Genetic Association of Interleukin 16 Gene Polymorphisms (rs11556218 & rs4778889) with Type 1 Diabetes in Egyptian Children: A Case-Control Study.

BACKGROUND: Type 1 diabetes (T1D) is a serious chronic autoimmune condition. Even though the underlying reason for the onset of T1D is unknown, due to their effector and regulatory roles in immune responses, cytokines are essential in developing autoimmune disorders. Interleukin (IL)16 is an immunomodulatory cytokine implicated in several inflammatory and autoimmune diseases. OBJECTIVE: This study was designed to examine the association of IL16 gene polymorphisms, rs11556218 T > G and rs4778889 T > C, with the risk of T1D in Egyptian children. METHODS: Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay, we analyzed rs11556218 T > G and rs4778889 T > C polymorphisms of the IL16 gene in 100 T1D subjects and 93 controls. RESULTS: Rs11556218 T > G polymorphism of the IL16 gene was not associated with the risk of developing T1D. Analysis of IL16 gene rs4778889 T > C showed that the TT genotype had a considerably higher risk of T1D than the TC genotype [OR = 2.195 (1.205-3.999)]. In comparison to patients with the C allele [OR = 0.6914 (0.38-1.2569)], patients with the T allele [OR = 1.45 (0.7956-2.6296)] were notably more likely to have T1D. A significant decrease was found in the frequency of GT (OR = 0.43, p = .03) and TC (OR = 0.32, p = .011) haplotypes of IL16 gene rs11556218 T > G and rs4778889 T > C polymorphisms in T1D patients compared with controls. CONCLUSION: IL16 gene rs4778889 T > C polymorphism might be associated with susceptibility to T1D. Egyptians with TT genotypes are more likely to develop T1D. However, GT and TC haplotypes of IL16 gene rs11556218 T > G and rs4778889 T > C polymorphisms highlight their protective role againstT1D disease.

Cytotoxic effect of combining two antisense oligonucleotides against telomerase rna component (hTR and mRNA of centromere protein B (CENP-B) in hepatocellular carcinoma cells.

Telomerase is a ribonucleoprotein enzyme that plays a crucial role in maintaining the malignancy and is responsible for cellular immortality and tumorigenesis. On another hand, Centromere protein B (CENP-B) plays an important role in cell cycle regulation and helping in the high rate proliferation of cancer cells. Our study is designed to evaluate the effect of using combined antisense oligonucleotides (ASOs) targeting (hTR) and mRNA of CENP-B on liver cancer cells. Compared with a single treatment, combination treatment with Locked Nucleic Acid (LNA) ASO (hTR) and (CENP-B) (6.25 nM from each) exhibit the maximum synergistic cytotoxic effect. hTR and CENP-B mRNA was abrogated while hTERT expression was disappeared. Caspase-3, Bax, and Bcl-2 were not detected, indicating caspase-independent cell death. A significant reduction in [Tumor necrosis factor (TNF-α) and Transforming growth factor (TGF-ß)] coincides with elevation in Nitric oxide (NO) secretions was observed. Taken together; our data suggest that combination treatment with LNA ASO (hTR) and (CENP-B) could provide a promising strategy for cancer treatment by controlling many pathways concurrently. This might open a new prospective application of antisense in cancer therapy.

Rhinoplasty Assisted by Endoscopic Septoplasty: Precise Job and an Educational Tool.

BACKGROUND: Septoplasty is a crucial step during rhinoplasty to correct the nose function and nasal aesthetics. The idea is not investigated regarding the educational purposes. Objective of the study is to evaluate the efficiency of endoscopic septoplasty during full job rhinoplasty and to observe its educational benefit. METHODS: Twenty-seven patients who submitted for prospective study of endoscopic septorhinoplasty operation; the analysis involves 16 female patients and 11 males. RESULTS: Endoscopic septoplasty during rhinoplasty showed an efficient illumination and visualization, which improved the precision and has an educational benefit during the reform of the posterior septum, isolated septal spurs, anterior septum, and middle turbinate attachments. CONCLUSION: The procedure allows a precise septal job with excellent visualization of the anterior and posterior septum. It also has an intraoperative educational benefit and helps to soothe the time down of patient's recovery.

Geomagnetic Shielding Enhances Radiation Resistance by Promoting DNA Repair Process in Human Bronchial Epithelial Cells.

