Advanced Ultrasound in Diagnosis and Therapy, 2020, 4(2): 67-72. doi: 10.37015/AUDT.2020.200025

Original Research

Application Value of Lung Ultrasound in Asymptomatic Patients with Confirmed COVID-19

Haidan Lin, MDa,b,1, Bingqi Zhang, MDb,1,1, Haiyan Kou, MDc, Yuanyuan Zhao, MDb, Keyan Li, MDb, Dudu Wu, MDb, Shiyue Zhao, MDb, Liuqiong Ren, MDb, Xingxi Lin, MDb, Zihao Zhang, MDd, Zhiye Chen, MDe, Xuexia Shan, MDb, Yuqing Huang, MDb, Shengzheng Wu, MD,b,*, Faqin Lv, MD,a,b,*

Department of Ultrasound, The First Medical Center of PLA General Hospital, Beijing, China

Department of Ultrasound, Hainan Hospital of PLA General Hospital, Sanya, China

Department of Ultrasound, The Third Medical Center of PLA General Hospital, Beijing, China

Department of Clinical Laboratory, Hainan Hospital of PLA General Hospital, Sanya, China

Department of Radiology, Hainan Hospital of PLA General Hospital, Sanya, China

*Corresponding authors: Department of Ultrasound, Hainan Hospital of PLA General Hospital, Sanya 572013, China e-mail:lvjin8912@163.com(FQ Lv) oremailwsz@126.com(SZ Wu)

First author contact: Co-first authors

Received: 2020-04-1   Accepted: 2020-04-9   Online: 2020-06-30

Abstract

Objective: To investigate the value of lung ultrasound (LUS) in asymptomatic patients with confirmed COVID-19.
Methods: A retrospective analysis was performed on nine patients in a designated isolation hospital in Sanya from February 22nd, 2020 to February 23rd, 2020. All patients were confirmed with COVID-19 pneumonia by PCR test, but none had the typical symptoms of COVID-19. All patients first underwent LUS examination and then chest computed tomography (CT) scanning. The application value of LUS in asymptomatic confirmed patients with COVID-19 was evaluated, compared with chest CT which was regarded as the golden standard.
Results: Among nine asymptomatic patients with COVID-19, there were two cases (22.22%) with abnormal ultrasonic manifestations, of which one (11.11%) showed a fusion B3-line in zone 5 of the right lung, and the other showed localized pulmonary consolidation in zone 6 of the left lung. The remaining seven cases (77.78%) showed no abnormal changes in LUS, but only clear pleura sliding sign and A-line. Chest CT showed abnormal changes in three cases (33.33%). Two of them (22.22%) showed flocculent high-density shadow at the base of both lungs (especially in the right lung), while the other case showed ground-glass opacity with thickened interlobular septal in the left lower lobe, involving the pleura. There were no abnormalities on chest CT of the remaining six cases (66.67%). The two (22.22%) LUS-positive patients were in complete coincidence with CT-positive patients. This study showed that the coincidence rate of the two examination methods was 88.89%. Taking chest CT as golden standard, the sensitivity, specificity, positive predictive value, negative predictive value, and Kappa value of lung ultrasound in the diagnosis of COVID-19 were 66.67%, 100%, 100%, 85.71%, and 0.727, respectively.
Conclusion: LUS can evaluate lung lesions in asymptomatic patients with COVID-19. Compared with chest CT, the diagnostic coincidence rate and diagnostic consistency of LUS are relatively higher. For this asymptomatic type of patient, ultrasound can be used as a diagnosis method, which can avoid the risk of radiation exposure in a short period of time. As a rapid and dynamic assessment method, LUS can cooperate with remote consultation to provide timely and accurate guidance for clinical diagnosis and treatment when necessary.

