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Four-Month Clinical Status of a Cohort of Patients After Hospitalization for COVID-19

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  What are the clinical outcomes after hospitalization for COVID-19?

Findings  Four months after hospitalization, in an uncontrolled cohort study of 478 survivors of COVID-19, at least 1 new-onset symptom was reported by telephone interview by 244 patients (51%), including fatigue in 134 of 431 (31%), cognitive symptoms in 86 of 416 (21%), and dyspnea in 78 of 478 (16%). Computed tomographic lung scan abnormalities were reported in 63% of 171 patients assessed at an ambulatory visit, mainly subtle ground-glass opacities. Fibrotic lesions were observed in 19% of these 171 patients.

Meaning  This study provides clinical status of a cohort of patients 4 months after hospitalization for COVID-19, but further research is needed to understand longer-term outcomes.

Abstract

Importance  Little is known about long-term sequelae of COVID-19.

Objective  To describe the consequences at 4 months in patients hospitalized for COVID-19.

Design, Setting, and Participants  In a prospective uncontrolled cohort study, survivors of COVID-19 who had been hospitalized in a university hospital in France between March 1 and May 29, 2020, underwent a telephone assessment 4 months after discharge, between July 15 and September 18, 2020. Patients with relevant symptoms and all patients hospitalized in an intensive care unit (ICU) were invited for further assessment at an ambulatory care visit.

Exposures  Survival of hospitalization for COVID-19.

Main Outcomes and Measures  Respiratory, cognitive, and functional symptoms were assessed by telephone with the Q3PC cognitive screening questionnaire and a checklist of symptoms. At the ambulatory care visit, patients underwent pulmonary function tests, lung computed tomographic scan, psychometric and cognitive tests (including the 36-Item Short-Form Health Survey and 20-item Multidimensional Fatigue Inventory), and, for patients who had been hospitalized in the ICU or reported ongoing symptoms, echocardiography.

Results  Among 834 eligible patients, 478 were evaluated by telephone (mean age, 61 years [SD, 16 years]; 201 men, 277 women). During the telephone interview, 244 patients (51%) declared at least 1 symptom that did not exist before COVID-19: fatigue in 31%, cognitive symptoms in 21%, and new-onset dyspnea in 16%. There was further evaluation in 177 patients (37%), including 97 of 142 former ICU patients. The median 20-item Multidimensional Fatigue Inventory score (n = 130) was 4.5 (interquartile range, 3.0-5.0) for reduced motivation and 3.7 (interquartile range, 3.0-4.5) for mental fatigue (possible range, 1 [best] to 5 [worst]). The median 36-Item Short-Form Health Survey score (n = 145) was 25 (interquartile range, 25.0-75.0) for the subscale “role limited owing to physical problems” (possible range, 0 [best] to 100 [worst]). Computed tomographic lung-scan abnormalities were found in 108 of 171 patients (63%), mainly subtle ground-glass opacities. Fibrotic lesions were observed in 33 of 171 patients (19%), involving less than 25% of parenchyma in all but 1 patient. Fibrotic lesions were observed in 19 of 49 survivors (39%) with acute respiratory distress syndrome. Among 94 former ICU patients, anxiety, depression, and posttraumatic symptoms were observed in 23%, 18%, and 7%, respectively. The left ventricular ejection fraction was less than 50% in 8 of 83 ICU patients (10%). New-onset chronic kidney disease was observed in 2 ICU patients. Serology was positive in 172 of 177 outpatients (97%).

Conclusions and Relevance  Four months after hospitalization for COVID-19, a cohort of patients frequently reported symptoms not previously present, and lung-scan abnormalities were common among those who were tested. These findings are limited by the absence of a control group and of pre-COVID assessments in this cohort. Further research is needed to understand longer-term outcomes and whether these findings reflect associations with the disease.

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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Corresponding Author: Xavier Monnet, MD, PhD, Service de Médecine Intensive-Réanimation, Hôpital de Bicêtre, 78, rue du Général Leclerc, 94 270 Le Kremlin-Bicêtre, France (xavier.monnet@aphp.fr).

Accepted for Publication: February 22, 2021.

