SARS-CoV-2 Infection in Venezuelan Pediatric Patients-A Single Center Prospective Observational Study.

Several studies suggest that children infected with SARS-CoV-2 have fewer clinical manifestations than adults; when they develop symptoms, they rarely progress to severe disease. Different immunological theories have been proposed to explain this phenomenon. In September 2020, 16% of the active COVID-19 cases in Venezuela were children under 19 years. We conducted a cross-sectional study of pediatric patients' immune response and clinical conditions with SARS-CoV-2 infection. The patients were admitted to the COVID-19 area of the emergency department of Dr José Manuel de los Ríos Children's Hospital (2021-2022). The lymphocyte subpopulations were analyzed by flow cytometry, and IFNγ, IL-6, and IL-10 serum concentrations were quantified using commercial ELISA assays. The analysis was conducted on 72 patients aged one month to 18 years. The majority, 52.8%, had mild disease, and 30.6% of the patients were diagnosed with MIS-C. The main symptoms reported were fever, cough, and diarrhea. A correlation was found between IL-10 and IL-6 concentrations and age group, lymphocyte subpopulations and nutritional status and steroid use, and IL-6 concentrations and clinical severity. The results suggest a different immune response depending on age and nutritional status that should be considered for treating pediatric COVID-19 patients.

Anti-inflammatory effect of Alpinia galanga extract on acute inflammatory cell model of peripheral blood mononuclear cells stimulated with TNF-α.

Aim Studies have shown that SARS-Cov-2 has the ability to activate proinflammatory cytokine leading to acute inflammation. During the SARS-Cov-2 infection, an increase of the secretion of production TNF-α in seen in COVID-19 patients along with a decrease in anti-inflammatory cytokine IL-10, and growth factor TGF-ß caused cytokine storm and damaged tissues. Alpinia galanga extract contains several secondary metabolites with strong antiinflammation and antioxidant effect. The aim of this study was to evaluate the effect of Alpinia galanga extract on peripheral blood mononuclear cells (PMBC) acute inflammation cells model stimulated with TNF-α. Methods Alpinia galanga was extracted under maceration methods on ethanol 96%. The PMBC was collected from three healthy humans and isolated using ficol reagent and cultured with the TNF-α 100pg/mL for 72 h. The TNF-α levels were evaluated under ELISA reader. Furthermore, the IL-10 and TGF-ß gene expression was analysed using qRT-PCR after 24 h treatment with Alpinia galanga extract. Results Alpinia galanga extract has no cytotoxic effect on Vero cells with IC50 value of >1000µg/mL. The PBMC acute inflammation cells model stimulated by TNF-α 100pg/mL, after 72 h induction the PBMC cells significantly expressed a high level of TNF-α up to 341±10.87 pg/mL. Furthermore, the treatment of Alpinia galanga significantly increased the anti-inflammatory cytokine IL-10 and growth factor TGF-ß in dose dependent manner. Conclusion These findings suggested that Alpinia galanga extract has strong antiinflammation activity.

IL-10/IL-6 ratio from nasal & oral swab samples, acts as an inflammatory indicator for COVID-19 patients infected with the delta variant.

