Generally, a screening test should be highly sensitive, allowing a large proportion of subjects affected by the disease to be correctly classified as having such disease. In our case series, Chest-CT identified COVID-19 lung abnormalities in all patients. On the contrary, the detection of COVID-19 lung abnormalities by LUS was impossible or inadequate in more than one third of cases. Therefore, LUS showed a lower global sensitivity (of about 52% in our casuistry) in detecting pulmonary lesions, compared to Chest-CT.
Indeed, with respect to CT-scan, LUS shows several technical limitations in lung parenchyma assessment. In particular, less than 70% of the pleura-pulmonary surface is visible with ultrasound8,18: part of the chest is US-probe-blinded, due to the overlying bone structures (i.e. ribs, scapulae); part of the lung is not adherent to pleural surface, preventing full US visibility of also big lesions due to the interposition of lung air content.
Intuitively, typical Chest-CT findings are more likely visible to LUS, being them distributed in a peripheral and posterior, diffuse or lower lung, zone. However, also the diagnostic accuracy of LUS in assessing typical CT findings in our case series was 65% (i.e. lower than that of Chest-CT), with a percent of true positive subjects (i.e. a sensitivity) of 60% and a probability of not having any typical alterations at CT scan in case of negative LUS (i.e. a negative predictive value) of only 28%. As a further confirm, the Cohen’s kappa coefficient between Chest-CT and Lung US in diagnosing Typical COVID-19 lung lesion was weak.
In particular, the sensitivity of an echographic pattern consisting in a blurred and thickened hyperechoic pleural line with B-lines below it in detecting a CT peripheral “crazy-paving” pattern of GGOs was of only 52%. Nevertheless, this artifactual US pattern is an unreliable, poor reproducible and potentially misleading diagnostic approach, due to variability among different intra- and inter-operator B-lines counting and ultrasound scan settings19. Indeed, the erroneous use of a medium-to-low frequency probe or excessive total gain and the lack of tissue harmonic imaging can generate a large number of such artifacts. Furthermore, the increase in the pleural line movement rate in dyspneic patients or the simple change of positioning of the probe with respect to the curvature of the patient's chest can influence the perceptual semi-quantitative evaluation of B-lines19.
Similar to chest-CT, LUS was able to assess subpleural consolidations in all cases (12/12). Despite this, it was possible to assess the exact number and extension of such consolidations only in a third of them. The reason for this discrepancy relies on the possibility that consolidated lung may be obscured also by a very thin layer of air in the more superficial lung or may be located in parts of the lung that are not accessible on US, such as the retro-scapular region, the mediastinal surface area or the costo-vertebral junction region. In such cases, the risk is to miss the detection of some lesions and/or underestimate the actual disease’s extent (figure 2).
The specificity and the positive predictive value in assessing US alterations in presence of typical CT findings were 92% and 97% respectively in our case series. This suggests that the probability of having typical CT patterns at Chest CT in a subject with positive LUS is high as well as the proportion of subjects without typical CT lesions and a negative LUS. This data, however, should be handled with care. In fact, this does not mean that LUS is highly specific in COVID-19 pneumonia. If correctly performed, LUS has a high specificity and a very high positive predictive value in assessing lesions that are adjacent to the viewable pleural surface, but, once again, it may not allow to visualize any alterations, if these are located in areas not accessible to US, such as in the case of the indeterminate Chest-CT lesions in our patients.
Nevertheless, it should be considered that the specificity and the positive predictive of the same LUS signs may be lowered in a normal setting of non epidemic COVID-19. Indeed, the sonographic findings described in our case series and in the current available literature on this topic11,12,13,14,15 shows a considerable overlap with many other lung diseases. An irregular pleural line with increased B-lines may be visible in ARDS, heart failure, nephrotic syndrome, bacterial pneumonia, other viral pneumonia, also minimal pleural effusion, hydropneumothorax, fibrosis, pulmonary contusion, exacerbations of chronic obstructive pulmonary diseases and neoplastic lymphangitis16. Subpleural consolidations may be visible in other viral pneumonia, non viral pneumonia, atelectasis and lung cancer16 and their LUS pattern - consisting in mixed hypo-echogenicity, with irregular, scarcely defined borders - is non-specific, not allows to distinguish one condition from another. Furthermore, some of these overlapping conditions may even be pre-existing in COVID-19 patients (especially in more severe cases) and LUS is often unable to discern a COVID-19 diagnosis in a population with such pre-existing cardiothoracic conditions, including chronic obstructive pulmonary disease, interstitial lung disease, cardiovascular disease and malignancies with cardiothoracic involvement18,20.
The American College of Radiology (ACR) does not recommend the use of chest CT to screen patients for COVID-19 pneumonia, due to the high possibility of typical CT findings’ overlapping with other viral and non-viral conditions21. Indeed, other preexisting pathologies may resemble the atypical or rare CT manifestations of this viral pneumonia22. Moreover, also confirmed positive patients can show negative chest CT23. For these reasons, it has been recommended a sparing use of CT, that has to be reserved for hospitalized, symptomatic patients with specific clinical indications. Viral testing remains the only specific method of diagnosis, whose confirmation is required, even if radiologic findings are suggestive of COVID-19.
In our COVID-19 patients, LUS resulted falsely negative in most cases, showing much less sensitivity than Chest CT in assessing disease-related lesions. This inevitable result is conform with the physical characteristics and limitations of the pleuro-pulmonary ultrasound examination and highlights LUS inadequacy for a screening purpose24. Furthermore, due to the high non-specificity of US findings and the difficulty to discriminate possible pre-existing cardio-pulmonary comorbidities, the incidental detection of alterations that could be attributable to COVID-19 pneumonia should be regarded and classified with much more attention. To date, no comparative studies have been performed between COVID-19 patients and patients with other possible overlapping cardio-pulmonary diseases. Therefore, LUS is not suitable for formulating diagnostic hypotheses based on conjecturally specific clues that are, actually, not reproducible, difficult to demonstrate, confusing in case of pre-existing comorbidities and have never received unanimous consensus or solid support24,25. Moreover, one must ask how a method like US, which only visualizes a small part of the pulmonary parenchyma could ever enable a reliable assessment of diseases extent and severity16,26. With these consideration in mind, if the role of CT in COVID-19 is still debated, that of LUS is not unexpectedly even more uncertain.
Otherwise, LUS is an excellent imaging method for the study of pleural effusions, being able to detect also minimal amount of liquid. In this respect, LUS is greatly superior to other standard thoracic imaging techniques (i.e. both chest X-Ray and CT), as showed also in our report. Although pleural effusions are not a typical feature of COVID-19, ultrasound may therefore be very useful to guide pleural punctures for safer fluid drainage and for the assessment of the changes in the amount of pleural fluid over time. It would be interesting to assess, by further studies on large case series, if LUS could prove useful in the follow-up during therapy of consolidations ascertained by CT and visible by ultrasound (i.e. consolidation strictly adherent to the superficial pleura).
In conclusion, to date, with the exception for US-guided procedures and interventions, the use of LUS should not be indicated for diagnostic screening and monitoring of COVID-19 patients. As bedside US implies a prolonged exposure of operators to patients and vice versa (longer and closer than that of a CT examinations), any US examination in patients with COVID-19 should be limited to essential imaging procedures for the ongoing clinical management of the patient (not just lung US, but rather thyroid, carotid artery, liver, renal or any other examinations), with operators protected by all the necessary personal protective equipment (PPE) in order to avoid infection transmission. Other LUS uses in patients with COVID-19 should be justified only within the context of a controlled research study.