key: cord-278629-8fva8fwr authors: Zhou, Jun; Liao, Xingnan; Cao, Jia; Ling, Gonghao; Xun; Long, QingYun title: Differential diagnosis between the coronavirus disease 2019 and Streptococcus pneumoniae pneumonia by thin-slice CT features date: 2020-10-06 journal: Clin Imaging DOI: 10.1016/j.clinimag.2020.09.012 sha: doc_id: 278629 cord_uid: 8fva8fwr OBJECTIVE: The chest computed tomography (CT) features of coronavirus disease 2019 (COVID-19) and Streptococcus pneumoniae pneumonia (S. pneumoniae pneumonia) were compared to provide further evidence for the differential imaging diagnosis of patients with these two types of pneumonia. METHODS: Clinical information and chest CT data of 149 COVID-19 patients between January 9, 2020 and March 15, 2020 and 97 patients with S. pneumoniae pneumonia between January 23, 2011 and March 18, 2020 in Zhongnan Hospital of Wuhan University were retrospectively analyzed. In addition, CT features were comparatively analyzed. RESULTS: According to the chest CT images, the probability of lung segmental and lobar pneumonia in S. pneumoniae pneumonia was higher than that in COVID-19(P<0.001); the probabilities of ground-glass opacity (GGO), the “crazy paving” sign, and abnormally thickened interlobular septa in COVID-19 were higher than those in S. pneumoniae pneumonia(P = 0.005, P<0.001, P<0.001, respectively); and the probabilities of consolidation lesions, bronchial wall thickening, centrilobular nodules, and pleural effusion in S. pneumoniae pneumonia were higher than those in COVID-19 (P<0.001, P = 0.001, P = 0.003, P = 0.001, respectively). CONCLUSION: The findings of GGO, the crazy paving sign, and abnormally thickened interlobular septa on chest CT were significantly higher in COVID-19 than S. pneumoniae pneumonia. The most important differential points on chest CT signs between COVID-19 and S. pneumoniae pneumonia were whether disease lesions were distributed in entire lung lobes and segments and whether the crazy paving sign, interlobular septal thickening, and consolidation lesions were found. announced that the COVID-19 outbreak is a public health emergency of international concern. On February 11, 2020, WHO named this disease COVID-19. The virus that causes this outbreak is a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1]. It is an RNA virus that shares 88% sequence homology with two coronaviruses (bat-SL-CoVZC45 and bat-SL-CoVZXC21) found in bats, 79% homology with the SARS coronavirus (SARS-CoV), and 50% homology with the Middle East respiratory syndrome coronavirus (MERS-CoV) [2] . Current epidemiological observation indicates that transmission routes of COVID-19 mainly include respiratory droplets and close contact. Aerosol transmission is possible only after long-term exposure to high-concentration aerosol in a relatively closed environment. It can also be transmitted through the fecal-oral route [3] [4] [5] . Extensive human-to-human transmission is obvious, and there are cluster infections within families and medical staff [5] . The main manifestations of COVID-19 are fever (83%), cough (82%), J o u r n a l P r e -p r o o f dyspnea (31%), and myalgia; less commonly runny nose, sore throat, and diarrhea; and acute respiratory distress syndrome(17%-29%) [1, 4] . Streptococcus pneumoniae (S. pneumoniae) is an opportunistic extracellular Gram-positive bacterium that usually colonizes the mucosa of the human upper respiratory organs. S. pneumoniae can cause many diseases, including diseases that have mild symptoms but are common, such as otitis media, sinusitis, and bacterial pneumonia, as well as severe invasive pneumococcal diseases (IPD) such as bacteremia and meningitis. S. pneumoniae is the most common pathogen in community-acquired pneumonia (CAP) and it is also the major pathogen in nosocomial pneumonia [6, 7] . Because the incidence and mortality of CAP among elderly people are both high, S. pneumoniae pneumonia has always been a focus of attention. The main symptoms are mostly fever and cough as well as dyspnea and shortness of breath. Although COVID-19 and S. pneumoniae pneumonia are characterized by pulmonary inflammation caused by different pathogens, they have similar clinical symptoms and incidence rates. The incidence of COVID-19 seems to be higher in older men and patients with comorbidities. Particularly when the reverse transcription-polymerase chain reaction (RT-PCR) detection result is negative, there are some difficulties in distinguishing between COVID-19 and S. pneumoniae