key: cord-0335733-pym0remz
authors: COMERT, R. G.; CINGOZ, E.; MESE, S.; DURAK, G.; TUNACI, A.; AGACFIDAN, A.; ONEL, M.; ERTURK, S. M.
title: Radiological Imaging of Viral Pneumonia Cases Identified Before the COVID-19 Pandemic Period and COVID-19 Pneumonia Cases Comparison of Characteristics
date: 2022-05-14
journal: nan
DOI: 10.1101/2022.05.11.22274305
sha: 19032685a7816f55d5f86ac181f9cd6491589ce5
doc_id: 335733
cord_uid: pym0remz

Background: Thoracic CT imaging is widely used as a diagnostic method in the diagnosis of COVID-19 pneumonia. Radiological differential diagnosis and isolation of other viral agents causing pneumonia in patients gained importance, especially during the pandemic period. Aims: We aimed to investigate whether there is a difference between the CT imaging findings characteristically defined in COVID-19 pneumonia and the findings detected in pneumonia due to other viral agents, and which finding may be more effective in the diagnosis. Study Design: The study included 249 adult patients with pneumonia found in thorax CT examination and positive COVID-19 RT-PCR test and 94 patients diagnosed with non-COVID pneumonia (viral PCR positive, no bacterial/fungal agents were detected in other cultures) from the last 5 years before the pandemic. It was retrospectively analyzed using the PACS System. CT findings were evaluated by two radiologists with 5 and 20 years of experience who did not know to which group the patient belonged, and it was decided by consensus. Methods: Demographic data (age, gender, known chronic disease) and CT imaging findings (percentage of involvement, number of lesions, distribution preference, dominant pattern, ground-glass opacity distribution pattern, nodule, tree in bud sign, interstitial changes, crazy paving sign, reversed halo sign, vacuolar sign, halo sign, vascular enlargement, linear opacities, traction bronchiectasis, peribronchial wall thickness, air trapping, pleural retraction, pleural effusion, pericardial effusion, cavitation, mediastinal/hilar lymphadenopathy, dominant lesion size, consolidation, subpleural curvilinear opacities, air bronchogram, pleural thickening) of the patients were evaluated. CT findings were also evaluated with the RSNA consensus guideline and the CORADS scoring system. Data were divided into two main groups as non-COVID-19 and COVID-19 pneumonia and compared statistically with chi-square tests and multiple regression analysis of independent variables. Results: Two main groups; RSNA and CORADS classification, percentage of involvement, number of lesions, distribution preference, dominant pattern, nodule, tree in bud, interstitial changes, crazy paving, reverse halo vascular enlargement, peribronchial wall thickness, air trapping, pleural retraction, pleural/pericardial effusion, cavitation and mediastinal/hilar lymphadenopathy were compared, significant differences were found between the groups (p < 0.01). Multiple linear regression analysis of independent variables found a significant effect of reverse halo sign ({beta} = 0.097, p <0.05) and pleural effusion ({beta} = 10.631, p <0.05) on COVID-19 pneumonia. Conclusion: Presence of reverse halo and absence of pleural effusion was found to be efficient in the diagnosis of COVID-19 pneumonia.