Background: Hyper-inflammatory immune response of SARS-CoV-2 is often characterized by the release of multiple pro-inflammatory cytokines with an impact on the expression of numerous other interleukins (ILs). However, from oral and nasal swab samples the specific quantitative association of the different IL-markers with the disease progression and its relationship with the status of vaccination remains unclear. Materials and methods: Patients' combined oral and nasal swab samples were collected from both non-vaccinated and double-vaccinated individuals with high (Ct value < 25) and low (Ct value > 30) viral loads, along with uninfected donors. None of the patients were critically ill, or needed ICU support. The expression of different cytokines (IL6, IL10, IL1B, IFNG) and mucin (MUC5AC, MUC1) markers were assessed between different groups by qRT-PCR. The important cytokine markers differentiating between vaccinated and non-vaccinated patients were identified by PCA. Conclusion: IL6 expression was higher in non-vaccinated COVID-19 patients infected with delta-variant irrespective of their viral-load compared to uninfected individuals. However, in double-vaccinated patients, only in high viral-load patients (Ct value < 25), IL6 expression increased. In high viral-load patients, irrespective to their vaccination status, IL10 expression was lower compared to the uninfected control group. Surprisingly, IL10 expression was lower in double-vaccinated patients with Ct value > 30. IL1B, and IFNG expression remained unaltered in uninfected and infected individuals. However, MUC5AC expression was lower in non-vaccinated patients with Ct value < 25 compared to control group. Our study unveiled that IL10/IL6 ratio can be used as a biomarker for COVID-19 patients upon proper establishment of it in a clinical setting.

B cells: The many facets of B cells in allergic diseases.

B cells play a key role in our immune system through their ability to produce antibodies, suppress a proinflammatory state, and contribute to central immune tolerance. We aim to provide an in-depth knowledge of the molecular biology of B cells, including their origin, developmental process, types and subsets, and functions. In allergic diseases, B cells are well known to induce and maintain immune tolerance through the production of suppressor cytokines such as IL-10. Similarly, B cells protect against viral infections such as severe acute respiratory syndrome coronavirus 2 that caused the recent coronavirus disease 2019 pandemic. Considering the unique and multifaceted functions of B cells, we hereby provide a comprehensive overview of the current knowledge of B-cell biology and its clinical applications in allergic diseases, organ transplantation, and cancer.

Evaluation of the immunomodulatory effects of interleukin-10 on peripheral blood immune cells of COVID-19 patients: Implication for COVID-19 therapy.

Objective: Several therapies with immune-modulatory functions have been proposed to reduce the overwhelmed inflammation associated with COVID-19. Here we investigated the impact of IL-10 in COVID-19, through the ex-vivo assessment of the effects of exogenous IL-10 on SARS-CoV-2-specific-response using a whole-blood platform. Methods: Two cohorts were evaluated: in "study population A", plasma levels of 27 immune factors were measured by a multiplex (Luminex) assay in 39 hospitalized "COVID-19 patients" and 29 "NO COVID-19 controls" all unvaccinated. In "study population B", 29 COVID-19 patients and 30 NO COVID-19-Vaccinated Controls (NO COVID-19-VCs) were prospectively enrolled for the IL-10 study. Whole-blood was stimulated overnight with SARS-COV-2 antigens and then treated with IL-10. Plasma was collected and used for ELISA and multiplex assay. In parallel, whole-blood was stimulated and used for flow cytometry analysis. Results: Baseline levels of several immune factors, including IL-10, were significantly elevated in COVID-19 patients compared with NO COVID-19 subjects in "study population A". Among them, IL-2, FGF, IFN-γ, and MCP-1 reached their highest levels within the second week of infection and then decreased. To note that, MCP-1 levels remained significantly elevated compared with controls. IL-10, GM-CSF, and IL-6 increased later and showed an increasing trend over time. Moreover, exogenous addition of IL-10 significantly downregulated IFN-γ response and several other immune factors in both COVID-19 patients and NO COVID-19-VCs evaluated by ELISA and a multiplex analysis (Luminex) in "study population B". Importantly, IL-10 did not affect cell survival, but decreased the frequencies of T-cells producing IFN-γ, TNF-α, and IL-2 (p<0.05) and down-modulated HLA-DR expression on CD8+ and NK cells. Conclusion: This study provides important insights into immune modulating effects of IL-10 in COVID-19 and may provide valuable information regarding the further in vivo investigations.

Excessive IL-10 and IL-18 trigger hemophagocytic lymphohistiocytosis-like hyperinflammation and enhanced myelopoiesis.

