key: cord-1017226-pud1rwnj authors: Jutant, Etienne-Marie; Meyrignac, Olivier; Beurnier, Antoine; Jaïs, Xavier; Pham, Tai; Morin, Luc; Boucly, Athénaïs; Bulifon, Sophie; Figueiredo, Samy; Harrois, Anatole; Jevnikar, Mitja; Noël, Nicolas; Pichon, Jérémie; Roche, Anne; Seferian, Andrei; Soliman, Samer; Duranteau, Jacques; Becquemont, Laurent; Monnet, Xavier; Sitbon, Olivier; Bellin, Marie-France; Humbert, Marc; Savale, Laurent; Montani, David title: Respiratory symptoms and radiologic findings in post-acute COVID-19 syndrome date: 2021-12-16 journal: ERJ Open Res DOI: 10.1183/23120541.00479-2021 sha: 641626bf2711e490a066c68d44491026521c43a2 doc_id: 1017226 cord_uid: pud1rwnj RATIONALE: The characteristics of patients with respiratory complaints and/or lung radiologic abnormalities after hospitalisation for COVID-19 are unknown. The objectives were to determine their characteristics and the relationships between dyspnoea, radiologic abnormalities and functional impairment. METHODS: In the COMEBAC cohort study, 478 hospital survivors were evaluated by telephone 4 months after hospital discharge, and 177 who had been hospitalised in an intensive care unit (ICU) or presented relevant symptoms underwent an ambulatory evaluation. New-onset dyspnoea and cough were evaluated, and the results of pulmonary function tests, high-resolution computed tomography of the chest were collected. RESULTS: Among the 478 patients, 78 (16.3%) reported new-onset dyspnoea, and 23 (4.8%) new-onset cough. The patients with new-onset dyspnoea were younger (56.1±12.3 versus 61.9±16.6 years), had more severe COVID-19 (ICU admission 56.4% versus 24.5%) and more frequent pulmonary embolism (18.0% versus 6.8%) (all p≤0.001) than patients without dyspnoea. Among the patients reassessed at the ambulatory care visit, the prevalence of fibrotic lung lesions was 19.3%, with extent <25% in 97% of the patients. The patients with fibrotic lesions were older (61±11 versus 56±14 years, p=0.03), more frequently managed in ICU (87.9 versus 47.4%, p<0.001), had lower total lung capacity (74.1±13.7 versus 84.9±14.8%pred, p<0.001) and diffusing lung capacity for carbon monoxide (DLCO) (73.3±17.9 versus 89.7±22.8%pred, p<0.001). The combination of new-onset dyspnoea, fibrotic lesions and DLCO <70%pred was observed in 8/478 patients. CONCLUSIONS: New-onset dyspnoea and mild fibrotic lesions were frequent at 4 months, but the association of new-onset dyspnoea, fibrotic lesions and low DLCO was rare. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has provoked an ongoing global pandemic of coronavirus disease 2019 (COVID- 19) , which has affected more than 240 million individuals to date [1] . There are multiple respiratory symptoms associated with COVID-19, ranging from mild upper respiratory tract symptoms to severe acute respiratory distress syndrome [2] [3] [4] [5] . There is also growing evidence that some patients have long-term effects of COVID-19 that can affect multiple organ systems. These effects have been grouped as "post-acute COVID-19 syndrome", defined by persistent symptoms and/or delayed or longterm complications of SARS-CoV-2 infection beyond 4 weeks from the onset of symptoms [6] . As part of post-acute COVID-19 syndrome, the persistence of respiratory symptoms seems to be common, affecting 15 to 81% of patients [7] [8] [9] [10] [11] [12] [13] . However, the characteristics of patients with persistent or residual respiratory complaints after hospitalization for COVID-19 remain poorly described and understood. Recently, the Consultation Multi-Expertise de Bicêtre Après COVID-19 (COMEBAC) cohort study reported the outcomes of 478 patients 4 months after hospitalization for COVID-19 [14] . Half of the patients reported at least one symptom that did not exist before the disease. High-resolution computed tomography (HRCT) of the chest frequently revealed persistent lung abnormalities, including fibrotic lung lesions, in a minority of patients [14] . The aims of this study were to determine: 1. the prevalence of persistent respiratory symptoms persistent or residual respiratory complaints after hospitalization for COVID -19, 2. the characteristics of patients with persistent respiratory symptoms, 3. the prevalence of fibrotic lung lesions, 4. the characteristics of patients with fibrotic lung lesions and 5. the relationships between respiratory complaints, respiratory function impairment and radiologic abnormalities 4 months after COVID-19 in the COMEBAC study cohort. The COMEBAC cohort study (NCT04704388) prospectively included adult patients admitted to the Bicêtre Hospital (Paris-Saclay University hospitals -Assistance Publique -Hôpitaux de Paris) for COVID-19 during the first hit of the pandemic in France [14] . There were two levels of enrolment in the study. First, patients who met the