The Open Public Health Journal




ISSN: 1874-9445 ― Volume 14, 2021
SYSTEMATIC REVIEW

Spectrum of Initial Computed Tomography Findings in RT-PCR Positive Patients with Novel Coronavirus 2019 Disease – A Systematic Review of 2327 Cases



Mishra Gaurav1, *, Dass Abhilasha2, Mahalaqua Nazli Khatib3, Quazi Syed Zahiruddin4
1 Department of Radiology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences, Wardha, Maharashtra, India
2 Department of Dentistry, Sharad Pawar Dental College, Sawangi, Maharashtra, India
3 Department of Division of Evidence Synthesis, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences, Wardha, Maharashtra, India
4 Department of Community Medicine, Datta Meghe Institute of Medical Sciences, Wardha, Maharashtra, India

Abstract

Coronavirus disease 2019 (COVID-19) is a highly infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of April 17, 2020, the total number of cases all over the world read as 2,182,823 positive cases with 145,551 deaths and 547,679 recovered cases. In India, the total number of affected cases has alarmingly increased up to 13,430, crossing the 10 thousand mark with 11,214 active cases and 1768 recovered cases. There have been multiple studies and reviews published regarding the nature of the disease, its clinical symptoms and their progression, as well as findings on chest radiography, computed tomography, and positron emission computed tomography.

A systematic literature search of the PubMed database was performed on April 8, 2020, using the suitable keywords and publications on novel coronavirus infection were also searched for in the WHO database. Only those articles published in the year 2020 were included. Data were collected, extracted, and tabulated for systematic reviewing from 26 original articles and 4 case series. The typical radiological findings on computed tomography for COVD 19 were ground-glass opacity with and without consolidation, isolated consolidation, air bronchogram, crazy paving, and interlobular septal thickening with subpleural lines.

With the progression of the disease, other atypical radiological findings are noted, such as pulmonary atelectasis, peribronchial thickening, pleural effusion, pericardial effusion, mediastinal lymphadenopathy, reverse halo or atoll sign, and tree in bud appearance with bronchiectasis. Computed tomography proved as a useful tool for screening COVID 19 cases to delineate the status and severity of lung pathology.

Keywords: Covid-19, Chest radiology, Positron emission computed tomography, SARS-CoV-2, Consolidation.


Article Information


Identifiers and Pagination:

Year: 2021
Volume: 14
Issue: Suppl-1, M2
First Page: 118
Last Page: 127
Publisher Id: TOPHJ-14-118
DOI: 10.2174/1874944502114010118

Article History:

Received Date: 04/05/2020
Revision Received Date: 03/08/2020
Acceptance Date: 16/08/2020
Electronic publication date: 22/03/2021
Collection year: 2021

© 2021 Gaurav et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


* Address correspondence to this author at Department of Radiology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences, Wardha, Maharashtra, India; Tel: 0912 706 7291; E-mail: drgvmishra@gmail.com





1. INTRODUCTION

Coronavirus disease 2019 (COVID-19) is a highly infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1Coronavirus disease 2019 (COVID-19)—Symptoms and causes. Mayo Clinic Retrieved 14 April 2020. Available from URL : https://www.mayoclinic.org/diseases-conditions/coronavirus/symptoms-causes/syc-20479963]. The disease was first identified in December 2019 in the city of Wuhan, the capital of Hubei province, China, which has now spread to other countries giving it the form of a pandemic [2Hui DS, I Azhar E, Madani TA, et al. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health - The latest 2019 novel coronavirus outbreak in Wuhan, China. Int J Infect Dis 2020; 91(February): 264-6.
[http://dx.doi.org/10.1016/j.ijid.2020.01.009] [PMID: 31953166]
, 3"WHO Director-General's opening remarks at the media briefing on COVID-19". World Health Organization (WHO)(Press release). Archived from the original on 11 March 2020 2020. Retrieved 12 March 2020. Available from URL : https://www.who.int/director-general/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020]. The World Health Organization(WHO) declared the 2019–20 coronavirus outbreak as a Public Health Emergency of International Concern(PHEIC) on January 30, 2020, and a pandemic on March 11, 2020 [4"Statement on the second meeting of the International Health Regulations (2005) Emergency Committee regarding the outbreak of novel coronavirus (2019-nCoV)".. World Health Organization(WHO). Archived from the original on 31 January 2020 2020. Retrieved 11 February 2020. Available from URL :https://www.who.int/news/item/30-01-2020-statement-on-the-second-meeting-of-the-international-health-regulations-(2005)-emergency-committee-regarding-the-outbreak-of-novel-coronavirus-(2019-ncov), 5"Hundreds of evacuees to be held on bases in California; Hong Kong and Taiwan restrict travel from mainland China".. The Washington Post Archived from the original on 7 February 2020 2020. Retrieved 11 February 2020. Available from URL :https://www.washingtonpost.com/world/asia_pacific/coronavirus-china-live-updates/2020/02/05/114ced8a-479c-11ea-bc78-8a18f7afcee7_story.html].

As of April 17, 2020, the total number of cases all over the world read as 2,182,823 positive cases, with 145,551 deaths and 547,679 recovered cases. In India, the total number of affected cases has alarmingly increased up to 13,430 cases, crossing the 10 thousand mark with 11,214 active cases and1768 recovered cases [6Coronavirus update (live).. Available from URL :https://www.worldometers.info/coronavirus/].

