key: cord-0851767-whm63bie authors: Trovato, Piero; Simonetti, Igino; Rinaldo, Chiara; Grimaldi, Dario; Verde, Francesco; Lomoro, Pascal; Codella, Umberto; Rosa, Ferdinando De; Corvino, Antonio; Giovine, Sabrina title: COVID-19 integrated imaging: our experience and literature review date: 2021-02-01 journal: Pol J Radiol DOI: 10.5114/pjr.2021.103861 sha: 28d889ea824a9d2ae541c3a04d0ec6e6b1f3ec23 doc_id: 851767 cord_uid: whm63bie PURPOSE: To investigate the imaging features of emerging COVID-19 pneumonia on chest ultrasound, radiographs and computed tomography examinations performed at admission. In addition, we provide a review of the literature and compare our results with recent evidence regarding the imaging characteristics of this novel disease. MATERIAL AND METHODS: From March 17, 2020 to April 25, 2020, 23 patients with real-time polymerase chain reaction (RT-PCR) assay confirmed COVID-19 were identified. All 23 patients were evaluated and admitted at San Giuseppe Moscati Hospital in Aversa, Italy. Multi-modality imaging findings were evaluated and compared. Literature research was conducted through a methodical search on PubMed. RESULTS: Twenty-three patients were included in the study. Chest transthoracic ultrasound (US), chest X-ray (CXR), and computed tomography (CT) were performed respectively in 11, 16 and 21 patients. Chest US findings were consistent with diffuse B lines (91%), subpleural consolidations (45%), and thickened pleural line (18%). CXR showed prevalent manifestations of consolidations (50%) and hazy increased opacities (37%). Typical CT features are bilateral and multilobar ground-glass opacities (GGO). Indeed GGO were present in 100% of our patients. Consolidations were visible in 76% of our study population. Notably both GGO and consolidations had a peripheral distribution in all our patients. Other CT imaging features included crazy-paving pattern, fibrous stripes, subpleural lines, architectural distortion, air bronchogram sign, vascular thickening and nodules. Our literature review identified thirty original studies supporting our imaging chest findings. CONCLUSIONS: At admission, COVID-19 pneumonia can manifest in chest imaging as B-lines and consolidations on US, hazy opacities and consolidations on CXR, multiple GGO and consolidations on CT scan. A new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported from Wuhan, China, in December 2019, and then quickly spread to other countries around the world [1] . It is an enveloped RNA virus responsible for SARS-CoV-2 disease, denominated COVID-19. Clinical expression of the disease ranges from asymptomatic to a severe life-threatening course [2] . The dominant clinical presentation is characterized by high temperature and cough [3] . Up to 5.0% of the patients were admitted to intensive care units, 2.3% of them underwent invasive mechanical ventilation, and 1.4% of the patients died [1] . At present, real-time polymerase chain reaction testing (RT-PCR) for SARS-CoV-2 is the standard for diagnostic confirmation [4] . Imaging plays an important role in the diagnosis: ultrasound (US) and chest radiography (CXR) are offered as the first step; computed tomography (CT) is reserved for more severe cases or cases of discrepancy between clinical and radiographic findings, especially in the early stage where a swab test may be negative [5] . Our study aimed to systematically evaluate and compare the imaging findings of COVID-19 detected in 23 patients admitted to our hospital who underwent CXR, lung US and chest CT examinations. In addition, we have provided a complete overview of the literature to compare our results with recent evidence regarding the imaging features of this novel disease. Our retrospective study was approved by the local institutional review board. From March 17, 2020 , to April 25, 2020, a total of twenty-three patients (13 men, 10 women; age range, 53 to 84 years; mean age 72.7 years) with CO-VID-19 confirmed by RT-PCR assay and hospitalized in San Giuseppe Moscati Hospital (Aversa, Italy), were included. All patients underwent a chest radiological evaluation upon admission to our Emergency Department using chest CT and/or CXR and/or lung US. Clinical and laboratory data were also evaluated. Bedside lung US was performed in the Emergency Department using low frequency (2) (3) (4) (5) convex probe and high frequency (5-10 MHz) linear probe. CXR was performed in the posteroanterior projection at full inspiration or in the anteroposterior projection in the supine patients. Chest CT examination was performed using a multi-detector CT scanner with 16 channels located in the emergency room and used exclusively for COVID-19 patients. The following were used as CT acquisition parameters: tube voltage of 120 kVp; tube current, standard (reference mAs, 60-120); slice thickness, 1.0 mm; reconstruction interval of 1.0 mm. The acquisition of all CT images was performed during full inspiration with the patient in full inspiration and without IV contrast medium. All lung US, CXR, and CT images were reassessed by two expert thoracic radiologists in consensus (S.G. and F.D. with 27 and 14 years of experience in thoracic radiology). The following lung US findings were investigated: A-lines, B-lines, thickened pleural line, pleural consoli-dation, and