The Use of Focused Lung Ultrasound in Patients Suspected of COVID-19
Conditions: COVID-19
Sponsor: University of Aarhus

Focused lung ultrasound 
for diagnosing and risk-
stratification of patients 
with COVID-19 symptoms 
 
April 8. 2020 
NCT 04327674 
 
 

Background 
COVID-19 is defined as an infectious disease caused by SAR-CoV-2 virus. It results in pneumonia and 
sometimes respiratory failure. SARS-CoV-2 pandemic has led to massive strain on health care facilities. A 
large proportion of the population is at risk of COVID-19 and some estimates suggest that up to 15% will need 
hospitalization. Such number of patients strains the health care system to its maximum as capacity has 
limitations even in highly developed countries.  
Early reports estimate that more than 80% of patients admitted to hospital with COVID-19 have abnormal 
findings on chest radiographs1. Thus, imaging seems to be an important part of the diagnostic work-up. In 
most hospitals however, access to CT-scanning of the thorax of all patients with COVID-19 or with suspicion 
of CODIV-19 is unrealistic due to restricted capacity. Chest radiographs are faster and easier to do, but may 
require transportation of the patient to the department of radiology which carries a risk of virus spreading in 
the hospital. On-site chest radiograph is often of such low quality that diagnosis or follow-up will be difficult.    
Focused ultrasound examination of the lungs, FLUS, is a diagnostic tool that can show changes in the lung 
parenchyma due to pneumonia. FLUS is a bed-side examination performed by the physician which results in 
reduced risk of in-hospital virus contamination. Furthermore, results from FLUS are immediately available to 
the physician. This allows rapid decision-making which is essential in cases of high patient burdens as seen in 
the COVID-19 pandemic.  
Furthermore, SARS-CoV-2 positive patients with pneumonia may be at higher risk of respiratory failure than 
those without pneumonia. Identifying patients at high risk can qualify decisions about monitoring level and 
organization of intensive care resources.  Conversely, patient with COVID-19 symptoms but without 
pneumonic FLUS finding could likely be managed as out-patients. Such a risk-stratification may optimize the 
allocation of limited healthcare resources and reserve in-hospital capacity to those patients who needs it.  
 
Hypothesis 
FLUS can risk-stratify patients with COVID-19 symptoms. 
FLUS can predict respiratory failure in patients with COVID-19 pneumonia. 
FLUS can diagnose COVID-19 pneumonia with high sensitivity and specificity using PCR-test and chest 
radiograph as reference. 

Aim 
To study the ability of FLUS in COVID-19 to predictive respiratory failure. 
To study the diagnostic capability of FLUS to find COVID-19 pneumonia. 
To study risk-stratifying capability of FLUS in patients with COVID-19 symptoms. 
 
Method 
Design 
Multicenter prospective cohort study with convenience sampling. 
Setting 
Emergency departments or internal medicine departments who admit patients with COVID-19 symptoms. 
Participants 
Patients who have COVID-19 symptoms and require diagnostic testing.  
Patients who have a positive SAR-CoV-2 PCR-test and require admission to hospital. 
Inclusion criteria 
• 
Patients who are seen in COVID-clinics or emergency departments due to symptoms that require 
diagnostic work-up to COVID-19. 
• 
Patients admitted to hospital with positive SARS-COV-2 PCR-test and in whom FLUS is performed less 
than 48 hours after admission.  
Exclusion criteria 
• 
Age less than 18 year. 
• 
Former participation in this study. 
• 
Pre-FLUS ventilator support. 
 
Double inclusion 
Inclusion in this study will not restrict patient from inclusion in other studies. 
 

Recruitment 
Participants are recruited at the local hospital. In Denmark the study is labelled quality assurance and the 
need for informed consent is thus waived. Local regulations are followed and it is the responsibility of each 
inclusion site to achieve appropriate regulatory permissions including need for approval from  local ethical 
committees and healthcare authorities.  
Variables 
Ultrasound variables: FLUS are performed according to ERS guidelines and to Standard of Operating 
Procedure specific to this study. Film clips are recorded and saved for later evaluation. 14 zones are scanned. 
Film clips are marked with scanning position (L1, L2…etc.). If the patient in unable to sit, only anterior and 
lateral zones are scanned. FLUS findings are assessed on the film clips by an observer blinded to other 
variables. Finding are coded with 1/0 for presents of pneumonia. Moreover, a scoring system is applied: 
FLUS findings 
Score 
Normal FLUS 
0 
Interstitial syndrome, defined as more than 3 B-lines in a single zone.  
Diverse B-lines or irregular pleura 
1 
interstitial syndrome, defined as more than 3 B-lines in a single zone. 
Confluent B-lines. 
2 
Consolidations (sub-pleurale, lobar, with or without air-bronchograms) 
3 
  
Data on FLUS operator:  Level of medical degree. Years of experience with lung ultrasound. Completed 
training in FLUS. 
From patient files the following data is extracted: 
Patient demographic: Sex, age, height, weight, co-morbidities. 
Clinical data on time of admission: Blood pressure, puls, peripheral saturation, respiratory frequency, 
temperature, length of illness, list of symptoms, limitation to treatment i.e. not suited or willing to intensive 
care treatment and intubation.  
Data from radiographic diagnostics: Result of chest radiograph, CT or HRCT scanning, if done for clinical 
reasons. No further review of radiographic examinations is performed. Results given by local radiology 
department is used. 
Microbiological data: Result of SARS-CoV-2 PCR-test form nasal/oral/laryngeal or tracheal samples. 

