Non-steroidal anti-inflammatory drugs (NSAIDs) and other eicosanoid pathway modifiers are among the most ubiquitously used medications in the general population. Their broad anti-inflammatory, antipyretic and analgesic effects are applied against symptoms of respiratory infections, including SARS-CoV-2, as well as in other acute and chronic inflammatory diseases that often coexist with allergy and asthma. However, the current pandemic of COVID-19 also revealed the gaps in our understanding of their mechanism of action, selectivity and interactions not only during viral infections and inflammation, but also in asthma exacerbations, uncontrolled allergic inflammation, and NSAIDs-exacerbated respiratory disease (NERD). In this context, the consensus report summarises currently available knowledge, novel discoveries and controversies regarding the use of NSAIDs in COVID-19, and the role of NSAIDs in asthma and viral asthma exacerbations. We also describe here novel mechanisms of action of leukotriene receptor antagonists (LTRAs), outline how to predict responses to LTRA therapy and discuss a potential role of LTRA therapy in COVID-19 treatment. Moreover, we discuss interactions of novel T2 biologicals and other eicosanoid pathway modifiers on the horizon, such as prostaglandin D2 antagonists and cannabinoids, with eicosanoid pathways, in context of viral infections and exacerbations of asthma and allergic diseases. Finally, we identify and summarise the major knowledge gaps and unmet needs in current eicosanoid research.

Background: Cysteinyl leukotrienes are pro-inflammatory mediators with a clinically established role in asthma and a potential human genetic and preclinical role in cardiovascular diseases. Given that cardiovascular disease has a critical inflammatory component, the use of a leukotriene antagonist may represent an innovative therapy to target inflammation in cardiovascular prevention. Methods: We performed an observational retrospective (three years) study on eight hundred asthmatic patients 18 years or older in Albania, equally classified in two cohorts, exposed or non-exposed to montelukast, matched by age and gender. Patients with a previous history of myocardial infarction or ischemic stroke were excluded. Results: we considered eight hundred asthmatic patients (368 male and 432 female) 18 years or older. Overall 37 (4.6%) of the asthmatic patients, 32 non-exposed and 5 exposed, suffered a major cardiovascular event during the 3 years observation period. All the cardiovascular events occurred among patients with an increased cardiovascular risk. Thus, we used both a propensity score (PS) matching and a PS adjusted Cox model for analysis. In both analyses exposure to montelukast remained a significant protective factor for incident ischemic events (HR = 0.222; HR = 0.241, respectively), independently from gender. The event-free Kaplan-Meier survival curves confirmed the lower cardiovascular incidence of patients exposed to montelukast (p = <0.0001). Conclusion: Collectively, our data indicates that there is a potential protective role of montelukast for incident ischemic events in the older asthmatic population, suggesting a co-morbidity benefit of montelukast in asthmatics and possible innovative therapy to target inflammation for cardiovascular prevention.