# Four- and sixteen-month clinical status of a cohort of patients following hospitalization for COVID-19

Tài Pham, Luc Morin, Laurent Savale, Romain Colle, Samy Figueiredo, Anatole Harrois, Matthieu Gasnier, Anne Lise Lecoq, Olivier Meyrignac, Nicolas Noel, et al.

► To cite this version:

Tài Pham, Luc Morin, Laurent Savale, Romain Colle, Samy Figueiredo, et al. Four- and sixteen-month clinical status of a cohort of patients following hospitalization for COVID-19. Respiratory Medicine and Research, 2024, 86, pp.101099. 10.1016/j.resmer.2024.101099. hal-04836042

HAL Id: hal-04836042

https://hal.science/hal-04836042v1

Submitted on 22 Jan 2025

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_1.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
Original article

Four- and sixteen-month clinical status of a cohort of patients following
hospitalization for COVID-19

<figure><img src="image_2.png" /></figure>

Check for
updates

Tài Pham<sup>c</sup>, Luc Morin<sup>a,*</sup>, Laurent Savale<sup>b</sup>, Romain Colle<sup>d</sup>, Samy Figueiredo<sup>e</sup>, Anatole Harrois<sup>e</sup>, Matthieu Gasnier<sup>d</sup>, Anne-Lise Lecoq<sup>f</sup>, Olivier Meyrignac<sup>g</sup>, Nicolas Noel<sup>h</sup>, Alain Abdo<sup>g</sup>, Elodie Baudry<sup>i</sup>, Marie-France Bellin<sup>g</sup>, Antoine Beurnier<sup>j</sup>, Walid Choucha<sup>d</sup>, Emmanuelle Corruble<sup>d</sup>, Laurent Dortet<sup>k</sup>, Eugénie Gosset<sup>d</sup>, Isabelle Hardy-Leger<sup>h</sup>, Marie Quinque<sup>d</sup>, François Radiguer<sup>e</sup>, Sabine Sportouch<sup>c</sup>, Christiane Verny<sup>i</sup>, Benjamin Wyplosz<sup>l</sup>, Mohamad Zaidan<sup>m</sup>, Laurent Becquemont<sup>f</sup>, David Montani<sup>b</sup>, Xavier Monnet<sup>c</sup>

ARTICLE INFO

Article History:

Received 1 December 2023

Revised 23 February 2024

Accepted 27 February 2024

Available online 4 March 2024

Keywords:

Post-COVID syndrome

Long-COVID

SARS-CoV-2

Post-viral

A B S T R A C T

**Background and objectives:** Although many symptoms of post-COVID syndrome have been described, a comprehensive evaluation of their prevalence is lacking. We aimed to describe symptoms at 16 months from hospitalization for COVID-19.

**Methods:** A telephone assessment was performed one year later in a cohort of COVID-19 survivors hospitalized between March and May 2020 and already evaluated four months after discharge. Patients with relevant symptoms at 16 months, patients who presented symptoms at four months, and all intensive care unit patients were invited for assessment at an outpatient facility. At telephone consultation, respiratory, cognitive, and functional symptoms were assessed. Patients underwent pulmonary function tests, lung CT scans, and psychometric and cognitive tests at the outpatient facility.

<footnote><sup>a</sup> Université Paris-Saclay, AP-HP, Service de réanimation pédiatrique et médecine néonatale, Hôpital de Bicêtre, DMU 3 Santé de l'enfant et de l'adolescent, Le Kremlin-Bicêtre, France</footnote>

<footnote><sup>b</sup> Université Paris-Saclay, AP-HP, Service de pneumologie et soins intensifs respiratoires, Hôpital de Bicêtre, DMU 5 Thorinno, Inserm UMR_S999, Le Kremlin-Bicêtre, France</footnote>

<footnote><sup>c</sup> Université Paris-Saclay, AP-HP, Service de médecine intensive-réanimation, hôpital de Bicêtre, DMU 4 CORREVE Maladies du cœur et des vaisseaux, Inserm UMR_S999, Le Kremlin-Bicêtre, France</footnote>

<footnote><sup>d</sup> 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</footnote>

<footnote><sup>e</sup> Université Paris-Saclay, AP-HP, Service de réanimation chirurgicale, Hôpital de Bicêtre, DMU 12 Anesthésie, réanimation, douleur, Le Kremlin-Bicêtre, France</footnote>

<footnote><sup>f</sup> 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 (Centre de Recherche en Epidémiologie et Santé des Populations), France</footnote>

<footnote><sup>g</sup> Université Paris-Saclay, AP-HP, Service de radiologie diagnostique et interventionnelle, Hôpital de Bicêtre, DMU 14 Smart Imaging, BioMaps, Le Kremlin-Bicêtre, France</footnote>

<footnote><sup>h</sup> 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</footnote>

<footnote><sup>i</sup> Université Paris-Saclay, AP-HP, Service de gériatrie aiguë, Hôpital de Bicêtre, DMU 1 Médecine territoire gériatrie, Le Kremlin-Bicêtre, France</footnote>

<footnote><sup>j</sup> 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</footnote>

<footnote><sup>k</sup> Université Paris-Saclay, AP-HP, Service de microbiologie, Hôpital de Bicêtre, DMU 15 Biologie-Génétique-PUI, INSERM 1193, Le Kremlin-Bicêtre, France</footnote>

<footnote><sup>l</sup> Université Paris-Saclay, AP-HP, Service des maladies infectieuses et tropicales, Hôpital de Bicêtre, DMU 7 Endocrinologie-immunités-inflammations-cancer-urgences, INSERM U1018, CESP (Centre de Recherche en Epidémiologie et Santé des Populations), Le Kremlin-Bicêtre, France</footnote>

<footnote><sup>m</sup> 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</footnote>

<footnote>**Abbreviations:** BDI, Beck Depressive Inventory; COVID-19, coronavirus disease 2019; HADS, Hospital Anxiety and Depression Scale; HVPT, hyperventilation provocation test; ICU, intensive care unit; mMRC, modified Medical Research Council; MoCA, Montreal Cognitive Assessment; RT-PCR, reverse transcriptase-polymerase chain reaction; SARS-CoV-2, severe acute respiratory coronavirus 2</footnote>

<footnote>The writing committee for the COMEBAC investigators</footnote>

<footnote>* Corresponding author at: Service de réanimation pédiatrique, Hôpital Bicêtre, 78, rue du Général Leclerc, 94 270 Le Kremlin-Bicêtre, France.
E-mail address: luc.morin@aphp.fr (L. Morin).</footnote>
**Results:** Among 478 patients evaluated four months after discharge, 317 (67 %) were assessed at telephone consultation and 124 at ambulatory assessment. At telephone assessment, ≥1 new symptom was reported by 216 patients (68 %), mainly fatigue (53 %), dyspnea (37 %), and memory difficulties (24 %). Seventy-nine patients (25 %) were asymptomatic at four months but declared ≥1 symptom one year later. In patients evaluated twice, the prevalence of cognitive impairment was 45 % at four months and 40 % at 16 months. Depression and post-traumatic symptoms prevalence remained stable, and the prevalence of anxiety significantly decreased. Dysfunctional breathing was detected in 32 % of patients. At 16 months after discharge, lung CT-scan exhibited abnormalities in 30/80 patients (38 %), compared to 52/85 patients (61 %) at four months.

