A nicotinic hypothesis for Covid-19 with preventive and therapeutic implications

Abstract

Background: Ivermectin is a widely used antiparasitic drug with known e cacy against several single-strain RNA viruses. Recent data shows signi cant 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. 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 pro le including behavioral and weight monitoring, full blood count, biochemistry, necropsy and histological examination of the lungs was conducted. The pharmacokinetic pro le of ivermectin in plasma 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, 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 animals received a higher ivermectin dose adjusted by adipose weight and reached higher plasma concentrations than females in the same dosing group (mean C max 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 and 27.3 ng/g for lowdose females. 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.

Exposure to health misinformation about COVID-19 and increased tobacco and alcohol use: a population-based survey in Hong Kong

“…Claims about smoking protecting against COVID-19 might have been facilitated by a widely publicised article hypothesising a protective role of nicotine in COVID-19 infection, 12 wherein the lead author had previously received funding from the tobacco industry. 13 The hypothesis was based on tentative data showing an under-representation of smokers in hospitalised patients with COVID-19.…”

Ivermectin as a Broad-Spectrum Host-Directed Antiviral: The Real Deal?

“…Evidence for activity against DNA viruses is more limited, but encompasses Pseudorabies, polyoma and adenoviruses [18][19][20]. The basis of ivermectin's broadspectrum antiviral activity appears to relate to the fact that ivermectin binds to, and inhibits, the nuclear transport role of the host importin α (IMPα) protein [11,18,20], which is known to mediate nuclear import of various viral proteins and key host factors, but other possible antiviral actions of ivermectin have been proposed (e.g., [12]), including in the case of SARS-CoV-2 (e.g., [21,22]). This mini-review will summarise the weight of evidence for ivermectin's broad-spectrum antiviral activity and the basis of its IMPα-directed activity in light of the possibility that ivermectin could be a critically useful antiviral in the current SARS-CoV-2 crisis [6,17].…”

Role of Cigarette Smoke on ACE-2 Protein Membrane Expression in Bronchial Epithelial Cells Using an Air-Liquid Interface Model

“…However, it is also known that ACE-2 downregulation may be dependent on inflammatory mediators increased production [11] and therefore it was conceivable that our results could be merely an epiphenomenon related to such mechanism. To this regard, cigarette smoke promote inflammation inducing the production of proinflammatory cytokines, such a TNF-α, IL-1, IL-6, IL-8 and granulocyte-macrophage colonystimulating factor (GM-CSF) [12].…”