BACKGROUND: Hyperinflammation is a life-threatening condition associated with various clinical disorders characterized by excessive immune activation and tissue damage. Multiple cytokines promote the development of hyperinflammation; however, the contribution of IL-10 remains unclear despite emerging speculations for a pathological role. Clinical observations from hemophagocytic lymphohistiocytosis (HLH), a prototypical hyperinflammatory disease, suggest that IL-18 and IL-10 may collectively promote the onset of a hyperinflammatory state. OBJECTIVE: We aimed to investigate the collaborative roles of IL-10 and IL-18 in hyperinflammation. METHODS: A comprehensive plasma cytokine profile for 87 secondary HLH patients was first depicted and analyzed. We then investigated the systemic and cellular effects of coelevated IL-10 and IL-18 in a transgenic mouse model and cultured macrophages. Single-cell RNA sequencing was performed on the monocytes/macrophages isolated from secondary HLH patients to explore the clinical relevance of IL-10/IL-18-mediated cellular signatures. The therapeutic efficacy of IL-10 blockade was tested in HLH mouse models. RESULTS: Excessive circulating IL-10 and IL-18 triggered a lethal hyperinflammatory disease recapitulating HLH-like phenotypes in mice, driving peripheral lymphopenia and a striking shift toward enhanced myelopoiesis in the bone marrow. IL-10 and IL-18 polarized cultured macrophages to a distinct proinflammatory state with pronounced expression of myeloid cell-recruiting chemokines. Transcriptional characterization suggested the IL-10/IL-18-mediated cellular features were clinically relevant with HLH, showing enhanced granzyme expression and proteasome activation in macrophages. IL-10 blockade protected against the lethal disease in HLH mouse models. CONCLUSION: Coelevated IL-10 and IL-18 are sufficient to drive HLH-like hyperinflammatory syndrome, and blocking IL-10 is protective in HLH models.

Effect of Convalescent Plasma Therapy on IL-10 and IL-12 Levels in COVID-19 Patients at Haji Surabaya General Hospital Randomly

Introduction: IL-12 and IL-10 are cytokines with different mechanisms in the pathogenesis of COVID-19. Differences in IL-12 and IL-10 levels in patients receiving convalescent plasma and non-convalescent plasma recipients need to be known because the total levels of IL-12 and IL-10 also determine the clinical condition of the patient. Materials and Methods: This study used 40 randomly selected blood serum samples with details of 20 samples of COVID-19 patients without convalescent plasma therapy and 20 samples of COVID-19 patients. The COVID-19 patients at the Haji General Hospital in Surabaya provided the patient serum that was utilized. Results: Based on the findings, there were differences in IL-10 levels between the control group and convalescent plasma therapy recipients (P<0.05). On IL-12 levels had no difference between the control and treatment groups (P>0.05). Conclusion: According to statistical estimates, convalescent plasma treatment made a difference to IL-10 but not IL-12 levels in COVID-19 patients. © 2023 UPM Press. All rights reserved.

Inflammatory Response and Activation of Coagulation after COVID-19 Infection.

SARS-CoV-2 (COVID-19) infection is responsible for causing a disease with a wide spectrum of clinical presentations. Predisposition to thromboembolic disease due to excessive inflammation is also attributed to the disease. The objective of this study was to characterize the clinical and laboratory aspects of hospitalized patients, in addition to studying the pattern of serum cytokines, and associate them with the occurrence of thromboembolic events. METHODOLOGY: A retrospective cohort study with 97 COVID-19 patients hospitalized from April to August 2020 in the Triângulo Mineiro macro-region was carried out. A review of medical records was conducted to evaluate the clinical and laboratory aspects and the frequency of thrombosis, as well as the measurement of cytokines, in the groups that presented or did not present a thrombotic event. RESULTS: There were seven confirmed cases of thrombotic occurrence in the cohort. A reduction in the time of prothrombin activity was observed in the group with thrombosis. Further, 27.8% of all patients had thrombocytopenia. In the group that had thrombotic events, the levels of IL1b, IL-10, and IL2 were higher (p < 0.05). CONCLUSIONS: In the studied sample, there was an increase in the inflammatory response in patients with thrombotic events, confirmed by the increase in cytokines. Furthermore, in this cohort, a link was observed between the IL-10 percentage and an increased chance of a thrombotic event.

