key: cord-0708878-jqcdo9p3
authors: Davide, Ippolito; Pecorelli, Anna; Maino, Cesare; Capodaglio, Carlo; Mariani, Ilaria; Giandola, Tersa; Gandola, Davide; Bianco, Ilaria; Ragusi, Maria; Cammillo, Talei Franzesi; Corso, Rocco; Sandro, Sironi
title: DIAGNOSTIC IMPACT OF BEDSIDE CHEST X-RAY FEATURES OF 2019 NOVEL CORONAVIRUS IN THE ROUTINE ADMISSION AT THE EMERGENCY DEPARTMENT: CASE SERIES FROM LOMBARDY REGION
date: 2020-05-26
journal: Eur J Radiol
DOI: 10.1016/j.ejrad.2020.109092
sha: 5215f49c01499ed3ad98a74d222c5c25b8c00b96
doc_id: 708878
cord_uid: jqcdo9p3

PURPOSE: To evaluate the diagnostic accuracy and the imaging features of routine admission chest X-ray in patients suspected for novel Coronavirus 2019 (SARS-CoV-2) infection. METHOD: We retrospectively evaluated clinical and X-ray features in all patients referred to the emergency department for suspected SARS-CoV-2 infection between March 1(st) and March 13(th). A single radiologist with more than 15 years of experience in chest-imaging evaluated the presence and extent of alveolar opacities, reticulations, and/or pleural effusion. The percentage of lung involvement (range <25% to 75-100%) was also calculated. We stratified patients in groups according to the time interval between symptoms onset and X-ray imaging (≤ 5 and > 5 days) and according to age (≤ 50 and > 50 years old). RESULTS: A total of 518 patients were enrolled. Overall 314 patients had negative and 204 had positive RT-PCR results. Lung lesions in patients with SARS-Cov2 pneumonia primarily manifested as alveolar and interstitial opacities and were mainly bilateral (60.8%). Lung abnormalities were more frequent and more severe by symptom duration and by increasing age. The sensitivity and specificity of chest X-ray at admission in the overall cohort were 57% (95% CI = 47-67) and 89% (83-94), respectively. Sensitivity was higher for patients with symptom onset > 5 days compared to ≤ 5 days (76% [62-87] vs 37% [24-52]) and in patients > 50 years old compared to ≤ 50 years (59% [48-69] vs 47% [23-72]), at the expense of a slightly lower specificity (68% [45-86] and 82% [73-89], respectively). CONCLUSIONS: Overall chest X-ray sensitivity for SARS-CoV-2 pneumonia was 57%. Sensitivity was higher when symptoms had started more than 5 days before, at the expense of lesser specificity, while slightly higher in older patients in comparison to younger ones.

Since February 21 st , 2020, several cases of pneumonia due to a novel coronavirus, named SARS-CoV-2 by the World Health Organization (WHO) (1), have been found in Lombardy, an Italian region. As of March 14 th , 2020, there are more than 21,000 confirmed cases and more than 1400 deaths in Italy. The SARS-CoV-2 is considered a relative of the deadly Severe Acute Respiratory Syndrome (SARS) and the Middle East respiratory syndrome (MERS) coronaviruses (2, 3, 4) .

Recent studies revealed that SARS-CoV-2 could spread from human to human, mainly through respiratory droplets, and also through contact (5) . The incubation period is generally 3-7 days, the longest not more than 14 days. Fever, fatigue, and dry cough are the main symptoms (6) . In severe cases, dyspnea occurs more than a week later and ARDS, septic shock, difficult to correct metabolic acidosis, and coagulation dysfunction rapidly develop (7) . SARS-CoV-2 founded cases are frequently diagnosed in emergency settings. The disease mainly occurs in elderly and fragile patients, especially with one or more comorbidities, who often leads to life-threatening conditions with a mortality rate estimated in Italy of about 4%. Countries all over the world adopted molecular assay to find out the presence of the virus in humans, according to WHO guidelines (8). All major decisions regarding SARS-CoV-2 management, including diagnostic and treatment issues, rely on the initial assessment.

Because suspected SARS-CoV-2 patients often are seen in the emergency department, developing strategies that improve early management is essential. The parenchymal lung disease involvement, required to make the diagnosis of pneumonia, is based on the evidence or absence of parenchymal infiltrates.

Early radiologic investigations consistently reported that the typical computed tomography (CT) findings of SARS-CoV-2 pneumonia were bilateral ground-glass opacities (GGOs) and consolidation with a peripheral and posterior lung distribution (9) .

Usually, the routine chest X-rays is the most widely available radiological procedure during hospital admissions, in particular, to complete differential diagnosis of respiratory symptoms, such as cough and dyspnea. A chest radiograph can establish the presence of pneumonia, define its extension and location, and can also diagnose complications like pleural effusion or abscess formation, while the CT may detect abnormalities that are not detectable with chest radiograph, due to its higher sensitivity.

To the best of our knowledge, there are no studies on X-ray imaging of SARS-CoV-2 pneumonia. This study aims to explore the impact of systematic early review of chest X-ray radiograph in patients admitted to the emergency department suspected for SARS-CoV-2, measuring the probability of making the diagnosis of SARS-CoV-2, as estimated by the attending emergency radiologist.