**Conclusion:** At 16 months after hospitalization for COVID-19, 68 % of patients declared symptoms, including patients whose symptoms appeared between 4 and 16 months.

**Trial registration:** ClinicalTrials.gov, NCT04704388

© 2024 The Author(s). Published by Elsevier Masson SAS. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

## Background

The severe acute respiratory coronavirus 2 (SARS-CoV-2) affects many organs in the acute phase, [1] and may induce persistent symptoms in the medium term [2]. In the context of this "long Coronavirus disease 2019 (COVID-19)" or "post-COVID" syndrome, a multitude of symptoms has been described [3–5]. The nature and the incidence of such symptoms must be precisely described to define the care of the patients who suffer from them. The impact of these symptoms on health status and quality of life can be significant, and the fact that the virus has infected so many patients worldwide makes it a significant public health issue [6]. A survey in the United States estimated that 7 % of the total population had ever had long COVID symptoms [7].

The post-COVID-19 syndrome has been the subject of many clinical investigations [8–13]. However, only some have systematically and thoroughly evaluated all possible symptoms several months after the acute episode of COVID-19, including psychiatric questionnaires, cognitive tests, lung CT scans, and respiratory function tests [10,13]. Our group of investigators previously reported on a cohort of 478 patients who had survived hospitalization for COVID-19 between March and May 2020 [14]. Among those, 51 % presented at least one persistent symptom four months after the initial episode. This incidence is close to the result of another large cohort [15]. In the present study, we followed up on those patients 16 months after the initial SARS-CoV-2 infection with a novel systematic assessment.

## Patients and methods

### Population

The COMEBAC (CONSultation Multi-Expertise de Bicêtre Après COVID-19) is a one-center cohort of patients hospitalized for acute COVID-19 at Bicêtre Hospital from March 1 to May 29, 2020, and who survived. Patients provided written informed consent. The Ethics Committee of the French Intensive Care Society (CE20-56) approved the study.

Inclusion and exclusion criteria have been described previously [14]. Briefly, adult patients were included if they had been hospitalized for ≥24 h primarily because of COVID-19; had a SARS-CoV-2 infection diagnosed by reverse transcriptase-polymerase chain reaction (RT-PCR) and/or by typical lung CT-scan associated with clinical features; had survived four months following hospital discharge, or Intensive Care Unit (ICU) discharge for patients who had been admitted to an ICU. Patients were excluded if they had died within 16 months after discharge, were still hospitalized, had end-stage cancer or dementia, had nosocomial COVID-19, and had incidental positive SARS-CoV-2 RT-PCR during a hospital stay for a different medical indication. At 4 and 16 months after discharge, the following assessment was performed.

### Telephone assessment

Patients were contacted by phone by a medical officer and administered a questionnaire that included general conditions and respiratory and cognitive symptoms (using the Q3PC questionnaire) [16] (see Online supplement). Four months after discharge, this assessment was offered to all eligible patients. At 16 months after discharge, it was provided to all patients who had already been evaluated at telephone consultation four months after discharge.

### Ambulatory setting

Four months after hospital or ICU discharge, all symptomatic at telephone assessment (except those with isolated anosmia) and all ICU patients were invited to an ambulatory setting. At 16 months after discharge, all patients who declared symptoms at the telephone assessment performed then, and all patients invited to the ambulatory setting at four months, were invited. This included patients who had not declared symptoms during the telephone assessment at four months but declared some one year later. This also included patients who had been invited at four months but could not attend at this time. During this ambulatory evaluation, the following assessment was performed in an outpatient facility from July to September 2020 and May to September 2021.

### General assessment

In addition to clinical examination, quality of life (36-item Short-Form Health Survey, SF-36 questionnaire) [17] and fatigue (Multidimensional Fatigue Inventory, MFI-20 scale) [18] were assessed (Supplementary Table 1).

### Pulmonary assessment

Dyspnea was assessed by the modified Medical Research Council (mMRC) scale. A 6-minute walk test [19] and pulmonary function tests were performed (see Online supplement). Dysfunctional breathing was assessed with the Nijmegen questionnaire [20] and a hyperventilation provocation test (HVPT, see Online supplement). Two pulmonologists analyzed patients' medical records reporting new-onset or increased dyspnea to determine its cause, reaching a consensus in case of disagreement.

### Lung CT scan

A high-resolution lung CT scan was performed in all patients (see Online supplement). Two readers (AA and OM) reviewed the CT scans, reaching a consensus regarding disagreements.
## Cognitive and psychiatric assessment

All patients underwent cognitive tests, a questionnaire for psychiatric symptoms, and an interview with a neuropsychologist and a psychologist. The global cognitive capacity (Montreal Cognitive Assessment (MoCA) [21] adapted to age and education level [22]), attention (d2-R test [23]), and memory (McNair self-questionnaire [23]) were assessed. "Cognitive complaint" was defined by an impaired McNair score or reported cognitive symptoms. "Cognitive impairment" was defined by an impaired MoCA (<21 to <25 depending on educational level) or d2-R score (<76). Anxiety symptoms (anxiety subscale of the Hospital Anxiety and Depression Scale (HADS-A) >7 [24]), depression symptoms (13-item Beck Depressive Inventory (BDI) score [25] > 7) and post-traumatic symptoms (Post Traumatic Stress Disorder scale >30) were also assessed (supplementary table S1).

## Statistical analysis

The REDCap electronic data capture tools [26,27] were used to record data. Data are presented as counts, percentages, means (standard deviation, SD), and medians [interquartile range, IQR]. The chi-square, Fisher exact, or McNemar tests for matched patients were used to compare proportions. Continuous variables were compared using the Student's t-test or Wilcoxon rank sum test, and the corresponding paired tests for matched patients. No assumptions were made for missing data. Analysis was performed using the R statistical package (version 4.0.0, R Foundation for Statistical Computing, Vienna, Austria).

