Clinical outcomes for COVID-19 patients with diabetes mellitus treated with convalescent plasma transfusion in Wuhan, China.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is wreaking havoc on public health systems worldwide. The diagnosis of COVID-19 is well defined, but efficacious treatment is lacking. There is a big gap in knowledge regarding COVID-19 patients receiving convalescent plasma transfusion (CPT), especially those also suffering from diabetes mellitus (DM). In this study, among 3059 COVID-19 patients admitted to Wuhan Huoshenshan Hospital of China, we documented the characteristics of 39 COVID-19 patients with DM receiving CPT and compared their baseline information and clinical outcomes to COVID-19 patients with DM receiving conventional treatment. We also performed the propensity-matched comparison of COVID-19 patients with DM between conventional treatment and CPT. The CPT was efficacious and beneficial for COVID-19 patients with DM, including severe or critically ill patients, without obvious adverse effects. Our data demonstrated that CPT significantly improved the clinical outcomes of COVID-19 patients with DM, especially the cure rate and duration of hospitalization compared with that in COVID-19 patients with DM receiving conventional treatment. This study not only provided a deeper understanding of characteristics in COVID-19 patients with DM receiving CPT but also highlighted the efficaciousness of CPT for COVID-19 patients with DM.

Interleukin-17 (IL-17)-induced microRNA 873 (miR-873) contributes to the pathogenesis of experimental autoimmune encephalomyelitis by targeting A20 ubiquitin-editing enzyme.

Interleukin 17 (IL-17), produced mainly by T helper 17 (Th17) cells, is increasingly recognized as a key regulator in various autoimmune diseases, including human multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Although several microRNAs (miRNAs) with aberrant expression have been shown to contribute to the pathogenesis of MS and EAE, the mechanisms underlying the regulation of abnormal miRNA expression in astrocytes upon IL-17 stimulation remain unclear. In the present study, we detected the changes of miRNA expression profiles both in the brain tissue of EAE mice and in cultured mouse primary astrocytes stimulated with IL-17 and identified miR-873 as one of the co-up-regulated miRNAs in vivo and in vitro. The overexpression of miR-873, demonstrated by targeting A20 (TNFα-induced protein 3, TNFAIP3), remarkably reduced the A20 level and promoted NF-κB activation in vivo and in vitro as well as increasing the production of inflammatory cytokines and chemokines (i.e. IL-6, TNF-α, MIP-2, and MCP-1/5). More importantly, silencing the endogenous miR-873 or A20 gene with lentiviral vector of miR-873 sponge (LV-miR-873 sponge) or short hairpin RNA (shRNA) of A20 (LV-A20 shRNA) in vivo significantly lessened or aggravated inflammation and demyelination in the central nervous system (CNS) of EAE mice, respectively. Taken together, these findings indicate that miR-873 induced by IL-17 stimulation promotes the production of inflammatory cytokines and aggravates the pathological process of EAE mice through the A20/NF-κB pathway, which provides a new insight into the mechanism of inflammatory damage in MS.

Sublytic C5b-9 complexes induce apoptosis of glomerular mesangial cells in rats with Thy-1 nephritis through role of interferon regulatory factor-1-dependent caspase 8 activation.

The apoptosis of glomerular mesangial cells (GMC) in rat Thy-1 nephritis (Thy-1N), a model of human mesangioproliferative glomerulonephritis, is accompanied by sublytic C5b-9 deposition, but the mechanism of sublytic C5b-9-mediated GMC apoptosis has not been elucidated. In the present study, the gene expression profiles both in the GMC stimulated by sublytic C5b-9 and the rat renal tissue of Thy-1N were detected using microarrays. Among the co-up-regulated genes, the up-regulation of interferon regulatory factor-1 (IRF-1) was further confirmed. Increased caspase 8 and caspase 3 expression and caspase 8 promoter activity in the GMC were also identified. Meanwhile, overexpression or knockdown of IRF-1 not only enhanced or inhibited GMC apoptosis and caspase 8 and 3 induction but also increased or decreased caspase 8 promoter activity, respectively. The element of IRF-1 binding to the caspase 8 promoter was first revealed. Furthermore, silencing IRF-1 or repressing the activation of caspases 8 and 3 significantly reduced GMC apoptosis, including other pathologic changes of Thy-1N. These novel findings indicate that GMC apoptosis of Thy-1N is associated with the IRF-1-activated caspase 8 pathway.

