French multicentre observational study on SARS-CoV-2 infections intensive care initial management:

Updated: Sep 21, 2021

French multicentre observational study on SARS-CoV-2 infections intensive care initial management: the FRENCH CORONA study


Abstract

Describing acute respiratory distress syndrome patterns, therapeutics management, and outcomes of ICU COVID-19 patients and identifying risk factors of 28-day mortality.


Methods

A prospective multicentre, cohort study was conducted in 29 French ICUs. Baseline characteristics, comorbidities, adjunctive therapies, ventilatory support at ICU admission and survival data were collected.


Results

From March to July 2020, 966 patients were enrolled with a median age of 66 (interquartile range 58–73) years and a median SAPS II of 37 (29–48). During the first 24 h of ICU admission, COVID-19 patients received one of the following respiratory supports: mechanical ventilation for 559 (58%), standard oxygen therapy for 228 (24%) and high-flow nasal cannula (HFNC) for 179 (19%) patients. Overall, 721 (75%) patients were mechanically ventilated during their ICU stay. Prone positioning and neuromuscular blocking agents were used in 494 (51%) and 460 (48%) patients, respectively. Bacterial co-infections and ventilator-associated pneumonia were diagnosed in 79 (3%) and 411 (43%) patients. The overall 28-day mortality was 18%. Age, pre-existing comorbidities, the severity of the respiratory failure and the absence of antiviral therapy on admission were identified as independent predictors of 28-day outcome.


French multicentre observational study on SARS-CoV-2 infections intensive care initial management: the FRENCH CORONA study

Introduction

Since December 2019, a new agent, the SARS-CoV-2 coronavirus, has been spreading originally from the region of Wuhan in China, and rapidly overseas, causing an international outbreak of respiratory illnesses, designated as COVID-19 by the World Health Organization (WHO). In France, the first cases of COVID-19 have been reported at the end of January 2020. The increasing numbers of patients requiring intensive care urged local health and government officials to significantly increase ICU beds capacity to face COVID-19 patients [1].

While the outbreak has progressed, it appeared that SARS-Cov-2 was responsible for a very specific disease leading to severe acute respiratory failure. Despite sharing a similar aetiology, COVID-19 patients may present quite different patterns from severely hypoxaemic patients to normally breathing hypoxaemic patients with or without associated hypercapnia and inconsistent response to prone position as an example It is therefore difficult to identify which patients could benefit from one therapy to another. Currently, a variety of therapeutic strategies to manage COVID-19 patients in ICU have been suggested from supportive care alone to prescribing unproven medications. Apart from corticosteroids and tocilizumab, evidence from randomised clinical trials that potential therapies could significantly improve outcomes in patients suffering from severe COVID-19 is still needed. Clinical features of hospitalised COVID-19 patients have been described in China, Europe and the United States Although male gender, older age, comorbidities such as diabetes, immunosuppression and severe obesity appear as the most common risk factors of COVID-19 outcome worldwide, a great heterogeneity in COVID-19 features is reported amongst countries limiting potential extrapolation from other countries

Accordingly, the primary objective was to perform a prospective, multicentre, observational study to provide a detailed description of the initial management of COVID-19 patients admitted to French ICUs. The secondary objective was to identify risk factors associated with 28-day mortality in a large cohort of ICU patients. These could promote an individualised therapeutic approach for COVID-19 patients during the current and potential future coronavirus-related outbreaks.


2. Methods

2.1. Study design and population

This study is reported by the STrengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines The AZUREA group, a French research network, conducted a prospective, observational, multicentre cohort study in 16 French universities and 13 general hospitals. The study was approved by the “Comité de Protection des Personnes – Sud Méditerranée IV” (2020-A00797-32) for prospective (from the 2nd of April to the 3rd of July 2020) data collection and the Institutional Review Board of Nimes University Hospital for retrospective (from the 4th of March to the 1st of April) data collection, respectively. This study was registered in ClinicalTrials.gov on the 9th of April 2020, NCT04340466. According to French law, written informed consent was waived due to the non-interventional design of the study Patient or his/her surrogate decision-maker received an information letter before patient enrolment when possible.

All patients admitted to the intensive care unit for a diagnosis of probable or confirmed SARS-CoV-2 infection were enrolled into the study according to the predefined following criteria:


A patient presenting a confirmed SARS-CoV-2 infection (defined as a positive result by reverse transcriptase-polymerase chain reaction (RT-PCR) testing of a nasopharyngeal or lower respiratory tract swab) OR a probable SARS-CoV-2 infection (defined as a severe acute respiratory infection associated with inconclusive or unavailable RT-PCR testing) according to WHO guidance. This guidance was implemented locally with the adjunct of consistent COVID-19 CT scan imaging to classify SARS-CoV-2 infection as probable (https://www.who.int/publications-detail/global-surveillance-for-human-infection-with-novel-coronavirus-(2019-Nov)).