following inclusion and exclusion criteria were screened for a telephone consultation. The inclusion criteria were as follows: survival 4 months after hospital discharge or after intensive care unit (ICU) discharge for patients who had been admitted to an ICU, age older than 18 years, hospitalization for greater than 24 hours primarily because of COVID-19, and diagnosis of SARS-CoV-2 infection by reverse transcriptase-polymerase chain reaction (RT-PCR), by typical HRCT of the chest associated with clinical features, or by both. The exclusion criteria were as follows: death within 4 months after discharge, persistent hospitalization, end-stage cancer, dementia, nosocomial COVID-19 infection, and incidental positive SARS-CoV-2 RT-PCR result during a hospital stay for a different medical indication. Second, all the ICU patients and those who were symptomatic at the telephone consultation were invited for further evaluation in the ambulatory care setting. Symptomatic patients were defined as those reporting symptoms (except for anosmia) at the telephone interview, those with persistent creatinine-level elevation, and those with persistent abnormalities on a lung CT scan conducted after hospitalization (including any residual ground-glass opacities, bronchial or bronchioloalveolar abnormalities, lung consolidations, or interstitial thickening). "New-onset dyspnoea or cough" was defined as the presence of symptoms that did not exist before COVID-19 or as the worsening of pre-existing symptoms. The telephone consultation was made three to four months after hospital discharge by a medical officer with a questionnaire focused on the general medical condition and symptoms (supplemental methods). The characteristics of the patients who were hospitalized for acute COVID-19 were extracted from electronic health records. The patients provided informed consent after ICU hospitalization or at the beginning of the telephone consultation and before the ambulatory care setting. The Ethics Committee of the French Intensive Care Society (CE20-56) approved this study. The functional impact of dyspnoea was evaluated using the modified Medical Research Council (mMRC) scale (Table E1) . A non-encouraged 6-minute walk test (6MWT) was performed according to current recommendations [15] . The patients completed standard pulmonary function tests (PFTs) with spirometry, whole-body plethysmography and singlebreath diffusing lung capacity for carbon monoxide (DLCO) according to the European Respiratory Society/American Thoracic Society (ERS/ATS) guidelines [16] . Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), total lung capacity (TLC) and DLCO are expressed as the percentages of predicted values (%pred) using the Global Lung Function Initiative (GLI) 2012 [17] and European Community for Coal and Steel (ECCS) 1993 equations [18, 19] . The Nijmegen questionnaire (Table E2 ) was given, and the patients were considered to have "functional respiratory complaints" when the Nijmegen questionnaire score was >22/64 [20] . HRCT of the chest was performed in patients assessed at the ambulatory care visit. Two radiologists (OM and SS) who were blinded to the clinical evaluation reviewed the HRCT images and reached a consensus regarding any disagreements. The presence and extension of consolidations, ground-glass opacities, crazy paving, reticulations, fibrosis and emphysema were assessed. The diagnosis of fibrotic lung lesions was based on the presence of traction bronchiectasis or on the association of interface signs with reticulations. All the patients who were admitted to the ICU, those who developed pulmonary embolism during hospitalization, and those with cardiac symptoms on examination at the outpatient clinic were evaluated with transthoracic echocardiography. Study data were collected and managed with Research Electronic Data Capture tools hosted at Assistance Publique Hôpitaux de Paris (AP-HP). Analysis was performed with the R statistical package version 4.0.1 (R Foundation for Statistical Computing). We report continuous variables as either the mean±SD or median [IQR] as appropriate and categorical variables as the number and frequency (percentage of group). Comparisons between patients with and without new-onset dyspnoea and patients with and without fibrotic lesions in lungs were performed using Student's t-test for normally distributed quantitative variables and the Mann-Whitney test for non-normally distributed quantitative variables. Pearson's chi-squared test or Fisher's exact test, as appropriate, was used to compare discrete variables between two groups. Differences were considered significant when the p value was less than 0.05. We performed multivariate analysis for new-onset dyspnoea among the population who had the telephone consultation and for lung fibrotic lesions among