## Results

### Patients

Among the 478 patients who had been evaluated four months after discharge, 317 (67%) were re-evaluated during a telephone consultation, including 209 of the 336 non-ICU patients (62%) and 108 of the 142 ICU patients (76%) (Fig. 1). Their characteristics during initial hospitalization are presented in Table 1. The majority were men. Fifty-eight (18%) had required invasive mechanical ventilation, and 51 (16%) high-flow oxygen through a nasal cannula. The characteristics of the patients who were not re-evaluated are presented in Table S2 and Table S3. The telephone and ambulatory assessments were performed 16 [15,16] and 16 [16,17] months after discharge.

Among the 317 patients evaluated at telephone consultation at 16 months, 124 (39%) were subsequently evaluated at the outpatient clinic. Of these, 86 had been assessed at the outpatient clinics four months post-discharge, and 38 had not (Fig. 1). The main reason patients eligible for the outpatient clinic assessment did not attend, was personal convenience.

## Telephone assessment

At least one symptom that did not exist before COVID-19 was reported by 216 patients (68%). This included 137 patients (43%) in whom at least one symptom was present both at four and sixteen months after discharge, 73 patients (23%) who had no symptom, neither at four nor at 16 months, 28 patients (9%) who declared at least one symptom at four months but no more at 16 months, and 79 patients (25%) who were asymptomatic at four months but who declared at least one symptom one year later.

Among the 216 patients who declared symptoms at telephone assessment 16 months from discharge, symptoms triggered an evaluation at the outpatient facility in 165 patients (52%) (Fig. 1). Among the latter, 125 (76%) presented at least one symptom four months after discharge, while in 40 patients (24%), symptoms were absent four months after discharge and appeared between both assessments.

Fatigue was reported by 166 patients (53%) (Table 2, Figures S1 and S2), including 83 patients in whom it had appeared between 4 and 16 months after discharge (Figure S1). Dyspnea was described by 117 patients (37%) (Table 2), among which it was not reported at four months in 80 patients (Figure S1). Paresthesia and headache were reported by 54 (18%) and 53 (17%) patients, respectively (Table 2). Memory difficulties were reported by 75 patients (24%). Among 79 patients (25%) who reported no symptoms at four months but who reported symptoms at 16 months, 38 (48%), 28 (35%), and 11 (14%) reported fatigue, dyspnea, and memory difficulties, respectively.

## Ambulatory assessment

### General condition

Among the 124 patients who attended the outpatient facility, 72 (58%) presented at least one symptom. The weight variation, evaluated in 85 patients, from baseline to 16 months post-discharge was 0 [-3;4] kg, and 23 (27%) patients had lost more than 5% of their baseline weight (Table S4).

<figure><img src="image_3.png" /><figcaption>Fig. 1. Flow chart.</figcaption></figure>
<table><caption>**Table 1**
Baseline and hospitalization characteristics of the patients who had the telephone assessment.</caption><thead><tr><th></th><th>All patients (n = 317)</th><th>No ambulatory visit (n = 193)</th><th>Attended the ambulatory visit (n = 124)</th><th>p-value</th><th>N</th></tr></thead><tbody><tr><td>Age, years, mean (SD)</td><td>57.7 (14.3)</td><td>57.1 (15.5)</td><td>58.5 (12.2)</td><td>0.376</td><td>317</td></tr><tr><td>Women/men No. (%)</td><td>129 (40.7 %) / 188 (59.3 %)</td><td>76 (39.4 %) / 177 (60.6 %)</td><td>53 (42.7 %) / 71 (57.3 %)</td><td>0.633</td><td>317</td></tr><tr><td>Body mass index, mean (SD) [No.]</td><td>29.4 (5.8)</td><td>29.1 (6.1)</td><td>29.8 (5.5)</td><td>0.345</td><td>243</td></tr><tr><td>Comorbidities, No. (%)</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Hypertension</td><td>138 (43.5 %)</td><td>82 (42.5 %)</td><td>56 (45.2 %)</td><td>0.724</td><td>317</td></tr><tr><td>Obesity</td><td>100 (41.2 %)</td><td>53 (39.3 %)</td><td>47 (43.5 %)</td><td>0.590</td><td>243</td></tr><tr><td>Diabetes</td><td>83 (26.2 %)</td><td>54 (28.0 %)</td><td>29 (23.4 %)</td><td>0.437</td><td>317</td></tr><tr><td>Chronic heart disease</td><td>34 (10.7 %)</td><td>23 (11.9 %)</td><td>11 (8.87 %)</td><td>0.503</td><td>317</td></tr><tr><td>Respiratory disease<br>(other than COPD)</td><td>50 (15.8 %)</td><td>28 (14.5 %)</td><td>22 (17.7 %)</td><td>0.540</td><td>317</td></tr><tr><td>Chronic kidney disease</td><td>28 (8.83 %)</td><td>20 (10.4 %)</td><td>8 (6.45 %)</td><td>0.320</td><td>317</td></tr><tr><td>Declared psychiatric disorder</td><td>16 (5.05 %)</td><td>11 (5.70 %)</td><td>5 (4.03 %)</td><td>0.690</td><td>317</td></tr><tr><td>Neurodegenerative disorder</td><td>3 (0.95 %)</td><td>3 (1.55 %)</td><td>0 (0.00 %)</td><td>0.283</td><td>317</td></tr><tr><td>Alcohol abuse</td><td>12 (3.97 %)</td><td>6 (3.26 %)</td><td>6 (5.08 %)</td><td>0.548</td><td>302</td></tr><tr><td>Active cancer</td><td>8 (2.52 %)</td><td>4 (2.07 %)</td><td>4 (3.23 %)</td><td>0.716</td><td>317</td></tr><tr><td>Other immunosuppression</td><td>13 (4.10 %)</td><td>9 (4.66 %)</td><td>4 (3.23 %)</td><td>0.734</td><td>317</td></tr><tr><td>COPD</td><td>7 (2.21 %)</td><td>6 (3.11 %)</td><td>1 (0.81 %)</td><td>0.253</td><td>317</td></tr><tr><td>Long-term dialysis</td><td>12 (3.79 %)</td><td>9 (4.66 %)</td><td>3 (2.42 %)</td><td>0.378</td><td>317</td></tr><tr><td>HIV infection</td><td>9 (2.84 %)</td><td>7 (3.63 %)</td><td>2 (1.61 %)</td><td>0.491</td><td>317</td></tr><tr><td>Solid organ transplantation</td><td>5 (1.58 %)</td><td>3 (1.55 %)</td><td>2 (1.61 %)</td><td>1.000</td><td>317</td></tr><tr><td>Liver disease</td><td>5 (1.58 %)</td><td>2 (1.04 %)</td><td>3 (2.42 %)</td><td>0.383</td><td>317</td></tr><tr><td>Pregnancy</td><td>4 (1.26 %)</td><td>2 (1.04 %)</td><td>2 (1.61 %)</td><td>0.646</td><td>317</td></tr><tr><td>Bone marrow transplantation</td><td>1 (0.32 %)</td><td>1 (0.52 %)</td><td>0 (0.00 %)</td><td>1.000</td><td>317</td></tr><tr><td>Smoking, No./total (%)</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Active</td><td>22 (7.28 %)</td><td>12 (6.52 %)</td><td>10 (8.47 %)</td><td>0.813</td><td>302</td></tr><tr><td>Former (≥5 pack-years)</td><td>50 (16.6 %)</td><td>31 (16.8 %)</td><td>19 (16.1 %)</td><td></td><td></td></tr><tr><td>No (&lt;5 pack-years)</td><td>230 (76.2 %)</td><td>141 (76.6 %)</td><td>89 (75.4 %)</td><td></td><td></td></tr><tr><td>Specific treatments, No. (%)</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Azithromycin</td><td>89 (28.1 %)</td><td>56 (29.0 %)</td><td>33 (26.6 %)</td><td>0.736</td><td>317</td></tr><tr><td>Tocilizumab (anti-IL-6)</td><td>32 (10.1 %)</td><td>15 (7.77 %)</td><td>17 (13.7 %)</td><td>0.128</td><td>317</td></tr><tr><td>Hydroxychloroquine</td><td>24 (7.57 %)</td><td>13 (6.74 %)</td><td>11 (8.87 %)</td><td>0.629</td><td>317</td></tr><tr><td>Corticosteroids</td><td>20 (6.31 %)</td><td>13 (6.74 %)</td><td>7 (5.65 %)</td><td>0.878</td><td>317</td></tr><tr><td>Lopinavir/ritonavir</td><td>13 (4.10 %)</td><td>7 (3.63 %)</td><td>6 (4.84 %)</td><td>0.810</td><td>317</td></tr><tr><td>Remdesivir</td><td>5 (1.58 %)</td><td>3 (1.55 %)</td><td>2 (1.61 %)</td><td>1.000</td><td>317</td></tr><tr><td>Anakinra (anti-IL-1RA)</td><td>10 (3.15 %)</td><td>4 (2.07 %)</td><td>6 (4.84 %)</td><td>0.197</td><td>317</td></tr><tr><td>Vasopressors, No. (%)</td><td>55 (17.4 %)</td><td>30 (15.5 %)</td><td>25 (20.2 %)</td><td>0.364</td><td>317</td></tr><tr><td>Active anticoagulation (at full therapeutic dose), No. (%)</td><td>59 (18.6 %)</td><td>38 (19.7 %)</td><td>21 (16.9 %)</td><td>0.641</td><td>317</td></tr><tr><td>Acute kidney injury during hospitalization, No. (%)</td><td>60 (20.8 %)</td><td>36 (20.9 %)</td><td>24 (20.7 %)</td><td>1.000</td><td>288</td></tr><tr><td>Pulmonary embolism during hospitalization, No. (%)</td><td>33 (11.4 %)</td><td>18 (10.2 %)</td><td>15 (13.4 %)</td><td>0.516</td><td>289</td></tr><tr><td>Hospitalization in ICU, No. (%)</td><td>108 (34.1 %)</td><td>60 (31.1 %)</td><td>48 (38.7 %)</td><td>0.202</td><td>317</td></tr><tr><td>Intubation in the ICU, No. (%)</td><td>58 (53.7 %)</td><td>29 (48.3 %)</td><td>29 (60.4 %)</td><td>0.290</td><td>108</td></tr><tr><td>High-Flow Humidified Oxygen, No. (%)</td><td>51 (47.2 %)</td><td>20 (42.6 %)</td><td>31 (50.8 %)</td><td>0.510</td><td>108</td></tr><tr><td>Duration of ICU stay, days median [Q1:Q3]</td><td>9.00 [4.00;20.0]</td><td>8.00 [4.00;16.0]</td><td>10.0 [4.00;22.2]</td><td>0.350</td><td>107</td></tr><tr><td>Total duration of hospitalization, days, median [Q1:Q3]</td><td>9.00 [4.00;16.0]</td><td>9.00 [4.00;14.0]</td><td>10.0 [5.00;18.5]</td><td>0.039</td><td>317</td></tr></tbody></table>

