Project description:ObjectiveWe evaluated whether ivermectin combined with doxycycline reduced the clinical recovery time in adults with COVID-19 infection.MethodsThis was a randomized, blinded, placebo-controlled trial in patients with mild-to-moderate COVID-19 symptoms randomly assigned to treatment (n = 200) and placebo (n = 200) groups. The primary outcome was duration from treatment to clinical recovery. Secondary outcomes were disease progression and persistent COVID-19 positivity by RT-PCR.ResultsAmong 556 screened patients, 400 were enrolled and 363 completed follow-up. The mean patient age was 40 years, and 59% were men. The median recovery time was 7 (4-10, treatment group) and 9 (5-12, placebo group) days (hazard ratio, 0.73; 95% confidence interval, 0.60-0.90). The number of patients with a ≤7-day recovery was 61% (treatment group) and 44% (placebo groups) (hazard ratio, 0.06; 95% confidence interval, 0.04-0.09). The proportion of patients who remained RT-PCR positive on day 14 and whose disease did not progress was significantly lower in the treatment group than in the placebo group.ConclusionsPatients with mild-to-moderate COVID-19 infection treated with ivermectin plus doxycycline recovered earlier, were less likely to progress to more serious disease, and were more likely to be COVID-19 negative by RT-PCR on day 14.Trial registrationClinicalTrials.gov Identifier: NCT04523831.Data repository idDryad. doi:10.5061/dryad.qjq2bvqf6.
Project description:Background The emergence of the novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to millions of infections and is exerting an unprecedented impact on society and economies worldwide. The evidence showed that heart failure (HF) is a clinical syndrome that could be encountered at different stages during the progression of COVID-19. Shenfu injection (SFI), a traditional Chinese medicine (TCM) formula has been widely used for heart failure therapy in China and was suggested to treat critical COVID-19 cases based on the guideline for diagnosis and treatment of COVID-19 (the 7th version) issued by National Health Commission of the People's Republic of China. However, the active components, potential targets, related pathways, and underlying pharmacology mechanism of SFI against COVID-19 combined with HF remain vague. Objective To investigate the effectiveness and possible pharmacological mechanism of SFI for the prevention and treatment of COVID-19 combined with HF. Methods In the current study, a network analysis approach integrating active compound screening (drug-likeness, lipophilicity, and aqueous solubility models), target fishing (Traditional Chinese Medicine Systems Pharmacology, fingerprint-based Similarity Ensemble Approach, and PharmMapper databases), compound-target-disease network construction (Cytoscape software), protein-protein interaction network construction (STRING and Cytoscape software), biological process analysis (STRING and Cytoscape plug-in Clue GO) and pathway analysis (Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis) was developed to decipher the active ingredients, potential targets, relevant pathways, and the therapeutic mechanisms of SFI for preventing and treating COVID-19 combined with HF. Results Finally, 20 active compounds (DL ≥ 0.18, 1≤Alog P ≤ 5, and −5≤LogS ≤ −1) and 164 relevant targets of SFI were identified related to the development of COVID-19 combined with HF, which were mainly involved in three biological processes including metabolic, hemostasis, and cytokine signaling in immune system. The C-T-D network and reactome pathway analysis indicated that SFI probably regulated the pathological processes of heart failure, respiratory failure, lung injury, and inflammatory response in patients with COVID-19 combined with HF through acting on several targets and pathways. Moreover, the venn diagram was used to identify 54 overlapped targets of SFI, COVID-19, and HF. KEGG pathway enrichment analysis showed that 54 overlapped targets were highly enriched to several COVID-19 and HF related pathways, such as IL-17 signaling pathway, Th17 cell differentiation, and NF-kappa B signaling pathway. Conclusions A comprehensive network analysis approach framework was developed to systematically elucidate the potential pharmacological mechanism of SFI for the prevention and treatment of SFI against COVID-19 combined with HF. The current study may not only provide in-depth understanding of the pharmacological mechanisms of SFI, but also a scientific basis for the application of SFI against COVID-19 combined with HF.
Project description:The unprecedented pandemic of coronavirus disease 2019 (COVID-19) demands effective treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The infection of SARS-CoV-2 critically depends on diverse viral or host proteases, which mediate viral entry, viral protein maturation, as well as the pathogenesis of the viral infection. Endogenous and exogenous agents targeting for proteases have been proved to be effective toward a variety of viral infections ranging from HIV to influenza virus, suggesting protease inhibitors as a promising antiviral treatment for COVID-19. In this Review, we discuss how host and viral proteases participated in the pathogenesis of COVID-19 as well as the prospects and ongoing clinical trials of protease inhibitors as treatments.
