key: cord-0890130-sqnqcd2k
authors: Zhao, Lina; Yu, Kanglong; Zhao, Qi; Tian, Rui; Xie, Hui; Xie, Lijun; Deng, Puyu; Xie, Guogang; Bao, Aihua; Yu, Kanglong; Du, Jiang
title: Lung Ultrasound Score in Evaluating The Severity Of Coronavirus Disease 2019 (COVID-19) Pneumonia
date: 2020-07-24
journal: Ultrasound Med Biol
DOI: 10.1016/j.ultrasmedbio.2020.07.024
sha: e770d1a56fd61852b17c235fa40a7cb3b829b036
doc_id: 890130
cord_uid: sqnqcd2k

The purpose of this study is to observe the potential of lung ultrasound in evaluating the severity of COVID-19 pneumonia. Lung ultrasound of patients was performed in ten zones of the chest walls. The features of the ultrasound images were observed, and a lung ultrasound score (LUS) was recorded. The ultrasound features and scores were compared between the refractory group (PaO2/FiO2≤100 mmHG or on ECMO) and the nonrefractory group. The prediction value of the LUS was studied by receiver operating characteristic (ROC) curve analysis. In total, 7 patients were enrolled in the refractory group and 28 in the nonrefractory group. B-line patterns and shred signs were the most common signs in all patients. Patients in the refractory group had significantly more ground-glass signs (median 6 [interquartile range (IQR), 2.5-6.5] vs median 0 [IQR, 0-3]), consolidation signs (median 1 [IQR, 1-1.5] vs median 0 [IQR, 0-3]) and pleural effusions (median 5 [IQR, 1.5-6] vs median 0 [IQR, 0-0.25]). The LUS was significantly higher in the refractory group (33.00 [IQR 27.50, 34.00] vs 25.50 [IQR 22.75, 30.00]). The ROC of the LUS showed a cutoff score of 32 with a specificity of 0.893 and a sensitivity of 0.571 in diagnosing refractory respiratory failure among patients. In COVID-19 patients, lung ultrasound is a promising diagnostic tool in diagnosing patients with refractory pneumonia.

A cluster outbreak of pneumonia now known as the novel coronavirus infectious disease occurred in Wuhan City, Hubei Province of China, beginning in December 2019 (Lu, et al. 2020) . The WHO has named the pneumonia caused by this coronavirus Coronavirus Disease 2019 and declared COVID-19 as a global health emergency. (Commission 2019 , Lu, et al. 2020 . As of June 2nd, 2020, there are more than 6,430,000 patients confirmed to have COVID-19 and 385,000 deaths worldwide. Nearly 14% of the patients need ICU management because of severe acute respiratory distress syndrome (ARDS) (Wu and Mcgoogan 2020) .

CT (computerized tomography) scan is the key imaging modality for these patients (Chung, et al. 2020 , Pan, et al. 2020 . However, the disadvantages of a CT scan include the need to transport the patient to the CT room, radiation exposure and, most importantly, the risk of virus dissemination. As a result, lung ultrasound seems to be a safer and more convenient alternative to CT scans in a transportation-limited setting such as when mechanical ventilation or even extracorporeal membrane oxygenation (ECMO) are needed. In an urgent situation when a patient's situation deteriorates, a rapid imaging tool is urgently needed. Lung ultrasound has evolved in recent decades, especially in critical care and emergency management. Studies of lung ultrasound have proven the value of this imaging modality in identifying pulmonary diseases including pulmonary edema and pneumonia, especially in the emergency and intensive care settings (Lichtenstein and Meziere 2008, Lichtenstein 2009 ). We have introduced bedside ultrasound for the imaging assessment of patients with severe COVID-19 to evaluate the severity of pneumonia. (1) severe type: respiratory distress with a respiratory rate ≥ 30 times/min and an oxygen saturation≤93% and a PaO2/FiO2 ≤ 300 mmHG in a resting state; (2) critical type: respiratory failure requiring mechanical ventilation, shock and other organ failure requiring ICU monitoring and treatment; (3) refractory type: refractory respiratory failure with a PaO2/FiO2≤100 mmHG or patients who were treated with ECMO. We included patients with refractory-type disease in the refractory group and those with severe-type and critical-type disease in the nonrefractory group. The lung ultrasound features and scores were studied and compared between the two groups.

