Acute pulmonary inflammatory reaction in COVID-19 - histological and immunohistochemical study.

Coronavirus disease 2029 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which enters the human body via the respiratory route and can infect nasal and bronchial epithelial cells, goblet cells, hair cells, pneumocytes, etc. COVID-19 caused the worst pandemic in centuries. SARS-CoV-2, once in the airway tree, penetrates the host cells and causes a strong inflammatory reaction by a rapid response of the innate immune system, in particular by activation of macrophages and dendritic cells that recognize the virus component proteins as non-self. Cells of the immune system secrete type I interferon and proinflammatory cytokines, initiating an antiviral state in neighboring cells and in the intercellular connective matrix, recruiting new immune mediators and new cells to the site of infection. This rapid response is crucial for limiting the spread of SARS-CoV-2. In the present study, we aimed at highlighting some microscopic aspects of the acute inflammatory reaction in the lung for SARS-CoV-2 infection. The analysis of the histological pieces suggested that the pulmonary inflammatory reaction begins with the accumulation of immune cells in the interalveolar septa in response to viral insult, congestion of pulmonary vessels with increased blood volume in pulmonary vessels, followed by the presence of alveolar exudate, which reduces the area of hematosis and triggers respiratory symptoms. The inflammatory reaction was totally inhomogeneous, varying widely from patient to patient and even within the same patient, probably depending on the immune status, age or comorbidities. It presented two phases, a predominantly exudative phase (EP) and a predominantly proliferative phase (PP), intricately intertwined; sometimes, on the same histopathological piece, we identified both areas of incipient inflammatory reaction (EP) and a very intense reaction in the PP, suggesting that the pulmonary inflammatory reaction developed rapidly. The inflammatory infiltrate had a complex composition: neutrophilic leukocytes, macrophages, mast cells, lymphocytes and plasma cells. The most abundant inflammatory cells were macrophages, both in the EP and PP. The use of anti-interleukin (IL) antibodies showed that ILs are mainly produced by cells of the monocyte-macrophage system, but also by conjunctival cells (fibroblasts).