ABSTRACT
Objective To assess the safety and efficacy of human umbilical cord-derived MSCs (UC-MSCs) for severe COVID-19 patients with lung damage. Design, Multicentre , randomised, double-blind, placebo-controlled trial. Setting Two hospitals in Wuhan, China, 5 March 2020 to 28 March 2020. Participants 101 severe COVID-19 patients with lung damage aged between 18-74 years. Intervention Patients were randomly assigned at a 2:1 ratio to receive either UC-MSCs (40 million cells per infusion) or placebo on days 0, 3, and 6. Main outcome measures The primary endpoints were safety and an altered proportion of whole lung lesion size from baseline to day 28, measured by chest computed tomography. Secondary outcomes were reduction of consolidation lesion sizeand lung function improvement (6-minute walk test, maximum vital capacity, diffusing capacity). Primary analysis was done in the modified intention-to-treat (mITT) population and safety analysis was done in all patients who started their assigned treatment. Results 100 patients were finally recruited to receive either UC-MSCs (n = 65) or placebo (n = 35). The patients receiving UC-MSCs exhibited a trend of numerical improvement in whole lung lesion size from baseline to day 28 compared with the placebo cases (the median difference was -13.31%, 95%CI -29.14%, 2.13%, P=0.080). UC-MSCs administration significantly reduced the proportions of consolidation lesion size from baseline to day 28 compared with the placebo (median difference: -15.45%, 95% CI -30.82%, -0.39%, P=0.043). The 6-minute walk test showed an increased distance in patients treated with UC-MSCs (difference: 27.00 m, 95% CI 0.00, 57.00, P=0.057). The incidence of adverse events was similar, and no serious adverse events were observed in the two groups. Conclusions UC-MSCs treatment is a safe and potentially effective therapeutic approach for COVID-19 patients with lung damage. A phase 3 trial is required to evaluate effects on reducing mortality and preventing long-term pulmonary disability.
Subject(s)
COVID-19 , Lung Diseases , Renal InsufficiencyABSTRACT
In COVID-19 caused by SARS-CoV-2 infection, the relationship between disease severity and the host immune response is not fully understood. Here we performed single-cell RNA sequencing in peripheral blood samples of five healthy donors and 13 COVID-19 patients including moderate, severe and convalescent cases. Through determining the transcriptional profiles of immune cells, coupled with assembled T cell receptor and B cell receptor sequences, we analyzed the functional properties of immune cells. Most cell types in COVID-19 patients showed a strong interferon-alpha response, and an overall acute inflammatory response. Moreover, intensive expansion of highly cytotoxic effector T cell subsets, such as CD4+ Effector-GNLY (Granulysin), CD8+ Effector-GNLY and NKT CD160, was associated with convalescence in moderate patients. In severe patients, the immune landscape featured a deranged interferon response, profound immune exhaustion with skewed T cell receptor repertoire and broad T cell expansion. These findings illustrate the dynamic nature of immune responses during the disease progression.
Subject(s)
COVID-19ABSTRACT
WHO has declared COVID-19 a pandemic with more than 300,000 confirmed cases and more than 14,000 deaths. There is urgent need for accurate and rapid diagnostic kits. Here we report the development and validation of a COVID-19/SARS-CoV-2 S1 serology ELISA kit for the detection of total anti-virus antibody (IgG+IgM) titers in sera from either the general population or patients suspected to be infected. For indirect ELISA, CHO-expressed recombinant full length SARS-CoV-2-S1 protein with 6*His tag was used as the coating antigen to capture the SARS-CoV-2-S1 antibodies specifically. The specificity of the ELISA kit was determined to be 97.5%, as examined against total 412 normal human sera including 257 samples collected prior to the outbreak and 155 collected during the outbreak. The sensitivity of the ELISA kit was determined to be 97.5% by testing against 69 samples from hospitalized and/or recovered COVID-19 patients. The overall accuracy rate reached 97.3%. Most importantly, in one case study, the ELISA test kit was able to identify an infected person who had previously been quarantined for 14 days after coming into contact with a confirmed COVID-19 patient, and discharged after testing negative twice by nucleic acid test. With the assays developed here, we can screen millions of medical staffs in the hospitals and people in residential complex, schools, public transportations, and business parks in the epidemic centers of the outbreaks to fish out the "innocent viral spreaders", and help to stop the further spreading of the virus.