COPD: chronic obstructive pulmonary disease, HIV: human immunodeficiency virus, ICU: intensive care unit.

<table><caption>**Table 2**
Results of the telephone assessment performed at 4 and 16 months.</caption><thead><tr><th></th><th>At 4 months</th><th>n</th><th>At 16 months</th><th>n</th><th>p-value</th><th>New symptom at 16 months</th><th>n</th></tr></thead><tbody><tr><td>Time from hospital discharge to telephone assessment, median (IQR), d [No.]</td><td>110 [93.0;127]</td><td>289</td><td>474 [454;498]</td><td>317</td><td></td><td></td><td></td></tr><tr><td>Declared symptoms No (%)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Dyspnea</td><td>65 (20.5 %)</td><td>317</td><td>117 (37.3 %)</td><td>314</td><td>&lt;0.001</td><td>80 (25.5 %)</td><td>314</td></tr><tr><td>Cough</td><td>17 (5.99 %)</td><td>284</td><td>35 (11.2 %)</td><td>312</td><td>0.0673</td><td>28 (10.0 %)</td><td>279</td></tr><tr><td>Chest Pain</td><td>31 (11.0 %)</td><td>282</td><td>36 (11.5 %)</td><td>313</td><td>1.00</td><td>18 (6.47 %)</td><td>278</td></tr><tr><td>Anorexia</td><td>21 (7.17 %)</td><td>293</td><td>13 (4.15 %)</td><td>313</td><td>0.170</td><td>9 (3.11 %)</td><td>289</td></tr><tr><td>Fatigue</td><td>95 (32.5 %)</td><td>292</td><td>166 (53.0 %)</td><td>313</td><td>&lt;0.001</td><td>83 (28.8 %)</td><td>288</td></tr><tr><td>Anosmia</td><td>22 (7.75 %)</td><td>284</td><td>18 (5.75 %)</td><td>313</td><td>0.286</td><td>8 (2.86 %)</td><td>280</td></tr><tr><td>Headache</td><td>19 (6.71 %)</td><td>283</td><td>53 (17.0 %)</td><td>311</td><td>&lt;0.001</td><td>38 (13.7 %)</td><td>277</td></tr><tr><td>Paresthesia</td><td>38 (13.4 %)</td><td>284</td><td>54 (17.6 %)</td><td>307</td><td>0.203</td><td>30 (10.9 %)</td><td>275</td></tr><tr><td>Cognitive testing (Q3PC questionnaire<sup>a,b</sup>, No (%)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Memory difficulties</td><td>49 (17.3 %)</td><td>284</td><td>75 (24.0 %)</td><td>312</td><td>0.002</td><td>42 (15.1 %)</td><td>279</td></tr><tr><td>Mental slowness</td><td>28 (9.89 %)</td><td>283</td><td>31 (9.94 %)</td><td>312</td><td>1.00</td><td>20 (7.19 %)</td><td>278</td></tr><tr><td>Concentration problems</td><td>29 (10.3 %)</td><td>281</td><td>32 (10.3 %)</td><td>312</td><td>0.863</td><td>18 (6.52 %)</td><td>276</td></tr><tr><td>Any cognitive symptom</td><td>165 (52.1 %)</td><td>317</td><td>216 (68.1 %)</td><td>317</td><td>&lt;0.001</td><td></td><td></td></tr></tbody></table>

