Death from COVID-19 of a 57-year-old man refusing medical care and self-medicating with ivermectin.

Since December 2019, the new SARS-CoV-2 coronavirus causes COVID-19 disease worldwide, which occurs mainly in unvaccinated elderly and polymorbid patients with a more severe course and increased risk of complications and death. Vaccination and specific therapy for the disease using mainly new antiviral drugs are the way to reduce the number of infected, hospitalized patients with a more severe course. We present a case report of an at-risk polymorbid 57-year-old man who refused vaccination and standard treatment for COVID-19 disease based on misinformation from the community. He self-treated himself with high dose of ivermectin. The patient died at home 14 days after the onset of symptoms.

The political polarization of COVID-19 treatments among physicians and laypeople in the United States.

In the United States, liberals and conservatives disagree about facts. To what extent does expertise attenuate these disagreements? To study this question, we compare the polarization of beliefs about COVID-19 treatments among laypeople and critical care physicians. We find that political ideology predicts both groups' beliefs about a range of COVID-19 treatments. These associations persist after controlling for a rich set of covariates, including local politics. We study two potential explanations: a) that partisans are exposed to different information and b) that they interpret the same information in different ways, finding evidence for both. Polarization is driven by preferences for partisan cable news but not by exposure to scientific research. Using a set of embedded experiments, we demonstrate that partisans perceive scientific evidence differently when it pertains to a politicized treatment (ivermectin), relative to when the treatment is not identified. These results highlight the extent to which political ideology is increasingly relevant for understanding beliefs, even among expert decision makers such as physicians.

COVID-19 Therapeutics: Use, Mechanism of Action, and Toxicity (Xenobiotics).

SARS-CoV-2 emerged in 2019 and led to the COVID-19 pandemic. Efforts to develop therapeutics against SARS-Cov-2 led to both new treatments and attempts to repurpose existing medications. Here, we provide a narrative review of the xenobiotics and alternative remedies used or proposed to treat COVID-19. Most repositioned xenobiotics have had neither the feared toxicity nor the anticipated efficacy. Repurposed viral replication inhibitors are not efficacious and frequently associated with nausea, vomiting, and diarrhea. Antiviral medications designed specifically against SARS-CoV-2 may prevent progression to severe disease in at-risk individuals and appear to have a wide therapeutic index. Colloidal silver, zinc, and ivermectin have no demonstrated efficacy. Ivermectin has a wide therapeutic index but is not efficacious and acquiring it from veterinary sources poses additional danger. Chloroquine has a narrow therapeutic index and no efficacy. A companion review covers vaccines, monoclonal antibodies, and immunotherapies. Together, these two reviews form an update to our 2020 review.

Ivermectin as a possible treatment for COVID-19: a review of the 2022 protocols.

Ivermectin is a safe and effective drug in humans and has been approved for use in numerous parasitic infections for over 50 years. In addition, many studies have already shown its antiviral activity. Ivermectin is generally well tolerated, with no indication of central nervous system-associated toxicity at doses up to 10 times the highest FDA-approved dose of 200 µg/kg. The in vitro results of ivermectin for reducing SARS-CoV-2 viral load are promising and show that Ivermectin kills SARS-CoV-2 within 48 hours. A hypothesized mechanism of action for this drug is a likely inhibition of IMPα/ß1-mediated nuclear import of viral proteins as demonstrated for other RNA viruses. However, controlled and randomized studies are needed to prove its effectiveness in COVID-19 in humans. In a single in vivo study with published results, patients confirmed to be infected with SARS-CoV-2 received at least one dose of ivermectin at any time during hospitalization. The use of ivermectin was associated with lower mortality during treatment with COVID-19, especially in patients who required increased inspired oxygen or ventilatory support. Additionally, 81 studies with the clinical use of ivermectin in humans are being carried out worldwide according to ClinicalTrials.gov. However, none of these data has been published so far. However, private and public entities in Brazil have been adopting this drug in their protocols as prophylaxis and in the initial phase of the disease. In addition, ivermectin has been used in mass treatment to prevent onchocerciasis and lymphatic filariasis in sub-Saharan Africa for many years. Surprisingly, this region has the lowest proportional mortality rate among the continents, despite the increasing numbers of infected people released by the World Health Organization.

