Comparison of initial high-resolution computed tomography (HRCT) features of coronavirus disease 2019 (COVID-19) pneumonia and other viral pneumonias

Introduction

Coronavirus disease 2019 (COVID-19) is highly infectious, has a long incubation period and is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (1,2). COVID-19 spreads at an alarming rate. As of April 20, COVID-19 had spread to 211 countries worldwide, with more than 2.3 million confirmed patients and 164,976 deaths. Currently, COVID-19 has become a global health crisis.

Early studies showed that almost all COVID-19 patients have pneumonia (3,4). However, at the same time of year, pneumonias caused by other pathogens are also common (5-7). Therefore, in this COVID-19 pandemic, the differential diagnosis of viral pneumonias is difficult but very important. Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) is the gold standard for the diagnosis of viral pneumonia. However, recent reports have shown that the sensitivity of qRT-PCR for the detection of COVID-19 is as low as 60–71% (8), and the high false-negative rate limits the rapid identification of viral pneumonia by qRT-PCR.

Computed tomography (CT) can play an important role in the diagnosis and treatment of viral pneumonia (9-11). Studies have shown that the typical CT findings of COVID-19 include ground-glass opacity (GGO) and partial consolidation in the peripheral areas of both lungs with a round shape and without cavities, pleural effusion and lymphadenopathy (12,13). After treatment, chest CT can detect the dynamic changes in COVID-19 (14,15). Other studies have shown that the imaging findings of viral pneumonias and bacterial pneumonias are different (9,10), but little is known about the differences in imaging findings between COVID-19 and other viral pneumonias.

Therefore, the purpose of this study was to clarify the basic clinical features and potential differences in high-resolution computed tomography (HRCT) findings of COVID-19 and other viral pneumonias.

We present the following article in accordance with the STROBE reporting checklist (available at http://dx.doi.org/10.21037/apm-20-2479).

Methods

Patients

The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The retrospective study was approved by the institutional committee of the First Affiliated Hospital of Kunming Medical University. Informed consent was waived because the study was retrospective in design. This multicenter study retrospectively analyzed patients who underwent chest CT for suspected viral pneumonia because of fever, fatigue or respiratory tract symptoms at 20 hospitals in Yunnan Province, China, from March 1, 2015, to March 15, 2020. qRT-PCR assays were performed to identify influenza A virus, influenza B virus, respiratory syncytial virus, parainfluenza virus, adenovirus, SARS coronavirus, SARS-CoV-2, Epstein-Barr virus, measles virus, and other viruses from nasopharyngeal swabs or bronchoalveolar lavage fluid. The study only included pneumonia patients infected with one virus, and patients with multiple respiratory viruses or bacterial or fungal infections were excluded (10 cases, 2.83%). A total of 353 viral pneumonia patients were included in this study. The selection process for viral pneumonia patients is shown in Figure 1. According to the clinical guidelines for COVID-19 (16),of 121 COVID-19 patients, 22 were mild, 76 were moderate, 20 were severe, and 3 were critical. In addition, the study excluded one case of Epstein-Barr virus, two cases of herpes virus, one case of measles virus, two cases of varicella virus, one case of mumps virus and one case of adenovirus. All patients were admitted within 4–7 days after the onset of acute symptoms. The patient’s age, sex, history of exposure, and clinical symptoms (fever, cough, fatigue, dyspnea, sore throat, runny nose, expectoration, headache, muscle aches, chest tightness, chest pain, nausea and vomiting, diarrhea or no obvious symptoms), underlying diseases [hypertension, diabetes, coronary heart disease, liver disease, tumor, acquired immunodeficiency syndrome (AIDS) and leukopenia], hospital admission time and CT examination time were recorded. Patients completed the chest CT examination within 48 h of admission. According to the virus found in the lungs, the patients were divided into four groups: cytomegalovirus (CMV), influenza A virus, influenza B virus and COVID-19. The number of cases from each hospital is shown in Table 1. All patients were from Yunnan Province, China.

Figure 1 Flowchart of the study design and the participants included in the analysis. COVID-19, coronavirus disease 2019; CMV, cytomegalovirus; CT, computed tomography. DR, digital radiography; DICOM, digital imaging and communications in medicine.

