key: cord-0889193-ixm8ge2y
authors: Tung-Chen, Yale; Algora-Martín, Ana; Llamas-Fuentes, Rafael; Rodríguez-Fuertes, Pablo; Virto, Ana María Martínez; Sanz-Rodríguez, Elena; Alonso-Martínez, Blanca; Núñez, Maria Angélica Rivera
title: “Point-of-care ultrasonography in the initial characterization of patients with COVID-19”
date: 2021-01-28
journal: Med Clin (Barc)
DOI: 10.1016/j.medcli.2020.12.007
sha: 153d6f304deb305c45bbef093dbd6ad48f2241a7
doc_id: 889193
cord_uid: ixm8ge2y

BACKGROUND: There is growing evidence regarding the imaging findings of coronavirus disease 2019 (COVID-19) in chest X-rays and computed tomography scans; however, their availability during this pandemic outbreak might be compromised. Currently, the role of point-of-care ultrasonography (POCUS) has yet to be explored. OBJECTIVES: To describe the POCUS findings of COVID-19 in patients with the disease admitted to the emergency department (ED), correlating them with vital signs, laboratory and radiologic results, therapeutic decisions, and the prognosis. METHODS: Prospective study performed in the ED of 2 academic hospitals. Patients with highly suspected or confirmed COVID-19 underwent a lung ultrasonography (lung POCUS), focused cardiac ultrasound (FOCUS), and inferior vena cava (IVC) exam. RESULTS: Between March and April 2020, 96 patients were enrolled. The mean age was 68.2 years (SD 17.5). The most common findings in the lung POCUS were an irregular pleural line (63.2%), bilateral confluence (55.2%), and isolated B-lines (53.1%), which were associated with a positive RT-PCR (odds ratio 4.327; 95% CI 1.216–15.401; p<.001), and correlated with IL-6 levels (rho = 0.622; p = .002). The IVC negatively correlated with levels of expiratory pO2 (rho = −0.539; p = .014) and inspiratory pO2 (rho = −0.527; p = 0.017), and expiratory diameter positively correlated with troponin I (rho = 0.509; p = .03). After the POCUS exam, almost 20% of the patients had an associated condition that required a change in their treatment or management. CONCLUSIONS: POCUS parameters have the potential to impact the diagnosis, management, and prognosis of patients with confirmed or suspected COVID-19.

OBJETIVOS: Describir los hallazgos POCUS en pacientes con COVID-que consultaron en el servicio de urgencias (SU), correlacionándolos con signos vitales, resultados analíticos y radiológicos, decisiones terapéuticas y pronóstico.

Estudio prospectivo realizado en los SU de 2 hospitales académicos. Los pacientes con COVID-19 con alta sospecha o confirmado se sometieron a una ecografía pulmonar (POCUS pulmonar), una ecocardioscopia y ecografía de la vena cava inferior (VCI).

J o u r n a l P r e -p r o o f RESULTADOS: Entre marzo y abril de 2020, se reclutaron 96 pacientes. La edad media fue de 68,2 años ( DE 17, 5) . Los hallazgos más comunes en el POCUS pulmonar fueron la línea pleural irregular (63,2%), las líneas B confluyentes bilateral (55,2%) y aisladas (53,1%), que se asociaron con una RT-PCR (odds ratio 4.327; 95% CI 1.216-15.401; p<.001), y se correlacionó con los niveles de IL-6 (rho = 0.622; p = .002). La VCI se correlacionó negativamente con los niveles de pO2 espiratorio (rho = −0,539; p = .014) y pO2 inspiratorio (rho = −0,527; p = 0,017), y el diámetro espiratorio se correlacionó positivamente con la troponina I (rho = 0,509; p =. 03). Coronavirus disease 2019 (COVID-19) is a highly contagious illness caused by infection with SARS-CoV-2. In this emergency, the ability to quickly characterize a confirmed or suspected case is critical, given almost any emergency department will struggle to keep up with the increasing number of patients and the shortage of health resources.

The primary diagnostic method is reverse transcription polymerase chain reaction (RT-PCR) of the nucleic acid of SARS-CoV-2 in nasopharyngeal swabs 3 . However, it has many limitations, such as low sensitivity and the technical difficulties associated with performing it 4 .

