Background: COVID-19 is a highly infectious respiratory disease. No therapeutics have yet been proven effective for treating severe COVID-19. Objectives: To determine whether human umbilical cord mesenchymal stem cell infusion may be effective and safe for the treatment of severe COVID-19. Methods: Patients with severe COVID-19 were randomly divided into 2 groups: the standard treatment group and the standard treatment plus hUC-MSC infusion group. The incidence of progression from severe to critical illness, 28-day mortality, clinical symptom improvement, time to clinical symptom improvement, hematologic indicators including C-reactive protein, lymphocyte number, and interleukin 6, and imaging changes were observed and compared between the two groups. Measurements and main results: The incidence of progression from severe to critical illness and the 28-day mortality rate were 0 in the hUC-MSC treatment group, while 4 patients in the control group deteriorated to critical condition and received invasive ventilation; 3 of them died, and the 28-day mortality rate was 10.34%. In the hUC-MSC treatment group, the time to clinical improvement was shorter than that in the control group. Clinical symptoms of weakness and fatigue, shortness of breath, and low oxygen saturation obviously improved beginning on the third day of stem cell infusion and reached a significant difference on day 7. CRP and IL-6 levels were significantly lower from day 3 of infusion, the time for the lymphocyte count to return to the normal range was significantly faster, and lung inflammation absorption was significantly shorter on CT imaging in the hUC-MSC group than in the control group. Conclusions: Intravenous transplantation of hUC-MSCs is a safe and effective method that can be considered a salvage and priority treatment option for severe COVID-19.

Purpose An ongoing outbreak of coronavirus disease 2019 (COVID-19) emerged in Wuhan since December 2019 and spread globally. However, information about critically ill patients with COVID-19 is still limited. We aimed to describe the clinical characteristics and outcomes of critically ill patients with COVID-19 and figure out the risk factors of mortality. Methods We extracted data retrospectively regarding 733 critically ill adult patients with laboratory-confirmed COVID-19 from 19 hospitals in China through January 1 to February 29, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were collected. The primary outcome was 28-day mortality. Data were compared between survivors and non-survivors. Results Of the 733 patients included in the study, the median (IQR) age was 65 (56–73) years and 256 (34.9%) were female. Among these patients, the median (IQR) APACHE II score was 10 (7 to 14) and 28-day mortality was 53.8%. Respiratory failure was the most common organ failure (597 [81.5%]), followed by shock (20%), thrombocytopenia (18.8%), central nervous system (8.6%) and renal dysfunction (8%). Multivariate Cox regression analysis showed that older age, malignancies, high APACHE II score, high d -dimer level, low PaO 2 /FiO 2 level, high creatinine level, high hscTnI level and low albumin level were independent risk factors of 28-day mortality in critically ill patients with COVID-19. Conclusion In this case series of critically ill patients with COVID-19 who were admitted into the ICU, more than half patients died at day 28. The higher percentage of organ failure in these patients indicated a significant demand for critical care resources. Electronic supplementary material The online version of this article (10.1007/s00134-020-06211-2) contains supplementary material, which is available to authorized users.

Background COVID-19 is a highly infectious respiratory disease. No effective therapeutics have yet been proved for treating of severe COVID-19. Objectives To determine whether human Umbilical Cord Mesenchymal Stem Cells infusion may be effectiveness and safety in the treatment of severe COVID-19. Methods The severe COVID-19 randomly divided into 2 groups, standard treatment group and standard treatment plus hUC-MSCs infusion group. The incidence of severe patients aggravated to critically illness, 28-day mortality, clinical symptoms improvement, time to clinical symptoms improvement, hematologic indicators including C-reaction protein, lymphocyte number, interleukin 6 and imaging changes were observed and compared between two groups. Measurements and Main Results The incidence of severe patients aggravated to critically illness and 28-day mortality were 0 in hUC-MSCs treatment group, while 4 patients in control group were deteriorated to critical illness and been used invasive ventilation, 3 of them died, and 28-day mortality was 10.34%. In hUC-MSCs treatment group, the time to clinical improvement was shorter, clinical symptoms of weakness and fatigue, shortness of breath, and low oxygen saturation had improved obviously began the third day of stem cells infusion, and reached the significant difference on the day 7, CRP and IL-6 were significantly decreased from day 3 of infusion, the time for lymphocyte count returned to normal range was significant faster, and lung inflammation absorption was significantly shorter from CT imaging. Conclusions Intravenous transplantation of hUC-MSCs is a safe and effective way that can be considered as salvage and priority choice in the treatment of severe COVID-19.

