PPP1R13L-Related Cardiomyopathy Stability Following IL1 Inhibition

Introduction: Variants in PPP1R13L are associated with severe childhood-onset cardiomyopathy resulting in rapid progression to death or cardiac transplantation. PPP1R13L is proposed to encode a protein that limits the transcriptional activity of the NFkappaB pathway leading to elevated IL-1, IL-6, and TNF-alpha production in murine models. Optimal medical management for PPP1R13L-related cardiomyopathy is unknown. Here we report usage of a targeted anti-IL-1 immuno-modulatory therapy resulting in cardiac stabilization in a pediatric patient with congenital cardiomyopathy secondary to PPP1R13L variants. Case Report: A 4-year-old boy presented acutely with fever in the setting of persistent abdominal pain, vomiting, fatigue, and decreased appetite for two months following a mild COVID-19 related illness. Echocardiogram revealed severely depressed biventricular systolic function with an ejection fraction of 30%. Due to acute decompensated heart failure symptoms with hemodynamic instability, he was intubated and placed on continuous inotropic infusions with aggressive diuresis. Cardiac MRI demonstrated extensive subepicardial to near transmural fibrosis by late gadolinium enhancement in right and left ventricles. An implantable cardioverter-defibrillator (ICD) was placed due to frequent runs of polymorphic non-sustained ventricular tachycardia. Testing for viral pathogens was positive for rhino/enterovirus. Initial genetic testing was non-diagnostic (82-gene cardiomyopathy panel) but given the patient's significant presentation whole genome sequencing was pursued that showed two separate PPP1R13L variants in trans (c.2167A>C,p.T723P and c.2179_2183del,p. G727Hfs*25, NM_006663.4). Patient serum cytokine testing revealed elevations in IL-10 (4.7 pg/mL) and IL-1beta (20.9 pg/mL). Given the patient's tenuous circumstances and concern for continued progression of his cardiac disease, a trial of IL-1 inhibition via anakinra dosed at 3 mg/kg or 45 mg daily was initiated following hospital discharge. With approximately 6 months of therapy, the patient's cardiac function is stable with normalization of IL-10 and IL-1beta serum levels. Notably, the ventricular arrhythmia decreased after initiation of anakinra with no ICD shocks given. Therapy overall has been well tolerated without infectious concerns. Conclusion(s): In patients with PPP1R13L-related cardiomyopathy, immuno-modulatory therapies should be considered in an attempt to slow cardiac disease progression.Copyright © 2023 Elsevier Inc.

COVID-19: An Update on the Latest Therapeutic Agents

The COVID-19 pandemic has plagued the world for over three years since discovering the causative virus, SARS-CoV-2, in China. The rampant spread of the virus led to the loss of livelihoods of millions across the globe. This public health emergency prompted the rapid development of vaccines and treatments to fight against viral infection. Vaccines against the viral infection started rolling out in late 2020, and the distribution of the vaccines worldwide managed to reduce the symptoms of COVID-19 and prevent outbreaks in local communities. However, COVID-19 infections are still prevalent, with patients suffering from severe symptoms which require oxygen support or mechanical ventilation. Thus, therapeutic agents for COVID-19 play a significant role in reducing the risk of disease progression into severe disease and improving hospitalized patients' clinical outcomes. Existing drugs such as remdesivir, molnupiravir, baricitinib, anakinra, and tocilizumab have been repurposed to treat COVID-19 earlier during the pandemic to meet the urgent demand for treatment. There are also novel antiviral and immunomodulating treatments (nirmatrelvir plus ritonavir, ensitrelvir, regdanvimab, sotrovimab, and vilobelimab) that were developed during the pandemic to fight against COVID-19 infections. These therapeutic agents have been reported to be effective and safe for use to treat COVID-19 infections of different severity. Nevertheless, continuous surveillance is imperative in ensuring that these treatment methods maintain efficacy and safety profiles in treating COVID-19 caused by different variants of the virus. © 2023, HH Publisher. All rights reserved.