Viruses are the most common cause of respiratory tract infections. It has been reported that viruses such as influenza, HPIV, Adenovirus, RSV, HMPV can cause lower respiratory tract infections in individuals with both normal immune systems and immunodeficiency; It is known that viruses such as rhinovirus, endemic coronaviruses, CMV, Herpes Simplex Virus (HSV), Varicella Zoster Virus (VZV), HBoV can cause lower respiratory tract infection only in those with immunodeficiency. 1 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 14, 2022. ;  https://doi.org/10.1101/2022.05.11.22274305 doi: medRxiv preprint Coronavirus disease (COVID) was first reported by the World Health Organization (WHO) on December 31, 2019, with pneumonia cases of unknown origin being reported in Wuhan, China, and then reached the pandemic stage in March 2020. 2 SARS-CoV-2, the causative agent of COVID-19 disease, is an enveloped virus whose genetic material consists of single-stranded RNA. The RT-PCR test, in which viral nucleic acid is detected, is accepted as the gold standard for the detection of SARS-CoV-2 virus. 3 It is reported that COVID-19 infection can be examined in 3 stages, including the first asymptomatic period, secondly the upper and lower respiratory tract response, and then widespread lung involvement that can progress to ARDS. 4 In the COVID-19 disease, approximately 80% of the patients are asymptomatic or limited to mild to moderate symptoms in the first two stages; It is reported that in the remaining 15-20% of the patients, pulmonary ground glass opacity-consolidation is detected as a radiological finding due to the inflammatory response in the lung. 4 If there is no risk factor for the progression of the disease in patients with mild clinical symptoms suspicious for COVID-19, there is no imaging indication, and imaging should be performed in cases with worsening respiratory system symptoms; It has been reported that imaging can be performed to provide medical triage in cases with high suspicion for COVID-19 with moderate-to-severe symptoms if clinical conditions require it. 5 A normal chest X-ray does not exclude COVID-19 pneumonia, especially in cases with mild pneumonia or in the early stage of the disease. 5, 6 It has been reported that CT cannot be used . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 14, 2022. ;  https://doi.org/10.1101/2022.05.11.22274305 doi: medRxiv preprint as a screening test, since the positive predictive value of thoracic CT in the diagnosis of COVID-19 is 92% high while the negative predictive value is 42% 7 and the absence of CT findings in the early phase of the disease should not exclude the possibility of COVID-19 disease. 2, 8 Clinical It has been reported that the combination of repetitive RT-PCR test and thoracic CT examination is beneficial in cases with suspected COVID- 19. 9 Imaging findings of viral pneumonia may overlap with non-viral infections and inflammatory conditions. Some diagnostic patterns of viral pneumonia help to make differential diagnoses in the early stages of infection, to reduce unnecessary antibiotic use, and to prevent contagion. 1 In thorax CT in viral pneumonia; reticular opacities due to interstitial inflammation, ground-glass opacity(GGO) due to alveolar edema, patchy consolidation, localized atelectasis, peribronchovascular thickening, centrilobular nodular opacities, tree in bud pattern, interlobular septal thickening, etc. findings develop, but it is reported that diagnosis cannot be made based on imaging findings alone. 10, 11 However, detection of centrilobular nodular opacities, pleural effusion, and lymphadenopathy more frequently in non-COVID-19 viral pneumonia has been reported to help differential diagnosis. 11 Computed tomography of the thorax is used as a common diagnosis method in the diagnosis of Coronavirus Disease 2019 (COVID-19) which causes pandemics. As in the pre-pandemic period, during the COVID-19 pandemic period, the radiological differential diagnosis of other viral agents that cause pneumonia in patients with normal immunity or in immunosuppressed patients with seasonal epidemics has gained importance in early diagnosis and isolation.

Therefore, it was aimed to investigate the difference between CT imaging findings defined as characteristic in COVID-19 pneumonia and CT findings detected in pneumonia due to other viral agents previously encountered.

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As the COVID group, 249 COVID-19 patients aged 18 years and older, who applied to our hospital, were found to have positive Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) in the nasopharyngeal swab samples taken at the application, and pneumonia was detected in the thorax CT examination at admission has been included. 

FTD Respiratory pathogens 21 (fast-tract DIAGNOSTICS, Luxembourg) kit, which is based on the reverse transcriptase Multiplex PCR method, was used for the Viral Respiratory Panel.

Artus CMV QS-RGQ kit QIAsymphony RGQ system (QIAGEN) as a CMV DNA quantitative test between January 2015 and September 2018 (measuring range of the kit: 79.4 copies / mL-100,000,000 copies / mL, 1 copy / mL = 1.64 IU / mL), COBAS Ampliprep / taqman CMV test and COBAS Ampliprep / Taqman system were used between September . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 

Thorax CT examination protocol; tube voltage 120kV with 64 detectors, Aquillion, Toshiba and 16 detectors Brilliance, Philips; tube current modulation 50-150 mA; range 0.85-1.4; image slice thickness is 1 mm-5 mm, CT images obtained in the supine position in full inspiratory in all patients are -600 to +1600 HU for lung parenchyma, +50 to +350 HU for mediastinum using window width; it was retrospectively analyzed using the PACS System. CT findings were evaluated by two radiologists with 5 and 20 years of experience who did not know to which group the patient belonged, and it was decided by consensus.