Table 1 Institution and number of cases in this multicenter study
Full table

CT protocol

HRCT examination: CT scanners with ≥16 detector rows (Siemens, Germany; Philips, The Netherlands; and GE, USA) were used. The patient was scanned in the supine position while breath holding after inhalation. The scanning range was from the thoracic inlet to the costophrenic angles. Scanning parameters: detector collimation width 64 mm × 0.6 mm or 128 mm × 0.6 mm, tube voltage 120 kV, adaptive tube current, high-resolution algorithm reconstruction, reconstruction layer thickness 1 or 1.5 mm and layer spacing 1.5 mm. CT machines dedicated to COVID-19 patients are used for chest examinations, using disposable sheets to avoid cross-infection. After the patient’s CT examination, disinfect the examination bed and floor, and disinfect the computer room and air with ultraviolet rays.

Chest CT analysis

Three radiologists were blinded to the qRT-PCR results, all patient information, and the type of viral pneumonia. First, two experienced radiologists (Yilong Huang and Yuanming Jiang) in the cardiothoracic group independently read the radiographs. When their opinions were inconsistent, they discussed them and reached a consensus, which was reviewed and confirmed by the third senior radiologist in the cardiothoracic group (Bo He). The morphological signs of the first CT examination after admission were analyzed. The CT imaging evaluation included lesion distribution (peripheral, central), location (left upper lobe, left lower lobe, right upper lobe, right middle lobe and right lower lobe) and signs (GGO, partial consolidation, multifocal consolidation, focal consolidation, fibrous stripes, septal thickening, intralobular interstitial thickening, subpleural lines, crazy-paving pattern, tree-in-bud, bronchial wall thickening, bronchiectasis, vascular thickening, air bronchogram, halo sign, mediastinal lymphadenectasis, pleural thickening and pleural effusion) (9,10,12,17). The window width and level were set to 1,600/–600 Hounsfield units, respectively.

Statistical analysis

SPSS 25.0 software was used for statistical analysis. Count data are expressed as frequency, and measurement data are expressed as x±s. One-way analysis of variance (ANOVA) was used for age, which had a normal distribution, and the least significant difference method was used for pairwise comparison. The distribution, location and signs of pulmonary lesions in different viral pneumonias were compared using χ² or Fisher’s exact probability method. The Z-test (Bonferroni method) was used for pairwise comparisons. A P value <0.05 was considered statistically significant.

Results

Patients’ clinical characteristics

This study included 262 patients with viral pneumonia, comprising 121 COVID-19 patients and 141 patients with non-COVID-19 pneumonias (CMV, 31 cases; influenza A virus, 82 cases, influenza B virus, 20 cases; other viruses with less than 2 cases, 8). The mean age of the COVID-19 patients (42.88±17.67) was lower than that of the influenza A patients (55.50±18.46). Of the 121 COVID-19 patients, 54 (44.63%) were male, and 97 (68.79%) of the 141 non-COVID-19 patients were male. All COVID-19 patients had a history of living in Hubei or had close contact with other COVID-19 patients. Five patients with influenza A had a history of poultry contact. Among the four viral pneumonias, fever and cough were the most common clinical symptoms, and the highest proportion was found in the influenza A patients (P<0.000). Compared with the COVID-19 patients, the non-COVID-19 patients had higher proportions of fatigue, sore throat, expectoration and chest tightness, whereas the COVID-19 patients were more likely to be asymptomatic, and the differences were statistically significant (all P<0.000). Compared with the other viral pneumonia patients, the CMV pneumonia patients had higher proportions of AIDS and leukopenia (all P<0.000). Table 2 shows the clinical characteristics of the included patients.

Table 2 Basic clinical characteristics of 262 patients with viral pneumonia
Full table

Distribution and location of the pulmonary lesions of COVID-19 and other viral pneumonias

On the first CT examination, 33 COVID-19 patients were negative. Figure 2 shows the comparisons of the distribution and location of pulmonary lesions found on the first CT examinations of CMV, influenza A virus, influenza B virus, non-COVID-19 and COVID-19 patients. There were no lesions in the central lung alone in the COVID-19 patients. The proportion of peripheral lesions in the COVID-19 patients was significantly higher than in the patients with other viral pneumonias (all P<0.000), and the pulmonary lesions of CMV pneumonia were mainly distributed in the peripheral and central lung. Regarding the pulmonary lesions in COVID-19, influenza A virus and influenza B virus, more were found in the left and right lower lobes than in other lung lobes (P<0.05). However, in the CMV pneumonia patients, there was no significant difference in the number of lesions found in the different lung lobes; however, more CMV patients than patients with other viral pneumonias had lesions in the left upper lobe, right upper lobe, and right middle lobe, and the differences were statistically significant (P<0.05).