Versatile Use of Mycobacterium indicus pranii (MIP) Vaccine

Mycobacterium indicus pranii (MIP) earlier known as Mw is a soil-borne, non-pathogenic, saprophytic and rapidly growing strain of mycobacteria. MIP is approved as a vaccine/ immunomodulator for various indications including mycobacterium infections like leprosy in humans. Its administration has resulted in satisfactory clinical improvement, accelerated bacillary clearance, and increased immune responses to Mycobacterium leprae antigens, thereby shortening the full recovery time of the patients. It also shares its antigens with M.tuberculosis. In the last decade, RCTs have been done establishing immunotherapeutic properties of MIP in the treatment of leprosy, tuberculosis, warts and experimently in leishmaniasis. Through its immune inducing and cytotoxic property, it has also proved beneficial for human use especially in treating lung cancer. The beneficial role of it is also being explored in breast, cervical, oral, liver, and bladder cancers. Various studies on MIP have shown that it has immune-modulating properties in humans. The curiosity of the human mind has led to it being tried in Covid treatment trials. The results have shown that administering MIP has lowered inflammatory markers in Covid 19 patients, promising us for it to be a potential treatment option. More RCTs with a larger sample size should be done to establish this. Cytokine storm seen in bacterial sepsis is also decreased with MIP administration. Considering the encouraging results in hastening recovery in various diseases it appears that MIP is perhaps not being exploited to its fullest potential. © 2023, Hind Kusht Nivaran Sangh (Indian Leprosy Association). All rights reserved.

Dendrobium officinale aqueous extract influences the immune response following vaccination against SARS-CoV-2.

BACKGROUND: Vaccination is the most effective way to prevent coronavirus disease 2019 (COVID-19). However, it is often less protective and does not significantly increase antibody levels, especially in individuals with impaired immune systems. Nevertheless, the immunocompetence can be enhanced using a natural immunomodulator, such as Dendrobium officinale aqueous extract (DoAE). METHODS: To determine whether DoAE promotes antibody production, we treated healthy volunteers with DoAE during COVID-19 vaccination. Meanwhile, the control volunteers were given a placebo (cornstarch) during the vaccination. Antibody levels were measured at three-week intervals in the DoAE and control groups. RESULTS: DoAE enhanced immunity and preserved immune cell homeostasis. However, the neutralizing antibody (nAb) levels in the DoAE group were lower than those in the control group. Analysis of the gut microbiota revealed that the abundance of anti-inflammatory flora was increased, while the pro-inflammatory flora was reduced in the DoAE group. CONCLUSION: DoAE has immunomodulatory and anti-inflammatory properties. Therefore, DoAE has the potential for COVID-19 prophylaxis, treatment, and recovery from the adverse effects of COVID-19. However, its anti-inflammatory activity affects the production of nAbs. Thus, DoAE may not be recommended for consumption during COVID-19 vaccination.

Korean Red Ginseng Potentially Improves Maintaining Antibodies after COVID-19 Vaccination: A 24-Week Longitudinal Study.

Despite the effectiveness and safety of COVID-19 vaccines, vaccine-induced responses decline over time; thus, booster vaccines have been approved globally. In addition, interest in natural compounds capable of improving host immunity has increased. This study aimed to examine the effect of Korean Red Ginseng (KRG) on virus-specific antibodies after COVID-19 vaccination. We conducted a 24 week clinical pilot study of 350 healthy subjects who received two doses of the COVID-19 vaccine and a booster vaccination (third dose). These subjects were randomized 1:2 to the KRG and control groups. We evaluated antibody response five times: just before the second dose (baseline), 2 weeks, 4 weeks, 12 weeks after the second dose, and 4 weeks after the third dose. The primary endpoints were changes in COVID-19 spike antibody titers and neutralizing antibody titers. The antibody formation rate of the KRG group was sustained higher than that of the control group for 12 weeks after the second dose. This trend was prominently observed in those above 50 years old. We found that KRG can help to increase and maintain vaccine response, highlighting that KRG could potentially be used as an immunomodulator with COVID-19 vaccines.

Herbs-derived phytochemicals - a boon for combating COVID-19.

