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.

Effects of Non-steroidal Anti-inflammatory Drugs (NSAIDs) and Gastroprotective NSAIDs on the Gastrointestinal Tract: A Narrative Review.

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used for their anti-inflammatory, antipyretic, and analgesic properties. However, their use is often associated with gastrointestinal tract (GIT) side effects due to the inhibition of both cyclooxygenase (COX)-1 and COX-2 enzymes, leading to a decrease in gastroprotective prostaglandins (PG). To minimize these adverse effects, various approaches have been explored, including selective COX-2 inhibitors, NO-NSAIDs (nitric oxide-releasing NSAIDs), and dual COX/LOX (lipoxygenase) NSAIDs. However, the effects of these gastroprotective NSAIDs on the GIT and their efficacy remains uncertain. This review aims to provide an overview of the current understanding of the effects of traditional NSAIDs and gastroprotective NSAIDs on GIT. We discuss the underlying mechanisms of GIT damage caused by NSAIDs, including mucosal injury, ulceration, and bleeding, and the potential of gastroprotective NSAIDs to mitigate these effects. We also summarize recent studies on the efficacy and safety of various gastroprotective NSAIDs and highlight the limitations and challenges of these approaches. The review concludes with recommendations for future research in this field.

Ibuprofen in the Management of Viral Infections: The Lesson of COVID-19 for Its Use in a Clinical Setting.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for the management of fever, pain, and inflammation. However, they have always been considered to have a double-faced role, according to their capacity to manage inflammation but also their possible reduction of immune system response and diagnosis delay. This last point could favor a dramatic increase of viral infection diffusion, possibly leading to a more severe outcome. The advent of severe acute respiratory syndrome coronavirus 2 excluded the use of NSAIDs, particularly ibuprofen, and then indicated this drug as the better NSAID to manage infected outpatients and prevent complications. Several authors described the role of NSAIDs and ibuprofen in preventing cytokine storm and modulating the immune system. However, the development of both adverse drug reactions (i.e., gastrointestinal, renal, hepatic, and cardiovascular) and drug interaction recalled the necessity of prescribing the better NSAID for each patient. In this narrative review, we describe the role of NSAIDs, particularly of ibuprofen, in the management of viral symptoms, suggesting that the NSAID may be chosen considering the characteristics of the patient, the comorbidity, and the polytherapy.

Patterns of Self-medication During the COVID-19 Pandemic in a Colombian population.

Introduction: Self-medication is considered one of the most relevant problems for public health, since it is described as the voluntary use of drugs by the patient. Since the beginning of the health crisis caused by the COVID-19 pandemic, it has been evident that this practice has increased considerably, especially in the adult population. Objective(s): To evaluate the different patterns that influence self-medication during the COVID-19 pandemic. Method(s): A survey was conducted among the population of two vicinities of Bogota and the statistical program SPSS was used for data analysis to identify the main practices that increase the risks derived from self-medication, the most used drugs and their adverse effects. Socioeconomic factors related to self-medication were evaluated. A comparative study was carried out to observe their behavior before and during the pandemic. Additionally, the influence of the people who are part of the family and social environment on self-medication was evaluated. Result(s): The total number of surveys carried out was 301. The average age was 44.18 years. It was found that before the pandemic there was a higher frequency of self-medication of analgesics (49.1 %) and anti-influenza drugs (19.5 %), and during the pandemic it was of non-steroidal anti-inflammatory drugs (4.43 %), home remedies (6.69 %) and antibiotics (30.38 %). In addition, it was found that those who had the greatest influence on self-medication were family members (23.9 %), friends or acquaintances (17.3 %) and the pharmaceutical chemist (5.0 %). Conclusion(s): It is evident that during the COVID-19 pandemic self-medication is higher than in the pre-pandemic era, increasing the risk of adverse events and compromised patient safety.Copyright © 2023, Editorial Ciencias Medicas. All rights reserved.

Modulation of the immune response to SARS-CoV-2 vaccination by NSAIDs.