the population who came to the ambulatory care visit. For the multivariate analysis, we focused on variables that in the univariate analysis had a p < 0.1 and were clinically important and not collinear (consensus among investigators). The flow chart of the study is presented in Figure 1 61.9±16.6 years, P=0.001), but there was no difference in the body mass index or the frequencies of diabetes and hypertension ( Table 1) ; these patients also experienced more severe initial episodes of COVID-19, with a longer duration of hospital stay (13 [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] vs. 8 [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] days, P<0.001) and more frequent admission to the ICU (56.4 vs. 24.5%, P<0.001). They also more frequently exhibited pulmonary embolism in the acute phase (18.0 vs. 6.8%, P<0.001). In the multivariate analysis, only ICU hospitalization and an episode of pulmonary embolism were significatively associated with new-onset dyspnoea ( Table E3 ). In all, 177 patients who still had symptoms and/or had been admitted to the ICU during the acute phase were reassessed at the outpatient clinic after a median time of 125 [107-144] days ( Table 2 ). As reported in Table 1 of the COMEBAC cohort study article [14] , patients reassessed at the ambulatory care visit were comparable to patients who had only a telephone consultation, except for a more severe initial COVID-19 with more hospitalizations in ICU. Among these patients, 78 (44.1%) had new-onset dyspnoea. The mMRC score was higher in the patients with new-onset dyspnoea than in those without, although 28 87.7±22.1%pred, P=0.57) ( Table 2) . Echocardiography was performed in 40 patients with newonset dyspnoea and revealed a mild decrease in left ventricular systolic function (ejection fraction 40-49%) in 6 (15%) patients, no signs of pulmonary hypertension and no significant difference compared with patients without new-onset dyspnoea ( Table 2) . Among the 177 patients reassessed at the outpatient clinic, 23 (13.0%) had new-onset cough. The majority of these 23 patients (60.9%) had been hospitalized in the ward for COVID-19 and 78.3% did not show fibrotic lesions on HRCT. As shown in the Table 2 , the pulmonary volumes (FVC, TLC, FEV1,) were normal in the majority of the 177 patients assessed at the ambulatory care visit but DLCO was decreased in 22% of the patients. Among the 177 patients assessed at the ambulatory care visit, an echocardiography was performed in 83 patients and 12% had a decreased left ventricular ejection fraction but none had echocardiographic signs of pulmonary hypertension. Among the 177 patients assessed at the ambulatory care visit, HRCT of the chest was performed in 171 (96.6%). One or more abnormalities related to COVID-19 were observed in 108 patients (63.2%). The most frequent abnormalities were reticulations (53.2%) and groundglass opacities (42.1%). Thirty-three patients (19.3%) demonstrated fibrotic lesions ( Table 3 ). The extent of lesions was limited to <10% of parenchymal involvement in the majority of the patients with ground-glass opacities (69.4%), consolidations (80.0%) and fibrotic lesions (51.5%). The extent of fibrotic lesions was <25% in 97% of the patients ( Table 3) . There was no significant difference in radiologic abnormalities (type of lesion and extension) between the patients with and without new-onset dyspnoea ( Table 2) . A typical HRCT image of the chest in a patient with mild fibrotic lesions (<10% parenchymal involvement) is shown in Figure 2 , and that of a patient with severe fibrotic lesions (> 50% parenchymal involvement) is shown in Figure 3 , compared with that for acute COVID-19. Of the patients with fibrotic lesions, 18 (54.5%) and 5 (15.1%) had new-onset dyspnoea and cough, respectively, which was not significantly different from patients without fibrotic lesions (58 (42.0%) and 17 (12.3%), respectively, all P>0.05) ( Table 4 ). Compared to patients without fibrotic lesions on HRCT, the patients with fibrotic lesions were older (61.2±10.9 vs. 56.3±13.6 years, P=0.03). There was no significant difference in the sex ratio, BMI, comorbidities or smoking status ( Table 4) . On the other hand, the patients with fibrotic lesions experienced significantly more severe episodes of COVID-19, with a longer duration of hospital stay (27 vs. 11 [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] days, P<0.001), more frequent admission to the ICU (87.9 vs. 47.4%, P<0.001), a longer duration of mechanical ventilation (28 vs. 18 [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] This study confirms that new-onset dyspnoea is not rare 4 months after hospitalization for COVID-19, as it affected at least 16.3% of patients who were discharged alive. This result is in accordance with previous studies in which