Keywords: Asymptomatic patients; COVID-19; Pneumonia; Lung ultrasound; CT

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Cite this article

Haidan Lin, MD, Bingqi Zhang, MD, Haiyan Kou, MD, Yuanyuan Zhao, MD, Keyan Li, MD, Dudu Wu, MD, Shiyue Zhao, MD, Liuqiong Ren, MD, Xingxi Lin, MD, Zihao Zhang, MD, Zhiye Chen, MD, Xuexia Shan, MD, Yuqing Huang, MD, Shengzheng Wu, MD, Faqin Lv, MD. Application Value of Lung Ultrasound in Asymptomatic Patients with Confirmed COVID-19. Advanced Ultrasound in Diagnosis and Therapy[J], 2020, 4(2): 67-72 doi:10.37015/AUDT.2020.200025

Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by a novel coronavirus, which was initially named the 2019 novel coronavirus (2019-nCoV) and finally named SARS-Cov-2 (severe acute respiratory syndrome coronavirus 2). As the disease progresses, about 50% of patients can experience dyspnea. The severe cases can develop rapidly to ARDS (acute respiratory distress syndrome), and the mortality rate is high [1]. Early diagnosis, treatment, and isolation are very helpful to improve patient's prognosis and control COVID-19 overspread.

Patients with COVID-19 are predominantly presenting with pneumonia-based lung changes, including patchy opacity, ground-glass opacity, infiltrates, pulmonary consolidation, etc. [2,3]. In the past, pulmonary inflammation has traditionally relied on diagnosis using chest X-ray (CXR) and chest CT scan, but there are many restrictive factors in CXR and CT. Due to the advantages of real-time dynamic monitoring, non-ionizing radiation, and strong repeatability, the clinical value of lung ultrasound (LUS) has been increasingly recognized and valued by more and more doctors. Volpicelli et al. [4] published an expert consensus on ultrasound diagnosis of lung diseases based on international medical evidence at the International Liaison Committee on Lung Ultrasound (ILC-LUS), and believed that ultrasound could be used to detect lung diseases. A study comparing the diagnostic accuracy of various examination methods for pneumonia points out that LUS is more sensitive than CXR, and is a reliable method for diagnosing pneumonia [5]. This study retrospectively compared LUS findings with CT manifestations of nine asymptomatic COVID-19 confirmed patients, and then investigated the features and the application of LUS in asymptomatic patients with confirmed COVID-19.

Materials and Methods

Clinical data

In the period of February 22nd through February 23rd, 2020, nine asymptomatic patients with confirmed infection of 2019-nCoV who were treated in a designated isolation hospital in Sanya were enrolled in this study. All patients were confirmed with COVID-19 pneumonia by PCR test, according to the diagnostic criteria of the "Novel Coronavirus Pneumonia Diagnosis and Treatment Plan (Trial Version 7)" issued by the National Health Commission of China. Inclusion criteria were: no fever and/or respiratory symptoms; a history of close contact with a confirmed or suspected case; positive viral nucleic acid testing or viral gene sequencing; imaging with or without pneumonia-like changes. Exclusion criteria were: upper respiratory tract infections caused by other viruses; non-infectious diseases such as vasculitis, dermatomyositis, and organizing pneumonia, etc.

Ultrasonic examination

Scanning was performed using a Clover 70 portable ultrasonic diagnostic instrument (manufactured by Wisonic, Shenzhen China), possessing a function of remote consultation. A convex array probe with the frequency of 1~5 MHz was applied.

(1) The unilateral lung is divided by the front axillary line and the posterior axillary line into three regions, the front lung, the lateral lung, and the rear lung. It is divided into upper and lower parts; that is, a total of six areas: front up, front down, side up, side down, back up, and back down (Fig. 1) [6]. Lung ultrasound was applied using a lung 12-zone method, performing a continuous longitudinal and transverse scan of each lung region.

Figure 1

Figure 1   Partitioning method for one-sided six-zone scheme. (A and B) Supine or lateral position (right side), divided by anterior axillary line and posterior axillary line, are divided into three regions of anterior lung, lateral lung, and posterior lung, each of which is further divided into upper and lower parts.


