Ivermectin for Prevention and Treatment of COVID-19 Infection: A Systematic Review, Meta-analysis, and Trial Sequential Analysis to Inform Clinical Guidelines

American Journal of Therapeutics, Journal Year: 2021, Volume and Issue: 28(4), P. e434 - e460

Published: June 19, 2021

Background: Repurposed medicines may have a role against the SARS-CoV-2 virus. The antiparasitic ivermectin, with antiviral and anti-inflammatory properties, has now been tested in numerous clinical trials. Areas of uncertainty: We assessed efficacy ivermectin treatment reducing mortality, secondary outcomes, chemoprophylaxis, among people with, or at high risk of, COVID-19 infection. Data sources: searched bibliographic databases up to April 25, 2021. Two review authors sifted for studies, extracted data, bias. Meta-analyses were conducted certainty evidence was using GRADE approach additionally trial sequential analyses mortality. Twenty-four randomized controlled trials involving 3406 participants met inclusion. Therapeutic Advances: Meta-analysis 15 found that reduced death compared no (average ratio 0.38, 95% confidence interval 0.19–0.73; n = 2438; I 2 49%; moderate-certainty evidence). This result confirmed analysis same DerSimonian–Laird method underpinned unadjusted analysis. also robust Biggerstaff–Tweedie method. Low-certainty prophylaxis infection by an average 86% (95% 79%–91%). Secondary outcomes provided less certain evidence. suggested there be benefit “need mechanical ventilation,” whereas effect estimates “improvement” “deterioration” clearly favored use. Severe adverse events rare difference as low certainty. Evidence on other very Conclusions: Moderate-certainty finds large reductions deaths are possible ivermectin. Using early course reduce numbers progressing severe disease. apparent safety cost suggest is likely significant impact pandemic globally.

Language: Английский

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Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19

American Journal of Therapeutics, Journal Year: 2021, Volume and Issue: 28(3), P. e299 - e318

Published: April 22, 2021

After COVID-19 emerged on U.S shores, providers began reviewing the emerging basic science, translational, and clinical data to identify potentially effective treatment options. In addition, a multitude of both novel repurposed therapeutic agents were used empirically studied within trials.

Language: Английский

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Ivermectin for preventing and treating COVID-19

Cochrane library, Journal Year: 2022, Volume and Issue: 2024(3)

Published: June 21, 2022

Language: Английский

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ESCMID COVID-19 living guidelines: drug treatment and clinical management

Clinical Microbiology and Infection, Journal Year: 2021, Volume and Issue: 28(2), P. 222 - 238

Published: Nov. 22, 2021

Language: Английский

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Ivermectin for preventing and treating COVID-19

Cochrane library, Journal Year: 2021, Volume and Issue: 2021(10)

Published: July 28, 2021

Language: Английский

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Antibiotics for the treatment of COVID-19

Cochrane library, Journal Year: 2021, Volume and Issue: 2022(7)

Published: Oct. 22, 2021

Language: Английский

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Effectiveness of Drug Repurposing and Natural Products Against SARS-CoV-2: A Comprehensive Review

Clinical Pharmacology Advances and Applications, Journal Year: 2024, Volume and Issue: Volume 16, P. 1 - 25

Published: Jan. 1, 2024

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a betacoronavirus responsible for the COVID-19 pandemic, causing respiratory disorders, and even death in some individuals, if not appropriately treated time. To face preventive measures have been taken against contagions application of vaccines to prevent severe disease cases. For treatment, antiviral, antiparasitic, anticoagulant other drugs reused due limited specific medicaments disease. Drug repurposing an emerging strategy with therapies that already tested safe humans. One promising alternative systematic experimental screening vast pool compounds computational drug (in silico assay). Using these tools, new uses approved such as chloroquine, hydroxychloroquine, ivermectin, zidovudine, ribavirin, lamivudine, remdesivir, lopinavir tenofovir/emtricitabine conducted, showing effectiveness vitro SARS-CoV-2 these, also clinical trials. Additionally, therapeutic options sought natural products (terpenoids, alkaloids, saponins phenolics) results use Among most studied are resveratrol, quercetin, hesperidin, curcumin, myricetin betulinic acid, which were proposed inhibitors. control SARS-CoV2, better observed remdesivir hospitalized patients outpatients. Regarding products, quercetin demonstrated antiviral activity vivo, nebulized formulation has alleviate symptoms COVID-19. This review shows evidence efficacy potential treatment this, search was carried out PubMed, SciELO ScienceDirect databases articles about or under study recognized their SARS-CoV-2.

