ImportanceNo therapy to date has been shown to improve survival for patients infected with SARS-CoV-2. Ivermectin has been shown to inhibit the replication of SARS-CoV-2 in vitro but clinical response has not been previously evaluated.

ObjectiveTo determine whether Ivermectin is associated with lower mortality rate in patients hospitalized with COVID-19.

Design and SettingRetrospective cohort study of consecutive patients hospitalized at four Broward Health hospitals in South Florida with confirmed SARS-CoV-2. Enrollment dates were March 15, 2020 through May 11, 2020. Follow up data for all outcomes was May 19, 2020.

Participants280 patients with confirmed SARS-CoV-2 infection (mean age 59.6 years [standard deviation 17.9], 45.4% female), of whom 173 were treated with ivermectin and 107 were usual care were reviewed. 27 identified patients were not reviewed due to multiple admissions, lack of confirmed COVID results during hospitalization, age less than 18, pregnancy, or incarceration.

ExposurePatients were categorized into two treatment groups based on whether they received at least one dose of ivermectin at any time during the hospitalization. Treatment decisions were at the discretion of the treating physicians. Severe pulmonary involvement at study entry was characterized as need for either FiO2 [≥]50%, or noninvasive or invasive mechanical ventilation.

Main Outcomes and MeasuresThe primary outcome was all-cause in-hospital mortality. Secondary outcomes included subgroup mortality in patients with severe pulmonary involvement and extubation rates for patients requiring invasive ventilation.

ResultsUnivariate analysis showed lower mortality in the ivermectin group (15.0% versus 25.2%, OR 0.52, 95% CI 0.29-0.96, P=.03). Mortality was also lower among 75 patients with severe pulmonary disease treated with ivermectin (38.8% vs 80.7%, OR 0.15, CI 0.05-0.47, P=.001), but there was no significant difference in successful extubation rates (36.1% vs 15.4%, OR 3.11 (0.88-11.00), p=.07). After adjustment for between-group differences and mortality risks, the mortality difference remained significant for the entire cohort (OR 0.27, CI 0.09-0.85, p=.03; HR 0.37, CI 0.19-0.71, p=.03).

Conclusions and RelevanceIvermectin was associated with lower mortality during treatment of COVID-19, especially in patients who required higher inspired oxygen or ventilatory support. These findings should be further evaluated with randomized controlled trials.

Abstract Background Healthcare workers (HCWs) are vulnerable to getting infected withSARS-CoV-2. Preventing HCWs from getting infected is a priority to maintain healthcare services. The therapeutic and preventive role of ivermectin in COVID-19 is being investigated. Based on promising results of in vitro studies of oral ivermectin, this study was conducted with the aim to demonstrate the prophylactic role of oral ivermectin in preventing SARS-CoV-2 infectionamong HCWs at All India Institute of Medical Sciences (AIIMS), Bhubaneswar.Methods A prospective cohort study was conducted at AIIMS Bhubaneswar, which provides both COVID and Non-COVID care since March 2020. All employees and students of the institute who provided written informed consent participated in the study.Uptake of two-doses of oral ivermectin (300 μg/kg at a gap of 72 hours) was considered as exposure. The primary outcome of the study was COVID-19 infection in the following month of ivermectin consumption diagnosed by RTPCR as per Government of India testing criteria guidelines.The log-binomial model was used to estimate adjusted relative risk, and the Kaplan-Meier failure plot was used to estimate the probability of COVID-19 infection with follow-up time.Results Of 3892 employees, 3532 (90.8%) participated in the study. The ivermectin uptake was 62.5% and 5.3% for two-doses and single-dose, respectively. Participants who took ivermectin prophylaxis had a lower risk of getting symptoms suggestive of SARS-CoV-2 infection(6% vs 15%). HCWs who had taken two-doses of oral ivermectin have a significantly lower risk of contracting COVID-19 disease during the following month (ARR 0.17; 95% CI, 0.12-0.23). Females had a lower risk of contracting COVID-19 than males (ARR 0.70 95% CI, 0.52-0.93). The absolute risk reduction of SARS-CoV-2 infection was 9.7%. Only 1.8% of the participants reported adverse events, which were mild and self-limiting.Conclusion and relevance Two-doses of oral ivermectin (300 μg/kg given 72 hours apart) as chemoprophylaxis among HCWs reduces the risk of COVID-19 infection by 83% in the following month. Safe, effective, and low-cost chemoprophylaxis have relevance in the containment of pandemic alongside vaccine.

