We present a Graphical Abstract that would represent the potential therapeutic effects of inhaled ibuprofenate on lung macrophages infected by SARS-CoV-2 and its link with the NLRP3 inflammasome. Furthermore, in the manuscript we will provide data on observational studies in pneumonias and Cards.

In this manuscript, we will describe and highlight the most important potential underlying mechanisms of action of the inhaled sodium ibuprofenate in hypertonic saline formulation-NaIHS aerosolisable, as a probable adjuvant treatment for moderate and severe pneumonia and coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome in COVID-19. In both pathological entities, we will refer exclusively to the pulmonary vasoplegic type and we will describe the following therapeutic effects of NaIHS: antiinflammatory, immunomodulatory and antiangiogenic. The synergistic action of these therapeutic effects anti-inflammatory and immunomodulatory together may exert their action at the pulmonary level through the possible reversal of pulmonary vasoplegia and may thereby restore hypoxic pulmonary vasoconstriction, correcting the uncoupling of the ventilation/ perfusion ratio and vasoplegic intrapulmonary shunting and, above all, it may reverse severe hypoxaemia and acute respiratory failure. We will also mention the potential virucidal effects of NaIHS on severe acute respiratory syndrome-coronavirus 2.

In this manuscript, we will describe the possible mechanisms of action of inhaled sodium ibuprofenate in hypertonic saline formulation-NaIHS, focusing primarily on vasoplegic pulmonary vascular dysfunction leading to severe pneumonia and Coronavirus Disease 2019-associated acute respiratory distress syndrome. We will address the anti-inflammatory, immunomodulatory and antiangiogenic therapeutic effects of NaIHS, which together would exert their action through the negative modulation of local inflammatory mediators, pro-inflammatory cytokines and inflammatory pathways. In such a manner, NaIHS may reverse pulmonary vasoplegia and may thereby restore hypoxic pulmonary vasoconstriction, correcting the uncoupling of the ventilation-perfusion ratio and vasoplegic intrapulmonary shunting and, above all, it may reverse severe hypoxaemia. We will also describe the potential virucidal effects of NaIHS on Severe Acute Respiratory Syndrome-Coronavirus 2. Likewise, we will mention the evidence obtained from the potential adjuvant treatment with NaIHS in two observational cohort studies done in Argentina, the most recent of them with 5146 patients, concluding that NaIHS reduces mortality by 48.7%, although randomised clinical trials are still needed to confirm these data.