Prognostic value of bedside lung ultrasound score in patients with COVID-19

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global threat, resulting in severe illnesses such as acute respiratory distress syndrome (ARDS), multi-organ dysfunction syndrome and even mortality [1]. Since there is no specific medicine to cure COVID-19, supportive care is the major treatment during hospitalization [2]. Close follow-up and medicine to relieve symptoms are sufficient for non-critically ill patients, while for severe and critically ill patients, aggressive treatment and admission to intensive care unit (ICU) are needed. However, many non-critically ill patients at admission may deteriorate suddenly during hospitalization [3]. Consequently, early prediction of disease progression may be fundamental in delivering appropriate health care for COVID-19 patients. Several demographic and clinical parameters have been recently shown to have some value for risk stratification in the development of the disease [4‐7]. However, COVID-19 is a kind of respiratory disease, and the lungs are the major organ affected [8]. Therefore, quantitative imaging data regarding lung lesions may be essential for in-hospital care to aid in identifying those who may benefit from more intensive monitoring and treatment.

Lung ultrasound (LUS) imaging is a fast, non-invasive, sensitive and quantitative tool to assess multiple pulmonary pathologies, such as pulmonary oedema, pneumonia and interstitial lung disease [9‐11]. More recently, LUS has also been used to detect lung involvement and monitor changes in patients with COVID-19, especially children and pregnant women [12, 13]. Indeed, ultrasound is the sole imaging modality with accessibility to the bedside of patients for timely identification of pulmonary and other organ complications, reducing the risk of contagiousness and the need to move unstable patients [14]. Recent studies have shown that LUS is an independent predictor of adverse outcomes in patients with pulmonary disease [15, 16]; however, the prognostic significance of LUS in patients with COVID-19 is unclear. Therefore, the purpose of this study was to investigate whether the LUS score at admission was independently predictive of poor outcomes in patients with COVID-19.

In this study, patients with the highest LUS score were more likely to have higher levels of cardiac injury, coagulopathy and inflammatory biomarkers, more mechanical ventilation therapy, higher incidence of respiratory failure, ARDS, sepsis and higher mortality. Patients with adverse events presented a higher rate of bilateral involvement, more involved zones, B-lines, pleural line abnormalities and consolidation, and a higher LUS score than event-free survivors. More importantly, the LUS score was able to predict a higher risk of adverse events in patients with COVID-19 independently. Therefore, the LUS score may be essential for risk stratification in COVID-19 patients.

Although chest CT has played a crucial role in characterizing pulmonary lesions during the COVID-19 pandemic, the increasing risk of infection and the need to move unstable patients make chest CT a limited choice. The histopathology of pulmonary lesions in COVID-19 patients begins in subpleural regions and is characterized by alveolar damage and oedema, interstitial thickening and consolidation [8]. Furthermore, lesions of this disease are mainly located peripherally and subpleurally [22, 23]. Therefore, ultrasound can identify pulmonary lesions in a timely and sensitive manner. Most patients in our cohort showed bilateral and posterior field involvement, which is consistent with chest CT features [22]. In our study, the predominant LUS abnormality of COVID-19 was B-lines (75%). Patients in our cohort also presented with irregular (35.4%) or blurred (11.1%) pleural line and lung consolidation (16.4%) on LUS. These imaging features characterized in our study are similar to prior studies targeting patients with COVID-19 [24‐27].

A previous study showed that the median time from illness onset to ARDS was 12 days (9.5–17.0), and the median time from illness onset to death was 18.5 days (15.0–22.0) [28]. A recent observation regarding the lung changes on chest CT demonstrated that the involvement of lung area and dense consolidation increased to the peak at 9–13 days after symptom onset [29]. In our study, due to the personnel and resource constraints in the early stage of pandemic, we performed LUS examination with some delay. The median time from admission to LUS examinations was 7 (3–10) days, and the median time from illness onset to LUS examinations was 10 days (IQR 5–15). Therefore, we acknowledged that some patients may be at the peak of the disease when performed LUS examinations. In addition, we described serial bedside LUS and corresponding CT findings in a severe (Additional file 1: Fig. 1) and a mild (Additional file 2: Fig. 2) COVID-19 patient to illustrate that performing LUS with some delay allowed the pulmonary lesions and LUS findings to be better developed. In recent studies, CT scans were performed in both the early-phase (within one week) and late-phase (one week later after symptom onset) COVID-19 patients. Their data showed that radiological findings can accurately predict poor outcome irrespective of the disease course [30, 31]. Accordingly, we reckon that the LUS score devised by our group may also have the predictive value in the late-phase patients.