As the primary site of involvement of novel coronavirus 2019 infection is the respiratory tract, both chest radiography and computed tomography are go-to modalities to screen the suspected cases. However, when both are compared in terms of accuracy, computed tomography fares better than the former, reinforcing its importance in both initial screenings of suspected cases and follow-up scans of such cases with the progression of timeline [7Jin YH, Cai L, Cheng ZS, et al. A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Mil Med Res 2020; 7(1): 4-5.
[http://dx.doi.org/10.1186/s40779-020-0233-6] [PMID: 32029004]
-9Pan Y, Guan H, Zhou S, et al. Initial CT findings and temporal changes in patients with the novel coronavirus pneumonia (2019-nCoV): a study of 63 patients in Wuhan, China. Eur Radiol 2020; 30(6): 3306-9. Epub ahead of print
[http://dx.doi.org/10.1007/s00330-020-06731-x] [PMID: 32055945]
]. The existing information regarding the dreaded disease is diffused and seemingly incomplete, owing to its scattered nature. There have been multiple studies and reviews published regarding the nature of the disease, its clinical symptoms and their progression, as well as radiological findings on chest radiography, computed tomography, and positron emission computed tomography [10Joob B, Wiwanitkit V. 18F-FDG PET/CT and COVID-19. Eur J Nucl Med Mol Imaging 2020; 47(6): 1348.
[http://dx.doi.org/10.1007/s00259-020-04762-6] [PMID: 32166511]
-13Lütje S, Marinova M, Kütting D, Attenberger U, Essler M, Bundschuh RA. Nuclear medicine in SARS-CoV-2 pandemia: 18F-FDG-PET/CT to visualize COVID-19. Nucl Med (Stuttg) 2020; 59(3): 276-80.
[http://dx.doi.org/10.1055/a-1152-2341] [PMID: 32259853]
].

Therefore, the purpose of this systematic review article is to delineate the initially presented radiological findings on computed tomography in real-time polymerase chain reaction positive cases for COVID-19 infection so as to assist the radiologist in pinpointing the desired direction in such scenarios.

2. MATERIALS AND METHODS

A systematic literature search of PubMed database was performed on April 8, 2020 using the keywords “(((((( (((“COVID 19”[Title/Abstract] OR “COVID 19”[Title/ Abstract]) OR “COVID 19”[Title/Abstract]) OR “SARS-CoV-2”[Title/Abstract]) OR “severe acute respiratory syndrome coronavirus 2”[Title/Abstract]) OR “ncov*”[Title/ Abstract]) OR “corona virus”[Title/Abstract]) OR “corona- virus”[Title/Abstract]) OR “coronavirus”[MeSH Terms]) OR “sars virus”[MeSH Terms]) AND ((((((((((((“radiolog*” [Title/Abstract] OR “radiograph*”[Title/Abstract]) OR “X-ray”[Title/Abstract]) OR “ct”[Title/Abstract]) OR “computed tomograph*”[Title/Abstract]) OR “MRI”[Title/Abstract]) OR “magnetic resonance imaging”[Title/Abstract]) OR “sonography” [Title/Abstract]) OR “ultrasound”[Title/ Abstract]) OR “ultrasonograph*”[Title/Abstract]) OR “radiography”[MeSH Terms]) OR “tomography, x-ray computed”[MeSH Terms]) OR “ultrasonography”[MeSH Terms]). Publications on novel coronavirus infection were also searched for in the WHO database[15]. Only those articles published in the year 2020 were included.

2.1. Eligibility Criteria and Study Selection

Studies included in this systematic review were those published in the perspective of novel coronavirus 2019 disease and included computed tomography as the diagnostic intervention. All studies other than original articles were excluded. All included studies were reviewed by two reviewers on the basis of criteria for eligibility [16National Heart, Lung, and Blood Institute website.. Study quality assessment tools [Accessed February 16, 2020]; Available from URL : www.nhlbi.nih. gov/health-topics/study-quality-assessment-tools]. Any discrepancy between reviewers was resolved by discussion.

2.2. Data Extraction and Synthesis

Data was collected in form of the following categories viz Name/ID of the study with year, Country, Study design, Population details (Total participants, Age range, Male: Female ratio, COVID confirmed/suspected), Diagnostic test details, Outcomes reported.

3. RESULTS

3.1. Results of the Search Strategy

Upon systematic searching of the PubMed database using suitable keywords, a total of 659 articles were retrieved. Additional literature search added 3 more articles. Upon removal of duplicate search records, a total of 129 records were identified. After the search records were screened, 30 studies consisting of 26 original articles and 4 case series with a total of 2327 patients were included in the final review (Fig. 1).

Fig. (1)
PRISMA 2009 Flow Diagram.


3.2. Overview of the Included Studies and Assessment of the Risk of Bias

Out of the included studies (n=30), 29 studies were from China and only one study was from Korea. Four studies were prospective, whereas 26 were retrospective. Studies with minimum and maximum number of participants, the total number of participants, and the characteristics of the included studies are presented in Table 2.

NIH quality assessment tool for systematic reviews and meta-analyses was referred for quality assessment of the included studies [17Liu KC, Xu P, Lv WF, et al. CT manifestations of coronavirus disease-2019: A retrospective analysis of 73 cases by disease severity. Eur J Radiol 2020; 126108941
[http://dx.doi.org/10.1016/j.ejrad.2020.108941] [PMID: 32193037]
]. The quality assessment of included studies was carried out by two reviewers on the basis of NIH quality assessment criteria as represented in Table 1, where the included studies have been assessed using NIH quality assessment tool. Out of 30 included studies, 4 were rated as poor by both observers and 26 were rated as fair by both.

