The pandemic of COVID-19 has ignited a global race to locate effective therapies with drug repositioning emerging as a leading strategy due to its cost-effectiveness and established safety profiles. Remdesivir, Favipiravir, Hydroxychloroquine, and Chloroquine have been the focus of rigorous clinical trials to determine their therapeutic potential against SARS-CoV-2. This article delves into the innovative synthetic strategies behind these drugs, providing a blueprint for researchers navigating the complex landscape of antiviral development. Beyond synthesis, we explore the fascinating mechanisms of action: hydroxychloroquine and chloroquine elevate lysosomal pH to impede autophagy and viral replication; favipiravir, a nucleoside analogue, induces lethal mutagenesis or RNA chain termination and remdesivir disrupts viral RNA synthesis through delayed chain termination. By merging synthetic methodologies with mechanistic insights, this article offers a comprehensive resource aimed at accelerating the development of potent COVID-19 therapies and underscores the crucial part that chemistry in addressing global health emergencies. It also underscores the vital function of chemistry in addressing global health emergencies and highlights how innovative drug design and repurposing can provide rapid responses to emerging infectious diseases. This fusion of chemistry and virology not only advances our understanding of drug action but also paves the way for the discovery of new therapeutic agents crucial in future pandemics.

The toxicity of hydroxychloroquine (HCQ) can impact the function of vital organs, leading to ocular and cardiovascular damage. This study aims to evaluate the toxicity of HCQ through electrocorticographic evaluation and blood biochemical parameters in Wistar rats. The animals received a dose of HCQ of 350 mg/kg via gavage every 12 hours for periods of 24, 48, 72 and 96 hours, with each group consisting of n = 9. After treatment, the animals underwent surgery to implant electrodes in the motor cortex region and subsequently underwent bipolar electrocorticography. The electrodes for acquiring electrocardiographic recordings were fixed in the D II position and blood samples were analyzed for liver and kidney function. The results demonstrated that high doses of HCQ altered electrocorticographic features, decreased cardiac activity throughout treatment, and significantly elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. However, assessment of renal function, as indicated by serum creatinine levels, revealed no significant changes. These results suggest that exposure to high doses of HCQ in rats may disrupt the structures and functions of vital organs.

Alzheimer's disease (AD), the most prevalent form of dementia, remains enigmatic in its origins despite the widely accepted "amyloid hypothesis," which implicates amyloid-beta peptide aggregates in its pathogenesis and progression. Despite advancements in technology and healthcare, the incidence of AD continues to rise. The traditional drug development process remains time-consuming, often taking years to bring an AD treatment to market. Drug repurposing has emerged as a promising strategy for developing cost-effective and efficient therapeutic options by identifying new uses for existing approved drugs, thus accelerating drug development.

This study aimed to examine two key drug repurposing methodologies in general diseases and specifically in AD, which are artificial intelligent (AI) approach and molecular docking approach. In addition, the hybrid approach that integrates AI with molecular docking techniques will be explored too.

This study systematically compiled a comprehensive collection of relevant academic articles, scientific papers, and research studies which were published up until November 2024 (as of the writing of this review paper). The final selection of papers was filtered to include studies related to Alzheimer's disease and general diseases, and then categorized into three groups: AI articles, molecular docking articles, and hybrid articles.

As a result, 331 papers were identified that employed AI for drug repurposing in general diseases, and 58 papers focused specifically in AD. For molecular docking in drug repurposing, 588 papers addressed general diseases, while 46 papers were dedicated to AD. The hybrid approach combining AI and molecular docking in drug repurposing has 52 papers for general diseases and 9 for AD. A comparative review was done across the methods, results, strengths, and limitations in those studies. Challenges of drug repurposing in AD are explored and future prospects are proposed.

Drug repurposing emerges as a compelling and effective strategy within AD research. Both AI and molecular docking methods exhibit significant potential in this domain. AI algorithms yield more precise predictions, thus facilitating the exploration of new therapeutic avenues for existing drugs. Similarly, molecular docking techniques revolutionize drug-target interaction modelling, employing refined algorithms to screen extensive drug databases against specific target proteins. This review offers valuable insights for guiding the utilization of AI, molecular docking, or their hybrid in AD drug repurposing endeavors. The hope is to speed up the timeline of drug discovery which could improve the therapeutic approach to AD.

Hydroxychloroquine (HCQ) is an antimalarial drug that has historically been used to treat and prevent malaria. However, its mechanism of action has not yet been fully elucidated. HCQ affects various cellular and molecular pathways through different mechanisms. HCQ has also been shown to be a disease‑improving agent for the treatment of rheumatic diseases, including systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis and primary Sjögren's syndrome. Although generally considered safe, adverse reactions have been reported with the use of HCQ and clinicians should carefully monitor patients with rheumatism when prescribing these drugs. The purpose of the present review is to strengthen the clinical use of HCQ for autoimmune diseases while highlighting the adverse effects that may occur during treatment.

Since SARS-CoV-2 has caused unprecedented changes in the epidemiology of other infectious diseases, investigations on coinfection between SARS-CoV-2 and one of the famous vector-borne diseases, malaria, are crucial for disease control, especially in malaria-endemic areas. The clinical profiles, possible mechanisms for interactions, and representative control measures of COVID-19 and malaria coinfections have recently garnered public attention. The overlap in epidemiology, infection incubation, and clinical symptoms between COVID-19 and malaria coinfections has been thoroughly discussed to provide a detailed diagnostic procedure for coinfections, thereby guiding appropriate clinical interventions. Immunological and genetic evidence has shown that previous malaria exposure may protect the body from the poor prognosis of COVID-19. ACE2 downregulation and TLR-induced pathways play a role in this protective effect, as do CD8 + and CD4 + T-cell activation and coinhibitory receptor upregulation, which help maintain a balance of immune reactions. Finally, multiple control measures for coinfections were discussed, and malaria control efforts were enriched in the context of COVID-19. These efforts included (1) developing vaccinations; (2) evaluating the efficacy of anti-malarial drugs in the SARS-CoV-2 treatment; (3) exploring recent advances in natural products that are potentially useful for coinfection treatment; (4) researching and implementing bioinsecticides for malaria control, such as gene-driven mosquitoes, fungi, and bacterial symbionts; and (5) improving national electronic disease surveillance platforms in malaria-endemic regions. At last, the above findings summarized valuable lessons about malaria and COVID-19 control and expedite further investigations on coinfections with complex clinical presentations.

The swift transmission rate and unfavorable prognosis associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have prompted the pursuit of more effective therapeutic interventions. Azithromycin (AZM) has garnered significant attention for its distinctive pharmacological mechanisms in the treatment of SARS-CoV-2. This study aims to elucidate the biological rationale for employing AZM in patients with chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) who are infected with SARS-CoV-2. Genetic data about COVID-19, COPD, and IPF were independently obtained from the GeneCards database. And 40 drug targets about AZM were retrieved from the STITCH database. The analysis revealed that 311 DEGs were common among COPD, IPF, and COVID-19, and we further found eight genes that interacted with AZM targets. We conducted an analysis of hub genes and their corresponding signaling pathways in these patient cohorts. Additionally, we explored the inhibitory effects of AZM on these hub genes. AZM demonstrated a significant inhibitory effect on eight key genes, except for AR and IL-17 A. These findings suggest that AZM may serve as a promising therapeutic agent for patients with COPD and IPF and SARS-CoV-2 infection.

