key: cord-0851314-d8ns05ck
authors: Belge, Catharina; Quarck, Rozenn; Godinas, Laurent; Montani, David; Escribano Subias, Pilar; Vachiéry, Jean-Luc; Nashat, Heba; Pepke-Zaba, Joanna; Humbert, Marc; Delcroix, Marion
title: COVID-19 in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: a reference centre survey
date: 2020-11-02
journal: ERJ Open Res
DOI: 10.1183/23120541.00520-2020
sha: 008dad5c5d68c93f6293db66f3ddaae7c298fe11
doc_id: 851314
cord_uid: d8ns05ck

This international survey highlights that a limited number of PAH and CTEPH patients suffered from severe #COVID19 infection https://bit.ly/3jGuBQq

therapy (59%), followed by monotherapy (21%) and only a minority were on triple therapy (7% and 13% on oral and parenteral prostanoids, respectively) (n=56). Very few patients were on immunosuppressive therapy (4%). Regarding CTEPH patients, 73% were inoperable or with post-operative residual PH, 18% were waiting for balloon pulmonary angioplasty (BPA) and 9% for pulmonary endarterectomy (PEA); 9% had BPA, but none had PEA delayed, because of the pandemic logistic situation (n=11).

Pneumonia was the most frequent presentation at diagnosis (56%), followed by only fever (28%), then upper respiratory tract infection (13%), other symptoms including myalgia, dyspnoea or cough (13%), PH exacerbation and/or right heart failure (5%); anosmia and/or ageusia was observed in 3% of the patients and 3% were asymptomatic. Venous thromboembolism or haemoptysis were not reported at diagnosis (n=61). Nasopharyngeal swabs (74%) and a few low-dose computed tomography (CT) scans (15%) were used to confirm COVID-19 diagnosis, irrespective of the geographic location (n=66). The diagnosis was clinically suspected but unproven in 11% and no patient received a bronchoalveolar lavage. Most of the patients displayed typical COVID-19 CT (54%), 7% harboured atypical CT and 39% did not undergo a CT scan at diagnosis; normal CT was not reported (n=46). The majority of the patients were hospitalised on a general ward (46%), 17% needed ICU admission, 6% were in other healthcare facilities (including nursing homes, intermediate care unit and social-sanitary centre) and 30% were treated at home (n=63). The median duration of symptoms was 6.0 days (range: 1-36 days). The median duration of hospitalisation was 3.4 days (range: 2-32 days) and patients were mostly hospitalised in the hospital of the responding centre (47%), 31% in a local hospital and 22% in another expert centre. Most of the patients needed respiratory support, 57% received oxygen, 12% required high-flow nasal cannula, 2% received continuous positive airway pressure or bilevel positive airway pressure, 11% required invasive mechanical ventilation and no patient was reported on extracorporal membrane oxygenation (ECMO) (n=65). COVID-19 treatment consisted in most of the cases of antibiotics (41%, including 20% azithromycin) followed by hydroxychloroquine or chloroquine (31%), lopinavir or ritonavir (14%), itraconazole (1%) and other treatments including tocilizumab, methylprednisolone, mycophenolate, favipiravir and rituximab (14%); none of them received remdesivir/GS-5734 (n=70). For all cases (n=70), mortality was 19%, 20% for PAH and 14% for CTEPH patients. 10 15 20 The results of this international survey show that few PAH and CTEPH patients required ICU admission or invasive ventilation and none were treated with ECMO, in contrast to expectations for patients with underlying respiratory or cardiovascular diseases [1] . The observed case-fatality rate, estimated as the number of deaths per 100 reported cases, was 19%, which is high in comparison with the rate observed in the general population (5.9% to 16.3%, in the USA and Belgium, respectively; data extracted on 25 May 2020 [8] ), and with hospital mortality in the large series from New York City (9.7% [9] ). However, comparing mortality to a general population is difficult; there was an important variability between countries (figure 1a), partially explained by age distribution (Pearson correlation between the number of deaths and the number of patients older than 60 years of age: r=0.93, p=0.02), and by disrupted systematic follow-up (correlation between the number of deaths and the proportion of patients without remote or live consultation: r=0.98, p=0.02), suggesting underestimation of benign cases.