(2) When there were difficulties in diagnosis, ultrasound images are transmitted at bedside through a 5G network-based telemedicine consultation system to determine the final diagnostic results. The remote consultation was completed by a senior ultrasound expert.

(3) To avoid infection, sonographers wore personal protection equipment (PPE) before access to the isolation ward, wrapped the ultrasound probe with a plastic film before the examination, removed it afterwards, and wiped the probe with 75% ethanol for disinfection.

Other inspections

(1) CT examination: Completed at the Local Disease Control Center before admission.

(2) Viral nucleic acid detection (PCR test): Using throat swab SARS-Cov-2 nucleic acid detection. The first detection was carried out in a hospital in Sanya. After being transferred to the isolation ward, nine patients were further detected as positive for COVID-19 via the viral nucleic throat swab specimens.

(3) Laboratory inspection: Completed in a hospital in Sanya. The periphery venous blood specimens of nine patients were simultaneously taken for a blood routine test and a blood biochemical test.

Statistical analysis

All data were processed by the SPSS 25.0 statistic package. Categorical variables are presented as a number and percentage, with group comparison using Fisher tests. Continuous variables are presented as mean ± standard deviation, with group comparison using t-tests. The sensitivity, specificity, positive predictive value, negative predictive value, kappa value, and significance were calculated when examining the diagnostic coincidence rate and diagnostic consistency of LUS and chest CT. A P < 0.05 was considered to indicate a significant difference.

Results

Clinical manifestations

In this group, there were five males (55.56%) and four females (44.44%), aged 9-57 years, with an average age of (34.00 ± 17.85) years. Five (55.56%) of them were from Wuhan, Hubei Province in China, one (11.11%) from other parts of Hubei Province in China, and three (33.33%) from provinces outside Hubei in China. All patients had no past medical history of tuberculosis and/or pneumonia; one (11.11%) had fatty liver, and one (11.11%) had hepatitis B.

Lung ultrasound and chest CT

Lung ultrasound

Of these nine cases, two (22.22%) had abnormal findings in their lungs on ultrasound. One (11.11%) of these two showed localized pulmonary consolidation under the pleura in zone 6 of the left lung (L6), just like "fragment" (Fig. 2A). In this case, the sonographers applied for remote consultation during the ultrasound examination, and obtained the final diagnosis through consultation. Another case showed a fusion B-3 line in zone 5 of the right lung (R5) (Fig. 2B). The remaining seven cases (77.78%) showed no obvious abnormality, but only clear pleura sliding sign and A-line.

Figure 2

Figure 2   Ultrasonic manifestations of lungs in asymptomatic confirmed patients with COVID-19. (A) Ultrasound showed that pulmonary consolidation was in zone 6 of the left lung (arrows); (B) Ultrasound showed that the B3-line was distributed in zone 5 of the right lung, which originated from the pleura line, and the pleura was uneven and thickened (arrow).


Chest CT

CT of the lung showed abnormal changes in three cases (33.33%), all of them were male. One (11.11%) showed ground-glass opacity with thickened interlobular septal in the left lower lobe, involving the pleura (Fig. 3A), the other two (22.22%) showed flocculent high-density shadow at the base of both lungs, especially in the right lung (Fig. 3B). The remaining six cases (66.67%) showed no abnormal manifestations on CT.

Figure 3

Figure 3   CT image features of lungs in asymptomatic confirmed patients with COVID-19. (A) CT showed ground-glass opacity with thickened interlobular septal in the left lower lobe, involving the pleura, and sign of air bronchus (arrow); (B) CT showed flocculent high-density shadow at the base of both lungs, especially in the right lung (arrow).


