Lung histopathological findings in COVID-19 disease – a systematic review

Abstract

Since December 2019, the global burden of the COVID-19 pandemic has increased rapidly and has impacted nearly every country in the world, affecting those who are elderly or with underlying comorbidities or immunocompromised states. Aim of this systematic review is to summarize lung histopathological characteristics of COVID-19, not only for diagnostic purpose but also to evaluate changes that can reflect pathophysiological pathways that can inform clinicians of useful treatment strategies. We identified following histopathological changes among our patients:: hyaline membranes; endothelial cells/ interstitial cells involvement; alveolar cells, type I pneumocytes/ type II pneumocytes involvement; interstitial and/ or alveolar edema; evidence of hemorrhage, of inflammatory cells, evidence of microthrombi; evidence of fibrin deposition and of viral infection in the tissue samples.The scenario with proliferative cell desquamation is typical of Acute Respiratory Distress Syndrome (ARDS) that can be classified as diffuse alveolar damage (DAD) and not DAD-ARDS. The proposed pathological mechanism concerns the role of both innate and adaptive components of the immune system. COVID-19 lethal cases present themselves as a heterogeneous disease, characterized by the different simultaneous presence of different histological findings, which reflect histological phases with corresponding different pathological pathways (epithelial, vascular and fibrotic changes), in the same patient.

The Role of Alveolar Edema in COVID-19

“…During the mechanism of dysfunction of the alveolar epitheliums, important roles are related to alveolar epithelial cells type I/II (AEI/AEII). AEII coordinates the host defense mechanisms, not only generating the restrictive alveolar epithelial barrier, but also secreting pulmonary surfactant, which reduces surface tension at the pulmonary air-liquid interface, thereby preventing atelectasis and alveolar edema [10][11][12][13][14]. Furthermore, the innate immune responses to infection of AEII lead both to the cell death by pyroptosis and apoptosis and to the activation alveolar macrophages [10][11][12][13][14].…”

“…AEII coordinates the host defense mechanisms, not only generating the restrictive alveolar epithelial barrier, but also secreting pulmonary surfactant, which reduces surface tension at the pulmonary air-liquid interface, thereby preventing atelectasis and alveolar edema [10][11][12][13][14]. Furthermore, the innate immune responses to infection of AEII lead both to the cell death by pyroptosis and apoptosis and to the activation alveolar macrophages [10][11][12][13][14]. In addition, the glucocorticoid receptor α acts as a cellular rheostat to ensure that a proper response is elicited by the neuro-endocrine and immune systems [6,15].…”

“…Actually, various chronic and acute diseases (including COVID-19) are associated with intensive inflammations [1,2]. Hyperplastic AEII are considered to be an essential part of the epithelialization processes and, consequently, endothelial injury healing [10][11][12][13][14].…”

Sphingolipids in Lung Pathology in the Coronavirus Disease Era: A Review of Sphingolipid Involvement in the Pathogenesis of Lung Damage

“…A histopathological study of changes in COVID-19 related lung disease revealed several changes from normal lung tissue, including damage to endothelial cell and epithelial/alveolar cells (Pannone et al, 2021). Endothelial alterations in COVID-19 include a hypercoagulability due to increased factor VIII and von Willebrand factor (Escher et al, 2020;Pannone et al, 2021). Additionally, there are elevated levels of plasma angiotensin II in COVID-19 patients.…”

“…Additionally, there are elevated levels of plasma angiotensin II in COVID-19 patients. Angiotensin II can lead to vascular permeability and further endothelial damage (Liu et al, 2020b;Pannone et al, 2021). The aggressive production of pro-inflammatory cytokines such as IL-6 and TNF-α disrupts normal anti-thrombotic and anti-inflammatory function of the endothelium, which can cause dysregulated complement activation (Pannone et al, 2021).…”