Age, gender, known chronic disease of the patients; CT findings include the percentage of involvement, number of lesions, distribution preference, dominant pattern, ground-glass opacity distribution pattern, nodule, tree in bud sign, interstitial changes, crazy paving sign, reversed halo sign, vacuolar sign, halo sign, vascular enlargement (vascular structures with . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 14, 2022. ; https://doi.org/10.1101/2022.05.11.22274305 doi: medRxiv preprint increased calibration relative to the proximal, which is thought to be due to mediators that cause hyperemia, in the area of inflammation or in the periphery of the lesion 12 ), linear opacities, traction bronchiectasis, peribronchial wall thickness, air trapping, pleural retraction, pleural effusion, pericardial effusion, cavitation, mediastinal/hilar lymphadenopathy, dominant lesion size, consolidation, subpleural curvilinear opacities, air bronchogram, pleural thickening were examined. CT findings were also evaluated with the RSNA consensus guideline and the CORADS scoring system, data obtained were divided into two main groups as non-COVID-19 pneumonia and COVID-19 pneumonia; statistically compared with chisquare tests and multiple regression analysis of independent variables.

In the study, the age ranged between 18 and 91, with a mean of 51.99±16.99, with a median value of 53. The age of the non-COVID-19 patient group ranged from 18 to 84, with a mean of 49.29±19.43. The age of the COVID-19 patient group ranged from 18 to 91, with a mean of 53.01±15.91. In the study, 59.5% (n=204) of the patients were male, while 40.5% (n=139) were female. While 58.5% (n=55) of the non-COVID-19 pneumonia patient group were male, 41.5% (n=39) were female. Of the COVID-19 pneumonia patient group, 59.8% (n=149) were male, while 40.2% (n=100) were female. (Table 1) While 33% (n=113) of the COVID-19 patient group had no chronic disease, the entire non- . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 14, 2022. ; https://doi.org/10.1101/2022.05.11.22274305 doi: medRxiv preprint n=2); chronic kidney disease (%2,3 n=8) vs (%19,4 n=21); extrapulmonary malignancy (%3,2 n=11) vs (%21,3 n=23); conditions related to immunodeficiency (%3,5 n=12) vs (%28,7 n=31); others (%14,9 n=51) vs (%14,8 n=16) compared to non-COVID-19 patients. (Table 1) In (Table 2) In the multiple linear regression analysis performed to determine the effect of independent variables on COVID-19 pneumonia; when the regression coefficients were examined, it was found that those with reversed halo sign (β = 0.097, p <0.05) and those with pleural effusion (β = 10.631, p <0.05) had a significant effect on COVID-19 pneumonia; it was found that COVID-19 pneumonia was more common in patients with reversed halo sign compared to those without pleural effusion. (Table 3 )

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In the literature, there is information that the pulmonary target sign, which is defined as a variant of the reversed halo sign by making a difference with the hyperdense dot sign in the center, is diagnostic in COVID-19 viral pneumonia. 16, 17 In our study, we did not evaluate the presence of central hyperdense dot as a separate parameter, but we think that we contributed to the literature by concluding that the presence of the reversed halo sign is valuable in differentiating other viral pneumonia from COVID-19. (Figure 6 .)