Coincidence rate and value analysis of two kinds of imaging examinations

The LUS findings in two patients were completely coincident with those of CT. Localized pulmonary consolidation was detected in zone 6 of the one patient’s left lung (L6) by LUS (Fig. 2A), which was exactly consistent with the findings of the CT scan (Fig. 3A). Another showed a fusion B-3 line in zone 5 of the right lung (R5) on LUS (Fig. 2B), and CT showed flocculent high-density shadow on the right lung base (Fig. 3B). The positive rates of the two examination methods were 22.22% and 33.33%, respectively, and there was no significant difference (P > 0.05) (Table 1). The diagnostic coincidence rate of LUS and chest CT was 88.89% (Table 2). Taking chest CT as gold standard, the sensitivity, specificity, positive predictive value, negative predictive value, and Kappa value of LUS in the diagnosis of asymptomatic patients with COVID-19 were 66.67%, 100%, 100%, 85.71%, and 0.727, respectively. The consistency between the two methods is better (Table 2).

Table 1   Comparison of the positive diagnosis rate on LUS and chest CT of COVID-19

Examination methodnPositiveNegativePositive rate
LUS9270.22
Chest CT9360.33
χ2 value0.90
P value>0.05

Data are presented as number. LUS, lung ultrasound; CT, computed tomography

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Table 2   Results of LUS and chest CT in the diagnosis of COVID-19

Diagnosis methodClassificationChest CTTotal
PositiveNegative
LUSPositive202
Negative167
Total369

Data are presented as number. LUS, lung ultrasound; CT, computed tomography

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Laboratory findings

Throat swab SARS-Cov-2 nucleic acid detection (PCR test)

All nine patients (100%) were positive for COVID-19 in the first nucleic acid test. There were four additional tests per patient after being transferred to the isolation ward. SARS-Cov-2 nucleic acid testing in three patients (33.33%) turned out negative upon the second and third tests.

Blood routine and blood biochemical

The blood routine tests in all patients were completely normal. However, two patients (22.22%) had abnormal results in the blood biochemical test: one (11.11%) patient with fatty liver had a normal liver enzyme index previously, while ALT and AST increased this time; another one (11.11%) with already diagnosed hepatitis B showed abnormal hepatitis B-related indicators.

Discussion

Since the outbreak of pneumonia caused by SARS-Cov-2 in Wuhan, Hubei province in China, COVID-19 has developed rapidly, and has caused large-scale infections in China and many overseas countries, which seriously threatened public health security and people’s physical and mental health [7,8]. It is a highly contagious public health emergency. Currently, with the epidemic in China under control, the infection rate of COVID-19 in other Asian countries, Europe, and North America is still rising, and some countries and regions are in a trend of outbreak. The diagnosis of COVID-19 is based on a combination of epidemiological history of exposure, clinical manifestations, and viral nucleic acid detection or viral gene sequencing. SARS-Cov-2-infected individuals and confirmed patients with COVID-19 without any clinical symptoms are still infectious. For those with no epidemiological history and/or atypical or asymptomatic clinical manifestations, imaging examination is a method of follow-up evaluation [2].