patients were assessed between 1 and 12 months after COVID-19 and that reported a prevalence of persistent dyspnoea ranging from 15 to 81% after hospitalization [12, [21] [22] [23] [24] [25] and approximately 12% in non-hospitalized patients with mild COVID-19 [26] . A recent meta-analysis on 15244 hospitalized during COVID-19 and 9011 nonhospitalized patients found a prevalence of dyspnea at 3 months after COVID-19 of 33.3% in hospitalized patients and of 19.1% in non-hospitalized patients [27] . Telephone interviews seem to be an effective approach to detect residual respiratory symptoms requiring complementary investigations at ambulatory care visits. Indeed, with more than 240 million people infected with COVID-19 worldwide [1] , the percentage of patients with new-onset dyspnoea after infection (16%) could have a major impact on public health programmes, potentially affecting nearly 40 million people worldwide. Previous data on SARS-CoV and MERS-CoV, which are responsible for epidemics of severe acute respiratory syndrome, showed that approximately 8 to 30% of patients developed fibrotic lesions on chest CT within 3 months after discharge [28, 29] . Because SARS-CoV-2 shares many similarities with SARS-CoV and MERS-CoV, with the frequent occurrence of severe pneumoniae or acute respiratory distress syndrome (ARDS), it was feared that the SARS-CoV-2 epidemic could be followed by a significant number of patients with respiratory sequelae leading to serious functional consequences [30] . This study demonstrated that the mechanisms of post-COVID-19 dyspnoea are rather multifactorial and cannot be related only to parenchymal sequelae. In particular, some patients with new-onset dyspnoea had a Nijmegen questionnaire score greater than 22, suggesting "functional respiratory complaints", while others had fibrotic lesions with lower respiratory volumes on pulmonary function tests. Indeed, despite generally normal PFTs results in the whole population, the patients with new-onset dyspnea had lower FCV and TLC, suggesting a possible role for lung sequalae in new-onset dyspnea. It has been suggested that dyspnoea could also be induced by cardiovascular dysfunction or muscular deconditioning independent of respiratory sequelae [9, 13, 31, 32] . However, in our study, left ventricular systolic dysfunction was not overrepresented in patients with new-onset dyspnoea, suggesting that left ventricular systolic dysfunction pre-existed in this at-risk population. The role of thromboembolic events in residual dyspnoea after COVID-19 remains unclear. In the studied population, pulmonary embolism during acute infection was more frequently observed in patients with new-onset dyspnoea, and this difference remained in multivariate analysis and could suggest the role of pulmonary embolism in residual dyspnoea; however, none of these patients had signs of persistent pulmonary hypertension on echocardiography. In this cohort, patients with fibrotic lesions experienced significantly more severe episodes of COVID-19, with more frequent hospitalization in the ICU and a longer duration of intubation. At 4 months, ground-glass opacities were frequently observed (>40%). Even in transient lesions, the long-term evolution of these abnormalities remains an unresolved issue. By contrast, fibrotic lesions were rare, as previously described [33] , and usually had limited extension and no functional impact. The precise characterization and evolving nature (irreversible, progressive or potentially regressive) of these lesions are matters of debate. Fibrotic lesions seem to be generally in the same areas as acute lesions as seen in [11] , and fibrotic lesions could also have a rapid onset in patients who never required mechanical ventilation [34] . COVID-19 patients with ARDS and diffuse alveolar damage can progress to the fibrosing pattern as seen on post-mortem analysis [35] even if traction bronchiectasis do not always correlate with the histologic fibrosis pattern [36] . However, histological data on surviving patients with radiological signs of fibrotic lesions in lungs are lacking. It has been suggested that the signs of fibrosis may represent areas of consolidation as in organizing pneumonia, which could reverse [37] . This hypothesis is reinforced by studies showing an improvement in residual interstitial lesions, including fibrotic lesions, after corticosteroid therapy or spontaneously [38, 39] . Fibrotic lung lesions were also more frequently associated with episodes of pulmonary embolism during COVID-19, and this difference was still present in multivariate analysis. This could suggest the presence of parenchymal sequelae of pulmonary embolism, such as pulmonary infarcts, intertwined with fibrosing lesions, but there was no evidence of typical pulmonary infarcts on the HRCT images. Even