pneumonia. Furthermore, although COVID-19 is somewhat under control in China, the number of COVID-19 patients worldwide still shows an increasing trend. Therefore, there are many reports on chest computed tomography (CT) findings of J o u r n a l P r e -p r o o f COVID-19 [8] [9] [10] . However, there is no report on differentiation of chest CT findings between COVID-19 patients and patients with S. pneumoniae pneumonia. Thus, this study retrospectively analyzed chest CT findings in COVID-19 patients and compared them with chest CT findings in patients with S. pneumoniae pneumonia in order to describe CT features which are more common in patients with COVID-19 when compared to patients with S. pneumoniae pneumonia, and which may aid in differentiating these two entities clinically. Clinical information and chest CT data of 151 consecutive COVID-19 patients The GE discovery, Philips Ingenuity, and Siemens Somatom Sensation spiral CT scanners were used. Patients took a supine position, and scanning was performed at the end of inspiration using the conventional dose. The scanning range was from the apex of the lung to the costophrenic angle, the slice thickness was 1.25 mm, the tube voltage was 120 kV, and the tube current was 100 mA. The combination of the high-resolution algorithm and the standard algorithm and the multiplane reconstruction and the maximum-intensity-projection reconstruction methods were used for image processing. Before reviewing images, neither doctor knew the blood culture, BAL fluid, or real-time RT-PCR results. The final diagnosis was agreed upon by both doctors. Analysis of distribution features of disease foci mainly included whether the disease foci showed distribution in entire lobes or segments and which lung lobes were involved. According to the involved lung lobes, foci were classified into bilateral lung lobe involvement, unilateral single-lobe involvement, and unilateral multilobe involvement. Image analysis was mainly performed using the pulmonary window and the mediastinal window. The ground-glass opacity (GGO), consolidation lesions, "crazy paving" sign, bronchial wall thickening, abnormally thickened interlobular septa, centrilobular nodules, and cavitary lung lesions were analyzed using pulmonary windows. The mediastinal lymph node enlargement and pleural effusion were analyzed using mediastinal windows [12, 13] . The specific image signs and analysis criteria are shown in Table 1 . J o u r n a l P r e -p r o o f Statistical analysis was performed with SPSS 22.0 software. Categorical data were compared using Fisher's exact test. All P values were from the two-sided tests. P < 0.05 indicated a significant difference. From the chest CT data of all 246 enrolled pneumonia patients, the distribution features of disease foci are analyzed and summarized in Table 2 . The bilateral lung, unilateral single lung, and unilateral multilobar lung distributions of disease foci between COVID-19 and S. pneumoniae pneumonia did not have significant differences (P＞0.05). S. pneumoniae pneumonia mainly had a segmental pneumonia, with a probability of 62.9%, which was higher than the 26.8% probability for COVID-19 (P＜0.001). COVID-19 disease foci had a significantly higher probability of non-lobe and non-segment pneumonia than S. pneumoniae pneumonia (P＜0.001). practice. Clinically, if S. pneumoniae can be isolated from the blood or pleural fluid of pneumonia patients, the diagnosis of S. pneumoniae pneumonia can be confirmed [14] . Positive microscopic examinations and culture of high-quality sputum specimens provide powerful evidence of S. pneumoniae pneumonia [15] . CT is convenient, easy, and fast imaging modality for the variable pneumonia. Chest CT examination has high value in diagnosing COVID-19 or S. pneumoniae pneumonia and assessing the treatment effect. Although the Diagnosis and Treatment of COVID-19 (the provisional 7th edition) already abolished the use of typical CT findings as independent criteria for the clinical diagnosis of suspected cases in Hubei Province, many scholars reported that abnormalities might be found in the chest CT of some patients with negative viral nucleic acid detection results [16] [17] [18] . Currently, CT examinations were performed in radiology suites, which lead to a gathering of patients and their families, increasing the risk of infection. Likewise, radiologists were at high risk of exposure to COVID-19. Imaging indications for COVID-19 were analyzed by physicians in 10 countries [19] . The first is the initial