The Dynamic Immunological Parameter Landscape in Coronavirus Disease 2019 Patients With Different Outcomes

ObjectivesThe longitudinal and systematic evaluation of immunity in coronavirus disease 2019 (COVID-19) patients is rarely reported.MethodsParameters involved in innate, adaptive, and humoral immunity were continuously monitored in COVID-19 patients from onset of illness until 45 days after symptom onset.ResultsThis study enrolled 27 mild, 47 severe, and 46 deceased COVID-19 patients. Generally, deceased patients demonstrated a gradual increase of neutrophils and IL-6 but a decrease of lymphocytes and platelets after the onset of illness. Specifically, sustained low numbers of CD8+ T cells, NK cells, and dendritic cells were noted in deceased patients, while these cells gradually restored in mild and severe patients. Furthermore, deceased patients displayed a rapid increase of HLA-DR expression on CD4+ T cells in the early phase, but with a low level of overall CD45RO and HLA-DR expressions on CD4+ and CD8+ T cells, respectively. Notably, in the early phase, deceased patients showed a lower level of plasma cells and antigen-specific IgG, but higher expansion of CD16+CD14+ proinflammatory monocytes and HLA-DR−CD14+ monocytic-myeloid-derived suppressor cells (M-MDSCs) than mild or severe patients. Among these immunological parameters, M-MDSCs showed the best performance in predicting COVID-19 mortality, when using a cutoff value of ≥10%. Cluster analysis found a typical immunological pattern in deceased patients on day 9 after onset, which was characterized as the increase of inflammatory markers (M-MDSCs, neutrophils, CD16+CD14+ monocytes, and IL-6) but a decrease of host immunity markers.ConclusionsThis study systemically characterizes the kinetics of immunity of COVID-19, highlighting the importance of immunity in patient prognosis.

Evaluation of Cocos nucifera and Sesamum indicum in comparison with Chlorhexidine on gingivitis - A double blind Clinico-Immunological study

Background: Myriad of synthetic products has been used in chemical plaque control. There is a constant search for cost effective herbal products with minimal adverse effect to substitute synthetic compounds. The objective of this study was to evaluate the anti-inflammatory properties of Cocos nucifera and Sesamum indicum and compare their effect with commercially available chlorhexidine on gingivitis. Methods: In this double blind, randomized, control clinical trial, a total of 45 samples from patients aged between 18 to 35 years reporting to the institution, diagnosed with gingivitis were selected and randomly divided into Group-A (Scaling + Cocos Nucifera mouthwash), Group-B (Scaling + Sesamum Indicum mouthwash) and Group C (Scaling + Chlorhexidine mouthwash). Clinical (Plaque index, Gingival index and Sulcus bleeding index), and Immunological (Interleukin-6) parameters were assessed at baseline and 45th day following scaling. Saliva samples were collected and stored at -200C till they were subjected to enzyme-linked immunosorbent assay (ELISA) analysis. Inferential statistics done were analysis of variance, paired t test, post hock Scheffe test and Chi- square test by using SPSS software (22.0). Results: In Clinical parameters, group B (p˂0.001) showed statistical significant reduction compared to group A and group C. In Immunological parameter group A (p˂0.001) showed statistical significant reduction in Interleukin-6 compared to group B and group C (p=0.126 & p=0.196 respectively). Conclusion: Cocos nucifera and Sesamum indicum mouth washes effectively decreased plaque formation and could be used as an adjunct to scaling in treating plaque induced gingivitis.

Outcome of Husband-to-Wife Kidney Transplantation With Mutual Children: Single Center Experience Using T Cell-Depleting Induction and Review of the Literature

Few data on husband-to-wife transplantations with mutual children (H2W) exist in the current era. We investigated the outcome of H2W transplantations (n = 25) treated with T cell-depleting induction compared to women with prior pregnancies also receiving their first HLA-mismatched kidney transplant, but from a different donor source: (i) other living donor (n = 52) and (ii) deceased donor (n = 120). Seventy-four percent of the women had ≥2 pregnancies; median follow-up time was 5 years. Death-censored allograft survival was significantly lower in the H2W group compared to the other two groups (p = 0.03). Three of four graft losses in the H2W group were due to rejection. 5-year patient survival in the H2W group was high and similar compared to the other living donor group (100 vs. 98%; p = 0.28). The incidence of (sub)clinical antibody-mediated rejection was higher in the H2W group (36 vs. 20 vs. 18%) (p = 0.10). The frequency of infections was similar among the three groups. No immunological parameter was predictive for rejection or graft loss in H2W transplantations. In conclusion, H2W transplantation is a valuable option, but associated with a higher risk for allograft loss due to rejection despite T cell-depleting induction. Further research is required for better risk prediction on an individual patient level.

