Dataset Information

Clinical, laboratory and immunohistochemical characterization of in situ pulmonary arterial thrombosis in fatal COVID-19.

ABSTRACT:

Background

COVID-19 patients carry an increased rate of thrombosis. It is controversial to which extent thrombi in the pulmonary arterial tree really contribute to disease severity with hypoxemia secondary to microvascular/lung parenchymal damage with viral alveolitis considered to play the main role in critical disease.

Objectives

The primary objective was to compare post-mortem lung disease from fatal COVID-19 pneumonia in patients with macroscopically evident pulmonary arterial tree thrombosis and patients without, by characterizing the immunohistochemical nature of thrombi, and by comparing clinical and laboratory features of these patients with other COVID-19 patients who died but without evidence of pulmonary arterial thrombosis (controls).

Patients and methods

13 COVID-19 pneumonia cases (mean age ± standard deviation: 74 ± 6.5 years) with macroscopically visible pulmonary arterial thrombosis were compared to 14 controls. Hematoxylin and Eosin stained slides were reviewed choosing those with visible pulmonary thrombi which were further characterized by immunohistochemistry, in particular for the inflammatory infiltrates. Ante mortem serum markers relevant to pulmonary embolism were evaluated in both groups.

Results

Twenty arterial thrombi (5 cases with multiple thrombi) were selected for study and were composed by white blood cells (WBC) [median, IQR range: 10 % (5-12.25)], mainly neutrophils [58 % (35.2-64.5)]. Cases with thrombosis showed significantly higher levels of platelet count [median, IQR range: 195000/mmc (157750-274,500) vs 143,500 (113000-175,250), p = 0.011], LDH [854 U/L (731-1315) vs 539 (391.5-660), p = 0.003] at admission, and D-dimer at ICU transfer [25,072 FEU (6951-50,531) vs 1024 (620-5501), p = 0.003].

Conclusions

Immunothrombotically driven arterial thrombi in COVID-19 patients are associated with D-Dimer and LDH elevations, thus linking inflammation, coagulopathy and organ damage in fatal COVID-19.

SUBMITTER: Quartuccio L

PROVIDER: S-EPMC9481474 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

Clinical, laboratory and immunohistochemical characterization of in situ pulmonary arterial thrombosis in fatal COVID-19.

Quartuccio Luca L Sonaglia Arianna A Casarotto Letizia L McGonagle Dennis D Di Loreto Carla C Pegolo Enrico E

Thrombosis research 20220917

<h4>Background</h4>COVID-19 patients carry an increased rate of thrombosis. It is controversial to which extent thrombi in the pulmonary arterial tree really contribute to disease severity with hypoxemia secondary to microvascular/lung parenchymal damage with viral alveolitis considered to play the main role in critical disease.<h4>Objectives</h4>The primary objective was to compare post-mortem lung disease from fatal COVID-19 pneumonia in patients with macroscopically evident pulmonary arterial ...[more]

PMID: 36152461

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Project description:BACKGROUND:Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become pandemic, with substantial mortality. OBJECTIVE:To evaluate the pathologic changes of organ systems and the clinicopathologic basis for severe and fatal outcomes. DESIGN:Prospective autopsy study. SETTING:Single pathology department. PARTICIPANTS:11 deceased patients with COVID-19 (10 of whom were selected at random for autopsy). MEASUREMENTS:Systematic macroscopic, histopathologic, and viral analysis (SARS-CoV-2 on real-time polymerase chain reaction assay), with correlation of pathologic and clinical features, including comorbidities, comedication, and laboratory values. RESULTS:Patients' age ranged from 66 to 91 years (mean, 80.5 years; 8 men, 3 women). Ten of the 11 patients received prophylactic anticoagulant therapy; venous thromboembolism was not clinically suspected antemortem in any of the patients. Both lungs showed various stages of diffuse alveolar damage (DAD), including edema, hyaline membranes, and proliferation of pneumocytes and fibroblasts. Thrombosis of small and mid-sized pulmonary arteries was found in various degrees in all 11 patients and was associated with infarction in 8 patients and bronchopneumonia in 6 patients. Kupffer cell proliferation was seen in all patients, and chronic hepatic congestion in 8 patients. Other changes in the liver included hepatic steatosis, portal fibrosis, lymphocytic infiltrates and ductular proliferation, lobular cholestasis, and acute liver cell necrosis, together with central vein thrombosis. Additional frequent findings included renal proximal tubular injury, focal pancreatitis, adrenocortical hyperplasia, and lymphocyte depletion of spleen and lymph nodes. Viral RNA was detectable in pharyngeal, bronchial, and colonic mucosa but not bile. LIMITATION:The sample was small. CONCLUSION:COVID-19 predominantly involves the lungs, causing DAD and leading to acute respiratory insufficiency. Death may be caused by the thrombosis observed in segmental and subsegmental pulmonary arterial vessels despite the use of prophylactic anticoagulation. Studies are needed to further understand the thrombotic complications of COVID-19, together with the roles for strict thrombosis prophylaxis, laboratory and imaging studies, and early anticoagulant therapy for suspected pulmonary arterial thrombosis or thromboembolism. PRIMARY FUNDING SOURCE:None.

Project description:BackgroundProgressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (Covid-19) pandemic. Despite widespread interest in the pathophysiology of the disease, relatively little is known about the associated morphologic and molecular changes in the peripheral lung of patients who die from Covid-19.MethodsWe examined 7 lungs obtained during autopsy from patients who died from Covid-19 and compared them with 7 lungs obtained during autopsy from patients who died from acute respiratory distress syndrome (ARDS) secondary to influenza A(H1N1) infection and 10 age-matched, uninfected control lungs. The lungs were studied with the use of seven-color immunohistochemical analysis, micro-computed tomographic imaging, scanning electron microscopy, corrosion casting, and direct multiplexed measurement of gene expression.ResultsIn patients who died from Covid-19-associated or influenza-associated respiratory failure, the histologic pattern in the peripheral lung was diffuse alveolar damage with perivascular T-cell infiltration. The lungs from patients with Covid-19 also showed distinctive vascular features, consisting of severe endothelial injury associated with the presence of intracellular virus and disrupted cell membranes. Histologic analysis of pulmonary vessels in patients with Covid-19 showed widespread thrombosis with microangiopathy. Alveolar capillary microthrombi were 9 times as prevalent in patients with Covid-19 as in patients with influenza (P<0.001). In lungs from patients with Covid-19, the amount of new vessel growth - predominantly through a mechanism of intussusceptive angiogenesis - was 2.7 times as high as that in the lungs from patients with influenza (P<0.001).ConclusionsIn our small series, vascular angiogenesis distinguished the pulmonary pathobiology of Covid-19 from that of equally severe influenza virus infection. The universality and clinical implications of our observations require further research to define. (Funded by the National Institutes of Health and others.).

Dataset Information

Clinical, laboratory and immunohistochemical characterization of in situ pulmonary arterial thrombosis in fatal COVID-19.

Background

Objectives

Patients and methods

Results

Conclusions

Publications

Clinical, laboratory and immunohistochemical characterization of in situ pulmonary arterial thrombosis in fatal COVID-19.

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