management of [20] have reported 80 COVID-19 patients, finding that the common chest CT findings of COVID-19 were GGO, consolidation and abnormally thickened interlobular septa in both lungs. Xu X et al [21] found that pleural effusion, pericardial effusion, and lymphadenopathy were uncommon findings and the probabilities of GGO, abnormally thickened interlobular septa and the crazy paving sign were basically consistent with the findings of this study. Xu YH et al [22] [23, 24] , we can infer the following: the GGO that develops in the early stage of COVID-19 might be mainly caused by alveolar and interstitial edema or alveolar hypoventilation. With the disease progression, viruses continue to spread to peripheral lung lobules and epithelium. The involved areas extend to form disease foci with a non-lobular or non-segmental distribution. In the advanced or severe stage, viruses already invade the alveolar parenchyma, and the alveolar wall collapses, leading to lung consolidation lesions (Fig. 1a, 1b) . The GGO is the most common (Fig. 1c, 1d) . When GGO and abnormally thickened interlobular septa are present together, the crazy paving sign also appears (Fig. 1e, 1f) . Mediastinal lymph node enlargement, cavitary lung lesions, and pleural effusion are rare in COVID-19. Previous CT findings of streptococcus pneumoniae pneumonia [25] [26] [27] (Fig. 2a, 2b) , with inflated bronchi inside (Fig. 2b ). CT images of S. pneumoniae pneumonia patients also show solid or ground-glass nodules that can travel along the bronchovascular bundles (Fig. 2c, 2d) . The pathogens of COVID-19 and S. pneumoniae pneumonia are SARS-CoV-2 and S. pneumoniae, respectively. S. pneumoniae is a Gram-positive bacterium, and the drugs for S. pneumoniae pneumonia are mainly antibiotics, such as β-lactams (penicillins and cephalosporins), quinolones, and macrocyclic lipids [28] [29] [30] [31] . SARS-CoV-2 is a novel coronavirus for which vaccines and specific medicines have not been developed. The Diagnosis and Treatment of COVID-19 (the provisional 6th edition) mentioned using α-interferon combined with antiviral drugs, such as lopinavir, for treatment and avoiding blind or inappropriate use of antimicrobial agents [11, 32] . Therefore, differential diagnosis of these two types of pneumonia will be significant for disease treatment and patient recovery. by the National Health Commission of People's Republic of China on January 15, 2020, it has been updated to the 6th edition in little more than a month, which shows the difficulty of COVID-19 diagnosis and treatment. Furthermore, the time of this writing is the season with a high incidence of respiratory diseases, and there are many CAP patients. However, whether it is S. pneumoniae pneumonia or COVID-19, the final diagnosis is achieved through nucleic acid detection. In some COVID-19 patients with positive CT findings, their nucleic acid detection results are not J o u r n a l P r e -p r o o f supportive, and they can even be contradictory [33] . Therefore, in the COVID-19 outbreak, familiarity with the CT signs of COVID-19 and its differential diagnosis from S. pneumoniae pneumonia not only can provide powerful imaging evidence for diagnosis but also can screen the patients who have symptoms but do not receive timely nucleic acid detection. Suspected patients should be isolated for treatment as soon as possible to avoid disease progression into severe illness, which is conducive to controlling the development of the disease and alleviating the shortage of medical resources. There are some limitations in our study. Because of time and sample-size constraints, dynamic imaging data of COVID-19 and S. pneumoniae pneumonia after treatment were not analyzed in this study, which could be included in future studies. In summary, the findings of GGO, the crazy paving sign, and abnormally thickened interlobular septa on chest CT were higher in COVID-19 than S. pneumoniae pneumonia in this study, whereas the findings of consolidation lesions, bronchial wall thickening, pleural effusion, and centrilobular nodule on chest CT were lower in COVID-19 than S. pneumoniae pneumonia. In addition, disease foci in S. pneumoniae pneumonia mainly showed a lung lobular and segmental distribution. The most important differential points were whether the disease foci had the CT features of lung lobular and segmental distribution, the crazy paving sign, abnormally thickened interlobular septa, and consolidation lesions. 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