The medical team from Xiangya Hospital to support Hubei, China

In recent years, oncolytic virotherapy has emerged as a promising anticancer therapy. Oncolytic viruses destroy cancer cells, without damaging normal tissues, through virus self-replication and antitumor immunity responses, showing great potential for cancer treatment. However, the clinical guidelines for administering oncolytic virotherapy remain unclear. Delivery routes for oncolytic virotherapy to patients vary in existing studies, depending on the tumor sites and the objective of studies. Moreover, the biosafety of oncolytic virotherapy, including mainly uncontrolled adverse events and long-term complications, remains a serious concern that needs to be accurately measured. This review provides a comprehensive and detailed overview of the delivery and biosafety of oncolytic virotherapy.

Background Coronavirus disease (COVID-19) has resulted in considerable morbidity and mortality worldwide. Thyroid hormones play a key role in modulating metabolism and the immune system. However, the prevalence of thyroid dysfunction (TD) and its association with the prognosis of COVID-19 have not yet been elucidated. In this study, we seek to address this gap and understand the link between TD and COVID-19. Methods Herein, we enrolled patients who were hospitalised with COVID-19 and had normal or abnormal thyroid function test results at the West Court of Union Hospital in Wuhan, China, between 29 January and 26 February 2020. We carried out follow up examinations until 26 April 2020. Data on clinical features, treatment strategies, and prognosis were collected and analysed. TD was defined as an abnormal thyroid function test result, including overt thyrotoxicosis, overt hypothyroidism, subclinical hypothyroidism, subclinical hyperthyroidism, and euthyroid sick syndrome. Results A total of 25 and 46 COVID-19 patients with and without TD, respectively, were included in the study. COVID-19 patients with TD had significantly higher neutrophil counts and higher levels of C-reactive protein, procalcitonin, lactate dehydrogenase, serum creatine kinase, aspartate transaminase, and high-sensitive troponin I and a longer activated partial thromboplastin time but lower lymphocyte, platelet, and eosinophil counts. A longitudinal analysis of serum biomarkers showed that patients with TD presented persistently high levels of biomarkers for inflammatory response and cardiac injury. COVID-19 patients with TD were more likely to develop a critical subtype of the disease. Patients with TD had a significantly higher fatality rate than did those without TD during hospitalisation (20% vs 0%, P<0.0001). Patients with TD were more likely to stay in the hospital for more than 28 days than were those without TD (80% vs 56.52%, P=0.048). Conclusions Our preliminary findings suggest that TD is associated with poor outcomes in patients with COVID-19.

Background We investigated the dynamic changes in lipid profiles and their correlations with disease severity and clinical outcome in patients with severe COVID-19. Methods We retrospectively reviewed 519 severe COVID-19 patients with confirmed outcomes (discharged or deceased), admitted to the West Court of Union Hospital in Wuhan, China, between 29 January and 8 April 2020. Results Altogether, 424 severe COVID-19 patients, including 34 non-survivors and 390 survivors, were included in the final analyses. During hospitalization, low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (apoA-I) showed an increasing trend in survivors, but showed a downward trend in non-survivors. The serum concentrations of HDL-C and apoA-I were inversely correlated with C-reactive protein (CRP), length of hospital stay of survivors, and disease severity score. For in-hospital deaths, the areas under the receiver operating characteristic curves (AUCs) of the ratios of CRP/HDL-C and CRP/apoA-I at admission were 0.84 and 0.83, respectively. Moreover, patients with high ratios of CRP/HDL-C (＞77.39) or CRP/apoA-I (＞72.37) had higher mortality rates during hospitalization (log-rank p < 0.001). Logistic regression analysis demonstrated that hypertension, lactate dehydrogenase, SOFA score, and High CRP/HDL-C ratio were independent predictors of in-hospital mortality. Conclusions During severe COVID-19, HDL-C and apoA-I concentrations are dramatically decreased in non-survivors. Moreover, High CRP/HDL-C ratio is significantly associated with an increase in mortality and a poor prognosis.

