Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 190
Filter
1.
Embase; 2021.
Preprint in English | EMBASE | ID: ppcovidwho-336111

ABSTRACT

Objective: We quantified changes in dispensing of common medicines proposed for “repurposing” due to their perceived benefits as therapeutic or preventive for COVID-19 in Australia, a country with relatively low COVID-19 incidence in the first year of the pandemic. Methods: We performed an interrupted time series analysis and cross-sectional study using nationwide dispensing claims data (January 2017-November 2020). We focused on six subsidised medicines proposed for re-purposing: hydroxychloroquine, azithromycin, ivermectin, colchicine, corticosteroids, and calcitriol (Vitamin D analogue). We quantified changes in monthly dispensing and initiation trends during COVID-19 (March-November 2020) using autoregressive integrated moving average models (ARIMA) and compared characteristics of initiators in 2020 and 2019. Results: In March 2020, we observed a 99% (95%CI 96%-103%) increase in hydroxychloroquine dispensing (of which approximately 22% attributable to new use), and a 199% increase (95%CI 184%-213%) in initiation, with a shift towards prescribing by general practitioners (42% in 2020 vs 25% in 2019) rather than specialists. These increases subsided following regulatory restrictions on prescribing to relevant specialties. There was a small but sustained increase in ivermectin dispensing over multiple months, with a 80% (95%CI 42%-118%) increase in initiation in May 2020 following its first identification as potentially disease-modifying in April. Other than increases in March related to stockpiling, we observed no increases in initiation of calcitriol or colchicine during COVID-19. Dispensing of corticosteroids and azithromycin remained lower than expected in April through November 2020. Conclusions: While most increases in dispensing observed early on during COVID-19 were temporary and appear to be related to stockpiling among existing users, we did observed increases in initiation of hydroxychloroquine and ivermectin and a shift in prescribing patterns which may be related to media hype around these medicines. A quick response by regulators can help limit inappropriate repurposing to lessen the impact on medicine supply and patient harms.

2.
Int J Pharm ; 619: 121719, 2022 May 10.
Article in English | MEDLINE | ID: covidwho-1838891

ABSTRACT

Recent studies have demonstrated that ivermectin (IVM) exhibits antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus of coronavirus disease 2019 (COVID-19). However, the repurposing of IVM for the treatment of COVID-19 has presented challenges primarily due to the low IVM plasma concentration after oral administration, which was well below IC50. Here, a red blood cell (RBC)-hitchhiking strategy was used for the targeted delivery of IVM-loaded nanoparticles (NPs) to the lung. IVM-loaded poly (lactic-co-glycolic acid) (PLGA) NPs (IVM-PNPs) and chitosan-coating IVM-PNPs (IVM-CSPNPs) were prepared and adsorbed onto RBCs. Both RBC-hitchhiked IVM-PNPs and IVM-CSPNPs could significantly enhance IVM delivery to lungs, improve IVM accumulation in lung tissue, inhibit the inflammatory responses and finally significantly alleviate the progression of acute lung injury. Specifically, the redistribution and circulation effects were related to the properties of NPs. RBC-hitchhiked cationic IVM-CSPNPs showed a longer circulation time, slower accumulation and elimination rates, and higher anti-inflammatory activities than RBC-hitchhiked anionic IVM-PNPs. Therefore, RBC-hitchhiking provides an alternative strategy to improve IVM pharmacokinetics and bioavailability for repurposing of IVM to treat COVID-19. Furthermore, according to different redistribution effects of different NPs, RBC-hitchhiked NPs may achieve various accumulation rates and circulation times for different requirements of drug delivery.


