Key words
coronavirus - SARS-CoV-2 - COVID-19 - chest ultrasound - X-ray
Background
At present, national health systems throughout the world are being overwhelmed by
the
amount of respiratory tract infections associated with the novel coronavirus 2019
(SARS-CoV-2) that can cause coronavirus disease 2019 (COVID-19). SARS-CoV-2 has
proved to be highly contagious, spreading globally within a very short time and
prompting the WHO to declare it a pandemic on March 11, 2020.
Referring to positive-stranded RNA viruses of the Coronaviridae family,
SARS-CoV-2 demonstrates a high sensitivity to the human airway epithelial cells,
resulting in a variety of respiratory symptoms including acute respiratory distress
syndrome occurring in up to 5% of cases due to its cytopathic effects [1]. Given the explosive spread of the virus as well as
the fact that an estimated 5% of patients with SARS-CoV-2 infections have
severe or critical symptoms that require hospitalization [2], clinicians are facing an enormous logistical and medical challenge,
including the appropriate choice of diagnostic imaging methods. Thoracic imaging has
turned out to be an essential part for the diagnostic workup and clinical management
of COVID-19 patients. In particular, computed tomography (CT) of the chest has been
shown to be a highly efficient tool and is the gold standard for the early detection
of COVID-19 pneumonia according to several studies [3]
[4]
[5].
However, routine chest CT upon admission to the emergency room may not be available
in most medical centers around the world and may expose patients with other upper
respiratory tract infections or a potential mild course of COVID-19 to unnecessary
radiation. Therefore, bedside diagnostic imaging is a desirable and rapid solution
that may have great potential to be implemented in algorithms for the early clinical
management of COVID-19 patients. Interestingly, conventional chest X-ray (CXR) may
often fail to capture early signs of COVID-19 pneumonia such as ground-glass opacity
[3]. In contrast, initial data from China and
Italy may indicate that point-of-care chest ultrasonography (ChUS) might be more
appropriate to diagnose patterns of interstitial syndrome and alveolar
consolidations, and may even reach similar diagnostic accuracy as CT scans [6].
Therefore, point-of-care ChUS might constitute a rapid, cost-effective and safe
imaging tool that may be positioned at the interface between CXR and chest CT. Here,
we aim to describe patterns of ChUS in COVID-19 patients and systematically compare
our findings with results from CXR.
Materials and Methods
Patients
24 patients with confirmed SARS-CoV-2 by RT-PCR were admitted to our university
hospital from March to April 2020. CXR was performed as a standard radiologic
investigation for the assessment of lung abnormalities. Furthermore, all
patients underwent routine bedside ChUS following admission. In addition,
clinical as well as laboratory data were recorded. Statistical tests were
performed using the Chi-squared test, and p-values <0.05 were considered
significant. The retrospective data analysis was approved by a decision of the
local ethics committee (№ 38/4/20).
Imaging techniques
Bedside ChUS was performed on Venue 50 and Logiq E9, GE Medical Systems, USA.
A standard ChUS protocol was used. In detail, patients were investigated by both
linear (8.4–13.0 MHz) and convex probes (4.0–5.0 MHz) in supine
and sitting position at six predetermined examination points (ventral, lateral
and dorsal chest wall in apical and basal position, respectively). The ChUS
assessment parameters included the amount (pathologic ≥3/field
of view) and distribution of B-lines (unilateral, bilateral, focal, multifocal,
confluent), pleural line abnormalities (unilateral, bilateral), consolidations
(unilateral, bilateral, focal, multifocal, confluent), abnormal lung sliding and
pleural effusions [6].
Depending on the clinical setting, CXR was performed either in the
posterior-anterior and lateral position or in the antero-posterior position with
findings described according to the glossary of the Fleischner Society [7]. CXR evaluation focused on the presence and
distribution of hazy increased opacities, consolidations, and pleural effusions.
The assessment of ChUS and CXR images was performed by two blinded
investigators.
