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

From the Authors:

We would like to thank Dr. Segura de la Cal and colleagues for their interest in our work (1) and dedication to these important questions. We share their wish that patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) might ultimately be found to have a lower-than-expected risk for poor outcomes from coronavirus disease (COVID-19). Nevertheless, we would like to caution against early speculation that pulmonary vascular disease or its treatments may be protective in the setting of COVID-19 infection.

Although case fatality rates for COVID-19 have been hard to estimate (2), overall and age-specific case fatality rates have been reported in the general population of New York and may be reasonable benchmarks (3). The overall case fatality rate in New York was 1.4%. For individuals <64 years old, the case fatality rate was <1%. The case fatality rate then rose dramatically with age. Those aged 65–74 had a case fatality rate of 4.9% and those aged ≥75 had a case fatality rate of 14.2%. We believe these numbers are important to keep in mind when interpreting available data in patients with PAH/CTEPH.

For example, case fatality rates in our United States–based survey (12%) and the international survey of PAH/CTEPH centers (4) (19%) approach or exceed case fatality rates expected for the oldest members of the population (≥75 yr old) in New York. In fact, most patients with COVID-19 in the international survey were <65 years old, making the reported case fatality rate of 19% even more concerning. Dr. Segura de la Cal and colleagues note that their data describing patients with PAH and COVID-19 show an 8% overall case fatality rate. All three deaths (among 39 total cases) were in patients with “significant advanced age.” If we presume that some patients with recognized COVID-19 were <65 years old, the case fatality rate in their older patients must have been over 8% and could possibly be significantly higher depending on the age of the other patients. As such, their data also do not appear to suggest clear protection in the older age group. Published case series include fewer than 100 patients; therefore, we do not yet have sufficient data to suggest or refute the likelihood for protection in younger patients with PAH/CTEPH relative to the general population of the same age (in which case fatality is <1%). Although we acknowledge age-related differences in pulmonary hypertension phenotypes, it seems unlikely that PAH/CTEPH or its treatments would exert a protective effect against COVID-19 in younger patients and a detrimental effect in older patients.

To the broader point, we emphatically agree that these interesting issues are worthy of further study. The respondents are correct to highlight limitations in available population data and to temper any rush to definitive conclusions. Current studies involve small numbers of patients and comparison with the broader population must be done with caution. Differences in confounders, health behaviors, and access to COVID-19 testing (especially early in the pandemic) among patients with PAH/CTEPH might make independent associations of COVID-19 and case fatality either more or less pronounced with respect to the general population than initially reported.

In summary, existing population studies consistently suggest the same or a higher risk for poor outcomes with COVID-19 in patients with PAH/CTEPH relative to the general population. There are deficiencies in available population data, and the results contrast with hypotheses at the bench that may suggest protection (5). We would enthusiastically welcome population data that support better outcomes for these patients; however, barring this evidence, we worry that a premature impression of disease-specific protection might lead some patients with PAH/CTEPH to avoid taking life-saving precautions against contracting COVID-19.