Key PointsQuestionWhat is the effect of convalescent plasma therapy added to standard treatment, compared with standard treatment alone, on clinical outcomes in patients with severe or life-threatening coronavirus disease 2019 (COVID-19)?FindingIn this randomized clinical trial that included 103 patients and was terminated early, the hazard ratio for time to clinical improvement within 28 days in the convalescent plasma group vs the standard treatment group was 1.40 and was not statistically significant.MeaningAmong patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment did not significantly improve the time to clinical improvement within 28 days, although the trial was terminated early and may have been underpowered to detect a clinically important difference.

21 Background: At present, PCR-based nucleic acid detection cannot meet the demands 22 for coronavirus infectious disease (COVID-19) diagnosis. Immunosorbent Assay (ELISA) kits based on recombinant SARS-CoV-2 nucleocapsid 27 protein (rN) and spike protein (rS) were used for detecting IgM and IgG antibodies, 28 and their diagnostic feasibility was evaluated.29 Results: Among the 214 patients, 146 (68.2%) and 150 (70.1%) were successfully 30 diagnosed with the rN-based IgM and IgG ELISAs, respectively; 165 (77.1%) and 31 159 (74.3%) were successfully diagnosed with the rS-based IgM and IgG ELISAs, 32 respectively. The positive rates of the rN-based and rS-based ELISAs for antibody 33 (IgM and/or IgG) detection were 80.4% and 82.2%, respectively. The sensitivity of 34 the rS-based ELISA for IgM detection was significantly higher than that of the 35 rN-based ELISA. We observed an increase in the positive rate for IgM and IgG with 36 an increasing number of days post-disease onset (d.p.o.), but the positive rate of IgM 37 dropped after 35 d.p.o. The positive rate of rN-based and rS-based IgM and IgG 38 ELISAs was less than 60% during the early stage of the illness 0-10 d.p.o., and that of 39 IgM and IgG was obviously increased after 10 d.p.o.40 Conclusions: ELISA has a high sensitivity, especially for the detection of serum 41 samples from patients after 10 d.p.o, it can be an important supplementary method for 42 on June 9, 2020 by guest http://jcm.asm.org/ Downloaded from COVID-19 diagnosis.43

21 Background: At present, PCR-based nucleic acid detection cannot meet the demands 22 for coronavirus infectious disease (COVID-19) diagnosis. Immunosorbent Assay (ELISA) kits based on recombinant SARS-CoV-2 nucleocapsid 27 protein (rN) and spike protein (rS) were used for detecting IgM and IgG antibodies, 28 and their diagnostic feasibility was evaluated. 29 Results: Among the 214 patients, 146 (68.2%) and 150 (70.1%) were successfully 30 diagnosed with the rN-based IgM and IgG ELISAs, respectively; 165 (77.1%) and 31 159 (74.3%) were successfully diagnosed with the rS-based IgM and IgG ELISAs, 32 respectively. The positive rates of the rN-based and rS-based ELISAs for antibody 33 (IgM and/or IgG) detection were 80.4% and 82.2%, respectively. The sensitivity of 34 the rS-based ELISA for IgM detection was significantly higher than that of the 35 rN-based ELISA. We observed an increase in the positive rate for IgM and IgG with 36 an increasing number of days post-disease onset (d.p.o.), but the positive rate of IgM 37 dropped after 35 d.p.o. The positive rate of rN-based and rS-based IgM and IgG 38 ELISAs was less than 60% during the early stage of the illness 0-10 d.p.o., and that of 39 IgM and IgG was obviously increased after 10 d.p.o.40Conclusions: ELISA has a high sensitivity, especially for the detection of serum

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Regulator of Cullins-1 (ROC1) or RING box protein-1 (RBX1) is an essential RING component of Cullin-RING ligase (CRL). Our previous studies showed that ROC1 is required for the growth of several cancer cell lines while ROC1 siRNA silencing inactivates CRL, leading to cell cycle arrest, cell senescence and/or apoptosis. However, it is completely unknown whether ROC1 knockdown triggers autophagic response by inactivating CRL. Moreover, the role of ROC1 in liver cancer remains elusive. In this study, we reported that ROC1 knockdown significantly inhibited the growth of liver cancer cells by sequentially and independently inducing autophagy and p21-dependent cell senescence. Mechanism analysis revealed that ROC1 silencing triggered autophagy by inhibition of mammalian target of rapamycin (mTOR) activity due to accumulation of mTOR-inhibitory protein Deptor, a substrate of CRL. Consistently, Deptor knockdown significantly blocked autophagy response upon ROC1 silencing. Biologically, autophagy response upon ROC1 silencing was a survival signal, and blockage of autophagy pathway sensitized cancer cells to apoptosis. Finally, we demonstrated that ROC1 was overexpressed in hepatocellular carcinomas, which is associated with poor prognosis of liver cancer patients. These findings suggest that ROC1 is an appealing drug target for liver cancer and provide a proof-of-concept evidence for a novel drug combination of ROC1 inhibitor and an autophagy inhibitor for effective treatment of liver cancer by enhancing apoptosis.