Non-steroidal anti-inflammatory drugs amid COVID-19 pandemic: An ally or an enemy?

As the current global pandemic of the novel coronavirus diseases 2019 (COVID-19) continues to rage, the scientific and medical worlds are working to establish an effective therapy against the illness. Recently questions regarding non-steroidal anti-inflammatory drugs (NSAIDs) as a potential therapeutic option for COVID-19 have surfaced. While some studies hint towards the possible benefit of NSAIDs against SARS-CoV-2 infection, the current body of evidence also sheds light on the potential risk of using NSAIDs in COVID-19 patients. Thus, the available literature does not provide conclusive evidence for or against the use of NSAIDs for treating COVID-19 patients. Given the limited data available, we suggest cautionary approaches for the public to avoid possible harm until further evidence emerges. NSAIDs should not be used as the first-line agents for COVID-19 unlessunder medical supervision. Moreover, patients with chronic inflammatory conditions should continue the NSAIDs as per their regular prescriptions.

Molecular docking and dynamics simulation of main protease of SARS-CoV-2 with naproxen derivative

Naproxen is a well-known anti-inflammatory drug that is frequently used to relieve inflammation, stiffness, and swelling. Naproxen has previously demonstrated antiviral activity, particularly against the influenza-A virus. There have been previous studies regarding naproxen effect on SARS-CoV-2 infection. Therefore, it is of interest to document the molecular docking and dynamics simulation data of main protease of SARS-CoV-2 with naproxen derivative for further consideration.

Anti-Inflammatory Therapy of Infections

Anti-inflammatory treatment of infections is challenging due to the heterogeneity of etiologic agents and complex immune interactions. Nevertheless, anti-inflammatory medications are commonly used in infections to reduce unpleasant symptoms and to modify host response. They may play a fundamental role in managing infection with over-inflammation by decreasing inflammatory organ damage, e.g., COVID-19. However, by its inherent inhibition of immune functions, they might also contribute to the development of serious bacterial infections. Moreover, reducing a patient's symptoms and signs may provide a false sense of security and delay diagnosing threatening infections. © 2022 Elsevier Inc. All rights reserved.

Glucocorticoid therapy in respiratory illness: bench to bedside.

Each year, hundreds of millions of individuals are affected by respiratory disease leading to approximately 4 million deaths. Most respiratory pathologies involve substantially dysregulated immune processes that either fail to resolve the underlying process or actively exacerbate the disease. Therefore, clinicians have long considered immune-modulating corticosteroids (CSs), particularly glucocorticoids (GCs), as a critical tool for management of a wide spectrum of respiratory conditions. However, the complex interplay between effectiveness, risks and side effects can lead to different results, depending on the disease in consideration. In this comprehensive review, we present a summary of the bench and the bedside evidence regarding GC treatment in a spectrum of respiratory illnesses. We first describe here the experimental evidence of GC effects in the distal airways and/or parenchyma, both in vitro and in disease-specific animal studies, then we evaluate the recent clinical evidence regarding GC treatment in over 20 respiratory pathologies. Overall, CS remain a critical tool in the management of respiratory illness, but their benefits are dependent on the underlying pathology and should be weighed against patient-specific risks.

A comprehensive nutritional support perspective in patients with COVID-19: a review

Purpose>Coronavirus disease-2019 (COVID-19) is becoming a crucial health problem worldwide. Continued and high-speed mutations of this virus result in the appearance of new manifestations, making the control of this disease difficult. It has been shown that well-nourished patients have strong immune systems who mostly have short-term hospitalization compared to others. The purpose of this study is to review the major nutrients involved in the immune system reinforcement and to explain nutritional aspects during the recovery of COVID-19.Design/methodology/approach>In this review paper, the mechanistic role of nutrients in boosting the immune system and the nutritional aspects during the recovery of COVID-19 patients were discussed. Papers indexed in scientific databases were searched using antioxidants, COVID-19, inflammation, immune system, macronutrient, micronutrient and probiotic as keywords from 2000 to 2022.Findings>Because of the adverse effects of drugs like thrombosis, pulmonary embolism and hypercholesterolemia, a balanced diet with enough concentrations of energy and macronutrients could increase the patient's durability. The inflammatory cytokines in a vicious cycle delay patients' rehabilitation. The main mechanistic roles of micronutrients are attributed to the downregulation of virus replication and are involved in energy homeostasis. Dysbiosis is defined as another disturbance among COVID-19 patients, and supplementation with beneficial strains of probiotics helps to exert anti-inflammatory effects in this regard. Being on a well-planned diet with anti-inflammatory properties could reverse cytokine storms as the major feature of COVID-19. Future studies are needed to determine the safe and effective dose of dietary factors to control the COVID-19 patients.Originality/value>Being on a well-planned diet with anti-inflammatory properties could reverse cytokine storms as the major feature of COVID-19. Future studies are needed to determine the safe and effective dose of dietary factors to control the COVID-19 patients.