<footnote><sup>a</sup> Signs were declared as newly-onset during, since or after hospitalization for COVID-19 and persistent at the time of telephone assessment.</footnote>

<footnote><sup>b</sup> The range, direction and characteristics of the Q3PC questionnaire can be found in Supp Table 1.</footnote>
<table><caption>**Table 3**
Results of the ambulatory visit performed at 16 months.</caption><thead><tr><th></th><th>N</th><th></th></tr></thead><tbody><tr><td>Time from hospital discharge to ambulatory visit, days median [Q1;Q3]</td><td>492 [473;517]</td><td>124</td></tr><tr><td>SF-36 subscales</td><td></td><td></td></tr><tr><td>Physical functioning</td><td>70.0 [55.0;85.0]</td><td>115</td></tr><tr><td>Role limitations due to physical health</td><td>25.0 [0.0;100]</td><td>115</td></tr><tr><td>Role limitations due to emotional problems</td><td>66.7 [0.0;100]</td><td>117</td></tr><tr><td>Energy/fatigue</td><td>50.0 [37.5;62.5]</td><td>118</td></tr><tr><td>Emotional well-being</td><td>75.0 [55.0;85.0]</td><td>120</td></tr><tr><td>Social functioning</td><td>75.0 [62.5;100]</td><td>115</td></tr><tr><td>Pain</td><td>70.5 [41.5;100]</td><td>124</td></tr><tr><td>General health</td><td>55.0 [40.0;70.0]</td><td>103</td></tr><tr><td>Respiratory assessment</td><td></td><td></td></tr><tr><td>Dyspnea, No (%)</td><td>45 (36.3 %)</td><td>124</td></tr><tr><td>mMRC scale score for dyspnea, median [Q1;Q3]</td><td>1.00 [0.00;2.00]</td><td>45</td></tr><tr><td>Persistent cough, No (%)</td><td>13 (10.6 %)</td><td>123</td></tr><tr><td>6-minute walk test, min median [Q1;Q3]</td><td>508 [426;562]</td><td>124</td></tr><tr><td>Abnormal lung CT scan result, No (%)</td><td>50 (43.1 %)</td><td>116</td></tr><tr><td>Persistent ground-glass opacities, No (%)</td><td>34 (29.1 %)</td><td>117</td></tr><tr><td>Lung fibrotic lesions, No (%)</td><td>21 (17.6 %)</td><td>119</td></tr><tr><td>FEV1 (expressed as% of theory), median [Q1;Q3]</td><td>95.0 [85.6;106]</td><td>118</td></tr><tr><td>FEV1/FVC, median [Q1;Q3]</td><td>81.7 [77.7;85.5]</td><td>118</td></tr><tr><td>TLC (expressed as% of theory), median [Q1;Q3]</td><td>83.6 [78.4;94.8]</td><td>39</td></tr><tr><td>DLCO &lt;70%, No (%)</td><td>7 (17.5 %)</td><td>40</td></tr><tr><td>Hyperventilation syndrome, No (%)</td><td>33 (32.4 %)</td><td>102</td></tr><tr><td>Neurologic and psychological assessment <sup>a</sup></td><td></td><td></td></tr><tr><td>Symptoms of anxiety (HADS-Anxiety), No (%)</td><td>24 (19.4 %)</td><td>124</td></tr><tr><td>Symptoms of depression (BDI test), No (%)</td><td>24 (22.0 %)</td><td>109</td></tr><tr><td>Symptoms of PTSD (PCL-5 score), No (%)</td><td>14 (14.3 %)</td><td>98</td></tr><tr><td>Cognitive complaint (impaired McNair score, reported cognitive symptoms, or both), No (%)</td><td>73 (60.3 %)</td><td>121</td></tr><tr><td>Cognitive impairment (impairment of either MoCA or d2-R score), No (%)</td><td>54 (45.0 %)</td><td>120</td></tr><tr><td>Any neurologic or cognitive symptom, No (%)</td><td>72 (58.1 %)</td><td>124</td></tr></tbody></table>

CT: computed tomography, DLCO: diffusing capacity of the lungs for carbon monoxide, FEV1: forced expiratory volume in one second, FVC: forced vital capacity, PTSD: post-traumatic stress disorder, TLC: total lung capacity.

<sup>a</sup> The range, direction and characteristics of the McNair, MoCA and d2R scores, of the HADS-Anxiety scale, of the BDI test, and of the ISI and PCL-5 scores can be found in Supp Table 1.

Results of the SF-36 score in the 124 patients who attended the outpatient facility at 16 months are presented in Table 3 and Figure S3. In the 77 patients who had already been assessed by this score at the outpatient facility in 2020, between 4 and 16 months after discharge, the SF36 median score had increased from 25.0 [25.0;50.0] to

50.0 [0.0;100.0] (p = 0.02) for the subscale "Role limited due to physical problems." The "Vitality" and "General Health" subscales remained unchanged (Table S4, Figure S4).

## Cognitive and psychiatric assessment

Cognitive impairment was detected in 135 patients (52 %) at 16 months (Table 2). In patients evaluated at 4 and 16 months after discharge, cognitive impairment was present in 37 (45 %) at four months and 34 patients (40 %) at 16 months (p = 0.83), including ten patients with new onset impairment (Table S4, Fig. 2). Among intubated patients evaluated four and 16 months after discharge, the prevalence of cognitive impairment remained stable (55 % versus 48 %, respectively, p = 0.522).

At 16 months, anxiety, depression, and post-traumatic stress symptoms were observed in 24/124 (19 %), 24/109 (22 %), and 14/98 (14 %) patients, respectively (Table 3). In patients evaluated twice, at 16 months after discharge, the prevalence of anxiety symptoms decreased (36 % versus 21 %, p = 0.0446). It remained stable for depression (26 % versus 20 %, p = 0.4533) and post-traumatic stress symptoms (17 % versus 11 %, p = 0.182) (Table S4). In patients intubated at the initial phase, the prevalence of anxiety, depression, and post-traumatic stress symptoms at 16 months were 6/29 (21 %), 5/26 (19 %), and 3/24 (12 %), respectively (Table S5). In the patients who declared a symptom at teleconsultation at 16 months that did not exist at four months and who attended the ambulatory visit, anxiety, depression, and post-traumatic stress symptoms were detected in 5/20 (25 %), 5/15 (33 %), and 4/15 (27 %) patients, respectively.