Establishment and application of suspension static method in blood group screening of automated blood group analyzer.

The accuracy of blood group identification is the basis of blood transfusion safety. In order to increase the detection rate of weak agglutination, unexpected antibodies (UAb) and blood subtypes for pre-transfusion testing, the blood group screening process of automated blood group analyzer (ABGA) is ameliorated by introducing one static step and establishing a suspension static method (SSM). One static step was introduced in the blood group screening process of ABGA and three static time conditions were designed: 300 s, 400 s and 500 s, from which the optimal static time was selected and SSM was established; By comparing the detection of weak agglutination and UAb before and after the application of SSM, the feasibility and effect of suspension static method were verified and evaluated. The last two steps of the automatic blood group screening process were replaced with static, light centrifugation and imaging. The optimal static time parameter was selected as 400 s and SSM was established; After the application of SSM, it was verified that: (1) The detection level of weak antibodies (anti-A and anti-B) and weak antigens (weak D phenotype) could be improved by SSM, including antibodies in plasma of known type O samples with 0, 2, 4, 8, 16 and 32 times serial dilutions(simulating weak anti-A and weak anti-B), weak antibodies (anti-B) in plasma of one normal A-type sample and weak antigens on red blood cells (RBC) of 5 weak D phenotype samples (weak D antigen); (2) Three blood donor samples (type A, O and B) with known UAb were detected by SSM. The results showed that SSM could detect both weak antibodies (anti-A and anti-B) and UAb; (3) SSM was applied to detect the samples of 3 A2B and 3 subtype B blood donors and the blood subtypes could be clearly detected; (4) The number of screening samples was 95,314 and 106,814 before SSM (2018) and after (2020) the application of SSM and the positive rate of UAb (63/95,314 and 187/106,814) increased after SSM, discrepancy of which was statistically significant (χ2 = 48.42, P < 0.01). The above results demonstrate that SSM of ABGA is conducive to the detection of weak agglutination, UAb and blood subtypes in blood samples, which can improve the sensitivity of blood group detection and ensure the safety of clinical blood transfusion to a certain extent.

A real-world study on the effectiveness of BBIBP-CorV and CoronaVac in Nanjing area.

Since the advent of COVID-19 vaccine, the long-term monitoring and evaluation of vaccine effectiveness worldwide has never stopped. Real-world research of the mainstream vaccines in China (BBIBP-CorV and CoronaVac) is extremely valuable as a supplement to clinical research data. Venous blood of this study was collected from 111 blood donors and from 6 volunteers, who had received 2 doses of SAR-CoV-2 vaccine. Cross-sectional study and cohort study was adopted. Venous blood of 11 COVID-19 convalescent plasma donors was collected as a positive control. The seroconversion rate of neutralizing antibodies in 111 vaccine recipients was 90.99% (101/111); The level of SAR-CoV-2 antibodies peaked around 28 days after inoculation, then fast descended followed by gentle descended until it was still detectable around 280 days later. The changes in antibody levels were similar to those of the 6 participants and those of convalescent plasma donors after infection. 5 of the 6 participants still maintained a high level of neutralizing antibodies (> 60% of the peak value) around 28 days after receiving 2 doses of vaccine; one participant had an antibody reaction that was almost always negative for 4 weeks. BBIBP-CorV and CoronaVac can produce good immune effects in most vaccinators aged 20 to 59 years in Nanjing area. Nevertheless, significant individual discrepancies of the humoral immunity are still existed.

Upregulated IL-6 Indicates a Poor COVID-19 Prognosis: A Call for Tocilizumab and Convalescent Plasma Treatment.