Table 1
Assessment of quality of studies included in present systematic review according to NIH Quality Assessment Tool for Case Series Studies.


Table 2
Characteristics of included studies.


3.3. Radiological Findings from Included Studies

3.3.1. CT Scan as a Screening Tool – Typical Findings

After taking into consideration the initial radiological findings noted in the included studies(Table 3), it was observed that there was a proper spectrum to it which included a rainbow in the form of ground-glass opacities which were isolated, then ground-glass opacities which coexisted with consolidation, followed by isolated consolidation patches, air bronchogram, crazy paving appearance, and interlobular septal thickening with subpleural lines.

Ground glass opacities were defined as ill-defined hazy areas with increased attenuation where bronchial, as well as vascular margins, were intact. Consolidation was defined as intra alveolar air being replaced by abnormal fluid and tissue due to an increase in attenuation, rendering bronchial and vascular margins obscured. Crazy paving was defined as thickened interlobular septa with superimposition on a surrounding ground-glass opacity. Air bronchogram referred to an air attenuation bronchus on a background of the hyperattenuating opaque atelectatic lung. Subpleural line referred to a thin curvilinear opacity having a maximum width of 1 to 3 mm and located within a distance of 1 cm from the pleural surface and parallel to the adjacent pleural surface [18Hansell DM, Bankier AA, MacMahon H, McLoud TC, Müller NL, Remy J. Fleischner Society: glossary of terms for thoracic imaging. Radiology 2008; 246(3): 697-722.
[http://dx.doi.org/10.1148/radiol.2462070712] [PMID: 18195376]
].

The total number of studies included in this systematic review article is 30 and the total number of cases reflected herein is 2327. Isolated ground-glass opacities were noted in 70.43% of cases (n=1639), ground-glass opacities coexisting with patchy consolidation were seen in 629 cases (27.03%), followed by isolated consolidation patches seen in 15.72%(n=366) cases.

3.3.2. CT Scan as a Diagnostic Tool – Atypical Findings

Other findings noted were interlobular septal thickening, crazy paving appearance and air bronchogram, which were noted in 312 (13.40%), 191 (8.20%), and 364 cases (15.64%), respectively. Subpleural lines were noted in 237 cases (10.18%).

The radiological findings which were far less common or atypically noted were pulmonary atelectasis(n=1, 0.04%), peribronchial thickening (n=38,1.63%), pleural effusion (n=72,3.09%), pericardial effusion (n=5,0.21%), mediastinal lymphadenopathy (n=36,1.54%), reverse halo or atoll sign defined as a focal rounded GGO surrounded by a more or less complete ring-like consolidation (n=9,0.38%), tree in bud appearance (n=2,0.08%) with bronchiectasis (n=88,3.78%) respectively. Amongst the included studies listed in Table 3, the total number of cases showing unilateral lung involvement was 19.03% (n=443) and those showing involvement of bilateral lungs were 74.17% (n=1726). Also, there was a number of cases that did not show any abnormal radiological findings on computed tomography in their initial scan (n=149, 6.40%) inspite of being tested positive for COVID 19 infection via real-time polymerase chain reaction testing.

The time period of the included cases from being tested positive for COVID-19 on RT-PCR testing and getting a CT chest done ranged in between 1 to 5 days.

Most of the included studies showed a predominant involvement of the peripheral one-third of the lung field irrespective of the laterality of the lesion with or without the involvement of the central two-thirds of bilateral lung fields. No isolated central lung involvement was noted in the included studies, which is consistent with the findings of Ooi GC et al. [18Hansell DM, Bankier AA, MacMahon H, McLoud TC, Müller NL, Remy J. Fleischner Society: glossary of terms for thoracic imaging. Radiology 2008; 246(3): 697-722.
[http://dx.doi.org/10.1148/radiol.2462070712] [PMID: 18195376]
, 19Ooi GC, Khong PL, Müller NL, et al. Severe acute respiratory syndrome: temporal lung changes at thin-section CT in 30 patients. Radiology 2004; 230(3): 836-44.
[http://dx.doi.org/10.1148/radiol.2303030853] [PMID: 14990845]
] and Wong KT et al. [20Wong KT, Antonio GE, Hui DS, et al. Severe acute respiratory syndrome: radiographic appearances and pattern of progression in 138 patients. Radiology 2003; 228(2): 401-6.
[http://dx.doi.org/10.1148/radiol.2282030593] [PMID: 12759474]
].

Table 3
Radiological findings in included studies.


4. DISCUSSION

In the present study, 70.43% of cases presented with ground glass opacities in isolation as the most common and frequent radiological finding, followed by 27.03% and 15.72% cases presenting with ground glass opacities in coexistence with patchy areas of consolidation and isolated patches of consolidation without ground-glass opacities, respectively. This resultant finding can be seen to envisage computed tomography as a perfect screening tool for investigating suspected cases.

According to an article published by theprint.in online (reference), the present scenario of COVID 19 in India states certain bitter facts that may prove true sooner than later if the present situation does not get hilted properly. According to its author, “It took India forty days to reach the first 50 cases, five more days to reach 100 cases, three more days to reach 150 cases and then just two more days to reach 200 cases.” It states that India has already hit the phase where it is showing exponential growth in the number of patients infected with COVID 19 disease, with special emphasis upon the meagre number of beds available per 1000 people in different states. According to the declared statistics in 2017, the official overall number of beds available per 1000 people in India is as less as 0.5. It also reinforces the fact that the rate of doubling of cases in India is as present about 5 days or less and, in not much later timeframe, it will grow less, putting India upon the same trajectory of affected cases as the USA where the same rate is about 2 days. At this rate, it is going to be a very difficult time to handle such cases for Indian healthcare workers [21Rukmini S. https://theprint.in/opinion/current-rate-india-30000-covid-19-deaths-may-no-hospital-bed-june-data/385386/2020.].