Language: Английский

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NSAIDs/nitazoxanide/azithromycin repurposed for COVID-19: potential mitigation of the cytokine storm interleukin-6 amplifier via immunomodulatory effects

Expert Review of Anti-infective Therapy, Journal Year: 2021, Volume and Issue: 20(1), P. 17 - 21

Published: June 5, 2021

Mediators of immunity and inflammation are playing a crucial role in COVID-19 pathogenesis complications as demonstrated by several genetic clinical studies. Thus, repurposing drugs that possess anti-inflammatory and/or immune-modulatory effects for is considered rational approach.

Language: Английский

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Blood Bacteria-Free DNA in Septic Mice Enhances LPS-Induced Inflammation in Mice through Macrophage Response

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(3), P. 1907 - 1907

Published: Feb. 8, 2022

Although bacteria-free DNA in blood during systemic infection is mainly derived from bacterial death, translocation of the gut into circulation (gut translocation) also possible. Hence, several mouse models with experiments on macrophages were conducted to explore sources, influences, and impacts sepsis. First, bacteriome demonstrated cecal ligation puncture (CLP) sepsis mice. Second, administration lysate (a source DNA) dextran sulfate solution (DSS)-induced mucositis mice elevated without bacteremia supported free DNA. The absence DSS implies an impact abundance intestinal contents Third, higher serum cytokines after injection combined lipopolysaccharide (LPS), when compared LPS alone, influence inflammation. synergistic effects macrophage pro-inflammatory responses, as indicated by supernatant (TNF-α, IL-6, IL-10), genes (NFκB, iNOS, IL-1β), profound energy alteration (enhanced glycolysis reduced mitochondrial functions), which was neutralized TLR-9 inhibition (chloroquine), demonstrated. In conclusion, presence partly due circulation, would enhance severity. Inhibition responses against could attenuate LPS-DNA synergy might help improve hyper-inflammation some situations.

Language: Английский

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Final Results of a Randomized, Placebo-Controlled, Two-Arm, Parallel Clinical Trial of Proxalutamide for Hospitalized COVID-19 Patients: A Multiregional, Joint Analysis of the Proxa-Rescue AndroCoV Trial

Cureus, Journal Year: 2021, Volume and Issue: unknown

Published: Dec. 25, 2021

Background The role of androgens on COVID-19 is well established. Proxalutamide a second-generation, non-steroidal antiandrogen (NSAA) with the highest potency among NSAAs and concurrent regulation angiotensin-converting enzyme 2 (ACE2) expression inflammatory response. has been demonstrated to be effective prevent hospitalizations in early randomized clinical trials (RCTs). Conversely, hospitalized patients, preliminary results from two different arms an RCT (The Proxa-Rescue AndroCoV Trial) also reduction all-cause mortality. This study aims report final, joint (North arm South arm) trial arms) combined, evaluate whether response proxalutamide was consistent across regions (Northern Brazil Southern Brazil). Materials methods Upon randomization, patients received either 300mg/day or placebo for 14 days, addition usual care, proxalutamide:placebo ratio 1:1 North 4:1 (ratio modified due high drug efficacy). Datasets were statistical analysis performed overall population. compared group 14-day 28-day recovery (discharge alive hospital) mortality rates, post-randomization hospitalization stay. Results groups between arms. Analysis stratified by sex baseline WHO COVID Ordinary Score. A total 778 subjects included (645 North, 317 328 group; 133 arm, 106 27 group). Recovery rate 121% higher than at day [81.1% vs 36.6%; (RecR) 2.21; 95% confidence interval (95% CI), 1.92-2.56; p<0.0001], 81% 28 (98.1% 47.6%; RecR, 1.81; CI, 1.61-2.03; p<0.0001). All-cause 80% lower Day [8.0% 39.2%; Risk (RR), 0.20; 0.14-0.29; 78% (10.6% 48.2%; RR, 0.22; CI 0.16-0.30). Post-randomization time-to-discharge shorter [median, 5 days; interquartile range (IQR), 3-8] (median, 9 IQR, 6-14) (p<0.0001). statistically similar all measured outcomes. Males females presented Patients that did not require oxygen use (scores 3 4) present significant improvement whereas scores 6 improvements outcomes (p<0.0001 all). Conclusion increased rate, reduced shortened hospital stay patients. arms, providing further consistency efficacy when used late-stage COVID-19.

Language: Английский

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