Inflammation plays a fundamental role in the pathogenesis and progression of COVID-19, ranging from common colds to fatal cases of pneumonia due to the cytokine release syndrome (CRS) that affected patients, determining the severe conditions. In COVID-19 the homeostatic equilibrium between TREG cells (IL-10) and Th17 cells (IL-17) is broken: inflammatory cytokine levels (IL-1, TNF) are elevated in the lungs of COVID-19 patients, resulting in an increase in HA-synthase-2 (HAS2) in alveolar epithelial cells CD31+, EpCAM+ and fibroblasts. The imbalance between pro-inflammatory and anti-inflammatory cytokines, leads to the CRS, an excessive and damaging host inflammation [28]. As a consequence of CRS [29], due to a severe infection of SARS-CoV-2 of the respiratory epithelium, the ARDS was observed in COVID-19 [30]. Edema and an IL-1β mediated proinflammatory response were increased in the lung parenchyma. Macrophages and dendritic cells produce IL-1β through macro-molecular complexes called inflammasomes, including the major element present in the pulmonary tissue and the nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome [20]. Following a precise stimulus, the activation and recruitment domain of caspase (ASC) and the catalytically inactive procaspase-1 assemble, the procaspase-1 turns into active caspase-1, the inactive pro-IL-1β matures in IL-1β and the NLRP3 inflammasome is activated. The NLRP3 inflammasomes and IL-1β driven proinflammatory cascades correlate with worsening of several respiratory diseases, including COVID-19.