Coming to the radiological front, according to a Fleischner Society consensus statement published on April 07, 2020 [22Rubin GD, Ryerson CJ, Haramati LB, et al. The role of chest imaging in patient management during the COVID-19 Pandemic: A multinational consensus statement from the fleischner society. Radiology 2020; 296(1): 172-80.
[http://dx.doi.org/10.1148/radiol.2020201365] [PMID: 32255413]
]:

  1. Imaging is not indicated in suspected cases of COVID 19 until and unless there is a potential risk of worsening of the disease.
  2. It is strongly indicated in positive COVID 19 case with deteriorating respiratory status.
  3. Imaging is indicated for medical triage of suspected COVID 19 cases with moderate to severe spectrum of clinical findings with high disease probability before the diagnostic test has been carried out.

Computed tomography of the chest is a strongly advised modality that can be used to screen cases affected by COVID 19 infection as well as for suspected cases that happen to come under the above-mentioned criteria by Fleischner [7Jin YH, Cai L, Cheng ZS, et al. A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Mil Med Res 2020; 7(1): 4-5.
[http://dx.doi.org/10.1186/s40779-020-0233-6] [PMID: 32029004]
, 22Rubin GD, Ryerson CJ, Haramati LB, et al. The role of chest imaging in patient management during the COVID-19 Pandemic: A multinational consensus statement from the fleischner society. Radiology 2020; 296(1): 172-80.
[http://dx.doi.org/10.1148/radiol.2020201365] [PMID: 32255413]
].

The main presenting features noted in a patient of COVID 19 are fever, dry cough with or without a sore throat, muscle fatigue, sputum production, and difficulty in breathing. Also, the patients of COVID 19 who succumbed to its brute nature either belonged to the age group of more than 60 years of age or had one or the other comorbidities, such as diabetes mellitus and hypertension being the most common ones [232020.https://www.who.int/publications-detail-redirect/report-of-the-who-china-joint-mission-on-coronavirus-disease-2019-(covid-19)].

The typical radiological findings noted in chest computed tomography are of ground-glass opacities which were isolated, then ground glass opacities which coexisted with consolidation, followed by isolated consolidation patches, air bronchogram, crazy paving appearance, interlobular septal thickening with subpleural lines. With the progression of the disease, other atypical radiological findings are noted, such as pulmonary atelectasis, peribronchial thickening, pleural effusion, pericardial effusion, mediastinal lymphadenopathy, reverse halo or atoll sign, and tree in bud appearance with bronchiectasis. The appearance of atypical findings denotes the progression of the disease with an added possibility of superadded bacterial infection giving rise to focal enlargement of mediastinal lymph nodes.

There are two zoonotic viruses from the family of coronaviruses that affect humans – COVID 19 being caused by one of them and the other one being Middle East Respiratory Syndrome virus. Both of these give a presentation of viral pneumonia in the affected lungs. As per Cotran, there are 4 stages of pneumonia – congestion, red hepatization or consolidation, grey hepatization, and lastly, resolution. Different types of viral pneumonia affect different areas, but the timeline progression of lung tissue damage and recovery is more or less the same throughout. The progression is chronological from the stage of congestion, which is marked by vascular engorgement around the pulmonary alveoli with intra alveolar fluid leak. The second stage sees an increase in vascular engorgement and congestion with leakage of blood cells into the intra alveolar fluid. This blood being rich in fibrin leads to a collectively hyperdense appearance to the affected part of the lung – solidification or consolidation. The third stage, called grey hepatization, sees the degeneration of these existing blood cells and deposition of fibrin in the intra alveolar compartment, the lung still giving consolidated appearance. Lastly, the stage of resolution sees the development of pulmonary fibrosis – marking the phase of recovery of affected lung tissue [24Cotran RS, Kumar V, Fausto N, Fausto N, Robbins SL, Abbas AK. Robbins and Cotran pathologic basis of disease 2005; 749. [ISBN 0-7216-0187-1.]].

Amongst the included studies, COVID 19 was graded by KC Liu into the mild type, common type, severe type, and the critical type. Mild type was defined as a case showing lung hilar enlargement with thickening of lung texture. The common type was defined as patchy GGO with crazy paving, air bronchogram, and interlobular septal thickening. The severe type was defined as extensive multilobular GGO, pulmonary consolidation, and peribronchial thickening. The critical type was defined as confluent GGO with pulmonary atelectasis, pleural effusion, and pulmonary fibrosis. They concluded that the size of the lesion as well as the type of the lesion is in direct proportion with the severity of the presenting disease. Also, they concluded that the disease severity also lies in direct proportion with the patient's age [17Liu KC, Xu P, Lv WF, et al. CT manifestations of coronavirus disease-2019: A retrospective analysis of 73 cases by disease severity. Eur J Radiol 2020; 126108941
[http://dx.doi.org/10.1016/j.ejrad.2020.108941] [PMID: 32193037]
].

Viral load of COVID 19 was reflected in the study by JFW Chan, indicating that the cycle threshold values for samples from patient sputum were 8-13 cycles earlier than samples taken from nasopharyngeal swabs meaning higher viral load of the present disease causative agent in the lower respiratory tract which can be regarded as a point of similarity between COVID 19 and MERS. Also, the viral load was noted in the stool samples of the included cases, indicating a possible fecal-oral route of infection for COVID 19 [25Chan Jasper Fuk-Woo, Yuan Shuofeng, Kok Kin-Hang, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster Lancet 2020; 395: 514-23. Published Online January 24, 2020].