effusion. CXR and CT features were classified according to the Fleischner Society Glossary [6] . The following chest radiographic findings were evaluated: hazy increased lung opacity, consolidation, and pleural effusion. CT images were analyzed in the pulmonary window, with a width of 1500 Hounsfield units (HU) and a level of -600 HU, and in the mediastinal window, using a width of 350 HU and a level of 50 HU. The following CT findings were assessed: distribution (peripheral, central or both), involved lung lobes (right upper lobe, middle lobe, lower lobe, left upper lobe, lower lobe), number of lobes involved (one, two, three, four, five), appearance (ground-glass opacity, consolidation, ground-glass opacity with consolidation), specific signs (air bronchogram sign, "crazy-paving" pattern, architectural distortion, fibrous stripes, subpleural lines, vascular thickening, and nodules), and extra-pulmonary alterations (pleural effusion and mediastinal enlarged lymph nodes). All twenty-three patients presented with clinical manifestations upon admission, including fever in twenty-three patients (100%), cough in eleven patients (48%), dyspnea in ten patients (43%), and fatigue in thirteen patients (56%). Laboratory tests showed low levels of lymphocytes in twenty patients (87%) and high C-reactive protein levels in twenty-two patients (91%). Available imaging examinations performed for each patient were as follows: CXR alone from six patients, CT alone from seven patients, while a combination of lung US and chest X-ray in two patients, lung US and chest CT in six patients, chest X-ray and CT in five patients and lung US, chest X-ray and CT in three patients. Bedside lung US was performed in eleven patients. In ten cases (91%), US showed various B-line patterns (focal, multifocal, confluent) with bilateral distribution, which indicated filling of intralobular or interlobular septa or opacities that did not obscure the underlying bronchial and lung structures. In five patients (45%) a subpleural consolidation was observed while in two cases (18%) US showed a thickened pleural line. In one case (9%), a mixed pattern was highlighted with A-and B-lines. Moreover, in one patient (9%), pleural effusion was also observed. Of these patients, chest X-ray was performed in five patients while chest CT was performed in nine patients; bilateral consolidations or hazy increased opacities were observed in chest X-ray examination ( Figure 1 ) while bilateral ground-glass opacities (GGO) with consolidations were highlighted at CT evaluation (Figures 2 and 3 ). Detailed lung US findings are reported in Table 1 . CXR was performed in a total of sixteen patients. Of these, two patients (12%) showed no abnormalities, although chest CT performed on the same day allowed bilateral GGO to be identified. In the remaining cases, eight patients (50%) showed a consolidation while in six patients (37%) a hazy increased opacity was identified; no pleural effusion was detected. The distribution of these features was bilateral in thirteen cases (81%) and unilateral in one patient (6%). Moreover, the lower lobes were involved in eight patients (50%), while similar lower and upper zone involvement was observed in six cases (37%) and upper zone involvement in only one patient (6%). Among these patients, CT was performed on the same day in eight patients, showing correlated characteristics, especially bilateral GGO with consolidations predominantly involving the lower lobes ( Figure 1 ). Detailed results of CXR findings are shown in Table 2 . Twenty-one patients underwent a chest CT examination, which showed abnormalities in all cases. The most common CT findings were GGO (Figure 4 ), detected in 21 cases (100%); among them, 16 (76%) also showed concomitant consolidations ( Figure 5 ). In all patients the lesions involved both lungs, generally 5 lobes (76%), in particular, the right lower lobe (100%) and the left lower lobe (100%), with a prevalent peripheral distribution in twenty-one cases (100%) while both peripheral and central localization was detected in sixteen patients (76%). Lung ultrasound with convex probe shows irregular pleural surface and multiple B lines. B) Chest X-ray shows bilateral, central and peripheral, lung opacities. C, D) Axial chest computed tomography images show patchy bilateral ground-glass opacities with interlobular septal and intralobular interstitial thickening ("crazy-paving" pattern) in the upper lobes, mainly peripheral and more consolidated areas nodes were detected in twelve patients (57%) and pleural effusion in two patients (9%). Detailed CT findings are reported in Table 3 . An updated literature review of imaging manifestations of COVID-19 pneumonia including CXR, ultrasound, and CT scans was performed on PubMed by two researchers independently. The search method included the terms "coronavirus", "SARS-CoV-2" and "COVID-19", and aimed to identify retrospective and prospective studies published up to 25th April 2020. We limited our search to English-language studies conducted on human subjects with more than 10 patients in which COVID-19 infection was investigated and we excluded studies focused on pediatric populations. From the literature search, we found 30 articles [2, 3, [34] [35] [36] that included a total of 4243 