Figure 2 Distribution and location of COVID-19 pneumonia and other viral pneumonias: (A) lesion distribution and (B) lesion location. Data are reported as percentages. *, P<0.05 vs. COVID-19 pneumonia. COVID-19, coronavirus disease 2019; CMV, cytomegalovirus.

Chest CT findings of viral pneumonia

The first CT images of pulmonary lesions in CMV, influenza A virus, influenza B virus, Non-COVID-19 and COVID-19 were compared (Table 3). Compared with Non-COVID-19 pneumonias, COVID-19 was more likely to present as GGO (96.59% vs. 46.81%, P<0.001), intralobular interstitial thickening (63.64% vs. 19.15%, P<0.001), vascular thickening (55.68% vs. 4.96%, P<0.001) and halo signs (59.09% vs. 14.89%, P<0.001). In the early stage of COVID-19, extensive consolidation (7.95% vs. 39.72%, P<0.001), fibrous stripes (15.91% vs. 34.75%, P=0.001), subpleural lines (7.95% vs. 39.72%, P<0.001), crazy-paving pattern (0.00% vs. 14.18%, P<0.001), tree-in-bud (1.14% vs. 27.66%, P<0.001), mediastinal lymphadenectasis (14.18% vs. 1.14%, P<0.001), pleural thickening (56.74% vs. 38.64%, P=0.013) and pleural effusion (25.53% vs. 0.00%, P<0.001) were rare. Table 4 shows the sensitivity, specificity, and accuracy of these meaningful signs in distinguishing COVID-19 from non-COVID-19. Figures 3-6 show representative cases of CMV, Influenza A virus, Influenza B virus, and COVID-19 pneumonia.

Table 3 Comparison of CT findings of different viral pneumonias
Full table

Table 4 Diagnosis performance of CT findings in distinguishing COVID-19 from Non-COVID-19
Full table

Figure 3 Chest CT findings in 54-year-old male with CMV pneumonia combined with AIDS and leukopenia. (A,B,C,D,E,F) Diffuse GGO and multifocal consolidation in both lungs. (A) Bronchiectasis (black arrow), (B) left intralobular interstitial thickening (white arrow), (E) mediastinal lymphadenectasis (white arrow), and (F) left pleural effusion (white arrow). (A,B,E,F): axial view; (C): coronal view; (D): sagittal view. AIDS, acquired immunodeficiency syndrome; COVID-19, coronavirus disease 2019; CMV, cytomegalovirus; CT, computed tomography; GGO, ground-glass opacity.

Figure 4 Chest CT findings of influenza A pneumonia in a 44-year-old male (H1N1 infection). (A,B,C,D) Multifocal GGO, partial consolidation and consolidation in both lungs (arrow in A, D shows consolidation in right middle lobe); (B) tree-in-bud (white arrow). (C) Coronal view. CT, computed tomography; GGO, ground-glass opacity.

Figure 5 Chest CT findings of influenza B pneumonia in (A,B,C) 6-year-old male and (D,E,F) 39-year-old male. (A,B,C) Multifocal GGO with partial consolidation in both lungs with a parenchymal band (A, black arrow), air bronchogram, pleural thickening, and pleural effusion. (D) Multifocal GGO and tree-in-bud in lower lobes of both lungs, with bronchial wall thickening (E) and partial consolidation and parenchymal band (F). (A,B,C,D,E,F) Axial view.

Figure 6 Chest CT findings of COVID-19 pneumonia in (A,B,C) 63-year-old female and (D,E,F) 66-year-old female. (A,B,C) Multifocal GGO in both lungs. (B) Vascular thickening and intralobular interstitial thickening, and (C) pleural thickening. (D,E,F) Multifocal GGO in both lungs. (D) Intralobular interstitial thickening, (D,E) vascular thickening and (F) pleural thickening. (A,B,D,F) Axial view; (C,F) coronal view.

Discussion

COVID-19 is threatening human health and safety worldwide. Considering the similarity in outbreak time and clinical manifestations between COVID-19 and other viral pneumonias, this study systematically analyzed the differences in the first chest CT findings between COVID-19 and other viral pneumonias. We found that although it is difficult to completely differentiate COVID-19 from other viral pneumonias, COVID-19 has some unique CT features.

