Certolizumab

Certolizumab is a Fab fragment of a humanized monoclonal antibody against tumor necrosis factor-alpha (TNF-alpha). Differing from the other TNF-alpha inhibitors due to the absence of Fc fragment and pegylation, it binds to both the soluble and transmembrane forms of TNF-alpha, creating a strong TNF-alpha blockage. Previously approved for psoriatic arthritis, certolizumab received another approval from FDA in 2018 for the treatment of moderate to severe chronic plaque psoriasis that does not respond to conventional systemic treatments or for which these treatments are contraindicated. Administered via subcutaneous injections, certolizumab also has a low-dose option for patients weighing less than 90 kg. Certolizumab is considered a safe biological drug that can be preferred during pregnancy and lactation.Copyright © 2022 by Turkish Society of Dermatology and Venereology.

Correlations of interleukin levels with the severity of SARS-CoV-2 coronavirus infection.

A new coronavirus infection caused by the SARS-CoV-2 virus is characterized by a systemic hyperinflammatory response with a pronounced increase in the content of pro-inflammatory cytokines. Materials and methods. The study was conducted on the basis of the Samara Regional Children's Infectious Diseases Hospital from 2021 to 2022. 40 patients with moderate (n = 20, group I) and severe forms (n = 20, group II) COVID-19 were studied, the comparison group consisted of patients with viral pneumonia of another etiology (n = 35, group III). Results. The infectious agent SARS-CoV-2 induces high levels of cytokines IL-6 (p < 0.005), IL-8 (p < 0.05) and a slight increase in TNF-alpha (p < 0.05). IL-8 was significantly associated with disease duration (p < 0.01). We assume that the value of this interleukin will increase in the post-COVID period. Conclusions. Changes in IL-6 and IL-8 levels in patients with COVID-19, along with clinical features, are important biomarkers for predicting the severity and duration of the disease.Copyright © Children Infections.All rights reserved

COVID-19 and stroke: A review.

COVID-19 patients have presented with a wide range of neurological disorders, among which stroke is the most devastating. We have reviewed current studies, case series, and case reports with a focus on COVID-19 patients complicated with stroke, and presented the current understanding of stroke in this patient population. As evidenced by increased D-dimer, fibrinogen, factor VIII and von Willebrand factor, SARS-CoV-2 infection induces coagulopathy, disrupts endothelial function, and promotes hypercoagulative state. Collectively, it predisposes patients to cerebrovascular events. Additionally, due to the unprecedented strain on the healthcare system, stroke care has been inevitably compromised. The underlying mechanism between COVID-19 and stroke warrants further study, so does the development of an effective therapeutic or preventive intervention.

Investigation of TNF-alpha and IL-4 in Pfizer/BioNTech vaccinated people: A comparative study

Background: The necessity for a vaccine to prevent this disease has been made abundantly clear by the appearance of the new SARS-CoV-2 and COVID-19. The most reliable method of halting the spread of infectious illnesses is vaccination. Since they were first made available to the general public more than 200 years ago, vaccines have saved millions of lives. Method(s): There were eighty-one (81) participants in total in the study. Individuals ranged in age from 18 to 66 and had recently received COVID-19 mRNA Pfizer/BioNTech [BNT162b2] vaccination injections. They were given two injections of the vaccine of 30 g and 0.3 mL, twenty-one (21) days apart. Before the first vaccination, blood samples were collected. This procedure was repeated on days 7-10 after the first vaccination, and on days 7-10 after the second dose. All samples were tested for IL-4, and TNF-alpha using a High Sensitivity Human ELISA Kit corresponding to each marker (Elabscience/United State). Result(s): There was no significant increase in IL-4 levels in all groups, TNF-alpha results showed increased after the first and second doses compared to before vaccination, and the increase after the second dose is greater than the first dose. Conclusion(s): Our research demonstrated that vaccinations caused Th1 biases and prevented Th2 responses in all groups.Copyright © 2023, Codon Publications. All rights reserved.

The ameliorating role of sofosbuvir and daclatasvir on thioacetamide-induced kidney injury in adult albino rats.

