Functional pathophysiology of SARS-CoV-2-induced acute lung injury and clinical implications

Abstract

The worldwide pandemic caused by the SARS-CoV-2 virus has resulted in over 84,407,000 cases with over 1,800,000 deaths when this paper was submitted, with comorbidities such as gender, race, age, body mass, diabetes, and hypertension greatly exacerbating mortality. This review will analyze the rapidly increasing knowledge of COVID-19 induced lung pathophysiology. Although controversial, the acute respiratory distress syndrome (ARDS) associated with COVID-19 (CARDS) seems to present as two distinct phenotypes: Type-L and Type-H. The 'L' refers to Low elastance, ventilation/perfusion ratio, lung weight, and recruitability, and the 'H' refers to High pulmonary elastance, shunt, edema, and recruitability. However, the LUNG SAFE and ESICM Trials Groups has shown that ~13% of the mechanically ventilated non-COVID-19 ARDS patients have the Type-L phenotype. However, other studies have shown that CARDS and ARDS respiratory mechanics overlap and that standard ventilation strategies apply to these patients. The mechanisms causing alterations in pulmonary perfusion could be caused by some combination of: 1) renin-angiotensin system (RAS) dysregulation, 2) thrombosis caused by loss of endothelial barrier, 3) endothelial dysfunction causing loss of hypoxic pulmonary vasoconstriction (HPV) perfusion control, and 4) hyper-perfusion of collapsed lung tissue that has been directly measured and supported by a computational model. A flow chart has been constructed highlighting the need for personalized and adaptive ventilation strategies, such as the time controlled adaptive ventilation (TCAV) method to set and adjust the airway pressure release ventilation (APRV) mode, which recently was shown effective at improving oxygenation and reducing FiO2, vasopressors, and sedation in COVID-19 patients.

Severe covid-19 pneumonia: pathogenesis and clinical management

“…Severe covid-19 pneumonia as defined by NIH1 overlaps significantly with the clinical definition of “classic” ARDS 60. However, several unique pathophysiological processes are postulated to be at play for CARDS, such as intravascular thrombosis caused by loss of endothelial barrier, prominent loss of hypoxic pulmonary vasoconstriction resulting from endothelial dysfunction, and excessive blood flow to collapsed lung tissue 61. Further, not all case series provide a clear semantic distinction between severe covid-19 pneumonia and CARDS, which confounds interpretation.…”

The Right Ventricle in COVID-19

“…While HPV is recognized as an important mechanism of increased pulmonary tone in non-COVID ARDS [91], its role in COVID-19 ARDS is currently controversial. Indeed, the latter may present as two distinct phenotypes, characterized by low or high elastance [93]. In the former, it has been claimed that inefficient HPV could favor massive intrapulmonary shunts in the affected lung areas, leading to profound hypoxemia with minimal hypoxemiarelated symptoms, as reported in 32% of COVID-19 patients [94].…”

Respiratory care for the critical patients with 2019 novel coronavirus

“…They challenged the concept of the two distinct phenotypes that were proposed in CARDS pathophysiology. Another study showed that CARDS and ARDS respiratory mechanics are remarkably overlapped so the standard ventilation strategy could be applied to these patients [ 119 ]. Naidoo et al , also found the clinical picture manifested in COVID-19 patients was largely consistent with classical ARDS so using traditional LPVS may be acceptable and do not warrant change at this stage.…”