Various studies have suggested that abnormalities as shown on computed tomography (CT) are highly sensitive for diagnosis of patients with COVID-19, and should be considered as a screening tool 4 . Moreover, various clinical, laboratory, and imaging parameters have been associated with prognosis 5 and have been used to guide therapy 6 .

However, because these diagnostic, laboratory, and therapeutic resources might not be ubiquitously available, we need alternative modalities to more rapidly characterize our patients.

Point-of-care ultrasonography (POCUS) is ubiquitous and quickly performed following simple and easy to apply protocols 5 ; therefore, it can be performed in mild or even unstable patients, in various settings. The presence of subpleural J o u r n a l P r e -p r o o f consolidations, thickened pleural lines, and B-lines are highly specific for lung involvement affecting the interstitium (interstitial syndrome), which in these cases suggests the presence of COVID-19 pneumonia 7-9 .

The role and impact of this technique in this pandemic has not yet been explored.

This was a prospective study performed in the emergency department (ED) of 2 academic hospitals, conducted in accordance with the Declaration of Helsinki, and approved by the Research Ethics Committee of each University Hospital involved.

Informed consent was obtained from each enrolled patient.

Patients admitted to the ED with a clinical suspicion of COVID-19 (temperature above 37.2ºC, acute respiratory symptoms, gastrointestinal symptoms, or fatigue) requiring X-ray for evaluation were included. We excluded patients <18 years or those who declined to participate. A convenience sample of patients who met these inclusion criteria were consecutively enrolled and prospectively studied.

Patients were followed-up the following week, either during hospitalization or after hospital discharge, as appropriate.

The initial evaluation of the patients included recording their medical history (demographic data, comorbidities, medications); symptoms; physical exam (temperature, blood pressure, heart rate, respiratory rate, and oxygen saturation); chest X-ray; and laboratory tests (hemogram, basic metabolic panel [e.g., glucose, The two sonographers were blinded to the patient's past medical history, vital signs, symptoms, laboratory measurements and therapy. The results of the ultrasound were recorded in the patient's medical history, and this information was available to the treating physician, who adjusted the therapy based on these findings.

The main purpose of this study was to describe and characterize the POCUS findings of the disease in patients with COVID-19 admitted to the ED. The primary outcome was to determine the impact of POCUS parameters on the prognosis of patients with J o u r n a l P r e -p r o o f highly suspected or confirmed COVID-19. The secondary outcome was to correlate these parameters with the physical exam, laboratory markers, and chest X-ray.

We defined a confirmed case as any patient with clinical symptoms and positive RT-PCR, and a high suspicion case as any patient with negative RT-PCR but compatible clinical symptoms and typical X-ray, CT scan, or lung POCUS.

Baseline characteristics are presented as mean and standard deviation (SD) for continuous variables and count and proportions for categorical variables. For group comparisons, we used a t-test for continuous variables and the chi-squared or Fisher's exact test for categorical variables. The correlations between continuous variables were tested using Spearman's rho test for categorical variables. Mean values were reported, along with 95% confidence intervals (CIs). Statistical significance was set at p < .05.

Statistical analyses were conducted with IBM SPSS software v20.0 (SPSS Inc., Chicago, IL, USA).

A total of 96 patients were enrolled between March and April 2020 (summarized in Table 1 

All the included patients underwent a POCUS study, and almost all of them had a chest X-ray (see Table 2 ).

The most frequent pattern in the chest X-ray was an interstitial pattern (56.4%), and more than one-third had ground-glass opacities (GGOs). Almost 30% of them had a normal chest X-ray.

Regarding the lung POCUS, the most common finding was an irregular pleural line After the POCUS exam, almost 20% of the patients had an associated condition that required a change in their treatment or management.

The presence of irregular pleural line (see Table 3 However, we did not find any significant association between isolated B-lines and interstitial pattern (p = .156), GGO (p = 0.928), or any pathologic X-ray findings (p = .831). These patients were more likely to receive anti-IL-6 therapy (rho = 0.612; p = .002).

We found a statistically significant negative correlation of pO2 levels with IVC diameter, both inspiratory (rho = −0.527; p = .017) and expiratory (rho = −0.539; p = .014). The IVC expiratory diameter positively correlated with troponin I levels (rho = 0.509; p = .03).