Death from COVID-19 of a 57-year-old man refusing medical care and self-medicating with ivermectin.

Since December 2019, the new SARS-CoV-2 coronavirus causes COVID-19 disease worldwide, which occurs mainly in unvaccinated elderly and polymorbid patients with a more severe course and increased risk of complications and death. Vaccination and specific therapy for the disease using mainly new antiviral drugs are the way to reduce the number of infected, hospitalized patients with a more severe course. We present a case report of an at-risk polymorbid 57-year-old man who refused vaccination and standard treatment for COVID-19 disease based on misinformation from the community. He self-treated himself with high dose of ivermectin. The patient died at home 14 days after the onset of symptoms.

Dispensing of Ivermectin From Veterans Administration Pharmacies During the COVID-19 Pandemic.

This cohort study compares changes in ivermectin dispensing during the COVID-19 pandemic between the Veterans Administration (VA) and retail pharmacy settings and examines the association of the VA national formulary restriction with ivermectin dispensing.

COVID-19 Therapeutics: Use, Mechanism of Action, and Toxicity (Xenobiotics).

SARS-CoV-2 emerged in 2019 and led to the COVID-19 pandemic. Efforts to develop therapeutics against SARS-Cov-2 led to both new treatments and attempts to repurpose existing medications. Here, we provide a narrative review of the xenobiotics and alternative remedies used or proposed to treat COVID-19. Most repositioned xenobiotics have had neither the feared toxicity nor the anticipated efficacy. Repurposed viral replication inhibitors are not efficacious and frequently associated with nausea, vomiting, and diarrhea. Antiviral medications designed specifically against SARS-CoV-2 may prevent progression to severe disease in at-risk individuals and appear to have a wide therapeutic index. Colloidal silver, zinc, and ivermectin have no demonstrated efficacy. Ivermectin has a wide therapeutic index but is not efficacious and acquiring it from veterinary sources poses additional danger. Chloroquine has a narrow therapeutic index and no efficacy. A companion review covers vaccines, monoclonal antibodies, and immunotherapies. Together, these two reviews form an update to our 2020 review.

A cellular and molecular biology-based update for ivermectin against COVID-19: is it effective or non-effective?

Despite community vaccination against coronavirus disease 2019 (COVID-19) and reduced mortality, there are still challenges in treatment options for the disease. Due to the continuous mutation of SARS-CoV-2 virus and the emergence of new strains, diversity in the use of existing antiviral drugs to combat the epidemic has become a crucial therapeutic chance. As a broad-spectrum antiparasitic and antiviral drug, ivermectin has traditionally been used to treat many types of disease, including DNA and RNA viral infections. Even so, based on currently available data, it is still controversial that ivermectin can be used as one of the effective antiviral agents to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or not. The aim of this study was to provide comprehensive information on ivermectin, including its safety and efficacy, as well as its adverse effects in the treatment of COVID-19.

Is the antiparasitic drug ivermectin a suitable candidate for the treatment of epilepsy?

There are only a few drugs that can seriously lay claim to the title of "wonder drug," and ivermectin, the world's first endectocide and forerunner of a completely new class of antiparasitic agents, is among them. Ivermectin, a mixture of two macrolytic lactone derivatives (avermectin B1a and B1b in a ratio of 80:20), exerts its highly potent antiparasitic effect by activating the glutamate-gated chloride channel, which is absent in vertebrate species. However, in mammals, ivermectin activates several other Cys-loop receptors, including the inhibitory γ-aminobutyric acid type A and glycine receptors and the excitatory nicotinic acetylcholine receptor of brain neurons. Based on these effects on vertebrate receptors, ivermectin has recently been proposed to constitute a multifaceted wonder drug for various novel neurological indications, including alcohol use disorders, motor neuron diseases, and epilepsy. This review critically discusses the preclinical and clinical evidence of antiseizure effects of ivermectin and provides several arguments supporting that ivermectin is not a suitable candidate drug for the treatment of epilepsy. First, ivermectin penetrates the mammalian brain poorly, so it does not exert any pharmacological effects via mammalian ligand-gated ion channels in the brain unless it is used at high, potentially toxic doses or the blood-brain barrier is functionally impaired. Second, ivermectin is not selective but activates numerous inhibitory and excitatory receptors. Third, the preclinical evidence for antiseizure effects of ivermectin is equivocal, and at least in part, median effective doses in seizure models are in the range of the median lethal dose. Fourth, the only robust clinical evidence of antiseizure effects stems from the treatment of patients with onchocerciasis, in which the reduction of seizures is due to a reduction in microfilaria densities but not a direct antiseizure effect of ivermectin. We hope that this critical analysis of available data will avert the unjustified hype associated with the recent use of ivermectin to control COVID-19 from recurring in neurological diseases such as epilepsy.

