Thoughts on the alveolar phase of COVID-19

Abstract

COVID-19 can be divided into three clinical stages, and one can speculate that these stages correlate with where the infection resides. For the asymptomatic phase, the infection mostly resides in the nose, where it elicits a minimal innate immune response. For the mildly symptomatic phase, the infection is mostly in the pseudostratified epithelium of the larger airways and is accompanied by a more vigorous innate immune response. In the conducting airways, the epithelium can recover from the infection, because the keratin 5 basal cells are spared and they are the progenitor cells for the bronchial epithelium. There may be more severe disease in the bronchioles, where the club cells are likely infected. The devastating third phase is in the gas exchange units of the lung, where ACE2-expressing alveolar type II cells and perhaps type I cells are infected. The loss of type II cells results in respiratory insufficiency due to the loss of pulmonary surfactant, alveolar flooding, and possible loss of normal repair, since type II cells are the progenitors of type I cells. The loss of type I and type II cells will also block normal active resorption of alveolar fluid. Subsequent endothelial damage leads to transudation of plasma proteins, formation of hyaline membranes, and an inflammatory exudate, characteristic of ARDS. Repair might be normal, but if the type II cells are severely damaged alternative pathways for epithelial repair may be activated, which would result in some residual lung disease.

A human disease model of SARS-CoV-2-induced lung injury and immune responses with a microengineered organ chip

“…Particularly, we found that human circulating immune cells play a key role in exacerbating inflammatory responses and the injury of alveolar-capillary-barrier induced by SARS-CoV-2. These findings provide new insight into the pathogenesis of SARS-CoV-2, in which virus-induced inflammatory responses and lung injury were possibly mediated by the complex and intrinsic cross-talk among epithelium-endothelium interface and immune cells.As known, the AT II cells have been demonstrated as the primary infected target of SARS-CoV-2 by histopathological studies[35]. In this study, we found human alveolar epithelial cells were more susceptible to SARS-CoV-2 infection than endothelial cells as identified on the chip.…”

Surface Active Agents and Their Health-Promoting Properties: Molecules of Multifunctional Significance

“…This is a multifactorial condition, also caused by pulmonary surfactant deficit and prolonged inflammatory responses. Importantly, COVID-19 can lead to ARDS as SARS-CoV-2 can infect and impair the function of type II cells in the lungs, affecting the production of pulmonary surfactants, at the third stage of the infection [ 140 ]. Current therapeutic approaches include anti-inflammatory agents, vasodilators and surfactant replacement therapy, among others [ 141 , 142 ].…”

Early COVID-19 lockdown in Greece and idiopathic pulmonary fibrosis: a beneficial “impact” beyond any expectation

“…It is postulated that the inhaled virus initially binds to nasal epithelial cells and starts propagating towards the lower respiratory tract reaching the alveoli where it infects preferentially alveolar type II cells [8]. Extensive viral replication leads to their apoptosis and cell-death, triggering through several inflammatory cascades DAD, clinically presenting as ARDS [9]. SARS-CoV-2 for its potential to induce pneumonia represents the novel infectious agent that could trigger in patients with IPF life-threatening AEs [10].…”