Evidence is scarce to guide the use of nonsteroidal anti-inflammatory drugs (NSAIDs) to mitigate SARS-CoV-2 vaccine related adverse effects, given the possibility of blunting the desired immune response. In this pilot study, we deeply phenotyped a small number of volunteers who did or did not take NSAIDs concomitant with SARS-CoV-2 immunizations to seek initial information on the immune response. A SARS-CoV-2 vaccine specific RBD-IgG antibody response and efficacy in the evoked neutralization titers were evident irrespective of concomitant NSAID consumption. Given the sample size, only a large and consistent signal of immunomodulation would have been detectable, and this was not apparent. However, the information gathered may inform the design of a definitive clinical trial. Here, we report a series of divergent omics signals that invite additional hypotheses testing. Significance Statement A SARS-CoV-2 vaccine specific immune response was evident irrespective of concomitant NSAID consumption in a clinical pilot study of small sample size.

Use of First-Line Oral Analgesics during and after COVID-19: Results from a Survey on a Sample of Italian 696 COVID-19 Survivors with Post-Acute Symptoms.

Background-Analgesics could be used to manage painful symptoms during and after COVID-19. Materials and methods-Persistence of painful symptoms was assessed during and after COVID-19 in a sample of patients admitted to a post-acute COVID-19 outpatient service in Rome, Italy. Data on type and frequency of use of first-line analgesics were collected. Pain severity was evaluated with a numeric rating scale (NRS) from 0 to 10. Results-Mean age of 696 participants was 57.1 ± 20.3 years and 61.7% were women. During COVID-19, the most prevalent symptoms were fever, fatigue, arthralgia, myalgia and headache. Acetaminophen was used by 40% of the sample. Only 6.7% needed to continue analgesic therapy after COVID-19. Frequent causes of analgesics consumption were persistent arthralgia and myalgia. The most common analgesics used amongst those who continued taking analgesics in the post-acute phase of COVID-19 were the following: acetaminophen (31%), ibuprofen (31%) and other non-steroidal anti-inflammatory drug (NSAID) (29.5%); in older subjects the most common analgesic used was acetaminophen (54%). Most of the subjects in this group said there was an improvement in pain perception after taking analgesic therapy (84%). Conclusions-Use of analgesics in the post-acute COVID-19 is common in subjects with persistent arthralgia and myalgia, and common analgesics were acetaminophen and ibuprofen. Further research on the safety and efficacy of those medications in COVID-19 is warranted.

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 associated with increased risk of complications of lower respiratory tract infections. 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.Copyright © 2023 Faculty of Anaesthesia, Pain and Intensive Care, AFMS. All rights reserved.

Heterotopic ossification post COVID-19: Report of two cases.

Heterotopic ossification is often associated with trauma and surgery, and infrequently reported with immobilization due to critical illness. We present 2 patients who developed heterotopic ossification following severe COVID-19 infection. Both patients were middle-aged females who were hospitalized for one month or greater due to COVID-19 requiring mechanical ventilation. Both developed shoulder pain and/or stiffness a few months after discharge, with imaging studies clearly illustrating development of heterotopic ossification around the shoulders. The etiology is unclear, with immobilization and hypoxia being the primary considerations. Physical examination and radiography are essential to diagnosis. Awareness of this complication and early diagnosis may help minimize functional impairment.

Serious Clinical Outcomes of COVID-19 Related to Acetaminophen or NSAIDs from a Nationwide Population-Based Cohort Study.

Acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) have been widely prescribed to infected patients; however, the safety of them has not been investigated in patients with serious acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our objective was to evaluate the association between the previous use of acetaminophen or NSAIDs and the clinical outcomes of SARS-CoV-2 infection. A nationwide population-based cohort study was conducted using the Korean Health Insurance Review and Assessment Database through propensity score matching (PSM). A total of 25,739 patients aged 20 years and older who tested for SARS-CoV-2 were included from 1 January 2015 to 15 May 2020. The primary endpoint was a positive result for a SARS-CoV-2 test, and the secondary endpoint was serious clinical outcomes of SARS-CoV-2 infection, such as conventional oxygen therapy, admission to the intensive care unit, need for invasive ventilation care, or death. Of 1058 patients, after propensity score matching, 176 acetaminophen users and 162 NSAIDs users were diagnosed with coronavirus disease 2019. After PSM, 162 paired data sets were generated, and the clinical outcomes of the acetaminophen group were not significantly different from those of the NSAIDs group. This suggests that acetaminophen and NSAIDs can be used safely to control symptoms in patients suspected of having SARS-CoV-2.