Subject(s)
COVID-19 , Nanoparticles , COVID-19/drug therapy , Erythrocytes , Humans , Ivermectin , Lung , SARS-CoV-2
3.
Bmj ; 377, 2022.
Article in English | ProQuest Central | ID: covidwho-1832404

ABSTRACT

In one damning example, participants in unethical studies of ivermectin were exposed to its side effects without knowing that they were given the drug (doi:10.1136/bmj.o917).1 Covid was also a free pass to tighten, loosen, or avoid public health measures, with little consultation or input from the public. [...]a terminally ill patient might wish for assisted death, but their doctor might disagree (doi:10.1136/bmj.o1014).3 Or a woman might decline the offer of sodium valproate in pregnancy if sufficiently aware of the risk of birth defects (doi:10.1136/bmj.o1013).4 The BMJ has attempted to bridge these gaps in perspective and information by appointing patient editors. Caitríona Cox and Zoë Fritz explain, with examples, how “some commonly used language confers petulance on patients, renders them passive, or blames them for poor outcomes” (doi:10.1136/bmj-2021-066720).7 To most clinicians, phrases such as “presenting complaint” and descriptions of patients “denying chest pain” are empty jargon, holding no more than functional meaning.

4.
Clin Toxicol (Phila) ; : 1-5, 2022 May 10.
Article in English | MEDLINE | ID: covidwho-1830818

ABSTRACT

BACKGROUND: In August 2021, the Centers for Disease Control and Prevention (CDC) released a health alert following the rapid increase in ivermectin prescriptions and reports of severe illness associated with use of products containing ivermectin for the prevention or treatment of COVID-19 infections. The United States Food and Drug Administration (FDA) and the CDC have explicitly discouraged the use of ivermectin in the prevention or treatment of COVID-19 outside of clinical trials. The study aims to describe the adverse events (AEs) related to ivermectin use for the prevention or treatment of COVID-19. METHODS: This is a prospective case series of adverse events related to therapeutics used in the prevention or treatment of COVID-19 submitted to the FDA ACMT COVID-19 ToxIC (FACT) Pharmacovigilance Project sub-registry between October 2020 and December 2021. This is an ongoing toxico-surveillance system at 15 major academic medical centers in 12 states. Data collected included sociodemographics, exposure related information including dose, frequency, route, duration, and reason for taking ivermectin as well as a clinical description of the adverse event and the outcome. RESULTS: A total of 40 patients who developed AEs following ivermectin use were reported to FACT over 15 months. Self-medication with veterinary formulations were reported in 18/40 patients Thirty-three patients presented to emergency departments and nineteen patients were admitted to the hospital. Patients reported using ivermectin for prevention (24/40), treatment of symptoms (19/40), and for treatment of documented COVID-19 (8/40). Neurological toxicity was the most frequent finding. Fifteen patients had minor symptoms while 25 developed severe toxicity. CONCLUSIONS: Ivermectin use for the attempted treatment of COVID-19 has potential adverse health effects primarily related to neurological function. This is especially true when patients are self-treating with this medication and when they are using formulations intended for non-human use.

5.
Revista Cubana de Farmacia ; 55(1), 2022.
Article in Spanish | EMBASE | ID: covidwho-1820621

ABSTRACT

Introduction: The university population may be vulnerable to self-medication due to COVID-19 due to their greater exposure to social networks and their tendency to imitate self-medication practices of their social environment. Objective: Assess the characteristics and factors associated with self-medication due to COVID-19 in undergraduate university students of a Peruvian university. Methods: An analytical cross-sectional study (October 1st to November 14, 2020) in which 166 surveys were analyzed among students of the National University of Central Peru selected through a probabilistic sampling stratified by faculties. The factors associated with self-medication were evaluated by Poisson regression of robust variances, in this way the prevalence ratios and corresponding confidence intervals were obtained. Results: 14.5% of the students self-medicated due to COVID-19 and the main reasons were sore throat (45.8%), fever (37.5%) and disease prevention (29.2%). The most commonly used drugs were paracetamol (70.8%), aspirin (62.5%) and influenza drugs (62.5%). Some participants (20.8%) reported experiencing side effects after taking medications such as aspirin, ivermectin, dexamethasone, and chlorine dioxide. The perception that self-medication is harmful to health (PR: 0.41;CI: 0.20-0.84) and having doctors as a source of drug information (PR: 0.46;CI: 0.21-0.99) were associated with self-medication due to COVID-19. Approximately 15 out of every 100 students in the studied population self-medicated due to COVID-19. Likewise, those who perceived self-medication as harmful to health and who had doctors as a source of drug information self-medicated less. Conclusions: The results allow us to characterize the problem of self-medication due to COVID-19 in university students, while offering information for the approach of strategies that reduce its negative impact.

