key: cord-0834761-sl42tq5k
authors: Jourdes, Aurélie; Lafaurie, Margaux; Martin-Blondel, Guillaume; Delobel, Pierre; Faruch, Marie; Charpentier, Sandrine; Minville, Vincent; Silva, Stein; Thalamas, Claire; Sommet, Agnès; Moulis, Guillaume
title: Clinical characteristics and outcome of hospitalized patients with SARS-CoV-2 infection at Toulouse University hospital (France). Results from the Covid-clinic-Toul cohort
date: 2020-10-07
journal: Rev Med Interne
DOI: 10.1016/j.revmed.2020.08.006
sha: 0fcb7d163fb7dcaf9f5c1e8fdf3e60a47121c15c
doc_id: 834761
cord_uid: sl42tq5k

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread worldwide from epicenter of Wuhan, China since December 2019. The aim of our study was to describe the clinical characteristics and outcome of hospitalized patients with SARS-CoV-2 pneumonia at the Toulouse university hospital, France. Patients and methods We selected the patients included from March 7, 2020 to April 20, 2020 in the retrolective Covid-clinic-Toul cohort that follows all hospitalized patients with SARS-CoV-2 infection at the Toulouse Hospital. Cases were confirmed by real-time reverse transcriptase polymerase chain reaction. We report demographics, clinical, biological and radiological features, as well as unfavorable outcome at Day 14 after admission (admission in an intensive care unit, mechanical ventilation, death). Results Among263 hospitalized patients, the median age was 65 years and 155 (58.9%) were males. Two hundred and twenty-seven patients (86.3%) had at least one comorbidity. The median time from first symptom to hospital admission was 7.0 days (interquartile range: 4-10). On day 14 after admission, 111 patients (42.2%) had been transferred to intensive care unit (ICU), including 50 (19.0%) on Day 1; 61 (23.1%) needed mechanical ventilation and 19 patients (7.2%) had died. Patients admitted to ICU at Day 1 of admission (n=50) were more frequently men (66.0% vs 57.3%), smokers (25.0% vs 7.1%), with obesity (42.0% vs 24.7%) and had a higher mean level of C-reactive protein (median: 110.9mg/L vs 46.2mg/L). Conclusion This cohort provides epidemiological data on SARS-CoV-2 in hospitalized patients in a University hospital in the South of France.

The Coronavirus disease 2019 , caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been first reported in Wuhan, China, in December 2019 [1, 2] . It has subsequently spread to other provinces of China and then worldwide. The World

Health Organization declared COVID-19 outbreak a pandemic on March 11, 2020 . SARS-CoV-2 causes viral pneumonia that can lead to severe acute respiratory distress syndrome (ARDS) and even death. Previous studies have reported the clinical, biological and radiological characteristics of the first infected patients in Wuhan area [3] [4] [5] , and other authors have compared the epidemiological and clinical features of patients with COVID-19 in Wuhan and other regions in China [6] [7] [8] . Especially, disease evolution and risk factors of complications, essentially ARDS, have been described in this population [9, 10] . Due to a lack of consensual hospitalization criteria, data about hospitalized patients are heterogeneous.

To date, clinical characteristics and outcomes of patients outside China have been reported mostly in Asia, Italy and in the Unites States of America, and mostly for patients admitted to intensive care units (ICU) [11] [12] [13] [14] [15] [16] [17] [18] . Descriptive data about clinical presentation, comorbidities, treatment, and outcomes of hospitalized patients in France are lacking [19] . Moreover, prognosis factors specific to European hospitalized patients must be identified. Therefore, we developed the Covid-clinic-Toul cohort, recording data about all patients hospitalized for a SARS-CoV-2 infection at the Toulouse University hospital, South of France (2800 beds, unique tertiary hospital covering an area of about 3 million inhabitants).

The aim of this study was to describe demographics, clinical, biological and radiological features, as well as outcome at Day 14 after admission (admission in an intensive care unit, mechanical ventilation, death) in patients included in the Covid-clinic-Toul cohort until April 20, 2020.

J o u r n a l P r e -p r o o f 5 

The Covid-clinic-Toul cohort records data about all patients hospitalized for SARS-CoV-2 at the Toulouse University hospital. First patients (from March 7 to April 1) were included retrospectively and data from subsequent patients hospitalized after April 1 were collected prospectively. All the patients primarily admitted at the Toulouse University hospital (not transferred from another hospital) were included. Exclusion criteria was the opposition to data collection. All patients, or their representatives for those not able to understand the purpose of the study, were informed by a letter given at admission to hospital and/or sent to their place of residency. This cohort has been approved by institutional review board (n°RnIPH 2020-31), in accordance with the French data protection authority (MR004, Commission Nationale de l'Informatique et des Libertés, CNIL).