OBJECTIVE:

Current evidence on the effectiveness of SARS-CoV-2 prophylaxis is inconclusive. We aimed to systematically evaluate published studies on repurposed drugs for the prevention of laboratory-confirmed SARS-CoV-2 infection and/or COVID-19 among healthy adults.

DESIGN:

Systematic review.

ELIGIBILITY:

Quantitative experimental and observational intervention studies that evaluated the effectiveness of repurposed drugs for the primary prevention of SARS-CoV-2 infection and/or COVID-19 disease.

DATA SOURCE:

PubMed and Embase (1 January 2020-28 September 2022).

RISK OF BIAS:

Cochrane Risk of Bias 2.0 and Risk of Bias in Non-Randomised Studies of Interventions tools were applied to assess the quality of studies.

DATA ANALYSIS:

Meta-analyses for each eligible drug were performed if ≥2 similar study designs were available.

RESULTS:

In all, 65 (25 trials, 40 observational) and 29 publications were eligible for review and meta-analyses, respectively. Most studies pertained to hydroxychloroquine (32), ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB) (11), statin (8), and ivermectin (8). In trials, hydroxychloroquine prophylaxis reduced laboratory-confirmed SARS-CoV-2 infection (risk ratio: 0.82 (95% CI 0.74 to 0.90), I2=48%), a result largely driven by one clinical trial (weight: 60.5%). Such beneficial effects were not observed in observational studies, nor for prognostic clinical outcomes. Ivermectin did not significantly reduce the risk of SARS-CoV-2 infection (RR: 0.35 (95% CI 0.10 to 1.26), I2=96%) and findings for clinical outcomes were inconsistent. Neither ACEi or ARB were beneficial in reducing SARS-CoV-2 infection. Most of the evidence from clinical trials was of moderate quality and of lower quality in observational studies.

CONCLUSIONS:

Results from our analysis are insufficient to support an evidence-based repurposed drug policy for SARS-CoV-2 prophylaxis because of inconsistency. In the view of scarce supportive evidence on repurposing drugs for COVID-19, alternative strategies such as immunisation of vulnerable people are warranted to prevent the future waves of infection.

PROSPERO REGISTRATION NUMBER:

CRD42021292797.

BACKGROUND:

The worldwide COVID-19 pandemic was caused by a newly discovered Coronavirus. The treatment methods for COVID-19 are emerging and rapidly evolving. Existing drugs, including Ivermectin and Hydroxychloroquine, offer the hope of effective treatment in early disease. In this study, we investigated and compared outcomes of Ivermectin-Doxycycline vs. Hydroxychloroquine-Azithromycin combination therapy COVID19 patients with mild to moderate disease.

METHODS:

Patients with mild to moderate COVID-19 disease, tested positive by RT PCR for SARS-CoV-2 infection at Chakoria Upazilla Health Complex, Cox's Bazar, Bangladesh, were included in this study. Patients were divided randomly into two groups: Ivermectin 200µgm/kg single dose + Doxycycline 100 mg BID for 10days in group A, and Hydroxychloroquine 400 mg 1st day, then200mg BID for 9days + Azithromycin 500 mg daily for 5 days in group B. PCR for SARS-CoV-2 was repeated in all symptomatic patients on the second day onward without symptoms, or, for those who were asymptomatic (throughout the process), on the 5th day after taking medication and repeated every two days onward if the result is positive. Time to negative PCR and time to full symptomatic recovery was measured for each group.

RESULTS:

All subjects in the Ivermectin-Doxycycline group (group A) reached a negative PCR for SARS-CoV-2, at a mean of 8.93days, and all reached symptomatic recovery, at a mean of 5.93days, with 55.10% symptom-free by the 5th day. In the Hydroxychloroquine-Azithromcyin group (group B), 96.36% reached a negative PCR at a mean of 6.99days and were symptoms-free at 9.33days. Group A patients had symptoms that could have been caused by the medication in 31.67% of patients, including lethargy in 14(23.3%), nausea in 11(18.3%), and occasional vertigo in 7(11.66%) of patients. In Group B, 46.43% had symptoms that could have been caused by the medication, including 13(23.21%) mild blurring of vision and headache; 22(39.2%) increased lethargy and dizziness, 10(17.85%) occasional palpitation, and 9(16.07%) nausea and vomiting.

CONCLUSION:

The Ivermectin-Doxycycline combination showed a trend toward superiority to the Hydroxychloroquine-Azithromycin combination therapy in the case of patients with mild to moderate COVID19 disease, though the difference in time to becoming symptom-free and the difference in time to negative PCR was not statistically significant.