Lung ultrasound assessment: All ultrasound evaluations were performed at the bedside by three physicians with over 5 years of critical care experience. Operators were dressed in protective clothing, gloves and goggles to enter the isolation ward. All precautions for respiratory, droplet and contact isolation were provided in this ward. The ultrasound probe was placed in a sterile plastic sleeve or sterile glove. The operator used a convex probe to perform an ultrasound of the lungs. Pulmonary ultrasound was screened first longitudinally and then transversely according to BLUE protocol (Lichtenstein 2009 ). The longitudinal examination began by finding the sonogram of the ribs and the pleural line between the two ribs to identify the lung tissue. A transverse examination was then performed to further clarify the images of the lungs. Image data were frozen and saved after obtaining the desired image, and the patient's name and examination location were marked. At the end of the procedure, we sterilize the probe in a dedicated area and placed the sterile plastic bag or sterile gloves in a medical recycling bag. All images were reviewed and scored by two physicians with over 5 years of critical care ultrasound experience with the operator. An M7 Expert ultrasound system with a 5-MHz curved (C60x) transducer was used for lung ultrasound assessment (Mindray Investment Co, Ltd, China). We examined each side of the chest wall in 5 examination zones: the anterosuperior and anteroinferior zones were the second and fifth intercostal space in the midclavicular line; the laterosuperior and lateroinferior zones were the same cross-sections at the midaxillary line; and the posterior zone was the subscapularis area on the back. In total, 10 zones were examined on every patient's chest wall. Patients were investigated in a semirecumbent or supine position. We focused on the following patterns, and a numeric value was assigned according to the most severe finding: (1) 0 points, normal pattern with a smooth and sliding pleural line with parallel A-lines; (2) 1 point, B-line patterns:

B-lines were defined as discrete laser-like vertical hyperechoic artifacts arising from the pleural line and extending to the bottom of the image without fading (Lichtenstein, et al. 1997 ); (3) 2 points, ground-glass sign with B-lines occupying the entire screen; (3) 3 points, shred sign that was fragmented similar to small consolidation under the pleural line; (4) 4 points, liver tissue-like consolidation sign; and (4) 4 points, pleural effusion. For one patient, the sum of the 10 zone numbers was recorded as the LUS score, which ranged from 0 to 40. The affected zones of each pattern were also recorded. This scoring system referenced some previously published scoring systems (Bouhemad, et al. 2011 , Soldati, et al. 2020 , Volpicelli, et al. 2020 ).

We compared the demographical and LUS data between the nonrefractory group and the refractory group. Statistical analysis was performed with Rstudio 1.2.1335 (RStudio, Inc., Boston, MA, USA). Normally distributed data are expressed as the mean (SD) and were analyzed by Student's t-test. Nonnormally distributed data are expressed as the median (interquartile range [IQR] ) and were analyzed by the Wilcoxon test. Proportions are expressed as numbers (percentages) and were compared by the chi-square test or Fisher's exact test. Linear regression was used to evaluate the relationship between LUS and PaO2/FiO2. Receiver operating characteristic (ROC) curves were plotted to illustrate the accuracy in recognizing patients with refractory pneumonia.

A total of 35 patients were enrolled in this study. In total, 28 patients were in the nonrefractory group, and 7 were in the refractory group. As shown in Table 1 , the mean age was not significantly different between the groups. In the nonrefractory group, there were 8 patients on mechanical ventilation, and 20 on HFNC. In the refractory group, all 7 patients were on ECMO in the end. In total, there were 15 patients who were mechanically ventilated. There were 7 patients from Wuhan and 5 patients who had traveled to Wuhan within 14 days (Table 1) .

Ultrasound morphology features and their distributions are shown in Table 2 . The B-line pattern ( Fig 1B) and shred sign ( Fig 1D) were the most typical ultrasound features that were frequently found in both groups. The median number of zones that showed a shred sign was 6 [IQR 6-7] in the refractory group and 8 [IQR 7-9] in the nonrefractory group. Patients in the refractory group showed less B-line patterns than those in the nonrefractory group (4 [IQR 2-7] vs 6 [IQR 6-7], p = 0.046). The ground-glass pattern ( Fig 1C) occurred significantly more frequently in the refractory group than in the nonrefractory group (6 [IQR 2.5-6.5] vs 0 [IQR 0-3]). Although the consolidation pattern ( Fig 1E) was not that frequently found in both groups, it seemed that the refractory group had significantly more consolidation patterns. For the effusion pattern (Fig 1F) , there were significantly more patients with this pattern in the refractory group than in the nonrefractory group (5 [IQR 1.5-6] vs 0 [IQR 0-0.25]).