Thioacetamide (TAA) exposure and hepatitis C virus infection are usually associated with renal dysfunction. Sofosbuvir (SFV) and daclatasvir (DAC) drugs combination has great value in the treatment of hepatitis C. The study aimed to identify the nephrotoxic effects of TAA and to evaluate the ameliorative role of SFV and DAC in this condition. Forty-eight adult male albino rats were divided into eight groups and received saline (control), SFV, DAC, SFV+DAC, TAA, TAA+SFV, TAA+DAC and TAA+SFV+DAC for eight weeks. Kidney and blood samples were retrieved and processed for histological (Hematoxylin and Eosin and Masson's trichrome), immunohistochemical (α-smooth muscle actin), and biochemical analysis (urea, creatinine, total protein, albumin, malondialdehyde, reduced glutathione, superoxide dismutase, and tumor necrosis factor-α). Examination revealed marked destruction of renal tubules on exposure to TAA with either hypertrophy or atrophy of glomeruli, increase in collagen deposition, and wide expression of α-smooth muscle actin. Also, significant disturbance in kidney functions, oxidative stress markers, and tumor necrosis factor-α. Supplementation with either SFV or DAC produced mild improvement in the tissue and laboratory markers. Moreover, the combination of both drugs greatly refined the pathology induced by TAA at the cellular and laboratory levels. However, there are still significant differences when compared to the control. In conclusion, SFV and DAC combination partially but greatly ameliorated the renal damage induced by TAA which might be enhanced with further supplementations to give new hope for those with nephropathy associated with hepatitis.

Association of Tumor Necrosis Factor-Alpha (TNF-alpha) and Suppressor of Cytokine Signaling-1 (SOCS-1) Gene Variants in Children with COVID-19

Objective The suppressor of cytokine signaling-1 (SOCS-1) gene is an essential physiological regulator of cytokine signaling. Tumor necrosis factor-alpha (TNF-alpha) is an important component of the immunological response. Herein, we aimed to investigate the effects of SOCS-1 (-1478 CA > Del) and TNF-alpha (-308) polymorphisms on disease susceptibility and prognosis in pediatric patients with coronavirus disease 2019 (COVID-19). Methods One-hundred fifty COVID-19 patients in the COVID-19 emergency department between September 2020 and April 2021 and 80 healthy volunteers (control group) without any additional disease were included. Baseline gene polymorphisms were compared between the patient and healthy control groups. Afterward, the gene polymorphism distribution was examined by forming two separate clinical patients' subgroups. Results While CA/CA and CA/Del gene variants of SOCS-1 were higher in the patient group, Del/Del genotype was more common in the control group (p < 0.05). The GG genotype of the TNF-alpha was significantly more common in the severe subgroup (p = 0.044). The GA genotype of TNF-alpha was associated with the risk of hospitalization (2.83-fold), while the GG genotype was found to be protective in terms of hospitalization (2.95-fold). Conclusions This study will be a guide in terms of the presence of high cytokine release genotypes and COVID-19-related cytokine release syndromes. Copyright © 2023 Georg Thieme Verlag. All rights reserved.

In Silico Study of Bioactive Compounds from Sungkai (Peronema Canescens) as Immunomodulator

Objective: This study aims to predict a bioactive compound from Peronema canescens (PC) with mechanisms inhibitor interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) potential as an immunomodulatory using in silico approach. Method(s): Autodock 4 was used to accomplish computer-assisted drug design with molecular docking simulation to discover binding energy, inhibition constant, and interactions with an amino acid in bioactive compounds from PC against IL-6 and TNF-alpha receptors. Lipinski predicts the drug-likeness of a bioactive compound for the oral route of administration. ADMET profiling of bioactive compounds to predict pharmacokinetic properties with pkCSM ADMET. Result(s): The results showed that the best binding energy, inhibition constant, and interactions with an amino acid of peronemin C1 against IL-6 and TNF-alpha receptors were (-7.19 kcal/mol;5.39 nM;Arg 179, Arg 182, Gln 175), and (-8.86 kcal/mol;320.42 nM;Tyr 119, Tyr 59, and Gly 121), respectively. All bioactive compounds from PC met Lipinski's rule of five requirements for oral administration. ADMET prediction results all bioactive compounds from PC are non-mutagenic, except peronemin D1 is mutagenic. Conclusion(s): The peronemin C1 bioactive compounds from PC have good immunomodulatory potential, effectively inhibiting human IL-6 and TNF-alpha receptors using in silico approach. Copyright © 2022 The Authors. Published by Innovare Academic Sciences Pvt Ltd.