With the advent of long-duration space explorations, ionizing radiation (IR) may pose a constant threat to astronauts without the protection of Earth's magnetic field, or hypomagnetic field (HMF). However, the potential biological effects of a HMF on the cellular response to IR have not been well characterized so far. In this study, immortalized human bronchial epithelial cells were exposed to X-rays under either a geomagnetic field (GMF, ~50 uT) or HMF (<50 nT) culture condition. A significant increase of the cell survival rate in HMF after radiation was observed by colony formation analysis. The kinetics of DNA double-strand breaks (DSBs), determined by γH2AX foci formation and disappearance, presented a faster decrease of foci-positive cells and a significantly lower mean number of γH2AX foci per nucleus in HMF-cultured cells than in GMF-cultured cells after radiation. In addition, a γH2AX/53BP1 colocalization assay showed an upregulated DSB recovery rate in HMF cultured cells. These findings provided the first evidence that HMF exposure may enhance the cellular DSB repair efficiency upon radiation, and consequently modulate the genotoxic effects of IR.

Correlation of myomir-206 and proinflammatory cytokines (IL-16 and IL-17) in patients with rheumatoid arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) is a persistent autoimmune disease in which the activity of proinflammatory cytokines and the imbalance, related to the inflammatory process, between elements of bone tissue remodeling such as osteoclasts and osteoblasts play a key role in development of erosions and bone destruction. MicroRNAs are important regulators of skeletal remodeling and are involved in RA pathogenesis. Myomir-206 (miR-206) is unrivalled among the myomirRs, where it is expressed in skeletal muscle and either absent or minimally expressed in other tissues. MATERIAL AND METHODS: This study was designed to analyze the miR-206 expression pattern in peripheral blood mononuclear cells (PBMCs) using quantitative real time polymerase chain reaction and its correlation with IL-16/IL-17 proinflammatory cytokines in two groups - 20 healthy individuals and 30 patients with RA. RESULTS: Elevated expression of miR-206 was observed in RA patients compared with healthy controls (p < 0.001). A significant increase in both IL-17 and IL-16 serum levels was found in the RA group (p < 0.01 and p < 0.05; respectively) compared to the control group. miR-206 expression level and IL-17 production were directly positively correlated (r = 0.491; p < 0.01). ROC analysis of miR-206 showed a cutoff value of 2.7 with 70% sensitivity, 85% specificity, and the area under the curve was 0.802 (p < 0.001) with the 95% confidence interval from 0. 676 to 0.927. CONCLUSIONS: Taken together, our results indicate the importance of miR-206 expression in patients with RA, as a potential new biomarker that affects bone loss/deformity and its collaborative role with proinflammatory cytokines such as IL-16 and IL-17 in RA bone metabolism. Particular interest should be given to further research to determine the contribution of expression of miR-206 in RA pathogenesis.

Two years' outcome of thread lifting with absorbable barbed PDO threads: Innovative score for objective and subjective assessment.

BACKGROUND: Thread-lifting rejuvenation procedures have evolved again, with the development of absorbable threads. Although they have gained popularity among plastic surgeons and dermatologists, very few articles have been written in literature about absorbable threads. This study aims to evaluate two years' outcome of thread lifting using absorbable barbed threads for facial rejuvenation. METHODS: Prospective comparative stud both objectively and subjectively and follow-up assessment for 24 months. RESULTS: Thread lifting for face rejuvenation has significant long-lasting effects that include skin lifting from 3-10 mm and high degree of patients' satisfaction with less incidence rate of complications, about 4.8%. Augmented results are obtained when thread lifting is combined with other lifting and rejuvenation modalities. CONCLUSION: Significant facial rejuvenation is achieved by thread lifting and highly augmented results are observed when they are combined with Botox, fillers, and/or platelet rich plasma (PRP) rejuvenations.

Factors affecting the adoption of metaverse in healthcare: The moderating role of digital division, and meta-culture.

