STUDY DESIGN AND SETTING:
This prospective cohort study was conducted from 14 March through 6 May 2020 in the Emergency Department (ED) of Hospital das Clinicas da Universidade de São Paulo (HC-FMUSP), a 2,200-bed urban, academic medical center comprising five institutes and two auxiliary hospitals. During the pandemic, the HC-FMUSP ED has been designated exclusively to the reception and care of patients with COVID-19.
The study protocol was approved by the local Ethics Committee (opinion number 3.990.817; CAAE: 30417520.0.0000.0068), which also waived the need for written informed consent. The present report adheres to the STROBE guidelines.
Selection Of Participants:
Patients aged 18 years and older who were admitted to the ED with suspected or confirmed COVID-19 were considered eligible. Patients who had advance directives (do not intubate or do not resuscitate) and pregnant women were excluded.
Patients who did not test positive for COVID-19 by reverse-transcriptase polymerase chain reaction (RT-PCR) assay of nasopharyngeal swab or tracheal aspiration specimens were also excluded (Fig. 1).
After selection, patients were asked for permission to be included in the study. Once permission has been granted, a researcher interviewed the patient and collected data using a standardized form in the TeamScope® software environment (TeamScope, BV). The following variables were collected: age, sex, day of illness, admission to the Emergency Department, and signs and symptoms on admission.
A second, blinded investigator who was not involved in patient care was called in to perform the lung ultrasound. Due to the investigators’ limited availability, scans were performed only from Monday through Thursday, from 8:00 a.m. to 8:00 p.m. The investigators were aware of the presenting symptoms and the most visible physical signs, but were blinded to all the other clinical information, including radiologic findings.
Subsequently, a third investigator prospectively completed a second questionnaire in the RedCap® software environment (Vanderbilt University) with the following variables collected from electronic medical records: chest CT findings, hospitalization outcome (including hospital discharge and death), need for ICU referral, and need for invasive mechanical ventilation.
Chest CT was performed only for clinical purposes, independently of the study protocol. Blinded attending radiologists reported chest CTs as consistent or inconsistent with the most typical pattern described in COVID-19, which includes ground-glass opacities, sometimes with superimposed interlobular septal thickening (crazy paving), consolidations and reversed halo, presenting a bilateral multilobar distribution, predominantly peripheral, with mild predilection for the posterior regions and lower lobes), and gave a visual estimate of the extent of parenchymal involvement (greater or lesser than 50%).
We performed transthoracic lung ultrasound with a Sonosite Edge II portable ultrasound system and a 2- to 5-MHz convex probe. The investigators were four emergency medicine attending physicians with at least 5 years’ experience in point-of-care emergency ultrasonography.
The patient was preferably examined in the sitting position. When this position could not be maintained due to clinical deterioration or poor compliance, the examination was performed in the supine or semi-recumbent position. The posterior lung fields were scanned in the sitting position or, when not feasible, by turning the patient onto lateral decubitus on both sides successively.
The Lung Ultrasound Score (LUSS) protocol involves the examination of 12 lung regions: upper and lower parts of the anterior, lateral, and posterior aspects of the left and right chest wall. Each region was scored according to four ultrasound aeration patterns: 0 points for normal aeration, characterized by the presence of lung sliding with horizontal A lines and, occasionally, one or two isolated vertical B lines; 1 point in the presence of moderate loss of lung aeration (either multiple well-defined and spaced B1 lines, issued from the pleural line or from small juxtapleural consolidations and corresponding to interstitial edema, or coalescent B2 lines, issued from the pleural line or from small juxtapleural consolidations, present in a limited portion of the intercostal space and corresponding to localized alveolar edema); 2 points for severe loss of lung aeration, characterized by multiple coalescent vertical B2 lines issued either from the pleural line or from juxtapleural consolidations, detected in the whole area of one or several intercostal spaces and corresponding to diffuse alveolar edema; and 3 points for complete loss of lung aeration, resulting in consolidation and characterized by the presence of tissue pattern containing either hyperechoic punctiform images representative of static air bronchograms, or hyperechoic tubular images representative of dynamic air bronchograms. For a given region of interest, we allocated points according to the worst ultrasound pattern observed. The final LUSS is the sum of points in all 12 regions, and ranges from 0 to 36.
The primary endpoint of the study was death from any cause by 20 July 2020. Secondary endpoints were any ICU admission and endotracheal intubation for respiratory failure by 20 July 2020. We chose this date solely to expedite communication of our findings.
Data are presented as percentages for categorical variables and mean ± standard deviations for continuous variables. All data were tested for normality using the Kolmogorov–Smirnov test. When distribution was normal, a two-tailed Student’s t-test was used. Logistic regression was performed to explore the associations of LUSS with intubation, ICU admission, and mortality. We calculated the area under the receiver operating characteristic (ROC) curve for each regression and accepted statistical significance at p ≤ 0.05. All analyses were performed in Stata 13 software (College Station, TX, USA).