By April 24, 2020, COVID-19, which refers to severe acute respiratory syndrome coronavirus
2 (SARS-CoV-2) infection, has been spread to almost all countries, contaminated more
than 2,600,000 individuals, and led to more than 180,000 deaths worldwide [1]. COVID-19
is caused by a type of coronavirus which infects both animals and human and predominantly
involves the respiratory system. The virus was initially introduced to humans from
bats in Wuhan, China [2]. Despite the Chinese government initiating the most aggressive
disease containment effort in history [3], the disease has rapidly grown to a pandemic.
So far in the USA, more than 869,000 have been infected and almost 50,000 died [4]
since the first case was recognized on January 20, 2020 [5].
COVID-19 when symptomatic presents with pneumonia or upper respiratory infection.
Fever is observed in almost all (83–98%) patients and cough (mostly dry) is manifested
in the majority of cases (46–82%). About one-third of patients (31%) may present with
shortness of breath. Myalgia and fatigue may also present (11–44%). Pharyngitis, productive
cough, hemoptysis, headache, and GI symptoms are less common manifestations. Of infected
individuals, 80% are asymptomatic or only manifest mild symptoms. The average age
of patients has been in their 50s with a slight male dominance [6–8]. The mean incubation
period is about 5 days after exposure but can be as long as 19 days during which the
infected individual is asymptomatic and suspected to be able to transmit disease [6].
Lymphopenia, elevated lactate dehydrogenase, and ferritin are the most common laboratory
findings observed in COVID-19 [6].
Definitive diagnosis is made by the detection of viral RNA in specimens collected
from patients’ respiratory secretions using reverse transcriptase-polymerase chain
reactions (RT-PCR) that are performed using pre-prepared laboratory kits [9]. Since
COVID-19 emerged very recently, the efficacy and accuracy of available kits have not
been evaluated thoroughly and the sensitivity of currently produced kits has been
reported to be as low as 59% in some studies [9]. With the increasing emergent need,
governments have encountered a shortage of kits and problems with their distribution,
administration, and storage. For instance, the kits stored in the Atlanta CDC facility
are reported to be contaminated with Coronavirus [10]. The diagnosis of the first
case of COVID-19 in Washington state was delayed due to issues with the results of
RT-PCR kits distributed by the CDC. Meanwhile, the suspected patient and exposed healthcare
providers were not isolated and freely moved about potential exposing many other individuals
to the disease [11].
CT in the diagnostic approach to COVID-19
The rapid widespread expansion of COVID-19 cases has raised concerns about possible
disease containment and has made control of further spread of the disease the priority
in the management of COVID-19 by WHO and CDC to prevent a pandemic [9]. Bill Gates
in his article published in NEJM compared COVID-19 pandemic with the 1918 influenza
pandemic and indicated that COVID-19 may evoke a worse pandemic because it has a higher
rate of contagiousness and kills both young and elderly [12]. Since there is currently
no vaccine for COVID-19, successful disease containment is contingent upon rapid identification
of infected individuals to isolate them and their close contacts [9, 13]. The urgent
need for an alternative diagnostic than RT-PCR kits has given rise to the possibility
of utilization of chest CT findings as a diagnostic aid and a screening tool in suspected
patients [13].
In a review of the worldwide approach to the management of COVID-19 outbreak, authors
reported that many countries are currently using CT scan as a screening tool for suspected
patients due to the lack of resources (under review). Recently, a large study from
Wuhan has suggested application of CT scan as an alternative diagnostic method which
as of today demonstrated higher sensitivity than existing RT-PCR kits [9] despite
that it has not yet been approved by major radiology associations. CT scan is a widely
available modality and can readily be performed. In this study, it was reported that
88% of suspected patients had findings suggestive of COVID-19 in chest CT while the
positive rate of RT-PCR kits was only 59% [9]. Of those with negative RT-PCR, CT findings
were suggestive of highly likely disease and probable disease 48% and 33% respectively
[9]. It was also shown that CT findings were detected in infected individuals before
the RT-PCR kits did in symptomatic individuals. In patients whose initial serologic
result was negative and subsequently were found to be positive on repeat testing,
the second positive test results took an average of 5.1 days. Ninety-seven percent
of those cases already had positive imaging findings, which were present with a mean
of 8 days before the second positive serologic test results were available [9].