Introduction Healthcare workers (HCWs) are vulnerable to getting infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Preventing HCWs from getting infected is a priority to maintain healthcare services. The therapeutic and preventive role of ivermectin in coronavirus disease 2019 (COVID-19) is being investigated. Based on promising results of in vitro studies of oral ivermectin, this study was conducted with the aim to demonstrate the prophylactic role of oral ivermectin in preventing SARS-CoV-2 infection among HCWs at the All India Institute of Medical Sciences (AIIMS) Bhubaneswar. Methods A prospective cohort study was conducted at AIIMS Bhubaneswar, which has been providing both COVID and non-COVID care since March 2020. All employees and students of the institute who provided written informed consent participated in the study. The uptake of two doses of oral ivermectin (300 μg/kg/dose at a gap of 72 hours) was considered as exposure. The primary outcome of the study was COVID-19 infection in the following month of ivermectin consumption, diagnosed as per Government of India testing criteria (real-time reverse transcriptase polymerase chain reaction [RT-PCR]) guidelines. The log-binomial model was used to estimate adjusted relative risk (ARR), and the Kaplan-Meier failure plot was used to estimate the probability of COVID-19 infection with follow-up time. Results Of 3892 employees, 3532 (90.8%) participated in the study. The ivermectin uptake was 62.5% and 5.3% for two doses and single dose, respectively. Participants who took ivermectin prophylaxis had a lower risk of getting symptoms suggestive of SARS-CoV-2 infection (6% vs 15%). HCWs who had taken two doses of oral ivermectin had a significantly lower risk of contracting COVID-19 infection during the following month (ARR 0.17; 95% CI, 0.12-0.23). Females had a lower risk of contracting COVID-19 than males (ARR 0.70; 95% CI, 0.52-0.93). The absolute risk reduction of SARS-CoV-2 infection was 9.7%. Only 1.8% of the participants reported adverse events, which were mild and self-limiting. Conclusion Two doses of oral ivermectin (300 μg/kg/dose given 72 hours apart) as chemoprophylaxis among HCWs reduced the risk of COVID-19 infection by 83% in the following month. Safe, effective, and low-cost chemoprophylaxis has relevance in the containment of pandemic alongside vaccine.

Mild to moderate COVID-19 can be found in about 80% of patients. Although mortality is low, mild to moderate COVID-19 may progress to severe or even critical stages in about one week. This poses a substantial burden on the health care system, and ultimately culminates in death or incapacitation and hospitalization. Therefore, pharmacological treatment is paramount for patients with this condition, especially those with recognized risk factors to disease progression. We conducted a comprehensive review in the medical literature searching for randomized studies carried out in patients with mild to moderate COVID-19. A total of 14 randomized studies were identified, enrolling a total of 6848 patients. Nine studies (64%) were randomized, placebo-controlled trials, whereas five were open-label randomized trials (35%). We observed that Bamlanivimab and nitazoxanide reduced viral load, whereas ivermectin may have shortened time to viral clearance; Interferon Beta-1 reduced time to viral clearance and vitamin D reduced viral load; Favirapir, peginterferon, and levamisole improved clinical symptoms, whereas fluvoxamine halted disease progression; inhaled budesonide reduced the number of hospitalizations and visits to emergency departments; colchicine reduced the number of deaths and hospitalizations. Collectively, therefore, these findings show that treatment of early COVID-19 may be associated with reduced viral load, thus potentially decreasing disease spread in the community. Moreover, treatment of patients with mild to moderate COVID-19 may also be associated with improved clinical symptoms, hospitalization, and disease progression. We suggest that colchicine, inhaled budesonide, and nitazoxanide, along with nonpharmacological measures, based on efficacy and costs, may be used to mitigate the effects of the COVID-19 pandemic in middle-income countries.

OBJECTIVE:

Several therapies are being used or proposed for COVID-19, and many lack appropriate evaluations of their effectiveness and safety. The purpose of this document is to develop recommendations to support decisions regarding the pharmacological treatment of patients hospitalized with COVID-19 in Brazil.

METHODS:

A group of 27 experts, including representatives of the Ministry of Health and methodologists, created this guideline. The method used for the rapid development of guidelines was based on the adoption and/or adaptation of existing international guidelines (GRADE ADOLOPMENT) and supported by the e-COVID-19 RecMap platform. The quality of the evidence and the preparation of the recommendations followed the GRADE method.