The cases were confirmed by real-time PCR and the demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Prognosis was defined as hospitalization, discharged survivor and death, which was followed up until March 12, 2020. ResultsOf the 258 hospitalized patients (63 with diabetes) with COVID-19, the median age was 64 years (range 23-91), and 138 (53.5%) were male. No significant differences in age and sex were identified between patients with and without diabetes.Common symptoms included fever (82.2%), dry cough (67.1%), polypnea (48.1%), and fatigue (38%). Patients with diabetes had significantly higher leucocyte and neutrophil counts, and higher levels of fasting blood glucose, serum creatinine, urea nitrogen and creatine kinase isoenzyme MB at admission compared with those without diabetes. COVID-19 patients with diabetes were more likely to develop severe or critical disease condition with more complications at presentation, and had

Background. Early identification of patients with severe coronavirus disease (COVID-19) at an increased risk of progression may promote more individualized treatment schemes and optimize the use of medical resources. This study is aimed at investigating the utility of the C-reactive protein to albumin (CRP/Alb) ratio for early risk stratification of patients. Methods. We retrospectively reviewed 557 patients with COVID-19 with confirmed outcomes (discharged or deceased) admitted to the West Court of Union Hospital, Wuhan, China, between January 29, 2020 and April 8, 2020. Patients with severe COVID-19 ( n = 465 ) were divided into stable ( n = 409 ) and progressive ( n = 56 ) groups according to whether they progressed to critical illness or death during hospitalization. To predict disease progression, the CRP/Alb ratio was evaluated on admission. Results. The levels of new biomarkers, including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, CRP/Alb ratio, and systemic immune-inflammation index, were higher in patients with progressive disease than in those with stable disease. Correlation analysis showed that the CRP/Alb ratio had the strongest positive correlation with the sequential organ failure assessment score and length of hospital stay in survivors. Multivariate logistic regression analysis showed that percutaneous oxygen saturation (SpO2), D-dimer levels, and the CRP/Alb ratio were risk factors for disease progression. To predict clinical progression, the areas under the receiver operating characteristic curves of Alb, CRP, CRP/Alb ratio, SpO2, and D-dimer were 0.769, 0.838, 0.866, 0.107, and 0.748, respectively. Moreover, patients with a high CRP/Alb ratio (≥1.843) had a markedly higher rate of clinical deterioration ( log − rank   p < 0.001 ). A higher CRP/Alb ratio (≥1.843) was also closely associated with higher rates of hospital mortality, ICU admission, invasive mechanical ventilation, and a longer hospital stay. Conclusion. The CRP/Alb ratio can predict the risk of progression to critical disease or death early, providing a promising prognostic biomarker for risk stratification and clinical management of patients with severe COVID-19.

Elderly patients with coronavirus disease 2019 (COVID-19) are more likely to develop severe or critical pneumonia, with a high fatality rate. To date, there is no model to predict the severity of COVID-19 in elderly patients. In this study, patients who maintained a non-severe condition and patients who progressed to severe or critical COVID-19 during hospitalization were assigned to the non-severe and severe groups, respectively. Based on the admission data of these two groups in the training cohort, albumin (odds ratio [OR] = 0.871, 95% confidence interval [CI]: 0.809 -0.937, P < 0.001), d-dimer (OR = 1.289, 95% CI: 1.042 -1.594, P = 0.019) and onset to hospitalization time (OR = 0.935, 95% CI: 0.895 -0.977, P = 0.003) were identified as significant predictors for the severity of COVID-19 in elderly patients. By combining these predictors, an effective risk nomogram was established for accurate individualized assessment of the severity of COVID-19 in elderly patients. The concordance index of the nomogram was 0.800 in the training cohort and 0.774 in the validation cohort. The calibration curve demonstrated excellent consistency between the prediction of our nomogram and the observed curve. Decision curve analysis further showed that our nomogram conferred significantly high clinical net benefit. Collectively, our nomogram will facilitate early appropriate supportive care and better use of medical resources and finally reduce the poor outcomes of elderly COVID-19 patients.

It has been shown that interleukin 18 (IL-18) exerts antitumor activity. In this study, we investigated whether oncolytic adenovirusmediated gene transfer of IL-18 could induce strong antitumor activity. A tumor-selective replicating adenovirus expressing IL-18 (ZD55-IL-18) was constructed by insertion of an IL-18 expression cassette into the ZD55 vector, which is based on deletion of the adenoviral E1B 55-kDa gene. It has been shown that ZD55-IL-18 exerted a strong cytopathic effect and significant apoptosis in tumor cells. ZD55-IL-18 significantly decreased vascular endothelial growth factor and CD34 expression in the melanoma cells. Treatment of established tumors with ZD55-IL-18 showed much stronger antitumor activity than that induced by ZD55-EGFP (enhanced green fluorescent protein) or Ad-IL-18. These data indicated that oncolytic adenovirus expressing IL-18 could exert potential antitumor activity through inhibition of angiogenesis and offer a novel approach to melanoma therapy.