Detection of the Serum Cytokines Predicts COVID-19 Pathogenesis in Egyptian Patients.

Cytokine storms can be triggered by various infectious or noninfectious diseases and cause severe damages to multiple organs. Cytokine storm plays an important role in the pathogenesis of severe cases of coronavirus disease 2019 (COVID-19). The pathogenesis of COVID-19 involves a potent inflammatory response involving a complex group of mediators, including interleukin (IL)-6 and IL-10. In this study, the serum levels of IL-6 and IL-10 cytokines were evaluated in 79 COVID-19 infected patients from the National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt. And 20 healthy individuals served as a control group. The patients were divided into moderate, severe, and critically ill. In this study, IL-6 and IL-10 levels were significantly elevated in COVID-19 patients compared with healthy controls. IL-6 levels were significantly higher in patients compared with controls (p = 0.001), although it was not varied within different severity groups except for moderate-critical ill cases (p < 0.033). IL-10 only showed a significant difference between critically ill and control cases (p < 0.002). Receiver operating characteristic curve analyses showed that IL-6 levels >120 pg/mL can predict moderate and critically ill patients with a sensitivity of 90.48% and a specificity of 62.50%, Area Under the Curve <0.0001. In conclusion, the serum levels of IL-6 cytokine are important noninvasive biomarkers to differentiate between moderate and critically ill COVID-19 infected patients.

An important call: Suggestion of using IL-10 as therapeutic agent for COVID-19 with ARDS and other complications.

The global coronavirus disease 2019 (COVID-19) pandemic has a detrimental impact on public health. COVID-19 usually manifests as pneumonia, which can progress into acute respiratory distress syndrome (ARDS) related to uncontrolled TH17 immune reaction. Currently, there is no effective therapeutic agent to manage COVID-19 with complications. The currently available anti-viral drug remdesivir has an effectiveness of 30% in SARS-CoV-2-induced severe complications. Thus, there is a need to identify effective agents to treat COVID-19 and the associated acute lung injury and other complications. The host immunological pathway against this virus typically involves the THαß immune response. THαß immunity is triggered by type 1 interferon and interleukin-27 (IL-27), and the main effector cells of the THαß immune response are IL10-CD4 T cells, CD8 T cells, NK cells, and IgG1-producing B cells. In particular, IL-10 exerts a potent immunomodulatory or anti-inflammatory effect and is an anti-fibrotic agent for pulmonary fibrosis. Concurrently, IL-10 can ameliorate acute lung injury or ARDS, especially those caused by viruses. Owing to its anti-viral activity and anti-pro-inflammatory effects, in this review, IL-10 is suggested as a possible treatment agent for COVID-19.

Saliva as a Potential Specimen to Monitor IL-6, TNF-α and IL-10 in COVID-19 Patients.