Case Report: New-Onset Rheumatoid Arthritis Following COVID-19 Vaccination.

Efficient protection against coronavirus disease 2019 (COVID-19) has been achieved by immunization with mRNA-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, efficient immune responses against this novel virus by vaccination are accompanied by a wide variety of side effects. Indeed, flares or new-onset of autoimmune disorders have been reported soon after the COVID-19 vaccination. Although pro-inflammatory cytokine responses play pathogenic roles in the development of autoimmunity, cytokines charactering COVID-19 vaccination-related autoimmune responses have been poorly understood. Given that mRNA derived from COVID-19 vaccine is a potent inducer for pro-inflammatory cytokine responses, these cytokines might mediate autoimmune responses after COVID-19 vaccination. Here we report a case with new-onset rheumatoid arthritis (RA) following COVID-19 vaccination. Serum concentrations not only of arthrogenic cytokines, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), but also of type I interferon (IFN) were elevated at the active phase in this case. Induction of remission by methotrexate and tocilizumab was accompanied by a marked reduction in serum concentrations of type I IFN, IL-6, and TNF-α. These results suggest that production of type I IFN, IL-6, and TNF-α induced by COVID-19 vaccination might be involved in this case with new-onset RA.

Evaluation of the effect of drug on physiotherapy methods on cytokines and chemokines of Covid-19 patients

Previous investigations have demonstrated that interleukin-6 (IL-6), C reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), in Coronavirus disease 2019 (COVID-19) patients are considerably increased, and their progressive elevation are clinical threat indicators of disease severity. The purpose of this systematic review is to evaluate the efficacy of physiotherapy, specifically chest physiotherapy, on different cytokines in Covid-19 and non-covid-19 patients. The main complications and symptoms of this virus are as follows;a dry cough, fever, and progressive dyspnea. Quickly, the coronavirus, which is named SARS-CoV-21, has spread worldwide, causing severe lung inflammation, respiratory distress syndrome, cardiac and renal injury, especially in comorbidities patients. Approximately 96% of the cases experience mild respiratory symptoms;some progress to pneumonia, respiratory insufficiency, acute respiratory distress syndrome, and multiorgan failure. The overall mortality rate per number of diagnosed cases is 4.6%;it can range from 0.2% to 15% according to age and health problems. Combination MeSH and text terms were used to perform the search strategy. Interventions in RCTs and clinical trials with or without comparison were assessed. Six studies met the inclusion criteria. Studies demonstrated that physiotherapy could have an effect on TNF-alpha, IL-6, IL-10, IL-1 beta and CRP.

Oxi-Inflammatory Stress and Biomolecular Deterioration: A Mysterious Convergence in Post COVID Patients

Background: Despite several scientific efforts against COVID 19, conundrum of biomolecular deterioration in Post COVID syndrome patients are still in dark at an unprecedented scale globally and affected the patient's health multidimensionally. It is conceivable that patients recovered from COVID-19 after second wave are at enhanced risk of secondary complications.Aim: The present study was carried out to estimate the serum vitamin D and total antioxidant activity (TAC) along with markers of oxi-inflammatory stress in post COVID patients diagnosed RT-PCR negative after second wave of COVID-19 and to determine their role in predicting secondary complications.Methodology: 50 subjects (30-55 years) of Delhi-NCR region were recruited and categorized into two groups (n=25 in each group;on the basis of their history of COVID infection). By using standard methods, study group parameters were estimated in Post COVID patients and statistically compared it with that of 25 non affected healthy controls by using student's t-test.Result: Serum CRP, TNF-alpha, MDA and uric acid levels were significantly high (p<0.05) in Post COVID patients as compared to healthy controls. Conversely, serum vitamin D and TAC levels along with SOD activities were found to be significantly low (P<0.001) in Post COVID patients as compared healthy controls. However, ceruloplasmin level was altered insignificantly (p<0.1) with respect to Group I subjects. Vitamin D levels were positively correlated with TAC and SOD activity (P<0.001) and negatively correlated with MDA, CRP, TNF-alpha and uric acid levels in post COVID patients.Conclusion: Therefore, the present study emphasizes the dire need of special attention to Post COVID population by providing vitamin D supplementation, antioxidant and mineral rich diet along with adoption of regular aerobic exercise not only to rejuvenate the biomolecular homeostasis but also to reduce oxi-inflammatory stress mediated future complications.