RESULTS:

Sixteen recommendations were generated. They include strong recommendations for the use of corticosteroids in patients using supplemental oxygen, the use of anticoagulants at prophylactic doses to prevent thromboembolism and the nonuse of antibiotics in patients without suspected bacterial infection. It was not possible to make a recommendation regarding the use of tocilizumab in patients hospitalized with COVID-19 using oxygen due to uncertainties regarding the availability of and access to the drug. Strong recommendations against the use of hydroxychloroquine, convalescent plasma, colchicine, lopinavir + ritonavir and antibiotics in patients without suspected bacterial infection and also conditional recommendations against the use of casirivimab + imdevimab, ivermectin and rendesivir were made.

CONCLUSION:

To date, few therapies have proven effective in the treatment of hospitalized patients with COVID-19, and only corticosteroids and prophylaxis for thromboembolism are recommended. Several drugs were considered ineffective and should not be used to provide the best treatment according to the principles of evidence-based medicine and promote economical resource use.

All species of coronavirus may cause infections in birds which is known to us since the 60s, but recently, from Nov 2019, the disease emerged in humans from the seafood market in Wuhan city. The previous viral outbreaks like SARS-CoV and MERS-CoV have also shown a greater mortality rate when transmitted to humans than other animals. An emerging concern in the 2019 novel coronavirus (SARS-CoV-2) is in terms of developing vaccine or discovery of new drugs to overcome the current viral pandemic. In this rapid-review, we aim to update the available data on coronavirus with the latest findings and achievements. So far, great steps have been taken such as hrsACE2 by a Swedish team from Karolinska Institute. Monash University announced the efficacy of Ivermectin to overcome COVID-19. The CRISPR/Cas13d as a new innovative therapeutics based might overcome the challenge of COVID-19. those strains of virus which lacking E protein-encoding regions are the perfect choice for vaccine development.

PURPOSE:

This executive summary of a national living guideline aims to provide rapid evidence based recommendations on the role of drug interventions in the treatment of hospitalized patients with COVID-19.

METHODS:

The guideline makes use of a systematic assessment and decision process using an evidence to decision framework (GRADE) as recommended standard WHO (2021). Recommendations are consented by an interdisciplinary panel. Evidence analysis and interpretation is supported by the CEOsys project providing extensive literature searches and living (meta-) analyses. For this executive summary, selected key recommendations on drug therapy are presented including the quality of the evidence and rationale for the level of recommendation.

RESULTS:

The guideline contains 11 key recommendations for COVID-19 drug therapy, eight of which are based on systematic review and/or meta-analysis, while three recommendations represent consensus expert opinion. Based on current evidence, the panel makes strong recommendations for corticosteroids (WHO scale 5-9) and prophylactic anticoagulation (all hospitalized patients with COVID-19) as standard of care. Intensified anticoagulation may be considered for patients with additional risk factors for venous thromboembolisms (VTE) and a low bleeding risk. The IL-6 antagonist tocilizumab may be added in case of high supplemental oxygen requirement and progressive disease (WHO scale 5-6). Treatment with nMABs may be considered for selected inpatients with an early SARS-CoV-2 infection that are not hospitalized for COVID-19. Convalescent plasma, azithromycin, ivermectin or vitamin D3 should not be used in COVID-19 routine care.

CONCLUSION:

For COVID-19 drug therapy, there are several options that are sufficiently supported by evidence. The living guidance will be updated as new evidence emerges.

OBJECTIVE:

To update the recommendations to support decisions regarding the pharmacological treatment of patients hospitalized with COVID-19 in Brazil.

METHODS:

Experts, including representatives of the Ministry of Health and methodologists, created this guideline. The method used for the rapid development of guidelines was based on the adoption and/or adaptation of existing international guidelines (GRADE ADOLOPMENT) and supported by the e-COVID-19 RecMap platform. The quality of the evidence and the preparation of the recommendations followed the GRADE method.

RESULTS:

Twenty-one recommendations were generated, including strong recommendations for the use of corticosteroids in patients using supplemental oxygen and conditional recommendations for the use of tocilizumab and baricitinib for patients on supplemental oxygen or on noninvasive ventilation and anticoagulants to prevent thromboembolism. Due to suspension of use authorization, it was not possible to make recommendations regarding the use of casirivimab + imdevimab. Strong recommendations against the use of azithromycin in patients without suspected bacterial infection, hydroxychloroquine, convalescent plasma, colchicine, and lopinavir + ritonavir and conditional recommendations against the use of ivermectin and remdesivir were made.

CONCLUSION:

New recommendations for the treatment of hospitalized patients with COVID-19 were generated, such as those for tocilizumab and baricitinib. Corticosteroids and prophylaxis for thromboembolism are still recommended, the latter with conditional recommendation. Several drugs were considered ineffective and should not be used to provide the best treatment according to the principles of evidence-based medicine and to promote resource economy.