Histological Evidence of Pulmonary Microthrombosis and Vasculitis in Life-Threatening Respiratory Virus Diseases

Abstract

Pulmonary microthrombosis and vasculitis occur in fatal coronavirus disease 2019. To determine whether these processes occur in other life-threatening respiratory virus infections, we identified autopsy studies of fatal influenza (n = 455 patients), severe acute respiratory syndrome ([SARS] n = 37), Middle East respiratory syndrome (n = 2), adenovirus (n = 34), and respiratory syncytial virus (n = 30). Histological evidence of thrombosis was frequently present in adults with fatal influenza and SARS, with vasculitis also reported.

Tissue Proteomic Analysis Identifies Mechanisms and Stages of Immunopathology in Fatal COVID-19

“…Similarly, while comparison of COVID-19 tissue to patients with ARDS from other aetiologies is conceptually of interest (to identify factors that are truly unique to COVID- 19), disease mechanisms that are shared with other causes of lung injury are also of interest as potential therapeutic targets. For example, histologic evidence of pulmonary microthrombosis is common to fatal influenza, SARS and non-selected ARDS, in addition to COVID-19 (48) and TYMP could therefore be a factor common to these different diseases. Similarly, the evidence provided here for the role of EN-RAGE in tissue inflammation adds to the existing literature reporting its relevance in non-selected ARDS.…”

Comparison of clinical features and outcomes in COVID-19 and influenza pneumonia patients requiring intensive care unit admission

“…Both FLU and COVID-19 are associated with severe cardiovascular and cardiorespiratory complications, mainly due to the occurrence of thrombotic events [ 7 , 9 , 28 , 50 ]. Although in the absence of statistical significance, we found a higher occurrence of thrombotic events in patients with COVID-19 than with FLU, confirming that coagulopathy represents a crucial aspect of this condition, possibly driven by the activation of NADPH oxidase and by an excessive harmful pro-inflammatory response [ 28 ].…”

“…SARS-CoV-2 and influenza viruses share similar aspects, from their ease of transmission from person-to-person through the respiratory droplet route to their clinical presentation. In fact, both viruses can cause acute respiratory failure that might require hospitalization in ICU, might be complicated by bacterial and fungal superinfections and might predispose subjects to the development of thrombosis [4][5][6][7][8][9][10][11].…”

Post-mortem dissection of COVID-19: a pathogenic role for macrophages?

“…In keeping with this, high genotype-inferred pulmonary expression of the monocyte–macrophage chemotactic receptor CCR2 is associated with severe disease, and numerous monocyte/macrophage chemotactic factors are elevated in blood, bronchoalveolar lavage fluid and whole lung tissue in COVID-19 [ 4 , 9 , 10 ]. These expanded macrophage populations are highly activated and with aberrant expression of key inflammation-associated molecules, often alongside expression of genes associated with tissue repair and fibrogenesis [ 2 , 11 , 12 ]. Interestingly, while epithelial cells are clearly the main viral target of SARS-CoV-2 infection, studies have reported viral S protein within macrophages [ 1 , 3 ].…”

“…Pulmonary vascular and endothelial pathology are also key features of fatal COVID-19, with multiple reports of thrombotic complications occurring despite anticoagulation therapy [ 11 ]. Ultrastructural endothelial damage is prevalent with intra- and extra-cellular SARS-CoV-2 endothelial infection reported, as well as a mononuclear-cell vasculitis affecting the intimal layer of small and medium-sized pulmonary arteries, mainly comprising MRP8 + monocyte-macrophage cells (and not T cells as reported in influenza) (Fig.…”