The rapid spread and mutation of SARS-CoV-2, the virus responsible for COVID-19, has set the foundation for extensive research into next-generation therapeutic strategies. A critical component of SARS-CoV-2 is the trimeric Spike (S) glycoprotein, which facilitates viral entry into host cells by interacting with the receptor-binding domain (RBD). To inhibit and block viral entry, we designed and developed molecularly imprinted synthetic nanogel antibodies (MIP-SNAs) that cap the Spike S1 RBD. This aims to provide a versatile, biosecure, and effective therapeutic tool for the prevention and treatment of SARS-CoV-2 infection. Herein, we employed reverse miniemulsion polymerization to synthesize MIP-SNAs using poly(ethylene glycol) diacrylate (PEGDA), a nontoxic, nonimmunogenic and FDA-approved polymer, able to interact noncovalently with the functional groups of template Spike S1 RBD. In addition, the formulation of MIP-SNAs was based on a preliminary investigation of protein conformation by circular dichroism. Characterization of the SNAs was conducted using several techniques to investigate the chemical structure, thermal stability, size, and morphology. Under optimal conditions, the MIP-SNAs exhibited high specificity, with rebinding capacities up to 6-fold higher compared to the control nonimprinted synthetic nanogel antibodies. MIP-SNAs also demonstrated notable selectivity toward the SARS-CoV-2 Spike S1 RBD protein compared to the structural resembling Spike proteins of Bat-CoV, while cytocompatibility assays confirmed the biocompatible character of the SNAs. Given the excellent features of the recently developed MIP-SNAs, we are one step closer to finding efficient but also patient-friendly prevention and treatment solutions for SARS-CoV-2 infection. Beyond immediate applications, this technology offers the potential for broader diagnostic and therapeutic uses against related viral pathogens.

Medicinal plants, mushrooms, and endophytes offer a rich source of secondary metabolites (SMs), including flavonoids, alkaloids, tannins, and terpenoids, with proven antiviral properties against SARS-CoV-2. Plant-associated microorganisms that colonize in living tissues of different parts of a plant possess the ability to produce SMs of immense therapeutic value and this biological interaction between plants and microbes can be exploited to develop antiviral drugs against SARS-CoV-2. The unprecedented lethality of the SARS-CoV-2 virus during the recent global pandemic has prompted extensive research into new treatment options and preventive strategies for COVID-19. Phytochemicals, particularly those derived from medicinal plants, microbes, and mushrooms, show promising results in combating the virus when combined with synthetic components. These natural compounds include terpenes, phenolics, flavonoids, and alkaloids that possess antiviral properties. Medicinal plants and their endophytic microbes, and mushrooms, offer a rich source of secondary metabolites (SMs) with potential antiviral effects against SARS-CoV-2. Given the urgency of addressing the swift spread of the new coronavirus strain, exploring and understanding these SMs could lead to the development of innovative and potent antiviral drugs. This review provides a comprehensive overview of plant-, microbial- and mushroom-derived SMs, their classification, and their applications in treating diseases caused by the coronavirus family, offering insights into the potential future production of natural medicines.

Targeting the specific RNA conformations that are crucial for SARS-CoV-2 replication is a viable antiviral approach. The SARS-CoV-2 genome contains GG repeats capable of forming unstable two-tetrad G-quadruplex (GQ) structures, which exist as a mix of conformations, including hairpin (Hp), intra-, and intermolecular GQs. RGQ-1, originating from the nucleocapsid gene's ORF, adopts a dynamic equilibrium of conformations, including intramolecular hairpin and G-quadruplex (Hp-GQ) structures, as confirmed by CD analysis. In this study, tetraphenylethene (TPE) derivatives were developed to target the Hp-GQ conformational equilibrium of RGQ-1. EMSA, fluorescence spectroscopy, and ITC assays confirmed that two TPE derivatives, TPE-MePy and TPE-Allyl Py, bind to RGQ-1. CD thermal melting experiments indicate that RGQ-1 is stabilized by 8.56 and 12.54 °C in the presence of TPE-MePy and TPE-Allyl Py, respectively. Additionally, luciferase assays demonstrated that TPE derivatives suppressed luciferase activity by 2.2-fold and 3.6-fold, respectively, shifting the HpGQ equilibrium toward the GQ conformation, as suggested by CD spectroscopy. Treatment of SARS-CoV-2-infected A549 cells with TPE derivatives reduced the levels of viral RNA, spikes, and nucleocapsid proteins. To explore their antiviral mechanism, preinfection and postinfection treatments were tested, revealing that the TPE derivatives specifically suppressed the postentry stages of viral replication without affecting viral entry. These findings highlight the therapeutic potential of TPE derivatives in inhibiting key gene expressions critical for SARS-CoV-2 replication.

Antiviral therapeutics have made a critical contribution in mitigating the symptoms and clinical outcomes of the coronavirus disease of 2019 (COVID-19), in which a single-stranded RNA viral pathogen, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causes multi-organ injuries. Several antivirals were widely prescribed to treat COVID-19, either through the emergency use authorization (EUA) by the governmental regulatory agencies (i.e., remdesivir, paxlovid, molnupiravir, and the SARS-CoV-2-targeted monoclonal antibodies - tixagevimab and cilgavimab), as well as the repurposed use of the existing antiviral or antimalarial drugs (e.g., hydroxychloroquine, chloroquine, and ivermectin). Despite their efficacy in ameliorating COVID-19 symptoms, some adverse side-effects of the antivirals were also reported during the COVID-19 pandemic. Our current review has aimed to gather and extrapolate the recently published information concerning cardiovascular adverse effects caused by each of the antivirals. We also provide further discussion on the potential cellular mechanisms underlying the cardiovascular adverse effects of the selected antiviral drugs, which should be carefully considered when evaluating risk factors in managing patients with COVID-19 or similar infectious diseases. It is foreseeable that future antiviral drug development assisted with the newest artificial intelligence platform may improve the accuracy to predict the structures of biomolecules of antivirals and therefore to mitigate their associated cardiovascular adversities.

Hydroxychloroquine and Chloroquine (CQ) and Hydroxychloroquine (HCQ) are antimalarial drugs with well-known anti-inflammatory and antiviral effects used to treat various diseases, with few side effects. After COVID-19 emergence, numerous researches from around the world have examined the potential of using CQ or HCQ as potential treatment of COVID-19. However, conflicting outcomes have been found in COVID-19 clinical trials after treatment with CQ or HCQ. This study aims to evaluate research on CQ and HCQ for COVID-19 treatment and prophylaxis control using bibliometric methods.