Yang S et al. graded the included cases in their study into 4 types on the basis of their type and size. Type 1 was defined as pure GGO with a mean lesion size of 1.37+_1.08cm. Type 2 was defined as GGO with pulmonary consolidation having a mean lesion size of 2.12 +_2 cm. Type 3 was defined as GGO with interlobular septal thickening having a mean size of 4.7 +_2.58 cm. Type 4 was defined as pure wide consolidation with a mean lesion size of 1.52+_0.88cm [26Yang S, Shi Y, Lu H, et al. Clinical and CT features of early stage patients with COVID-19: a retrospective analysis of imported cases in Shanghai, China. Eur Respir J in press
[http://dx.doi.org/10.1183/13993003.00407-2020] [PMID: 32217649]
].

A study conducted by Soon Ho Yoon et al. in Korea, the only study in this systematic review outside of China, graded the disease on a 5 point scale – 1 as normal findings, 2 as patchy GGO with or without hyperinflation with or without bronchial wall thickening, 3 as unifocal alveolar consolidation in a single lung segment or a lung lobe, 4 as multifocal alveolar consolidation in multiple lung segments or lung lobes whereas 5 as diffuse alveolar consolidation [27Yoon SH, Lee KH, Kim JY, et al. Chest radiographic and CT findings of the 2019 novel coronavirus disease (COVID-19): Analysis of nine patients treated in korea. Korean J Radiol 2020; 21(4): 494-500.
[http://dx.doi.org/10.3348/kjr.2020.0132] [PMID: 32100485]
]. Out of the included 2327 patients, 10 patients died. These were reported in a study conducted by Mingli Yuan et al. with the study mortality rate being equal to 2.7% [28Yuan M, Yin W, Tao Z, Tan W, Hu Y. Association of radiologic findings with mortality of patients infected with 2019 novel coronavirus in Wuhan, China. PLoS One 2020; 15(3)e0230548
[http://dx.doi.org/10.1371/journal.pone.0230548] [PMID: 32191764]
]

Another study by Feng Pan et al. graded COVID 19 cases on the basis of patient quartiles observed from the day of first CT examination of chest till the 26th day as follows: Stage 1 (0-4 days): ground-glass opacities (GGO); Stage-2 (5-8d days): increased crazy-paving pattern 9; Stage-3 (9- 13days): consolidation; Stage-4 (≥14 days): gradual resolution of consolidation without crazy-paving pattern [29Pan F, Ye T, Sun P, et al. Time course of lung changes on chest CT during recovery from 2019 novel coronavirus (COVID-19) pneumonia. Radiology 2020; •••200370].

Taking selective involvement of lung lobes, a study conducted by Chung M et al. reported that the right lower lobe was the most affected, followed by right upper, left upper, and left lower lobes equally [30Chung M, Bernheim A, Mei X, et al. CT imaging features of 2019 novel coronavirus (2019-nCoV). Radiology 2020; 295(1): 202-7.
[http://dx.doi.org/10.1148/radiol.2020200230] [PMID: 32017661]
]. On the same note, Bernheim reported that the most affected lung lobe was the right lower lobe, followed by the left lower lobe, left upper lobe, right upper lobe and right middle lobe at last [31Bernheim A, Mei X, Huang M, et al. Chest CT findings in coronavirus disease-19 (COVID-19): Relationship to duration of infection. Radiology 2020; 295(3)200463
[http://dx.doi.org/10.1148/radiol.2020200463] [PMID: 32077789]
]. Therefore, the right lower lobe was reported as the most affected lobe in 2 different independent retrospective studies.

The role of computed tomography as a screening modality remains incomplete without proper points of differentiation of COVID 19 from its distant relatives – adenovirus pneumonia, H1N1 influenza, SARS, and MERS. There are some points of differentiation, which are subtle but notable. Adenovirus pneumonia mostly affects children and presents with pleural effusion, pneumothorax, enlargement of lung hila, emphysematous changes in both mediastinum as well as the subcutaneous planes [32Zhao W, Zhong Z, Xie X, Yu Q, Liu J. Relation Between Chest CT Findings andClinical Conditions of Coronavirus Disease (COVID-19) Pneumonia: A MulticenterStudy. AJR Am J Roentgenol 2020; •••: 1-6.
[http://dx.doi.org/10.2214/AJR.20.22834] [PMID: 32603222]
].

Typical CT features in H1N1 influenza include GGO and consolidation along with peribronchial thickening, whereas those of SARS include large areas of consolidation along with air bronchograms [33Li P, Zhang JF, Xia XD, et al. Serial evaluation of high-resolution CT findings in patients with pneumonia in novel swine-origin influenza A (H1N1) virus infection. Br J Radiol 2012; 85(1014): 729-35.
[http://dx.doi.org/10.1259/bjr/85580974] [PMID: 22167502]
, 34Wang JT, Sheng WH, Fang CT, et al. Clinical manifestations, laboratory findings, and treatment outcomes of SARS patients. Emerg Infect Dis 2004; 10(5): 818-24.
[http://dx.doi.org/10.3201/eid1005.030640] [PMID: 15200814]
]. MERS-CoV shows ground-glass opacity followed by consolidation. Both ground-glass opacity and consolidation are apparent in 1/10 th of cases. Consolidation can be patchy, confluent, or nodular with an intertwined air bronchogram, as well as a peripheral mid lung zone and peripheral lower lung zone predominance with lung parenchymal abnormalities eventually spreading to the central area and bilateral upper lobes. Unifocal involvement is more common than multifocal involvement [35Das KM, Lee EY, Enani MA, et al. CT correlation with outcomes in 15 patients with acute Middle East respiratory syndrome coronavirus. AJR Am J Roentgenol 2015; 204(4): 736-42.
[http://dx.doi.org/10.2214/AJR.14.13671] [PMID: 25615627]
, 36Das KM, Lee EY, Al Jawder SE, et al. Acute Middle East respiratory syndrome coronavirus: temporal lung changes observed on the chest radiographs of 55 patients. AJR 2015; 205(web): W267-74.
[http://dx.doi.org/10.2214/AJR.15.14445]
].

