Pulmonary post-mortem findings in a large series of COVID-19 cases from Northern Italy

Abstract

Importance. The analysis of lung tissues of patients with COVID-19 may help understand pathogenesis and clinical outcomes in this life-threatening respiratory illness. Objective.To determine the histological patterns in lung tissue of patients with severe COVID-19.Design and participants. Lungs tissues of 38 cases who died for COVID-19 in two hospital of Northern Italy were systematically analysed. Hematoxylin-eosin staining, immunohistochemistry for the inflammatory infiltrate and cellular components, electron microscopy were performed.Results. The features of the exudative and proliferative phases of Diffuse Alveolar Disease (DAD) were found: capillary congestion, necrosis of pneumocytes, hyaline membrane, interstitial oedema, pneumocyte hyperplasia and reactive atypia, platelet-fibrin thrombi. The inflammatory infiltrate was composed by macrophages in alveolar lumens and lymphocytes mainly in the interstice. Electron microscopy revealed viral particles in the cytoplasm of pneumocytes.Conclusions and relevance. The predominant pattern of lung lesions in COVID-19 patients is DAD, as described for the other two coronavirus that infect humans, SARS-CoV and MERS-CoV. Hyaline membrane formation and pneumocyte atypical hyperplasia are frequently found. The main relevant finding is the presence of platelet-fibrin thrombi in small arterial vessels; this important observation fits into the clinical context of coagulopathy which dominates in these patients and which is one of the main targets of therapy.

Lung and Kidney Perfusion Deficits Diagnosed by Dual-Energy Computed Tomography in COVID–19 Patients: Evidence Supporting Systemic Microangiopathy

“…A similar observation was recently described [18]. Angiopathic microvascular occlusion has been proposed as the underlying mechanism [19].Another recent study showed brin thrombi of small arterial vessels less than 1 mm in diameter in 33 of 38 patients with high D-dimer levels [20]. Increased D-dimer levels in our patients with PDs are supportive of these observations.…”

Dissecting the common and compartment-specific features of COVID-19 severity in the lung and periphery with single-cell resolution

“…Post-mortem examinations of COVID-19 patients reveal the aftermath of these disease dynamics: diffuse alveolar damage, multi-organ infiltration of lymphocytes and alveolar macrophages [1,7,15,16], and pneumocyte hyperplasia and peribronchiolar metaplasia in the epithelium resembling adenocarcinomas [15,16,17]. These morphological findings suggest local and systemic activation and infiltration of inflammatory immune cells that may contribute to the inflammatory injuries of the respiratory system consistent with ARDS phenotypes in severe COVID-19 [15].…”

“…Significant transcriptional changes in cells of the BALF were abundant in all cell types with the exception of plasma cells. We first directed our attention to the epithelium, where substantial morphological damage and histological atypia were observed in deceased COVID-19 patients [1,7,15,17,16]. At the level of individual gene regulation, we first noted a surprisingly strong significant upregulation of FOS and JUN, which code for proteins implicated in the development of cancer ( Figure 3A).…”

SARS-CoV-2 Infection-Associated Hemophagocytic Lymphohistiocytosis: An autopsy series with clinical and laboratory correlation

“…[6][7][8] Despite these clinical observations, there has been relatively little clinicopathologic correlation with the post-mortem findings in COVID-19 which to date have generally focused on the pulmonary histology of diffuse alveolar damage. [9][10][11][12] Herein we report the first cases of SARS-CoV-2 associated HLH diagnosed post-mortem using histologic, clinical and laboratory criteria.…”