We analyzed bibliometric data on HCQ and COVID-19 (HCQ-C19) quantitatively and semantically (2020-2023) using the Scopus database VOSviewer, Bibliometrix, and MS Excel.

Analyses of 7471 original and conference articles revealed that the total number of publications has continually increased. The country producing the most articles in this field was the United States, followed by Italy, India, and Spain. The top-productive authors on HCQ-C19 are Mussini, C., and Raoult, D. (Italy) with 23 and 21 articles, respectively. The top-impactful organization is IHU Méditerranée Infection, France. A Bibliometrix's network analysis based on the co-occurrence of keywords revealed the following themes HCQ-C19, including "clinical research/practice," "COVID-19," "thrombosis," "HCQ," "epidemiology," and "infectious disease."

In conclusion, the analysis reveals a growing interest in HCQ-C19 research. Prominent contributions come from the United States, Italy, India, and Spain. Key themes include clinical research/practice, COVID-19, thrombosis, HCQ, epidemiology, and infectious disease. Future recommendations include conducting well-designed clinical trials and fostering collaborative interdisciplinary efforts.

In the initial stage of the COVID-19 pandemic, high case fatality was noted. The case fatality during this was associated with the cytokine storm (CS) or cytokine storm syndrome (CSS). Sometimes, virus infections are due to the excessive secretion of pro-inflammatory cytokines, leading to cytokine storms, which might be directed to ARDS, multi-organ failure, and death. However, it was noted that several miRNAs are involved in regulating cytokines during SARS-CoV-2 and other viruses such as IFNs, ILs, GM-CSF, TNF, etc. The article spotlighted several miRNAs involved in regulating cytokines associated with the cytokine storm caused by SARS-CoV-2 and other viruses (influenza virus, MERS-CoV, SARS-CoV, dengue virus). Targeting those miRNAs might help in the discovery of novel therapeutics, considering CS or CSS associated with different virus infections.

Antibiotic resistance (AMR) has reached critical levels globally, especially in developing economies like Kazakhstan, largely due to improper antibiotic use. The aim of this study was to examine seven years of azithromycin sales data in Kazakhstan to uncover consumption patterns during the COVID-19 pandemic and develop effective strategies to combat AMR. This study analyzes two data sets: one from a comprehensive review of documents regulating azithromycin use in Kazakhstan. The second data set consists of a pharmaco-epidemiological analysis of azithromycin consumption from procurement data provided by Vi-ORTIS. Azithromycin consumption (ATC group J01FA10) from 2017 to 2023 was measured in DDD/1000 inhabitants/day (DID) using the ATC/DDD methodology. Azithromycin is extensively used in adult and pediatric care in Kazakhstan. Its consumption, measured in DDD per 1,000 inhabitants, surged in 2020 with the COVID-19 outbreak. The steady annual increase in "Watch" antibiotics, including azithromycin, should alarm Kazakhstan's healthcare system. This trend highlights the need for stronger stewardship programs, targeted interventions, and comprehensive monitoring to prevent antibiotic overuse and misuse. Addressing this is crucial to maintaining antibiotic effectiveness and safeguarding public health.

Leading up to the 2020 U.S. presidential elections, the scientific consensus on hydroxychloroquine's ineffectiveness in treating COVID-19 was dismissed by Executive branch scientists, who promoted it as both a therapeutic solution and a political tool. This article examines how experimental pharmaceuticals were rationalized even before the pandemic declaration, aligning with medical advocacy groups linked to Donald Trump, who criticized the crisis management capacity of existing health institutions. Framing the emergency as requiring extraordinary measures, White House researchers advocated for executive unilateralism and eventually sought to securitize public health by replacing key health authorities with operational medicine specialists. The most controversial case involved an attempt of planned pharmaceutical intervention aimed at saving lives and restoring public confidence in the administration's pandemic response before the 2020 election. The article draws on confidential documents released by the 2022 House Select Subcommittee on the Coronavirus Crisis.

Azithromycin (AM) is one of the prescribed drugs in pandemic medication treatment which has paid great attention. We developed in this study a simply modified carbon paste electrode (CPE) to detect AM using poly-threonine (PT). PT or similar polymers are used as carriers to enhance the delivery and effectiveness of AM. The work was characterised via Cyclic Voltammetry (CV), electrochemical impedance spectroscopy (EIS) and scanning electron microscopy (SEM). We take into consideration the effects of pH, scan rate, accumulation time, interference, and calibration curve.A very sensitive response to the oxidation of 1.0 mM from AM in phosphate buffer solution (PBS) over a pH range of 5.0 to 10.0 was observed using the developed poly-threonine carbon paste electrode (PTCPE). The impact of different AM concentrations was investigated resulting in a detection limit of 0.32 µM and a quantification limit of 1.07 µM at PBS (pH 7.4). Finally, the recently used electrode realized acceptable sensitivity and consistency for AM detection in pharmaceutical drugs.

Malaria continues to be the primary cause of mortality worldwide, and timely recognition and prompt intervention are crucial in mitigating adverse consequences. This review article aims to examine the effectiveness and structural characteristics of quinoline-based compounds as antimalarial agents. It specifically focuses on their therapeutic effects as well as potential prospects for exploring structure-activity relationship (SAR). In addition, this study aims to identify lead compounds that can efficiently battle multidrug-resistant forms of Plasmodium falciparum and Plasmodium vivax.

A comprehensive review was conducted to evaluate the effectiveness of quinoline-based antimalarial medications in eradicating P. falciparum and P. vivax. The mechanism of action and SAR of these compounds were analyzed.

Quinoline-based antimalarials demonstrated significant effectiveness in eliminating P. falciparum parasites, particularly in regions severely impacted by malaria, including Africa and Asia. These compounds were found to exhibit tolerance and immune-modulating properties, indicating their potential for more widespread utilization. The investigation identified various new quinoline compounds with improved antimalarial activity, including metal-chloroquine complexes, diaminealkyne chloroquines, and cinnamoylated chloroquine hybrids. This study explored different mechanisms by which these compounds interact with parasites, including their ability to accumulate in the parasite's acidic food vacuoles and disrupt heme detoxification. The derivatives demonstrated strong efficacy against chloroquine-resistant strains and yielded positive results.

Quinoline-based compounds represent a promising avenue for combating malaria due to their demonstrated efficacy against P. falciparum and P. vivax parasites. Further research on their mechanisms of action and SAR could lead to the development of more effective antimalarial medications.