6.
Computation ; 10(4):25, 2022.
Article in English | Web of Science | ID: covidwho-1820189

ABSTRACT

Some clinical studies have indicated activity of ivermectin, a macrocyclic lactone, against COVID-19, but a biological mechanism initially proposed for this anti-viral effect is not applicable at physiological concentrations. This in silico investigation explores potential modes of action of ivermectin and 14 related compounds, by which the infectivity and morbidity of the SARS-CoV-2 virus may be limited. Binding affinity computations were performed for these agents on several docking sites each for models of (1) the spike glycoprotein of the virus, (2) the CD147 receptor, which has been identified as a secondary attachment point for the virus, and (3) the alpha-7 nicotinic acetylcholine receptor (alpha 7nAChr), an indicated point of viral penetration of neuronal tissue as well as an activation site for the cholinergic anti-inflammatory pathway controlled by the vagus nerve. Binding affinities were calculated for these multiple docking sites and binding modes of each compound. Our results indicate the high affinity of ivermectin, and even higher affinities for some of the other compounds evaluated, for all three of these molecular targets. These results suggest biological mechanisms by which ivermectin may limit the infectivity and morbidity of the SARS-CoV-2 virus and stimulate an alpha 7nAChr-mediated anti-inflammatory pathway that could limit cytokine production by immune cells.

7.
J Dermatol ; 2022 Apr 27.
Article in English | MEDLINE | ID: covidwho-1816488

ABSTRACT

Despite poor evidence, the antiparasitic ivermectin has been advocated as a potential COVID-19 therapy. This has led to a rise in calls to poison-control centers by people self-medicating with ivermectin, which is sold over the counter for veterinary uses. We aimed to investigate the association between severe cutaneous adverse reactions (SCARs) and ivermectin. Postmarketing data from the FDA Adverse Event Reporting System (FAERS), gathered between 2014 and 2021, was employed to detect disproportional signals of SCARs following systemic ivermectin therapy. The reporting odds ratio (ROR) was used to quantify the strength of association, while adjusting for age, sex, and region. The search yielded 517 reports of systemic ivermectin (median age 54 years, 46.8% female), of which 25 (4.8%), 81 (15.7%), and 411 (79.5%) were classified as SCARs, nonsevere cutaneous adverse events (AEs), or noncutaneous AEs, respectively. The regional distribution differed between SCAR reports (32.0% from Africa and 12.0% from North America) compared with other AEs, which originated from North America in over half of cases. The most common SCARs were toxic epidermal necrolysis (seven cases), Stevens-Johnson syndrome (seven cases), and drug reaction with eosinophilia and systemic symptoms (four cases). Five SCAR cases (20.0%) resulted in death and 12 (48.0%) lead to hospitalization. There was a strong safety signal for any SCAR (adjusted ROR 3.34, 95% confidence interval [CI] 2.17-5.12) and toxidermias (adjusted ROR 7.08, 95% CI 4.23-11.84). This study suggests that ivermectin is associated with SCARs on rare occasions. Dermatologists should be aware of this given the increase in ivermectin misuse.

8.
J Biomol Struct Dyn ; : 1-14, 2022 Apr 26.
Article in English | MEDLINE | ID: covidwho-1805903

ABSTRACT

Ivermectin is an antiparasitic drug that results in the death of the targeted parasites using several mechanical actions. While very well supported, it can induce in rare cases, adverse effects including coma and respiratory failure in case of overdose. This problem should be solved especially in an emergency situation. For instance, the first pandemic of the 21th century was officially declared in early 2020, and while several vaccines around the worlds have been used, an effective treatment against this new strain of coronavirus, better known as SARS-CoV-2, should also be considered, especially given the massive appearance of variants. From all the tested therapies, Ivermectin showed a potential reduction of the viral portability, but sparked significant debate around the dose needed to achieve these positive results. To answer this general question, we propose, using simulations, to show that the nanovectorization of Ivermectin on BN oxide nanosheets can increase the transfer of the drug to its target and thus decrease the quantity of drug necessary to cope with the disease. This first application could help science to develop such nanocargo to avoid adverse effects.Communicated by Ramaswamy H. Sarma.