The SARS-CoV-2 instigated "cytokine storm" elicited upon infection is known to majorly cause lung injury and even mortality in severe cases. Early clinical prognosis to alleviate the exaggerated release of inflammatory cytokines is thus looked upon. Considering the recent attention and advantages of saliva as a clinical specimen, i.e. ease and painlessness of collection, which does not require trained staff and could allow self-sampling, the present study attempts to explore saliva for detection of IL-6, TNF-α and IL-10 which constitute major inflammatory genes that are elevated in COVID-19 using RT-PCR. Blood specimens of the same patients were also parallelly assessed to compare and validate the inflammatory marker expression. A total of 64 COVID-19 subjects who met the inclusion criteria were enrolled in this pilot study. Paired samples of blood and saliva from each patient were collected as per standard sampling protocols. RNA from all specimens were extracted using Qiagen RNA Blood Mini Kit and subjected to RT-PCR. IL-6, TNF-α and IL-10 expression were assessed in Ct (cycle threshold) values. It was observed that all 64 (100%) patients expressed IL-6 gene and TNF-α gene, whereas only 7 (5.19%) patients expressed IL-10 in both blood and saliva samples. The mean Ct values of IL-6 gene expressed in blood and saliva were 26.68 ± 2.26 and 28.53 ± 3.11 respectively. Similarly, the mean Ct values of TNF-α gene expressed in blood and saliva were 27.98 ± 2.45 and 28.92 ± 3.70 respectively. The observed mean Ct values of IL-10 gene expressed in blood and saliva were 31.26 ± 3.96 and 30.11 ± 4.12 respectively. Accordingly, the results indicate that inflammatory genes IL-6, TNF-α and IL-10 were detectable in both patient saliva as well as in blood. Moreover, mean Ct values of IL-6, TNF-α and IL-10 in both samples were found to be comparable. This finding thus suggests the possible use of saliva as an alternative specimen to blood for monitoring inflammation in COVID-19 patients.

Beneficial effects of L-Arginine in patients hospitalized for COVID-19: New insights from a randomized clinical trial.

We have recently demonstrated in a double-blind randomized trial the beneficial effects of L-Arginine in patients hospitalized for COVID-19. We hypothesize that one of the mechanisms underlying the favorable effects of L-Arginine is its action on inflammatory cytokines. To verify our hypothesis, we measured longitudinal plasma levels of pro-inflammatory and anti-inflammatory cytokines implied in the pathophysiology of COVID-19 in patients randomized to receive oral L-Arginine or placebo. The study was successfully completed by 169 patients. Patients in the L-Arginine arm had a reduced respiratory support evaluated at 10 and 20 days; moreover, the time to hospital discharge was significantly shorter in the L-Arginine group. The assessment of circulating cytokines revealed that L-Arginine significantly reduced the circulating levels of pro-inflammatory IL-2, IL-6, and IFN-γ and increased the levels of the anti-inflammatory IL-10. Taken together, these findings indicate that adding L-Arginine to standard therapy in COVID-19 patients markedly reduces the need of respiratory support and the duration of in-hospital stay; moreover, L-Arginine significantly regulates circulating levels of pro-inflammatory and anti-inflammatory cytokines.

Combined plasma levels of IL-10 and testosterone, but not soluble HLA-G5, predict the risk of death in COVID-19 patients.

BACKGROUND: The identification of biomarkers correlated with coronavirus disease 2019 (COVID-19) outcomes is a relevant need for clinical management. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by elevated interleukin (IL)-6, IL-10, HLA-G, and impaired testosterone production. OBJECTIVES: We aimed at defining the combined impact of sex hormones, interleukin-10, and HLA-G on COVID-19 pathophysiology and their relationship in male patients. MATERIALS AND METHODS: We measured by chemiluminescence immunoassay, electrochemiluminescent assays, and enzyme-linked immunosorbent assay circulating total testosterone, 17ß-estradiol (E2 ), IL-10, and -HLAG5 as well as SARS-CoV-2 S1/S2 Immunoglobulin G from 292 healthy controls and 111 COVID-19 patients with different disease severity at hospital admission, and in 53 COVID-19 patients at 7-month follow-up. RESULTS AND DISCUSSION: We found significantly higher levels of IL-10, HLA-G, and E2 in COVID-19 patients compared to healthy controls and an inverse correlation between IL-10 and testosterone, with IL-10, progressively increasing and testosterone progressively decreasing with disease severity. This correlation was lost at the 7-month follow-up. The risk of death in COVID-19 patients with low testosterone increased in the presence of high IL-10. A negative correlation between SARS-CoV-2 Immunoglobulin G and HLA-G or IL-10 at hospitalization was observed. At the 7-month follow-up, IL-10 and testosterone normalized, and  HLA-G decreased. CONCLUSION: Our findings indicate that combined evaluation of IL-10 and testosterone predicts the risk of death in men with COVID-19 and support the hypothesis that IL-10 fails to suppress excessive inflammation by promoting viral spreading.

