Brief summaryNearly 50% patients of novel coronavirus (SARS-CoV-2)-infected pneumonia could not reach obvious clinical and radiological remission within 10 days after hospitalization. These refractory COVID-19 patients showed an obvious difference with the general patients in clinical characteristics. AbstractBackground: Since December 2019, novel coronavirus (SARS-CoV-2)-infected pneumonia (COVID-19) occurred in Wuhan, and rapidly spread throughout China.This study aimed to clarify the characteristics of patients with refractory COVID-19. Methods:In this retrospective single-center study, we included 155 consecutive patients with confirmed COVID-19 in Zhongnan Hospital of Wuhan University from January 1 st to February 5 th . The cases were divided into general and refractory COVID-19 groups according to the clinical efficacy after hospitalization, and the difference between groups were compared. Results:Compared with general COVID-19 patients (45.2%), refractory patients had an older age, male sex, more underlying comorbidities, lower incidence of fever, higher levels of maximum temperature among fever cases, higher incidence of breath shortness and anorexia, severer disease assessment on admission, high levels of neutrophil, aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and C-reactive protein, lower levels of platelets and albumin, and higher incidence of bilateral pneumonia and pleural effusion (P<0.05). Refractory COVID-19 patients were more likely to receive oxygen, mechanical ventilation, expectorant, and adjunctive treatment including corticosteroid, antiviral drugs and immune enhancer (P<0.05). After adjustment, those with refractory COVID-19 were also more likely to have a male sex and manifestations of anorexia and fever on admission, and receive oxygen, expectorant and adjunctive agents (P<0.05) when considering the factors of disease severity on admission, mechanical ventilation, and ICU transfer.Conclusion: Nearly 50% COVID-19 patients could not reach obvious clinical and radiological remission within 10 days after hospitalization. The patients with male sex, anorexia and no fever on admission predicted poor efficacy.

Background In December 2019, the coronavirus disease 2019 (COVID-19) emerged in Wuhan city and spread rapidly throughout China and the world. In this study, we aimed to describe the clinical course and outcomes of older patients with COVID-19. Methods This is a retrospective investigation of hospitalized older patients with confirmed COVID-19 at Zhongnan Hospital of Wuhan University from January 1, 2020, to February 10, 2020. Results In total, 203 patients were diagnosed with COVID-19, with a median age of 54 years (interquartile range, 41–68; range, 20–91 years). Men accounted for 108 (53.2%) of the cases, and 55 patients (27.1%) were more than 65 years of age. Among patients who were 65 years and older, the mortality rate was 34.5% (19/55), which was significantly higher than that of the younger patients at 4.7% (7/148). Common symptoms of older patients with COVID-19 included fever (94.5%; n = 52), dry cough (69.1%; n = 38), and chest distress (63.6%; n = 35). Compared with young patients, older patients had more laboratory abnormalities and comorbidities. Through a multivariate analysis of the causes of death in older patients, we found that males, comorbidities, time from disease onset to hospitalization, abnormal kidney function, and elevated procalcitonin levels were all significantly associated with death. Conclusions In the recent outbreak of COVID-19, our local hospital in Wuhan found that patients aged 65 and older had greater initial comorbidities, more severe symptoms, and were more likely to experience multiorgan involvement and death, as compared to younger patients.

2 6 Sweden 2 7 2 8 Abstract = 186 words, Main text = 1722 words, Figures =2. Abstract 3 0 Objectives: Comorbidities have significant indications for the disease outcome of COVID-19, 3 1 however which underlying diseases that contribute the most to aggravate the conditions of 3 2 COVID-19 patients is still largely unknown. SARS-CoV-2 viral clearance is a golden standard 3 3 for defining the recovery of COVID-19 infections. To dissect the underlying diseases that 3 4 could impact on viral clearance, we enrolled 106 COVID-19 patients who were hospitalized in 3 5 Methodology: We comprehensively analyzed demographic, clinical and laboratory data, as 3 8 well as patient treatment records. Survival analyses with Kaplan-Meier and Cox regression 3 9 modelling were employed to identify factors influencing the viral clearance negatively. 4 0 Results: We found that increasing age, male gender, and angiotensin-converting enzyme 2 4 1 (ACE2) associated factors (including hypertension, diabetes, and cardiovascular diseases) 4 2 adversely affected the viral clearance. Furthermore, analysis by a random forest survival 4 3 model pointed out hypertension, cortisone treatment, gender, and age as the four most 4 4 important variables. 4 5 Conclusions: We conclude that patients at old age, males, and/or having diseases 4 6 associated with high expression of ACE2 will have worse prognosis during a COVID-19 4 7 infections. 4 8 4 9