Therefore, it is clear that there exists an increasing resemblance between the radiological features of these two siblings – COVID 19 and MERS CoV apart from a single feature that unifocal involvement is more common in MERS, which is quite the opposite in the case of COVID 19. It is on this note that computed tomography of the chest derives its importance as a screening modality and makes itself well accounted for in this perspective.

5. STUDY LIMITATIONS

Most of the included studies were limited in terms of proper demographic details as well as the availability of data and detailed methodology therein.

CONCLUSION

This systematic review article aims at disseminating and clarifying the initial presenting radiological features on computed tomography scan of the chest in an RT-PCR positive case, providing a map for the radiologist to diagnose COVID 19 and help in differentiating it from its potential mimics, planning further treatment and management of such cases, thus cementing its position as a priceless screening modality for the same.

CONSENT FOR PUBLICATION

Not applicable.

STANDARDS OF REPORTING

PRISMA guidelines and methodology were followed.

FUNDING

None.

CONFLICT OF INTEREST

The authors declare no conflict of interest, financial or otherwise.

ACKNOWLEDGEMENTS

Declared none.

REFERENCES

[1] Coronavirus disease 2019 (COVID-19)—Symptoms and causes. Mayo Clinic Retrieved 14 April 2020. Available from URL : https://www.mayoclinic.org/diseases-conditions/coronavirus/symptoms-causes/syc-20479963
[2] Hui DS, I Azhar E, Madani TA, et al. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health - The latest 2019 novel coronavirus outbreak in Wuhan, China. Int J Infect Dis 2020; 91(February): 264-6.
[http://dx.doi.org/10.1016/j.ijid.2020.01.009] [PMID: 31953166]
[3] "WHO Director-General's opening remarks at the media briefing on COVID-19". World Health Organization (WHO)(Press release). Archived from the original on 11 March 2020 2020. Retrieved 12 March 2020. Available from URL : https://www.who.int/director-general/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020
[4] "Statement on the second meeting of the International Health Regulations (2005) Emergency Committee regarding the outbreak of novel coronavirus (2019-nCoV)".. World Health Organization(WHO). Archived from the original on 31 January 2020 2020. Retrieved 11 February 2020. Available from URL :https://www.who.int/news/item/30-01-2020-statement-on-the-second-meeting-of-the-international-health-regulations-(2005)-emergency-committee-regarding-the-outbreak-of-novel-coronavirus-(2019-ncov)
[5] "Hundreds of evacuees to be held on bases in California; Hong Kong and Taiwan restrict travel from mainland China".. The Washington Post Archived from the original on 7 February 2020 2020. Retrieved 11 February 2020. Available from URL :https://www.washingtonpost.com/world/asia_pacific/coronavirus-china-live-updates/2020/02/05/114ced8a-479c-11ea-bc78-8a18f7afcee7_story.html
[6] Coronavirus update (live).. Available from URL :https://www.worldometers.info/coronavirus/
[7] Jin YH, Cai L, Cheng ZS, et al. A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Mil Med Res 2020; 7(1): 4-5.
[http://dx.doi.org/10.1186/s40779-020-0233-6] [PMID: 32029004]
[8] Kim JY, Choe PG, Oh Y, et al. The first case of 2019 novel coronavirus pneumonia imported into Korea from Wuhan, China: implication for infection prevention and control measures. J Korean Med Sci 2020; 35: e61-6.
[9] Pan Y, Guan H, Zhou S, et al. Initial CT findings and temporal changes in patients with the novel coronavirus pneumonia (2019-nCoV): a study of 63 patients in Wuhan, China. Eur Radiol 2020; 30(6): 3306-9. Epub ahead of print
[http://dx.doi.org/10.1007/s00330-020-06731-x] [PMID: 32055945]
[10] Joob B, Wiwanitkit V. 18F-FDG PET/CT and COVID-19. Eur J Nucl Med Mol Imaging 2020; 47(6): 1348.
[http://dx.doi.org/10.1007/s00259-020-04762-6] [PMID: 32166511]
[11] Zou S, Zhu X. FDG PET/CT of COVID-19. Radiology 2020; 296(2)E118
[http://dx.doi.org/10.1148/radiol.2020200770] [PMID: 32142399]
[12] Deng Y, Lei L, Chen Y, Zhang W. The potential added value of FDG PET/CT for COVID-19 pneumonia. Eur J Nucl Med Mol Imaging 2020; 47(7): 1634-5.
[http://dx.doi.org/10.1007/s00259-020-04767-1] [PMID: 32198615]
[13] Lütje S, Marinova M, Kütting D, Attenberger U, Essler M, Bundschuh RA. Nuclear medicine in SARS-CoV-2 pandemia: 18F-FDG-PET/CT to visualize COVID-19. Nucl Med (Stuttg) 2020; 59(3): 276-80.