PD-1 and ICOS counter-regulate tissue resident regulatory T cell development and IL-10 production during flu.

Regulatory T cells that express the transcription factor Foxp3 (Treg cells) are a highly heterogenous population of immunoregulatory cells critical for maintaining immune homeostasis and preventing immunopathology during infections. Tissue resident Treg (TR-Treg) cells are maintained within nonlymphoid tissues and have been shown to suppress proinflammatory tissue resident T cell responses and promote tissue repair. Human populations are repetitively exposed to influenza infections and lung tissue resident effector T cell responses are associated with flu-induced long-term pulmonary sequelae. The kinetics of TR-Treg cell development and molecular features of TR-Treg cells during repeated and/or long-term flu infections are unclear. Utilizing a Foxp3RFP/IL-10GFP dual reporter mouse model along with intravascular fluorescent in vivo labeling, we characterized the TR-Treg cell responses to repetitive heterosubtypic influenza infections. We found lung tissue resident Treg cells accumulated and expressed high levels of co-inhibitory and co-stimulatory receptors post primary and secondary infections. Blockade of PD-1 or ICOS signaling reveals that PD-1 and ICOS signaling pathways counter-regulate TR-Treg cell expansion and IL-10 production, during secondary influenza infection. Furthermore, the virus-specific TR-Treg cell response displayed distinct kinetics, when compared to conventional CD4+ tissue resident memory T cells, during secondary flu infection. Our results provide insight into the tissue resident Foxp3+ regulatory T cell response during repetitive flu infections, which may be applicable to other respiratory infectious diseases such as tuberculosis and COVID.

Photobiomodulation Improves Serum Cytokine Response in Mild to Moderate COVID-19: The First Randomized, Double-Blind, Placebo Controlled, Pilot Study.

Background: Because the major event in COVID-19 is the release of pre- and inflammatory cytokines, finding a reliable therapeutic strategy to inhibit this release, help patients manage organ damage and avoid ICU admission or severe disease progression is of paramount importance. Photobiomodulation (PBM), based on numerous studies, may help in this regard, and the present study sought to evaluate the effects of said technology on cytokine reduction. Methods: This study was conducted in the 2nd half of 2021. The current study included 52 mild-to-moderately ill COVID-19, hospitalized patients. They were divided in two groups: a Placebo group and a PBM group, treated with PBM (620-635 nm light via 8 LEDs that provide an energy density of 45.40 J/cm2 and a power density of 0.12 W/cm2), twice daily for three days, along with classical approved treatment. 28 patients were in Placebo group and 24 in PBM group. In both groups, blood samples were taken four times in three days and serum IL-6, IL-8, IL-10, and TNF-α levels were determined. Results: During the study period, in PBM group, there was a significant decrease in serum levels of IL-6 (-82.5% +/- 4, P<0.001), IL-8 (-54.4% ± 8, P<0.001), and TNF-α (-82.4% ± 8, P<0.001), although we did not detect a significant change in IL-10 during the study. The IL-6/IL-10 Ratio also improved in PBM group. The Placebo group showed no decrease or even an increase in these parameters. There were no reported complications or sequelae due to PBM therapy throughout the study. Conclusion: The major cytokines in COVID-19 pathophysiology, including IL-6, IL-8, and TNF-α, responded positively to PBM therapy and opened a new window for inhibiting and managing a cytokine storm within only 3-10 days.

Oxidant- induced preconditioning: A pharmacologic approach for triggering renal 'self defense'.

