Post-mortem lung tissue: the fossil record of the pathophysiology and immunopathology of severe COVID-19

Abstract

The lungs are the main site that is affected in severe COVID-19, and post-mortem lung tissue provides crucial insights into the pathophysiology of severe disease. From basic histology to state-of-the-art multiparameter digital pathology technologies, post-mortem lung tissue provides snapshots of tissue architecture, and resident and inflammatory cell phenotypes and composition at the time of death. Contrary to early assumptions that COVID-19 in the lungs is a uniform disease, post-mortem findings have established a high degree of disease heterogeneity. Classic diffuse alveolar damage represents just one phenotype, with disease divisible by early and late progression as well as by pathophysiological process. A distinct lung tissue state occurs with secondary infection; extrapulmonary causes of death might also originate from a pathological process in the lungs linked to microthrombosis. This heterogeneity of COVID-19 lung disease must be recognised in the management of patients and in the development of novel treatment strategies.

Association between Coagulation Profile and Clinical Outcome in Children with SARS-CoV-2 Infection or MIS-C: A Multicenter Cross-Sectional Study

“…Altogether, our findings highlight the role of a Covid-induced pro-coagulative inflammatory state that seems to affect the clinical outcomes in children as well, as reported in the adult literature [ 30 ]. Recent post-mortem adult studies have clearly documented that lung disease is characterized by “microthrombi”, endothelial inflammation and platelet activation, even in the absence of classic macroscopic embolic events [ 30 ]. This condition has now been defined as “thromboinflammation” [ 31 ].…”

Persistent Lung Injury and Prothrombotic State in Long COVID

“…As weak parts of the alveolar membrane are destroyed, blood components such as water molecules, plasma proteins, and platelets enter the alveolar cavity, forming pulmonary edema ( 6 ) ( Figure 1A ). Many histopathological findings showed that the most frequently reported morphological feature of COVID-19 disease is diffuse alveolar damage, characterized by a variable degree of edema in the exudate phase ( 42 , 66 , 67 ). As long as reduction of alveolar volume is compensated and thrombosis can be prevented or dissolved, the trend towards severe complications can be blocked.…”

COVID-19 Vasculitis and vasculopathy-Distinct immunopathology emerging from the close juxtaposition of Type II Pneumocytes and Pulmonary Endothelial Cells

“…Pathology from the primary lung target organ in COVID-19 have consistently shown that viral alveolitis is accompanied by peri-capillary myeloid and lymphoid cell infiltration [ 29 , 30 ]. Pulmonary capillary, pulmonary arteriolar and pulmonary venular vessel wall inflammation has been associated with extensive and pervasive vascular luminal thrombosis[ 2 , 31 ]. Initially, it was considered that endothelial inflammation due to direct viral infection or “viral endotheliitis” accounted for the immunothrombosis [ 29 , 32 ].…”

“…The novel highly transmissible SARS-CoV-2 virus resulted in fatal pneumonia in a subset of patients and quickly garnered great interest in the cardiovascular and rheumatology arenas, because of the prominent vascular immunopathology. The most striking pathological feature was extensive viral alveolitis but also vascular thrombosis and reports of vascular wall inflammation [ 1 , 2 ]. Compelling evidence for extrapulmonary vasculitis and vasculitis mimics also emerged during the COVID-19 pandemic which are described in in this article.…”