Patients who showed confluent B-lines were more likely to receive anti-IL-6 therapy (rho = 0.206; p = .045), and patients who showed a lobar consolidation were more likely to receive therapy with hydroxychloroquine (rho = 0.810; p = .001).

Remarkably, this correlation was much lower when small consolidations (rho = 252, p = .013) or confluent (rho = 0.262; p = .01) or isolated (rho = 0.279, p = .006) B-lines were present.

At the end of the first week of follow-up, 6 (6.3%) patients had died and 17 (17.1%) were discharged home. The remaining 73 (76.0%) patients were still hospitalized.

Normal chest X-ray had a weak correlation with ED discharge (rho = 0.235; p = .022). Abnormal chest X-ray was not associated with mortality (p = .178) or poor outcome (ICU admission, the need for mechanical ventilation, inotropic drugs or death; p = .115). Normal lung POCUS had a moderate correlation with ED discharge (rho = .444; p < .001). Abnormal lung POCUS findings were not associated with mortality (p = .514) or poor outcome (p = .446).

Patients with comorbid diseases were more prone to have apical lung involvement: There is growing literature regarding the prognostic factors 5 , diagnosis [3] [4] , and therapeutic challenges 6 in patients with COVID-19.

In diagnosis, the sensitivity of RT-PCR for diagnosing SARS-CoV-2 has been quantified as 63% in nasal swab and 32% in pharyngeal swab 14 , which is similar to our results; we found a positive rate of only 59.5% in patients with clinical suspicion J o u r n a l P r e -p r o o f of COVID-19. Therefore, imaging methods play a key role in the diagnosis and assessment of these patients.

A study of 1049 patients undergoing chest CT scan and RT-PCR testing determined that CT abnormalities had a high sensitivity for diagnosing patients with COVID- 19 4 , suggesting that a CT scan should be considered as a screening tool, especially in epidemic areas with high pretest probability. However, the use of CT in the ED has many limitations, such as radiation exposure, especially for mild illness, its low availability, and the contraindication for its use in unstable patients.

Therefore, in many centers, CT scans have been replaced by chest X-ray. However, as we have seen, chest X-rays have been shown to have a very low NPV (34.9%). In a study of patients undergoing an initial screening for COVID-19, they found a sensitivity of 25% and a specificity of 90% 15 .

In our study, we found that of 27 patients with normal chest X-ray, 23 (85.1%) had a pathological POCUS finding. A previous study found that a normal chest X-ray was present in 31% of patients with positive RT-PCR for COVID-19 16 , which is similar to our results (28.4%). We hypothesize that this low percentage is due to the low accuracy of X-ray for detecting interstitial abnormalities 5 , represented in our study as isolated B-lines on lung POCUS, and becoming apparent on X-ray as the disease progresses, with the appearance of confluent B-lines and other findings. Regarding therapy, by adding POCUS to our protocol, we could determine the presence of synchronous or comorbid diseases, such as heart failure or lobar pneumonia (viral or bacterial), or confirm the presence of deep vein thrombosis or pericardial effusion, which in our study was observed in approximately 1 of 5 (18.8%) patients. These findings should trigger the initiation or adjustment of therapy (e.g., antibiotics, anticoagulants, diuretics, or colchicine).

Moreover, we showed that that the number of affected lung areas correlated with inflammatory markers, such as IL-6, which in turn could serve as a guide to start therapy with an anti-IL-6 therapy (e.g., tocilizumab). Remarkably, but understandably, this marker was associated with a higher respiratory rate, acute phase reactants (CRP, procalcitonin, ferritin) and LDH, which according to previous studies are also prognostic markers 5 . We did not observe a correlation with ICU admission, therapeutic or invasive procedures, or death, possibly due to the short follow-up (1 week).

Evidence in follow-up and prognosis, dynamic changes in chest CT findings (GGO lesions, crazy-paving pattern, and consolidation) have been proposed to occur during the time course and progression of the disease [19] [20] , which could be a marker of the disease stage. Given this disease tends to have a rapid progression, a CT scan might not be available, or the patient's condition might not allow its performance 14 The presence of apical lung involvement in POCUS correlated in our study with various comparable comorbid diseases (hypertension, cardiomyopathy, dementia) that yielded specific laboratory markers (creatinine, lymphocyte count, procalcitonin), and as expected, prognoses 5 .