An overview on the treatments and prevention against COVID-19.

BACKGROUND: The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to plague the world. While COVID-19 is asymptomatic in most individuals, it can cause symptoms like pneumonia, ARDS (acute respiratory distress syndrome), and death in others. Although humans are currently being vaccinated with several COVID-19 candidate vaccines in many countries, however, the world still is relying on hygiene measures, social distancing, and approved drugs. RESULT: There are many potential therapeutic agents to pharmacologically fight COVID-19: antiviral molecules, recombinant soluble angiotensin-converting enzyme 2 (ACE2), monoclonal antibodies, vaccines, corticosteroids, interferon therapies, and herbal agents. By an understanding of the SARS-CoV-2 structure and its infection mechanisms, several vaccine candidates are under development and some are currently in various phases of clinical trials. CONCLUSION: This review describes potential therapeutic agents, including antiviral agents, biologic agents, anti-inflammatory agents, and herbal agents in the treatment of COVID-19 patients. In addition to reviewing the vaccine candidates that entered phases 4, 3, and 2/3 clinical trials, this review also discusses the various platforms that are used to develop the vaccine COVID-19.

Impact of meloxicam on respiratory virus titers and health outcomes when administered concurrently with a modified live respiratory vaccine in abruptly weaned beef steers

Abruptly weaned crossbred steer calves (N = 271) were used in a randomized, blinded 2-arm clinical trial to assess the impact of a long-acting non-steroidal anti-inflammatory drug on bovine herpesvirus type 1, bovine respiratory syncytial virus, parainfluenza virus type 3, and coronavirus titers and health outcomes when administered concurrently with a modified live respiratory vaccine upon arrival at a feedlot. Treatment groups included a control (saline, n = 135) and an experimental group (injectable meloxicam, n = 136). Viral antibody titers and body weight were measured on arrival, day 7, and day 21, along with a final weight on day 45. Body weight and antibody titers for all viruses increased over time (P < 0.001), however, there were no differences by treatment group or a significant group × time interaction when evaluated using repeated measures analysis of variance. Interestingly, the use of meloxicam was associated with increased treatment risk (P < 0.05). In conclusion, the administration of meloxicam may adversely affect health, however, a decreased vaccine response is likely not a contributing factor.

Structural characterization and anti-inflammatory activity of fucoidan isolated from Ecklonia maxima stipe

Enzyme-assisted hydrolysis is frequendy used as a cost-effective and efficient method to obtain functional ingredients from bioresources. This study involved die enzyme-assisted hydrolyzation and purification of fucoidan from Ecklonia maxima stipe and die investigation of its anti-inflammatory activity in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Fucoidans of Viscozyme-assisted hydrolysate from E. maxima (EMSFs) harvested in Jeju, Korea. Structural and chemical characterizations were performed using fourier transform infrared spectroscopy, scanning electron microscope, and monosaccharide analysis. Among fucoidans, EMSF6 was rich in fucose and sulfate and had a similar structural character to commercial fucoidan. EMSF6 showed a strong inhibitory effect on nitric oxide generation in LPS-induced RAW 264.7 cells and significantly decreased die production of LPS-induced pro-inflammatory cytokines, including interleukin-6, interleukin-1 p, and tumor necrosis factor a. The anti-inflammatory potential of EMSF6 was mediated through the down-regulation of inducible nitric oxide synthase and cyclooxygenase-2 expression. Thus, fucoidans from&temppound;. maxima stipe are promising candidates for functional food products.

Cross-Reactivity between Pfizer/BioNTech and Johnsson Vaccines: A Case Report: An International Journal of Medical Toxicology and Drug Experience