## Lung CT scan

At 16 months after discharge, lung CT scans exhibited abnormalities in 29/80 patients (36 %), while they were present in 52/85 patients (61 %) at four months (p = 0.08). No patient exhibited a new abnormal CT scan. Among the 84 patients evaluated twice, fibrotic lesions that had been detected in 20/84 patients (24 %) at four months were still present in 18/83 (22 %) one year later (p = 0.80) (Fig. 2, Figure S5). When present, fibrotic lesions involved <25 % of the parenchyma in all cases. These persisting fibrotic lesions were present in 10/26 patients (39 %) previously intubated. The other lesions observed at 16 months were ground glass opacities (Table 3).

## Respiratory assessment

Among the 86 patients assessed at both times, dyspnea was present in 45/86 patients (52 %) at four months and 31/86 patients (36 %)

<figure><img src="image_4.png" /><figcaption>**Fig. 2.** The evolution of symptoms and findings that did not exist before COVID-19 infection in 86 patients who attended two outpatient clinic visits four months and 16 months after COVID-19 hospitalization.</figcaption></figure>

Persistent symptom: symptom or finding found at 4- and 16-month outpatient clinics. New symptom: symptom or result found at 16 months that did not exist at 4-month evaluation. Recovered symptom: symptom or finding found at four months but absent at 16 months outpatient clinic. No symptom: symptom or finding absent at 4- and 16-month outpatient clinic.
at 16 months (p = 0.02) (Table 3), including 21 patients with persistent and 10 patients with new-onset dyspnea. Among the patients with persistent dyspnea, 6/21 (29 %) had been intubated. Persistent dyspnea was attributed to dysfunctional breathing in 18/21 cases (86 %), persistent lung lesions at CT-scan in 1/21 patients (5 %), and no specific cause was found in 2/21 cases (10 %).

Dysfunctional breathing was detected in 33/102 patients (32 %). Among patients evaluated both at 4 and 16 months, it was present in 23/69 patients (33 %) at 16 months and 14/69 patients (25 %) at four months (p = 0.15) (Fig. 2). Among patients evaluated twice at functional respiratory tests, a DLCO <70 % was present at 16 months in 2/20 patients (10 %), while it had been measured in 7/20 patients (35 %) at four months (p = 0.07).

Discussion

This study, conducted on 317 patients who presented an episode of COVID-19 that required hospitalization from March to May 2020, showed that 68 % of patients had at least one symptom 16 months after the initial hospitalization, mainly fatigue and dyspnea. This prevalence was 51 % of patients at four months from discharge. At 16 months, 25 % of patients presented a symptom that did not exist four months after the initial episode. At the outpatient clinic at 16 months, the prevalence of cognitive impairment tended to decrease but was still 40 %. Within the group of patients who underwent both 4- and 16-month ambulatory evaluations, the prevalence of anxiety symptoms halved and reached 22 %; depression and post-traumatic stress symptoms were still found in 20 % and 11 % of the patients, respectively. Lung CT scan abnormalities were still present in 36 % of patients.

Among the studies that have reported post-COVID-19 symptoms at 12 months or more from discharge, few have documented the evolution of symptoms over time in large numbers [10-12,28-32]. Three of these studies have conducted a comprehensive clinical assessment [10,32]. We repeated the same evaluation one year after an initial assessment of COVID-19 patients Field [12]. In addition to the functional symptoms, as in other studies [8,9,11], we carried out a systematic, objective assessment, including psychometric tests, pulmonary function tests, and lung CT scans.

At 16 months from discharge, 68 % of patients still declared at least one symptom, a prevalence in the middle range of those reported at this term [9-13,28,30,33,34]. The most frequent symptom remained fatigue, reported by 53 % of patients. This symptom is the most common post-COVID-19 syndrome [4,35]. More than a third of patients still described dyspnea. An exciting data from our 4-month evaluation was the demonstration of dysfunctional breathing in almost a third of the dyspneic patients [14]. It was still present in a similar proportion of dyspneic patients a year later, as reported by other studies [36,37]. Functional respiratory complaints are frequently reported after COVID-19. The physiological responses to incremental cardiopulmonary exercise testing may help diagnosing dysfunctional breathing, deconditioning or cardio-vascular disease [38]. This diagnosis is essential as dysfunctional breathing may be accessible to some specific treatment [39].

The standardized assessment at the outpatient clinic confirmed that the reported prevalence of symptoms did not decrease significantly for many of them. The SF36 quality of life score improved significantly only for the "Role limited due to physical problems" subscale. Still, it remained impaired in its three components 16 months after the initial episode. At cognitive tests, cognitive impairment was observed in 40 % of the patients at 16 months, while they were present in 45 % of the patients one year earlier [14].

Among psychiatric symptoms, only anxiety symptoms decreased significantly between 4 and 16 months after discharge, while the prevalence of depressive symptoms remained unchanged.

Post-traumatic stress syndrome persisted in 11 % of patients, a proportion lower than a comparable study [40].

As observed by Huang et al. [10] and others [32,41], the lesions on the pulmonary CT scan performed at 16 months tended to decrease compared to 12 months earlier. In 39 % of patients previously intubated at the initial phase, CT lesions were found. The prevalence of fibrotic lesions roughly did not change, although parenchymal abnormalities may improve during the first 6 to 12 months following acute illness, including abnormalities associated with the fibrotic process [32]. It should be noted, however, that such lesions only concerned a minority of patients with an acute episode requiring hospitalization and never involved more than 25 % of the lung parenchyma.

Symptoms were most frequent in patients who had been intubated. Respiratory sequelae were also more frequent in these patients, as previously found [42]. The prevalence of fibrotic lesions on lung CT scans and abnormal respiratory function tests were higher. These data confirm that the prevalence of long COVID-19 symptoms is positively related to the severity of the disease, as shown, for example, by Huang et al. [10].

An interesting result might be that, at telephone assessment, 26 % of the patients reported a symptom at 16 months that they did not report at four months. These were fatigue, dyspnea, and memory problems. At the outpatient facility, tests evidenced mainly psychiatric symptoms and dysfunctional breathing. Huang et al. also found an increase in the prevalence of dyspnea and reported anxiety between 6 months and 12 months after the acute infection [10]. This declaration of subjective symptoms appearing between 4 and 16 months after hospitalization may find different explanations.

