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Introduction: Corona virus disease (COVID-19) was declared as a Pandemic by WHO on March 11, 2020. Since health care workers play an important role in providing care to infected patients, they are exposed to unprecedented levels of risk. At the initial phase of this pandemic, no definitive treatment was available, the only way to combat this disease was prevention. A number of prophylactic drugs were being studied during that time for use by health care workers. On 23rd March 2020, Government of India issued recommendation through National Task Force for Covid-19, for using Hydroxychloroquine as prophylaxis for SARS COV-2. Preclinical studies of Azithromycin have shown immunomodulation and in vitro activity against SARS-COV-2, that has led to its widespread usage during COVID-19. Ivermectin, an antiparasitic drug was reported to have an in vitro activity against SARS-COV-2. This orally administered drug was included in India's revised National COVID-19 treatment protocol for people with mild infection. Vitamin C, a water soluble vitamin has been considered for potential beneficial effects in COVID-19 disease. Many animal studies have indicated that a daily intake of vitamin C may prevent infections. Aim(s): To evaluate the pattern of drugs (HCQ, AZITHROMYCIN, IVERMECTIN,and VITAMIN C) used for COVID-19 prophylaxis among health care workers at GMC, Srinagar. MATERIALS AND METHODS: This study is being conducted by using a survey questionnaire. A survey questionnaire in English has been developed after literature review. The responses will be analyzed using descriptive statistics of frequency and percentage.
ABSTRACT
An outburst of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become a grave threat to global health and the economy. As of May 13, 2020, a total of 42,81,838 cases have been confirmed, with over 2,92,376 deaths worldwide. In India, 75,048 cases have been reported to date with 2,440 deaths. Management of this new coronavirus (COVID19) has mainly focused on infection prevention, case detection, monitoring, and supportive care. As there is no vaccine or specific antiviral treatment for human SARS-CoV-2, therefore identifying the drug treatment options as soon as possible is critical for the response to the COVID19 outbreak. Pro-inflammatory cascade and cytokine storm play a key role in the pathogenesis of new coronavirus. A large number of therapeutic interventions such as antiviral, antimalarial, convalescent plasma therapy, BCG vaccine, mTOR inhibi-tors, Tissue Plasminogen Activator, Human monoclonal antibodies, Anti-parasitic agents, Immunoen-hancers, Nutritional interventions, JAK-STAT signaling inhibitors, ACE2 receptor modulators, and An-giotensin II receptor blockers have been either tried or suggested for effective treatment of patients with SARS-CoV-2 disease. Hence, we recommend that all the above potential interventions must be imple-mented in terms of their safety and efficacy through proper clinical experiments to control the emerging SARS-CoV-2 disease.Copyright © 2021 Bentham Science Publishers.
ABSTRACT
The search for an effective and safe COVID-19 therapy involves, among other things, assessment of efficacy of medicines already used for the treatment of other diseases, and having potential antiviral activity against SARSCoV-2. The relevance of the presented study stems from ambiguous data on the off-label use of the antiparasitic medicine ivermectin for the treatment of COVID-19 patients. The aim of the study was to analyse ivermectin efficacy and safety for COVID-19 treatment, as reflected in the scientific literature. Ivermectin, an antiparasitic medicine from the group of macrocyclic lactones produced by Streptomyces avermitilis, stimulates release of the inhibitory neurotransmitter gamma-aminobutyric acid, which leads to impaired transmission of nerve impulses, paralysis and death of parasites. The results of preclinical studies show ivermectin's inhibitory activity against a number of RNA and DNA viruses, including SARS-CoV-2. The results of ivermectin clinical studies are ambiguous: a number of studies demonstrated a positive effect on the condition of COVID-19 patients, however, there is currently no convincing evidence of the validity and efficacy of ivermectin use for the prevention and treatment of COVID-19 patients. The safety profile of ivermectin is relatively favourable. Large randomised controlled trials are needed to fully assess the feasibility of using ivermectin in COVID-19.