The IVC, as a marker of fluid status, moderately correlated with levels of pO2 and troponin I, which could represent hemodynamic congestion (higher inspiratory and expiratory diameters) and poorer oxygenation. Therefore, we believe that integrating IVC into our current practice is appropriate, given it more physiologically addresses the assessment of the volume status.

In our study, we found a higher prevalence of pleural effusion (23%) than previously reported 16, 20 , which could be due to the accuracy of the technique compared with CT scan or chest X-ray 12 ; therefore, its mere presence should not be considered as a prognostic factor.

The main strengths of our study, is that to our knowledge, this is the first study evaluating the potential impact of POCUS on patients with COVID-19, with diagnostic, prognostic, and therapeutic implications.

We would like to share our study findings, given the urgent need for various strategies in order to better manage patients with COVID-19, and to diminish the SARS-CoV-2 spread and its prognosis in the current pandemic context. Given the shortage of resources constitutes an undeniable public health threat, we consider POCUS to be a potential solution, and recommend that it be performed as a first-line imaging test for patients with COVID-19.

There are several limitations to consider. The main limitation is that lung POCUS findings overlap with those from other pneumonia etiologies or incidental chronic findings (e.g., chronic heart failure or pulmonary fibrosis). In epidemic areas, however, positive lung POCUS features, even with negative RT-PCR or chest X-ray, can still be highly suggestive of COVID-19 infection, which could preclude that the sensitivity and specificity reported of lung POCUS might be higher. Thus, more studies should be performed comparing it with other techniques (e.g., CT scan). Many patients with COVID-19 in our ED with negative RT-PCR or chest X-ray do not always receive a chest CT, and therefore there is a chance of misdiagnosis. This limitation was minimized, given the patients were followed-up by reviewing their electronic history, and any complications were recorded. In addition, we have to highlight that the main purpose of the study was to compare the performance of POCUS in COVID-19 patients, and the study was not powered to evaluate the performance of a diagnostic or management strategy based on POCUS findings; therefore, for this purpose, the study can only be considered hypothesis generating.

Another limitation is that selection bias might have occurred. Two expert sonographers performed all ultrasound scans on a consecutive sample selected based on their availability (during their working hours), which limits the generalizability of our results. The impact of this limitation is minimized by variable schedules and changing shifts, unpredictable a priori (in continuous care). Additionally, false negative ultrasounds might be found in the initial stage of the disease, before lung involvement.

Thus, the results from this study provide an opportunity to further investigate the use of ultrasound in various settings and clinical scenarios.

In conclusion, in this pandemic era, given the shortage of resources constitutes an undeniable public health threat, POCUS presents the potential to impact the diagnosis, management, and prognosis of patients with confirmed or suspected COVID-19.

 The authors have declared no conflicts of interest. 

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ARTICLE SUMMARY: 1. Why is this topic important?

COVID-19) is a highly contagious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)era, with the low sensitivity of diagnostic tests and a shortage or difficult-to-access resources, such as CT scan, specific laboratory markers such as IL-6 or therapy, and the lack of reliable prognostic markers (e.g., need for ICU admission or mechanical ventilation)

The role of point-of-care ultrasonography (POCUS) has yet to be explored

What does this study attempt to show? We aimed to describe and characterize the POCUS findings in patients with COVID-19 admitted to the emergency department (ED), to correlate these parameters with vital signs, laboratory prognostic markers

What are the key findings? -Diagnostic: POCUS findings correlated with the result of the reverse transcription-polymerase chain reaction (RT-PCR) and chest X-ray abnormalities. -Therapeutic: After POCUS, approximately 20% of the patients had an associated condition that required a change in their treatment or management. POCUS findings correlated with IL-6 levels

Apical involvement in lung POCUS correlated with a poor outcome (ICU admission, need for mechanical ventilation, inotropic drugs, and death). IVC correlated with troponin I and levels of pO2

How is patient care impacted? Diagnostic imaging plays a key role in the management of patients with COVID-19, and POCUS might be a potential solution to the limitations in the various strategies used to manage these patients. We recommend that POCUS should be performed as a first-line imaging test for patients