Renal arcuate vein thrombosis-induced acute kidney injury: a rare multiple-Hit-mediated disease.

Background: Renal arcuate vein thrombosis (RAVT) is a rare and recently recognized cause of acute kidney injury (AKI) in young adults. However, the precise incidence and underlying pathophysiologic mechanisms leading to AKI in these patients remain elusive. Methods: This study included all patients who underwent a kidney biopsy over a 40-month period sent to the pathology department of Necker-Enfants Malades Hospital, with evidence of RAVT. We performed coagulation tests, genetic testing for thrombophilia, complete urine toxicologic screening and kidney metagenomic sequencing to identify an underlying cause of thrombosis. Results: We report five pediatric cases of RAVT discovered on kidney biopsy performed in the setting of unexplained AKI. Investigations did not reveal an underlying cause of thrombosis but only a significant nonsteroidal anti-inflammatory drugs (NSAIDs) use was reported in 4/5 patients, supporting a potential link between NSAIDs use and RAVT. By performing metagenomic sequencing on kidney biopsy samples, we detected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in the kidney of one patient. These results suggest that systemic SARS-CoV-2 infection may also be a key contributing factor of renal thrombosis, particularly by inducing potential endothelial disruption. Conclusions: In conclusion, RAVT-induced AKI appears to be a multiple hit-mediated disease in which NSAIDs consumption and viral infection such as SARS-CoV-2 may be crucial contributing factors. These findings may have significant public health implications given the prevalence of NSAIDs use in the general population. Increased awareness and additional study of future cases may lead to a better understanding of this rare cause of AKI in children and young adults.

Is Primary Bone Marrow Edema of the Knee Associated with Thyroid Disorders? A Retrospective Clinical Study.

Primary bone marrow edema (BME) of the knee is still an elusive condition. This retrospective study was undertaken to gain insight into its characteristic features. The records of 48 patients with primary BME of the knee diagnosed by magnetic resonance imaging were reviewed. Demographic data, medical history, current medications, pain type, smoking and drinking habits, allergies, occupation, sports practiced, environmental factors, and life events predating symptom onset were examined. Data analysis demonstrated that 56.3% of patients had experienced a stressful event before BME pain onset and that 50% suffered from thyroid disorders. Standard conservative treatment resulted in pain resolution irrespective of the use of anti-inflammatories. However, most patients reported new persistent symptoms: dysesthesia/hypoesthesia on palpation in the skin area overlying the previous edema and a reduced ipsilateral patellar reflex. To our knowledge, this is the first study characterizing a substantial cohort of patients with BME. We found that middle-aged, sedentary, and slightly overweight women smokers are the typical patients with primary BME of the knee. The appearance and persistence of cutaneous dysesthesia/hypoesthesia at the site of the earlier lesion and ipsilateral patellar hyporeflexia implicate an autonomous nervous system dysfunction in BME pathogenesis and warrant further investigation.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and nucleotide analog GS-441524 conjugates with potent in vivo efficacy against coronaviruses.

Coronaviruses (CoVs) infect a broad range of hosts, including humans and various animals, with a tendency to cross the species barrier, causing severe harm to human society and fostering the need for effective anti-coronaviral drugs. GS-441524 is a broad-spectrum antiviral nucleoside with potent anti-CoVs activities. However, its application is limited by poor oral bioavailability. Herein, we designed and synthesized several conjugates via covalently binding NSAIDs to 5'-OH of GS-441524 through ester bonds. The ibuprofen conjugate, ATV041, exhibited potent in vitro anti-coronaviral efficacy against four zoonotic coronaviruses in the alpha- and beta-genera. Oral-dosed ATV041 resulted in favorable bioavailability and rapid tissue distribution of GS-441524 and ibuprofen. In MHV-A59 infected mice, ATV041 dose-dependently decreased viral RNA replication and significantly reduced the proinflammatory cytokines in the liver and the lung at 3 dpi. As a result, the MHV-A59-induced lung and liver inflammatory injury was significantly alleviated. Taken together, this work provides a novel drug conjugate strategy to improve oral PK and offers a potent anti-coronaviral lead compound for further studies.