This research aims to find out the factors affecting the adoption of Metaverse in healthcare. This study explores the effect of perceived ease of use, perceived usefulness, and trust on adopting Metaverse in healthcare by keeping digital division and metaculture as moderating variables. The philosophical foundation is rooted in the positivism paradigm, the methodology is quantitative, and the approach used is deductive. Data was collected in Pakistan and China through judgmental sampling from 384 respondents. Partial Least Square Structural Equation Modelling (PLS-SEM) was used to analyze the collected data. The findings validate the relationship between perceived ease of use and the adoption of metaverse with ß-value 0.236, t-value 5.207 and p-value 0.000, the relationship between perceived usefulness and the adoption of metaverse with ß-value 0.233, t-value 4.017 and p-value 0.000, and the relationship between trust and adoption of a metaverse with ß-value 0.192, t-value 3.589 and p-value 0.000. Results also show that the digital divide moderates the relation between perceived ease of use and adopting the metaverse having ß-value 0.078, t-value 1.848 and p-value 0.032. Similarly, the findings also show that the digital divide does not moderate the relationships of perceived usefulness and trust with adopting the metaverse. Moreover, the meta culture also does not moderate the relationships of perceived ease of use, usefulness, and trust with adopting the metaverse. The study contributes to theoretical research on adopting a metaverse in healthcare by examining various factors necessary for its development. It also provides guidelines for the developers and adopters of suitable metaverse technology.

Role of epinephrine in attenuating cytokine storm, decreasing ferritin, and inhibiting ferroptosis in SARS-CoV-2.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for coronavirus disease 2019. It presents one of the most threatening pandemics in the history of humanity. The mortality and morbidity represent an unprecedented challenge to the modern medical era. SARS-CoV-2 results in acute respiratory distress syndrome, high concentrations of proinflammatory mediators, cytokine storm (CS) due to massive release of cytokines, hypercoagulation, and hemoglobin disintegration. Dysregulation of iron homeostasis, iron overload as indicated by high ferritin level, and ferroptosis are major factors in the pathogenesis of the disease. We report a case of SARS-CoV-2 in which the use of epinephrine (Epi) resulted in an unexpected attenuation of CS, decreasing ferritin level and inhibiting ferroptosis. CASE PRESENTATION: A 64-year-old male patient with a history of multiple medical comorbidities had been diagnosed with SARS-CoV-2. Further evaluation showed marked increase in inflammatory markers, severe hyperferritinemia, and lymphopenia in laboratory blood tests. The characteristic score of CS was strongly positive, and in addition to regular treatment, the patient received Epi due to development of acute generalized skin rash, severe itching, and edema of lips and tongue. Epi may have successfully terminated not only the acute cutaneous condition, but also have attenuated CS, decreased ferritin level, and other inflammatory markers in addition to complete patient's recovery. CONCLUSION: Epinephrine may attenuate CS and inhibit ferroptosis which is an iron-dependent, non-apoptotic mode of cell death. Epi interacts with ferric and/or ferrous iron and built a stable complex that impedes activation of beta-adrenergic receptors. Epi may cause marked decrease of ferritin and other inflammatory markers. Epi may be used to decrease iron overload which is associated with many medical diseases like type 2 diabetes mellitus and cardiometabolic diseases such as coronary heart disease and cerebrovascular disease. As a new clinical indication extensive studies are required for further assessment and possible therapeutic uses.

Investigating the role of Cybersecurity's perceived threats in the adoption of health information systems.

Information technology is one of the most rapidly growing technologies globally. Over the last decade, its usage in healthcare has been remarkable. Over the last decade, its usage in healthcare has been remarkable. The study examines the impact of various factors as barriers to adopting the information system in healthcare. These factors are categorized into three major types: external attacks, which include phishing attacks and ransomware; employee factors, including lack of skills and the issue of information misuse; and technological factors, including complexity and vulnerability. The findings show that external attacks and technological factors are the main barriers to adopting information systems, while employee factors have no significant impact on the adoption of information systems in the healthcare industry of Pakistan. The study provides implications for healthcare policy makers, professionals and organziations regarding the successful adoption of health information system.

Investigating the role of green behavior and perceived benefits in shaping green car buying behavior with environmental awareness as a moderator.

As the planet faces the challenge of global warming, every individual and organization must adopt green practices to protect nature. The automobile industry is one of the primary industries which can contribute significantly towards sustainability. This study aims to examine the impact of green behavior and green perceived benefits on the green buying behaviors of automobiles. The research also explores the moderating influence of environmental awareness on the mechanism. The research is based on a quantitative method for which primary data was gathered from 406 respondents across Pakistan, China and Saudi Arabia via Quota-based purposive sampling. The gathered data was analyzed via SmartPLS. The results show that green behavior and perceived benefits positively and significantly influence green buying behavior. The findings also show the moderating role of environmental awareness on green behavior towards green buying and show no impact on the perceived benefits towards buying behavior. The study has practical and theoretical implications for managers, researchers, policymakers and institutions in the context of green automobile development and businesses. The study also contributes to the attainment of sustainable development goals.