The recent pandemic, the novel coronavirus (COVID-19), has put the whole world on alert with the threat of the virus that targets the human respiratory system. The disease has affected more than 633.6 million people globally and caused 6.5 million deaths since November 18, 2022. About 12.94 billion people are vaccinated as of November 18, 2022. Due to varied climatic conditions, SARS-CoV-2 has shown rapid mutation in recent years. Because of the lack of appropriate therapeutic drugs, inadequate diagnostic mechanisms, life-supporting medical facilities, and lack of awareness, the spread of SARS-CoV-2 has become severe. Thus, the most efficient strategy to control this disease is to follow preventive measures. However, treating SARS-CoV-2 cases in Wuhan using traditional Chinese herbs has set an example to show how traditional health can contribute to treating this novel virus. Medicinal herbs are known for their antimicrobial, antibacterial, antiviral, immunomodulatory, immunoadjuvant, and anti-inflammatory properties. These medicinal herbs are used during cooking and consumed regularly worldwide. In this view, medicinal herbs gained evident attention. These herbs can serve as a potential and economical remedy for combating the lethal effects of COVID-19. The present review highlights the phytochemicals and their mechanisms of action in preventing SARS-CoV-2. Supplementary Information: The online version contains supplementary material available at 10.1007/s42535-023-00601-9.

Immunomodulation Impact of Curcumin and Its Derivative as a Natural Ingredient

Curcumin is a phytochemical derived from the bulb of the plant Curcuma longa and is the major component of turmeric. The herb has been used for thousands of years in traditional Ayurvedic and Asian medicine, initially to heal wounds but also to treat diverse conditions. There is a definite need to develop effective, inexpensive, safe treatments for the millions of patients with chronic diseases, including cancer, autoimmune diseases, and degenerative conditions such as arthritis. From the current scenario and study of curcumin, it is believed that data from ongoing and future research will continuously boost researchers to enhance the use of natural, synthetic, and semi synthetic derivatives of the compound as both a primary and secondary therapeutic in a variety of disease states. It has also been reported that curcumin is capable of inhibiting the development of cancer cells and/or inducing many signaling pathways affecting chronic inflammation, including nuclear factor kappa beta (NF-κB) and cyclooxygenase-2 enzymes (COX-2). Curcumin has also shown antiviral and anti-inflammatory effects and to be helpful for both prevention and treatment of the new coronavirus. However, well-designed clinical trials are needed to demonstrate the potential efficacy of curcumin against SARS-CoV-2 infection and its ensuing complications. © The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022.

Hydroxychloroquine and COVID-19 - A narrative review.

COVID 19 infection is unarguably the worst pandemic of this century. Till date there is no promising drug and vaccine available to treat this deadly viral infection. In the early phase chloroquine phosphate and hydroxychloroquine sulphate have been used to fight this illness on the basis of handful observational and small randomized and small-randomized studies. The paucity of clinical evidences of an unequivocal beneficial effect of chloroquine and hydroxychloroquine on COVID-19 has resulted in the passionate use of the drug for moderate to severe cases only and stimulated the need for large clinical trials for this and other molecules. In this review, we describe in brief the mechanism of action, the clinical studies, factors for cardiac toxicity, guidelines and future directions for hydroxychloroquine use in management of COVID-19 infection.

SARS-CoV-2 infection and COVID19 vaccination across eight immune-mediated inflammatory disorders: A prospective, real-life Belgian cohort study - the BELCOMID study.

Background: The risks and impact of COVID19 disease and vaccination in patients with Immune Mediated Inflammatory Diseases (IMID) remain incompletely understood. IMID patients and particularly patients receiving immunosuppressive treatment were excluded from the original, registrational phase-3 COVID19 vaccination efficacy and safety trials. Real-world observational data can help to fill this gap in knowledge. The BELCOMID study aims to explore the interaction between IMIDs, immune-modulating treatment modalities and SARS-CoV-2 infection and vaccination in a real-life patient cohort. Methods: A multidisciplinary, prospective, observational cohort study was set up. Consecutive patients with IMIDs of the gut, joints and skin followed at two high-volume referral centers were invited. Both patients under conventional treatment or targeted immune modulating therapies were included. Patient data and serological samples were collected at 3 predefined periods (before COVID19 vaccination, before booster vaccination, after booster vaccination). Primary endpoints were positive PCR-test and SARS-CoV-2 serology reflecting previous SARS-CoV-2 infection or vaccination. Associations with IMID treatment modality and IMID disease activity were assessed. Results of the first two inclusion periods (before booster vaccination) are reported. Results: At the first inclusion period data was assessed of 2165 IMID-patients before COVID19 vaccination. At the second inclusion period, data of 2065 patients was collected of whom 1547 had received complete baseline COVID19 vaccination and 222 were partially vaccinated. SARS-CoV-2 infection rate remained low in both groups. No significant increase in IMID flare-up rate was noted in patients with prior SARS-CoV-2 infection. Multiple logistic regression analyses did not show a significant influence of IMID-treatment modality or IMID activity on SARS-CoV-2 infection risk (based on PCR positivity or N-serology). Patients treated with conventional immunomodulators, systemic steroids, and patients on advanced therapies such as biologics or small molecules, had reduced S-antibody seroconversion. S-antibody response was also lower in patients without prior SARS-CoV-2 infection and in active smokers. A subset of patients (4.1%) had no S- nor N-antibody seroconversion following complete baseline vaccination. Conclusion: The BELCOMID study results confirm the benign course of COVID19 infection and vaccination in a large real-life IMID-population. However, our results underscore the need for repeated vaccination and smoking cessation in patients with IMIDs treated with immune-modulating therapies or systemic steroids during the pandemic.