Post obturation analgesia in patients recently vaccinated against Covid-19, after Root canal treatment: A short observational study

Aim: The aim of this study was to evaluate the need for analgesia in patients undergoing single-visit root canal treatment, within 2 days after COVID-19 immunisation. Method(s): Two days after receiving the COVID-19 vaccination, 50 patients undergoing Single visit root canal treatments for acute pulpits in molar teeth were divided into two groups of 25 each (Group M for males and Group F for females). Each patient was given a prescription for 650 mg of acetaminophen (Dolo 650 mg) tablets to be taken eight hours a day, with instructions to use the same only if needed for pain. They were instructed to keep a record of the number of tablets consumed as per record sheet 1, and if the pain did not subside then a stronger analgesic, Ketorolac DT 10 mg twice a day, had to be taken and recorded. Result(s): In Group M, the mean number of analgesic tablets required was 0.44+/-0.64 and in Group F, the mean number of analgesic tablets required was 0.80+/-1.09. Although the mean analgesic requirement was higher in females as compared to males, the difference of 0.80+/-1.09 between the two groups was not significant statistically (0.360). Conclusion(s): Within the limitations of this study, it is concluded that acetaminophen is effective in relieving post-obturation pain after a single-visit RCT in patients recently vaccinated against the CoVid-19. Copyright © 2022 Ubiquity Press. All rights reserved.

Efficacy and safety profile of corticosteroids and non-steroidal anti-inflammatory drugs in COVID-19 management: A narrative review.

Due to the fact that coronavirus disease 2019 (COVID-19) is still prevalent, and current reports show that some parts of the world have seen increase in incidence, it is relevant that health professionals and scientists know about recent or novel trends, especially drug treatments. Additionally, the safety profiles of these drug treatments need to be documented and shared with the public. Some studies have demonstrated the clinical benefits of non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids in COVID-19 treatment. On the contrary, others have also reported that NSAIDs and corticosteroids may worsen symptoms associated with COVID-19. While some researchers have suggested that corticosteroids may be helpful if used in the early stages of COVID-19, there are still some conflicting findings regarding the use of corticosteroids in certain viral infections. Our review suggests that methylprednisolone, dexamethasone, and ibuprofen have therapeutic potential in reducing mortality due to COVID-19 among hospitalized patients. This review also highlights the fact that the use of NSAIDs is not associated with adverse outcomes of COVID-19. In reality, evidence suggests that NSAIDs do not increase the risk of COVID-19 infections. Also, the literature reviewed suggests that corticosteroid treatment in COVID-19 was linked with a decrease in all-cause mortality and disease progression, without increase in adverse events when compared to no corticosteroid treatment.

Strategies Tackling Viral Replication and Inflammatory Pathways as Early Pharmacological Treatment for SARS-CoV-2 Infection: Any Potential Role for Ketoprofen Lysine Salt?

COVID-19 is an infective disease resulting in widespread respiratory and non-respiratory symptoms prompted by SARS-CoV-2 infection. Interaction between SARS-CoV-2 and host cell receptors prompts activation of pro-inflammatory pathways which are involved in epithelial and endothelial damage mechanisms even after viral clearance. Since inflammation has been recognized as a critical step in COVID-19, anti-inflammatory therapies, including both steroids and non-steroids as well as cytokine inhibitors, have been proposed. Early treatment of COVID-19 has the potential to affect the clinical course of the disease regardless of underlying comorbid conditions. Non-steroidal anti-inflammatory drugs (NSAIDs), which are widely used for symptomatic relief of upper airway infections, became the mainstay of early phase treatment of COVID-19. In this review, we discuss the current evidence for using NSAIDs in early phases of SARS-CoV-2 infection with focus on ketoprofen lysine salt based on its pharmacodynamic and pharmacokinetic features.