9.
Front Public Health ; 10: 788972, 2022.
Article in English | MEDLINE | ID: covidwho-1798916

ABSTRACT

The COVID-19 pandemic has been characterized by a lack of clear evidence to guide healthcare professionals, the public and policymakers. The resulting uncertainty, coupled with changing guidelines as additional evidence became available, added to the stress and anxiety reported by decision-makers. Research results are key to providing evidence to guide healthcare decisions. Important questions have arisen about whether various interventions are safe and effective. The evidence found guides those making treatment decisions, and influences those selecting interventions for further evaluation in research studies. As the COVID-19 pandemic intensified, the effectiveness and safety of many pharmaceuticals was queried. Ivermectin will be used to explore the ethics of how healthcare evidence must be critically appraised, even, or especially, during a pandemic. This drug is alleged to be effective in treating COVID-19, with various studies and systematic reviews finding supportive evidence. Some of these have now been linked to concerns about fraud or poor research reporting. This article will focus on the scientific literature and how apparently fraudulent studies were published and influenced treatment decisions, on-going research and public health guidelines. Research evidence is critical during emergencies like pandemics, but urgency should not overtake ethical responsibilities to critically appraise (or evaluate) studies as they become available. These responsibilities apply in various ways to editors, peer-reviewers, news media reporters, and those making treatment decisions, including clinicians, policymakers and the general public. While research article authors have the primary ethical responsibility to reject fraudulent or inaccurate claims, the readers of health research must carefully evaluate all publications. To detect and reject fraudulent healthcare claims, readers need critical appraisal skills that match their level of engagement with those articles. The core principles of critical appraisal will be described in the article, and how they can be adapted for different types of readers. Exemplar tools that develop critical appraisal skills will be noted, with reviews of ivermectin's efficacy explored as examples. As stakeholders in healthcare evidence are increasingly able to identify well-conducted and ethical research they will simultaneously be able to spot and reject fraudulent reports and prevent them from influencing healthcare decisions.


Subject(s)
COVID-19 , Ivermectin , COVID-19/drug therapy , Decision Making , Delivery of Health Care , Humans , Ivermectin/therapeutic use , Pandemics
11.
Non-conventional in English | WHOIRIS, Grey literature | ID: grc-754192
12.
Antibiotics (Basel) ; 11(4)2022 Mar 25.
Article in English | MEDLINE | ID: covidwho-1792851

ABSTRACT

The capacity for social media to influence the utilization of re-purposed medicines to manage COVID-19, despite limited availability of safety and efficacy data, is a cause for concern within health care systems. This study sought to ascertain links between social media reports and utilization for three re-purposed medicines: hydroxychloroquine (HCQ), ivermectin and colchicine. A combined retrospective analysis of social media posts for these three re-purposed medicines was undertaken, along with utilization and clinical trials data, in South Africa, between January 2020 and June 2021. In total, 77,257 posts were collected across key social media platforms, of which 6884 were relevant. Ivermectin had the highest number of posts (55%) followed by HCQ (44%). The spike in ivermectin use was closely correlated to social media posts. Similarly, regarding chloroquine (as HCQ is not available in South Africa), social media interest was enhanced by local politicians. Sentiment analysis revealed that posts regarding the effectiveness of these repurposed medicines were positive. This was different for colchicine, which contributed only a small number of mentions (1%). Of concern is that the majority of reporters in social media (85%) were unidentifiable. This study provides evidence of social media as a driver of re-purposed medicines. Healthcare professionals have a key role in providing evidence-based advice especially with unidentifiable posts.

13.
Plant Archives ; 21(2):533-541, 2021.
Article in English | GIM | ID: covidwho-1791230

ABSTRACT

At the end of 2019 in December, a bunch of deadly pneumonia cases were found in Huanan sea food market in city of Wuhan in Hubei province, china. They were caused by a previously unknown corona virus. All patients had been associated with the Wuhan Whole food market, where seafood and live animals are sold. The virus spread at an alarming speed and lead authorities in China to initiate effort and investigation. However, by that time, the great row of travelers had carried the virus to many countries, sparking memories of the previous corona virus epidemics, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and causing widespread media attention and panic. Based on clinical criteria and available serological and molecular information, the new disease was called corona virus disease of 2019 (COVID-19), and the novel corona virus was called SARS Corona virus -2 (SARS-CoV-2), emphasizing its close relationship to the 2002 SARS virus (SARS-CoV). The scientific community raced to uncover the origin of the virus, understand the pathogenesis of the disease, develop treatment options, define the risk factors, and work on vaccine development. In this manuscript we portray the causes, mechanisms and possible treatments for corona virus.