Health and disease are intricately intertwined and often determined by the delicate balance of biological processes. Cytokines, a family of small signalling molecules, are pivotal in maintaining this balance, ensuring the body's immune system functions optimally. In a healthy condition, cytokines act as potent mediators of immune responses. They orchestrate the activities of immune cells, coordinating their proliferation, differentiation, and migration. This intricate role of cytokine signalling enables the body to effectively combat infections, repair damaged tissues, and regulate inflammation. However, the delicate equilibrium of cytokine production is susceptible to disruption. Excessive or abnormal cytokine levels can lead to a cascade of pathological conditions, including autoimmune diseases, chronic inflammation, infections, allergies, and even cancer. Interestingly, from the bunch of cytokines, few cytokines play an essential role in maintaining the balance between normal physiological status and diseases. In this review, we have appraised key cytokines' potential role and feedback loops in augmenting the imbalances in the body's biological functions, presenting a critical link between inflammation and disease pathology. Moreover, we have also highlighted the significance of cytokines and their molecular interplay, particularly in the recent viral pandemic COVID-19 disease. Hence, understandings regarding the interplay between viral infection and cytokine responses are essential and fascinating for developing effective therapeutic strategies.

At the end of 2019, the world witnessed the beginning of the COVID-19 pandemic. As an aggressive viral infection, the entire world remained attentive to new discoveries about the SARS-CoV-2 virus and its effects in the human body. The search for new antivirals capable of preventing and/or controlling the infection became one of the main goals of research during this time. New biocompounds from marine sources, especially microalgae and cyanobacteria, with pharmacological benefits, such as anticoagulant, anti-inflammatory and antiviral attracted particular interest. Polysaccharides (PS) and extracellular polymeric substances (EPS), especially those containing sulfated groups in their structure, have potential antiviral activity against several types of viruses including HIV-1, herpes simplex virus type 1, and SARS-CoV-2. We review the main characteristics of PS and EPS with antiviral activity, the mechanisms of action, and the different extraction methodologies from microalgae and cyanobacteria biomass.

Antibiotics are indispensable in modern healthcare, playing a critical role in mitigating bacterial infections. Azithromycin is used to fight upper respiratory tract infections, however has potential toxic effects that remain inadequately understood. In our present study, azithromycin exposure to Caenorhabditis elegans led to significant physiological and behavioral change, with pronounced effects observed at the studied concentration. The study employs an N2 wild-type strain to examine key physiological and behavioral parameters within the worm. C.elegans were exposed to two concentrations of azithromycin (0.0038 and 0.00038 mg/ml) from the embryonic stage to the L4 stage for 48 hours. The study assessed key endpoints including body length, thrashing behavior, brood size, embryonic viability, lipid accumulation via Nile red staining, pharyngeal pumping rate, and response to 1-Nonanol (which assesses neurotransmitter function). Results showed that at 0.0038 mg/ml, azithromycin significantly reduced body length, increased progeny production, altered lipid deposition, delayed response to 1-Nonanol, and decreased feeding rates. Even at the lowest concentration (0.00038 mg/ml), changes in body length and lipid accumulation were observed. These findings suggest that the toxicity of azithromycin in C.elegans is dose-dependent and varies with exposure duration and developmental stage. Further research is needed to elucidate the molecular mechanisms underlying these toxic effects, particularly at environmentally relevant concentrations of azithromycin.

COVID-19 pandemic has turned our world upside down by meddling with our normal lives. While there is no definitive drug against SARS-CoV-2, antiviral drugs that are already in the market, are being repurposed against it, could now complete long-term as well as all age-specific investigations, and they are successful in saving millions of lives. Nevertheless, side-effects are emergingly seen in the patients undergoing treatment, and ineffectiveness is increasingly found due to the emerging notorious variants of the virus. Many of them are also facing serious co-infections including black fungus, Zika, and H1N1 virus to name a few.

Therefore, this review highlights both drug resistance, their side-effects, and the significance for proper and long-term clinical trials of all age groups including children.

We have explored and proposed the mechanisms of drug resistance that may arise due to the misuse or overuse of drugs based on available experimental reports.

The review provides solutions to the aforesaid issues of drug-resistance and side-effects by providing combination therapies, ancillary treatments, and other preventive strategies that can be useful in preventing drawbacks thereby curbing COVID-19 or similar future infections to maintain our normal lives.

COVID-19 and its long-term effects, if any, can be eradicated with strategic and mindful use of related therapeutics in a controlled manner.

Social media has become a vital tool for health care providers to quickly share information. However, its lack of content curation and expertise poses risks of misinformation and premature dissemination of unvalidated data, potentially leading to widespread harmful effects due to the rapid and large-scale spread of incorrect information.

We aim to determine whether social media had an undue association with the prescribing behavior of hydroxychloroquine, using the COVID-19 pandemic as the setting.

In this retrospective study, we gathered the use of hydroxychloroquine in 48 hospitals in the United States between January and December 2020. Social media data from X/Twitter was collected using Brandwatch, a commercial aggregator with access to X/Twitter's data, and focused on mentions of "hydroxychloroquine" and "Plaquenil." Tweets were categorized by sentiment (positive, negative, or neutral) using Brandwatch's sentiment analysis tool, with results classified by date. Hydroxychloroquine prescription data from the National COVID Cohort Collaborative for 2020 was used. Granger causality and linear regression models were used to examine relationships between X/Twitter mentions and prescription trends, using optimum time lags determined via vector auto-regression.

A total of 581,748 patients with confirmed COVID-19 were identified. The median daily number of positive COVID-19 cases was 1318.5 (IQR 1005.75-1940.3). Before the first confirmed COVID-19 case, hydroxychloroquine was prescribed at a median rate of 559 (IQR 339.25-728.25) new prescriptions per day. A day-of-the-week effect was noted in both prescriptions and case counts. During the pandemic in 2020, hydroxychloroquine prescriptions increased significantly, with a median of 685.5 (IQR 459.75-897.25) per day, representing a 22.6% rise from baseline. The peak occurred on April 2, 2020, with 3411 prescriptions, a 397.6% increase. Hydroxychloroquine mentions on X/Twitter peaked at 254,770 per day on April 5, 2020, compared to a baseline of 9124 mentions per day before January 21, 2020. During this study's period, 3,823,595 total tweets were recorded, with 10.09% (n=386,115) positive, 37.87% (n=1,448,030) negative, and 52.03% (n=1,989,450) neutral sentiments. A 1-day lag was identified as the optimal time for causal association between tweets and hydroxychloroquine prescriptions. Univariate analysis showed significant associations across all sentiment types, with the largest impact from positive tweets. Multivariate analysis revealed only neutral and negative tweets significantly affected next-day prescription rates.

During the first year of the COVID-19 pandemic, there was a significant association between X/Twitter mentions and the number of prescriptions of hydroxychloroquine. This study showed that X/Twitter has an association with the prescribing behavior of hydroxychloroquine. Clinicians need to be vigilant about their potential unconscious exposure to social media as a source of medical knowledge, and health systems and organizations need to be more diligent in identifying expertise, source, and quality of evidence when shared on social media platforms.

Secondary pneumonia has a significant clinical impact on critically ill patients with COVID-19.

Considering potential geographic variations, this study explores the clinical implications of secondary pneumonia within East Asian populations.

This multicenter, retrospective cohort study enrolled critical COVID-19 patients requiring intensive care units (ICUs) admission in Taiwan from December 31, 2020, to June 1, 2022.