The refractory group showed a higher LUS score than the nonrefractory group ( Fig 2 A) . In different scanning zones, the refractory group always have a higher LUS score (Fig 2 B) . The scores in the nonrefractory group were equal between zones. In the refractory group, the scores were higher in the gravity-dependent zones. However, Wilcoxon analysis found no significant difference between zones in patients with refractory disease. When LUS was utilized in distinguishing patients with refractory disease, the cutoff point was 32 points (Fig 3A) . At this point, predicting a refractory situation had a specificity of 0.893 and a sensitivity of 0.571. The ROC curve of the PaO2/FiO2 is also shown in Fig 3, and the cutoff point is 114 , with a specificity of 0.74 and a sensitivity of 100%. The AUC of the PaO2/FiO2 ROC was 0.894. However, LUS did not differentiate well between the two severe and critical groups of patients, with an AUC of only 0.52 (Fig 3B) .

COVID-19 has already involved nearly 6,430,000 people all over the world. Although CT is the most important imaging modality for viral pneumonia, the high risk of transporting ventilated patients or patients on ECMO with hemodynamic failure makes CT have limited availability. Furthermore, the risk of the contagiousness of the coronavirus should be evaluated before transportation. In addition, in the ICU, protective clothing makes stethoscopes have limited utility. `Lung ultrasound has significantly evolved in the critical care and emergency department due to its theoretical and practical aspects. We introduced ultrasound for the examination of COVID-19 lesions because in critical care, ultrasound is an optimal tool for patients on mechanical ventilation or ECMO. Both convex and linear probes can be used for ultrasound of the lungs (Radzina and Biederer 2019 , Soldati, et al. 2019 . However, because the convex probe may be more suitable for obese patients, it can also be used for abdominal and even cardiac examinations; thus, a convex probe was used in this study instead of a linear probe. Both Bounsenso and Soldati have suggested that wireless probes and tablets represent the most appropriate ultrasound equipment , Soldati, et al. 2020 ). These devices can easily be wrapped in single use plastic covers to reduce the risk of contamination and allow simple sterilization procedures. However, the unavailability of these devices limited our choice. Daily assessment of the lungs can provide an assessment of the severity of lung disease since patients with refractory disease have more decreased lung aeration that can be evaluated by the lung ultrasound score. The LUS could differentiate between the two groups when they were divided into refractory and nonrefractory groups (p = 0.047). We haven't divided the patients into three groups (the severe group, the critical group and the refractory group) because the lung ultrasound score (LUS) could not differentiate well between the severe group and the critical group (p = 0.18).

More ground-glass patterns and pleural effusions may indicate a more critical status.

Ground-glass sign indicates a high ratio of fluid to air. This pattern was more frequently found in the refractory group. Previous CT studies have found few effusions (Chung, et al. 2020 , Fang, et al. 2020 , Pan, et al. 2020 . However, in the current study, more pleural effusions may have been related to refractory respiratory failure. The reason may be that patients with refractory disease in this study had more severe disease or were in progressed stages, and mechanical ventilation may have further injured the lungs of these patients. When the density of the lung increases to that of solid tissue, consolidation appears. Although there were more consolidation patterns in the refractory group, consolidation patterns were not so frequently found in either groups. Previous CT studies have also found few consolidation patterns (Chung, et al. 2020 , Fang, et al. 2020 , Pan, et al. 2020 ).

The shred sign and B-line patterns were the most typical ultrasound features but were not specific to distinguish patients with refractory disease because we found many B-lines and shred signs in both groups. Previous literature regarding CT scan disclosed that COVID-19 lesions are always distributed at the peripheral part of the lungs (Pan, et al. 2020 ). This characteristic is beneficial for lung ultrasound to detect small fragments such as the shred sign in the shallow part of the lungs. The B-line pattern is considered to be highly reliable in diagnosing interstitial lesions and viral etiologies (Lichtenstein, et al. 1997 , Cortellaro, et al. 2012 ) such as H1N1 and H7N9 (Testa, et al. 2012 , Tsai, et al. 2014 ). However, this pattern is not related to a more critical status in COVID-19 patients. The reason may be that the number of B-lines was not described and analyzed in detail in this study.