On the one hand, the resumption of professional and social life may have favored the appearance of symptoms that had been masked until then. On the other hand, the relief experienced by patients who had survived the acute episode, which was severe enough to require hospitalization, could have led to a minimization of symptoms at four months, which were revealed secondarily. Also, the long COVID-19 syndrome was relatively unknown to patients in the summer of 2020, when we conducted the first assessment. Patients could become aware of their symptoms by discovering that they were typically part of this syndrome. Finally, a delayed effect of SARS-CoV-2 infection cannot be ruled out, as autoimmune mechanisms have been suspected following the infection [43,44] as it may happen after other viral infections [45]. However, the absence of objective symptoms revealed by the tests carried out at the outpatient clinic does not support this hypothesis.

Our study has several limitations. First, several patients assessed at four months could not be reevaluated a year later. Second, this cohort only included patients hospitalized in the initial phase. Third, our study only looked at patients hospitalized during the first phase of the outbreak, while the alpha-one SARS-CoV-2 variant was the only one circulation; no vaccination nor specific treatments were available. Fourth, our study is limited by its monocentric nature; hence, the symptoms' prevalence probably depends on the selected population. Fifth, despite being a standardized assessment, most symptoms are reported as present or absent, leading to a missing granularity and lack of precision. Fifth, we did not assess whether patients experienced a new COVID-19 infection between the initial hospitalization and the reevaluation.

In conclusion, our study conducted 16 months after hospitalization for COVID-19 shows that, even if the prevalence of post-COVID-19 symptoms is decreasing, it remains high, particularly in patients who have stayed in critical care. Fatigue and psychiatric symptoms are the most prevalent. Pulmonary sequelae, particularly radiological, are minimal. Functional symptoms with no organic substrate appeared in some patients between the 4-month and 16-month evaluations.
## Ethics approval and consent to participate

Patients provided written informed consent. The Ethics Committee of the French Intensive Care Society (CE20-56) approved the study.

## Consent for publication

Not applicable.

## Availability of data and materials

The datasets used and analyzed during the current study are available from the corresponding author upon reasonable request.

## Authors' contributions

All the writing committee members collected the data, analyzed the data, and drafted the manuscript. All these members approved the final version of the manuscript.

## Authors' information

None.

## Declaration of competing interest

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:

Xavier Monnet reports financial support was provided by Public Assistance Hospitals Paris. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

## Funding

Assistance publique-Hôpitaux de Paris funded this study. This 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 control the decision regarding the journal to which the paper was submitted.

## Acknowledgments

We thank the patients who participated in this cohort, the doctors, psychologists, nurses, care helpers, biologists, pharmacists, other allied health professionals, and the administrators of the Bicêtre Hospital.

The authors would like the names of the individual members of the Group to be searchable through their PubMed records.

## Supplementary materials

Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.resmer.2024.101099.

## References

[1] Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese center for disease control and prevention. JAMA 2020;323:1239-42. doi: 10.1001/jama.2020.2648.

[2] Carfi A, Bernabei R, Landi F. Gemelli against C-P-ACSG. persistent symptoms in patients after acute COVID-19. JAMA 2020;324:603-5. doi: 10.1001/jama.2020.12603.

[3] Nalbandian A, Sehgal K, Gupta A, Madhavan MV, McGroder C, Stevens JS, et al. Post-acute COVID-19 syndrome. Nat Med 2021;27:601-15. doi: 10.1038/s41591-021-01283-z.

[4] Montani D, Savale L, Noel N, Meyrignac O, Colle R, Gasnier M, et al. Post-acute COVID 19 syndrome. Eur Respir Rev 2021;31.

[5] Soriano JB, Murthy S, Marshall JC, Relan P, Diaz JV. Condition WHOCCDWGoP-C., a clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect Dis 2022;22:e102-e7. doi: 10.1016/S1473-3099(21)00703-9.

[6] Montani D, Savale L, Beurnier A, Colle R, Noel N, Pham T, et al. Multidisciplinary approach for post-acute COVID-19 syndrome: time to break down the walls. Eur Respir J 2021;58. doi: 10.1183/13993003.01090-2021.

[7] Blanchflower DG, Bryson A. Long COVID in the United States. PLoS One 2023;18: e0292672. doi: 10.1371/journal.pone.0292672.

[8] Wynberg E, van Willigen HDG, Dijkstra M, Boyd A, Kootstra NA, van den Aardweg JG, et al. Evolution of COVID-19 symptoms during the first 12 months after illness onset. Clin Infect Dis 2021. doi: 10.1093/cid/ciab759.

[9] Zhang X, Wang F, Shen Y, Zhang X, Cen Y, Wang B, et al. Symptoms and health outcomes among survivors of COVID-19 infection 1 year after discharge from hospitals in Wuhan, China. JAMA Netw Open 2021;4:e2127403. doi: 10.1001/jamanetworkopen.2021.27403.

[10] Huang L, Yao Q, Gu X, Wang Q, Ren L, Wang Y, et al. 1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study. Lancet 2021;398:747-58. doi: 10.1016/S0140-6736(21)01755-4.

[11] Maestre-Muniz MM, Arias A, Mata-Vazquez E, Martin-Toledano M, Lopez-Larramona G, Ruiz-Chicote AM, et al. Long-term outcomes of patients with coronavirus disease 2019 at one year after hospital discharge. J Clin Med 2021;10. doi: 10.3390/jcm10132945.

[12] Liu T, Wu D, Yan W, Wang X, Zhang X, Ma K, et al. Twelve-month systemic consequences of COVID-19 in patients discharged from hospital: a prospective cohort study in Wuhan, China. Clin Infect Dis 2021. doi: 10.1093/cid/ciab703.

[13] Zhao Y, Yang C, An X, Xiong Y, Shang Y, He J, et al. Follow-up study on COVID-19 survivors one year after discharge from hospital. Int J Infect Dis 2021;112:173-82. doi: 10.1016/j.ijid.2021.09.017.

[14] Writing Committee for the Comebac Study Group, Morin L, Savale L, Pham T, Colle R, Figueiredo S, et al. Four-month clinical status of a cohort of patients after hospitalization for COVID-19. JAMA 2021;325:1525-34. doi: 10.1001/jama.2021.3331.

[15] Huang C, Huang L, Wang Y, Li X, Ren L, Gu X, et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet 2021;397:220-32. doi: 10.1016/S0140-6736(20)32656-8.

[16] Metral M, Nadin I, Locatelli I, Tarr PE, Calmy A, Kovari H, et al. How helpful are the European AIDS Clinical Society cognitive screening questions in predicting cognitive impairment in an aging, well-treated HIV-positive population? HIV Med 2020;21:342-8. doi: 10.1111/hiv.12828.

[17] Ware Jr JE, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992;30:473-83.

