Pulmonary vascular inflammation with fatal coronavirus disease 2019 (COVID-19): possible role for the NLRP3 inflammasome

Respiratory Research

Leslie Litzky¹  Michael Feldman¹  Kathleen Montone¹  Chamith Rajapakse²  Christian Bermudez³  Shampa Chatterjee⁴  Oindrila Paul⁴  Jian Qin Tao⁴  Eric West⁴ 

[1] Department of Pathology, University of Pennsylvania School of Medicine, 19104, Philadelphia, PA, USA;Department of Radiology, University of Pennsylvania School of Medicine, 19104, Philadelphia, PA, USA;Department of Surgery, University of Pennsylvania School of Medicine, 19104, Philadelphia, PA, USA;Institute for Environmental Medicine and Department of Physiology, University of Pennsylvania Perelman School of Medicine, 3620 Hamilton Walk, 19104, Philadelphia, PA, USA;

关键词: NLRP3 inflammasome;    Lung inflammation;    Microthrombosis;    COVID-19;    Vascular endothelium;    Mechanical ventilation;   

DOI  :  10.1186/s12931-022-01944-8

来源: Springer

【 摘 要 】

BackgroundPulmonary hyperinflammation is a key event with SARS-CoV-2 infection. Acute respiratory distress syndrome (ARDS) that often accompanies COVID-19 appears to have worse outcomes than ARDS from other causes. To date, numerous lung histological studies in cases of COVID-19 have shown extensive inflammation and injury, but the extent to which these are a COVID-19 specific, or are an ARDS and/or mechanical ventilation (MV) related phenomenon is not clear. Furthermore, while lung hyperinflammation with ARDS (COVID-19 or from other causes) has been well studied, there is scarce documentation of vascular inflammation in COVID-19 lungs.MethodsLung sections from 8 COVID-19 affected and 11 non-COVID-19 subjects, of which 8 were acute respiratory disease syndrome (ARDS) affected (non-COVID-19 ARDS) and 3 were from subjects with non-respiratory diseases (non-COVID-19 non-ARDS) were H&E stained to ascertain histopathological features. Inflammation along the vessel wall was also monitored by expression of NLRP3 and caspase 1.ResultsIn lungs from COVID-19 affected subjects, vascular changes in the form of microthrombi in small vessels, arterial thrombosis, and organization were extensive as compared to lungs from non-COVID-19 (i.e., non-COVID-19 ARDS and non-COVID-19 non-ARDS) affected subjects. The expression of NLRP3 pathway components was higher in lungs from COVID-19 ARDS subjects as compared to non-COVID-19 non-ARDS cases. No differences were observed between COVID-19 ARDS and non-COVID-19 ARDS lungs.ConclusionVascular changes as well as NLRP3 inflammasome pathway activation were not different between COVID-19 and non-COVID-19 ARDS suggesting that these responses are not a COVID-19 specific phenomenon and are possibly more related to respiratory distress and associated strategies (such as MV) for treatment.

【 授权许可】

CC BY