though patients with fibrotic lesions had significantly lower respiratory volumes and DLCO, functional impairment was usually mild and was not associated with a poor impact on the mMRC scale. Indeed, the presence of new-onset dyspnoea, fibrotic lesions and decreased DLCO <70% was found in only 1.6% of the whole population. While other studies have reported that lung radiologic abnormalities are correlated with poor pulmonary function and lung diffusion disorder [8, 10, 40] , no study has demonstrated a clear association with dyspnoea or limited effort capacity [7-11, 25, 41] . According with that, in a recent study, while there was an improvement in lung function and DLCO between 3 and 6 months after COVID-19, there was no improvement in dyspnea and quality of life [42] . Interestingly, 13.0% of the patients investigated at outpatient clinics and 4.8% of the whole population had new-onset cough. This finding is in agreement with studies showing that cough can persist for weeks or months after SARS-CoV-2 infection with a prevalence in a recent metaanalysis of 10.4% in hospitalized patients and 6.7% in non-hospitalized patients [27, 43] . Cough should therefore be included in the respiratory complaints after hospitalization for COVID-19 and does not seem to be associated with lung sequelae, as cough appeared to be similarly distributed in patients with or without lung fibrosis. Even if long-term studies are still needed to determine whether respiratory symptoms and radiologic lesions could resolve or worsen over time, the first 1-year follow-up studies after COVID-19 have recently been published and allow us to better understand the evolution of respiratory symptoms and sequelae of COVID-19 at a distance from the acute episode. Wu et al were the first to show that among 83 patients reassessed 1 year after severe COVID-19 who did not require mechanical ventilation, dyspnoea scores and exercise capacity improved over time but that a subgroup had persistent physiological and radiographic changes [12] . In a recent study comparing symptoms and respiratory assessment between 6 and 12 months after COVID-19, it was shown on the contrary that dyspnea score slightly worsen between 6 and 12 months and that there was no improvement in DLCO while TLC and lung imaging abnormality gradually recovered [44] . As some studies have shown improvement in both FVC and DLCO and in lung imaging abnormality from 6 months after COVID-19 [42, 45] , the precise evolution of respiratory symptoms, of functional and radiological lung damage, remains to be described and specified in long-term prospective follow-up studies. This prospective study has some limitations. First, there was a selection bias for the comparison of the results of PFTs and lung CT scans between patients with and without newonset dyspnoea, given that patients who were evaluated at ambulatory care visits were selected on the basis of the initial severity of the episode (ICU stay) or the presence of persistent symptoms. This bias was alleviated by comparing the characteristics of patients with and without new-onset dyspnoea among the entire cohort who was consulted via telephone. Second, of the 177 patients reassessed at the ambulatory care visit, 5 had negative SARS-CoV-2 serologic test, and we cannot rule out that some patients included in the study did not in fact have COVID-19 initially. Moreover, the design of this study did not allow us to assess the prevalence of respiratory symptoms in outpatients. Additionally, this study was conducted during the first hit of the pandemic, and at that time, the use of corticosteroids and anti-IL6 was limited. We cannot evaluate the impact of anti-inflammatory treatments and new variants on the occurrence of persistent or residual respiratory complaints after hospitalization for COVID-19. In conclusion, persistent respiratory symptoms, especially new-onset dyspnoea and cough, are not rare 4 months after hospitalization for COVID-19. New-onset dyspnoea was rarely associated with severe fibrotic lesions, and the association between new-onset dyspnoea, fibrotic lesions and low DLCO was rare. There was no difference in echocardiographic results according to the presence of a new-onset dyspnoea either. Radiologically persistent lesions were mainly associated with the initial severity of COVID-19 but had mild functional consequences. Therefore, new-onset dyspnoea is the direct consequence of neither fibrotic lesions nor cardiologic sequalae but may be a multifactorial consequence of lung sequalae, vascular sequalae of pulmonary embolism, dysfunctional breathing, muscular deconditioning and probably other unknown causes, and the importance of each of these causes may be different in each patient. Due to the large number of COVID-19 patients worldwide, the longterm respiratory complications