Results
The median age of patients was 65 years (range: 25–95 years) with 16 males
and 8 females. The most common symptom was dyspnea (n=14/24)
followed by cough (n=10/24) and fever (n=7/24). 10
patients (42%) required at least 2 liters of oxygen per minute and 9
(37%) demonstrated increased breathing frequency (>18/min)
at rest. Notably, 6 patients (25%) were SARS-CoV-2 carriers and only
admitted due to either general deterioration (n=1) or co-morbidity
(lymphoma, cholangiocarcinoma, stroke, bradycardic atrial fibrillation, and retinal
detachment, respectively). Considering laboratory tests, the median values on the
day of investigation were as follows: WBCs 6.4×109/L, CRP
19 mg/dl, PCT 0.08 ng/ml and LDH 316 U/L. None of the
patients died during the period of this study. The clinical and laboratory
characteristics of all patients are summarized in [Table
1].
Table 1 Clinical and laboratory characteristics of the 24 patients
with confirmed SARS-CoV-2.
|
All patients, n=24
|
COVID-19, n=18; SARS-CoV-2 carrier, n=6
|
|
Males: females
|
16:8
|
|
Median age, years (range)
|
65
|
(25–95)
|
|
Type of symptoms
|
18/24
|
(75%)
|
|
Dyspnea
|
14
|
(58%)
|
|
Cough
|
10
|
(42%)
|
|
Fever
|
7
|
(29%)
|
|
Chest pain
|
1
|
(4%)
|
|
Oxygen inhalation
|
|
<2 L/min
|
14
|
(58%)
|
|
≥2 L/min
|
10
|
(42%)
|
|
Respiratory rate
|
|
≤18/min
|
15
|
(62%)
|
|
>18/min
|
9
|
(38%)
|
|
Laboratory tests
|
|
WBCs×109/L, median (range)
|
6.4
|
(2.0–19.0)
|
|
CRP mg/dl, median (range)
|
19
|
(0.3–164)
|
|
PCT ng/ml, median (range)
|
0.08
|
(0.01–0.4)
|
|
LDH U/L, median (range)
|
316
|
(108–882)
|
|
Status at last follow-up
|
|
Alive
|
24
|
(100%)
|
|
Dead
|
0
|
(0%)
|
Of 18 COVID-19 patients, 17 (94%) demonstrated pathologic B-lines with
bilateral distribution in 14 (82%) cases. For B-lines, multifocal appearance
was predominantly found (10/17; 59%) whereas confluent B-lines were
only detected in two patients ([Fig. 1a, d]). Of
note, 16 of 18 patients (89%) showed pleural irregularities that occurred
most frequently bilaterally. In contrast to pleural irregularities, pleural
thickening ([Fig. 1a]) was less frequently detected
(8/18; 44%). Pulmonary consolidations were detected in 14 of 18
COVID-19 patients (77%) demonstrating with mostly focal character
(10/14) ([Fig. 1b]), and an equal uni- and
bilateral distribution (7/14 each). Again, no confluent pattern for
consolidations was present as well. Along this line, abnormal lung sliding was
observed only in 3 of 18 patients (17%) and occurred only in cases with
multifocal consolidations. 10 cases (56%) showed small pleural effusions
with a mostly bilateral manifestation (7/10) ([Table 2]) ([Fig. 1c]).
Fig. 1
a-d: pleural line thickening a, focal subpleural
consolidation b, pleural effusion c and multifocal B-lines
d as common findings revealed by ChUS, e ground-glass
opacification and consolidation in the right upper lobe and left lower as
well as upper lobe with peripheral distribution, f bilateral patchy
consolidation predominantly in the lower zone with sparing of the right and
left apex.