Introduction: Polyethylene glycol (PEG) is one of the ingredients in the Pfizer/BioNTech COVID 19 vaccine (mRNA vaccine) and has been known to cause hypersensitivity [1-3]. Polysorbate is an ingredient in the Johnson vaccine (adenovirus vaccine) which may crossreact with PEG. Objective: We report a case of cross-reactivity between Pfizer/ BioNTech and Johnsson vaccines. Methods: This observation was notified in the pharmacovigilance center of Sfax, Tunisia (faculty of medicine of Sfax). The study of drug imputability was carried out according to the WHO method. Results: We report the case of a 32-year-old Tunisian woman with a history of atopy and intolerance to non-steroidal anti-inflammatory drugs (NSAIDs) but no history of SARS-CoV-2 infection. On August 15, 2021 (at 08:30), she developed sweating, vomiting and dizziness immediately after receiving the initial dose of Johnson COVID-19 vaccine. Her blood pressure became lower (less than 90/60 mmHg). She had to stay at the vaccination centre for one hour, and the clinical signs improved spontaneously after one hour. In the evening of the same day, the patient presented a febrile maculopapular eruption in the abdomen, trunk, and face. The rash resolved spontaneously over a week. The patient was referred to the pharma-covigilance center of Sfax (Tunisia). The messenger RNA vaccine was advocated for the second vaccine. On December 2021, she was received the second dose of the Pfizer/BioNTech COVID 19 vaccine (mRNA vaccine). Six hours later, she experienced a pruritic maculopapular rash on the abdomen, trunk, neck, and face. These clinical signs improved spontaneously after two days. the diagnosis of cross-allergy between these two vaccines was retained for this patient Conclusion: To our knowledge, this is the first cross-allergy between mRNA and adenovirus COVID-19 vaccines notified in Tunisian population. Healthcare professionals should be aware that hypersen-sitivity can occur with COVID-19 vaccines containing macrogols/ PEGs and those containing polysorbates. Its recognition may be challenging and often require skin testing. Per CDC guidance, con-sultation with an allergist-pharmacologist should be considered to help determine if the patient can safely receive vaccination [4].

NSAIDs in COVID-19, friend or foe?

At the beginning of COVID-19 pandemic the use of NSAIDS was avoided. This was because the previous studies suggesting that NSAIDs may be linked to an increased risk of lower respiratory tract infection consequences. Later on studies involved the patients who used NSAIDs for some chronic conditions and showed no additional harm among these patients. Then many studied assessed the benefit of using NSAIDs in COVID-19 patients for management of pain and fever and showed no additional risk among these patients. [ FROM AUTHOR] Copyright of Anaesthesia, Pain & Intensive Care is the property of Department of Anaesthesia, Pain & Intensive Care and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

[Current and future therapeutic options for COVID-19]

The anti-inflammatory agents dexamethasone (corticosteroid), and tocilizumab and sarilumab (IL6-inhibitors) are effective in the treatment of late COVID-19. Other anti-inflammatory agents, like anakinra (IL1-inhibitor), baricitinib and tofacitinib (JAK-inhibitors) and lenzilumab (GM-CSF-inhibitor) have also shown positive results in late COVID-19. For the treatment of early COVID-19, the inhalation corticosteroid budesonide is regarded as an off-label treatment option. Virus-inhibitors, like remdesivir, molnupiravir and nirmatrelvir/ritonavir decrease the risk of hospitalization and the development of severe COVID-19 by patients with early symptoms. Monoclonal antibodies have shown limited or no efficacy against the omicron-variant of SARS-CoV-2. Fluvoxamine, l-arginine, AT-527 and ensovibep are considered as potential promising new therapies for the treatment of early COVID-19.

ROLE OF NELUMBO NUCIFERA (LOTUS) STEM AS IMMUNITY BOOSTER AND ANTI-INFLAMMATORY FOOD

In China and India, Nelumbo nucífera, a perennial aquatic plant, has been used as a medicinal herb. The various sections of plants, such as leaves, seeds, flowers and rhizomes, have been reported to have beneficial effects in the treatment of pharyngopathy, pectoralgia, spermatorrhoea, leucoderma, smallpox, dysentery, cough, haematemesis, epistaxis, haemoptysis, haematuria, metrorrhagia, hyperlipidaemia, fever, cholera, hepatopathy and hyperdipsia in the traditional medicine system. Different pharmacological activities such as anti-ischaemic activity, antioxidant activity, hepatoprotective activity, anti-inflammatory activity, anti-fertility activity, antiarrhythmic activity, anti-fibrosis activity, antiviral activity, anti-proliferative activity, anti-diarrhoeal activity, psychopharmacological activity, antipyretic activity, immune-modulatory activity, hypoglycaemic activity, aldose reductase inhibitory activity, antibacterial, aphrodisiac activity, anti-platelet activity, cardiovascular activity, anti-obesity activity, lipolytic activity, hypo-cholesterolaemic activity, hepato-protective activity, anticancer activitydiuretic activity, antioxidant activity have been clinically evaluated for N.nucifera. Different pharmacological activities such as anti-ischaemic activity, antioxidant activity, hepato-protective activity, anti-inflammatory activity, anti-fertility activity, anti-arrhythmic activity, antifibrosis activity, antiviral activity, anti-proliferative activity, anti-diarrhoeal activity, psychopharmacological activity, diuretic activity, antioxidant activity have been clinically evaluated for N.nucifera. A wide number of phytoprinciples from the plant have been isolated. The present review seeks to consolidate the traditional, ethno-botanical, phytochemical and pharmacological data available on N.nucifera stem and to explore its role as an immunity booster and anti-inflammatory food.

Prophylactic Anticoagulant Treatment Might Have an Anti-inflammatory Effect and Reduce Mortality Rates in Hospitalized COVID-19 Patients?

