Clinical characteristics and treatment outcome of COVID-19 patients with stroke in China: A multicenter retrospective study.

OBJECTIVE: Previous studies mainly reported the clinical characteristics of novel coronavirus 2019 (COVID-19) infections, but the research on clinical characteristics and treatment outcomes of COVID-19 patients with stroke is still rare. METHODS: A multi-center retrospective study was conducted at 11 hospitals in 4 provinces of China, and COVID-19 patients with stroke were enrolled from February 24 to May 4, 2020. We analyzed epidemiological, demographic, and clinical characteristics of cases as well as the laboratory test results, treatment regimens and outcomes, and the clinical characteristics and therapeutic outcomes were compared between severe and nonsevere patients, and by age group, respectively. RESULTS: A total of 27 patients [mean age: 66.41 (SD 12.1) years] were enrolled. Among them, 9 (33.3%) were severe patients and 18 (66.7%) were nonsevere patients; 17 (63.0%) were female; 19 (70.4%) were aged 60 years and above. The most common symptoms were fever [19 (70.4%)], fatigue [12 (44.4%)] and cough [11 (40.7%)], respectively. Abnormal laboratory findings of COVID-19 patients with stroke included high levels of C-reactive protein [19 (73.1%)], D-dimer [14 (58.3%)], blood glucose [14 (53.8%)], fibrinogen [13 (50.0%)], and decreased lymphocytes [12 (44.4%)]. Comparing to nonsevere cases with stroke, severe patients with stroke were likely to be older, susceptible to receiving oxygen inhalation, and had more complications (p < 0.05). In addition, there were significant differences in lymphocytes, neutrophils, lactate dehydrogenase, C-reactive protein, creatine kinase between the severe cases and nonsevere cases (p < 0.05). The older patients had a decreased platelet count and elevated fibrinogen, compared with the younger (p < 0.05). All patients (100%) received antiviral treatment, 12 (44.4%) received antibiotics treatment, 26 (96.3%) received Traditional Chinese Medicine (Lung cleansing & detoxifying decoction), and oxygen inhalation was in 18 (66.7%). The median duration of hospitalization was 16 days. By May 4, 2020, a total of 26 (96.3%) patients were cured and discharged, and 1 (3.7%) patients died. CONCLUSION: COVID-19 patients with stroke had poor indicators of coagulation system, and severe and older patients might have a higher risk of complications and unfavorable coagulation system. However, the overall treatment outcome is favorable.

Association of Overlapped and Un-overlapped Comorbidities with COVID-19 Severity and Treatment Outcomes: A Retrospective Cohort Study from Nine Provinces in China.

OBJECTIVE: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. METHODS: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( OR) and 95% confidence interval (95% CI) of the associations between comorbidities (cardiometabolic or non-cardiometabolic diseases), clinical severity, and treatment outcomes of COVID-19. RESULTS: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. CONCLUSION: Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.

Fusion protein of adenovirus E4orf4 and human epidermal growth factor inhibits tumor cell growth.

Adenovirus early region 4 open reading frame 4 (E4orf4) protein is a novel cell death factor that selectively induces apoptosis in cancer cells. This study evaluated tumor inhibitory effects of a protein made by fusion E4orf4 and human epidermal growth factor (EGF). EGF was used to ensure the selective targeting of EGF receptor (EGFR)-overexpressing tumor cells. Results showed that EGF-E4orf4 stimulated EGFR phosphorylation in a time- and dose-dependent manner. Confocal microscopy analysis showed both EGF-E4orf4 and EGF could be internalized via EGFR but they had different intercellular trafficking pathways. In vitro study showed that EGF-E4orf4 significantly inhibited the proliferation of BGC823 and in vivo study showed EGF-E4orf4 suppressed tumor growth in a dose-dependent fashion with an inhibition rate of 79% for MDA-MB-231 and 49% for BGC 823 (p < 0.05). No toxic effects were observed in the nude mice with a dose as high as 10 mg/kg of EGF-E4orf4. These results indicated that EGF-E4orf4 could be a potential drug for cancer therapy.

Cytotoxicity of a recombinant fusion protein of adenovirus early region 4 open reading frame 4 (E4orf4) and human epidermal growth factor on p53-deficient tumor cells.

Adenovirus early region 4 open reading frame 4 (E4orf4) protein is a novel cell death factor that selectively induces p53-independent apoptosis in cancer cells, but not in normal human cells. This study presents an approach for inhibiting p53-deficient tumor cell growth by using protein-based E4orf4 that had been genetically fused to epidermal growth factor (EGF) to ensure selective targeting of EGF receptor-overexpressing tumor cells. EGF-E4orf4 enables binding onto the cell surface and is then internalized into Saos-2 cells. The success of the process had been demonstrated by immunofluorescence assay and confocal laser microscopy. After prolonged exposure, E4orf4 remained mostly in the nuclei. EGF-E4orf4 treatment of Saos-2 cells showed dose-dependent cytotoxicity. Nearly 50% of the Saos-2 cells were killed at a concentration of 250 nmol/l. In contrast, EGF-E4orf4 showed no significant inhibitory effect iresn primary cells of human umbilical vein endothelial cells. To confirm the ability of EGF-E4orf4 to induce apoptosis, DNA fragmentation was detected using BrdUTP end-labeling. Flow cytometric analysis revealed a significant increase of apoptotic cells in Saos-2 cells treated with EGF-E4orf4, but not in the case of cells cultured in plain medium (t=0.028, P<0.05). In conclusion, these preliminary results indicate that EGF-E4orf4 could show promise as a new reagent that is more efficient and less toxic in anti-cancer therapy.