Pulmonary pathology of ARDS in COVID-19: A pathological review for clinicians

Abstract

COVID-19 has quickly reached pandemic levels since it was first reported in December 2019. The virus responsible for the disease, named SARS-CoV-2, is enveloped positive-stranded RNA viruses. During its replication in the cytoplasm of host cells, the viral genome is transcribed into proteins, such as the structural protein spike domain S1, which is responsible for binding to the cell receptor of the host cells. Infected patients have initially flu-like symptoms, rapidly evolving to severe acute lung injury, known as acute respiratory distress syndrome (ARDS). ARDS is characterized by an acute and diffuse inflammatory damage into the alveolarcapillary barrier associated with a vascular permeability increase and reduced compliance, compromising gas exchange and causing hypoxemia. Histopathologically, this condition is known as diffuse alveolar damage which consists of permanent damage to the alveoli epithelial cells and capillary endothelial cells, with consequent hyaline membrane formation and eventually intracapillary thrombosis. All of these mechanisms associated with COVID-19 involve the phenotypic expression from different proteins transcription modulated by viral infection in specific pulmonary microenvironments. Therefore, this knowledge is fundamentally important for a better pathophysiological understanding and identification of the main molecular pathways associated with the disease evolution. Evidently, clinical findings, signs and symptoms of a patient are the phenotypic expression of these pathophysiological and molecular mechanisms of SARS-CoV-2 infection. Therefore, no findings alone, whether molecular, clinical, radiological or pathological axis are sufficient for an accurate diagnosis. However, their intersection and/or correlation are extremely critical for clinicians establish the diagnosis and new treatment perspectives.

COVID-19-associated acute respiratory distress syndrome (CARDS): Current knowledge on pathophysiology and ICU treatment – A narrative review

“…In this early exudative phase, the inactivation of surfactant, fibrin deposition [ 48 ] and hyaline membrane generation, extensive tissue inflammation, and the disruption of cellular homeostasis, including apoptosis and necrosis is observed (e.g., in type II pneumocytes [ 47 ]) [ 49 ], often results in “diffuse alveolar damage” (DAD). Furthermore, proliferation is often triggered, with exacerbated fibroblast and myofibroblast proliferation, which can lead to organize pneumonia [ 49 ].…”

“…In this early exudative phase, the inactivation of surfactant, fibrin deposition [ 48 ] and hyaline membrane generation, extensive tissue inflammation, and the disruption of cellular homeostasis, including apoptosis and necrosis is observed (e.g., in type II pneumocytes [ 47 ]) [ 49 ], often results in “diffuse alveolar damage” (DAD). Furthermore, proliferation is often triggered, with exacerbated fibroblast and myofibroblast proliferation, which can lead to organize pneumonia [ 49 ]. However, in addition to exudation, proliferation and pulmonary vasculopathy (due to virus-induced endotheliitis, microangiopathy, and thrombosis) [ 49 ], lung fibrosis with the irreversible destruction of the pulmonary architecture can develop, which is considered to be cytokine-driven, e.g., by transforming-growth factor beta (TGF-β) [ [50] , [51] , [52] ] and Interleukin (IL)-1β [ 53 ].…”

“…Furthermore, proliferation is often triggered, with exacerbated fibroblast and myofibroblast proliferation, which can lead to organize pneumonia [ 49 ]. However, in addition to exudation, proliferation and pulmonary vasculopathy (due to virus-induced endotheliitis, microangiopathy, and thrombosis) [ 49 ], lung fibrosis with the irreversible destruction of the pulmonary architecture can develop, which is considered to be cytokine-driven, e.g., by transforming-growth factor beta (TGF-β) [ [50] , [51] , [52] ] and Interleukin (IL)-1β [ 53 ].…”

Severe COVID-19 and Sepsis: Immune Pathogenesis and Laboratory Markers

“…This highly-vulnerable subset of patients with COVID-19 has exceptionally alarming laboratory and clinical biomarkers that include very high serum ferritin and D-dimer levels, lymphopenia, hepatic dysfunction, thrombotic tendency, disseminated intravascular coagulation (DIC), and inflammatory bursts that result in multiple-organ failure (MOF) and ultimately death. Additionally, moderate and severe COVID-19 cases present predominantly with respiratory pathology that includes alveolar damage, acute respiratory distress syndrome (ARDS), and reduced oxygen saturation [ 4 ]. Severe COVID-19 cases can trigger severe inflammatory responses [ 4 ] and patients may end up with septic shock or MOF.…”

“…Additionally, moderate and severe COVID-19 cases present predominantly with respiratory pathology that includes alveolar damage, acute respiratory distress syndrome (ARDS), and reduced oxygen saturation [ 4 ]. Severe COVID-19 cases can trigger severe inflammatory responses [ 4 ] and patients may end up with septic shock or MOF. The possible causes of this sepsis-like picture might be a dysregulated immune response incapable of controlling the production of excessive amounts of cytokines and chemokines.…”