2.2. Data collection

For each included patient, the following data were recorded: demographic data (age, gender, weight, height), clinical data (admission diagnosis, comorbidities, Charlson score ), severity scores (SAPS II (Simplified Acute Physiology Score) SOFA (Sequential Organ Failure Assessment) scores) at ICU admission, and day 7 and 14 for SOFA. Additionally, biological data (including serum creatinine concentration, lactate, ferritin, troponin, CRP, WBC count, haemoglobin, d-dimers, fibrinogen), infection data including clinical symptoms, antimicrobial therapy modalities (timing of initiation, dosing regimen, combination therapy), sedatives and respiratory support mode (invasive mechanical ventilation (IVM), non-invasive mechanical ventilation (NIV), oxygen mask, high-flow nasal cannula oxygen), adjunctive therapies, microbiological and imaging data (chest X-ray, thoracic CT scan, US exam) were collected. Moreover, complications (pulmonary embolism, acute kidney injury, cardiac arrhythmias, myocarditis, ventilator-associated pneumonia (VAP), liver failure) were recorded until hospital discharge or death. VAP was diagnosed based on French VAP/HAP guidelines and microbiological cultures. Date of death was recorded and mortality at day 7, at ICU discharge and day 28, and organ support requirement during 28-day follow-up were also reported.

ARDS was graded according to the Berlin Definition for patients receiving mechanical ventilation on ICU admission [18]. Mild ARDS was defined as a PaO2/FIO2 ratio of ≤ 300 mmHg to 200 mmHg with PEEP or continuous positive airway pressure of ≥ 5 H2O, moderate ARDS was defined as PaO2/FIO2 ratio of ≤ 200 mmHg to 100 mmHg with PEEP ≥ 5 H2O and severe ARDS defined as PaO2/FIO2 ≤ 100 mmHg with PEEP ≥ 5 cm H2O.


2.3. Data management

Data collection was performed by trained staff at each participating centre. Data were entered into a structured electronic password-protected and secured web-based case report form (eCRF). The eCRF was developed using the REDCap Data Management Platform designed to support data capture for research studies Data monitoring was handled by the coordinating Centre (Nîmes University Hospital, France). Outstanding queries regarding the completion of the CRF were undertaken with each participating centre when necessary to ensure the accuracy of data.


2.4. Study outcomes

The primary outcome was all-cause mortality determined from the patient medical chart on day 28. The secondary outcomes were ICU and hospital mortality, ICU and hospital length of stay (LOS), all-cause mortality at day 7 and requirement of organ support.


2.5. Statistical analysis

Simple descriptive statistics were used to characterise the study population; continuous data were summarized by median and interquartile range or median and (min; max), categorical data as n (%). Comparisons between survivors and non-survivor patients at 28 days were performed using Student’s t-test for quantitative variables, or the Mann–Whitney U test when the distribution of variables was non-Gaussian, and the Chi-square test for qualitative variables. We used a mixed logistic regression model with a centre-specific random intercept to assess relationships with mortality at day 28, considering the clustered structure of the data.

A primary analysis focused on patients’ characteristics at inclusion: age, gender, BMI (> 40 vs. < = 40), SOFA score without respiratory SOFA score component (< 2 vs. > = 2), chronic obstructive pulmonary disease, chronic heart failure, chronic kidney failure, cancer, arterial hypertension (with or without angiotensin-receptor blockers or ACE inhibitors treatment), and partial oxygen arterial blood pressure (PaO2) to fraction of inspired oxygen (FiO2) ratio (PaO2/FiO2 ratio).

A secondary analysis focused on care at admission with adjustment on characteristics at admission. Care parameters included in the model were: type of respiratory support, anticoagulants, antiviral therapy, hydroxychloroquine and corticosteroids.

Sensitivity analyses were made using a generalised estimating equation (GEE) model with an exchangeable correlation matrix and Cox proportional hazards model with gamma frailty distribution. Statistical analyses were performed at the conventional two-tailed α level of 0.05 using SAS statistical software, version 9.4 (SAS Institute Inc).


Results

Between the 4th of March and the 3rd of July 2020, data from 966 patients admitted to 29 ICUs were analysed study flow diagram). The distribution of included patients among the different participating hospitals is shown in Table S1 (Supplemental data). Baseline characteristics of the study cohort are presented in Among patients under mechanical ventilation on admission, 44 (8%) presented mild 249 (47%) moderate ARDS and 224 (42%) severe ARDS. The main symptoms at ICU admission were fever (71%, n = 691), shortness of breath (69%, n = 666) and cough (58%, n = 565). Lymphopenia, elevated d-dimer, fibrinogen and ferritin levels were the most frequent biological abnormalities observed at ICU admission. Most patients underwent CT scan (76%, n = 740) and/or PCR testing (98%, n = 944) for SARS-CoV-2 infection diagnosis (Table 2).



Conclusion

The severity of hypoxaemia on admission, older age (> 70 years), cardiovascular and renal comorbidities were associated with worse outcomes in COVID-19 patients. Antiviral treatment on admission was identified as a protective factor for 28-day mortality. Ascertaining the outcomes of critically ill COVID-19 patients is crucial to optimise hospital and ICU resources and provide the appropriate intensity level of care.

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