Functional respiratory complaints among COVID-19 survivors: a prospective cohort study

Antoine Beurnier; Laurent Savale; Xavier Jaïs; Romain Colle; Tai Pham; Luc Morin; Sophie Bulifon; Nicolas Noël; Athénaïs Boucly; Benoit Delbarre; Nathan Ebstein; Samy Figueiredo; Matthieu Gasnier; Anatole Harrois; Etienne-Marie Jutant; Mitja Jevnikar; Sophia Keddache; Anne-Lise Lecoq; Olivier Meyrignac; Florence Parent; Jérémie Pichon; Mariana Preda; Anne Roche; Andrei Seferian; Marie-France Bellin; Thomas Gille; Emmanuelle Corruble; Olivier Sitbon; Laurent Becquemont; Xavier Monnet; Marc Humbert; David Montani; and the Comebac Investigators; Comebac Investigators

doi:10.1183/23120541.00063-2023

Functional respiratory complaints among COVID-19 survivors: a prospective cohort study

ERJ Open Res. 2023 May 2;9(3):00063-2023. doi: 10.1183/23120541.00063-2023. eCollection 2023 Jul.

Authors

Antoine Beurnier^{1

2

3

4}, Laurent Savale^{1

2

5

4}, Xavier Jaïs^{1

2

5}, Romain Colle^{1

6}, Tai Pham^{1

7

8}, Luc Morin^{1

9}, Sophie Bulifon^{1

2

5}, Nicolas Noël^{1

10}, Athénaïs Boucly^{1

2

5}, Benoit Delbarre⁵, Nathan Ebstein^{1

2

5}, Samy Figueiredo^{1

11}, Matthieu Gasnier^{1

6}, Anatole Harrois^{1

11}, Etienne-Marie Jutant^{1

2

5}, Mitja Jevnikar^{1

2

5}, Sophia Keddache^{1

2

5}, Anne-Lise Lecoq^{1

12}, Olivier Meyrignac^{1

13}, Florence Parent^{1

2

5}, Jérémie Pichon^{1

2

5}, Mariana Preda^{1

2

5}, Anne Roche^{1

2

5}, Andrei Seferian^{1

2

5}, Marie-France Bellin^{1

13}, Thomas Gille^{14

15}, Emmanuelle Corruble^{1

6}, Olivier Sitbon^{1

2

5}, Laurent Becquemont^{1

12}, Xavier Monnet^{1

2

7}, Marc Humbert^{1

2

5}, David Montani^{1

2

5}; and the Comebac Investigators; Comebac Investigators

Affiliations

¹ Université Paris-Saclay, Faculty of Medicine, Le Kremlin-Bicêtre, France.
² INSERM UMR_S 999, Pulmonary Hypertension: Pathophysiology and Novel Therapies, Hôpital Marie Lannelongue, Le Plessis Robinson, France.
³ AP-HP, Department of Physiology - Pulmonary Function Testing, DMU 5 Thorinno, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.
⁴ These authors contributed equally.
⁵ AP-HP, Department of Respiratory and Intensive Care Medicine, Pulmonary Hypertension National Referral Centre, Hôpital Bicêtre, DMU 5 Thorinno, Le Kremlin-Bicêtre, France.
⁶ AP-HP, Service de psychiatrie, Hôpital de Bicêtre, DMU 11, Equipe MOODS, INSERM U1018, CESP (Centre de Recherche en Epidémiologie et Santé des Populations), Le Kremlin-Bicêtre, France.
⁷ AP-HP, Service de Médecine Intensive-Réanimation, Hôpital de Bicêtre, DMU 4 CORREVE Maladies du Cœur et des Vaisseaux, FHU Sepsis, Le Kremlin-Bicêtre, France.
⁸ INSERM UMR_S1018, Equipe d'Epidémiologie Respiratoire Intégrative, CESP, Villejuif, France.
⁹ AP-HP, Service de Réanimation Pédiatrique et Médecine Néonatale, Hôpital de Bicêtre, Santé de l'Enfant et de l'Adolescent, Le Kremlin-Bicêtre, France.
¹⁰ AP-HP, Service de Médecine Interne et Immunologie Clinique, Hôpital de Bicêtre, DMU 7 Endocrinologie-Immunités-Inflammations-Cancer-Urgences, Le Kremlin-Bicêtre, France AP.
¹¹ HP, Service de Réanimation Chirurgicale, Hôpital de Bicêtre, DMU 12 Anesthésie, Réanimation, Douleur, Le Kremlin-Bicêtre, France.
¹² AP-HP, Centre de Recherche Clinique Paris-Saclay, DMU 13 Santé Publique, Information Médicale, Appui à la Recherche Clinique, INSERM U1018, CESP, Le Kremlin-Bicêtre, France.
¹³ AP-HP, Service de Radiologie Diagnostique et Interventionnelle, Hôpital de Bicêtre, DMU 14 Smart Imaging, BioMaps, Le Kremlin-Bicêtre, France.
¹⁴ INSERM U1272, Hypoxia and the Lung, UFR SMBH Léonard de Vinci, Université Sorbonne Paris Nord, Bobigny, France.
¹⁵ AP-HP, Department of Physiology and Functional Explorations, DMU NARVAL, Hôpitaux Universitaires de Paris Seine-Saint-Denis, Sites Avicenne (Bobigny) et Jean Verdier (Bondy), France.

Abstract

Background: Dyspnoea is a common persistent symptom after COVID-19. Whether it is associated with functional respiratory disorders remains unclear.

Methods: We assessed the proportion and characteristics of patients with "functional respiratory complaints" (FRCs) (as defined by Nijmegen Questionnaire >22) among 177 post-COVID-19 individuals who benefited from outclinic evaluation in the COMEBAC study (i.e., symptomatic and/or intensive care unit (ICU) survivors at 4 months). In a distinct explanatory cohort of 21 consecutive individuals with unexplained post-COVID-19 dyspnoea after routine tests, we also analysed the physiological responses to incremental cardiopulmonary exercise testing (CPET).

Findings: In the COMEBAC cohort, 37 patients had significant FRCs (20.9%, IC95: 14.9-26.9). The prevalence of FRCs ranged from 7.2% (ICU patients) to 37.5% (non-ICU patients). The presence of FRCs was significantly associated with more severe dyspnoea, lower 6-min walk distance, more frequent psychological and neurological symptoms (cognitive complaint, anxiety, depression, insomnia and post-traumatic stress disorders) and poorer quality of life (all p<0.01). In the explanatory cohort, seven out of 21 patients had significant FRCs. Based on CPET, dysfunctional breathing was identified in 12 out of 21 patients, five out of 21 had normal CPET, three out of 21 had deconditioning and one out of 21 had evidence of uncontrolled cardiovascular disease.

Interpretation: FRCs are common during post-COVID-19 follow-up, especially among patients with unexplained dyspnoea. Diagnosis of dysfunctional breathing should be considered in those cases.