14.
Rev. Univ. Soc. ; 14:479-487, 2022.
Article in Spanish | Web of Science | ID: covidwho-1790305

ABSTRACT

Through a literature review in high impact journals, it was determined that ivermectin, besides being a drug widely recognized for its ability to treat and control parasitic infections, has several relevant clinical actions, such as the possibility of eradicating onchocerciasis or "river blindness", considering this fact as a triumph of humanity by the WHO in 2009. The broadspectrum antiviral potential of this drug against a variety of RNA viruses is raised, due to its ability to specifically inhibit nuclear transport mediated by alpha / beta importin, capable of blocking nuclear trafficking of viral proteins. The proposed anti-SARS-CoV-2 action of ivermectin involves its binding to the IMP alpha / beta 1 heterodimer that will bind to the coronavirus cargo protein causing the viral load to reduce the antiviral response of the host cell, improving the clinical conditions of the patient. Several clinical trials of the use of ivermectin in relation to COVID-19 have shown that this drug could produce a slight improvement in its symptomatology, so this literature review aims to determine the pharmacokinetics and adverse effects of ivermectin, as a possible treatment of SARS-CoV-2.

15.
Indian Journal of Pharmaceutical Sciences ; 84:87-91, 2022.
Article in English | Scopus | ID: covidwho-1789980

ABSTRACT

Ivermectin is widely prescribed as a potential treatment for coronavirus disease 2019, despite uncertainty about its clinical benefit. To determine whether ivermectin is an efficacious treatment for mild coronavirus disease 2019 is the objective of the study. A total of 476 adult patients with mild symptoms for 7 d or fewer in Jinan, China, were enrolled and followed up. Patients were randomly selected to receive ivermectin, 300 μg/kg body weight per day for 5 d or placebo. The median time to resolution of symptoms was 10 d (interquartile range, 9-13) in the ivermectin group whereas it was 12 d (interquartile range, 9-13) in the placebo group (hazard ratio for resolution of symptoms, 1.07 [95 % confidence interval, 0.87 to 1.32];p=0.53 by log-rank test). By d 21, 82 % in the ivermectin group and 79 % in the placebo group had resolved symptoms. The most common solicited adverse event was headache, reported by 104 patients (52 %) who received ivermectin and 111 patients (56 %) who received placebo. The most serious adverse event was multiorgan failure. Among adults with mild coronavirus disease 2019, a 5 d course of ivermectin, compared with placebo, did not significantly improve the time to resolution of symptoms. The findings do not support the use of ivermectin for treatment of mild coronavirus disease 2019. © 2022 Indian Pharmaceutical Association. All rights reserved.

16.
Lung ; 200(2): 141-148, 2022 04.
Article in English | MEDLINE | ID: covidwho-1782799

ABSTRACT

Strongyloidiasis has been estimated to affect over 600 million people worldwide. It is caused by Strongyloides stercoralis, a roundworm endemic to the tropics and subtropics, especially areas where sanitation is suboptimal Autochthonous transmission has been documented in rural areas of the USA and Europe. Humans are infected when larvae penetrate the skin or are ingested. Autoinfection, in which larvae generated in the host go on to re-infect the host, leads to a state of chronic asymptomatic infection often with eosinophilia. Hyperinfection syndrome may develop when patients develop immune suppression, due to medications such as corticosteroids or following solid-organ transplantation. Hyperinfection is characterized by exponential increase in parasitic burden, leading to tissue invasion and life-threatening disease and associated bloodstream infections due to enteric organisms. Cases following use of corticosteroids for COVID-19 pneumonia have been described. Strongyloidiasis can be diagnosed by direct visualization of larvae in stool or other body fluids, or by serology. Ivermectin is highly effective in treating the disease. Patients with exposure to endemic areas and those expected to become immune suppressed should be screened and treated before starting immune suppressive agents. Empiric treatment should be considered when timely testing is not readily available.