Bilateral ground-glass opacities (GGO) and/or consolidation have been suggested as
the hallmark of COVID-19 infection on chest CT images [7, 9, 13–15]. While they may
be nonspecific, these findings are easily identifiable on CT and should in the proper
clinical setting aid diagnosis. GGO is an increased attenuation with preserved vascular
and airway markings. With consolidation, these markings are obscured by the infiltration’s
effect on images. In a recent study, 78% of symptomatic patients had these findings
on CT; of those, 60% demonstrated bilateral lung involvement. Imaging findings were
detected in 91% of cases within 3–5 days after symptom onset. Interestingly, the serologic
tests result became available at almost the same time in this study (4.5 days) [14].
Low- and ultra-low-dose CT scan protocol
In emergent situations such as COVID-19 pandemic, the demand for performing CT scans
may significantly increase due to the high rate of infected individuals. Myers et
al. have recently suggested that radiology departments should prepare for the flood
of COVID-19 patients during the outbreak and therefore should be engaged in creating
the hospital’s mass casualty incident plan [16]. Furthermore, severely symptomatic
patients will often undergo multiple imaging studies during the course of their illness.
The cumulative effect of these multiple exams can significantly increase the cumulative
radiation dose these patients may receive during their hospitalization and recovery.
The as low as reasonably achievable (ALARA) principle states that whenever radiation
is expected, the exposure should be as low as reasonably achievable [17]. Keeping
this important principle in mind, it is critical that we remember that any CT scan
we perform should be accompanied by the justification of examination and optimization
of radiation dose [18]. This is of particular importance when evaluating more radiation-sensitive
patient populations such as pregnant patients and children. While CT imaging has been
shown to be a great help in establishing the diagnosis of COVID-19, the potential
for increased radiation exposure to a large number of patients across the country
cannot be ignored. Balancing the need for effective imaging to aid rapid diagnosis
while also trying to minimize radiation exposure will be important for radiologists
and clinicians alike as we work together to manage to COVID-19 outbreak.
Replacing conventional CT (CCT) with low-dose CT (LDCT) and ultra-low-dose CT (ULDCT)
has been proposed as a method to decrease radiation exposure in these patients (Figs. 1
and 2). In a retrospective study [13], LDCT with iterative reconstruction (IR) demonstrated
sensitivity, specificity, positive predictive value, negative predictive value, and
accuracy of about 90% in the diagnosis of COVID-19. These parameters further increased
to up to 96% when patients were symptomatic for more than 48 h. The likelihood of
COVID-19 diagnosis increased to 91% from pre-LDCT value of 43% in patients with suggestive
imaging findings whereas it was decreased to 9% in those with normal or atypical imaging
findings. The respective post-LDCT values in patients with > 48 h of symptoms were
91% and 3%. Furthermore, LDCT demonstrated an additive diagnostic benefit in patients
with concomitant bacterial pneumonia or an alternative diagnosis other than COVID-19.