Renal tubular dysfunction in children with sickle cell haemoglobinopathy.

AIM: Children with sickle cell disease (SCD) are remarkably more prone than others to renal dysfunction. The kidneys, as one of the systemic long-term hazards in SCD, may be affected by both the haemodynamic changes of chronic anaemia as well as by the consequences of vaso-occlusion. The aim of this study was to evaluate the proximal tubular function in a group of Saudi children with established SCD. METHODS: This study was conducted in Al-Khafji Joint Operations (KJO) Hospital, in Saudi Arabia during the period from June 2011 to August 2012. Thirty-four children: Group I (18 males and 16 females) with SCD (HBSS) and 27 children: Group II (17 males and 10 females) with sickle cell trait (HBAS) were evaluated for urinary excretion of retinol binding protein (RBP) and - Beta 2 microglobulin (ß2 MG). RESULTS: Group I patients showed a significantly impaired urinary concentrating ability compared to that of Group II (417 ± 94 mOsm/kg vs 581 ± 165 mOsm/kg). The urinary excretions of RBP and ß2-microglobulin were significantly higher in Group I than in Group II. The values were 762.01 ± 124.20 µg/L and 841.84 ± 389.02 µg/L versus 198.12 ± 42.24 µg/L and 298.3 ± 38.11 µg/L, respectively. CONCLUSION: Significant proximal tubular dysfunction was a feature in the SCD group, indicated by high urinary RBP and ß2-microglobulin excretion. Assessing the urinary excretion of these low molecular weight proteins in children with sickle cell disease at different points of diagnosis may add key clinical information to the follow up of renal tubular function in patients with SCD.

Crosstalk between miR-146a and pro-inflammatory cytokines in patients with systemic lupus erythematosus.

microRNA-146a (miR-146a) plays an essential role in immune anomalies and organ injury of systemic lupus erythematosus (SLE) by regulating the disease's inflammation and complications. Here, we analyzed the expression of miR-146a in SLE and a panel of pro-inflammatory cytokines (IL-1, IL-6, IL-8, IL-17, and TNF-α). Association between all measured parameters and the disease's clinical manifestation and response to treatment was monitored. Our study populations were 113 SLE patients and 104 healthy volunteers. miR-146a expression in peripheral blood mononuclear cells (PBMCs) was measured by quantitative real-time PCR (RT-qPCR). The content of the plasma cytokines (IL-1ß, IL-6, IL-8, IL-17, and TNF-α) was detected by enzyme-linked immunosorbent assay (ELISA). Compared with healthy controls, miR-146a expression was significantly increased (p < 0.05) in lupus patients. The analysis of the receiver operator characteristic curve (ROC) of miR-146a showed 91% sensitivity and 70% specificity. IL-1ß, IL-6, and IL-17 cytokines were significantly increased (p < 0.001), while IL-8 and TNF-α were significantly decreased (p < 0.001) in SLE patients against controls. The expression of miR-146a and TNF-α was upregulated considerably in SLE patients with severe disease activity. miR-146a expression was positively correlated with IL-6. Our results pointed to the elevation of miR-146a as a trade marker of SLE patients. Reduction of IL-8 and TNF-α in combination with an elevation of IL-1ß, IL-6, and IL-17 might refer to miR-146a's dual effect in controlling inflammation in lupus. Although we shed some light on the role of miR-146a in SLE, further study is recommended to improve our results.

Ligament Preservation in Open Rhinoplasty: Prospective Analysis.

BACKGROUND: In the open rhinoplasty technique, the soft tissue and ligaments are vulnerable to injury. Reconstruction of the ligaments is not performed routinely. The authors aimed to assess the effect of preservation of the nasal ligaments (ie, scroll, septocolumellar, and Pitanguy ligaments) in open-approach rhinoplasty. METHODS: In this prospective cohort study, 32 patients underwent open rhinoplasty with ligament preservation after receiving precise training on five cadavers. RESULTS: All patients had improved aesthetic and functional outcome in the early postoperative period with long-lasting preservation of tip projection and results. No patient needed secondary revision surgery for tip dropping or malrotation. The objective findings and subjective assessments were satisfying for the patients and surgeons. CONCLUSIONS: Refinements of nasal surgery have no limits. This study suggests that nasal ligament reconstruction, including of the scroll, septocolumellar, and Pitanguy ligaments, could maintain nasal tip projection and rotation for a long time. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

An empirical evaluation of technology acceptance model for Artificial Intelligence in E-commerce.