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Previously, we demonstrated the therapeutic effects of human umbilical cord mesenchymal stromal cells (hUC-MSCs) in severe coronavirus disease 2019 patients. In this 3-month follow-up study, we examined discharged patients who had received hUC-MSC therapy to assess the safety of this therapy and the healthrelated quality of life (HRQL) of these patients. The follow-up cohort consisted of 28 discharged severe COVID-19 patients who received either the standard treatment (the control group) or the standard treatment plus hUC-MSC therapy. We examined liver function, kidney function, pulmonary function, coagulation, tumor markers, and vision. We also conducted electrocardiography (ECG) analysis, let the patients answer the St. George's Respiratory Questionnaire (SGRQ), and performed computed tomography (CT) imaging for assessing the lung changes. No obvious adverse effects were observed in the hUC-MSC group after 3 months. Measurements of blood routine index, C-reactive protein and procalcitonin, liver and kidney function, coagulation, ECG, tumor markers, and vision were almost within the normal ranges in both the treatment and control groups. Forced expiratory volumes in 1 s (FEV1) (% of predicted) were 71.88% -8.46% and 59.45% -27.45% in the hUC-MSC and control groups (P < 0.01), respectively, and FEV1/forced vital capacity (FEV1/FVC) ratios were 79.95% -8.00% and 58.97% -19.16% in the hUC-MSC and control groups, respectively (P < 0.05). SGRQ scores were lower in the hUC-MSC group than in the control group (15.25 -3.69 vs. 31.9 -8.78, P < 0.05). The rate of wheezing in the hUC-MSC group was also significantly lower than that in the control group (37.5% vs. 75%, P < 0.05). There were no significant differences in CT scores between the two groups (0.60 -0.88 vs. 1.00 -1.31, P = 0.917). Overall, the intravenous transplantation of hUC-MSCs accelerated partial pulmonary function recovery and improved HRQL, indicating relative safety and preliminary efficacy of this treatment for patients with severe COVID-19.

BackgroundThe benefits of intravenous immunoglobulin administration are controversial for critically ill COVID-19 patients.MethodsWe analyzed retrospectively the effects of immunoglobulin administration for critically ill COVID-19 patients. The primary outcome was 28-day mortality. Inverse probability of treatment weighting (IPTW) with propensity score was used to account for baseline confounders. Cluster analysis was used to perform phenotype analysis.ResultsBetween January 1 and February 29, 2020, 754 patients with complete data from 19 hospitals were enrolled. Death at 28 days occurred for 408 (54.1%) patients. There were 392 (52.0%) patients who received intravenous immunoglobulin, at 11 (interquartile range (IQR) 8, 16) days after illness onset; 30% of these patients received intravenous immunoglobulin prior to intensive care unit (ICU) admission. By unadjusted analysis, no difference was observed for 28-day mortality between the immunoglobulin and non-immunoglobulin groups. Similar results were found by propensity score matching (n = 506) and by IPTW analysis (n = 731). Also, IPTW analysis did not reveal any significant difference between hyperinflammation and hypoinflammation phenotypes.ConclusionNo significant association was observed for use of intravenous immunoglobulin and decreased mortality of severe COVID-19 patients. Phenotype analysis did not show any survival benefit for patients who received immunoglobulin therapy.

In this paper, polyethylene glycol (PEG)‐based ultrasonic‐assisted enzymatic extraction (UAEE) was employed in polysaccharides extraction from Lonicerae japonica leaves (LJLP). The optimal extraction conditions (extraction time of 33 min, PEG concentration of 30%, and ultrasonic power of 191 W) were obtained by Box–Behnken design (BBD). Under this condition, the LJLP yield was 14.76%. Furthermore, LJLP was identified as a typical heteropolysaccharide considering the main constitutive monosaccharides include galactose (32.3%), glucose (20.9%), and ribose (15.2%). Moreover, LJLP exhibited high total reducing power and considerable scavenging activities on superoxide radicals, in a concentration‐dependent manner in vitro. In addition, antioxidant analysis in vivo revealed that for the LJLP‐treated mice, the superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px), catalase (CAT) activities, and total antioxidant capacity (TAOC) were significantly increased, while the level of malondialdehyde (MDA) was decreased in both serum and liver.

Background: Currently, coronavirus disease 2019 (COVID-19) is continuously and rapidly circulating, causing heavy damage on public health. No effective antiviral treatment has been proved thus far. Traditional Chinese medicine (TCM) has been widely applied in the treatment of a variety of infection diseases in China, hoping to produce clinical effects and reduce the use of antibiotics and glucocorticoid. The aim of this study is to evaluate the efficacy and safety of Shenhuang granule in treatment of severe COVID-19. Methods/design: This multicenter, open-label randomized controlled trial is conducted in 160 participants with severe COVID-19. The participants will be randomly (1:1) divided into treatment group or control group. All participants are given standard therapy at the same time. The experiment will receive Shenhuang granule treatment twice a day for 14 days. The clinical indicators of patients will be assessed at baseline and at 3, 5, 7, and 14 days after treatment initiation. The primary outcome is 14-day clinical outcome. Adverse events will be monitored throughout the trial. Discussion: This will be the first randomized controlled trial, which evaluate the effect of Shenhuang granule in patients with severe COVID-19 in China. The results of this trial may not only provide evidence-based recommendations to clinicians to treat severe COVID-19, but also enrich the theory and practice of TCM in treating infectious diseases.