Infliximab as a potential treatment for COVID-19.

INTRODUCTION: As the third year of the SARS-CoV-2 pandemic approaches, COVID-19 continues to cause substantial morbidity and mortality due to waning vaccine efficacy and the emergence of new, highly contagious subvariants and better therapies are urgently needed. AREAS COVERED: Hospitalized patients who develop hypoxia due to SARS-CoV-2 infection are typically treated with an antiviral agent, remdesivir, as well as an immunomodulator, dexamethasone, but mortality rates for severe COVID-19 remain unacceptably high. Mounting evidence suggests a second immunomodulator added to the standard of care may benefit some hospitalized patients; however, the optimal treatment remains controversial. EXPERT OPINION: On 2 June 2022, the United States National Institutes of Health reported results from a large, randomized placebo-controlled clinical trial known as ACTIV-1. The study found a mortality benefit and substantially improved clinical status for adults hospitalized with COVID-19 who were treated with infliximab, a chimeric monoclonal antibody that binds to and inhibits TNF-α, and is widely used to treat a variety of autoimmune conditions, including rheumatoid arthritis, Crohn's disease, and ulcerative colitis. This manuscript reviews what is known about infliximab as an immunomodulator for patients with COVID-19 and explores how this agent may be used in the future to address the SARS-CoV-2 pandemic.

The Effects of Apium graveolens and Eucalyptus globulus in Decreasing Stress and Protecting Folliculogenesis Marker on Woman Reproductive Health during COVID-19 Pandemic

Stress during Coronavirus disease-2019 (COVID-19) pandemic affects the physiological and immunological response to women's reproductive health. Meanwhile, Apium graveolens and Eucalyptus globulus are immunomodulators related to women's reproductive health. This investigation had a goal to examine the effectiveness of A. graveolens and E. globulus towards the expression of Heat Shock Protein-70 (HSP70) as the primary biomarker of stress, Tumor Necrosis Factor-Alpha (TNF-alpha) as a pro-inflammatory protein, along with Luteinizing Hormone (LH) and Growth Differentiation Factor 9 (GDF-9) as folliculogenesis markers. An experimental randomized controlled trial was utilized by using a pre-test and post-test control group design. Sixty women, who had stress based on DASS-21 questionnaire, were divided into two groups in Nusukan Health Center, Indonesia. The intervention group was orally administered with 300 mg A. graveolens capsules and E. globulus essential oil for 14 days, while the control group was given a placebo. Blood samples and stress levels were then evaluated before and after the intervention. No significant difference was found in the stress levels of the control and treatment groups at the pre-test. Meanwhile, the intervention group had the decreased HSP70, TNF-alpha, and stress levels (p<0.001). In contrast, increased LH and GDF-9 levels were displayed in the intervention group compared to the control group (p<0.001). These findings revealed that A. graveolens supplementation and E. globulus essential oil have the ability to decrease stress and are able to protect folliculogenesis markers on women's reproductive health due to stressful conditions during pandemic COVID-19. Copyright © 2022 by Indonesian Journal of Pharmacy (IJP).

The antimicrobial and immunomodulatory effects of Ionophores for the treatment of human infection.