Artificial Intelligence (AI) has become essential to Electronic-Commerce technology over the past decades. Its fast growth has changed the way consumers do online shopping. Using the Technology Acceptance Model (TAM) as a theoretical framework, this research examines how AI can be made more effective and profitable in e-commerce and how entrepreneurs can make AI technology to assist in achieving their business goals. In this regard, an online survey was conducted from the online purchasers of e-commerce firms. The Partial Least Square (PLS) Smart was used to examine the data. The broadly used TAM was identified as an appropriate hypothetical model for studying the acceptance of AI technology in e-commerce. The findings of this study show that Subjective Norms positively impact Perceived Usefulness (PU) and Pursued Ease of Use (PEU), trust has a positive effect on PEU, and PEU positively impacts PU and attitudes toward use. Similarly, PU also has a positive effect on attitudes toward use and intention to use. Furthermore, the findings do not support the impact of Trust on PU and attitudes towards behavioural intention to use. Lastly, behavioural intention to use positively impacted the actual use of AI technology. This study adds theoretical and practical knowledge for adopting the TAM model in the E-commerce sector. It helps entrepreneurs to implement the TAM model in their business to use AI in a better and more appropriate way.

Nandrolone decanoate safely combats catabolism in burned patients: A new potential indication after recall.

INTRODUCTION: The hyper-catabolic state is a devastating pathophysiological response to severe injury, infection or burns. Nandrolone decanoate (ND) is a potent anabolic steroid have many clinical indications, but not investigated in burn injuries yet. PATIENTS AND METHODS: A prospective randomized control study included 40 burned patients who were treated in Burn unit from burn injuries ranged from 20 to 40%. Both groups are objectively assessed, clinically and laboratory during treatment period till full recovery from burns' injury. Recall assessment of the drug safety after many years is achieved. RESULTS: ND showed highly significant results supporting its use in combating catabolic insults in burns patient. Both clinical findings and laboratory findings are correlated and highly support the use of ND in burns as new effective and safe long-lasting indication. CONCLUSION: This study results showed preservation of lean body mass and protein partition, as well as the near normal nitrogen balance in burn patients. Study proposes that nandrolone decanoate could be used in safe and effective way to combat hypercatabolic impact in burn injury.

Clock in radiation oncology clinics: cost-free modality to alleviate treatment-related toxicity.

A large number of studies have reported that tumor cells are often out of sync with the surrounding healthy tissue. Exploiting this misalignment may be a way to obtain a substantial gain in the therapeutic window. Specifically, based on reports to date, we will assess whether radiotherapy outcomes differ depending on the administration time. Collectively, 24 studies met the inclusion criteria, out of which 12 at least reported that radiation therapy is less toxic when administered at a particular time, probably because there is less collateral damage to healthy cells. However, discrepancies exist across studies and urge further investigation. Mechanistic studies elucidating the relationship between radiotherapy, circadian rhythms, and cell cycle, combined with either our "digital" or "biological" chronodata, would help oncologists successfully chronotype individual patients and strategize treatment plans accordingly.

The Use of Sustained Release Intravitreal Steroid Implants in Non-Infectious Uveitis Affecting the Posterior Segment of the Eye.

The treatment of non-infectious uveitis affecting the posterior segment of the eye has been revolutionized by the development of sustained-release corticosteroid implants over the past decade. Their use is now supported by healthcare systems that have licensed and commissioned them on the basis of the high-quality randomised controlled trials that formed part of their development and which have informed clinicians as to their benefits and risks. In particular, they have provided an alternative mode of treatment for patients who do not wish to be systemically immunosuppressed, or in whom such immunosuppression is less desirable, such as those with unilateral disease or those with concurrent illnesses such as diabetes mellitus, renal disease or osteoporosis that are negatively impacted by systemic corticosteroids or other immunosuppressive agents. In this article, we review the evidence for the use of the major licensed corticosteroid implants and assess the advantages and disadvantages of each.

Combining Bevacizumab with Knocked-Down ß-Catenin Reduces VEGF-A and Slug mRNA in HepG2 but not in Caco-2 Cell Lines.