PEGylated Polyester Nanoparticles Trigger Adverse Events in a Large Animal Model of Trauma and in Naïve Animals: Understanding Cytokine and Cellular Correlations with These Events.

Intravenously infusible nanoparticles to control bleeding have shown promise in rodents, but translation into preclinical models has been challenging as many of these nanoparticle approaches have resulted in infusion responses and adverse outcomes in large animal trauma models. We developed a hemostatic nanoparticle technology that was screened to avoid one component of the infusion response: complement activation. We administered these hemostatic nanoparticles, control nanoparticles, or saline volume controls in a porcine polytrauma model. While the hemostatic nanoparticles promoted clotting as marked by a decrease in prothrombin time and both the hemostatic nanoparticles and controls did not active complement, in a subset of the animals, hard thrombi were found in uninjured tissues in both the hemostatic and control nanoparticle groups. Using data science methods that allow one to work across heterogeneous data sets, we found that the presence of these thrombi correlated with changes in IL-6, INF-alpha, lymphocytes, and neutrophils. While these findings might suggest that this formulation would not be a safe one for translation for trauma, they provide guidance for developing screening tools to make nanoparticle formulations in the complex milieux of trauma as well as for therapeutic interventions more broadly. This is important as we look to translate intravenously administered nanoparticle formulations for therapies, particularly considering the vascular changes seen in a subset of patients following COVID-19. We need to understand adverse events like thrombi more completely and screen for these events early to make nanomaterials as safe and effective as possible.

A randomized clinical trial to stimulate the cholinergic anti-inflammatory pathway in patients with moderate COVID-19-pneumonia using a slow-paced breathing technique.

Purpose: A characteristic problem occurring in COVID-19 is excessive elevations of pro-inflammatory cytokines (e.g. IL-6 and CRP) which are associated with worse clinical outcomes. Stimulation of the vagally-mediated cholinergic anti-inflammatory reflex by slow paced breathing with prolonged exhalation may present a clinically relevant way to reduce circulating IL-6. Method: Single-center randomized controlled clinical trial with enrolment of 46 patients hospitalized with confirmed severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection and moderate COVID-19 pneumonia (primary diagnosis). Differences between intervention (4sec inhalation, 6sec exhalation for 20 minutes 3x daily) and control group in IL-6 calculated using multilevel mixed-effect linear regression models with random slope including the covariates relevant comorbidities, COVID-19 medication, and age. Both groups received standard care. Results: Mean age was 57 years ± 13 years, N= 28 (60%) male, N=30 (65%) with relevant comorbidities. The model including group-by-time interaction revealed a significantly lower trajectory of IL-6 in the intervention group (effect size Cohens f2 = 0.11, LR-test p=.040) in the intention-to-treat sample, confirmed by per-protocol analysis (f2 = 0.15, LR-test p=.022). Exploratory analysis using the median split of practice time to predict IL-6 of the next morning indicated a dose-response relationship with beneficial effects of practice time above 45 minutes per day. Oxygen saturation remained unchanged during slow-paced breathing (95.1% ± 2.1% to 95.4% ± 1.6%). Conclusion: Patients practicing slow-paced breathing had significantly lower IL-6 values than controls with a small to medium effect size and without relevant side effects. Further trials should evaluate clinical outcomes and an earlier start of the intervention. Slow-paced breathing could be an easy to implement, low-cost, safe and feasible adjuvant therapeutic approach to reduce circulating IL-6 in moderate COVID-19 pneumonia. Clinical Trial Registration: https://www.drks.de, identifier DRKS00023971, Universal Trial Number (UTN) U1111-1263-8658.

