Preeclampsia and COVID-19: the Role of Inflammasome Activation

Abstract

Purpose of ReviewIt is well established that controlled immune activation and balance is critical for women's reproductive health and successful pregnancy outcomes. Research in recent decades in both clinical and animal studies has demonstrated that aberrant immune activation and inflammation play a role in the development and progression of women's reproductive health and pregnancy-related disorders. Inflammasomes are multi-protein cytoplasmic complexes that mediate immune activation. In this review, we summarize current knowledge on the role of inflammasome activation in pregnancy-related disorders.Recent Findings Increased activation of inflammasome is associated with multiple women's health reproductive disorders and pregnancy-associated disorders, including preeclampsia (PreE). Inflammasome activation is also associated with the novel coronavirus disease 2019 (COVID-19) disease caused by the SARS-Cov-2 virus. We and others have observed a positive association between increased PreE incidences with the onset of the COVID-19 pandemic. Here, we present our recent data indicating increased inflammasome activation, represented by caspase-1 activity, in women with COVID-19 and PreE compared to normotensive pregnant women COVID-19. Summary The role of inflammation in pregnancy-related disorders is an area of intense research interest. With the onset of the COVID-19 pandemic and the associated increase in PreE observed clinically, there is a greater need to identify mechanisms of pathophysiology and targets to treat this maternal disorder. Inflammasome activation is associated with PreE and COVID-19 infection and may hold therapeutic potential to improve outcomes associated with PreE and curb the morbidity attributed to PreE. Keywords Inflammasome • Preeclampsia • COVID-19 • NLRP3This article is part of the Topical Collection on Preeclampsia

Role of biomarkers (sFlt-1/PlGF) in cases of COVID-19 for distinguishing preeclampsia and guiding clinical management

“… [28] , [29] Other inflammatory markers that are altered are interleukins and cytokines, mostly decreasing the expression of IL-1β, which may indicate the state of clinical evolution depending on their high expression, especially in the cytokine storm state. [30] , [31] In our study, we did not evaluate these inflammatory markers.…”

COVID‐19 and preeclampsia: The unique and the mutually nonexclusive clinical manifestations

“…In patients with PE, there is a significant increase in the levels of adhesion molecules like VCAM-1 and ICAM-1 and proinflammatory cytokine, that is soluble TNF-receptor I (sTNFRI), 50 but normal levels of heparan sulfate (HS). 29 In comparison, COVID-19 patients show marginally increased VCAM-1, ICAM-1 and sTNFRI, but there is a significant increase in HS levels . 42,51 HS is a biomarker for endothelial barrier disruption and the levels of HS directly correlate with the severity of COVID-19 ; more studies should confirm these observations to utilize these markers for the differential diagnosis of PE and COVID-19.…”

“…28 Additionally, increased caspase-1 levels has been reported in women with COVID-19 and PE as compared to healthy controls. 29 Inflammasomes which are multiprotein complexes, have an important role not only in innate immune responses but also in regulating inflammation which makes them crucial in hyper-inflammatory diseases like PE and COVID-19. Among the various inflammasomes, NLRP3 is the most widely studied inflammasome in inflammation and antiviral action .…”

“…The common laboratory abnormalities are thrombocytopenia, increased serum ferritin levels and pro‐inflammatory cytokines which include IL‐1b, IL‐2, IL‐6, IL‐7, IFN‐g and tumor necrosis factor‐α (TNFα) resulting in a cytokine storm and multi‐organ failure 28 . Additionally, increased caspase‐1 levels has been reported in women with COVID‐19 and PE as compared to healthy controls 29 . Inflammasomes which are multiprotein complexes, have an important role not only in innate immune responses but also in regulating inflammation which makes them crucial in hyper‐inflammatory diseases like PE and COVID‐19.…”

“…Differential patterns of biomarkers of endothelial activation and damage have been reported for PE and COVID‐19. In patients with PE, there is a significant increase in the levels of adhesion molecules like VCAM‐1 and ICAM‐1 and proinflammatory cytokine, that is soluble TNF‐receptor I (sTNFRI), 50 but normal levels of heparan sulfate (HS) 29 . In comparison, COVID‐19 patients show marginally increased VCAM‐1, ICAM‐1 and sTNFRI, but there is a significant increase in HS levels 42,51 .…”