BACKGROUND: Bevacizumab (Bev) resistance is hypothesized to be overcome by combining inhibitors of other signalling pathways. OBJECTIVE: We aimed to study the effect of combining Bev with knocked down ß-catenin (Bev-ß-cat-siRNA) on the expression of VEGF-A, Slug, NFκB, and its two target genes, c-Flip and FasR, in HepG2. Expression of VEGF-A and Slug was also studied in Caco-2 cells. METHODS: Cultured cells were divided into six groups 1) cells treated with Bev, 2) cells treated with ß-catenin-siRNA, 3) cells treated with Bev-ß-cat-siRNA, 4) cells treated with negative control, 5) cells treated with Bev-negative control, and 6) untreated cells. Expressions were assessed using qPCR and western blotting. RESULTS: Bev-ß-cat-siRNA significantly reduced the mRNA level of VEGF-A, which was initially increased in response to Bev alone in HepG2 but not in Caco-2. Additionally, Bev-ß-cat-siRNA significantly decreased Slug mRNA level compared to Bev treated HepG2 cells. In contrast, VEGF-A and Slug mRNA levels in Bev group were remarkably lower than Bev-ß-cat-siRNA in Caco-2 cells. Distinct ß-catenin and Slug protein expressions were noticed in HepG2 and Caco-2 cells. On the other hand, Bev-ß-catsiRNA remarkably reduced the level of NFκB, FasR, and c-Flip compared to Bev treated HepG2 cells, although the difference was not statistically significant. CONCLUSION: We conclude that combining Bevacizumab with knocked down ß-catenin reduces the expression of VEGF-A and Slug in HepG2 but not in Caco-2 cells.

mir-146a genetic polymorphisms in systemic lupus erythematosus patients: Correlation with disease manifestations.

This study aimed to investigate the genetic polymorphisms of miR-146a SNPs (rs2910164, rs57095329, and rs2431697) in systemic lupus erythematosus (SLE) patients and their association with clinical manifestations. The implication of SNPs on miR-146a expression level was also evaluated. SLE patients (113) and healthy controls (104) were registered in this study. The miR-146a SNPs were genotyped by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). Quantitative real-time PCR was used to measure the miR-146a expression in peripheral blood mononuclear cells (PBMCs). Our results showed that the genotype frequency of miR-146a SNPs didn't deviate significantly from the Hardy-Weinberg equilibrium (HWE). The AG genotype and G allele of miR-146a (rs57095329 A/G) might be considered a risk factor for the disease (OR = 2.27; CI: 0.78-6.57 and OR: 2.35; CI: 0.79-6.92 for AG genotype and G allele, respectively). Although, no statistical significance in the distribution of miR-146a SNPs (rs2910164, rs57095329, and rs2431697) was found, indicating the lack of association between the three SNPs and SLE susceptibility. Significantly, the higher frequency of the AA genotype of miR-146a (rs57095329) was associated with pancytopenia (P < 0.05), while the CT genotype of miR-146a (rs2431697) was associated (P < 0.05) with the antiphospholipid syndrome (APS). SLE patients had significantly higher levels of miR-146a compared to controls (P < 0.05). Elevation of miR-146a was independent of any SNP genotypes. In conclusion, this pilot study shows no association between miR-146a SNPs in our population group and susceptibility to lupus. Studies concerning other miRNAs in larger sample sizes are essential for a better understanding of their role in susceptibility to SLE disease.

Therapeutic role of immunomodulators during the COVID-19 pandemic- a narrative review.

The emergency state caused by COVID-19 saw the use of immunomodulators despite the absence of robust research. To date, the results of relatively few randomized controlled trials have been published, and methodological approaches are riddled with bias and heterogeneity. Anti-SARS-CoV-2 antibodies, convalescent plasma and the JAK inhibitor baricitinib have gained Emergency Use Authorizations and tentative recommendations for their use in clinical practice alone or in combination with other therapies. Anti-SARS-CoV-2 antibodies are predominating the management of non-hospitalized patients, while the inpatient setting is seeing the use of convalescent plasma, baricitinib, tofacitinib, tocilizumab, sarilumab, and corticosteroids, as applicable. Available clinical data also suggest the potential clinical benefit of the early administration of blood-derived products (e.g. convalescent plasma, non-SARS-CoV-2-specific immunoglobins) and the blockade of factors implicated in the hyperinflammatory state of severe COVID-19 (Interleukin 1 and 6; Janus Kinase). Immune therapies seem to have a protective effect and using immunomodulators alone or in combination with viral replication inhibitors and other treatment modalities might prevent progression into severe COVID-19 disease, cytokine storm and death. Future trials should address existing gaps and reshape the landscape of COVID-19 management.