Down-regulation of RdRp complex and activated immune response due to increased arsenic level leads to decreased corona virus replication.

Corona virus is pandemic and responsible for more than 5.6 million deaths. It was observed that its severity was reported in varied ways in different countries and even in different states of India. This variation was critically evaluated in the area with high contamination of Arsenic (As) to understand the arsenic toxicity and Covid epidemiology and associated health effects in the human population. It was reported that the area with low arsenic contamination has a very high incidence rate of Corona infection in the world. Even in the Indian scenario, high As-contaminated states like West Bengal, Jharkhand and Bihar, the incidence rate is 1.994%, 1.114% and 0.661%, respectively. In contrast, states with the least arsenic contamination have a very high corona incidence rate like 6.308, 17.289 and 4.351, respectively. It was evident that Arsenic inhibits the RdRp complex, which leads to the inhibition of viral genome replication. The PAMP associated pathway was activated by Arsenic and effectively bound with viral spike proteins leading to effective clearance of virus through activation of TNF alpha and IL-1. It finally leads to increased production of IgE, IgG and IGA. Arsenic also enhances inflammatory response against the virus through increased production of cytokine. The high arsenic level also induces apoptosis in viral infected cells through Bax/Bak pathway. It activates cytochrome-c and caspase-3 activity, inducing apoptosis in viral infected cells through PARP activation in the nucleus. These combined findings suggest that high arsenic contamination causes replication inhibition, activates an inflammatory response, increases antibody production, and finally leads to apoptosis through the mitochondrial pathway. People residing in arsenic hit areas are at a very low threat of corona infection.

Association between lymphopenia and disease severity in Covid 19 patients with single pulmonary nodule

Introduction: Based on the results of recent studies, the presence of lymphopenia has been suggested as a predictor factor in patients with Quid-19. This study aimed to evaluate the association between lymphopenia and disease severity in Covid 19 patients with single pulmonary nodule. Materials & Methods: This study is a descriptive-correlational study that was performed on 32 Covid-19 patients with single pulmonary nodule. In this study, demographic characteristicsand information about laboratory data such as lymphopenia as well as radiological findings of patients were collected and analyzed using Chi-square, independent t-test and regression logistics. Results: The results showed that most of the patients participating in the study (68.8%) were male with a mean age of 38.9 years. There was a statistically significant association between lymphopenia and disease severity (P = 0.039), while there was no significant association between age, sex, and nodule type with disease severity (P> 0.05). Conclusion:Lymphopenia is a valid predictor for disease severity and mortality in patients with Covid-19.

Vaccination Recommendations for Psoriasis and Atopic Dermatitis Patients on Biologic Therapy: A Practical Guide

Novel biologic therapies have revolutionized the treatment of psoriasis and atopic dermatitis. Although they are generally safe, they are immunomodulatory and therefore unique considerations apply in regards to infections and vaccine administration. This review aims to provide a clear and practical guide for dermatologists or other healthcare providers to reference when caring for psoriasis or atopic dermatitis patients being treated with biologic therapies using currently available guidelines and clinical data. Vaccinations for approved biologics including TNF alpha, IL-12/23, IL-23, IL-17, and IL-4/13 inhibitors will be discussed, with a special note on current COVID-19 vaccination recommendations.

COVID-19-induced psoriatic arthritis: a case report.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which may lead to uncontrolled immune activation and cytokine response in some. The pattern of pro-inflammatory cytokines is similar to that which has been observed to be involved in rheumatic diseases and target treatments. Viral arthritis is common with a wide variety in spectrum ranging from arthralgia to spurious and chronic arthritis. However, recent studies have demonstrated a correlation with endemic coronaviruses and increased risk of developing rheumatoid arthritis (RA). Cases are being identified that describe a post-COVID reactive; however, to date, no report has been published describing the onset of psoriasis and concomitant development of psoriatic arthritis after COVID-19 infection. We report an interesting case of psoriatic arthritis in a post-COVID-19 infection patient with review of the current literature.

SOLVx therapeutics vaccine - Activate T-cell immunity using broad surveillance epitope strategy against mutant strains SARS-COV2.