of COVID-19 can lead to major use of health resources. Physicians should be aware of this condition and of the mechanisms that could lead to persistent dyspnoea in these patients to propose individual management adapted to each condition. Further long-term studies are needed to determine the evolution of respiratory symptoms and radiologic lesions over time. 33 3 (9.1%) 0 (0%) 3 (20%) 0.08 Remdesivir 33 0 (0%) 0 (0%) 0 (0%) 1 Service de réanimation pédiatrique et médecine néonatale, Hôpital de Bicêtre, DMU 3 Santé de l'enfant et de l'adolescent Service de pneumologie et soins intensifs respiratoires Service de médecine intensive-réanimation DMU 11, équipe MOODS, INSERM U1178, CESP (Centre de Recherche en Epidémiologie et Santé des Populations) DMU 13 Santé publique, Information médicale, Appui à la recherche clinique, INSERM U1018 Service de radiologie diagnostique et interventionnelle, Hôpital de Bicêtre, DMU 14 Smart Imaging Service de médecine interne et immunologie clinique, Hôpital de Bicêtre, DMU 7 Endocrinologie-immunités-inflammations-cancer-urgences Service de physiologie et d'explorations fonctionnelles respiratoires DMU 15 Biologie-Génétique-PUI, INSERM 1193 Service des maladies infectieuses et tropicales, Hôpital de Bicêtre Endocrinologie-immunités-inflammations-cancer-urgences, INSERM U1018, CESP (Centre de Recherche en Epidémiologie et Santé des Populations) Hôpital de Bicêtre, DMU 4 CORREVE Maladies du coeur et des vaisseaux Clinical Characteristics of Coronavirus Disease 2019 in China Clinical characteristics and outcomes of hospitalised patients with COVID-19 treated in Hubei (epicentre) and outside Hubei (non-epicentre): a nationwide analysis of China Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study Clinical Features of 85 Fatal Cases of COVID-19 from Wuhan. 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Persistent Post-COVID-19 Inflammatory Interstitial Lung Disease: An Observational Study of Corticosteroid Treatment The characteristics and evolution of pulmonary fibrosis in COVID-19 patients as assessed by AI-assisted chest HRCT Residual ground glass opacities three months after Covid-19 pneumonia correlate to alteration of respiratory function: The post Covid M3 study Pulmonary fibrosis 4 months after COVID-19 is associated with severity of illness and blood leucocyte telomere length Changes in pulmonary function and patient-reported outcomes during COVID-19 recovery: a longitudinal, prospective cohort study Prevalence of Post-COVID-19 Cough One Year After SARS-CoV-2 Infection: A Multicenter Study 1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study A Longitudinal Study of Respiratory, Physical and Psychological Outcomes Hôpital Marie Lannelongue Service de radiologie diagnostique et interventionnelle, Hôpital de Bicêtre, DMU 14 Smart Imaging Department of Physiology -Pulmonary Function Testing, DMU 5 Thorinno, Hôpital Bicêtre Service de Médecine Intensive-Réanimation, Hôpital de Bicêtre, DMU 4 CORREVE Maladies du Coeur et des Vaisseaux, FHU Sepsis Service de Réanimation Pédiatrique et Médecine Néonatale, Hôpital de Bicêtre, DMU3 Santé de l'Enfant et de l'Adolescent Service d'anesthésie-réanimation et médecine péri-opéartoire, Hôpital de Bicêtre, DMU 12 Anesthésie, réanimation, douleur Service de médecine interne et immunologie clinique AP-HP, Centre de recherche Clinique Paris-Saclay, DMU 13 Santé publique, Information médicale, Appui à la recherche clinique The authors thank the patients, their families, and all the health care professionals and administrative staff from Bicêtre Hospital for their outstanding support. During the last 2 weeks, and significantly more than previously, do you: -Have memory losses (for eg., Missed an appointment, forgotten a recent event, or misplaced a daily object)? [Rarely: less than once a week; Sometimes: once a week; Often: Several times a week but not every day; Very often: Almost all the time] -Feel like you were slower for reasoning, activity planification or problem solving? [Rarely: less than once a week; Sometimes: once a week; Often: Several times a week but not every day; Very often: Almost all the time] -Experience difficulties to concentrate or muster your attention (for eg., follow a conversation, read the paper or follow a tv program)? [Rarely: less than once a week; Sometimes: once a week; Often: Several times a week but not every day; Very often: Almost all the time] We would like to inform you that your personal data, recorded during this teleconsultation may be used for medical research under the responsibility of the Assistance publiquehôpitaux de Paris. You can refuse now, or any time by contacting us, your primary doctor at the hospital or the data protection officer at the hospital. Information was given and the patient did not express refusal: [YES / NO]