The dangers of non-randomized, observational studies: experience from the COVID-19 epidemic.

In regulatory evaluations, high-quality randomized controlled trials (RCTs) are considered the gold standard for assessing the efficacy of medical interventions. However, during the COVID-19 pandemic, the urgent need for treatment options led to regulatory approvals being made based on evidence from non-randomized, observational studies. In this study we contrast results from observational studies and RCTs of six drugs to treat COVID-19 infection. Across a range of studies evaluating hydroxychloroquine, remdesivir, ivermectin, aspirin, molnupiravir and tenofovir for COVID-19, there was statistically significant evidence of benefit from non-randomized observational studies, which was then not seen in RCTs. We propose that all observational studies need to be labelled as 'non-randomized' in the title. This should indicate that they are not as reliable for evaluating the efficacy of a drug and should not be used independently for regulatory approval decisions.

Ivermectin compared with placebo in the clinical course in Mexican patients with asymptomatic and mild COVID-19: a randomized clinical trial.

BACKGROUND: Despite the development and application of vaccines against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) around the world, the scientific community is still trying to find some therapies to avoid or ameliorate the fatal evolution of the Coronavirus disease 2019 (COVID-19). Since the publication of the potential use of ivermectin as a treatment against the disease, a pleiad of information about it has been published. However, the evidence is not strong or weak enough to conclude its usefulness in the clinical evolution of patients infected with SARS-CoV-2. We evaluate the efficacy and safety of ivermectin in the treatment of Mexican patients with asymptomatic and mild COVID-19 in a three-day administration in comparison to placebo. METHODS: A randomized, double-blind, placebo-controlled trial was carried out in 66 adults with asymptomatic and mild COVID-19. Patients were randomly assigned 1:1 ratio to ivermectin plus acetaminophen or placebo plus acetaminophen. The primary endpoint was the proportion of subjects without a disease progression to severity according to COVID-19 guidelines by the National Institutes of Health (NIH) since randomization to 14 days. RESULTS: None of the participants presented progression to a severe state in either group. Viral load was measured on Days 1, 5, and 14. No significant differences were observed in baseline or 14-day between groups (p = 0.720 and 0.362, respectively). However, on Day 5, a significant difference in viral load was observed between groups (p = 0.039). The frequency of symptoms was similar between groups, and no significant differences were observed. The most frequent symptom was cough. One severe adverse event associated with SARS-CoV-2 infection was observed in the ivermectin group. CONCLUSIONS: At standard doses, ivermectin is not effective to prevent progression to a severe state or reducing symptoms in adults with asymptomatic and mild COVID-19. Trial registration The study was registered with ClinicalTrial.gov (NCT04407507) on May 29, 2020.

A Case of Pharmaceutical Messianism Amidst the COVID-19 Pandemic: An Infodemiological Study of Ivermectin in the Philippines.

Pharmaceutical messianism is a manifestation of medical populism. It arises during extraordinary crises, is built on the familiar, endorsed by heterodox authorities, and involves a highly accessible panacea. Amid the politics and public desperation in the Philippines during the COVID-19 pandemic, pharmaceutical messianism can be observed in the form of Ivermectin, a panacea offered to prevent and treat COVID-19. Thus, it may be worthwhile to determine the changes and patterns of public interest toward Ivermectin. This infodemiological study utilized and described Search Volume Index and related queries for Ivermectin from Google Trends vis-à-vis reported societal events in the Philippines to determine changes in public interest in Ivermectin use. It revealed that a tremendous increase in public interest in Ivermectin has emerged during surges of COVID-19 cases, endorsement by politicians and heterodox health authorities, and public distribution of Ivermectin. It also showed that public interest increased as the number of component characteristics of pharmaceutical messianism increased. Search-related queries and topics also showed that the public might be using the internet to inform themselves regarding the use of Ivermectin for humans, including its use for COVID-19. These findings suggest that people may study the endorsed panacea and weigh it against conventional and orthodox treatment during rising COVID-19 cases. Thus, easily understandable, highly searchable, reliable, and trustworthy online information is ever-crucial in this age of information and disinformation.

