Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients, EBioMedicine (2020), doi: https://doi.Abstract Background: The dynamic changes of lymphocyte subsets and cytokines profiles of patients with novel coronavirus disease (COVID-19) and their correlation with the disease severity remain unclear. Methods: Peripheral blood samples were longitudinally collected from 40 confirmed COVID-19 patients and examined for lymphocyte subsets by flow cytometry and cytokine profiles by specific immunoassays. Findings: Of the 40 COVID-19 patients enrolled, 13 severe cases showed significant and sustained decreases in lymphocyte counts [0·6 (0·6-0·8)] but increases in neutrophil counts [4·7 (3·6-5·8)] than 27 mild cases [1.1 (0·8-1·4); 2·0 (1·5-2·9)].Further analysis demonstrated significant decreases in the counts of T cells, especially CD8 + T cells, as well as increases in IL-6, IL-10, IL-2 and IFN-γ levels in the peripheral blood in the severe cases compared to those in the mild cases. T cell counts and cytokine levels in severe COVID-19 patients who survived the disease gradually recovered at later time points to levels that were comparable to those of the mild cases.Moreover, the neutrophil-to-lymphocyte ratio (NLR) (AUC=0·93) and neutrophil-to-CD8 + T cell ratio (N8R) (AUC =0·94) were identified as powerful prognostic factors affecting the prognosis for severe COVID-19.Interpretation: The degree of lymphopenia and a proinflammatory cytokine storm is higher in severe COVID-19 patients than in mild cases, and is associated with the disease severity. N8R and NLR may serve as a useful prognostic factor for early 4 identification of severe COVID-19 cases.

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Background The objectives of this study were to analyze the clinical features of coronavirus disease 2019 and evaluate the diagnosis and treatment. Methods A retrospective analysis of the clinical manifestation and auxiliary examination of 19 patients with COVID-19 from the Liyuan Hospital intensive care unit (ICU) between January 16, 2020 and February 20, 2020 was undertaken. Results There were 11 male and 8 female cases among the patients. The median (range) age was 73 (38-91) years. Of these patients, 8 (42.1%) had died and the median duration from ICU admission to death was 2 (interquartile range (IQR): 1-10.75) days. Seven of these 8 patients had underlying diseases. The auxiliary examination showed fever (68.4%), dry cough (15.8%), dyspnea (10.5%), and diarrhea (5.3%). All 19 cases showed ground-glass changes on chest computed tomography. Serum hypersensitive C-reactive protein (hs-CRP) and serum amylase A (SAA) were clearly increased in all of the cases. Among the 19 cases, there were 16 (84.2%) cases in which the total number of lymphocytes decreased, 12 cases (63%) had reduced liver function, and 11 cases (58%) had deviant results for fibrinogen (FIB) and D-dimer, in particular, the D-dimer level was significantly higher in the non-survivors compared with the survivors. Conclusion There were more men than women among critically ill patients. All of the cases showed ground-glass changes on chest computed tomography and the vast majority of patients displayed fever and dry cough. The clinical laboratory indices change significantly, especially the D-dimer level among non-survivors.

Gene therapy provides a promising strategy for curing monogenetic disorders and complex diseases. However, there are challenges associated with the use of viral delivery vectors. The advent of nanomedicine represents a quantum leap in the application of gene therapy. Recent advances in stimulus-responsive nonviral nanocarriers indicate that they are efficient delivery systems for loading and unloading of therapeutic nucleic acids. Some nanocarriers are responsive to cues derived from the internal environment, such as changes in pH, redox potential, enzyme activity, reactive oxygen species, adenosine triphosphate, and hypoxia. Others are responsive to external stimulations, including temperature gradients, light irradiation, ultrasonic energy, and magnetic field. Multiple stimuli-responsive strategies have also been investigated recently for experimental gene therapy.