Subject(s)
COVID-19 , Eosinophilia , Sepsis , Strongyloides stercoralis , Strongyloidiasis , Animals , Eosinophilia/complications , Humans , Sepsis/complications , Strongyloidiasis/complications , Strongyloidiasis/diagnosis , Strongyloidiasis/drug therapy
17.
Pharmaceuticals (Basel) ; 15(4)2022 Apr 02.
Article in English | MEDLINE | ID: covidwho-1776312

ABSTRACT

Over the past two years, several variants of SARS-CoV-2 have emerged and spread all over the world. However, infectivity, clinical severity, re-infection, virulence, transmissibility, vaccine responses and escape, and epidemiological aspects have differed between SARS-CoV-2 variants. Currently, very few treatments are recommended against SARS-CoV-2. Identification of effective drugs among repurposing FDA-approved drugs is a rapid, efficient and low-cost strategy against SARS-CoV-2. One of those drugs is ivermectin. Ivermectin is an antihelminthic agent that previously showed in vitro effects against a SARS-CoV-2 isolate (Australia/VI01/2020 isolate) with an IC50 of around 2 µM. We evaluated the in vitro activity of ivermectin on Vero E6 cells infected with 30 clinically isolated SARS-CoV-2 strains belonging to 14 different variants, and particularly 17 strains belonging to six variants of concern (VOC) (variants related to Wuhan, alpha, beta, gamma, delta and omicron). The in vitro activity of ivermectin was compared to those of chloroquine and remdesivir. Unlike chloroquine (EC50 from 4.3 ± 2.5 to 29.3 ± 5.2 µM) or remdesivir (EC50 from 0.4 ± 0.3 to 25.2 ± 9.4 µM), ivermectin showed a relatively homogeneous in vitro activity against SARS-CoV-2 regardless of the strains or variants (EC50 from 5.1 ± 0.5 to 6.7 ± 0.4 µM), except for one omicron strain (EC50 = 1.3 ± 0.5 µM). Ivermectin (No. EC50 = 219, mean EC50 = 5.7 ± 1.0 µM) was, overall, more potent in vitro than chloroquine (No. EC50 = 214, mean EC50 = 16.1 ± 9.0 µM) (p = 1.3 × 10-34) and remdesivir (No. EC50 = 201, mean EC50 = 11.9 ± 10.0 µM) (p = 1.6 × 10-13). These results should be interpreted with caution regarding the potential use of ivermectin in SARS-CoV-2-infected patients: it is difficult to translate in vitro study results into actual clinical treatment in patients.

18.
Pharmacol Res ; 179: 106201, 2022 May.
Article in English | MEDLINE | ID: covidwho-1768452

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic had grounded the world to a standstill. As the disease continues to rage two years on, it is apparent that effective therapeutics are critical for a successful endemic living with COVID-19. A dearth in suitable antivirals has prompted researchers and healthcare professionals to investigate existing and developmental drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although some of these drugs initially appeared to be promising for the treatment of COVID-19, they were ultimately found to be ineffective. In this review, we provide a retrospective analysis on the merits and limitations of some of these drugs that were tested against SARS-CoV-2 as well as those used for adjuvant therapy. While many of these drugs are no longer part of our arsenal for the treatment of COVID-19, important lessons can be learnt. The recent inclusion of molnupiravir and Paxlovid™ as treatment options for COVID-19 represent our best hope to date for endemic living with COVID-19. Our viewpoints on these two drugs and their prospects as current and future antiviral agents will also be provided.

