COVID-19 Experience and Pulmonary Arterial Hypertension: Do Earlier Theses and New Data Still Match?

We read with interest the survey estimating the incidence and outcomes of coronavirus disease (COVID-19) in patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) (1) and its associated editorial (2). It is indeed valuable knowledge regarding the impact of this pandemic on the PAH/CTEPH population in the United States, estimating a higher COVID-19–related mortality compared with the general population. Data are consistent with the survey recently published in the European Respiratory Journal, in which most of the information was collected from European countries (3). Nevertheless, it is our opinion that this information needs to be cautiously read in view of the number of patients included (70 and 50 in European Respiratory Society and AnnalsATS, respectively), the high variability between patients’ age, collection methods, andmortality figures across the countries. Although the PAH/CTEPH fatality rate is inevitably higher than in the general population, it is important to keep in mind that initial case-reports published at the beginning of this pandemic emphasized the surprisingly uneventful course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in these patients, and efforts were made trying to explain these observations (4, 5). We still have the impression, based on our own updated data with 38 confirmed COVID-19 cases in a cohort of 770 patients under follow-up, that their COVID-19–associated risk continues to be lower than expected back inMarch 2020. In fact, only 3 of these 38 (8%) patients died, all of them belonging to low-risk PAH/CTEPH scores but with significant advanced age and comorbidities. On the contrary, younger patients with higher-risk PAH score hospitalized with bilateral pneumonia performed surprisingly well and could be discharged, whereas their usual mortality risk from respiratory failure processes reaches 20%. We enjoyed the editorial reviewing how the substrates inherent to the vascular remodeling that characterizes both PAH and CTEPH could modify COVID-19 course by various mechanisms. In a recent review of this topic, it was indeed pointed out how difficult it was to estimate the net effect of this PAH/CTEPH-underlying histopathology (6). Many theories in different directions have been formulated about the role of ACE2 receptor, the ventilation–perfusion mismatch, or the tertiary lymphoid tissue that characterizes PAH. The same is true for the impact of PAH-targeted treatments. Although this net effect might be difficult to estimate, we should not forget that it has drawn the attention of the scientific community, and several trials are ongoing exploring the effectiveness of PAH-specific therapies in COVID-19 (6). We are awaiting with particular interest the results of the randomized clinical trial evaluating ambrisentan. We would also like to stress the importance of the prothrombotic status that accompanies COVID-19 and the current consensus on the use of prophylactic heparin in COVID-19 pneumonia. Notably, no thromboembolic events were reported in the European Respiratory Journal survey despite thromboembolism being a well-recognized complication of COVID-19 (3). This endorses our theory of chronic anticoagulation being another potential gamechanger in the course of COVID-19 in patients with CTEPH, in whom it may offset this thrombogenic environment. In this line, ongoing clinical trials are evaluating the use of different anticoagulant drugs in COVID-19 (6). In conclusion, large international surveys are indeed necessary to better estimate the impact of COVID-19 in patients with PAH/CTEPH However, collection methods and baseline characteristics of patients among countries make still difficult to draw conclusions. Although their overall risk related to COVID-19 might be understandably higher than that for the general population, it is our experience that is not as catastrophic as we initially expected. Moreover, some of the observations made in the field of COVID-19–PAH/CTEPH have prompted the design of clinical trials that may allow us to broaden the knowledge of this disease and hopefully to improve its management.