ABSTRACT
Background: COVID-19, first reported in China, from the new strain of severe acute respiratory syndrome coronaviruses (SARS-CoV-2), poses a great threat to the world by claiming uncountable lives. SARS-CoV-2 is a highly infectious virus that has been spreading rapidly throughout the world. In the absence of any specific medicine to cure COVID-19, there is an urgent need to develop novel thera-peutics, including drug repositioning along with diagnostics and vaccines to combat the COVID-19. Many antivirals, antimalarials, antiparasitic, antibacterials, immunosuppressive anti-inflammatory, and immunoregulatory agents are being clinically investigated for the treatment of COVID-19. Objectives: The earlier developed one parameter regression model correlating the dock scores with in vitro anti-SARS-CoV-2 main protease activity well predicted the six drugs viz remdesivir, chloroquine, favipiravir, ribavirin, penciclovir, and nitazoxanide as potential anti-COVID agents. To further validate our earlier model, the biological activity of nine more recently published SARS-CoV-2 main protease inhibitors has been predicted using our previously reported model. Methods: In the present study, this regression model has been used to screen the existing antiviral, an-tiparasitic, antitubercular, and anti pneumonia chemotherapeutics utilizing dock score analyses to explore the potential including mechanism of action of these compounds in combating SARS-CoV-2 main prote-ase. Results: The high correlation (R=0.91) explaining 82.3% variance between the experimental versus predicted activities for the nine compounds is observed. It proves the robustness of our developed model. Therefore, this robust model has been further improved, taking a total number of 15 compounds to formu-late another model with an R-value of 0.887 and the explained variance of 78.6%. These models have been used for high throughput screening (HTS) of the 21 diverse compounds belonging to antiviral, an-tiparasitic, antitubercular, and anti pneumonia chemotherapeutics as potential repurpose agents to combat SARS-CoV-2 main protease. The models screened that the drugs bedaquiline and lefamulin have higher binding affinities (dock scores of-8.989 and-9.153 Kcal/mol respectively) than the reference compound {N}-[2-(5-fluoranyl-1~{H}-indol-3-yl)ethyl]ethanamide (dock score of-7.998 Kcal/Mol), as well as higher predicted activities with pEC50 of 0.783 and 0.937 µM and the 0.611 and 0.724 µM respectively. The clinically used repurposed drugs dexamethasone and cefixime have been predicted with pEC50 val-ues of-0.463 and-0.622 µM and-0.311 and-0.428 µM respectively for optimal inhibition. The drugs such as doxycycline, cefpodoxime, ciprofloxacin, sparfloxacin, moxifloxacin, and TBAJ-876 showed moderate binding affinity corresponding to the moderate predicted activity (-1.540 to-1.109 µM). Conclusion: In the present study, validation of our previously developed dock score-based one parametric regression model has been carried out by predicting 9 more SARS-CoV-2 main protease inhibitors. Another model has been formulated to explore the model's robustness. These models have been taken as a barometer for the screening of more potent compounds. The HTS revealed that the drugs such as bedaqui-line and lefamulin are highly predicted active compounds, whereas dexamethasone and cefixime have optimal inhibition towards SARS-CoV-2 main protease. The drugs such as doxycycline, cefpodoxime, ciprofloxacin, sparfloxacin, moxifloxacin, and TBAJ-876 have moderately active compounds towards the target inhibition.