Table 2 Ultrasound findings of n=18 COVID-19 patients.
|
COVID-19 patients
|
n=18
|
|
Pathologic B-lines
|
17/18
|
(94%)
|
|
|
3/17
|
(18%)
|
|
|
14/17
|
(82%)
|
|
|
5/17
|
(29%)
|
|
|
10/17
|
(59%)
|
|
|
2/17
|
(12%)
|
|
Pleura irregularity
|
16/18
|
(89%)
|
|
|
2/16
|
(13%)
|
|
|
14/16
|
(87%)
|
|
Pleura thickening
|
8/18
|
(44%)
|
|
|
5/8
|
(57%)
|
|
|
3/8
|
(43%)
|
|
Pleural effusion
|
10/18
|
(56%)
|
|
|
3/10
|
(30%)
|
|
|
7/10
|
(70%)
|
|
Pulmonary consolidation
|
14/18
|
(77%)
|
|
|
7/14
|
(50%)
|
|
|
7/14
|
(50%)
|
|
|
10/14
|
(71%)
|
|
|
4/14
|
(29%)
|
|
|
0/14
|
(0%)
|
|
Abnormal lung sliding
|
3/18
|
(17%)
|
|
|
2/3
|
(67%)
|
|
|
1/3
|
(33%)
|
|
Distribution of lung abnormalities
|
|
|
|
|
9/18
|
(50%)
|
|
|
1/18
|
(6%)
|
|
|
7/18
|
(38%)
|
|
|
1/18
|
(6%)
|
Regarding the anatomical distribution of lung abnormalities by ChUS, the lower lobe
(9/18) or both the lower and the upper lobe (7/18) were
predominantly affected, whereas isolated upper lobe involvement was observed in only
one case. Interestingly, patients with both lower and upper lobe involvement
demonstrated a more severe clinical and laboratory course of COVID-19 than the cases
with isolated lobe affection: intermediate care unit admission (5/7 vs.
2/10); O2 ≥2 L/min (6/7 vs. 3/10);
respiratory rate >18/min (5/7 vs. 4/10); median
WBCs, CRP, PCT and LDH (7.1 vs. 5.4×109/L; 87 vs. 29
mg/dl; 0.11 vs. 0.09 ng/ml and 372 vs. 322 U/L,
respectively). However, due to the limited number of patients, no significant
differences were found.
Of note, pathological findings were not seen on ChUS in 7 out of 24 patients
(29%). However, only one of these patients had COVID-19 whereas the
remaining six cases were asymptomatic SARS-CoV-2 carriers.
Comparing the ChUS results to standard CXR (available for 23 out of 24 patients),
the
most common sign in COVID-19 patients (n=18) was hazy increased opacity
([Fig. 1e]) in 11/18 (61%,
p<0.02 compared to B-lines on ChUS) cases followed by consolidations ([Fig. 1f]) (7/18; 38%; p<0.02
compared to consolidations on ChUS), and pleural effusion (5/18;
28%; p=0.09 compared to ChUS) ([Table
3]).
Table 3 X-ray findings of n=18 COVID-19 patients.
|
COVID-19 patients
|
n=18
|
|
X-ray abnormalities
|
|
a. Hazy increased opacity
|
11/18
|
(61%)
|
|
b. Consolidation
|
7/18
|
(39%)
|
|
c. Pleural effusion
|
5/18
|
(28%)
|
|
Distribution of lung abnormalities
|
|
a. Unilateral
|
3/18
|
(17%)
|
|
b. Bilateral
|
13/18
|
(72%)
|
|
c. Lower lobe
|
8/18
|
(44%)
|
|
d. Upper lobe
|
1/18
|
(6%)
|
|
e. Both lower and upper lobe
|
7/18
|
(39%)
|
|
f. Neither upper nor lower
|
2/18
|
(11%)
|
The lesions in CXR were predominantly present in the lower (8/18;
44%) or in both the lower and the upper lobes (7/18; 39%)
and tended to be distributed bilaterally (13/18; 72%). Of note, only
5/9 lesions (55%) in the lower lobe and 4/7 lesions
(57%) in the upper and the lower lobe were detected by both ChuS and CXR,
suggesting poor agreement between ChuS and CXR. Regarding asymptomatic SARS-CoV-2
carriers (CXR for 5/6 available), only 1/5 demonstrated local hazy
increased opacity and none of them had consolidations.
Discussion
Currently, multiple challenges are associated with the management of the COVID-19
pandemic. Regarding thoracic imaging, rapid and cost-effective diagnostic tools are
urgently needed to cope with the large number of patients. In our study, we
investigated patterns of bedside ChUS for the assessment of COVID-19 patients and
compared them to findings of conventional CXR.