Data from admission: Time of admission. Place of admission. Time of dismission. Admission to intensive care. 
Intubation. Time in ventilator. Death, survival. In hospital survival, 14- and 30-days survival. 
Endpoints 
Primary endpoint: FLUS (binary: positive/negative pneumonia) related to intubation (yes/no). 
Secondary endpoints: Relationship between FLUS and SARS-CoV-2 PCR result. 
Relationship between FLUS and radiographic findings. 
Relationship between FLUS and admission to intensive care (not intubation). 
Relationship between FLUS and re-admission (Patient returning to emergency department or COVID-clinic). 
Scores of FLUS findings in different zones. 
Data management 
The study uses convenience sampling as FLUS may not be available at all times. FLUS is performed by the 
clinician such that only doctors with clinically relevant work are allowed to scan the patient. This minimizes 
the risk of disease transfer to doctors and reduces the use of protection equipment.  
Ultrasound film clips are recorded according to standard operating procedure. Film clips are stored securely, 
according to local legal regulations. All variables extracted from patient files are stored in an eCRF using 
REDCap supplied by Aarhus University Hospital.  
Every site will have access to enter data in data capture instruments. Access to REDCap is managed by the 
project steering committee at Aarhus University Hospital. 
Data analysis 
All data are analyzed in Stata.  
Binary endpoints, including primary endpoint, are analyzed using Chi-2 test. Continuous data are assessed 
for parametric distribution and analyzed with Student´s T-test on logarithmic transformed data in case of 
non-parametric distribution.  
Level of statistical significance is set to 5%. 
A logistic prediction model will be developed. Dependent variable is intubation.  Independent variables are 
age (continuous), FLUS result (Binary or ordinal), SARS-CoV-2 status (Binary) and peripheral oxygen saturation 
(continuous).   

The data set will be divided in two. One is used for model development and one is used for validation of the 
model. Geographic external validity is tested. Internal validity is tested with bootstrapping method. 
Sensitivity, specificity and ROC AUC is calculated.  
Sample size 
No prior publications are available for sample size estimation.  
For the prediction model we wish to include 10-15 events per independent variable, 50-75 events. From early 
estimations about 20% of admitted patients requiring intubation our estimate is 375-400 participants.  
Inclusion period 
An end date is set to May 15 2020. If COVID-19 pandemic in ongoing at this time point the study may extent. 
Blinding 
Ultrasound film clips are analyzed blinded to other variables.  
Plan for publication 
Data analysis is estimated to end July 1. 2020. Article submission is estimated to October, 2020.  
Preliminary data analysis 
Available data will be analyzed soon after 15. May.   
Ethical considerations 
FLUS is without any risk to patients. COVID-19 is an infectious disease and isolation is needed. Contamination 
during the study needs to be avoided. For this reason, FLUS is only performed by the physicians who are 
required to see the patient regardless of this study. The ultrasound equipment is cleaned after each 
examination in accordance with local guidelines.  
Legal regulations 
In Denmark the study is classified as a quality assurance project. Arrangements and permission to access to 
patient files in each site is required. According to guidance from the legal office at Region Midt a data 
management agreement in not needed.  
International data agreements are required to data transfer from international sites to Denmark. 
All international sites must adhere to local regulation. Responsibility of this is on the international site. 
 

Publication 
All results (negative, inconclusive or positive) are submitted to peer-reviewed medical journals. Qualification 
for authorship follows ICJME recommendations. A number of 50 patients included per site is set as the 
minimal limit of contribution required for authorship.  
Group 
Primary investigator 
 
Søren Helbo Skaarup. Læge, Ph.d. stud. Lungemedicinsk Afdeling. AUH. 
Sub investigator: 
 
Rasmus Aagaard. Læge, ph.d. Bedøvelse og operation. AUH 
Stig Holm Jensen. Stud.med. Aarhus Universitet. Center for Akutforskning. AUH.  
Hans Kirkegaard. Professor. Center for Akutforskning. AUH. 
Jesper Weile. Læge, ph.d. Akutafdelingen. Regionshospitalet Horsens. 
Christian B. Laursen. Læge, Ph.d. Lungemedicinsk Afdeling. OUH.  
Jesper Rømhild Davidsen. Læge, Ph.d. Lungemedicinsk Afdeling. OUH. 
Klaus Nielsen Jeschke. Læge. Lungemedicinsk Afdeling. Hvidovre Hospital. 
Hans Henrik Schultz. Læge, Ph.d. Lungemedicinsk Afdeling. Gentofte og Herlev Hospital. 
Emil Shwarz Walsted, Læge, Ph.d. Lungemedicinsk Afdeling. Bispebjerg Hospital. 
 
Perspective 
The COVID-19 pandemic has had a tremendous impact on hospital resources. Optimal use of limited 
resources is essential when managing high level strain on health care systems. 
Point-of-care FLUS allows for a rapid answer to the central question of whether the patient has pneumonia 
or not with the lowest possible use of resources. Demands on radiological resources will likely lead to long 
waiting time.  

A large proportion of COVID-19 patients will need ventilatory support with intubation. Early identification of 
patients who are at high risk of respiratory failure will allow planning of intensive care resources. Conversely, 
patient without FLUS pathological findings may be managed safely as out-patients. 
Results from this study will enhance our knowledge on COVID-19 related respiratory failure and give us an 
ability to manage large strains on health care resources.  
Referencer 
1.  
Guan W, Ni Z, Hu Y, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med 
2020;NEJMoa2002032.  
2.  
Laursen CB, Rahman NM, Volpicelli G, editors. Thoracic Ultrasound. Sheffield, United Kingdom: 
European Respiratory Society; 2018.