Fig. 1
A 57-year-old male presented with fever and shortness of breath in an epidemic area
of COVID-19 (Iran) for diagnostic work-up. Low-dose CT demonstrates multifocal basilar
predominant peripheral ground-glass opacities, characteristic of SARS-CoV-2 pneumonia
(a, b). The low-dose CT chest radiation dosimetry of the patient was DLP of 78.34 mGy × cm
and CTDIvol of 2.03 mGy. Conventional CT chest protocol in the same patient would
result in DLP of 301.14 mGy × cm and CTDIvol of 7.87 mGy, which means that low-dose
protocol decreased the radiation dose to less than 50% without a significant impact
on the diagnostic value. (CT protocol: 100 kVp, 40 mAs, 0.5 s without iterative reconstruction)
Fig. 2
Low-dose chest CT in a 77-year-old male with high-grade fever, shortness of breath,
malaise, and cough in an epidemic area of COVID-19 (Iran) demonstrate left upper lobe
ground-glass opacity (a). The patient had areas of consolidation superimposed on ground-glass
opacity in bilateral lung bases (b). The constellation of findings is in keeping with
SARS-CoV-2 pneumonia. The low-dose CT chest radiation dosimetry of the patient was
DLP of 68.21 mGy × cm and CTDIvol of 2.10 mGy. Conventional CT chest protocol in the
same patient would result in DLP of 264.55 mGy × cm and CTDIvol of 5.92 mGy, which
means that low-dose protocol decreased the radiation dose to about 50% without a significant
impact on the diagnostic value. (CT protocol: 100 kVp, 50 mAs, 0.5 s without iterative
reconstruction)
Since GGO and consolidation are the primary CT presentations of COVID-19 that have
been shown to be effectively detected in LDCT or ULDCT, these low-dose image acquisition
methods can be utilized for the evaluation of more radiation-sensitive individuals
such as pregnant patients. The radiation dose with chest CCT is estimated at 7 mSv,
which is reduced to 1–1.5 mSv with the new LDCT methods and as low as 0.3 mSv with
ULDCT ones [18]. LDCT and ULDCT have shown efficacy to detect lung abnormalities (Table
1). Park et al. suggested that utilization of LDCT in the evaluation of patients suspected
to have lower respiratory infections had successfully detected GGO and small consolidation
when these pathologic findings were not detectable in the radiographic images [22].
Kubo et al. compared the detection of GGO and reticular opacities of LDCT with a previous
CCT and reported an agreement rate of 83% between them [25]. In contrast, Christe
et al. showed that sensitivity of LDCT (77%) is less than CCT (89%) in the detection
of GGO particularly for patchy lesions but no significant difference was observed
in the detection of consolidation between these scans. In fact, of the missed GGO
lesion, half were detected as a nodule [26]. Kim Y. et al. observed no significant
differences between LDCT and ULDCT in the detection of GGO and consolidation [19].
Table 1
Studies assessed application of chest low-dose CT or ultra-low-dose CT in evaluation
of pneumonia
Study
Protocol
Effective dose
IR
Imaging output
Kim et al. (2014) [19]
LDCT
120 kVp; 30 mAs
1.06 ± 0.11 mSv
+
There was no difference in detection of consolidation and GGO. Diagnosis was clear
in 100% of LDCT and 96% of ULDCT.
ULDCT A 100 kVp; 20 mAs
0.44 ± 0.05 mSv
+
ULDCT B 80 kVp; 30 mAs
0.31 ± 0.0.3 mSv
+
Dorneles et al. (2018) [20]
ULDCT
80 kVp; 15–30 mAs; 0.5 s
0.39 ± 0.15 mSv
+
Image qualities were excellent or diagnostic in 99% of ULDCTs.
Sun et al. (2017) [21]
LDCT
120 kVp; 10–350 mAs; 0.8 s
0.59 ± 0.19 mSv
+
IR demonstrated better detection of pulmonary lesions and lesser noise than FBP.
Park et al. (2015) [22]
LDCT
100 kVp; 30 mAs; 0.5 s
Not reported
−
LDCT detected GGO and small consolidation which were undetected in radiograph.
Dorobisz et al. (2017) [23]
LDCT
120 kVp; 25, 50, 75, 100 mAs
0.748–2.55 mSv
+
LDCT successfully detected GGO and consolidation
Alamdaran et al. (2019) [24]
LDCT
120 kVp; 30, 50 mAs,
Not reported
−
Diagnoses of LDCTs were concordant with final diagnoses.
