Since the outbreak of the novel coronavirus pneumonia (COVID-19), it is urgently to develop the effective strategies for its clinical test or treatments world widely. Extracellular vesicles (EV)/exosomes could function as effective carriers for intercellular communication. Increasing evidence revealed that mesenchymal stem cell-derived EV/exosomes could be considered as an alternative cell-free therapy against the acute respiratory distress syndrome. Moreover, the EV-related metabolomics, proteomics, relapsing, deep-vein-thrombosis, myocardial-toxicity, liquid-biopsy and bio-therapeutic researches focusing on the COVID-19 will not only extended our knowledge for the diagnosis, but also provide novel ideas for treatment of this fatal disease. This article will systemically review the progresses of EV/exosomes in the diagnosis and treatment of COVID-19.

Objective:To investigate the difference and characteristics of autoantibodies expression in patients infected by 2019-nCoV with various severity, and explore the associations between expression profile of autoantibodies and prognosis of COVID-19 patients.Methods:This retrospective study was conducted on patients with COVID-19 admitted to Zhongnan Hospital, Wuhan University from January 30, 2020 to March 16, 2020. Data on medical records, expression of autoantibodies including antinuclear antibody profile (ANA), anticardiolipin antibody (ACA), inflammatory factor and other laboratory indexes were collected and analyzed. The age and sex matched disease controls (cases of pulmonary infection unrelated to 2019-nCoV infection and autoimmune disease) and healthy controls (healthy check-up individuals) were also included. Following groups were established, ANA test groups: 72 cases of COVID-19 group (including 17 critical and severe cases, and 55 mild cases), 37 disease controls and 44 healthy controls; ACA test groups: 111 cases of COVID-19 group (including 37 critical and severe cases, and 74 mild cases), 37 disease controls and 40 healthy controls. The difference of positive rate or expression level of autoantibodies among various groups was analyzed, and the difference of inflammatory biomarkers and other parameters were compared between patients with ANA positive results and negative results. The Spearman correlation test was applied to determine the relationship between ACA and other parameters. Kaplan-Meier estimation was used to plot survival curves, the log-rank analysis was utilized to explore the association between antibodies and outcome of COVID-19 patients.Results:The positive rate of antibodies was significantly higher in the COVID-19 group than disease and healthy control groups, the ANA fluorescence: 22.22% (16/72), 5.41% (2/37), 6.82% (3/44); ANA spectrum:26.39% (19/72), 8.11% (3/37), 9.09% (4/44); and ACA:37.84% (42/111), 8.11% (3/37), 5.00% (2/40); all P<0.05. The positive rate of ANA, ACA-IgM and the expression level of ACA-IgM were significantly higher in severe COVID-19 subgroups (critically and severe COVID-19 patients) than in the mild COVID-19 patients (the ANA fluorescence: 47.06% [8/17] vs. 14.55% [8/55], ANA spectrum:66.67% [9/17] vs. 18.18% [10/55], ACA-IgM:30.43% [10/37] vs. 9.46% [7/74]; all P<0.05). There were significant differences in the number of red blood cells, hemoglobin concentration, hematocrit, activated partial thromboplastin time, C-reactive protein, interleukin-6 and serum amyloid A between COVID-19 ANA-positive group and COVID-19 ANA-negative group (all P<0.05). The level of ACA-IgM was positively correlated with white blood cell count ( r=0.354, P<0.001), neutrophil count ( r=0.344, P<0.001), platelet count ( r=0.198, P=0.038), D-Dimer ( r=0.260, P=0.009), glutamic-pyruvic transaminase ( r=0.214, P=0.024), γ-glutamyl transpeptidase ( r=0.283, P=0.003), blood urea nitrogen ( r=0.223, P=0.019), and negatively correlated with superoxide dismutase ( r=-0.228, P=0.020). Survival analysis showed that cumulative survival rate of event-free survival (EFS) was lower in patients with positive ANA/ACA-IgM results than in patients with negative ANA/ACA-IgM results ( P<0.05). Conclusions:ANA and ACA autoantibodies can be detected in COVID-19 patients. The positive rate and the expression level of ANA and ACA increase in proportion with the severity of COVID-19 patients. ANA and ACA-IgM could be used as risk stratification determinants for predicting survival of COVID-19 patients.