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MeSH Disease

Human Phenotype

Transmission

gender (2)


Seroprevalence
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    Nebulized ivermectin for COVID-19 and other respiratory diseases MESHD, a proof of concept, dose-ranging study in rats

    Authors: Carlos Chaccour; Gloria Abizanda; Ángel Irigoyen-Barrio; Aina Casellas; Azucena Aldaz; Fernando Martínez-Galán; Felix Hammann; Ana Gloria Gil

    doi:10.21203/rs.3.rs-64501/v1 Date: 2020-08-23 Source: ResearchSquare

    Background: Ivermectin is a widely used antiparasitic drug with known efficacy against several single-strain RNA viruses. Recent data shows significant reduction of SARS-CoV-2 replication in vitro by ivermectin concentrations not achievable with safe doses orally. Inhaled therapy has been used with success for other antiparasitics. Methods: An ethanol-based ivermectin formulation was administered once to 14 rats using a nebulizer capable of delivering particles with alveolar deposition MESHD. Rats were randomly assigned into three target dosing groups, lower dose (80-90 mg/kg), higher dose (110-140 mg/kg) or ethanol vehicle only. A toxicology profile including behavioral and weight monitoring, full blood SERO count, biochemistry, necropsy and histological examination of the lungs was conducted. The pharmacokinetic profile of ivermectin in plasma SERO and lungs was determined in all animals. Results: There were no relevant changes in behavior or body weight. There was a delayed elevation in muscle enzymes compatible with rhabdomyolysis HP rhabdomyolysis MESHD, that was also seen in the control group and has been attributed to the ethanol dose which was up to 11 grams/kg in some animals. There were no histological anomalies in the lungs of any rat. Male TRANS animals received a higher ivermectin dose adjusted by adipose weight and reached higher plasma SERO concentrations than females TRANS in the same dosing group (mean Cmax 86.2 ng/ml vs 26.2 ng/ml in the lower dose group and 152 ng/ml vs 51.8 ng/ml in the higher dose group). All subjects had detectable ivermectin concentrations in the lungs at seven days post intervention, up to 524.3 ng/g for high-dose male TRANS and 27.3 ng/g for low-dose females TRANS. Conclusion: nebulized ivermectin can reach pharmacodynamic concentrations in the lung tissue of rats, additional experiments are required to assess the safety of this formulation in larger animals.

    Nebulized ivermectin for COVID-19 and other respiratory diseases MESHD, a proof of concept, dose-ranging study in rats

    Authors: Carlos Chaccour; Gloria Abizanda; Ángel Irigoyen-Barrio; Aina Casellas; Azucena Aldaz; Fernando Martínez-Galán; Felix Hammann; Ana Gloria Gil

    doi:10.21203/rs.3.rs-64501/v2 Date: 2020-08-23 Source: ResearchSquare

    Background: Ivermectin is a widely used antiparasitic drug with known efficacy against several single-strain RNA viruses. Recent data shows significant reduction of SARS-CoV-2 replication in vitro by ivermectin concentrations not achievable with safe doses orally. Inhaled therapy has been used with success for other antiparasitics. Methods: An ethanol-based ivermectin formulation was administered once to 14 rats using a nebulizer capable of delivering particles with alveolar deposition MESHD. Rats were randomly assigned into three target dosing groups, lower dose (80-90 mg/kg), higher dose (110-140 mg/kg) or ethanol vehicle only. A toxicology profile including behavioral and weight monitoring, full blood SERO count, biochemistry, necropsy and histological examination of the lungs was conducted. The pharmacokinetic profile of ivermectin in plasma SERO and lungs was determined in all animals. Results: There were no relevant changes in behavior or body weight. There was a delayed elevation in muscle enzymes compatible with rhabdomyolysis HP rhabdomyolysis MESHD, that was also seen in the control group and has been attributed to the ethanol dose which was up to 11 grams/kg in some animals. There were no histological anomalies in the lungs of any rat. Male TRANS animals received a higher ivermectin dose adjusted by adipose weight and reached higher plasma SERO concentrations than females TRANS in the same dosing group (mean Cmax 86.2 ng/ml vs 26.2 ng/ml in the lower dose group and 152 ng/ml vs 51.8 ng/ml in the higher dose group). All subjects had detectable ivermectin concentrations in the lungs at seven days post intervention, up to 524.3 ng/g for high-dose male TRANS and 27.3 ng/g for low-dose females TRANS. Conclusion: nebulized ivermectin can reach pharmacodynamic concentrations in the lung tissue of rats, additional experiments are required to assess the safety of this formulation in larger animals.

    Obstetrical and intensive care strategies in a high-risk pregnancy with critical respiratory failure HP respiratory failure MESHD due to COVID-19: a case report

    Authors: Zuzana Kolkova; Martin Bjurstrom; John-Kalle Lansberg; Eimantas Svedas; Maria Andrada; Stefan Hansson; Andreas Herbst; Mehreen Zaigham

    doi:10.21203/rs.3.rs-39188/v1 Date: 2020-06-30 Source: ResearchSquare

    BackgroundWith the disease burden increasing daily, there is a lack of evidence regarding the impact of COVID-19 in pregnancy. Healthy pregnant women are still not regarded as a susceptible group despite physiological changes that make pregnant women more vulnerable to severe infection HP infection MESHD. However, high-risk pregnancies may be associated with severe COVID-19 disease with respiratory failure HP respiratory failure MESHD, as outlined in this report. We discuss the importance of timely delivery and antenatal steroid administration in a critically ill patient.CaseA 27-year-old pregnant woman (1-para) with type I diabetes MESHD, morbid obesity HP obesity MESHD, hypothyroidism and a previous Caesarean section, presented with critical respiratory failure HP respiratory failure MESHD secondary to COVID-19 at 32 weeks of gestation. A preterm emergency Caesarean section was performed, after steroid treatment for foetal lung maturation. The patient benefited from prone positioning however, transient acute renal injury MESHD, rhabdomyolysis HP rhabdomyolysis MESHD and sepsis HP sepsis MESHD led to prolonged intensive care and mechanical ventilation for 26 days post-Caesarean. The baby had an uncomplicated recovery.ConclusionCOVID-19 infection MESHD in high-risk pregnancies may result in severe maternal-neonatal outcomes such as critical respiratory failure MESHD requiring mechanical ventilation and premature termination of the pregnancy. Antenatal steroids may be of benefit for foetal lung maturation but should not delay delivery in severe cases.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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