Kubo et al. (2016) [25]
CCT
120 kVp; 150 mAs; 0.5 s
10.7
−
There were > 83% concordance between CCT findings and LDCT and no significant difference
in detection rate.
LDCT
120 kVp; 150 mAs; 0.5 s
3.57
−
Christe et al. (2012) [26]
CCT
120 mKv; 150 mAs
Not reported
−
LDCT had lower sensitivity for GGO with no significant difference for consolidation.
LDCT
120 mKv; 40 mAs
Not reported
−
Ohno et al. (2012) [27]
CCT
120kVp; 150mAs; 0.5 s
Not reported
−
Image quality of LDCT methods was significantly low when IR was not applied. There
was >80% concordance between detection of GGO and reticular opacities in all three
methods.
LDCT A
120 kVp; 50 mAs; 0.5 s
Not reported
±
LDCT B
120kVp; 25mAs; 0.5 s
Not reported
±
GGO, ground-glass opacity; CCT, conventional CT; LDCT, low-dose CT; ULDCT, ultra-low-dose
CT; IR, iterative reconstruction; FBP, filtered back projection
Likewise, pediatric patients benefit from dose reduction as they are at increased
risk of malignancy following radiation due to their longer life expectancy and higher
cell proliferation. A 1-year-old child is 10 times more susceptible to the adverse
effects of ionizing radiation than an adult [28]. In a study published in JAMA, the
routine effective dose delivered to pediatric patients during chest CT was calculated
between 5 and 8 mAs. The lifetime attributable risk of solid organ malignancies per
10,000 CT scans was measured as high as 30 and 9 for girls and boys respectively.
As it is expected, the projected radiation dose to body organs is higher in thyroid,
lung, breast, and esophagus during a chest CT acquisition. It was reported that as
low as 350 CT scans are needed to be performed to observe 1 cancer in girls [29].
LDCT scan has been also suggested in the evaluation of lung abnormalities in pediatrics
and successfully detected GGOs and consolidations. Sun et al. measured an overall
radiation dose of 0.59 mSv for evaluation of necrotizing pneumonia in different methods
of irritative reconstruction which was significantly lower than CCT. They also demonstrated
better detection and lower noise for lung lesions using LDCT performed with iterative
reconstruction [21]. Therefore, low-dose CT image acquisition methods are of value
in the evaluation of pediatric patients.
IR methods have been used to improve image quality in low-dose image acquisition and
decrease noise while reducing radiation dose. Sakai et al. used simulated GGO and
reticular opacity lesions and implemented them inside the apex and lower lobe of the
lung [30]. They obtained LDCT images using the IR method in various levels of radiation
dose and compared it with filtered back projection (FBP) method which is widely used
in scanners. They observed that although there was no significant difference in visual
detection of reticular opacity between these two modalities, IR dramatically improved
GGO visualization at low radiation doses. In a clinical study, IR demonstrated better
detection of necrotizing lesions in children evaluated for necrotizing pneumonia [21].
Ohno et al. showed that without the implementation of IR, the image quality of LDCT
was significantly lower than CCT. Following the addition of IR, no significant difference
was noted [27].
Conclusion
Since CT scan is capable to aid the diagnosis of COVID-19 in conjunction with other
clinical findings, the utilization of LDCT and ULDCT with iterative reconstruction
can be potentially recommended for the evaluation of these patients particularly in
pregnant and pediatric populations to reduce radiation exposure. Although LDCT and
ULDCT have demonstrated comparable efficacy in the detection of GGO and consolidation
in patients with pneumonia, no studies have evaluated the efficacy of LDCT and ULDCT
in the detection of pulmonary findings in the setting of COVID-19. A head to head
comparison of low-dose and conventional protocol in very early stages of the disease
is needed, while in intermediate and advanced stages, probably the low-dose CT protocol
will provide adequate image quality and diagnostic accuracy.