Published Online: March 17, 2021. doi:10.1001/jama.2021.3331

Correction: This article was corrected on November 9, 2021, to add a supplement listing the nonauthor collaborators of the COMEBAC study.

Authors/Writing Committee for the COMEBAC Study Group Luc Morin, MD, MSc; Laurent Savale, MD, PhD; Tài Pham, MD, PhD; Romain Colle, MD, PhD; Samy Figueiredo, MD, PhD; Anatole Harrois, MD, PhD; Matthieu Gasnier, MD; Anne-Lise Lecoq, MD, PhD; Olivier Meyrignac, MD, PhD; Nicolas Noel, MD, PhD; Elodie Baudry, MD; Marie-France Bellin, MD; Antoine Beurnier, MD; Walid Choucha, MD; Emmanuelle Corruble, MD, PhD; Laurent Dortet, PharmD, PhD; Isabelle Hardy-Leger, MA; François Radiguer, MA; Sabine Sportouch, MA; Christiane Verny, MD; Benjamin Wyplosz, MD, PhD; Mohamad Zaidan, MD, PhD; Laurent Becquemont, MD, PhD; David Montani, MD, PhD; Xavier Monnet, MD, PhD.

Affiliations of Authors/Writing Committee for the COMEBAC Study Group: Université Paris-Saclay, AP-HP, Service de Réanimation Pédiatrique et Médecine Néonatale, Hôpital de Bicêtre, Santé de l'Enfant et de l'Adolescent, Le Kremlin-Bicêtre, France (Morin); Université Paris-Saclay, AP-HP, Service de Pneumologie et Soins Intensifs Respiratoires, DMU 5, Thorinno, Inserm UMR_S999, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France (Savale, Montani); Université Paris-Saclay, 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 (Pham, Sportouch, Monnet); Université Paris-Saclay, AP-HP, Service de Psychiatrie, Hôpital de Bicêtre, DMU 11 Psychiatrie, Santé Mentale, Addictologie et Nutrition, Équipe MOODS, INSERM U1178, CESP (Centre de Recherche en Epidémiologie et Santé des Populations), Le Kremlin-Bicêtre, France (Colle, Gasnier, Choucha, Corruble); Université Paris-Saclay, AP-HP, Service de Réanimation Chirurgicale, Hôpital de Bicêtre, DMU 12 Anesthésie, Réanimation, Douleur, Le Kremlin-Bicêtre, France (Figueiredo, Harrois, Radiguer); Université Paris-Saclay, 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 (Lecoq, Becquemont); Université Paris-Saclay, AP-HP, Service de Radiologie Diagnostique et Interventionnelle, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France (Meyrignac, Bellin); Université Paris-Saclay, AP-HP, Service de Médecine Interne et Immunologie Clinique, Hôpital de Bicêtre, DMU 7 Endocrinologie-Immunités-Inflammations Cancer-Urgences, Le Kremlin-Bicêtre, France (Noel, Hardy-Leger); Université Paris-Saclay, AP-HP, Service de Gériatrie Aiguë, Hôpital de Bicêtre, DMU 1 Médecine Territoire Gériatrie, Le Kremlin-Bicêtre, France (Baudry, Verny); Université Paris-Saclay, AP-HP, Service de Physiologie et d'Explorations Fonctionnelles Respiratoires, Hôpital de Bicêtre, DMU 5 Thorinno, Inserm UMR_S999, Le Kremlin-Bicêtre, France (Beurnier); Université Paris-Saclay, AP-HP, Service de Microbiologie, Hôpital de Bicêtre, DMU 15 Biologie-Génétique-PUI, INSERM 1193, Le Kremlin-Bicêtre, France (Dortet); Université Paris-Saclay, AP-HP, Service des Maladies Infectieuses et Tropicales, Hôpital de Bicêtre, DMU 7 Endocrinologie-Immunités-Inflammations Cancer-Urgences, INSERM U1018, CESP, Le Kremlin-Bicêtre, France (Wyplosz); Université Paris-Saclay, AP-HP, Service de Néphrologie Transplantation, Hôpital de Bicêtre, DMU 4 CORREVE Maladies du Cœur et des Vaisseaux, Le Kremlin-Bicêtre, France (Zaidan).