19.
Cureus ; 14(1): e21272, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1766138

ABSTRACT

BACKGROUND: Ivermectin has demonstrated different mechanisms of action that potentially protect from both coronavirus disease 2019 (COVID-19) infection and COVID-19-related comorbidities. Based on the studies suggesting efficacy in prophylaxis combined with the known safety profile of ivermectin, a citywide prevention program using ivermectin for COVID-19 was implemented in Itajaí, a southern city in Brazil in the state of Santa Catarina. The objective of this study was to evaluate the impact of regular ivermectin use on subsequent COVID-19 infection and mortality rates. MATERIALS AND METHODS: We analyzed data from a prospective, observational study of the citywide COVID-19 prevention with ivermectin program, which was conducted between July 2020 and December 2020 in Itajaí, Brazil. Study design, institutional review board approval, and analysis of registry data occurred after completion of the program. The program consisted of inviting the entire population of Itajaí to a medical visit to enroll in the program and to compile baseline, personal, demographic, and medical information. In the absence of contraindications, ivermectin was offered as an optional treatment to be taken for two consecutive days every 15 days at a dose of 0.2 mg/kg/day. In cases where a participating citizen of Itajaí became ill with COVID-19, they were recommended not to use ivermectin or any other medication in early outpatient treatment. Clinical outcomes of infection, hospitalization, and death were automatically reported and entered into the registry in real time. Study analysis consisted of comparing ivermectin users with non-users using cohorts of infected patients propensity score-matched by age, sex, and comorbidities. COVID-19 infection and mortality rates were analyzed with and without the use of propensity score matching (PSM). RESULTS: Of the 223,128 citizens of Itajaí considered for the study, a total of 159,561 subjects were included in the analysis: 113,845 (71.3%) regular ivermectin users and 45,716 (23.3%) non-users. Of these, 4,311 ivermectin users were infected, among which 4,197 were from the city of Itajaí (3.7% infection rate), and 3,034 non-users (from Itajaí) were infected (6.6% infection rate), with a 44% reduction in COVID-19 infection rate (risk ratio [RR], 0.56; 95% confidence interval (95% CI), 0.53-0.58; p < 0.0001). Using PSM, two cohorts of 3,034 subjects suffering from COVID-19 infection were compared. The regular use of ivermectin led to a 68% reduction in COVID-19 mortality (25 [0.8%] versus 79 [2.6%] among ivermectin non-users; RR, 0.32; 95% CI, 0.20-0.49; p < 0.0001). When adjusted for residual variables, reduction in mortality rate was 70% (RR, 0.30; 95% CI, 0.19-0.46; p < 0.0001). There was a 56% reduction in hospitalization rate (44 versus 99 hospitalizations among ivermectin users and non-users, respectively; RR, 0.44; 95% CI, 0.31-0.63; p < 0.0001). After adjustment for residual variables, reduction in hospitalization rate was 67% (RR, 0.33; 95% CI, 023-0.66; p < 0.0001). CONCLUSION: In this large PSM study, regular use of ivermectin as a prophylactic agent was associated with significantly reduced COVID-19 infection, hospitalization, and mortality rates.

20.
J Infect Public Health ; 15(5): 566-572, 2022 May.
Article in English | MEDLINE | ID: covidwho-1763843

ABSTRACT

An unprecedented global health crisis has developed due to the emergence of the mysterious coronavirus-2 of the severe acute respiratory syndrome, which has resulted in millions of deaths around the globe, as no therapy could control the 'cytokine storm'. Consequently, many vaccines have been developed and several others are being developed for this infection. Although most of the approved vaccines have been highly effective, many developing, and economically poor countries are still deprived of vaccination against SARS-CoV-2 due to the unequal distribution of vaccines worldwide. Furthermore, the uncertainty about the effectiveness of the available vaccines against the emerging mutants and variants also remains a matter of concern. Due to the multistep pathogenesis and unique features, combination therapy using safe immunomodulatory and antiviral drugs should be considered as the most effective and acceptable therapeutic regimen for this infection. Based on a thorough assessment of the literature, it was determined that it would be interesting to study the therapeutic potential of ivermectin and doxycycline, given their roles in several biological pathways involved in SARS CoV-2 pathogenesis. Following that, a comprehensive literature search was undertaken using Scopus, Web of Science, and Pubmed, depending on the inclusion and exclusion criteria. The present study provides a mechanism and comprehensive report, highlighting the role of combined therapy with ivermectin and doxycycline in alleviating the 'cytokine storm' of COVID-19 infection.


Subject(s)
COVID-19 , Cytokine Release Syndrome , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/prevention & control , Doxycycline/therapeutic use , Humans , Ivermectin/therapeutic use , SARS-CoV-2 , Vaccination
SELECTION OF CITATIONS
SEARCH DETAIL