Background: Viral clearance is one important indicator for the recovery of SARS-CoV-2 infected patients. Suboptimal T and B cell responses can delay viral clearance in MERS and SARS patients. The role of leukomonocytes in viral clearance of COVID-19 patients is not yet well defined.Methods: From January 26 to February 28, 2020, an observational study was launched at Zhongnan Hospital of Wuhan University, Wuhan, China. We enrolled 25 laboratory-confirmed COVID-19 patients, whose throat-swab specimens were tested positive for SARS-CoV-2 infection by qRT-PCR. We comprehensively analyzed clinical records, counts of lymphocyte subsets including CD3+, CD4+, CD8+ T cells, B cells and NK cells in the patients who successfully cleared SARS-CoV-2, and compared to those that failed to, after a standardized treatment of 8-14 days. Findings: In 25 enrolled COVID-19 patients, lymphopeniawas a common feature. After the treatment, 14 patients were tested negative for SARS-CoV-2. The patients that cleared the infection had restored the numbers of CD3+, CD4+, CD8+ T cellsand B cells as compared to the still viral RNA positive patients, while the recovered patients had a higher count of leukomonocytes. Conclusions: By comparison of leukomonocytes counts in COVID-19 patients at different stages of the disease, we found that CD3+, CD4+, CD8+ T cells and B cells appear to play important roles in viral clearance. The restoration of leukomonocytes counts from peripheral blood can be used as prognosis for the recovery of an COVID-19 infection. We propose that restoration of leukomonocytes counts can be added to the COVID-19 diagnostic guidanceas a criterion for releasing and discharging patients.

Background Inflammation and oxidative stress play a crucial role in the pathogenesis of renal ischemia/reperfusion injury (IRI). Maresin 1 (MaR1), which has shown strong anti-inflammatory and antioxidant effects, was recently reported to have protective properties in several different animal models. Aim The objectives of our study were to determine whether MaR1 alleviates renal IRI and to identify the underlying mechanisms. Materials and methods The mouse model in this study was induced by ischemia of the left kidney for 45 minutes and by nephrectomy of the right kidney. All mice were intravenously injected with a vehicle or MaR1. Renal histopathologic changes, function, proinflammatory cytokines, and oxidative stress were assessed. The expression of proteins was measured by Western blot. Results The results indicated that MaR1 markedly protected against renal IRI. The protective effects were accompanied by the reduction of histologic changes and reduction of renal dysfunction. Meanwhile, MaR1 remarkably mitigated renal IRI-induced inflammation and oxidative stress. In addition, our results showed that MaR1 significantly inhibited the expression of TLR4 and the expression of phosphorylated Erk, JNK, and P38. Furthermore, MaR1 decreased the nuclear translocation of NF-κB and increased the nuclear translocation of Nrf2. Conclusion MaR1 protects against renal IRI by inhibiting the TLR4/MAPK/NF-κB pathways, which mediate anti-inflammation, and by activating the Nrf2 pathway, which mediates antioxidation.

Coronavirus disease 2019 (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infection was first detected in Wuhan, China in late December 2019. The virus was spreading rapidly to other cities of China and accumulating cases had been reported (Li et al. 2020). On March 11, 2020, WHO declared the outbreak of SARS-CoV-2 as a pandemic. As of June 28, around 10 million COVID-19 cases have been reported in 216 countries or territories and the worldwide death toll has passed 490,000 according to data from WHO (https://www.who.int/emer gencies/diseases/novel-coronavirus-2019). Until now, there is no effective drug or vaccine available against SARS-Cov-2 infection. In addition to the recent emerged SARS-CoV-2, hepatitis B virus (HBV) is one of the viruses which cause a global infection and threat public health. In worldwide, the prevalence of HBsAg is about 3.9% (Polaris Observatory 2018). According to a nationwide epidemiological survey of population whose ages range from 1 to 59 years in China, 2006, the prevalence of HBsAg was 7.2% (Liang et al. 2009). As SARS-CoV-2 and HBV both can cause liver damage (Fan et al. 2020), further understanding of the risk of SARS-CoV-2 on patients with HBV infection is urgently required in order to design an optimized treatment strategy. However, the impacts of SARS-CoV-2 infection on HBV patients are still not clear. For example, we do not yet know whether the SARS-CoV-2 infection is more severe in HBV patients and we also do not have much knowledge about the impact of SARS-CoV-2 on the course of HBV infection. In this retrospective study, we investigated the clinical characterizes of the patients coinfected with SARS-CoV-2 and HBV by analyzing the clinical records and laboratory tests of 123 COVID-19 patients admitted to

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These findings strongly suggest that berberine is a potential antiangiogenic agent and a promising antitumor drug for HCC.