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Background. Antimicrobials are empirically used in COVID-19 patients resulting in inappropriate stewardship and increased antimicrobial resistance. Our objective was to assess antimicrobial use among suspected COVID-19 in-patients while waiting for the COVID-19 test report. Methods. From March to August 2020, we collected data from in-patients of 12 tertiary-level hospitals across Bangladesh. We identified suspected COVID-19 patients;collected information on antimicrobial received within 24 h before and on hospitalization;and tested nasopharyngeal swab for SARS-CoV-2 using rRT-PCR. We used descriptive statistics and a regression model for data analysis. Results. Among 1188 suspected COVID-19 patients, the median age was 34 years (IQR:2-56), 69% were male, 40% had comorbidities, 53% required oxygen, and 1% required ICU or ventilation support after admission. Antibiotics were used in 92% of patients, 47% within 24 h before, and 89% on admission. Patients also received antiviral, mostly favipiravir (1%) and antiparasitic drugs particularly ivermectin (3%). Third-generation cephalosporin use was the highest (708;60%), followed by macrolide (481;40%), and the majority (853;78%) who took antibiotics were SARS-CoV-2 negative. On admission, 77% mild and 94% moderately ill patients received antibiotics. Before admission, 3% patients had two antibiotics, and on admission, 27% received two to four classes of antibiotics at the same time. According to WHO AWaRe classification, the Watch group antibiotics were mostly used before (43%) as well as on admission (80%). Reserve group antibiotic particularly linezolid was used in 1% patients includes mild cases on admission. Antibiotic use on admission was higher among severely ill patients (AOR = 11.7;95%CI:4.5-30.1) and those who received antibiotics within 24 h before hospital admission (AOR = 1.6;95%CI:1.0-2.5). Antimicrobials used among suspected COVID-19 patients and SARS-CoV-2 positive and negative patients 24 h before and on hospital admission at 12 selected hospitals in Bangladesh, March-August 2020 Antimicrobials used on admission among suspected COVID-19 patients according to disease severity at 12 selected hospitals in Bangladesh, March-August 2020 Conclusion. Antimicrobial use was highly prevalent among suspected COVID-19 in-patients in Bangladesh. Initiating treatment with Watch group antibiotics like third-generation cephalosporin and azithromycin among mild to moderately ill patients were common. Promoting antimicrobial stewardship with monitoring is essential to prevent blanket antibiotic use, thereby mitigating antimicrobial resistance.
ABSTRACT
Background. There is a continued and pressing need for safe and effective treatment of COVID-19. Significant survival benefits have been shown by dexamethasone, tocilizumab and sarilumab, however they are only recommended in hospitalised COVID-19 patients. Ivermectin is a well-established and readily available antiparasitic drug which may be suitable for treatment in mild and moderate disease stages. It recently demonstrated anti-viral properties in vitro and now over 80 clinical trials have been registered worldwide to test its effectiveness in COVID-19 patients. This meta-analysis aims to collect data on adverse events reported in new COVID-19 treatment trials for the use of ivermectin as a repurposed medication. Methods. Data was extracted from randomised trials of COVID-19 treatment trials identified through systematic searches of PUBMED, EMBASE, MedRxiv and trial registries. The primary outcome of this meta-analysis is the frequency of adverse events. Key safety events included serious, gastrointestinal, neurological, cardiovascular and dermatological adverse events. Results. Overall, 18 trials investigating ivermectin for COVID-19 in a total of 2496 participants reported safety data and were included. There was no significant difference in the proportion of all adverse events between ivermectin and the comparator. There were 371/1261 (29%) adverse events recorded in the ivermectin containing arms and 376/1284 (29%) in the control arms (RR 1.02 [95% CI 0.77 - 1.34];p = 0.91). There was no significant difference in the rate of serious adverse events across treatment arms (RR 1.95 [95% CI 0.75 - 5.11];p = 0.18). No significant differences between ivermectin and the control were seen across different subcategories of adverse events. Figure 1 shows a summary of the results for all adverse events. Forest plot comparing ivermectin and the control for all adverse events in COVID-19 trials, subdivided into single-day dosing trials and multi-day dosing trials. Conclusion. The results of recent COVID-19 trials show that overall, ivermectin is safe and well-tolerated. No significant difference in adverse event reporting was found across all subgroups in single and multi-day treatment regimens for the studies analysed. Safety reporting methodologies often varied across trials. Future and ongoing trials should be encouraged to collect and monitor safety data systematically.