In the literature 18 Compared with a study 19 conducted with COVID-19 patients whose diagnosis was confirmed by RT-PCR and who had pneumonia on thorax CT and non-COVID-19 patients whose respiratory panel PCR was positive and pneumonia on CT, our study differed from COVID- 19 . We compared two groups without COVID-19 for the RSNA consensus guideline and the is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 14, 2022. ; https://doi.org/10.1101/2022.05.11.22274305 doi: medRxiv preprint COVID-19 pneumonia in terms of RSNA consensus guideline and CORADS with patients diagnosed with non-COVID-19 viral pneumonia as in our study. According to the RSNA consensus guidelines; the scores of atypical group and CORADS 2, indetermined group and CORADS 3 correspond to each other and were found to be significant in favor of non-COVID-19 viral pneumonia. The RSNA typical group and the CORADS 5 score also correspond to each other and were found to be similarly significant in favor of COVID-19 pneumonia. We think that the lack of diagnostic difference between the groups in the CORADS 4 score may be due to the fact that frequent findings in other viral pneumonia such as small but peripherally localized unilateral GGO and multifocal consolidation without other typical findings are included in this category. Although it has been reported in studies reporting that dividing the RSNA indeterminate category into 3 and 4 in the CORADS system limits the intra-observer variability 8 , since these assessment systems were developed during the pandemic process, when the prevalence of COVID-19 decreases after the pandemic is over, it is an issue that needs to be studied how much it can be applied to incidental thoracic CT findings independent of the clinic and In the future, these studies may contribute to improving the diagnostic efficiency of CORADS. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 14, 2022. ; https://doi.org/10.1101/2022.05.11.22274305 doi: medRxiv preprint viral pneumonia from the last 5 years before the pandemic were retrospectively scanned, and the thorax CT imaging closest to the date of PCR test was evaluated, but the CT-laboratory time interval in this group is longer than the COVID-19 pandemic period. Since the non-COVID-19 viral pneumonia group includes 5 years retrospectively, access to information about the time from the onset of symptoms to imaging is limited. The presence of co-infection in patients diagnosed with COVID-19 pneumonia is not known since most of these patients did not have additional microbial culture examinations during the pandemic period, but we expect that the presence of hospital-acquired coinfection will be lower since we have evaluated the first thorax CT examinations of these patients diagnosed with COVID-19 pneumonia.

In conclusıon; ın the diagnosis of viral pneumonia, radiological imaging, which is evaluated together with laboratory examinations, especially clinical and gold-standard RT-PCR test, has an important role in diagnosis and patient management. RSNA classification and CORADS scoring system can be used to distinguish COVID-19 pneumonia from non-COVID-19

pneumonia. The presence of reversed halo sign and absence of pleural effusion was found to be efficient in the diagnosis of COVID-19 pneumonia.

There is no conflict of interest between the authors.

Funding Statement: No supporting funds were used for our study.

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The copyright holder for this preprint this version posted May 14, 2022. ; Table 1 .

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The copyright holder for this preprint this version posted May 14, 2022. ; https://doi.org/10.1101/2022.05.11.22274305 doi: medRxiv preprint Table 2. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 14, 2022 Chi-Square Testi **p<0,01

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The copyright holder for this preprint this version posted May 14, 2022 

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The copyright holder for this preprint this version posted May 14, 2022. ; https://doi.org/10.1101/2022.05.11.22274305 doi: medRxiv preprint Figure 1 . A female patient in her 70s, diagnosed with HCoV-OC43 pneumonia, chronic lymphocytic leukemia (CLL). According to the RSNA guidelines 'typically', the CORADS score was evaluated as 5. GGO (crazy paving) (black arrow) accompanied by interlobular and intralobular septal thickening on the axial CT section and patchy consolidation areas, faint GGO areas (black arrowhead); pleural effusion (asterisks). . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted May 14, 2022. ; https://doi.org/10.1101/2022.05.11.22274305 doi: medRxiv preprint Figure 5 . An female patient in in the late 2nd decade, with parainfluenza (HPIV 3) pneumonia, with bone marrow transplantation due to acute lymphoblastic leukemia.

According to the RSNA guidelines in 'indetermine', CORADS score was evaluated as 3.

Diffuse centrilobular ground glass density nodules (black arrow) and focal peripheral consolidation areas (black arrowhead), increased peribronchial wall thickness (white arrowhead) are observed.

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The copyright holder for this preprint this version posted May 14, 2022. ; https://doi.org/10.1101/2022.05.11.22274305 doi: medRxiv preprint Figure 6 . A male patient in his 30s, with COVID-19 pneumonia, known diagnosis of asthma.

'Typical' according to RSNA guidelines, CORADS score was evaluated as 5. Bilateral lung parenchyma rounded, multifocal GGO lesions (black arrows); reversed halo sign (white arrow) central part is relative normal, with GGO in the periphery are observed.

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The copyright holder for this preprint this version posted May 14, 2022. ; https://doi.org/10.1101/2022.05.11.22274305 doi: medRxiv preprint Figure 7 . A male patient his 20s, diagnosed with known primary immunodeficiency with adenovirus pneumonia. According to the RSNA guidelines 'indetermine', CORADS score was evaluated as 4. İ rregular peripheral consolidation (black arrows) and increased peribronchial thickness (white arrowhead) are observed.

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