Acute Oral Toxicity Studies of the Crude Extract of Endophytic Fungi Isolated from Annona senegalensis Pers

Establishment of safety and toxicity profiles of metabolites of endophytic organisms from known medicinal plants are crucial in their pharmacological and biological applications. The aim of this study was to evaluate the oral acute toxicity (LD50) of crude extract of endophytic fungi isolated from Annona senegalensis Pers. The endophytic fungal metabolite was extracted with ethyl acetate. The LD50 was estimated following the method described by Lorke. Three dose levels (10, 100, and 1000 mg/kg) of the crude extract were administered to three mice each for the first phase using oral gavage needle in a single dose disposable syringe. The animals were observed for possible deaths or other side effects of the test substance in each group within 24 hours of the treatment. In the second phase, which was deduced from the first phase, eight mice were sub-divided into four groups of two mice each and they were treated with doses of 1200, 1600, 2900 and 5000 mg/kg orally. They were also observed within 24 hours and final LD50 value was determined. Results showed that the endophytic fungal extract exhibited no mortality or any histological defect in the liver tissues of the mice. More so, the immunological parameter tested showed significant increase in neutrophils and lymphocytes relative to the control in all the fungal isolates. Additionally, the LD50 for the crude metabolites was > 5000 mg/kg. This study has revealed that crude extract of endophytic fungi isolated from Annona senegalensis Pers did not show oral acute toxicity in mice. Further studies will evaluate long term-toxicity of the crude extract. Keywords: Endophytes, LD50, Annona senegalensis, Metabolites, Fungi

Hypoxia increases susceptibility of Pacific white shrimp to whitespot syndrome virus (WSSV)

The present study aimed to evaluate the mortality, reactive oxygen species production (ROS) and total hemocyte counts (THC) of the marine shrimp Litopenaeus vannamei infected with the white spot syndrome virus (WSSV) at three levels of oxygen saturation. For this, 360 shrimp (20±2g) were distributed in 24 tanks (60L), divided in two groups (infected and non-infected), which were subjected to 30, 60 and 100% of dissolved oxygen saturation (in quadruplicate). During 96 hours after infection, daily hemolymph samples were collected for hemato-immunological parameter evaluation (THC and ROS) and dead animals were removed and computed to assess cumulative mortality rates. In the infected group, animals subjected to 100% saturation showed higher ROS production (P<0.05) after 48 hours, while THC was significantly reduced (P<0.05), regardless of oxygen saturation. The hypoxia resulted in high mortality when compared to 100% saturation condition. In the uninfected group, no significant differences were observed in all evaluated parameters. Thus, the hypoxia condition increased the susceptibility of shrimp to the infection of WSSV, which may be partly related to the low ROS production showed by the animals subjected to 30% oxygen saturation.

Genetic markers to gastrointestinal nematode resistance in sheep: a review

Nematode parasites are the major animal health constraint in sheep production on pasture and cause serious economic losses. Because of failure of anthelmintic drenches, a major research effort has been underway to examine alternatives to chemical control. One of them is selecting sheep which are genetically resistant to parasitic nematodes. However, this last is not widely practiced because of the difficulty of measuring parasite resistance which mostly relies on indirect criteria such as number of nematode eggs passed in the sheep faeces (FEC) packed cell volume (PCV) or enhanced number of eosinophils in peripheral blood. Despite the well known host immune reaction it has been impossible to standardize any immunological parameter and use it as an indicator of parasitic infection. The aim of finding some genetic markers associated with resistance/susceptibility to nematodes is to make diagnostic work easier and conduct an earlier selection of desirable genotypes. However, searching for reliable genetic markers is rather difficult due to different sheep’s manifestation of resistance to either the adult or larval stages of the same parasite species and against the same parasitic stage and various manifestations of the immune responses and antigens against parasites. This review summarizes findings reported in the literature relating to genetic markers to gastrointestinal nematodes resistance in sheep.