The lung ultrasound score exhibits a high specificity of 89.4% in distinguishing refractory respiratory failure in COVID-19 patients. Although the AUC of the LUS is lower than that of the PaO2/FiO2, the LUS exerts a much higher specificity than the PaO2/FiO2. If we combined the high specificity of the LUS and the high sensitivity of the PaO2/FiO2, we may have a much more reliable diagnosis. While one patient had a PaO2/FiO2 lower than 114, we had a 100% sensitivity in distinguishing patients with refractory disease. A further LUS assessment of more than 32 points on the LUS can improve the specificity to nearly 90%.

Thus, we can have a more accurate model to differentiate refractory respiratory failure among patients who might need urgent life-saving maneuvers such as ECMO. ECMO was recommended by the WHO interim guidelines for eligible COVID-19 patients who had developed refractory ARDS (Ramanathan, et al. 2020) . Available evidence from similar patient populations suggests that carefully selected patients with severe ARDS who do not benefit from conventional treatment might be successfully supported with venovenous ECMO. In this study, the patients in the refractory group were all put on venovenous ECMO, and the lung ultrasound score exhibited a high specificity of 89.4% in distinguishing refractory respiratory failure in COVID-19 patients. A previous study disclosed that lung ultrasound is a valuable tool for bedside assessment of lung aeration in subjects supported by ECMO (Lu, et al. 2019) .

However, such a practice has not been reported in COVID-19 patients.

Based on ultrasound findings, we have utilized lung ultrasound in the following routine works: (1) daily assessment of the severity of lung lesions: B-lines gradually disappear and are replaced by A-lines, and consolidation that progressively disappears might indicate an improvement in the lungs, while more interstitial syndrome or more consolidation may indicate progression of the disease; (2) management of ECMO patients in put-on or weaning: an LUS more than 32 might indicate a refractory status in this patient; namely, more interstitial syndrome and more consolidations detected by the LUS are directly correlated with the severity of the lung injury, which may indicate the need for venovenous ECMO; (3) diagnosis of the reason for rapid deterioration among patients; and (4) reducing the need for CT scan.

Our study has limitations. First, this is a retrospective experience-based study with a small sample size; thus, the extrapolations of the conclusion may not be strong enough to be suitable for other critical COVID-19 patients. Second, the acoustic beam cannot reach the deeper part of the lungs, and ultrasound features are always indirect artifacts of the lesions.

Third, with ultrasound, some parts of the thorax cannot be screened, especially the back because patients with severe disease are always in the supine position. According to Soldati's recommendation (Soldati, et al. 2020) , all patients should have a lung ultrasound at 14 sites.

However, 15 patients in this study were mechanically ventilated, and a good ultrasound examination of the back could not be obtained. Therefore, we focused only on evaluating lung ultrasound in the lower back segment in all patients. There were 4 fewer sites examined than Soldati's recommendation; thus, the patient score may have been underestimated. Even though we used conservative fluid therapy for all of our patients, we were still not completely sure if the patient had fluid overload and congestive heart failure. These conditions might also influence the B-lines and the analysis of the lung ultrasound scores.

In summary, COVID-19 patients share common ultrasound patterns such as B-lines and shred signs. However, patients with refractory COVID-19 have more ground-glass signs, consolidation patterns and pleural effusion. The lung ultrasound score can be utilized to distinguish critical patients who might need ECMO with a high specificity of 90%.

Ultrasound can be used as a routine tool for daily assessment of the lung aeration of severely critical COVID-19 patients.

The authors declare that they have no potential financial or ethical conflicts of interest regarding the contents of this manuscript. ultrasound score in the refractory group was higher than that in the nonrefractory group. B In most scanning zones, the LUS was higher in the refractory group than in the non-ECMO group. In refractory group, grand glass pattern, consolidation pattern and pleural effusions were significantly more than in the non-refractory group.

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