LUS has played a critical role in the pandemic caused by SARS-CoV-2, with growing evidence of its usefulness both to screen for lung involvement and to evaluate disease severity. Sequential LUS has also been used as an efficient tool to monitor the progression of lung lesions in individuals with more severe lung disease. Despite all these indications, the prognostic power of LUS in COVID-19 is also important to evaluate. Here, we searched for correlations between pathological LUS signs and patient outcomes. The main results of the present study were that 1 month after LUS screening, LUS signs (especially subpleural consolidations) were associated with the presence of persistent respiratory symptoms and general fatigue. The LUS findings strongly predicted the need for hospitalization (including in the ICU) and death. In addition, the LUS aeration score was correlated with the persistence of respiratory manifestations at 1 month after ultrasound examination. Finally, we also observed a strong relationship between aeration scores and poor outcomes, such as the need for hospitalization (including in the ICU) and death. To our knowledge, this study is the first to evaluate the relationship between pathological LUS signs and 1-month clinical outcomes.
The mid- and long-term complications of COVID-19, including those related to the respiratory system, should be identified, and affected patients require follow-ups by appropriate services. In the present study, we observed that respiratory manifestations (such as dyspnoea and cough) and systemic manifestations (such as fever and general fatigue) were associated with LUS signs diagnosed 1 month before the prospective evaluation. Since ultrasound equipment is increasingly available and LUS can be performed at the bedside within a few minutes and in patients with mild disease or even in unstable patients [23], we believe that these interrelationships may be of great clinical interest in the context of the COVID-19 pandemic. Although LUS signs may not be specific for COVID-19 compared to some other lung diseases, the identification of certain patterns in the epidemiological context of the pandemic can certainly help clinicians to identify individuals likely to exhibit worsening clinical conditions and to develop sequelae after resolution of the acute phase of the disease [24, 25].
The clinical significance of B-lines depends mainly on their quantity (the number of B-lines per area examined and the presence or absence of confluent B-lines) and is usually associated with interstitial syndromes [2]. As the disease progresses, the air content decreases and lung density and the number of B-lines increase, leading to confluent areas equivalent to ground-glass opacities (GGOs) on CT [2, 24]. In the present study, we observed that coalescent B-lines were associated with older age, obesity, and diabetes, which are considered risk factors for COVID-19 exacerbation [4, 26, 27]. However, the strongest associations with persistent respiratory symptoms 1 month after LUS were observed for previously diagnosed subpleural consolidations. In fact, as the pneumonic process progresses in COVID-19, lung density increases even more because of alveolar infiltration with inflammatory cells, causing loss of aeration and consolidation areas [2, 24]. Thus, the finding of subpleural consolidations on LUS may not only predict worsening of symptoms in the course of the disease [23] but may also indicate a more severe course in terms of pulmonary sequelae in SARS-CoV-2 infection.
The use of a scoring system to assess pathological LUS signs in patients infected with SARS-CoV-2 has been increasingly widespread during the pandemic [11, 28]. In our study, we observed that the LUS aeration score was strongly related to dyspnoea and cough 1 month after ultrasound screening. Interestingly, Lichter et al. [29] evaluated 120 consecutive patients with COVID-19 who underwent LUS within 24 h after admission. These authors observed that clinical deterioration was associated with increased follow-up LUS scores, mainly due to loss of aeration in anterior lung segments. Using an LUS scoring system and the need for supplemental oxygen at the time of examination, Manivel et al. [30] proposed a protocol to assist clinicians with decision-making in patients with COVID-19 and to facilitate provision planning within emergency departments. Because our study examined 1-month outcomes, we think that our results provide additional evidence that the LUS score can be used as a prediction tool for clinical outcomes of the disease after the acute phase and can be used as an additional tool for clinical reasoning.
In COVID-19, lung lesions play a key role in determining the clinical course and prognosis [31]. In this sense, one of the objectives of the current study was to evaluate the correlations of LUS findings with poor outcomes. We observed that the pathological LUS signs (particularly subpleural consolidations) and a higher aeration score were associated with the need for hospitalization, the need for ICU admission, and death. In line with our findings, some researchers have observed that early LUS signs (including the LUS score) are effective for assessing the need for prolonged hospitalization [15, 32]. Other studies have shown the potential of LUS to stratify early risk in COVID-19 patients who visit emergency departments according to mortality risk and the need for IMV, with this risk being higher in individuals with more pathological lung areas [29, 33, 34]. Given the scarcity of equipment and trained health professionals, the use of a relatively simple diagnostic procedure that does not use ionizing radiation, such as LUS, may have clinical and public health implications [34]. In contrast to studies evaluating short-term consequences, our study assessed 1-month outcomes, which may have important implications from the perspective of utilizing scarce resources in disadvantaged socioeconomic areas.
When using LUS, the criteria for positivity must be defined considering the possibility of alternative diagnoses and levels of probability [20, 21]. Because LUS signs are nonspecific, LUS cannot be used alone to establish a definitive diagnosis of COVID-19 infection [35]. In fact, almost 10% of our cases had LUS patterns more consistent with other diagnoses (including cardiogenic pulmonary oedema and bacterial pneumonia), although the diagnosis of COVID-19 was confirmed in all participants by RT-PCR. Importantly, our study showed that patients with high-probability LUS patterns had higher aeration scores and more dyspnoea 1 month after LUS screening and more often required hospitalization and ICU admission. Although more studies are needed, the use of categories of the probability of COVID-19 pneumonia can be an interesting strategy to predict the evolution of the disease in the short and medium term.
Several limitations in our study should be noted. First, our study was conducted at a single reference centre during the screening of COVID-19 pneumonia; therefore, generalization of our results to other periods of the pandemic should be executed with caution. However, with the emergence of the second wave of the pandemic in many regions of the world, the role of LUS may become even more prominent in the process of implementing local and global measures efficiently. Second, ultrasound evaluates only approximately 1/16 of the total lung and detects only changes closely related to the pleural surface [36]; therefore, other chest imaging methods may have a greater prognostic role than LUS. Third, we performed only a single evaluation by LUS; serial LUS examinations can be useful for tracking the clinical trajectory of an apparently unpredictable disease course, thus improving the prediction of clinical outcomes.