Keywords
COVID-19 - diagnosis - high resolution computed tomography
Background
COVID-19 induced viral pneumonia pandemic has now raged for more than 10 months across
the world and has severely affected several countries including India. As of early
November 2020, more than 8.7 million cases have been reported in India with nearly
1,29,000 deaths. Of these, the highest number (nearly 1.74 million) have been reported
from state of Maharashtra.
Despite the promise of vaccine and ever-evolving treatment strategies; case identification,
isolation, contact tracing remain the cornerstone of the strategy to control the pandemic.
Though RT-PCR is the gold standard for diagnosis of COVID-19, limitations include
limited availability, long turn-around times, false-negative reports means that the
sensitivity remains around 70%.[[1]] Previous researchers have shown that the false-negative ratio of RT-PCR test for
patients infected with COVID-19 is approximately 1 in 5.[[2]]
HRCT has been widely accepted for prognostication of COVID-19 pneumonia.[[3]]
We evaluated the sensitivity of HRCT in symptomatic and asymptomatic cases and contacts
in the setting of a stand-alone diagnostic centre in Nashik, Maharashtra.
Objectives
The objective was to test the hypothesis that HRCT is a sensitive tool for the primary
diagnosis of COVID-19 pneumonia irrespective of symptoms.
Methods
Study design: This was a retrospective, cross-sectional study. HRCT is already proven
to be of significant prognostic value in diagnosed cases of COVID-19 pneumonia. A
total of 1,499 patients who presented to the clinic in a 2-month duration of September
and October were included. This was a stand-alone diagnostic centre in a Tier II city
in Maharashtra, India.
HRCT was performed in a single breath-hold on a 16 slice- MDCT scanner (GE Healthcare,
Brivo- CT385).
The patients included were either index cases who had been recently diagnosed for
COVID-19 or patients whose testing was performed and results awaited but were clinically
symptomatic. Also included were patients who were in close contact with already proven
patients—these included both symptomatic as well as asymptomatic contacts. HRCT was
deemed “positive” for diagnosis of COVID-19 pneumonia if either one or a combination
of several well-described signs were seen—including but not limited to ground-glass
opacities in typical peripheral subpleural distribution, subpleural/interlobular interstitial
thickening, atoll sign, halo and reverse halo signs,[[4], [5], [6], [7], [8]] to name a few. Further, CT severity index was evaluated for the patients who had
a “positive” HRCT to assess the severity in these patients.
Statistical Analysis and Results
Statistical Analysis and Results
Though its well-known fact that 80% of all COVID-19 infections are asymptomatic, only
15.1% (226) of our patient population were asymptomatic [[Figure 1]]. This highlights the fact that most clinicians did not order for a HRCT in the
asymptomatic—this further reflects the current belief that HRCT serves as a good diagnostic
test and prognostic indicator in symptomatic individuals. However, its utility and
accuracy in the asymptomatic group is not widely known. Of these asymptomatic individuals,
132 (58.7%) had at least one CT finding described in literature for a COVID-19 pneumonia
[[Figure 2]]. Infact, 14 of these asymptomatic patients had a proven negative RT-PCR and yet
had a CT finding suggesting a COVID-19 pneumonia on CT, these were very likely false
negative on RT PCR. Thus, HRCT helps to identify the COVID-19 pneumonia even in asymptomatic
individuals irrespective of RT-PCR. This is crucial and means that HRCT can and should
be used for initial diagnosis of patients irrespective of symptoms and RT-PCR.
Figure 1: Pie chart showing symptomatic vs asymptomatic patients in the present cohort
Figure 2: How many patients show findings compatible with COVID 19 Pneumonia on HRCT
in both symptomatic and asymptomatic individuals
84.9% (1273) of all patients were symptomatic (defined for purpose of this study as
at least one of the common symptoms described for COVID-19 infection including fever,
cough, breathlessness, weakness, body ache, headache, throat pain). Of these, 928
(72.8%) had at least one CT finding described in literature for a COVID-19 pneumonia.
Infact, 34 (3%) of these patients had a proven negative RT-PCR and yet had a CT finding
suggesting a COVID-19 pneumonia on CT, indicating that these were very likely false
negative on RT-PCR. Additionally, 557 were RT-PCR status unknown (either not done
or result was not available). So a total of 591 patients (39.42%) were diagnosed faster/more
accurately because CT was done in these patients.
At the time of the scan, RT-PCR results were available for 499 patients. There were
a total of 392 positive, 107 proven negative subjects. RT-PCR status was not known
or not available for a total of 1,000 subjects. This number is large and includes
patients who were waiting for the results, those who had not been tested for a variety
of reasons, those who were reluctant to declare their RT-PCR results. These highlight
the real-world problems in a typical tier II city in India and further stress the
need for a multipronged strategy to diagnose, isolate, and treat patients using all
available means.