Among the 187 critical COVID-19 patients, 80 (42.8%) developed secondary pneumonia. The primary causative pathogens were gram-negative bacilli (GNB) (76.8%). Gram-positive cocci and fungi were mainly observed during the initial two weeks of ICU stay. Notably, the incidence of pulmonary aspergillosis was 9.2% during the first week of ICU stay and all Staphylococcus aureus were susceptible to methicillin. Multi-drug resistant organisms (MDROs) were responsible for 28.3% of the cases, exhibiting significantly longer ICU stays compared to the non-MDRO group (median, 27 vs. 14 days, P < 0.001). In the multivariate analysis, Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores were associated with a significantly increased risk of secondary pneumonia. In-hospital mortality was significantly higher in patients with secondary pneumonia than in those without (37.7% vs. 16.7%, P = 0.02) and survival analysis demonstrated gram-negative bacilli-related secondary pneumonia contributed to a worse prognosis.

Secondary pneumonia in critical COVID-19 patients significantly raised in-hospital mortality and extended hospital and ICU stays. Moreover, the presence of GNB notably predicted an unfavorable prognosis.

The most destructive period the world has experienced seems to be behind us. Not a single nation was spared by this disease, and many continue to struggle today. Even after recovering from COVID, patient may continue to experience some post-COVID effects, such as heart irregularities or a decline in lung vitality. In the past three years (2019-2022), the world has witnessed the power of a small entity, a single peculiar virus. Science initially appeared to be helpless in this regard, but due to the emergence of disease, pharmaceutics (the development of anti-covid drugs), immunology (the rapid antigen test), microbiology (the isolation of viruses from infected people), biotechnology (the development of recombinant vaccines), biochemistry (the blood profile, the D-dimer test), and biochemistry (blood profile, D-dimer test), biophysics (PCR, RT-PCR, CT Scan, MRI) had worked together to fight the disease. The results of these efforts are the development of new diagnostic techniques, possible treatment and finally the availability of vaccines against COVID-19. However, it is not proven that the treatment through the traditional medical system is directly active on SARS-CoV-2 but is instead indirectly acting on SARS-CoV-2 effects by improving symptoms derived from the viral disease. In India, the traditional system of medicine and tradition knowledge together worked in the pandemic and proved effective strategies in prevention and treatment of SARS-CoV-2. The use of effective masks, PPE kits, plasma therapy, yoga, lockdowns and social seclusion, use of modern antiviral drugs, monoclonal antibodies, herbal remedies, homoeopathy, hygienic practice, as well as the willpower of people, are all contributing to the fight against COVID. Which methods or practices will be effective against COVID nobody is aware since medical professionals who wear PPE kits do not live longer, and some people in India who remained unprotected and roamed freely were not susceptible to infection. The focus of this review is on the mode of transmission, diagnosis, preventive measures, vaccines currently under development, modern medicine developed against SARS-CoV-2, ayurvedic medicine used during pandemic, homoeopathic medicine used during pandemic, and specific yoga poses that can be used to lessen COVID-related symptoms.

Early in the course of the SARS-CoV-2 pandemic it was hypothesised that host genetics played a role in the pathophysiology of COVID-19 including a suggestion that the CCR5-Δ32 mutation may be protective in SARS-CoV-2 infection. Leronlimab is an investigational CCR5-specific humanized IgG4 monoclonal antibody currently in development for HIV-1 infection. We aimed to explore the impact of leronlimab on the severity of disease symptoms among participants with mild-to-moderate COVID-19.

The TEMPEST trial was a randomized, double-blind, placebo-controlled study in participants with mild-to-moderate COVID-19. Participants were randomly assigned in a 2:1 ratio to receive subcutaneous leronlimab (700 mg) or placebo on days 0 and 7. The primary efficacy endpoint was assessed by change in total symptom score based on fever, myalgia, dyspnea, and cough, at end of treatment (day 14).

Overall, 84 participants were randomized and treated with leronlimab (n = 56) or placebo (n = 28). No difference was observed in change in total symptom score (P = 0.8184) or other pre-specified secondary endpoints between treatments. However, in a post hoc analysis, 50.0% of participants treated with leronlimab demonstrated improvements from baseline in National Early Warning Score 2 (NEWS2) at day 14, compared with 20·8% of participants in the placebo group (post hoc; p = 0.0223). Among participants in this trial with mild-to-moderate COVID-19 adverse events rates were numerically but not statistically significantly lower in leronlimab participants (33.9%) compared with placebo participants (50.0%).

At the time the TEMPEST trial was designed although CCR5 was known to be implicated in COVID-19 disease severity the exact pathophysiology of SARS-CoV-2 infection was poorly understood. Today it is well accepted that SARS-CoV-2 infection in asymptomatic-to-mild cases is primarily characterized by viral replication, with a heightened immune response, accompanied by diminished viral replication in moderate-to-severe disease and a peak in inflammatory responses with excessive production of pro-inflammatory cytokines in critical disease. It is therefore perhaps not surprising that no differences between treatments were observed in the primary endpoint or in pre-specified secondary endpoints among participants with mild-to-moderate COVID-19. However, the results of the exploratory post hoc analysis showing that participants in the leronlimab group had greater improvement in NEWS2 assessment compared to placebo provided a suggestion that leronlimab may be associated with a lower likelihood of people with mild-to-moderate COVID-19 progressing to more severe disease and needs to be confirmed in other appropriately designed clinical trials.

gov number, NCT04343651 https://classic.

gov/ct2/show/NCT04343651.

Coronavirus disease 2019 (COVID-19) the most contagious infection caused by the unique type of coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), produced a global pandemic that wreaked havoc on the health-care system, resulting in high morbidity and mortality. Several methods were implemented to tackle the virus, including the repurposing of existing medications and the development of vaccinations. The purpose of this article is to provide a complete summary of the current state and future possibilities for COVID-19 therapies. We describe the many treatment classes, such as antivirals, immunomodulators, and monoclonal antibodies, that have been repurposed or developed to treat COVID-19. We also looked at the clinical evidence for these treatments, including findings from observational studies and randomized-controlled clinical trials, and highlighted the problems and limitations of the available evidence. Furthermore, we reviewed existing clinical trials and prospective COVID-19 therapeutic options, such as novel medication candidates and combination therapies. Finally, we discussed the long-term consequences of COVID-19 and the importance of ongoing research into the development of viable treatments. This review will help physicians, researchers, and policymakers to understand the prevention and mitigation of COVID-19.

