Mar 162020
 

Jon-Emile S. Kenny MD [@heart_lung] with illustrations by Carla M. Canepa MD [@_carlemd_]

He found a glimmer of hope in the ruins of disaster …

- Gabriel García Márquez

Background 

The coronavirus moniker originates from the appearance of the virus under the electron microscope – protein peplomers radiating from the viral envelope like a crown.  Prior to 2019, there were 6 known human-infecting coronaviruses, four of which caused only mild respiratory disease [e.g. the common cold].  Two, however, of the betacoronavirus genus caused more severe disease – SARS-CoV discovered in 2002 and MERS-CoV in 2012.

In late 2019, a novel bat-origin coronavirus originated in Wuhan, Hubei, China.  The virus was named severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] and the clinical disease caused by SARS-CoV-2 was termed coronavirus disease 2019 [i.e. COVID-19].  Although SARS-CoV-2 is a member of the coronavirus family, it is more distant from SARS-CoV and MERS-CoV and, therefore, considered to be a new type of betacoronavirus.

While there are innumerable aspects of this explosive pandemic to explore, this concise review will focus mostly on the chest CT and how this test may be an integral part of screening patients for COVID-19 as the SARS-CoV-2 virus spreads across North America.

Rapid Screening

A basic principle when screening for disease is to use a highly sensitive test; often a highly sensitive test has diminished specificity.  Put another way, a screening test attempts to capture all patients with true disease [i.e. high sensitivity, low false negatives] at the cost of more false positive results.  Further, when a pathogen can spread swiftly within the population – as SARS-CoV-2 can – the ideal test is both sensitive and rapid so that the affected individual can be isolated and treated expeditiously.

While the focus of COVID-19 testing in the lay press has centred around nasal swabs employing reverse transcriptase polymerase chain reaction [RT-PCR] to detect SARS-CoV-2, this test may have an initial high false negative rate.  Further, there is a relatively long turnaround time for the PCR test and some countries have been slow to deploy the PCR assays; accordingly, there was a ‘strong recommendation’ in China to employ early chest CT in patients suspected of having COVID-19 to help triage and isolate early disease prior to the results of molecular assays.  The chest CT has high sensitivity for detecting viral pneumonia, even before clinical symptoms develop.  Further, the chest CT varies with disease course and severity as touched upon below.

Chest CT Abnormalities before Symptoms

Shi and colleagues retrospectively reviewed the chest CT findings of 81 patients with confirmed COVID-19.  Of note, the patients were subdivided into 4 groups based on duration of clinical symptoms.  Group 1 consisted of 15 patients who had a chest CT prior to any clinical symptoms, group 2 had a CT scan performed within 7 days of symptom onset, group 3 patients were scanned 7-14 days from symptom onset and group 4 were evaluated beyond 14 days.

Importantly, all 81 patients [including those without symptoms] had an abnormal chest CT consistent with viral pneumonia.  In the asymptomatic group, the typical pattern was unilateral, multifocal and peripherally-based ground glass opacities [GGO] [see figure 1].  Interlobular septal thickening, thickening of the adjacent pleura, nodules, round cystic changes, bronchiolectasis, pleural effusion, and lymphadenopathy were rarely observed in the asymptomatic group.

Figure 1: Illustration of chest CT evolution during COVID-19. A.) is normal lungs for comparison, top illustration represents upper lung zones while bottom shows lower lung zones. B.) is hypothetical early stage with unilateral (right), multifocal, peripherally-based GGO.

Interestingly, a more recent report from the "Diamond Princess" cruise ship by Inui and colleagues reveals a diminished sensitivity of the Chest CT in asymptomatic, but RT-PCR positive patients as compared to Shi et al.  It is key to realize, however, that 'asymptomatic' in the analysis by Inui et al. was defined solely on the presence or absence of symptoms at the time of admission - not whether or not the patient was ever symptomatic.  Because RT-PCR can remain positive for weeks after symptoms abate, one wonders if the CT scans were performed after illness had resolved?  This is particularly curious given that those patients with symptoms in this investigation displayed strikingly lower frequencies of fever, sore throat and dyspnea than previously reported in COVID-19.

Chest CT Abnormalities before PCR

Early chest CT abnormalities have been echoed in other publications.  For instance, Li and Xia reviewed the chest CT scans of 53 patients [51 with COVID-19 and 2 with adenovirus pneumonia] and found that chest CT abnormalities diagnostic of viral pneumonia were available before a positive laboratory test result in 37 patients [i.e. 70%].  Furthermore, the CT-based diagnosis was available a full 3 days earlier than molecular assays.

Huang and colleagues reported on a 36 year old patient with high clinical suspicion for COVID-19 and a negative PCR both on presentation and again on day 3 of hospitalization.  However, his chest CT initially demonstrated multiple peripheral ground-glass opacities in both lungs; it wasn’t until day 6 that the PCR turned positive [i.e. the third assay]!