There are several reports regarding lung score. In intensive care units, the most frequently used score distinguishes four steps of progressive loss of aeration, A-lines or two or fewer B-lines (normal aeration, score 0), three or more well-spaced B-lines (moderate loss of aeration, score 1), coalescent B-lines (severe loss of aeration, score 2) and a tissue-like pattern (complete loss of aeration, score 3) [21]. In heart failure patients, the number and spatial extent of B-lines on the antero-lateral chest is usually summed to generate a B-line score to estimate extravascular lung water (EVLW) semi-quantitatively (B-lines ≤ 5, score 0; 6–15, score 1; 16–30, score 2; > 30, score 3) [32]. These lung score, which were based on B-lines, can provide useful information regarding the presence and degree of pulmonary lesions. B-lines are non-specific artefacts associated with increased extravascular lung water or partial loss of lung aeration [20], and they can be detected in a variety of pulmonary diseases, including interstitial lung disease, heart failure, acute respiratory distress syndrome, etc. However, LUS manifestations in COVID-19 patients shared not only the features of an increase in B-lines but also consolidations, irregular or blurred pleural line. The comprehensive assessment of these abnormalities can accurately reflect lung involvement and then serve as a predictor of poor outcomes in patients with COVID-19. Therefore, we proposed the LUS score as an LUS quantitative indicator, which takes into account multiple LUS signs, such as the number of B-lines, consolidation or not, and pleural line changes.

There are limited data regarding the prognostic value of the LUS score in pulmonary disease. In a recent study of 40 elderly patients, Bouhemad et al. found that LUS alone may identify elderly patients at high risk of weaning or extubation failure [33]. Another observation was reported by Platz et al., who demonstrated that pulmonary congestion assessed by ultrasound is associated with other features of clinical congestion and identified those who have a worse prognosis [34]. Similarly, residual pulmonary congestion assessed by a B-line count ≥ 30 is a strong predictor of all-cause death or heart failure hospitalization [35]. These studies employed LUS, which was based on B-lines, for the prediction of pulmonary disease. In our study, we identified that patients with poor outcomes presented a higher rate of bilateral involvement, more involved zones and B-lines, pleural line abnormalities and consolidation, and a higher LUS score. These results revealed that the number of B-lines and the extent of lung consolidation and pleural line abnormality increased with illness severity, suggesting that the LUS score may aid in the classification of disease severity and triage of COVID-19 patients.

COVID-19 can lead to varying degrees of illness, and some patients with mild symptoms at admission may progress rapidly during hospitalization [3]. It is significant to recognize patients with COVID-19 at higher risk for adverse outcomes who might benefit from watchful monitoring. Prior research suggests that patients with COVID-19 who had an older age, lymphopenia, elevated CRP or comorbidity are at higher risk for adverse outcome and death [4‐7]. However, quantitative imaging data characterizing the pulmonary lesions would help us to identify patients who are at higher risk of poor outcomes. To the best of our knowledge, this is the first study to assess the prognostic implication of the LUS score in patients with COVID-19. Indeed, patients with a higher LUS score were more likely to experience more adverse clinical events, including mortality or ARDS. Patients with adverse outcomes presented more B-lines, a wider range of pleural line abnormalities and consolidation and a higher LUS score. The LUS score was able to predict a higher risk of adverse outcomes in COVID-19 patients, independent of and incrementally to other clinical parameters. A higher LUS score was not specific for COVID-19-associated lung injury but instead could identify the patients at higher risk for poor outcome.

Several limitations of our study should be highlighted. This was a single-centre study with a relatively limited sample size, which could limit the generalizability of our results. Therefore, further multi-centre studies with a larger sample size are needed to assess the prognostic value of the LUS score in patients with COVID-19. Moreover, LUS can only evaluate peripheral lesions due to echo attenuation, and the actual severity of lung involvement in this cohort may be underestimated. Furthermore, due to the personnel and resource constraints in the early stage of pandemic, we performed LUS examination with some delay, which may limit the prognostic value of LUS score in our study. Additionally, we excluded some patients due to a suboptimal ultrasound window, which might have introduced a bias. Finally, a comparison between the LUS score and chest CT was not performed because we had extremely limited CT image data.

The LUS score devised by our group performs well at predicting adverse outcomes in patients with COVID-19 and is important for risk stratification in COVID-19 patients.