Central Effects of Ivermectin in Alleviation of Covid-19-induced Dysauto-nomia.

Covid-19 may be associated with various neurological disorders, including dysautonomia, a dysfunction of the autonomic nervous system (ANS). In Covid-19, hypoxia, immunoinflammatory abnormality, and deregulation of the renin-angiotensin system (RAS) may increase sympathetic discharge with dysautonomia development. Direct SARS-CoV-2 cytopathic effects and associated inflammatory reaction may lead to neuroinflammation, affecting different parts of the central nervous system (CNS), including the autonomic center in the hypothalamus, causing dysautonomia. High circulating AngII, hypoxia, oxidative stress, high pro-inflammatory cytokines, and emotional stress can also provoke autonomic deregulation and high sympathetic outflow with the development of the sympathetic storm. During SARS-CoV-2 infection with neuro-invasion, GABA-ergic neurons and nicotinic acetylcholine receptor (nAChR) are inhibited in the hypothalamic pre-sympathetic neurons leading to sympathetic storm and dysautonomia. Different therapeutic modalities are applied to treat SARS-CoV-2 infection, like antiviral and anti-inflammatory drugs. Ivermectin (IVM) is a robust repurposed drug widely used to prevent and manage mild-moderate Covid-19. IVM activates both GABA-ergic neurons and nAChRs to mitigate SARS-CoV-2 infection- induced dysautonomia. Therefore, in this brief report, we try to identify the potential role of IVM in managing Covid-19-induced dysautonomia.

Effect of Ivermectin vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19: A Randomized Clinical Trial.

Importance: The effectiveness of ivermectin to shorten symptom duration or prevent hospitalization among outpatients in the US with mild to moderate symptomatic COVID-19 is unknown. Objective: To evaluate the efficacy of ivermectin, 400 µg/kg, daily for 3 days compared with placebo for the treatment of early mild to moderate COVID-19. Design, Setting, and Participants: ACTIV-6, an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial, was designed to evaluate repurposed therapies in outpatients with mild to moderate COVID-19. A total of 1591 participants aged 30 years and older with confirmed COVID-19, experiencing 2 or more symptoms of acute infection for 7 days or less, were enrolled from June 23, 2021, through February 4, 2022, with follow-up data through May 31, 2022, at 93 sites in the US. Interventions: Participants were randomized to receive ivermectin, 400 µg/kg (n = 817), daily for 3 days or placebo (n = 774). Main Outcomes and Measures: Time to sustained recovery, defined as at least 3 consecutive days without symptoms. There were 7 secondary outcomes, including a composite of hospitalization or death by day 28. Results: Among 1800 participants who were randomized (mean [SD] age, 48 [12] years; 932 women [58.6%]; 753 [47.3%] reported receiving at least 2 doses of a SARS-CoV-2 vaccine), 1591 completed the trial. The hazard ratio (HR) for improvement in time to recovery was 1.07 (95% credible interval [CrI], 0.96-1.17; posterior P value [HR >1] = .91). The median time to recovery was 12 days (IQR, 11-13) in the ivermectin group and 13 days (IQR, 12-14) in the placebo group. There were 10 hospitalizations or deaths in the ivermectin group and 9 in the placebo group (1.2% vs 1.2%; HR, 1.1 [95% CrI, 0.4-2.6]). The most common serious adverse events were COVID-19 pneumonia (ivermectin [n = 5]; placebo [n = 7]) and venous thromboembolism (ivermectin [n = 1]; placebo [n = 5]). Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with ivermectin, compared with placebo, did not significantly improve time to recovery. These findings do not support the use of ivermectin in patients with mild to moderate COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04885530.