Spontaneous Breathing and Evolving Phenotypes of Lung Damage in Patients with COVID-19: Review of Current Evidence and Forecast of a New Scenario

Abstract

The mechanisms of acute respiratory failure other than inflammation and complicating the SARS-CoV-2 infection are still far from being fully understood, thus challenging the management of COVID-19 patients in the critical care setting. In this unforeseen scenario, the role of an individual's excessive spontaneous breathing may acquire critical importance, being one potential and important driver of lung injury and disease progression. The consequences of this acute lung damage may impair lung structure, forecasting the model of a fragile respiratory system. This perspective article aims to analyze the progression of injured lung phenotypes across the SARS-CoV-2 induced respiratory failure, pointing out the role of spontaneous breathing and also tackling the specific respiratory/ventilatory strategy required by the fragile lung type.

Keywords: COVID-19; SARS-CoV-2; acute respiratory distress syndrome; acute respiratory failure; mechanical ventilation; spontaneous breathing.

Figure 1

Mechanisms of progression between phenotype: Different hypothetical mechanisms, involving physical stimuli and biological modifications, can determine the progression between COVID-19 phenotypes. Progression from type L to type H may result from excessive inspiratory effort (SILI) and from recruitment of neutrophils into the lung parenchyma with secretion of proteases and reactive oxygen species. Furthermore, a role of activation of Fc receptors immune cells through antibody-virus immune complexes has been hypothesized. Progression from type H to type F results from damage to the scaffolding of the lung and vascular lesions with disorganized repair and imbalance between profibrotic and antifibrotic mediators. Physical factors, such as lung parenchyma stretch, may also contribute via transforming growth factor-beta (TGFB) secretion. See the text for more details.

Figure 2

Hypothetical role of inspiratory effort in progression from type L to type H and F: Figure 2 shows DPes monitoring in two patients with SARS-CoV-2 pneumonia undergoing non-invasive ventilation (NIV) with Helmet. Patient 1, at the top of the figure, shows type L phenotype on computed tomography (CT) scan, and modest inspiratory effort (DPes 11 cm H₂O). Over time, a progressive clinical and radiological improvement with ground glass changes resolutions was recorded. Patient 2, at the bottom of the figure, shows significant inspiratory effort (DPes 32 cm H₂O). Over time, there was a progression from type L to type H required intubation and invasive mechanical ventilation. Progression from type H to type F was documented after 45 days from Intensive Care Unit admission. DPes: Change in esophageal pressure.