Objectives: COVID-19 associated coagulopathy and prophylactic anticoagulant therapy (PAT) are ongoing topics globally. Using PAT for anti-inflammatory effect may prevent thromboembolic events (TEEs). The objective of this study was to determine the anti-inflammatory effects of PAT in hospitalized COVID-19 patients. Methods: We conducted a retrospective observational study in a tertiary pandemic hospital. Patients were divided into two categories according to their PAT therapy status (PAT (+) and PAT (-)) and into three categories according to clinical features (mild: group 1; moderate: group: 2; and severe: group 3). We then evaluated laboratory parameters and clinical courses. Results: We included 662 hospitalized COVID-19 patients in this study. Enoxaparin sodium was given to all patients as PAT therapy. TEE was developed in five patients in the PAT (+) group. Pulmonary embolism developed in 3/5 patients and deep venous thrombosis in 2/5 patients. Disseminated intravascular coagulation (DIC) was detected in 54 patients in group 3. No statistically significant difference was found in 28-day mortality, development of DIC rates, intubation rates, and TEEs. Conclusions: The use of PAT in critically ill patients was not effective in reducing C-reactive protein, which is one of the biomarkers of inflammation.

COVID-19 Outcomes in Patients Who Started GLP1-RAs during Hospitalization

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been hypothesized to exert beneficial effects on COVID-19 outcomes due to their anti-inflammatory properties. In our COVID-19 ward, patients admitted for severe interstitial bilateral pneumonia due to SARS-COV2 infection and having type 2 diabetes (T2D) or in-hospital hyperglycemia (IHH) were treated with GLP-1 RAs in addition to standard therapy according to usual care. Aim of the present study was to evaluate if GLP-1 RAs therapy was related with outcomes. A retrospective analysis was performed to assess if the GLP1-RAs were associated with a lower risk of a composite outcome (death or admission to intensive care unit) . During the COVID-19 pandemics, 135 patients were admitted (61.5% men, age 66.3±13.7 years, 49.6% with T2D and 50.4% with IHH) , of whom 23.1% initiated GLP1-RA during the hospitalization (39.1% of patients with T2D and 7.6% of patients with IHH) . Almost all patients were treated with once-weekly subcutaneous semaglutide, while dulaglutide was administered in 2 cases. Overall, 26.3% of patients not treated vs. 7.1% of patients treated with GLP1-RAs reached the composite outcome (p=0.03) . At multivariate analysis adjusted for age, gender, T2D, history of cardio/cerebrovascular disease, hypertension, pulmonary disease, and dementia, the use of GLP-1 RAs was associated with a reduced risk of composite outcome of 80% (OR 0.20;95% confidence intervals 0.04-0.95) . Dementia resulted the only other independent correlate of the outcome. These preliminary results suggest that the addition of GLP1-RAs to standard care during hospitalization for SARS-CoV2 infection could play a role in improving clinical outcomes in patients with COVID-19 and T2D or IHH: at the best of our knowledge this is the first study showing such an effect when GLP1-RAs were started during hospitalization.

Key Considerations for Phase 2 or 3 Clinical Study Design of Anti-Inflammatory Agent for COVID-19 Treatment.

Purpose: Current understanding of COVID-19 disease progression suggests a major role for the "cytokine storm" as an important contributor to COVID-19 mortality. To prevent an exaggerated immune response and improve COVID-19 patient endpoints, anti-inflammatory therapeutics have been proposed as clinically useful in severe patients with COVID-19. The purpose of this study was to propose a clinical trial design for the development of anti-inflammatory agents for the treatment of COVID-19, taking into account the physiological and immunological process of COVID-19 and the treatment mechanism of anti-inflammatory agents. Methods: We reviewed and analyzed the guidelines for the development of COVID-19 treatments and the treatment of COVID-19 by regulatory agencies and previously conducted clinical trials on anti-inflammatory drugs for COVID-19. Finally, after discussing with an advisory group, a synopsis was presented for an example protocol for a COVID-19 anti-inflammatory agent phase 2 or 3 study that considers the drug mechanism and the disease progression of COVID-19. Results: A randomized, placebo-controlled, double-blind parallel-group design was suggested as a phase 2 or 3 trial design for developing an anti-inflammatory agent as a COVID-19 treatment. A key item of the example protocol specific to anti-inflammatory agents was the inclusion and exclusion criteria, taking into account the immunosuppressive effects of the drug, clinical time course of COVID-19 disease, and treatment guidelines for COVID-19. Time to recovery is the primary endpoint associated with clinical efficacy and is generally well accepted by many experts. Conclusion: Through this suggested phase 2 or 3 study design of an anti-inflammatory drug for COVID-19, we provide a basis for a study design that can be utilized in clinical development by pharmaceutical companies which are developing a potential anti-inflammatory agent for COVID-19.