Acute kidney injury (AKI) is a common event, occurring in ~5% and ~35% of hospitalized and ICU patients, respectively. The development of AKI portends an increased risk of morbidity, mortality, prolonged hospitalization, and subsequent development of chronic kidney disease (CKD). Given these facts, a multitude of experimental studies have addressed potential methods for inducing AKI prevention in high-risk patients. However, successful clinical translation of promising experimental data has remained elusive. Over the past decade, our laboratory has focused on developing a method for safely triggering AKI protection by inducing "kidney preconditioning" in mice by the intravenous administration of a combination of Fe sucrose (FeS) + tin protoporphyrin (SnPP). These agents induce mild, but short lived, 'oxidant stress' which synergistically activate a number of kidney 'self-defense' pathways (e.g., Nrf2, ferritin, IL-10). Within 18-24 h of Fe/SnPP administration, marked protection against diverse forms of experimental toxic and ischemic AKI results. FeS/SnPP-mediated reductions in kidney injury can also indirectly decrease injury in other organs by mitigating the so called "organ cross talk" phenomenon. Given these promising experimental data, three phase 1b clinical trials were undertaken in healthy subjects and patients with stage 3 or 4 CKD. These studies demonstrated that FeS/SnPP were well tolerated and that they up-regulated the cytoprotective Nrf2, ferritin, and IL-10 pathways. Two subsequent phase 2 trials, conducted in patients undergoing 'on-pump' cardiovascular surgery or in patients hospitalized with COVID 19, confirmed FeS/SnPP safety. Furthermore, interim data analyses revealed statistically significant improvements in several clinical parameters. The goals of this review are to: (i) briefly discuss the historical background of renal "preconditioning"; (ii) present the experimental data that support the concept of FeS/SnPP- induced organ protection; and (iii) discuss the initial results of clinical trials that suggest the potential clinical utility of an 'oxidant preconditioning' strategy.

Serum Levels of Interleukin-10 and D-Dimer as Biomarkers of Coronavirus Disease

Background: Coronavirus 2019 is one of the most remembered pandemics, and it is regarded as one of the most significant occurrences of the twenty-first century. Clinical signs and symptoms, as well as reverse tianscription-polymerase chain reaction (RT-PCR) test, are used to diagnose COVID19. Several biomarker molecules are being researched for their potential utility in evaluating the severity and prognosis of severe acute respiratory syndrome corona vims-2 (SARS-CoV-2). This study was designed to assess the level of IL-10 and D-Dimer in patients who were suffering from COVID-19. Materials and Methods: This prospective study included 168 participants who were attending Imam Hussein Hospital in Karbala. They were divided into two groups (I & II) based on the result of RT-PCR test;IL-10 and D-Dimer were analyzed for studied groups. Results: The median age of 41.6 years, 86 males and 82 females. A noteworthy increase was observed in the level of IL-10 (9.803 +/- 0.44) and D-Dimer (1511.534 +/- 192.56) in the positive PCR group as compare with negative PCR group. Conclusion: The levels of IL-10 and D-Dimer can be utilized to estimate the severity and prognosis of COVID-19 patients, according to our findings. D-dimer levels, among these biomarkers, correspond more closely with severity and can be used as a solid prognostic indicator.

G6PD Insufficiency, Redox Equilibrium, and Viral Infections: Insinuations for SARS-CoV-2