The human innate immune system recognizes dsRNA as a pathogen-associated molecular pattern that induces a potent inflammatory response. The primary source of pathogenic dsRNA is cells infected with replicating viruses, but can also be released from uninfected necrotic cells. Here, we show that the dsRNA poly(I:C) challenge in human macrophages activates the p38 MAPK-MK2 signalling pathway and subsequently the phosphorylation of tristetraprolin (TTP/ZFP36). The latter is an mRNA decay-promoting protein that controls the stability of AU-rich mRNAs (AREs) that code for many inflammatory mediators. Hydroxychloroquine (HCQ), a common anti-malaria drug, is used to treat inflammatory and autoimmune disorders and, controversially, during acute COVID-19 disease. We found that HCQ reduced the dsRNA-dependent phosphorylation of p38 MAPK and its downstream kinase MK2. Subsequently, HCQ reduced the abundance and protein stability of the inactive (phosphorylated) form of TTP. HCQ reduced the levels and the mRNA stability of poly (I:C)-induced cytokines and inflammatory mRNAs like TNF, IL-6, COX-2, and IL-8 in THP-1 and primary blood monocytes. Our results demonstrate a new mechanism of the anti-inflammatory role of HCQ at post-transcriptional level (TTP phosphorylation) in a model of dsRNA activation, which usually occurs in viral infections or RNA release from necrotic tissue.

Drug repurposing, also known as drug repositioning, is a currently tested approach by which new uses are being assigned for already tested drugs. In this case there are antibiotics that are used to combat bacterial infections. However, antibiotics are among the drugs that have been studied for possible antiviral activities. Therefore, the aim of this work is to carry out a review of the studies of antibiotics that could be repositioned for the treatment of viral infections. Among the main antibiotics that have demonstrated antiviral activity are macrolides and glycopeptides. In addition, several antibiotics from the group of tetracyclines, fluoroquinolones, cephalosporins and aminoglycosides have also been studied for their antiviral activity. These antibiotics have demonstrated antiviral activity against both RNA and DNA viruses, including the recent pandemic virus SARS-CoV-2. Some of these antibiotics were selected in addition to its antiviral activity for their immunomodulatory and anti-inflammatory properties. Of the antibiotics that present antiviral activity, in many cases the mechanisms of action are not exactly known. The use of these antibiotics to combat viral infections remains controversial and is not generally accepted, since clinical trials are required to prove its effectiveness. Therefore, there is currently no antibiotic approved as antiviral therapy. Hence is necessary to present the studies carried out on antibiotics that can be repositioned in the future as antiviral drugs.

The threat of emerging viral outbreaks has increased the need for fast and effective development of therapeutics against emerging pathogens. One approach is to modify the structure of existing therapeutic agents to achieve the desired antiviral properties. Here, we attempted to synthesize a new antiviral compound by modifying the structure of chloroquine using the N-alkylation of the primary amine (N1,N1-diethylpentane-1,4-diamine) that is used in chloroquine synthesis. Chloroquine is commonly used to treat malaria. Like chloroquine, chloroquine is used for treating conditions such as rheumatoid arthritis, lupus, and malaria. For instance, in malaria treatment, it targets and inhibits the growth of the malaria parasite, aiding in its elimination from the body. The synthesized compounds MP1, C1, and TT1 were further tested in vitro against the B.1 lineage of SARS-CoV-2. One of the compounds, MP1, demonstrated minor effectiveness, with an IC50 of XX at only a high concentration (at a concentration of 60 μM) and decreased both the number of SARS-CoV-2 copies and the amount of infectious virus. Although the synthesized compounds failed to markedly inhibit SARS-CoV-2, this could be a pontial mechanism for manipulating the drug structure against other pathogens. MP1, TT1, C1, and chloroquine diphosphate were used as ligands for molecular docking to determine the principal interactions between these compounds and the active site of the protein downloaded from the Protein Data Bank (PDB ID: 6lzg). Finally, ADMET assays were performed on the synthesized compounds to determine their pharmacokinetics and bioavailability.

South African research ethics committees (RECs) faced significant challenges during the COVID-19 pandemic. Research ethics committees needed to find a balance between careful consideration of scientific validity and ethical merit of protocols, and review with the urgency normally associated with public health emergency research. We aimed to explore the views of South African RECs on their pandemic preparedness and response during COVID-19. We conducted in-depth interviews with 21 participants from RECs that were actively involved in the review of COVID-19 related research, at seven academic institutions across South Africa. Interviews were conducted remotely using an in-depth interview guide that included questions regarding REC preparedness and response to COVID-19. Interviews were conducted until data saturation, and audio-recordings were transcribed verbatim and coded. An inductive approach to thematic analysis was used to organise data into themes and sub-themes. This study focused on three main themes: coping during COVID-19, building REC capacity during pandemic times and a consistently cautious approach to mutual recognition of REC reviews. Despite an initial sense of unpreparedness, RECs were able to adapt and maintain careful ethical oversight of both COVID and non-COVID research, and the rigour of REC reviews. Several important lessons for preparedness and response to future pandemics were identified, including heightened awareness of publication, funding and political pressures, the importance of regular training for RECs and researchers, and strategies to enhance moral resilience of REC members. Incremental steps are needed to build trust and authentic partnerships among RECs in inter-pandemic times, to facilitate collaboration during future public health emergencies.

In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in adults with pneumonia in Wuhan, China.

It is now believed that several billion humans have been infected with SARS-CoV-2 and more than ten million have died from coronavirus disease 2019 (COVID-19), the disease caused by SARS-CoV-2.

The first five years of the SARS-CoV-2 pandemic have been marked by unfathomable suffering as well as remarkable scientific progress. This manuscript examines what has been learned about the treatment of inpatients with COVID-19 and explores how the therapeutic approach may evolve in the years ahead.