At present, radiological examination (CXR and chest CT) is a common inspection method for COVID-19 pneumonia; however, CXR has limited sensitivity and specificity [9]. Although chest CT remains a more sensitive diagnostic modality, it has inherent defects such as ionizing radiation, long waiting time, poor repeatability, limitation of posture, high cost, difficulty in disinfection, etc. Furthermore, neither CT nor CXR can achieve real-time repeated detection and/or dynamic monitoring. In the process of diagnosis and treatment of critical patients, there is also a threat that the transport/transmission risk increases due to the inconvenient handling [10]. Ultrasound, as a portable, real-time, non-invasive tool, can compensate for the above-mentioned shortcomings of CT and CXR [11,12]. Miguel et al. [13] conducted a meta-analysis involving 1,172 patients, comparing the accuracy of ultrasound and chest CT in the diagnosis of pneumonia in adults, found that the sensitivity and specificity of LUS in the diagnosis of pneumonia were 94% and 96%, respectively. Stadler et al. [14] analyzed the literature of ultrasound for diagnosing childhood pneumonia, and found that LUS in the diagnosis of pneumonia in children is also highly sensitive and specific. A meta-analysis by Alzahrani et al. [15] in 2,513 patients showed that the sensitivity and specificity of ultrasound for diagnosing pneumonia in all age groups were 85% and 93%, respectively. These studies suggest that LUS has no significant difference in the diagnosis of pneumonia between adults and children, and compared with CXR and chest CT, LUS is more accurate and practical [4,15]. Besides the diagnosis of lung lesions in COVID-19, LUS can also diagnose and differentially diagnose the dyspnea caused by COVID-19 through BLUE and FALLS schemes [16-18]. Because LUS is non-radiative and repeatable, it can also be used to keep track of the patient's progress [19,20]. Coupled with the development and application of remote robotic ultrasound, such problems as lack of sonographers and backward equipment in the SARS-Cov-2 quarantine zone can be greatly alleviated. The off-site ultrasonic technology and remote consultation can be delivered to quarantine zone through 5G network, which avoids direct contact between medical staff and patients and reduces the chance of infection spread or transmission.

The results of this study indicated that the sensitivity, specificity, positive predictive value, negative predictive value, and Kappa value of LUS in the diagnosis of asymptomatic patients with COVID-19 pneumonia, taking chest CT as the gold standard, were 66.67%, 100%, 100%, 85.71%, and 0.727, respectively. They are different from the results reported by Yan et al. [21], which may be due to the limited amounts of samples in the study. However, there was no significant difference in the positive diagnostic rate of LUS and chest CT in asymptomatic confirmed patients with COVID-19 pneumonia (P > 0.05), which is similar to that reported by Chen et al. [22], a group of Chinese academics. In addition, it was found that the location of the lesions in each patient with LUS-positive was exactly consistent with that on CT after comparison. The inflammation lesions of two patients were fortunately distributed near the pleura, so ultrasound can determine the location and size [14,23]. As for blood-test results, one of nine patients (11.11%) showed elevated ALT and AST (164U/L, 94U/L, normal value <40U/L). Since this patient suffers from fatty liver, whether SARS-Cov-2 is mainly responsible for the increase in ALT and AST remains unclear, which still needs to be further confirmed based on a larger-scaled sample and study [2,24,25].

The main advantages of ultrasound for asymptomatic patients with confirmed COVID-19 are: (1) Although some patients are asymptomatic, they have minor changes in LUS. Dynamic observation of the lesions is conducive to taking further measures clinically, whenever necessary. (2) Avoiding repeated radiation exposure is more suitable for asymptomatic infection patients especially for pregnant women and children. (3) The ultrasonic instrument is fully and easily accessible to patients who are bedridden, in quarantine, where CXR/CT machines are not currently available. Therefore, LUS is beneficial to the differential diagnosis of complications and underlying diseases in asymptomatic patients with COVID-19.

In conclusion, LUS certainly has auxiliary value in the diagnosis and treatment of patients with COVID-19. Especially for asymptomatic patients, the dynamic monitoring can serve as an early screening method to assess outcome, predict patients' prognosis, and release from quarantine. Ultrasound can work in a variety of environments, and, where necessary, it can cooperate with the ability for remote consultation to provide timely and accurate guidance for clinical diagnosis and treatment.

Acknowledgments

Funding was provided by Military Medical Research Program of PLA General Hospital of China (No. CX19025 and No. QNC19050), Major Science and Technology Project of Hainan Province of China (No. ZDKJ2019012), National MOST “13.5” Key Projects of China (No. 2016YFC0105006), Talents Development Project of Sanya City of China (PI: Faqin Lv), and Medical and Health Science and Technology Innovation Project of Sanya City (No. 2018YW01).

Conflict of Interest

The authors have no conflict of interest to declare.

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