We included 262 patients with confirmed viral pneumonia. The main clinical manifestations of all patients were fever and cough. However, the incidence of fever and cough in COVID-19 patients was low, which was consistent with previous results from Zhao et al. (18) and Tang et al. (19) and may be related to the low virulence of SARS-CoV-2. In this study, 15 patients (12.40%) showed no obvious clinical symptoms, and 33 patients (27.27%) had negative CT findings, which was consistent with the results of Guan et al. (2). However, the patients’ RT-PCT results were still positive for SARS-CoV-2, indicating that they were still infectious and should be isolated for observation and antiviral treatment. It is worth noting that patients with AIDS or leukopenia were more prone to developing CMV pneumonia.

The periphery of the lower lobes of both lungs was the most common area for lesions in COVID-19 and influenza pneumonias, which is consistent with the results of previous studies (17). However, we found that a high proportion of COVID-19 lesions occurred in the peripheral area, whereas CMV pneumonia was usually diffusely distributed in both lungs. This study systematically analyzed and compared the CT findings of COVID-19 and other viral pneumonias. We found that GGO was more common in COVID-19 than in other viral pneumonias, and multifocal consolidation was more common in other viral pneumonias, a result that was consistent with previous studies (17,19). To the best of our knowledge, studies comparing the microscopic differences between COVID-19 and other viral pneumonias are still rare. The GGO, intralobular interstitial thickening, vascular thickening and halo sign were more likely to occur in COVID-19 than in other viral pneumonias, and fibrous stripes, subpleural lines, crazy-paving pattern, tree-in-bud, pleural effusion and mediastinal lymphadenectasis occurred less frequently in COVID-19 than in other viral pneumonias. The pathophysiological mechanisms of these characteristic imaging changes are still unclear. However, the difference in CT findings in COVID-19 and other viral pneumonia may be closely related to the difference in virus types. After autopsy of patients who died of COVID-19 and influenza (20), histological results revealed diffuse alveolar injury with perivascular T cell infiltration in the peripheral lung tissue of COVID-19. The pulmonary vessels of Covid-19 patients have severe endothelial damage, and extensive thrombosis is accompanied by microvascular disease. The incidence of alveolar capillary thrombosis in Covid-19 patients is 9 times that of influenza patients. And this also may be related to the slower development of COVID-19 than other viral pneumonias (19).It is worth noting that tree-in-bud was observed in 27.66% of influenza pneumonia cases, and similar results were observed by Shiley et al. (21), but almost no tree-in-bud was observed in COVID-19. Compared with other viral pneumonias, CMV pneumonia often presents as a characteristic bronchiectasis, and immunocompromise is an important risk factor. In previous studies, it has been called “AIDS associated bronchiectasis” (22). With this information combined with the clinical data, radiologists can better identify the type of viral pneumonia (23). Currently, Duan et al. and Gu et al. observe the CT findings of COVID-19 patients in different populations, such as children, adults, and the elderly (24,25). They found that compared with adults, pediatric COVID-19 patients are characterized by lower incidence, milder clinical symptoms, shorter course of disease, and fewer severe cases. In the elderly, lung lesions are more likely to progress. Study has shown that age is an independent wind direction factor for COVID-19 (26). In-hospital mortality increases linearly with age, with the highest mortality in patients over 80 years of age.

This study has some limitations. First, although we tried our best to collect the clinical and imaging data of patients with viral pneumonia in Yunnan Province, the numbers of confirmed cases of adenovirus, measles virus, herpes virus and other viruses were relatively small, but the differences in imaging signs among them are very interesting and will be studied in the future. Second, most of the included CMV pneumonia patients had AIDS, which is likely to cause a selection bias regarding other CMV pneumonia patients. Third, different populations, such as infants, children and elderly adults, may be susceptible to different viruses, and their signs of pulmonary lesions on imaging might be different. Because of the sample size, we did not perform a subgroup analysis for age. In future studies, more effort should be made to determine the differences in the imaging characteristics of different populations.

In summary, the analysis and comparison of the chest CT findings of COVID-19 and other viral pneumonias showed that the chest CT findings partially overlapped, but many significant imaging features could still be observed, which is helpful for the early differential diagnosis of COVID-19 and the development of more accurate clinical diagnosis and treatment strategies.

Acknowledgments

The authors express their appreciation for all the hospital staff for their efforts to combat the COVID-19 outbreak. Thank you to all the patients who participated in this study.

Funding: None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at http://dx.doi.org/10.21037/apm-20-2479

Data Sharing Statement: Available at http://dx.doi.org/10.21037/apm-20-2479

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/apm-20-2479). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The retrospective study was approved by the institutional committee of the First Affiliated Hospital of Kunming Medical University. Informed consent was waived because the study was retrospective in design.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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(English Language Editor: A. Kassem)