Background: During the coronavirus disease (COVID)-19 pandemic several drugs were used to manage the patients mainly those with a severe phenotype. Potential drugs were used off-label and major concerns arose from their applicability to managing the health crisis highlighting the importance of clinical trials. In this context, we described the mechanisms of the three repurposed drugs [Ivermectin-antiparasitic drug, Chloroquine/Hydroxychloroquine-antimalarial drugs, and Azithromycin-antimicrobial drug]; and, based on this description, the study evaluated the clinical efficacy of those drugs published in clinical trials. The use of these drugs reflects the period of uncertainty that marked the beginning of the COVID-19 pandemic, which made them a possible treatment for COVID-19. Methods: In our review, we evaluated phase III randomized controlled clinical trials (RCTs) that analyzed the efficacy of these drugs published from the COVID-19 pandemic onset to 2023. We included eight RCTs published for Ivermectin, 11 RCTs for Chloroquine/Hydroxychloroquine, and three RCTs for Azithromycin. The research question (PICOT) accounted for P-hospitalized patients with confirmed or suspected COVID-19; I-use of oral or intravenous Ivermectin OR Chloroquine/Hydroxychloroquine OR Azithromycin; C-placebo or no placebo (standard of care); O-mortality OR hospitalization OR viral clearance OR need for mechanical ventilation OR clinical improvement; and T-phase III RCTs. Results: While studying these drugs' respective mechanisms of action, the reasons for which they were thought to be useful became apparent and are as follows: Ivermectin binds to insulin-like growth factor and prevents nuclear transportation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), therefore preventing cell entrance, induces apoptosis, and osmotic cell death and disrupts viral replication. Chloroquine/Hydroxychloroquine blocks the movement of SARS-CoV-2 from early endosomes to lysosomes inside the cell, also, this drug blocks the binding between SARS-CoV-2 and Angiotensin-Converting Enzyme (ACE)-2 inhibiting the interaction between the virus spike proteins and the cell membrane and this drug can also inhibit SARS-CoV-2 viral replication causing, ultimately, the reduction in viral infection as well as the potential to progression for a higher severity phenotype culminating with a higher chance of death. Azithromycin exerts a down-regulating effect on the inflammatory cascade, attenuating the excessive production of cytokines and inducing phagocytic activity, and acts interfering with the viral replication cycle. Ivermectin, when compared to standard care or placebo, did not reduce the disease severity, need for mechanical ventilation, need for intensive care unit, or in-hospital mortality. Only one study demonstrated that Ivermectin may improve viral clearance compared to placebo. Individuals who received Chloroquine/Hydroxychloroquine did not present a lower incidence of death, improved clinical status, or higher chance of respiratory deterioration compared to those who received usual care or placebo. Also, some studies demonstrated that Chloroquine/Hydroxychloroquine resulted in worse outcomes and side-effects included severe ones. Adding Azithromycin to a standard of care did not result in clinical improvement in hospitalized COVID-19 participants. In brief, COVID-19 was one of the deadliest pandemics in modern human history. Due to the potential health catastrophe caused by SARS-CoV-2, a global effort was made to evaluate treatments for COVID-19 to attenuate its impact on the human species. Unfortunately, several countries prematurely justified the emergency use of drugs that showed only in vitro effects against SARS-CoV-2, with a dearth of evidence supporting efficacy in humans. In this context, we reviewed the mechanisms of several drugs proposed to treat COVID-19, including Ivermectin, Chloroquine/Hydroxychloroquine, and Azithromycin, as well as the phase III clinical trials that evaluated the efficacy of these drugs for treating patients with this respiratory disease. Conclusions: As the main finding, although Ivermectin, Chloroquine/Hydroxychloroquine, and Azithromycin might have mechanistic effects against SARS-CoV-2 infection, most phase III clinical trials observed no treatment benefit in patients with COVID-19, underscoring the need for robust phase III clinical trials.

This article discusses the complexity of the relationship between "law," "science," and "clinical practice" in the age of COVID-19.

The COVID-19 outbreak has garnered significant global attention due to its impact on human health. Despite its relatively low fatality rate, the virus affects multiple organ systems, resulting in various symptoms such as palpitations, headaches, muscle pain, and hearing loss among COVID-19 patients and those recovering from the disease. These symptoms impose a substantial physical, psychological, and social burden on affected individuals. On February 15, 2020, the Chinese government advised incorporating antimalarial drugs into the guidelines issued by the National Health Commission of China for preventing, diagnosing, and treating COVID-19 pneumonia. We examine the adverse effects of Chloroquine (CQ) in treating COVID-19 complications to understand why it is no longer the primary treatment for the disease.

The global mortality rate has been significantly impacted by the COVID-19 pandemic, caused by the SARS CoV-2 virus. Although the pursuit for a potent antiviral is still in progress, experimental therapies based on repurposing of existing drugs is being attempted. One important therapeutic target for COVID-19 is the main protease (Mpro) that cleaves the viral polyprotein in its replication process. Recently minocycline, an antimycobacterium drug, has been successfully implemented for the treatment of COVID-19 patients. But it's mode of action is still far from clear. Furthermore, it remains unresolved whether alternative antimycobacterium drugs can effectively regulate SARS CoV-2 by inhibiting the enzymatic activity of Mpro. To comprehend these facets, eight well-established antimycobacterium drugs were put through molecular docking experiments. Four of the antimycobacterium drugs (minocycline, rifampicin, clofazimine and ofloxacin) were selected by comparing their binding affinities towards Mpro. All of the four drugs interacted with both the catalytic residues of Mpro (His41 and Cys145). Additionally, molecular dynamics experiments demonstrated that the Mpro-minocyline complex has enhanced stability, experiences reduced conformational fluctuations and greater compactness than other three Mpro-antimycobacterium and Mpro-N3/lopinavir complexes. This research furnishes evidences for implementation of minocycline against SARS CoV-2. In addition, our findings also indicate other three antimycobacterium/antituberculosis drugs (rifampicin, clofazimine and ofloxacin) could potentially be evaluated for COVID-19 therapy.

Our study aimed to describe the group of severe COVID-19 patients at an institutional level, and determine factors associated with different outcomes.

A retrospective chart review of patients admitted with severe acute hypoxic respiratory failure due to COVID-19 infection. Based on outcomes, we categorized 3 groups of severe COVID-19: (1) Favorable outcome: progressive care unit admission and discharge (2) Intermediate outcome: ICU care (3) Poor outcome: in-hospital mortality.

Eighty-nine patients met our inclusion criteria; 42.7% were female. The average age was 59.7 (standard deviation (SD):13.7). Most of the population were Caucasian (95.5%) and non-Hispanic (91.0%). Age, sex, race, and ethnicity were similar between outcome groups. Medicare and Medicaid patients accounted for 62.9%. The average BMI was 33.5 (SD:8.2). Moderate comorbidity was observed, with an average Charlson Comorbidity index (CCI) of 3.8 (SD:2.6). There were no differences in the average CCI between groups(p = 0.291). Many patients (67.4%) had hypertension, diabetes (42.7%) and chronic lung disease (32.6%). A statistical difference was found when chronic lung disease was evaluated; p = 0.002. The prevalence of chronic lung disease was 19.6%, 27.8%, and 40% in the favorable, intermediate, and poor outcome groups, respectively. Smoking history was associated with poor outcomes (p = 0.04). Only 7.9% were fully vaccinated. Almost half (46.1%) were intubated and mechanically ventilated. Patients spent an average of 12.1 days ventilated (SD:8.5), with an average of 6.0 days from admission to ventilation (SD:5.1). The intermediate group had a shorter average interval from admission to ventilator (77.2 hours, SD:67.6), than the poor group (212.8 hours, SD:126.8); (p = 0.001). The presence of bacterial pneumonia was greatest in the intermediate group (72.2%), compared to the favorable group (17.4%), and the poor group (56%); this was significant (p<0.0001). In-hospital mortality was seen in 28.1%.

Most patients were male, obese, had moderate-level comorbidity, a history of tobacco abuse, and government-funded insurance. Nearly 50% required mechanical ventilation, and about 28% died during hospitalization. Bacterial pneumonia was most prevalent in intubated groups. Patients who were intubated with a good outcome were intubated earlier during their hospital course, with an average difference of 135.6 hours. A history of cigarette smoking and chronic lung disease were associated with poor outcomes.