A comprehensive understanding of the dynamic changes in interleukin-6 (IL-6) levels is essential for monitoring and treating patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). By analyzing the correlations between IL-6 levels and health conditions, underlying diseases, several key laboratory detection indices, and the prognosis of 1,473 patients with the coronavirus disease 2019 (COVID-19), the role of IL-6 during SARS-CoV-2 infection was demonstrated. Our results indicated that IL-6 levels were closely related to age, sex, body temperature, oxygen saturation (SpO2) of blood, and underlying diseases. As a stable indicator, the changes in IL-6 levels could indicate the inflammatory conditions during a viral infection. Two specific treatments, namely, tocilizumab and convalescent plasma therapy (CPT), decreased the level of IL-6 and relieved inflammation. CPT has an important role in the therapy for patients with critical COVID-19. We also found that patients with IL-6 levels, which were 30-fold higher than the normal level, had a poor prognosis compared to patients with lower levels of IL-6.

3044 Cases reveal important prognosis signatures of COVID-19 patients.

Critical patients and intensive care unit (ICU) patients are the main population of COVID-19 deaths. Therefore, establishing a reliable method is necessary for COVID-19 patients to distinguish patients who may have critical symptoms from other patients. In this retrospective study, we firstly evaluated the effects of 54 laboratory indicators on critical illness and death in 3044 COVID-19 patients from the Huoshenshan hospital in Wuhan, China. Secondly, we identify the eight most important prognostic indicators (neutrophil percentage, procalcitonin, neutrophil absolute value, C-reactive protein, albumin, interleukin-6, lymphocyte absolute value and myoglobin) by using the random forest algorithm, and find that dynamic changes of the eight prognostic indicators present significantly distinct within differently clinical severities. Thirdly, our study reveals that a model containing age and these eight prognostic indicators can accurately predict which patients may develop serious illness or death. Fourthly, our results demonstrate that different genders have different critical illness rates compared with different ages, in particular the mortality is more likely to be attributed to some key genes (e.g. ACE2, TMPRSS2 and FURIN) by combining the analysis of public lung single cells and bulk transcriptome data. Taken together, we urge that the prognostic model and first-hand clinical trial data generated in this study have important clinical practical significance for predicting and exploring the disease progression of COVID-19 patients.

Successful recovery of COVID-19-associated recurrent diarrhea and gastrointestinal hemorrhage using convalescent plasma.

BACKGROUND: Gastrointestinal symptoms are not rare among coronavirus disease 2019 (COVID-19) patients, but there have been no reports regarding convalescent plasma therapy for the recovery of gastrointestinal problems in COVID-19 patients. CASE PRESENTATION: We present two cases of patients with COVID-19-associated recurrent diarrhea and positive fecal occult blood who successfully recovered after a one-time convalescent plasma administration. CONCLUSION: When COVID-19 patients develop recurrent or refractory gastrointestinal symptoms and fail to respond to the available treatment, alternative therapy with convalescent plasma administration may be considered.

Anti-SARS-CoV-2 virus antibody levels in convalescent plasma of six donors who have recovered from COVID-19.

BACKGROUND: Anti-SARS-CoV-2 virus antibody levels in convalescent plasma (CP), which may be useful in severe Anti-SARS-CoV-2 virus infections, have been rarely reported. RESULTS: A total of eight donors were considered for enrollment; two of them were excluded because of ineligible routine check. Of the six remaining participants, five samples were tested weakly positive by the IgM ELISA. Meanwhile, high titers of IgG were observed in five samples. The patient treated with CP did not require mechanical ventilation 11 days after plasma transfusion, and was then transferred to a general ward. CONCLUSIONS: Our serological findings in convalescent plasma from recovered patients may help facilitate understanding of the SARS-CoV-2 infection and establish CP donor screening protocol in COVID-19 outbreak. METHODS: Anti-SARS-CoV-2 antibodies including IgM and IgG were measured by two enzyme-linked immunosorbent assays (ELISA) in convalescent plasma from six donors who have recovered from coronavirus disease 2019 (COVID-19) in Nanjing, China. CP was also utilized for the treatment of one severe COVID-19 patient.

Evolution of COVID-19 in patients with autoimmune rheumatic diseases.