The COVID-19 epidemic has inflicted damage on more than 4 crore 50 lakh people worldwide, resulting in over 10 lakh deaths. Infestation with the pathogenic SARS-CoV-2 virus leads to excessive inflammation and a cytokine storm, which leads to cell rupture due to a redox imbalance. The severe type of pneumonia caused by the human coronavirus (hCoV)-SARS-CoV-2 has caused heavy casualties, especially among the old age and those with comorbid illnesses all-inclusive of their age. The high mortality in African-American males, in general, raises the concern for a possible X-linked modulated process that could affect the viral pathogenesis and the immune system. When exposed to oxidants or infection, patients who lack the enzyme Glucose-6-Phosphate Dehydrogenase (G6PD) may have a haemolysis phenomenon. People with a G6PD deficiency are more prone to take up a virus than people with normal G6PD. G6PD deficiency causes a distinct immunological reaction to viral infections in people. G6PD insufficiency appears to be a predisposing factor for COVID-19 infection. Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD) is known to suppress the antioxidant system and is likely to aggravate severity of COVID-19 infection, which results in a pro-oxidant response leading to higher morbidity and mortality.

Navigating the cellular landscape in tissue: Recent advances in defining the pathogenesis of human disease.

Over the past decade, our understanding of human diseases has rapidly grown from the rise of single-cell spatial biology. While conventional tissue imaging has focused on visualizing morphological features, the development of multiplex tissue imaging from fluorescence-based methods to DNA- and mass cytometry-based methods has allowed visualization of over 60 markers on a single tissue section. The advancement of spatial biology with a single-cell resolution has enabled the visualization of cell-cell interactions and the tissue microenvironment, a crucial part to understanding the mechanisms underlying pathogenesis. Alongside the development of extensive marker panels which can distinguish distinct cell phenotypes, multiplex tissue imaging has facilitated the analysis of high dimensional data to identify novel biomarkers and therapeutic targets, while considering the spatial context of the cellular environment. This mini-review provides an overview of the recent advancements in multiplex imaging technologies and examines how these methods have been used in exploring pathogenesis and biomarker discovery in cancer, autoimmune and infectious diseases.

Study of ACE2 gene expression and evaluated some cellular and humoral immunity parameters of COVID-19 patients in Ramadi City

The new coronavirus SARS-CoV-2 is responsible for the COVID-19 epidemic. SARS-CoV-2 accesses host cells by ACE2, which is abundantly expressed in the heart, kidneys, and lungs and shed into the plasma. Many SARS-CoV-2 patients' neutralizing antibody titers and memory B cell responses may be transient, exposing them to re-infection. Notably, neutralizing antibody titers and the number of virus-specific T cells had a substantial relationship. Our findings lay the groundwork for additional research into protective immunity against SARS-CoV-2 and the etiology of COVID-19, particularly in severe instances. The most important characteristic of our findings a positive correlation between all parameters (cellular and humoral) and COVID-19 patients compared with healthy group excepting neutrophil cells where no significant difference was observed between the two groups. Lymphopenia and elevated levels of specific cytokines, such as IL-6, IL-10, and TNF-α, have been linked to illness severity in general. T cells are thought to play a key role in the first immune response. In extreme situations, a significant drop in T cell counts is virtually always detected. We observed that lymphocytes were significantly decreased (p < 0.001) in COVID-19 patients (630±0.7678) cells/mm3, as compared to healthy controls (2247±0.1497), Generally COVID-19 patients at severe stage suffering leucopenia and stimulate neutrophils to reduce formazan dye. On the other hand significant increase was recorded in cytokines storm that Hyper-production of mostly pro-inflammatory cytokines, such as IL-6, IL-10, and TNF-, which selectively target lung tissue, can significantly impair the prognosis in the most severe cases. Average of IL6, IL-10, TNF- α were significantly increased (p < 0.001) in COVID-19 patients (38.2±6.228, 94.87±8.426, 23.61±4.13 pg/ml), as compared to healthy controls (2.66±0.21, 8.06±0.85, 10.53±1.13 pg/ml) respectively. Gene expression of ACE2 significantly decreased at P <0.001 in severe patients to (0.1262±0.0072) whereas reported (1) for healthy controls, thus Fold of expression 7.92 (down regulation). Their impact on results will aid in the development of more effective COVID-19 management strategies. © 2022 Universidad Tecnica de Manabi. All Rights Reserved.