Gliomas are primary tumors that originate in the central nervous system. The conventional treatment options for gliomas typically encompass surgical resection and temozolomide (TMZ) chemotherapy. However, despite aggressive interventions, the median survival for glioma patients is merely about 14.6 months. Consequently, there is an urgent necessity to explore innovative therapeutic strategies for treating glioma. The foundational study of regulated cell death (RCD) can be traced back to Karl Vogt's seminal observations of cellular demise in toads, which were documented in 1842. In the past decade, the Nomenclature Committee on Cell Death (NCCD) has systematically classified and delineated various forms and mechanisms of cell death, synthesizing morphological, biochemical, and functional characteristics. Cell death primarily manifests in two forms: accidental cell death (ACD), which is caused by external factors such as physical, chemical, or mechanical disruptions; and RCD, a gene-directed intrinsic process that coordinates an orderly cellular demise in response to both physiological and pathological cues. Advancements in our understanding of RCD have shed light on the manipulation of cell death modulation - either through induction or suppression - as a potentially groundbreaking approach in oncology, holding significant promise. However, obstacles persist at the interface of research and clinical application, with significant impediments encountered in translating to therapeutic modalities. It is increasingly apparent that an integrative examination of the molecular underpinnings of cell death is imperative for advancing the field, particularly within the framework of inter-pathway functional synergy. In this review, we provide an overview of various forms of RCD, including autophagy-dependent cell death, anoikis, ferroptosis, cuproptosis, pyroptosis and immunogenic cell death. We summarize the latest advancements in understanding the molecular mechanisms that regulate RCD in glioma and explore the interconnections between different cell death processes. By comprehending these connections and developing targeted strategies, we have the potential to enhance glioma therapy through manipulation of RCD.

Inpatient antibiotic use increased during the early phases of the COVID-19 pandemic. We sought to determine whether these changes persisted in persons with and without COVID-19 infection.

Retrospective cohort analysis.

108 Veterans Affairs (VA) facilities.

Persons receiving acute inpatient care from January 2016 to October 2022.

Data on antibacterial use, patient days present, and COVID-19 care were extracted from the VA Corporate Data Warehouse. Days of therapy (DOT) per 1000 days present (DP) were calculated and stratified by Centers for Disease Control and Prevention-defined antibiotic classes.

Antibiotic use increased from 534 DOT/1000 DP in 11/2019-2/2020 to 588 DOT/1000 DP in 3/2020-4/2020. Subsequently, antibiotic use decreased such that total DOT/1000 DP was 2% less in 2020 as a whole than in 2019. Driven by treatment for community acquired pneumonia, antibiotic use was 30% higher in persons with COVID-19 than in uninfected persons in 3/2020-4/2020, but only 4% higher for the remainder of 2020. In 2022 system-wide antibiotic use was 9% less in persons with COVID-19; however, antibiotic use remained higher in persons with COVID-19 in 25% of facilities.

Although antibiotic use increased during the early phases of the COVID-19 pandemic, overall use subsequently decreased to below previous baseline levels and, in 2022, was less in persons with COVID-19 than in persons without COVID-19. However, further work needs to be done to address variances across facilities and to determine whether current levels of antibiotic use in persons with COVID-19 are justified.

During the COVID-19 pandemic, a multitude of surveys have analyzed the impact virus spreading on the everyday medical practice, including neurosurgery. However, none have examined the perceptions of neurosurgeons towards the pandemic, their life changes, and the strategies they implemented to be able to deal with their patients in such a difficult time.

From April 2021 to May 2021 a modified Delphi method was used to construct, pilot, and refine the questionnaire focused on the evolution of global neurosurgical practice during the pandemic. This survey was distributed among 1000 neurosurgeons; the responses were then collected and critically analyzed.

Outpatient department practices changed with a rapid rise in teleservices. 63.9% of respondents reported that they have changed their OT practices to emergency cases with occasional elective cases. 40.0% of respondents and 47.9% of their family members reported to have suffered from COVID-19. 56.2% of the respondents reported having felt depressed in the last 1 year. 40.9% of respondents reported having faced financial difficulties. 80.6% of the respondents found online webinars to be a good source of learning. 47.8% of respondents tried to improve their neurosurgical knowledge while 31.6% spent the extra time in research activities.

Progressive increase in operative waiting lists, preferential use of telemedicine, reduction in tendency to complete stoppage of physical clinic services and drop in the use of PPE kits were evident. Respondents' age had an impact on how the clinical services and operative practices have evolved. Financial concerns overshadow mental health.

We studied whether the use of hydroxychloroquine (HCQ) for COVID-19 resulted in supply shortages for patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).

We used US claims data (IQVIA PHARMETRICS® Plus for Academics [PHARMETRICS]) and hospital electronic records from Spain (Institut Municipal d'Assistència Sanitària Information System [IMASIS]) to estimate monthly rates of HCQ use between January 2019 and March 2022, in the general population and in patients with RA and SLE. Methotrexate (MTX) use was estimated as a control.

More than 13.5 million individuals (13,311,811 PHARMETRICS, 207,646 IMASIS) were included in the general population cohort. RA and SLE cohorts enrolled 135,259 and 39,295 patients, respectively, in PHARMETRICS. Incidence of MTX and HCQ were stable before March 2020. On March 2020, the incidence of HCQ increased by 9- and 67-fold in PHARMETRICS and IMASIS, respectively, and decreased in May 2020. Usage rates of HCQ went back to prepandemic trends in Spain but remained high in the United States, mimicking waves of COVID-19. No significant changes in HCQ use were noted among patients with RA and SLE. MTX use rates decreased during HCQ approval period for COVID-19 treatment.

Use of HCQ increased dramatically in the general population in both Spain and the United States during March and April 2020. Whereas Spain returned to prepandemic rates after the first wave, use of HCQ remained high and followed waves of COVID-19 in the United States. However, we found no evidence of general shortages in the use of HCQ for both RA and SLE in the United States.

The GRADE system of clinical recommendations has deontic implications and can discriminate between mandatory, prohibited, and merely permitted medical decisions.

The recommendation categories of the GRADE framework map onto deontological imperatives that can lead to a better understanding and management of allegations of imprudence and appropriateness of treatments. Allegations made during the worst phase of COVID-19 pandemic are used as a case study for exploring the deontic implications of GRADE.

Conceptual theoretical analysis, case study analysis, and argumentation in defence of hypotheses.

Strong GRADE recommendations for or against treatment are justified by high-quality evidence and can be construed as ethical obligations and prohibitions. In contrast, when evidence for benefit or harm is of lower quality, GRADE yields weak, discretionary recommendations. In such grey area cases, the absence of a duty to prescribe or refuse to prescribe a requested treatment is compatible with the privilege of considering unproven but possibly beneficial options in a private setting. This privilege, however, does not extend to healthcare policymakers, who have a duty to promote actions that serve the public and whose recommendations should not be guided by personal or idiosyncratic preferences or values.

If there is no prima facie evidence that a proposed treatment is harmful, doctors are not negligent in considering it in shared doctor-patient decision-making. But these clinical decisions under uncertainty do not transfer obligations to health authorities, who are not part of the decision-making process in clinical settings. The clinical decision-making process concerns particulars and is guided by contextual and specific reasons that do not fall within the scope of a general policy. Thus, in the context of a serious epidemic in which patients need and demand treatments, if the body of evidence is still changing and fragile, an attitude of tolerance and connivance may ensure a smoother transition to a more stable phase of progress, both in scientific and clinical medicine.