Treatment with human umbilical cord-derived mesenchymal stem cells for COVID-19 patients with lung damage: a randomised, double-blind, placebo controlled phase 2 trial

BACKGROUNDTreatment of severe Corona Virus Disease 2019 (COVID-19) is challenging. We performed a phase 2 trial to assess the efficacy and safety of human umbilical cord-mesenchymal stem cells (UC-MSCs) to treat severe COVID-19 patients with lung damage, based on our phase 1 data. METHODSIn this randomized, double-blind, and placebo-controlled trial, we recruited 101 severe COVID-19 patients with lung damage. They were randomly assigned to receive either UC-MSCs (4 x 107 cells per infusion) or placebo on day 0, 3, and 6. The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28. Other imaging outcomes, 6-minute walk test, maximum vital capacity, diffusing capacity, and adverse events were recorded and analysed. RESULTS100 COVID-19 patients were finally recruited to receive either UC-MSCs (n = 65) or placebo (n = 35). UC-MSCs administration exerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo (the median difference was -13.31%, 95%CI -29.14%, 2.13%, P=0.080). UC-MSCs significantly reduced the proportions of solid component lesion volume 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 in the two groups. CONCLUSIONSUC-MSCs treatment is a safe and potentially effective therapeutic approach for COVID-19 patients with lung damage. (Funded by The National Key R&D Program of China and others. ClinicalTrials.gov number, NCT04288102.)

Single-cell landscape of immunological responses in COVID-19 patients

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.

Serological diagnostic kit of SARS-CoV-2 antibodies using CHO-expressed full-length SARS-CoV-2 S1 proteins

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.

[Application effect of pericardial devascularization plus gastric fundus transaction in advanced schistosomiasis].

OBJECTIVE: To discuss the effect of pericardial devascularization plus gastric fundus transaction in advance schistosomiasis patients with portal hypertension. METHODS: Thirty-six advanced schistosomiasis patients with portal hypertension treated with devascularization plus gastric fundus transaction (a portal hypertension group), as well as 10 patients treated with modified Sugiura operation (a modified Sugiura operation group) in the Third People's Hospital of Yangxin County since 2006 were chosen as the observation objects, and the clinical effects of the two groups were observed and compared. RESULTS: The operation time, indwelling time of stomach tube, time to taking food after operation, drainage tube removal time of the portal hypertension group were all shorten than those of the modified Sugiura operation group (all P＜0.05). The hospitalization expenses of the two groups were (25 466.00 ± 2 888.48) Yuan and (34 517.10 ± 4 948.39) Yuan respectively, and the difference was also statistically significant (P＜0.05). The incidence rates of portal thrombosis of the portal hypertension group and modified Sugiura operation group were 33.33% (12/36) and 40.00% (4/10), respectively, and the incidence rates of rehaemorrhagia of the two groups 12 months after the operation were 16.67% (6/36) and 10.00% (1/10), respectively, but the differences had no statistically significance (both P ＞ 0.05). In addition, 1 case with delayed gastric emptying and 1 case with stomal leak of esophagus happened in the modified Sugiura operation group, while no corresponding complications happened in the portal hypertension group. CONCLUSIONS: Pericardial devascularization plus gastric fundus is a relatively easy procedure which has a good short-term clinical effect, and therefore it is suitable for application in primary hospitals. However, its long-term effect still needs further observation.

Correlation of CKP and VEGF expression and microvessel density to spiral CT manifestations of thymoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the correlation of cytokeratin pan (CKP), vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) to spiral CT manifestations of thymoma.</p><p><b>METHODS</b>Eighty-four thymoma patients were underwent spiral CT examination, and 40 of the patients also had enhanced CT examination. All the CT findings were carefully reviewed to analyze their correlation to the expressions of CKP, VEGF and MVD.</p><p><b>RESULTS</b>The enhancement on spiral CT images increased with the levels of VEGF expression and MVD counting (P<0.01). Significant correlations were observed between VEGF expression, MVD counting and such spiral CT findings as lobular contours, cusp-like or sawtooth-like margins and tumor invasions of the pleural membrane, pericardium and great vessels (P<0.05). CKP expression showed no obvious correlation to these findings by spiral CT.</p><p><b>CONCLUSION</b>Spiral CT can reflect the pathological characteristics of thymoma, and may serve as a noninvasive modality for preoperative evaluation of thymoma.</p>

Effect of percutaneous intratumoral injection of lipiodol emulsion of chemotherapie agents on implanted VX2 tumor in rabbits / 南方医科大学学报

<p><b>OBJECTIVE</b>To assess the therapeutic effect of percutaneous intratumoral injection with lipiodol emulsion of chemotherapie agents (CALE) on implanted VX2 tumor in rabbits.</p><p><b>METHODS</b>Twelve New Zealand rabbits with implanted VX2 tumor (24 models) were divided into lipiodol group, chemotherapeutic agent group and CALE group with intratumoral injections of the corresponding agents. The pathological changes of all the lesions were observed and the expression of proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF) were evaluated 7 days after the operation.</p><p><b>RESULTS</b>Compared with the lipiodol group and chemotherapie agent group, intratumoral injection of CALE resulted in the highest tumor necrosis rate and greatest tumor necrosis (P<0.01). The labeling indices of PCNA and VEGF expressions in CALE group were markedly lower than those in the other two groups (P<0.01).</p><p><b>CONCLUSION</b>Percutaneous intratumoral injection of CALE is an effective ablation approach for treatment of malignant solid tumors.</p>

Endovascular graft exclusion with digital subtraction angiography for treatment of Stanford type B aortic dissection / 南方医科大学学报

<p><b>OBJECTIVE</b>To assess value of endovascular graft exclusion (EVGE) with digital subtraction angiography (DSA) in the treatment of Stanford type B aortic dissection (AD).</p><p><b>METHODS</b>On the basis of diagnosis with multi-slice spiral CT (MSCT), DSA was performed in 20 Stanford B AD cases for further diagnostic confirmation and EVGE was conducted for treatment. The DSA findings of the cases and the therapeutic effect of EVGE were evaluated.</p><p><b>RESULTS</b>In the 20 cases of Stanford type B AD, altogether 22 stents were implanted during EVGF with a stent release success rate of 100%. Postoperative examination revealed no obvious leakage or false lumen in 15 cases, and death occurred in 1 case 6 days after the operation due to right renal hemorrhage and infection, and the rest 19 patients were cured and discharged. Follow-up of the patients demonstrated improvement in the clinical symptoms, and MSCT showed that all the dissections were sealed successfully. No severe complications were observed 3 months after the treatment in these patients.</p><p><b>CONCLUSION</b>DSA can identify the fine anatomy of AD and allowed intraoperative monitoring in EVGE, which is an effective and safe means for treatment of Stanford type B AD.</p>