Renal Papillary Necrosis Associated with Multiple Risk Factors: A Case Report

Introduction: Renal papillary necrosis (RPN) is a multifactorial complication that occurs under the following conditions: Pyelonephritis, obstruction of the urogenital tract, non-steroidal anti-inflammatory drugs (NSAIDs) abuse, diabetes mellitus (DM2), and coronavirus disease 2019 (COVID-19). The present report presented a case of right ureteral obstruction due to RPN. Case Presentation: The patient was a 68-year-old woman referred to the hospital due to flank pain, fever, vomiting/nausea, frequency, and nocturia. She also had a history of DM2, hypertension, dialysis, COVID-19, and the use of NSAIDs and antihypertensive. The results of computed tomography (CT) scan suspected a clot, bladder fungus or RPN, and COVID-19. After performing the ultra-sound, mild hydroureteronephrosis and two echogenic foci were seen in the right kidney, suggesting a possible RPN. The patient was transferred to the urology service. After cystoscopy and urethroscopy, a severe stenosis was seen in the distal right ureter. As soon as inserting double J, lots of pus came out. The definitive diagnosis was RPN, ureteral obstruction, and pyelonephritis. Conclusion(s): It is important to pay enough attention to the disorders related to the urinary system, especially in the elderly with a history of NSAIDs abuse, DM2, hypertension, COVID-19, and renal diseases. Additionally, the underlying diseases, blood glucose, infection, dehydration, and use of NSAIDs must be well-controlled to protect nephro-ureteral structures. Copyright © 2022, Author(s).

Drugs for COVID-19: An Update.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was the seventh known human coronavirus, and it was identified in Wuhan, Hubei province, China, in 2020. It caused the highly contagious disease called coronavirus disease 2019 (COVID-19), declared a global pandemic by the World Health Organization (WHO) on 11 March 2020. A great number of studies in the search of new therapies and vaccines have been carried out in these three long years, producing a series of successes; however, the need for more effective vaccines, therapies and other solutions is still being pursued. This review represents a tracking shot of the current pharmacological therapies used for the treatment of COVID-19.

Management of Subacute Thyroiditis - A Systematic Review of Current Treatment Protocols.

Purpose: This systematic review endeavors to find an effective treatment protocol for subacute thyroiditis (SAT) to minimize side effects, recurrence and long-term hypothyroidism. Materials and Methods: We analyzed available original studies on treatment protocols for SAT. A thorough literature search was performed on the following online databases PubMed, Cochrane library nd Google Scholar using appropriate keywords for choosing relevant articles. Two reviewers assessed the methodological quality of selected articles independently using a critical appraisal instrument. The results were analyzed and synthesized qualitatively using the level of evidence method. Results: The literature search retrieved a total of 460 publications after abstract screening; out of which 36 articles met the inclusion criteria. After full text screening, 23 articles were further excluded as they were focusing on aspects of SAT other than management, the remaining 15 articles were investigated for both reliability and validity. Thirteen studies provided low-quality evidence, and two randomized control trials (RCT) provided a high quality of evidence. Steroid therapy was found to be the most effective for moderate to severe SAT and provided relief from acute symptoms but was found to not be a risk factor for recurrence. Low initial doses of steroid (15 mg) were preferred over high initial dosage (30-40 mg). Furthermore, a look into the mode of steroid delivery (RCT) revealed that intrathyroidal steroid therapy can potentially become a safer and faster mode of therapy. The duration of tapering was found to be of significance as a short tapering period was linked with greater recurrence rates. Conclusion: Low initial doses of steroid along with an extended tapering period may help lower recurrence rates; also, intrathyroidal steroid injections are potentially a better alternative to oral prednisone (PSN) with regard to safety and speed of action. However, the evidence is of moderate quality and further investigation is required.