Ionophores are a diverse class of synthetic and naturally occurring ion transporter compounds which demonstrate both direct and in-direct antimicrobial properties against a broad panel of bacterial, fungal, viral and parasitic pathogens. In addition, ionophores can regulate the host-immune response during communicable and non-communicable disease states. Although the clinical use of ionophores such as Amphotericin B, Bedaquiline and Ivermectin highlight the utility of ionophores in modern medicine, for many other ionophore compounds issues surrounding toxicity, bioavailability or lack of in vivo efficacy studies have hindered clinical development. The antimicrobial and immunomodulating properties of a range of compounds with characteristics of ionophores remain largely unexplored. As such, ionophores remain a latent therapeutic avenue to address both the global burden of antimicrobial resistance, and the unmet clinical need for new antimicrobial therapies. This review will provide an overview of the broad-spectrum antimicrobial and immunomodulatory properties of ionophores, and their potential uses in clinical medicine for combatting infection.

The Effects of Apium graveolens and Eucalyptus globulus in Decreasing Stress and Protecting Folliculogenesis Marker on Woman Reproductive Health during COVID-19 Pandemic

Stress during COVID-19 pandemic affects the physiological and immunological response to women's reproductive health. Meanwhile, A. graveolens and Eucalyptus globulus are immunomodulators related to women's reproductive health. This investigation had a goal to examine the effectiveness of A. graveolens and E. globulus towards the expression of Heat Shock Protein-70 (HSP70) as the primary biomarker of stress, Tumor Necrosis Factor-Alpha (TNF-alpha) as a pro-inflammatory protein, along with Luteinizing Hormone (LH) and Growth Differentiation Factor 9 (GDF-9) as folliculogenesis markers. An experimental randomized controlled trial was utilized by using a pre-test and post-test control group design. Sixty women, who had stress based on DASS-21 questionnaire, were divided into two groups in Nusukan Health Center, Indonesia. The intervention group was orally administered with 300 mg A. graveolens capsules and E. globulus essential oil for 14 days, while the control group was given a placebo. Blood samples and stress levels were then evaluated before and after the intervention. No significant difference was found in the stress levels of the control and treatment groups at the pre-test. Meanwhile, the intervention group had the decreased HSP70, TNF-alpha, and stress levels (p < 0.001). In contrast, increased LH and GDF-9 levels were displayed in the intervention group compared to the control group (p < 0.001). These findings revealed that A. graveolens supplementation and E. globulus essential oil have the ability to decrease stress and are able to protect folliculogenesis markers on women's reproductive health due to stressful conditions during pandemic COVID-19.

Thiopurine therapy in inflammatory bowel disease in the pandemic era: Safe or unsafe?

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract. Crohn's disease (CD) and Ulcerative colitis (UC) are the two major types affecting millions across the globe. Various immunomodulatory drugs consisting of small molecules (thiopurines, methotrexate and tofacitinib) and biologics are used to treat IBD. Thiopurines (TP) are widely used in the treatment of IBD and it plays an important role both alone and in combination with anti-TNF agents as IBD maintenance therapy. Although the advent of biologics therapy has significantly advanced the management of IBD, TP remains the mainstay of treatment in resource-limited and low economic settings. However, the recently commenced pandemic has raised uncertainty over the safety of the use of immunosuppressant drugs such as TP among healthcare care providers and patients, as there is a scarcity of data on whether IBD patients are at higher risk of COVID-19 infection or more prone to its severe outcomes. AIM: This review aims to encapsulate evidence on the risk of COVID-19 infection and its severe prognosis in IBD patients on TP. Additionally, it also evaluates the role of TP in inhibiting the viral protease, a potential drug target, essential for the replication and pathogenesis of the virus. CONCLUSION: Emerging evidence suggests that TP therapy is safe during the current pandemic and does not carry an elevated risk when used as monotherapy or in combination with other IBD drugs. In-vitro studies demonstrate that TP is a potential therapeutic for present and future betacoronavirus pandemics.