The characteristics of COVID-19 patients with autoimmune rheumatic diseases (AIRD) have rarely been reported. Patients with AIRD have suppressed immune defense function, which may increase their susceptibility to COVID-19. However, the immunosuppressive agents AIRD patients routinely used may be beneficial for protecting the cytokine storm caused by SARS-CoV-2. In this retrospective study, we included all confirmed cases in Huoshenshan Hospital from February 4 to April 9. Data were extracted from electronic medical records and were analyzed for clinical and laboratory features using SPSS (version 25.0). Of 3059 patients, 21 had the comorbidities with systematic lupus erythematosus (SLE) and/or rheumatoid arthritis (RA), including 5 with SLE, 15 with RA, and 1 with Rhupus. The proportion was 57.1% for severe cases, 61.9% for either severe or critical cases, and 4.8% for critical cases. The main manifestations, ARDS and ICU admission rate, as well as the mortality and length of hospital stay of COVID-19 in AIRD patients were similar to COVID-19 patients in the general population. Our preliminary experience shows that patients with AIRD tend to have a higher risk of SARS-CoV-2 infection, and may be at risk for a severe but less likely critical disease course. Further investigation is needed to understand the immunological features of these diseases.

Synthesis of a MoS x -O-PtO x Electrocatalyst with High Hydrogen Evolution Activity Using a Sacrificial Counter-Electrode.

Water splitting is considered to be a very promising alternative to greenly produce hydrogen, and the key to optimizing this process is the development of suitable electrocatalysts. Here, a sacrificial-counter-electrode method to synthesize a MoS x /carbon nanotubes/Pt catalyst (0.55 wt% Pt loading) is developed, which exhibits a low overpotential of 25 mV at a current density of 10 mA cm-2, a low Tafel slope of 27 mV dec-1, and excellent stability under acidic conditions. The theory calculations and experimental results confirm the high hydrogen evolution activity that is likely due to the fact that the S atoms in MoS x can be substituted with O atoms during a potential cycling process when using Pt as a counter-electrode, where the O atoms act as bridges between the catalytic PtO x particles and the MoS x support to generate a MoS x -O-PtO x structure, allowing the Pt atoms to donate more electrons thus facilitating the hydrogen evolution reaction process.

IL-17-triggered downregulation of miR-497 results in high HIF-1α expression and consequent IL-1ß and IL-6 production by astrocytes in EAE mice.

Interleukin 17 (IL-17) is increasingly recognized as a key factor that contributes to the pathogenesis of multiple sclerosis (MS) and its experimental mouse autoimmune encephalomyelitis (EAE) model. However, the roles and regulatory mechanisms of IL-17-induced pro-inflammatory cytokine production in EAE mice remain largely unclear. In this study, the expression of IL-17, hypoxia inducible factor-1α (HIF-1α), IL-1ß, IL-6 and microRNA-497 (miR-497), as well as their intrinsic associations, was investigated using EAE model mice and cultured astrocytes exposed to IL-17 in vitro. We observed markedly increased production of IL-17, HIF-1α, IL-1ß and IL-6 in the brain tissues of EAE mice, while the expression and secretion of HIF-1α, IL-1ß and IL-6 were also significantly increased when cultured primary astrocytes from mice were stimulated with IL-17. Meanwhile, the expression of miR-497 was downregulated both in vivo and in vitro. Subsequent in vitro experiments revealed that IL-17 induced the production of IL-1ß and IL-6 in astrocytes through the upregulation of HIF-1α as a transcriptional factor, indicating that IL-17-mediated downregulation of miR-497 enhanced HIF-1α expression. Furthermore, astrocyte-specific knockdown of IL-17RA and HIF-1α or astrocyte-specific overexpression of miR-497 by infection with different lentiviral vectors containing an astrocyte-specific promotor markedly decreased IL-1ß and IL-6 production in brain tissues and alleviated the pathological changes and score of EAE mice. Collectively, these findings indicate that decreased miR-497 expression is responsible for IL-17-triggered high HIF-1α expression and consequent IL-1ß and IL-6 production by astrocytes in EAE mice.Cellular & Molecular Immunology advance online publication, 1 May 2017; doi:10.1038/cmi.2017.12.