Highly mutable Coronavirus-19 continuously reconstructs its genome and renders prophylactic vaccines ineffective. The objective of the present study was to demonstrate the anti-viral efficacy and safety of the SOLVx therapeutics vaccine. The peptides were designed with Neo7Logix R&D and synthesized with Genescript GLP laboratory with 95 % purity. BALB/C mice were used to develop the HCoV-229E mutant coronavirus model and viral mRNA confirmation in the lung tissue was assessed with qPCR. Mice were euthanized and effects of treatment on various parameters (Viral mRNA in lungs, cytokine levels, PBMC differentiation, hematological and biochemical) were assessed with respective biological samples. Immuno-typing analysis of PBMCs by flowcytometry showed marked increase in T cell subsets, % of B cells and NK cell population in mice treated with SOLVx (Series 1) in a dose dependent manner. Serum immunoglobulin G, and M levels were increased significantly (P < 0.001). In the peptide treatment groups, there was a dose dependent statistically significant decrease in IL-6, IL-10 and TNF-α levels (P < 0.001). IFN-γ was elevated in treatment group significantly (P < 0.001). In conclusion, the qPCR results suggested that the SOLVx vaccine (Series 1) reduced the SARS-COV2 virus infectivity in a dose dependent manner. The humoral, cellular and functional activity of the SOLVx showed that it worked through multi-mechanistic targeting the virus evolution, offering immune response, defense and eradication of the SARS-COV2 virus.

Haematological Parameters in Covid-19 Patients-An East Nimar Hospital Based Study

Background: The Coronavirus disease 2019 (Covid-19) is caused by the virus SARS COV-2 and is declared as a global pandemic by WHO. It is known that in SARS COV-2 virus infection causes haematological changes and often present the potential to optimize the monitoring of infectious process or to indicate the suspicion of their severity. The present study was conducted to study the routine haematological parameters including NLR (Neutrophil lymphocyte Ratio) in Covid-19 patients and to assess their utility in identifying severity of the disease. Methods: This retrospective study was conducted on 257 Covid-19 RT PCR positive cases. The cases were divided into mild, moderate, and severe category as per MoHFW. Haematological parameters were measured by Fully Automated Hematology cell counter using blood sample collected in EDTA vacutainers. MS Excel was used for data analysis and ANOVA tests were applied to test statistical significance. P<0.05 was considered statistically significant. Results: Degree of severity of Covid-19 cases could be correlated with older age group. Most important haematological parameters noted in adults are Eosinopenia in 84%, Monocytopenia in 64%, NLR >3 in 18.32 %, and Leucopoenia (17.5%). Severe category showed higher proportion of NLR >3 in 40.6%, Neutrophilia in 31.2%, Leucocytosis in 28.2% and lymphocytopenia in 12.5%. Conclusions: Haematological parameters in Covid-19 positive cases could help to predict a patient risk and outcome in the Indian scenario that will provide guidance to subsequent clinical practice.

Cardiovascular complications in the Post-Acute COVID-19 syndrome (PACS).

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) or coronavirus disease 2019 (COVID-19) initially surfaced in December 2019 from Wuhan, China, sweeping the world with various strains, forcing the WHO to declare a pandemic epidemic in March 2020. Furthermore, COVID-19 manifests with a wide array of presentations from fever and fatigue to severe respiratory and cardiovascular complications. Post-COVID-19 syndrome is poorly understood affecting COVID-19 survivors at all levels of disease severity. The disease is most associated with post-discharge dyspnea and fatigue. However, other persistent symptoms as chest pains, palpitations, smell, and taste dysfunctions. Patients with high concentrations of CRP and creatinine in the acute phase of Covid-19 are more prone to cardiac sequelae. Therefore, high levels of cardiac-sensitive troponin and hypokalaemia can also be used for risk stratification. Furthermore, Cardiac damage can manifest as myocarditis, pericarditis, rhythm abnormalities. The use of different diagnostic modalities like electrocardiogram (ECG), echocardiogram, and cardiac magnetic resonance imaging (MRI)(CMR) to evaluate the myocardial damage were studied. However, Cardiovascular complications are a common manifestation of PASC, classification of severity of cardiac symptoms and the emergence of CMR as a diagnostic tool needs more evidence.