Project description:As of January 2021, SARS-CoV-2 has killed over 2 million individuals across the world. As such, there is an urgent need for vaccines and therapeutics to reduce the burden of COVID-19. Several vaccines, including mRNA, vector-based vaccines, and inactivated vaccines, have been approved for emergency use in various countries. However, the slow roll-out of vaccines and insufficient global supply remains a challenge to turn the tide of the pandemic. Moreover, vaccines are important tools for preventing the disease but therapeutic tools to treat patients are also needed. As such, since the beginning of the pandemic, repurposed FDA-approved drugs have been sought as potential therapeutic options for COVID-19 due to their known safety profiles and potential anti-viral effects. One of these drugs is ivermectin (IVM), an antiparasitic drug created in the 1970s. IVM later exerted antiviral activity against various viruses including SARS-CoV-2. In this review, we delineate the story of how this antiparasitic drug was eventually identified as a potential treatment option for COVID-19. We review SARS-CoV-2 lifecycle, the role of the nucleocapsid protein, the turning points in past research that provided initial 'hints' for IVM's antiviral activity and its molecular mechanism of action- and finally, we culminate with the current clinical findings.
Project description:Ivermectin has become a controversial potential medicine for coronavirus disease 2019. Some early studies suggested clinical benefits in treatment of infection. However, the body of evidence includes studies of varying quality. Furthermore, some trials have now been identified as potentially fraudulent. We present a subgroup meta-analysis to assess the effects of stratifying by trial quality on the overall results. The stratification is based on the Cochrane Risk of Bias measures and raw data analysis where possible. The results suggest that the significant effect of ivermectin on survival was dependent on largely poor-quality studies. According to the potentially fraudulent study (risk ratio [RR], 0.08; 95% CI, 0.02-0.35), ivermectin improved survival ~12 times more in comparison with low-risk studies (RR, 0.96; 95% CI, 0.56-1.66). This highlights the need for rigorous quality assessments, for authors to share patient-level data, and for efforts to avoid publication bias for registered studies. These steps are vital to facilitate accurate conclusions on clinical treatments.
Project description:Most but not all observational studies of statin treatment of COVID-19 patients suggest that treatment improves outcomes. However, almost all of these studies fail to consider that withdrawing statins after hospital admission may have detrimental effects, a finding which cardiovascular investigators have known for 15-20 years. Continuing or starting statin treatment after hospital admission consistently improves cardiovascular outcomes. Similarly, inpatient statin treatment of COVID-19 improves survival. For this reason, observational studies of the effectiveness of outpatient-documented statin treatment of COVID-19 patients must consider the negative consequences of statin withdrawal after hospital admission.
Project description:INTRODUCTION: Infections can impact the reproductive health of women and hence may influence pregnancy related outcomes for both the mother and the child. These infections range from sexually transmitted infections (STIs) to TORCHS infections to periodontal disease to systemic infections and may be transmitted to the fetus during pregnancy, labor, delivery or breastfeeding. METHODS: A systematic review and meta-analysis of the evidence was conducted to ascertain the possible impact of preconception care for adolescents, women and couples of reproductive age on MNCH outcomes. A comprehensive strategy was used to search electronic reference libraries, and both observational and clinical controlled trials were included. Cross-referencing and a separate search strategy for each preconception risk and intervention ensured wider study capture. RESULTS: Preconception behavioral interventions significantly declines re-infection or new STI rates by 35% (95% CI: 20-47%). Further, condom use has been shown to be the most effective way to prevent HIV infection (85% protection in prospective studies) through sexual intercourse. Intervention trials showed that preconception vaccination against tetanus averted a significant number of neonatal deaths (including those specifically due to tetanus) when compared to placebo in women receiving more than 1 dose of the vaccine (OR 0.28; 95% CI: 0.15-0.52); (OR 0.02; 95% CI: 0.00-0.28) respectively. CONCLUSION: Preconception counseling should be offered to women of reproductive age as soon as they test HIV-positive, and conversely women of reproductive age should be screened with their partners before pregnancy. Risk assessment, screening, and treatment for specific infections should be a component of preconception care because there is convincing evidence that treatment of these infections before pregnancy prevents neonatal infections.