In fact, the vast majority of COVID-19 patients demonstrated lung abnormalities on
ChUS. Notably, these results are in line with two other recent studies that
investigated COVID-19 patients by ChUS [8]
[9]. In particular, ChUS was especially informative for
revealing different manifestations of interstitial syndrome. The same refers to the
detection of lung consolidations by ChUS. In particular, consolidations in COVID-19
cases were characterized by a rather focal and mostly subpleural appearance
presenting frequently not only in basal but also in apical parts of the lung. In
conjunction with the frequent presence of alveolar consolidations, pleural line
abnormalities were the third most common sign among patients with symptomatic
COVID-19. Although it is difficult to directly correlate anatomical locations of
lung abnormalities between ChUS and CXR without having chest CT imaging as an
anatomical reference, our results suggest relatively poor agreement between ChUS and
CXR for the anatomical locations of lung pathologies.
Recently, Peng et al. reported the rare presence of pleural effusion in 20 COVID-19
patients investigated by ChUS [6]. In contrast, our
data provide evidence that small pleural effusions were present in almost half of
COVID-19 patients and detected more often by ChUS compared to CXR. Regarding the
anatomical distribution of involved lung lobes, ChUS predominantly showed affection
of the lower lobes, but simultaneous lower and upper lobe involvement was also
recorded. Simultaneous affection of the upper lobe was associated with a more severe
clinical course as evidenced by frequent intermediate care unit admission, more
severe dyspnea, and a higher rate of systemic inflammation. Thus, we conclude that
US examinations should always involve apical parts of the lung independent of basal
findings.
Interestingly, all six asymptomatic SARS-CoV-2 carriers showed no abnormalities on
ChUS which was in accordance with CXR results. This aspect may be of interest
especially in emergency departments where clinicians have to make decisions as to
whether additional imaging modalities such as CXR or CT scans need to be employed,
and ultimately whether the patient can be dismissed to ambulatory care or has to be
admitted. Following the ongoing active exploration of the diagnostic role of ChUS
in
the COVID-19 pandemic, clinical and sonographic classification of COVID-19 pneumonia
was recently suggested.[10].
Finally, the frequent finding of bilateral and multilobar lesions on ChUS in our
study confirmed earlier observations by CT scans that peripheral subpleural
distribution of lung lesions is frequently found in COVID-19 patients [3]
[4]
[11]. To that end, several studies could show the
association of ChUS findings with CT abnormalities in direct comparison with each
other [6]
[8]
[9]. Using chest CT as the reference standard, Lu et al.
reported on the successful application of lung ultrasound score in COVID-19 patients
with a diagnostic accuracy of 76.7%, 76.7% and 93.3% for
mild, moderate and severe lung lesions, respectively [12]. Despite all of the advantages of ChUS, deep lung lesions cannot be
evaluated by ultrasound, and there are limitations for several patient groups, such
as patients with high body mass index or restricted mobility.
Our study has several limitations: First, we only compare ChUS and CXR and do not
provide a gold standard with chest CT imaging. Second, the described lung
pathologies on ChUS and CXR are by no means diagnostic for COVID-19 and could also
be found in several other pulmonary conditions such as viral pneumonia, lung
embolisms or congestive heart failure. Furthermore, ChUS is highly
observer-dependent and can only capture peripheral lung pathologies.
In summary, ChUS represents a useful tool for rapid and informative lung assessment
in COVID-19 patients at first clinical presentation and is convenient as a follow-up
investigation that could potentially reduce radiation exposure and support clinical
decision making. Although ChUS may not be as accurate and sensitive as chest CT
scans, it seems to be highly sensitive with respect to detecting peripheral
pulmonary pathologies. Further multicenter studies should evaluate the diagnostic
power and clinical value of ChUS in the initial assessment and follow-up
examinations of COVID-19 patients as well as define criteria regarding whether and
when ChUS may replace CXR and/or CT.
Ethics Approval
The retrospective data analysis was approved by a decision of the local ethics
committee № 38/4/20.