patients, with a mean age of 49.63 years old, male: 2245 and female: 1998. Chest CT abnormalities were reported in all studies whereas only three studies [2, 18, 29] included CXR findings; finally, lung US abnormalities such as various B-line patterns, subpleural consolidation and thickened pleural line were investigated in one original studies and discussed in two letters to the editor [2, 32, 33 ]. As reported in the literature review, to date, there are still few studies with a large population available reporting detailed analysis regarding CXR manifestations. Chen et al. [18] reported bilateral pneumonia as the most common result on CXR, while in the Ng et al. study [29] , only five patients underwent CXR and of these, three had parenchymal consolidations, two showed no alterations, and none had pleural effusion. The CXR results of the included studies are displayed in Table 4 . On the other hand, chest CT abnormalities were largely investigated in recent published works and the most common reported abnormalities associated with COVID-19 pneumonia were isolated GGO, followed by consolidations and GGO in combination with consolidative opacities; the predominant distribution was bilateral, peripheral, subpleural and of the lower lobes. Other CT signs showed heterogeneous results; in particular, the air bronchogram, the crazy-paving pattern and the interstitial thickening (i.e. reticulation pattern) had a detection rate which ranged from 8% to 80%, from 17.5% to 81.8%, and, from 8.4% to 56.5%, respectively. Moreover, the reversed halo sign was described in only three studies: Bernheim et al. found it in 2% [12] , Li et al. in 3.9% [14] , Bai et al. in 5% [22] . According to the revised studies, lymphadenopathy and pleural effusion were rarely observed. Chest computed tomography axial image shows bilateral and diffuse ground-glass opacities with superimposed interlobular septal thickening and intralobular septal thickening ("crazy paving" pattern) and more consolidated areas with air bronchogram sign Interestingly, recent evidence focused on the reliability of disease staging using CT scores [34, 35] , identifying a correlation between the signs, symptoms, and the stage of the disease. Liu et. al. [34] reported the initial and follow-up characteristics of CT in COVID-19 patients by classifying them based on severity, in patients with mild, common, severe, and critical type. Atelectasis and pleural effusion findings were rarely observed and were found only in critically ill patients, suggesting a worse prognosis when these signs occurred; in the follow-up, CT scans, mostly in patients who had recovered from the disease, GGO, and consolidation were resolved, while the interlobular septum and bronchial wall thickening, band opacities and scattered patchy consolidation were still visible in a minority of patients. Ding et al. [35] classified the disease into six stages according to the time of the initial symptoms; this study showed no abnormalities at the initial presentation (symptoms of 0-4 days) in 21.2% of performed chest CT scans while variable lesions were observed in the progressive phase (5-9 days). In later stages, the presence of crazy paving pattern, consolidation, and linear opacities increased significantly, reflecting the pathological changes with the development of interstitial edema and alveolar exudation. Furthermore, they analyzed the adherence of semiquantitative CT score to the severity of the different stages, showing that the total CT scores of the bilateral lungs were lower in the first stage compared to the other stages, but there was no significant difference between the other stages, suggesting the permanence of disease within ten days after the onset of the initial symptoms. Regarding our case series, it is interesting to note that, unlike the data reported in the literature relating to chest CT abnormalities, the most frequently detected CT lung findings were GGO with concomitant consolidative opacities (76%), rather than isolated GGO, visible only in 24% of cases. Instevisiblead, according to the revised studies, also in our case series, the predominant distribution was bilateral and peripheral with lower zone involvement (100%); however, the high central distribution frequency (76%) should be considered. Similarly, we highlighted a high frequency of presence of air bronchogram sign (76%) and "crazy paving" pattern (57%). Regarding the presence of perilesional vascular thickening, we detected this sign in 47% of cases, which represents an incidence lower than that reported by of Li [11] ; this sign is thought to be caused by hyperemia induced by an acute inflammatory response [2] . Regarding the extrapulmonary manifestations, it is interesting to note that in 57% of cases we detected mediastinal enlarged lymph node, an uncommon finding according to literature data. According to the revised studies, pleural effusion was rarely observed (9%). Therefore, the set of our findings suggests a higher incidence of more severe and critical disease cases in our case series, as also confirmed by the high mortality rate of our case series (6 patients: 26%). These data can be explained by patients' access to the hospital at a later stage in the history of the disease. 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