosis from 4-OI in THP-1 cells. Additionally, the protection of 4-OI for ALI was abolished in Nrf2-knockout mice. We concluded that ferroptosis was one of the critical mechanisms contributing to sepsis-induced ALI. Itaconate is promising as a therapeutic candidate against ALI through inhibiting ferroptosis.

Acute lung injury (ALI), a critical respiratory disorder that causes diffuse alveolar injury leads to high mortality rates with no effective treatment. ALI is characterized by varying degrees of ventilation/perfusion mismatch, severe hypoxemia, and poor pulmonary compliance. The diffuse injury to cells is one of most important pathological characteristics of ALI. Pyroptosis is a form of programmed cell death distinguished from apoptosis induced by inflammatory caspases, which can release inflammatory cytokines to clear cells infected by pathogens and promote monocytes to reassemble at the site of injury. And pyroptosis not only promotes inflammation in certain cell types, but also regulates many downstream pathways to perform different functions. There is increasing evidence that pyroptosis and its related inflammatory caspases play an important role in the development of acute lung injury. The main modes of activation of pyroptosis is not consistent among different types of cells in lung tissue. Meanwhile, inhibition of inflammasome, the key to initiating pyroptosis is currently the main way to treat acute lung injury. The review summarizes the relationship among inflammatory caspases, pyroptosis and acute lung injury and provides general directions and strategies to conduct further research.

Esophageal microbiota plays important roles in esophageal cancer. Esophagectomy, as the most important therapeutic way, contributes to changes of esophageal microbiome. However, there are few studies examining the esophageal microbiome and the metabolic changes before and after esophagectomy. The present study characterized the esophageal microbiome of 17 patients with esophageal squamous cell carcinoma (ESCC), 11 patients with esophagogastric junction (EGJ) cancer, 15 patients at 9-12 months after radical esophagectomy and 16 healthy controls (HC). 16S ribosomal RNA gene sequencing was used to evaluate the microbiome and predict the metabolic pathways. Our results showed that the microbial diversity was significantly lower in ESCC, EGJ and post-ESCC groups than that in the HC group. The abundance of Fusobacteria was higher (7.01 vs. 1.12%, P = 0.039) and the abundance of Actinobacteria (1.61 vs. 4.04%) was lower in the ESCC group than that in the HC group. We found significant differences in the abundance of Bacteroidetes (20.45 vs. 9.86%, P = 0.026), Fusobacteria (7.01 vs. 1.66%, P = 0.030) between ESCC and post-ESCC groups. The results of microbial composition analysis and PICRUSt demonstrated significant differences between ESCC and HC groups. The β diversity and PICRUSt suggested that the microbial composition and metabolic pathways were similar to HC group after esophagectomy. The monitoring of the esophagus microbiota may be an essential method to predict the recurrence of tumor.