In the present study, we selected the patients included in the Covid-Clinic-Toul up to April 20, 2020 and with a SARS-CoV-2 infection proven by reverse transcriptase polymerase chain reaction (RT-PCR). All patients enrolled in this cohort were diagnosed according to interim guidance of theWorld Health Organization [20] .

We collected demographics, clinical, laboratory, radiological (description of chest computed tomography -CT-scans), and treatment data within the first 24 hours after admission, as well as outcome at Day 14 after admission (see below). Data were extracted from electronic medical records and recorded in an electronic data collection form.

The date of disease onset was defined by the day on which the first symptom was noticed.

Duration of symptoms was defined by the time between first symptoms and admission at the hospital. Chest-CT scans were classified as mild, moderate, severe, or critical by the extent of J o u r n a l P r e -p r o o f 6 lung lesions, according to the severity score of the French Society of Radiology that assesses the extent of lesions [21] .

The primary outcome was composite, including admission to ICU, need of mechanical ventilation and death occurring during the 14 days after admission to the hospital.

We described the characteristics of the whole population, and then by two categories of subgroups: first, the patients admitted to ICU at Day 1 of admission to the hospital versus others; then, among the patients not admitted to ICU at Day 1, those with occurrence of the composite outcome versus others. Continuous variables were expressed as mean and standard deviation (SD) or median and interquartile range (IQR) depending on their distribution.

Categorical variables were presented as numbers of patients and percentages. We described, using Kaplan-Meier curves, the occurrence of the composite outcome and of death within the 14 days after admission in the subgroup of patients not admitted to ICU at Day 1, as well as the occurrence of death within the 14 days after admission in the whole population.

A total of 263 patients were included in this study. Data are summarized in Table 1 Most patients (96.2%) had a chest CT-scan at admission, with a « moderate » and « severe » score in 139 (54.9%) and 64 (25.3%) patients, respectively.

Thirty-three patients (12.5%) had received hydroxychloroquine, 9 (3.4%) lopinavir/ritonavir and only one patient (1.9%) remdesivir within the first 24 hours after admission. Most patients (62.7%) were given antibiotic treatment, mostly cephalosporins, amoxicillin/clavulanic acid and macrolides.

Of the 263 patients, 111 (42.2%) were admitted to ICU because of the development of organ dysfunction, ARDS or need of oxygen therapy ≥ 5 L/minute during the 14 first days of hospitalization. The median time from onset of symptoms to ICU admission was 8.0 days (IQR: 5.0-11.0). Mechanical ventilation was required in 61 patients (23.2%).

Nineteen patients (7.2%) had died within the 14 days after admission, including 7 in ICU.

Characteristics of these 19 patients are presented in Table 2 . All of them were aged >65 years Limitation of life-sustaining treatment was made in 14 patients (73.7%). Causes of death was ARDS for all the patients, plus pulmonary embolism (n=3), acute heart failure (n=4) and sepsis (n=3).

Occurrence over time of death in the whole population, as well as occurrence of death and of the composite outcome in patients not admitted to ICU at Day 1 are presented in Fig. 1-3. 

On admission, 213 patients (81.0%) were admitted to general wards and 50 patients (19.0%) were admitted to the ICU at Day 1. In the subgroup of those admitted to the ICU, patients were more frequently men (66.0% vs 57.3%) and smokers (25.0% vs 7.1%). Except for obesity (42.0% vs 24.7%), there was no other predominance in comorbidities. They were not more frequently exposed to ACEis, corticosteroids or NSAIDs but were more frequently 15 .6%). They were more frequently exposed to ARBs (20.8% vs 12.8%). Anosmia and dysgeusia were less frequently reported in patients with unfavorable outcome (18.2% and 19.0% vs 35.3% and 50.0% respectively). These patients were given more frequently antibiotic and hydroxychloroquine treatments during the first 24 hours after admission (76.4% and 12.5% vs 44.0% and 3.5%, respectively).

We report here a case series of 263 hospitalized patients with laboratory-confirmed SARS-CoV-2 infection. One hundred and eleven patients (42.2%) needed ICU and nineteen patients died (7.2%) within 2 weeks after their admission.

