Effect of Coronavirus Disease 2019 in Pulmonary Circulation. The Particular Scenario of Precapillary Pulmonary Hypertension

Abstract

The Coronavirus Disease of 2019 (COVID-19) has supposed a global health emergency affecting millions of people, with particular severity in the elderly and patients with previous comorbidities, especially those with cardiovascular disease. Patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) could represent an especially vulnerable population because of the high mortality rates reported for respiratory infections. However, the number of COVID-19 cases reported among PAH and CTEPH patients is surprisingly low. Furthermore, the clinical picture that has been described in these patients is far from the severity that experts would expect. Endothelial dysfunction is a common feature between patients with PAH/CTEPH and COVID-19, leading to ventilation/perfusion mismatch, vasoconstriction, thrombosis and inflammation. In this picture, the angiotensin-converting enzyme 2 plays an essential role, being directly involved in the pathophysiology of both clinical entities. Some of these common characteristics could explain the good adaptation of PAH and CTEPH patients to COVID-19, who could also have obtained a benefit from the disease’s specific treatments (anticoagulant and pulmonary vasodilators), probably due to its protective effect on the endothelium. Additionally, these common features could also lead to PAH/CTEPH as a potential sequelae of COVID-19. Throughout this comprehensive review, we describe the similarities and differences between both conditions and the possible pathophysiological and therapeutic-based mechanisms leading to the low incidence and severity of COVID-19 reported in PAH/CTEPH patients to date. Nevertheless, international registries should look carefully into this population for better understanding and management.

COVID-19 and Pulmonary Hypertension in Children: What Do We Know So Far?

“…Hemodynamic profiles in COVID-19 patients with ARDS are consistent with the elevated diastolic pulmonary gradient (the difference between the diastolic pulmonary artery pressure and the pulmonary artery wedge pressure) of >7 and pulmonary vascular resistance (PVR) >3 Wood units x m 2 , suggesting a pre-capillary type of PH [ 23 , 24 ]. RV dysfunction by elevated PVR is a poor prognostic factor in patients with COVID-19 [ 25 ].…”

COVID-19 in Pulmonary Artery Hypertension (PAH) Patients: Observations from a Large PAH Center in New York City

“…A small survey and other COVID-19 PAH/CTEPH series reported to date [ 5 , 6 , 7 , 8 ] have suggested that COVID-19 has a relatively benign course in the setting of PAH and surprisingly favorable clinical outcomes. Postulated mechanisms for the presumed low risk for severe COVID-19 included protective effects of known low ACE2 levels in PAH, resulting in decreased viral entrance in the lung cells, mitigation from the COVID-19 cytokine storm afforded by the chronic inflammatory milieu of PAH, or theoretical (and controversial) hemodynamic beneficial effects on the ventilation/perfusion matching in COVID pneumonia/ARDS of specific PAH medication [ 5 , 6 , 7 , 8 , 9 ]. A larger survey of 58 pulmonary hypertension comprehensive centers in the US showed more sobering findings with an estimated hospitalization rate of PAH/CTEPH patients with recognized COVID-19 of 30% and mortality of 12%, which are worse outcomes compared to those in general population [ 11 ].…”

“…Additionally, in published series to date, PAH patients that developed COVID-19 had seemingly favorable clinical outcomes [ 5 , 6 , 7 , 8 ]. Pathophysiologic mechanisms that could explain the paucity of reported cases and the surprisingly favorable outcomes of COVID-19 in patients with PAH and CTEPH have been reviewed in detail [ 9 ]. The chronic inflammatory status implicated in the pathobiology of pulmonary vascular remodeling in PAH, as well as the reduced expression ACE2 (the transmembrane receptor of the SARS-CoV-2 virus) in PAH might contribute to decreased cytokine storm and reduced viral entrance in PAH.…”

“…Anticoagulation used in CTEPH could afford protective effect from the widespread prothrombotic milieu in COVID-19. In addition, specific PAH medications could have beneficial effect in SARS-CoV-2 pneumonitis and ARDS, either by hemodynamic, or anti-inflammatory mechanism [ 9 ]. Other groups have expressed concerns about the potential consequences of the optimistic message in these reports [ 10 ].…”

SARS-CoV-2 Spike Protein Elicits Cell Signaling in Human Host Cells: Implications for Possible Consequences of COVID-19 Vaccines

“…PAH is hard to detect because its symptoms (e.g., shortness of breath, fatigue, and dizziness) are similar to those of other common non-life threatening conditions, and the official diagnosis for PAH must be made through invasive right heart catheterization [ 36 ]. Endothelial dysfunction is a common feature of patients with PAH and COVID-19 [ 37 , 38 ].…”