Author Contributions: Dr Monnet had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Morin, Savale, Pham, Colle, Figueiredo, Harrois, Gasnier, Lecoq, Meyrignac, Noel, Baudry, Bellin, Beurnier, Corruble, Dortet, Hardy-Leger, Sportouch, Wyplosz, Zaidan, Becquemont, Montani, Monnet.

Acquisition, analysis, or interpretation of data: Morin, Savale, Pham, Colle, Figueiredo, Harrois, Gasnier, Lecoq, Meyrignac, Noel, Bellin, Beurnier, Choucha, Corruble, Dortet, Radiguer, Sportouch, Verny, Wyplosz, Zaidan, Becquemont, Montani, Monnet.

Drafting of the manuscript: Morin, Savale, Pham, Colle, Figueiredo, Harrois, Meyrignac, Noel, Baudry, Bellin, Beurnier, Corruble, Dortet, Hardy-Leger, Sportouch, Wyplosz, Zaidan, Becquemont, Montani, Monnet.

Critical revision of the manuscript for important intellectual content: Morin, Savale, Pham, Colle, Figueiredo, Harrois, Gasnier, Lecoq, Meyrignac, Noel, Baudry, Bellin, Beurnier, Choucha, Corruble, Dortet, Radiguer, Verny, Wyplosz, Zaidan, Becquemont, Montani, Monnet.

Statistical analysis: Morin, Pham, Colle, Figueiredo, Noel, Dortet, Radiguer, Wyplosz, Monnet.

Obtained funding: Savale, Baudry, Wyplosz, Becquemont, Monnet.

Administrative, technical, or material support: Morin, Pham, Figueiredo, Harrois, Lecoq, Baudry, Bellin, Beurnier, Sportouch, Wyplosz, Becquemont, Montani, Monnet.

Supervision: Morin, Savale, Pham, Figueiredo, Noel, Baudry, Choucha, Corruble, Dortet, Sportouch, Wyplosz, Zaidan, Becquemont, Montani, Monnet.

Other: Sportouch.

Conflict of Interest Disclosures: Dr Harrois reported personal fees from LFB Laboratory and Edwards, and fees from Mindray Fees to his institution, outside the submitted work. Dr Lecoq reported nonfinancial support from Pfizer SAS and from Sanofi Aventis France outside the submitted work. Dr Noel reported personal fees from MSD and from Biogen outside the submitted work. Dr Beurnier reported personal fees from Sanofi outside the submitted work. Dr Becquemont reported grants from Sanofi Genzyme for a presentation concerning Gaucher disease, and pharmacogenetics and drug interactions with Eliglustat outside the submitted work. Dr Montani reported personal fees from Actelion, GSK, Pfizer, MSD, Chiesi, Boehringer, and Incyte Biosciences France; grants from Bayer and MSD; and nonfinancial support from Acceleron, outside the submitted work. Dr Monnet reported personal fees from Getinge Pulsion Medical and Baxter outside the submitted work. No other disclosures were reported.

Funding/Support: This study was funded by Assistance Publique-Hôpitaux de Paris.

Role of the Funder/Sponsor: The funder was not involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The sponsor did not have the right to veto publication or to control the decision regarding to which journal the paper was submitted.

Group Information: The COMEBAC study investigators are listed in Supplement 2.

Data Sharing Statement: The data sets generated during the current study are available from the corresponding author on request.

Additional Contributions: We thank Thomas Piraino, RRT, FCST (Department of Anesthesia, Division of Critical Care, McMaster University), for English editing. He did not receive financial compensation for his contribution. We thank Jackie Abdel Nour, Younes Boujana, Marie Deloncle, Tatiana Fouasse, Nassim Hamidat, Mario Hindie, Yasmine Iftene, Jean-Vincent Laqua, Jules Madjarian, Dalil Sadki, and Sabrina Safer, all from Paris-Saclay Medical School, for their help in data collection. They received financial compensation for their contribution. We thank Cassandre Sainrose, Paris 8 University, for her help in data collection. She did not receive financial compensation for her contribution. We thank the patients who participated in this cohort, as well as the physicians, psychologists, nurses, care helpers, biologists, pharmacists, other allied health professionals, and the administrators of the Bicêtre Hospital.

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