Regular Exercise of Moderate Intensity and Lemon Peel Essential Oil as Immunomodulator during Covid-19

Regular exercise can increase the sensitivity of endogenous antioxidants so that it can increase the immune system against viral infections. Antioxidants like bioflavonoids, which are found in lemon peel essential oil, help shield the body from the damaging effects of free radicals and immunomodulators. The goal of this research was to find out whether or not frequent moderate -intensity exercise and the lemon peel essential oil can boost immunity during the Covid-19 Pandemic. The experimental animals were separated into two groups at random, with ten white rats in each group: group P1 consisted of rats that participated in swimming activities of moderate intensity for forty minutes;group P2 consisted of rats that participated in swimming activities of moderate intensity for forty minutes, but also received 0.05 milliliters of lemon peel essential oil every hour for the preceding hour before the rats participated in swimming activities. The average TAC level in the RDF group (pre-test 320.34 +/- 44.05 mu mol;post-test 353.01 +/- 70.22 mu mol) and average CRP level (pre-test 0.54 +/- 0.11 ng/ml;post-test 0.49 +/- 0.04 ng/ml). The average TAC level in the RE groups (pre-test 338.15 +/- 29.14 mu mol;post-test 356.48 +/- 44.34 mu mol) and average CRP level (pre-test 0.56 +/- 0.04 ng/ml;post-test 0.53 +/- 0.09 ng/ml). There were no significantly increased TAC (p>0.05) and decreased CRP (p>0.05) after the exercise test compared to before. There were no substantial differences between the two groups (p>0.05).

Isoprinosine along with Favipiravir or Oseltamivir in Patients with Moderate Covid-19 at RSD Dr. Soebandi Jember

Background: Isoprinosine is an immunomodulator that is now being used to treat Covid-19 patients. Objectives: To evaluate Isoprinosine with Favipiravir or Oseltamivir in moderate Covid-19. Methods: In a retrospective observational analysis, in-hospital moderate Covid-19 patients treated between June 2020 and June 2021 were included. Results: Inclusion criteria for 364 patients were met, with 135 receiving Favipiravir-Isoprinosine (Group 1) and 229 receiving Oseltamivir-Isoprinosine (Group 2). In group 1, the majority of patients (58.50%) were female (35.60%), had no comorbidities (71.60%), were discharged with a positive PCR (74.80%), did not require a breathing apparatus (99.26%), had leukocyte levels between 4,5-11,0 (82.22%), lymphocyte levels between 25-33 (34.07%), and were discharged with no ground-glass opacity (34.07%) (54.10%), LOS was 9-13 days (50.37%), while the mortality rate was 0.70%. In group 2, the majority of patients were male (54.10%), with the highest age range being 42-56 years (35.80%), without comorbidities (69.0%), discharged with a positive PCR (72.50 %), and without the need for a breathing apparatus (99.13%), with leukocyte levels ranging from 4.5 - 11.0 (81.22 %), with lymphocyte levels ranging from 25.0 - 33.0 (26.20 %), and were discharged with no ground-glass opacity (49.34 %), LOS was 9 - 13 days (34.06 %), and the mortality rate was 0.87%.Conclusion: In this trial, it was determined that combining isoprinosine with antivirals favipiravir or Oseltamivir could produce significant clinical improvement. [ FROM AUTHOR]

Parapoxvirus-based therapy eliminates SARS-CoV-2-loaded fine aerosol and blocks viral transmission in hamster models.

Currently, it is believed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an airborne virus, and virus-containing aerosol particles have been found concurrent with the onset of COVID-19, which may contribute to the noncontact transmission of SARS-CoV-2. Exploring agents to block SARS-CoV-2 transmission is of great importance to prevent the COVID-19 pandemic. In this study, we found that inactivated Parapoxvirus ovis (iORFV), a kind of immunomodulator, could compress the proportion of small particle aerosols exhaled by Syrian golden hamsters. Notably, the concentration of SARS-CoV-2 RNA-containing aerosol particles was significantly reduced by iORFV in the early stages after viral inoculation. Importantly, smaller aerosol particles (<4.7 µm) that carry infectious viruses were completely cleared by iORFV. Consistently, iORFV treatment completely blocked viral noncontact (aerosol) transmission. In summary, iORFV may become a repurposed agent for the prevention and control of COVID-19 by affecting viral aerosol exhalation and subsequent viral transmission.