Xie et al. published their experience on 167 cases of confirmed COVID-19 where both PCR testing and chest CT were performed on the same day.  Of this group, 155 had concordance between PCR and chest CT [i.e. both positive for disease].  There were 5 cases of PCR negative, but chest CT positive cases which all later became positive by PCR within 2-8 days.  Additionally, there were 7 cases of chest CT negative, but PCR positive cases lending credence to performing both PCR testing and chest CT scanning in all patients with intermediate pre-test probability for disease.

Finally, in a large, retrospective evaluation of over 1000 patients who underwent both chest CT and RT-PCR tests during evaluation for COVID-19, the sensitivity of chest CT was quite high.  Compared to RT-PCR as the reference standard, 580/601 patients had an abnormal chest CT [i.e. sensitivity of 97% for chest CT].  Importantly, however, as RT-PCR may be an imperfect gold standard, 308 cases of positive chest CT but negative PCR were evaluated for ‘clinical likelihood’ of COVID-19.  Of these 308 discordant cases [i.e. chest CT positive, PCR negative], 147 were considered as ‘highly likely’ cases and an additional 103 as ‘probable’ cases by comprehensive clinical evaluation.  Thus, chest CT detected an additional 250 ‘probable’ or ‘highly likely’ COVID-19 cases that were missed by PCR.

Chest CT Evolution in COVID-19

Returning to the work of Shi and colleagues, radiographic progression was observed following first symptoms.  In group 2 [i.e. the first 7 days of symptoms] lesions on the chest CT become bilateral in 90% and diffuse in over 50% and were predominantly GGO [see figure 2]. One pleural effusion and a few cases of lymphadenopathy were detected in group 2 as well.  In group 3 [i.e. 7 to 14 days after symptoms], GGO was still the predominant CT finding in more than 50%; however, consolidation patterns were also noted in about one-third.  Lastly, in group 4 [i.e. more than 14 days after symptoms], GGO and reticular patterns were most common.

Figure 2: Illustration of further evolution of peripherally-based GGO. Lesions are now bilateral and multi-focal.

The radiographic sequence seen by Shi et al. was similar to that identified by Zhou and colleagues; in their study of 62 patients with confirmed COVID-19, single lesions were observed after a mean of 2 days of symptoms while multiple abnormalities were noted at a mean of 7 days of symptoms.  Further, when the course of COVID-19 was specifically divided into an 'early phase' [i.e. ≤ 7 days after the onset of symptoms] and an 'advanced phase' [i.e. 8–14 days after the onset of symptoms], the frequency of GGO was significantly higher in the early phase group. The occurrences of GGO plus a reticular pattern, vacuolar sign, fibrotic streaks, a sub-pleural line, a sub-pleural transparent line, air bronchogram, bronchus distortion, and pleural effusion were also significantly greater in those with advanced phase as compared to those with early phase [see figure 3].

Figure 3: Progression of lesions to multi-focal consolidations with air bronchograms. As well, there is bibasilar reticulations with 'crazy-paving' morphology.  Note these are stylized illustrations and lung lesions needn't necessarily follow such linear evolution.

Overall, the distribution was predominantly peripheral without significant difference between the right and left lungs.  The upper lung zones were less affected than the middle and lower zones.  Similarly, the anterior lung was significantly less involved than the posterior area.

Chest CT Differences between Mild and Severe Disease

Finally, Zhao and colleagues evaluated the chest CT scans of 101 COVID-19 patients and grouped them into those with ‘mild disease’ and into those with ‘severe and fatal disease.’  Notably, those with the latter, severe course, were more likely to have architectural distortion, traction bronchiectasis, intra-thoracic lymph node enlargement, and pleural effusions than those with milder disease. The craniocaudal, transverse, and lung region distributions were not significantly different between the two groups, but, as one might expect, diffuse lesions were more common in severe disease.

Thoughts

Overall, it looks certain that the diagnosis of COVID-19 will initially present challenges as North America begins to grapple with SARS-CoV-2 in a way that other continents and countries, particularly China, already have.  Nevertheless, it may be wise to follow the screening strategy adopted in China as their approach appears to have been quite successful.  ‘Fever clinics’ established in China embraced aggressive use of both PCR and chest CT to help catch all possible infections.  Given the early and sensitive findings of viral pneumonia detected by CT, its role as a screening adjunct seems clear.  Nevertheless, chest CT is a limited resource and this may open the door for other, more available, modalities [e.g. point-of-care ultrasound, POCUS] to aide in the rapid diagnosis of viral pneumonia.  Thus, intensivists may ultimately need to find POCUS love in the time of coronavirus.

Please check out this 'illustrated primer' on COVID-19 therapy,

JE

Dr. Kenny is the cofounder and Chief Medical Officer of Flosonics Medical; he also the creator and author of a free hemodynamic curriculum at heart-lung.org

 

 

 

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An Illustrated Guide to the Chest CT in COVID-19