The median age of this cohort (65 years, IQR 54-76) is higher than in the three largest cohorts from China (median ages between 47 and 56 years). We also observed a higher prevalence of comorbidities [8] [9] [10] . Among hospitalized patients with COVID-19 in China, the percentage of patients who required ICU care ranged from 5% to 32% [8] , less than in our cohort which included both "critical care unit" and "intensive care unit" patients. Compared to national epidemiological data, median age of the patients included in the Covid-Clinic-Toul cohort was slightly higher (65 versus 61.5 years). However, characteristics of the ICU-hospitalized patients were consistent with national data with a male predominance and high prevalence of chronic medical illnesses [22] . Mortality rate among hospitalized patients ranged from 0% to 11% in the first reports [4, 5, 11] . Mortality rate in our study may have been underestimated due to an initially broad hospitalization criteria. Moreover, we censored the follow-up at Day J o u r n a l P r e -p r o o f 10 65 years. Causes of death were ARDS for all the patients. We also observed pulmonary embolism in 15.8% of the deceased patients, in accordance with previous reports [23] .

We observed more smokers and overweight patients among those admitted to the ICU at Day 1, which is concordant with previous studies [24] [25] [26] . In our cohort, we observed a predominance of male gender, hypertension, and diabetes in patients with poor outcome within the 14 days after their admission. Grasseli et al. also reported a high prevalence of men and patients with chronic hypertension in their cohort of ICU patients [12] . Zhou et al. and

Whu et al. also identified hypertension as a risk factor of ARDS [9, 10] . This may explain the higher proportion of patients exposed to ARBs among those with unfavorable outcome [27] [28] . However, we found no difference in proportion of older and other chronic medical illnesses between ICU patients and non-ICU patients. Severe patients had also higher biological inflammatory parameters and troponin levels at admission. Myocardial injury has been described and associated with severity [5, 10, 24, 29] .

We did not observe a more frequent outcome occurrence in patients who had taken NSAIDs or corticosteroids before admission, but few patients were exposed. This may be explained by public information before the onset of the epidemic in France.

Anosmia and dysgeusia were less frequently reported in critically ill patients, which is consistent with previous studies reporting these symptoms as associated with mild cases [30] .

However, this finding must be taken with caution due to missing data regarding these symptoms.

This study has several limitations. First, only patients with laboratory-confirmed COVID-19 were included; suspected but undiagnosed cases were ruled out, especially those with typical clinical and radiological presentation but with negative RT-PCR (10% of the COVID-19 patients admitted to the emergency department at the Toulouse University hospital; J o u r n a l P r e -p r o o f 11 unpublished data). However, chest-CT has higher sensitivity than RT-PCR assay [31, 32] .

The characteristics of patients with compatible CT-scan and negative RT-PCR need to be further described. Second, some data were missing. In particular, smoking status, anosmia and dysgeusia were not systematically searched in the beginning of the pandemics. Third, the first patients were retrospectively included. Fourth, criteria for admission to ICU may have varied over time during the study period with improved knowledge of the disease by physicians.

Lastly, we presented patient characteristics at admission and outcome at Day 14. This is useful for predictive models, but we did not assess in detail what happened between Day 1 and Day 14 (including treatments administered after the first 24 hours following admission [32] [33] [34] [35] [36] [37] [38] [39] [40] [41] ) .

This cohort provides data on patients hospitalized for COVID-19 in a University hospital in the south of France, the Toulouse University hospital, and confirms some epidemiological findings: a high frequency of comorbidities in hospitalized patients, a high frequency of male gender and obesity for initial severity; and important rates of admission to ICU, mechanical ventilation, and death.

The authors declare that they have no competing interest related to this study. The Covidclinic-Toul cohort is funded by the Toulouse University hospital. *Missing values: current smoker, n=148; time from first symptoms to admission, n=2; temperature, n=7 ; heart rate, n=7 ; respiratory rate, n=12 ; arterial pressure, systolic/diastolic, n=6; oxygen saturation, n=2 ; lymphocyte count, n=35; platelet count, n=10; C-reactive protein, n=9; creatinine level, n=6; serum ferritin, n=200; D-dimers, n=227; troponin, n=150, lactate dehydrogenase, n=213. Table 2 

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The authors deeply thank Christophe Morin, Gaëlle Barencourt, Caroline Hurault-Delarue, Charlotte Vert and Julien Jacquot for their help in data acquisition and Isabelle Olivier for reglementary aspects. 

* Lymphopenia was defined by lymphocyte count < 1.5 G/L; thrombocytopenia was defined by platelet count < 150 x 10 9 /L. Abbreviation: ARDS: acute respiratory distress syndrome; COPD: chronic obstructive pulmonary disease; ICU: intensive care unit; NA: Not available.