Shielding at home could, in part, explain the low number of cases reported in this survey since the PAH and CTEPH population is medically educated, thereby better prepared to respect social distancing instructions, and sometimes socially isolated by the disease and its consequences. HORN et al. [7] also suggested a potential protective effect of PAH medication by different mechanisms involving pulmonary endothelial cells. In the current international survey, most patients actually benefited from combination therapy of endothelin receptor antagonists, phosphodiesterase 5 inhibitors and/or prostanoids (62%), showing a net progress in comparison with most recent registries (i.e. 41% in COMPERA) [10] , in agreement with the most recent European Society of Cardiology/European Respiratory Society recommendations [11] . The use of anticoagulants was not queried in this survey; however, no case of venous thromboembolism was reported despite the increased prevalence of pulmonary embolism/ thrombosis [12] [13] [14] [15] and the presence of microthrombi within pulmonary capillaries [14, 15] reported in COVID-19 patients.

In summary, this survey, although incomplete, highlights that a limited number of PAH and CTEPH patients suffered from COVID-19, whereas the case-fatality rate related to COVID-19 was rather high in comparison with the general population. Further comprehensive investigation would be required to elucidate 1) whether underreporting of benign cases can explain the heterogeneity of outcome among different countries, and 2) whether tight adherence to social distancing is the main explanation or other physiopathological factors may prevent COVID-19 infection in severe PH. 

Gul Öngen (Cerrahpaşa Medical Faculty, Istambul, Turkey), Caneva Jorge Osvaldo (Fundacion Favaloro

The Netherla,ds)

People at increased risk and other people who need to take extra precautions

Aetiology and outcomes of severe right ventricular dysfunction

Outcomes of hospitalisation for right heart failure in pulmonary arterial hypertension

Prognostic factors of acute heart failure in patients with pulmonary arterial hypertension

Characteristics and outcome after hospitalization for acute right heart failure in patients with pulmonary arterial hypertension

Care of patients with pulmonary arterial hypertension during the coronavirus (COVID-19) pandemic

Could pulmonary arterial hypertension patients be at a lower risk from severe COVID-19?

Mortality analysis

Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area

Elderly patients diagnosed with idiopathic pulmonary arterial hypertension: results from the COMPERA registry

ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the

Incidence of thrombotic complications in critically ill ICU patients with COVID-19

Pulmonary embolism in patients with Covid-19 pneumonia

Endothelial cell dysfunction: a major player in SARS-CoV-2 infection (COVID-19)

Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19

Conflict of interest: C. Belge reports personal fees from Actelion/Janssen and MSD/Bayer outside the submitted work. R. Quarck has nothing to disclose. L. Godinas reports personal fees from Actelion outside the submitted work. D. Montani reports grants and personal fees from Actelion and Bayer, personal fees from GSK and Pfizer, grants, personal fees and nonfinancial support from MSD, personal fees from Chiesi and Boerhinger, and nonfinancial support from Acceleron, outside the submitted work. P. Escribano Subias reports personal fees and grants from Janssen, and personal fees from MSD, GlaxoSmithKline and Ferrer, outside the submitted work. J-L. Vachiery reports grants from Actelion J&J, and other support from Bayer HealthCare, Bial Portela, PhaseBio, Respira Therapeutics and United Therapeutics, outside the submitted work. H. Nashat reports grants from Actelion Pharmaceuticals outside the submitted work. J. Pepke-Zaba reports grants, personal fees and nonfinancial support from Actelion, grants and personal fees from Merck, and personal fees from Bayer, outside the submitted work. M. Humbert reports grants and personal fees from Actelion, and personal fees from GSK, Merck and Acceleron, outside the submitted work. M. Delcroix reports grants and other support from Actelion/J&J, and other support from Bayer, MSD, Reata, Bellarophon and Acceleron, outside the submitted work.