[http://dx.doi.org/10.1055/a-1152-2341] [PMID: 32259853]
[14] WHO database of publications on coronavirus disease (COVID-2019).. World Health Organization (WHO)(Press release) Accessed February 19, 2020. Available from URL :www.who.int/emergencies/diseases/ novel-coronavirus-2019/global-research-on-novelcoronavirus-2019-ncov2019
[15] Moher D, Liberati A, Tetzlaff J, Altman DG. PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009; 6e100009
[http://dx.doi.org/10.1371/journal.pmed.1000097]
[16] National Heart, Lung, and Blood Institute website.. Study quality assessment tools [Accessed February 16, 2020]; Available from URL : www.nhlbi.nih. gov/health-topics/study-quality-assessment-tools
[17] Liu KC, Xu P, Lv WF, et al. CT manifestations of coronavirus disease-2019: A retrospective analysis of 73 cases by disease severity. Eur J Radiol 2020; 126108941
[http://dx.doi.org/10.1016/j.ejrad.2020.108941] [PMID: 32193037]
[18] Hansell DM, Bankier AA, MacMahon H, McLoud TC, Müller NL, Remy J. Fleischner Society: glossary of terms for thoracic imaging. Radiology 2008; 246(3): 697-722.
[http://dx.doi.org/10.1148/radiol.2462070712] [PMID: 18195376]
[19] Ooi GC, Khong PL, Müller NL, et al. Severe acute respiratory syndrome: temporal lung changes at thin-section CT in 30 patients. Radiology 2004; 230(3): 836-44.
[http://dx.doi.org/10.1148/radiol.2303030853] [PMID: 14990845]
[20] Wong KT, Antonio GE, Hui DS, et al. Severe acute respiratory syndrome: radiographic appearances and pattern of progression in 138 patients. Radiology 2003; 228(2): 401-6.
[http://dx.doi.org/10.1148/radiol.2282030593] [PMID: 12759474]
[21] Rukmini S. https://theprint.in/opinion/current-rate-india-30000-covid-19-deaths-may-no-hospital-bed-june-data/385386/2020.
[22] Rubin GD, Ryerson CJ, Haramati LB, et al. The role of chest imaging in patient management during the COVID-19 Pandemic: A multinational consensus statement from the fleischner society. Radiology 2020; 296(1): 172-80.
[http://dx.doi.org/10.1148/radiol.2020201365] [PMID: 32255413]
[23] 2020.https://www.who.int/publications-detail-redirect/report-of-the-who-china-joint-mission-on-coronavirus-disease-2019-(covid-19)
[24] Cotran RS, Kumar V, Fausto N, Fausto N, Robbins SL, Abbas AK. Robbins and Cotran pathologic basis of disease 2005; 749. [ISBN 0-7216-0187-1.]
[25] Chan Jasper Fuk-Woo, Yuan Shuofeng, Kok Kin-Hang, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster Lancet 2020; 395: 514-23. Published Online January 24, 2020
[26] Yang S, Shi Y, Lu H, et al. Clinical and CT features of early stage patients with COVID-19: a retrospective analysis of imported cases in Shanghai, China. Eur Respir J in press
[http://dx.doi.org/10.1183/13993003.00407-2020] [PMID: 32217649]
[27] Yoon SH, Lee KH, Kim JY, et al. Chest radiographic and CT findings of the 2019 novel coronavirus disease (COVID-19): Analysis of nine patients treated in korea. Korean J Radiol 2020; 21(4): 494-500.
[http://dx.doi.org/10.3348/kjr.2020.0132] [PMID: 32100485]
[28] Yuan M, Yin W, Tao Z, Tan W, Hu Y. Association of radiologic findings with mortality of patients infected with 2019 novel coronavirus in Wuhan, China. PLoS One 2020; 15(3)e0230548
[http://dx.doi.org/10.1371/journal.pone.0230548] [PMID: 32191764]
[29] Pan F, Ye T, Sun P, et al. Time course of lung changes on chest CT during recovery from 2019 novel coronavirus (COVID-19) pneumonia. Radiology 2020; •••200370
[30] Chung M, Bernheim A, Mei X, et al. CT imaging features of 2019 novel coronavirus (2019-nCoV). Radiology 2020; 295(1): 202-7.
[http://dx.doi.org/10.1148/radiol.2020200230] [PMID: 32017661]
[31] Bernheim A, Mei X, Huang M, et al. Chest CT findings in coronavirus disease-19 (COVID-19): Relationship to duration of infection. Radiology 2020; 295(3)200463
[http://dx.doi.org/10.1148/radiol.2020200463] [PMID: 32077789]
[32] Zhao W, Zhong Z, Xie X, Yu Q, Liu J. Relation Between Chest CT Findings andClinical Conditions of Coronavirus Disease (COVID-19) Pneumonia: A MulticenterStudy. AJR Am J Roentgenol 2020; •••: 1-6.
[http://dx.doi.org/10.2214/AJR.20.22834] [PMID: 32603222]
[33] Li P, Zhang JF, Xia XD, et al. Serial evaluation of high-resolution CT findings in patients with pneumonia in novel swine-origin influenza A (H1N1) virus infection. Br J Radiol 2012; 85(1014): 729-35.
[http://dx.doi.org/10.1259/bjr/85580974] [PMID: 22167502]
[34] Wang JT, Sheng WH, Fang CT, et al. Clinical manifestations, laboratory findings, and treatment outcomes of SARS patients. Emerg Infect Dis 2004; 10(5): 818-24.