COVID-19 prophylactic & management studies based on Electro-Homeopathy

Electro-Homeopathy (EH) is a herbal spagyric based safe & scientific medical system. The usual homeostasis balance between blood and lymph in human body is deviated during illness. In EH, disease is cured by restoring homeostasis balance, using minute amount of specially made spagyric complex remedies. Precise dose of complex set of remedies act on vitiated blood or lymph or both to establish a balanced condition. During this process, various variants of T and B lymphocytes get stimulated by absorbing living plant energy stored in EH remedies. Hence, the harmful invaders are identified and destroyed by lymphocytes (WBC) on and around the diseased organ. Total excretory system simultaneously gets stimulated by EH remedy enabling to drive out quickly the toxic cluster of dead harmful invaders and the infected cells. This process results a complete cure. The EH remedy neither kill any virus directly nor allow virus to reside inside the body for lengthy time. The set of remedy is chosen, such that it does not allow Corona virus to cause harm, even at the cell and tissue level of respiratory, gastro intestinal and other related systems. Suitable dose of medicine applied beforehand, acts as the prophylactic remedy and prescribed medicines applied to Covid patient cures them successfully. A study using EH remedies on 2384 Covid and non Covid mixed population, was carried out during March, 2020 to July, 2021. A prolong consistent result proves that the EH remedy is irrespective of virus strains. The treatment summary has been presented here. © 2022, National Institute of Science Communication and Policy Research. All rights reserved.

Nanocarriers for effective delivery: modulation of innate immunity for the management of infections and the associated complications.

Innate immunity is the first line of defense against invading pathogens. Innate immune cells can recognize invading pathogens through recognizing pathogen-associated molecular patterns (PAMPs) via pattern recognition receptors (PRRs). The recognition of PAMPs by PRRs triggers immune defense mechanisms and the secretion of pro-inflammatory cytokines such as TNF-α, IL-1ß, and IL-6. However, sustained and overwhelming activation of immune system may disrupt immune homeostasis and contribute to inflammatory disorders. Immunomodulators targeting PRRs may be beneficial to treat infectious diseases and their associated complications. However, therapeutic performances of immunomodulators can be negatively affected by (1) high immune-mediated toxicity, (2) poor solubility and (3) bioactivity loss after long circulation. Recently, nanocarriers have emerged as a very promising tool to overcome these obstacles owning to their unique properties such as sustained circulation, desired bio-distribution, and preferred pharmacokinetic and pharmacodynamic profiles. In this review, we aim to provide an up-to-date overview on the strategies and applications of nanocarrier-assisted innate immune modulation for the management of infections and their associated complications. We first summarize examples of important innate immune modulators. The types of nanomaterials available for drug delivery, as well as their applications for the delivery of immunomodulatory drugs and vaccine adjuvants are also discussed.

Combination therapy with remdesivir and immunomodulators improves respiratory status in COVID-19: A retrospective study.

Immunomodulators (tocilizumab/baricitinib) improve outcomes of coronavirus disease 2019 (COVID-19) patients, but the synergistic effect of remdesivir is unknown. The effect of combination therapy with remdesivir, immunomodulators, and standard treatment in COVID-19 patients was investigated. This retrospective, single-center study included COVID-19 patients who were treated with tocilizumab or baricitinib. The severity of respiratory status in the two groups on Days 14 and 28 and the duration to respiratory recovery in both groups were compared, and the effect of remdesivir use on respiratory status was examined in a multivariate analysis. Ninety-eight patients received tocilizumab or baricitinib; among them, 72 used remdesivir (remdesivir group) and 26 did not (control group). The remdesivir group achieved faster respiratory recovery than the control group (median 11 vs. 21 days, p = 0.033), faster weaning from supplemental oxygen (hazard ratio [HR]: 2.54, 95% confidence interval [CI]: 1.14-5.66, p = 0.021). Age, body mass index, diabetes mellitus, and time from onset to oxygen administration were independent prognostic factors. The remdesivir group achieved better severity level at Days 14 and 28 (p = 0.033 and 0.003, respectively) and greater improvement from baseline severity (p = 0.047 and 0.018, respectively). Remdesivir combination therapy did not prolong survival (HR: 0.31, 95% CI: 0.04-2.16, p = 0.23). Among severely ill COVID-19 patients who received immunomodulator, remdesivir contributed to a shorter respiratory recovery time and better respiratory status at Days 14 and 28. Concomitant remdesivir with immunomodulators and standard treatment may provide additional benefit in improving respiratory status of COVID-19 patients.