Diagnostic HRCT findings were seen in 68% of all patients irrespective of symptoms
and day of scan from the onset of symptoms/exposure [[Table 1]].
Table 1
Sensitivity, specificity and predictives values of findings on HRCT compatible with
COVID 19 Pneumonia in both asymptomatic and symptomatic individuals
|
Asymptomatic (in %)
|
Symptomatic (in %)
|
|
Sensitivity
|
73.1
|
71.2
|
|
Specificity
|
50
|
57
|
|
Positive predictive value
|
84.4
|
85.5
|
|
Negative predictive value
|
33.3
|
35.2
|
|
Accuracy
|
68.2
|
68.1
|
Discussion
In the fight against the coronavirus pandemic, early and accurate diagnosis of patients,
including those with little or no symptoms is crucial.[[3], [9]] This is especially because nearly 80% of all infections have little or no symptoms
and yet, these individuals are equally infective and thus play a major role in spreading
the pandemic. Existing serological tests including RT-PCR swab test, rapid antigen,
and antibody tests each have their limitations. In particular, the dangers of a false-negative
result have been highlighted previously.[[10]] RT-PCR has a turnaround time of at least 24–48 h. For an asymptomatic individual
in the infectious period, however, these 24–48 h can be crucial as she/he can still
spread the infection to close contacts.[[11], [12], [13], [14]] Thus, the need for fast turn-around time for an accurate test is crucial. Also,
the invasive nature of the test, social taboo increasingly associated with the testing
are deterrents especially for asymptomatic individuals to get themselves tested.
Especially in places where prevalence is high, a fast, non-invasive, accurate, and
inexpensive test for screening and diagnosis is essential. The sensitivity of HRCT,
when compared with RT-PCR, has been previously studied and was shown to be higher
than RT-PCR.[[2]]
In the present study, we have proven that HRCT chest is a sensitive test with high
positive predictive value, most importantly, in the present study the accuracy was
the same irrespective of symptoms.[[15]] Additionally, with immediate availability of the result of the scan, crucial time
is saved.
The cost for HRCT chest study in India (about 2,500-6,000 INR) being a fraction of
those in the rest of the world is a unique advantage which must be leveraged. From
an infrastructure point of view for the administration, already existing facilities
in both public and private healthcare providers mean that no additional ramping up
of the facilities is required, saving costs and even more crucially, time. From healthcare
providers perspective as well, since the scan is no different from other “routine”
chest scans for non-COVID indications—thus the only “additional cost” for the scanner—facilities
include those for protection of the healthcare personnel (for PPE, sanitization).
Others being fixed costs (e.g., scanners, facility costs), there is only a marginal
increase in the cost-burden to the providers.
Additional prognostic information provided with the CT severity index means it can
be used as an important metric for a triage system to determine who needs to be admitted/home
quarantined and so on.[[16]] Easy scalability with high throughput, the possibility of remote diagnosis by leveraging
teleradiology facilities mean that the HRCT chest is a very useful tool for initial
diagnosis. Additional information for other causes of breathlessness (e.g., cardiomegaly/pleural
effusions/pulmonary edema and even malignancies) may also be available. One of the
problems always highlighted with CT scans is radiation burden. Average dose per study
being about 7 mSV. This is much well within the limit of the max allowable dosage
of 5 per year lower than the average 5 year dose of 100 mSv or 20 mSv/year as recommended
by ICRP. Infact, accuracy of LDCT which has a lower overall average effective dose
(approximately 2 mSv as compared with an average effective dose of 5–7 mSv for a typical
standard-dose chest CT examination)[[17]] needs to be further explored for the purpose of diagnosing COVID-19 pneumonia.[[18]]
Limitations of our study include using the diagnostic criteria for COVID-19 pneumonia,
these patients were labelled as “Findings consistent with or suspicious for COVID
19 pneumonia.” We are aware that several other processes including other viral pneumonia
can appear similar on HRCT imaging. However, in view of the pandemic situation with
high percentage positivity in RT-PCR results, we did not think this as a major limitation.
Importantly, the radiologists were not blinded to the RT-PCR results. Though this
was less relevant as nearly 2/3rd of the patients did not have a result, yet this could be a source of bias in the
rest.
As of mid-November, India had performed about 12 million serological tests.[[19]] Yet, only about 40% of these tests were with RT-PCR kits, and the remaining were
rapid antigen tests. Though reports from China the epicenter of the pandemic when
it started did give an indication of the important role of CT scan,[[2]] guideline reports from the US and Europe in fact gave discouraging reports afterwards.
We have proven that HRCT is a very useful tool for the initial diagnosis of patients
suspected to have COVID-19 irrespective of symptoms or day of onset of CT. Considering
the many overall advantages, HRCT for the chest deserves to be included in the official
diagnostic guidelines for diagnosis.