The effect of choral music on emotions, immune parameters and lung function during physiotherapy treatment of pneumonia and bronchitis

Introduction: Music, processed by the brain, has a strong impacton the emotions and health. The Magnificat in D major of JS Bach communicates not only a positive emotion of happiness but also motivational behaviour. Infectious lung conditions are often associated with negative emotions which develop due to physiological changes. The hormonal action of the hypothalamuspituitary-adrenal axes (HPA) could be negatively affected by emotions of anger and depression. This will result in a disturbance of the mind-body inter-action. Music therefore can exert a powerful influence on therapeutic benefits by changing the psychological status and the immune endocrine functions. The purpose of this study was to determine the effect of music, during respiratory physiotherapy treatment on a) theemotional status, b) neuroendocrine responses, c) immune functions and d) lung functions of subjects with infected lung conditions.Method and Materials: Forty subjects attending physiotherapy treatment was selected according to set criteria and randomly assigned to an experimental and control group. The parameters (Profile Of Mood State [POMS]; CD4:CD8 cell ratios; Cortisol; the Cortisol: DHEA ratio; PF; FEV1; FVC and FEV1/FVC %) were measured on day 1before the treatment and on day 3 after the treatment. Data were analysed with Statistica (Statsoft) using the RepeatedANOVA tests. Results: Results indicated that the intervention of music had a positive effect on the immunological parameter (CD4+:CD8+ cell ratios) and on the cortisol and cortisol:DHEA ratio levels. At the same time the psychological status as measured by Profile of Mood States (POMS scale) improved with a significant improvement in the lung functions.Conclusion: The research provided sufficient scientific evidence that music affects both the biomedical and psycho-somatic aspects of infectious lung conditions.

Preferential Th2 Polarization at the Onset of Thrombotic Microangiopathy (TMA): Immunological Comparison of TMA Versus Acute GVHD in Terms of Peripheral T Cell Subsets, Dendritic Cell Subsets and Cytokine Profiles.

Thrombotic microangiopathy (TMA) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a serious complication with a high mortality. Acute GVHD (aGVHD) is one of risk factors for TMA and often overlaps it. In particular, gastrointestinal endothelium is a common target of aGVHD and TMA, which makes clinical diagnosis of TMA difficult, leading to delay early and appropriate treatment for it. In this study, to gain more insight into differences between TMA and aGVHD, comprehensive immunological analysis was performed. Methods: We determined kinetics of peripheral T cell subsets (CD4, CD8, Th1, Th2, γδ-T, NKT) and dendritic cell (DC) subsets (CD11c+DC and CD123+DC), serum 17 different cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, TNF-α, IFN-γ, G-CSF, GM-CSF, MIP-1β, MCP-1), and C-reactive protein (CRP) at the onsets of aGVHD or TMA in 25 patients undergoing allo-HSCT. T cell subsets including CD4 (CD3+CD4+CD8−), CD8 (CD3+CD4−CD8+), Th1 (CD4+CXCR3+CCR4−), Th2 (CD4+CXCR3−CCR4+), γδ-T (CD3+TCR-Vδ2+), and NKT (CD3+CD161+) and DC subsets were determined with a flow cytometer. TMA was diagnosed, following Iacopino’s criteria (Iacopino et al, Bone Marrow Tranplant. 24: 47, 1999). Data of aGVHD or TMA were compared with those of control without either aGVHD nor TMA between on 30 days and 60 days after allo-HSCT. Results: There was a significant decrease in the percentage of Th1 cells in CD4+T cells in TMA (9.1%, n=10), compared to in aGVHD (24.9%, n=9, p=0.003) or in control (21.6%, n=12, p=0.009). In contrast, the percentage of Th2 cells in CD4+T cells was higher in TMA (20.2%) than in aGVHD (9.3%, p<0.001) or in control (12.1%, p=0.003). Accordingly, a significant increase in Th2/Th1 ratio was observed in TMA (4.0), compared to in aGVHD (0.4, p<0.001) or in control (0.7, p<0.001). In addition, a significant increase in the percentage of CD4 cells in CD3+T cells in TMA (59.2%, n=9) was found, compared to in aGVHD (31.2%, n=8, p=0.005) or in control (34.8%, n=11, p=0.007). The percentage of CD8+ cells in CD3+T cells was lower in TMA (26.3%) than in aGVHD (45.8%, p=0.03) or in control (54.4%, p=0.002). On the other hand, there was a significant increase in the ratio of CD11c+DC/CD123+DC in aGVHD (3.6, n=8), compared to in TMA (1.4, n=5, p=0.02) or in control (n=1.8, p=0.02). γδ-T and NKT did not show any significant changes among aGVHD, TMA and control. Moreover, no significant changes were observed in either 17 different cytokines among aGVHD, TMA and control. Of note, in TMA but not in aGVHD nor in control, positive correlations of Th2/Th1 ratio were found with IL-6 (p=0.01, r=0.91, n=6), IL-10 (p=0.03, r=0.86, n=6), and CRP (p<0.001, r=0.93, n=9). Conclusion: Preferential Th2 and CD4 polarizations were observed at the onset of TMA. Thus, simultaneous monitoring of Th1, Th2, CD4 and CD8 was suggested to become a useful immunological parameter for differentiating TMA from aGVHD after allo-HSCT.