[http://dx.doi.org/10.3201/eid1005.030640] [PMID: 15200814]
[35] Das KM, Lee EY, Enani MA, et al. CT correlation with outcomes in 15 patients with acute Middle East respiratory syndrome coronavirus. AJR Am J Roentgenol 2015; 204(4): 736-42.
[http://dx.doi.org/10.2214/AJR.14.13671] [PMID: 25615627]
[36] Das KM, Lee EY, Al Jawder SE, et al. Acute Middle East respiratory syndrome coronavirus: temporal lung changes observed on the chest radiographs of 55 patients. AJR 2015; 205(web): W267-74.
[http://dx.doi.org/10.2214/AJR.15.14445]
[37] Huang Chaolin, Wang Yeming, Li Xingwang, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China Lancet 2020; 395: 497-506.
[38] Xie C, Jiang L, Huang G, et al. Comparison of different samples for 2019 novel coronavirus detection by nucleic acid amplification tests. Int J Infect Dis 2020; 93: 264-7.
[http://dx.doi.org/10.1016/j.ijid.2020.02.050] [PMID: 32114193]
[39] Liu F, Xu A, Zhang Y, et al. Patients of COVID-19 may benefit from sustained Lopinavir-combined regimen and the increase of Eosinophil may predict the outcome of COVID-19 progression. Int J Infect Dis 2020; 95: 183-91.
[http://dx.doi.org/10.1016/j.ijid.2020.03.013] [PMID: 32173576]
[40] Xu Xi, Yu Chengcheng, Qu Jing, et al. Imaging and clinical features of patients with 2019 novel coronavirus SARS-CoV-2 European Journal of Nuclear Medicine and Molecular Imaging 2019.
[41] Xu X-W, Wu X-X, Jiang X-G, et al. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series. BMJ 2020; 368: m606.
[http://dx.doi.org/10.1136/bmj.m606] [PMID: 32075786]
[42] Li Yan, Xia Liming. Coronavirus Disease 2019 (COVID-19): Role of Chest CT in Diagnosis and Management AJR 2020.
[43] Xia W, Shao J, Guo Y, Peng X, Li Z, Hu D. Clinical and CT features in pediatric patients with COVID-19 infection: Different points from adults. Pediatr Pulmonol 2020; 55(5): 1169-74.
[http://dx.doi.org/10.1002/ppul.24718] [PMID: 32134205]
[44] Li W, Cui H, Li K, Fang Y, Li S. Chest computed tomography in children withCOVID-19 respiratory infection. Pediatr Radiol 2020.
[http://dx.doi.org/10.1007/s00247-020-04656-7]
[45] Han R, Huang L, Jiang H, Dong J, Peng H, Zhang D. Early clinical and ct manifestations of coronavirus disease 2019 (COVID-19) pneumonia. AJR Am J Roentgenol 2020; 215(2): 338-43.
[http://dx.doi.org/10.2214/AJR.20.22961] [PMID: 32181672]
[46] Xiong Y, Sun D, Liu Y, et al. Clinical and High-Resolution CT Features of the COVID-19 Infection: Comparison of the Initial and Follow-up Changes. Invest Radiol 2020; 55(6): 332-9.
[http://dx.doi.org/10.1097/RLI.0000000000000674] [PMID: 32134800]
[47] Wu J, Wu X, Zeng W, et al. Chest CT findings in patients with coronavirus disease 2019 and its relationship with clinical features. Invest Radiol 2020; 55(5): 257-61.
[http://dx.doi.org/10.1097/RLI.0000000000000670] [PMID: 32091414]
[48] Zhang X, Cai H, Hu J, et al. Epidemiological, clinical characteristics of cases of SARS-CoV-2 infection with abnormal imaging findings. Int J Infect Dis 2020; 94: 81-7.
[http://dx.doi.org/10.1016/j.ijid.2020.03.040] [PMID: 32205284]
[49] Wu J, Feng CL, Xian XY, et al. Zhonghua Jie He He Hu Xi Za Zhi 2020; 43(0)E030 [Novel coronavirus pneumonia (COVID-19) CT distribution and sign features]. [Chinese.].
[50] Guan CS, Lv ZB, Yan S, et al. Imaging Features of Coronavirus disease 2019 (COVID-19): Evaluation on Thin-Section CTAcad Radiol 2020; S1076-6332(20): 30143-4.
[51] Song F, Shi N, Shan F, et al. Emerging 2019 Novel Coronavirus (2019-nCoV) Pneumonia. Radiology 2020; 295(1): 210-7.
[http://dx.doi.org/10.1148/radiol.2020200274] [PMID: 32027573]
[52] Xu YH, Dong JH, An WM, et al. Clinical and computed tomographic imaging features of novel coronavirus pneumonia caused by SARS-CoV-2. J Infect 2020; 80(4): 394-400.
[http://dx.doi.org/10.1016/j.jinf.2020.02.017] [PMID: 32109443]
[53] Fang Y, Zhang H, Xie J, et al. Sensitivity of chest CT for COVID-19: Comparison to RT-PCR. Radiology 2020; •••200432
[54] Shi H, Han X, Jiang N, et al. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect Dis 2020; 20(4): 425-34.
[http://dx.doi.org/10.1016/S1473-3099(20)30086-4] [PMID: 32105637]
[55] Yang W, Cao Q, Qin L, et al. Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19):A multi-center study in Wenzhou city, Zhejiang, China. J Infect 2020; 80(4): 388-93.
[http://dx.doi.org/10.1016/j.jinf.2020.02.016] [PMID: 32112884]
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