Do inflammasome impact COVID-19 severity?

Abstract

COVID-19 pandemic has proven to be a dramatic challenge, introducing huge clinical differences that demand extensive investigations. Severe and critical patients may present coagulopathies and microthrombi, which results in varied complications, or acute respiratory distress syndrome that leads to fatality. Although the lung to be the major site of clinical manifestations, COVID-19 has shown extrapulmonary manifestations, especially on the heart and kidney, directly linked to worse disease outcomes. According to the fast-moving of clinical description and scientific publications, the injuries in multiple organs and systemic inflammation appear to be caused by a deregulated immune response, and the NLRP3 inflammasome could be a relevant influencer in this imbalance. However, until now, the precise drivers of the pathophysiology of these injuries remain unknown. In this review, we discuss how inflammasome seems to be directly involved in the clinical profile of patients infected with SARS-CoV-2 and shed light on the mechanisms that lead to fatality.

Keywords: ARDS; Coagulation; IL-1b; Inflammation; NLRP3; SARS-CoV-2.

Fig. 1

Schematic representation of signaling pathways of pro-inflammatory cytokines involved on COVID-19. a Inflammasome assembly after PAMP and DAMP recognition activate caspase-1, essential for the cleavage of pro-IL-1b and IL-18 into their active form. After externalization, these cytokines can induce pyroptosis and biding their respective receptors to promote the expression of pro-inflammatory molecules. b Signal transduction of IL-6 after binding IL-6 receptor and activates Janus Kinases (JAK) leads to activation of different mediators to promote gene expression. The recognition of TNFa by TNFR2 triggers different cascades which promotes inflammation or gene expression mediated by NFk-B. In parallel, the biding on TNFR1 causes subsequent apoptosis mediated by caspases

Fig. 2

The clinical features of COVID-19 patients are resulting from simultaneous events, promoting complex crosstalk between immune components. When SARS-CoV-2 infect host cell through Spike protein binding with ACE2 receptor, a wave of PAMPs and DAMPs ensues, activating pathways that enable inflammasome activation and leads to cleavage of IL-1β and IL-18, creating pro-inflammatory signals and leads to airway inflammation. Consequently, occurs platelet activation, fibrin deposition, and NETs release, which promotes tissue damage. A cascade involving inflammasome assembly and inflammation leads to ARDS development