[18] Gentile S, Delaroziere JC, Favre F, Sambuc R, San Marco JL. Validation of the French 'multidimensional fatigue inventory' (MFI 20). Eur J Cancer Care 2003;12:58-64. doi: 10.1046/j.1365-2354.2003.00295.x.

[19] Holland AE, Spruit MA, Troosters T, Puhan MA, Pepin V, Saey D, et al. An official European Respiratory Society/American Thoracic Society technical standard: field walking tests in chronic respiratory disease. Eur Respir J 2014;44:1428-46. doi: 10.1183/09031936.00150314.

[20] Boulding R, Stacey R, Niven R, Fowler SJ. Dysfunctional breathing: a review of the literature and proposal for classification. Eur Respir Rev 2016;25:287-94. doi: 10.1183/16000617.0088-2015.

[21] Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 2005;53:695-9. doi: 10.1111/j.1532-5415.2005.53221.x.

[22] Roussel M., Godefroy O. La batterie GRECOGVASC. Évaluation et diagnostic des troubles neurocognitifs vasculaires avec ou sans contexte d'accident vasculaire cérébral. D. B. Supérieur;2016.

[23] Brickenkamp R, Schmidt-Atzert L, Liepmann D. Aufmerksamkeits- und Konzentrationstest. Hogrefe 2010.

[24] Barczak P, Kane N, Andrews S, Congdon AM, Clay JC, Betts T. Patterns of psychiatric morbidity in a genito-urinary clinic. A validation of the Hospital Anxiety Depression scale (HAD). Br J Psychiatry 1988;152:698-700. doi: 10.1192/bjp.152.5.698.

[25] Beck A.T., Beamesderfer A. Assessment of depression: the depression inventory. psychological measurements. In: editors. Psychopharmacology. Mod. Probl. In Pharmacopsychiatry, Paris, Karger, Basel: Pichot; 1974, p. 151-9.

[26] Harris PA, Taylor R, Minor BL, Elliott V, Fernandez M, O'Neal L, et al. The REDCap consortium: building an international community of software platform partners. J Biomed Inform 2019;95:103208. doi: 10.1016/j.jbi.2019.103208.

[27] Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009;42:377-81. doi: 10.1016/j.jbi.2008.08.010.

[28] Maestrini V, Birtolo LI, Francone M, Galardo G, Galea N, Severino P, et al. Cardiac involvement in consecutive unselected hospitalized COVID-19 population: in-hospital evaluation and one-year follow-up. Int J Cardiol 2021;339:235-42. doi: 10.1016/j.ijcard.2021.06.056.
[29] Seessle J, Waterboer T, Hippchen T, Simon J, Kirchner M, Lim A, et al. Persistent symptoms in adult patients one year after COVID-19: a prospective cohort study. Clin Infect Dis 2021. doi: 10.1093/cid/ciab611.

[30] Wu X, Liu X, Zhou Y, Yu H, Li R, Zhan Q, et al. 3-month, 6-month, 9-month, and 12-month respiratory outcomes in patients following COVID-19-related hospitalisation: a prospective study. Lancet Respir Med 2021;9:747–54. doi: 10.1016/S2213-2600(21)00174-0.

[31] Group P-CC. Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study. Lancet Respir Med 2022;10:761–75. doi: 10.1016/S2213-2600(22)00127-8.

[32] Schlemmer F, Valentin S, Boyer L, Guillaumot A, Chabot F, Dupin C, et al. Respiratory recovery trajectories after severe-to-critical COVID-19: a 1-year prospective multicentre study. Eur Respir J 2023;61. doi: 10.1183/13993003.01532-2022.

[33] Zhan Y, Zhu Y, Wang S, Jia S, Gao Y, Lu Y, et al. SARS-CoV-2 immunity and functional recovery of COVID-19 patients 1-year after infection. Signal Transduct Target Ther 2021;6:368. doi: 10.1038/s41392-021-00777-z.

[34] Bowe B, Xie Y, Al-Aly Z. Postacute sequelae of COVID-19 at 2 years. Nat Med 2023;29:2347–57. doi: 10.1038/s41591-023-02521-2.

[35] Han Q, Zheng B, Daines L, Sheikh A. Long-term sequelae of COVID-19: a systematic review and meta-analysis of one-year follow-up studies on post-COVID symptoms. Pathogens 2022;11. doi: 10.3390/pathogens11020269.

[36] Singh I, Joseph P, Heerdt PM, Cullinan M, Lutchmansingh DD, Gulati M, et al. Persistent exertional intolerance after COVID-19: insights from invasive cardiopulmonary exercise testing. Chest 2022;161:54–63. doi: 10.1016/j.chest.2021.08.010.

[37] Taverne J, Salvator H, Leboulch C, Barizien N, Ballester M, Imhaus E, et al. High incidence of hyperventilation syndrome after COVID-19. J Thorac Dis 2021;13:3918–22. doi: 10.21037/jtd-20-2753.

[38] Beurnier A, Savale L, Jais X, Colle R, Pham T, Morin L, et al. Functional respiratory complaints among COVID-19 survivors: a prospective cohort study. ERJ Open Res 2023;9. doi: 10.1183/23120541.00063-2023.

[39] Courtney R. Breathing training for dysfunctional breathing in asthma: taking a multidimensional approach. ERJ Open Res 2017;3. doi: 10.1183/23120541.00065-2017.

[40] Guillen-Burgos HF, Galvez-Florez JF, Moreno-Lopez S, Gonzalez I, Guillen M, Anaya JM. Factors associated with mental health outcomes after COVID-19: a 24-month follow-up longitudinal study. Gen Hosp Psychiatry 2023;84:241–9. doi: 10.1016/j.genhosppsych.2023.08.009.

[41] Luger AK, Sonnweber T, Gruber L, Schwabl C, Cima K, Tymoszuk P, et al. Chest CT of lung injury 1 year after COVID-19 pneumonia: the CovILD Study. Radiology 2022;211670. doi: 10.1148/radiol.211670.

[42] Faverio P, Luppi F, Rebora P, Busnelli S, Stainer A, Catalano M, et al. Six-month pulmonary impairment after severe COVID-19: a prospective, multicentre follow-up study. Respiration 2021;100:1078–87. doi: 10.1159/000518141.

[43] Moller M, Borg K, Janson C, Lerm M, Normark J, Niward K. Cognitive dysfunction in post-COVID-19 condition: mechanisms, management, and rehabilitation. J Intern Med 2023;294:563–81. doi: 10.1111/joim.13720.

[44] Poenaru S, Abdallah SJ, Corrales-Medina V, Cowan J. COVID-19 and post-infektious myalgic encephalomyelitis/chronic fatigue syndrome: a narrative review. Ther Adv Infect Dis 2021;8 20499361211009385. doi: 10.1177/20499361211009385.