J o u r n a l P r e -p r o o f

Local Ethical Committee's review of the protocol deemed that formal approval was not required owing to the retrospective, observational, and anonymous nature of this study.

All patients admitted to the emergency department (Hospital San Gerardo, Lombardy, Italy) a tertiary referral hospital Center, with cough, dyspnea, and fever, during the period March 1 st to March 13 th were enrolled in the study. Patients with a clinical suspicion of SARS-CoV-2 infection, based on referring physician's judgment, underwent the RT-PCR test. Patients without clinical suspicion of SARS-CoV-2 infection were managed as appropriate.

Patients were eligible for study inclusion if they (1) underwent RT-PCR test for SARS-CoV-2; (2) had at least one bedside chest X-ray. For each patient, the following demographic, clinical and imaging data were recorder: 1) age, 2) sex, 3) fever, 4) cough, 5) dyspnea, 6) white blood cell count (WBC), 7) neutrophil count, 8) lymphocyte count, 9) platelets (PLT); 10) C-reactive protein (CRP) value, and 11) onset of symptoms.

A standard chest X-ray was performed in anteroposterior projection only, obtained in patients at the bedside. A senior attending radiologist (with 15 years of experience in chest imaging) reviewed the chest radiographs in picture archiving and communication systems (PACS, Enterprise Imaging, AGFA Healthcare, Belgium). X-ray images were assessed for the presence and distribution of parenchymal abnormalities including 1) alveolar opacities, defined as a hazy increase in lung attenuation with no obscuration of the underlying vessels, 2) reticular opacities, defined as fine or coarse linear shadows and, 3) pleural effusion.

The locations of the lesions were specified as superior, middle, and inferior, dividing each lung into three portions. Moreover, the lesions were defined as isolated, when focal lesions involved only one segment, multiple when multiple segments are involved, unilateral or bilateral.

Finally, for each chest X-ray we evaluated the extent of pathological findings according to the percentage of lung involvement: <25%, from 25% to 50%, from 50% to 75%, and >75%. 

Patients were classified according to SARS-CoV-2 positive or negative infection based on the result of the RT-PCR test. Continuous variables are expressed as mean and SD, after assessing for normal distribution using Kolmogorov-Smirnov test, and compared using t-Student; categorical variables are expressed as number and percentage. Patients positive for SARS-CoV-2 infection were also classified according to the time interval between symptoms onset and chest X-ray ( 5 days and > 5 days) and according to age ( 50 years old and > 50 years old). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and total accuracy of chest X-ray were estimated. For each parameter 95% confidence intervals (95% CI) were computed. A p-value < 0.05 was considered statistically significant. All the statistical analyses were performed using SPSS v21 statistical package (SPSS Incorporated, Chicago, Illinois, USA).

A total of 518 patients were enrolled. The majority of patients were male (290; 56.0%) with a mean age of 59 years (±18.4). The most common symptom was fever (450; 86.9%), followed by cough (290; 56.0%) and dyspnea (208; 40.1%). Only 18 patients had gastrointestinal symptoms. Overall 314 patients were negative and 204 positive for SARS-CoV-2 infection. The comparison of demographic, clinical, and laboratory data showed a higher mean age in patients with confirmed SARS-CoV-2 infection who had a significantly lower value of white blood cells, neutrophils, lymphocytes, and platelets counts and higher PCR value (Table 1 ). More often they had fever and dyspnea (Table 1) . Patients with symptoms onset more than 5 days from X-ray more frequently had dyspnea with lower WBC count, monocytes, and higher PCR value ( Table 2) . Older patients (> 50 years old) mainly presented fever and dyspnea and had lower lymphocytes and PLT values and higher CRP (Table 2) .

All bedside chest X-ray showed good diagnostic quality, without significant artifacts. Considering the entire study population, the extent of lung abnormalities was  25% in 92 (45.5%) patients, 25%-50% in 84 (41.6%) and 50%-75% in 26 (12.9%) (Figure 3 , 4, and 5). None of the patients has an extension greater than 75% of lung parenchyma.

Interestingly patients with an interval  5 days between symptoms onset and ED admission more frequently had a lung disease extension  25% in comparison to those with an interval > 5 days [58 

Overall sensitivity, specificity, PPV, NPV and accuracy of chest X-ray in the diagnosis of SARS-CoV-2 related pneumonia were 57% (95% CI= 47-67) 89% (95%CI= 83-94), 77% (95%CI= 68-85), 76% (95%CI= 72-80) and 76% (95%CI= 71-81) respectively.

Sensitivity and PPV of chest X-ray were lower when symptoms had appeared  5 days before performing imaging technique while specificity, NPV and accuracy were higher [37% (95% CI= 24- In this study, patients were stratified into two groups: the first group with an interval of less or equal to 5 days between symptom onset and chest X-ray examination, and the second group with an interval greater than 5 days between symptom onset and the chest radiograph. When patients' conditions get worst or in case of a longer course of the disease, the lungs showed diffuse lesions, and the density of both lungs increased widely, demonstrating multiple diffuse alveolar and reticular opacities. In fact, we found out that chest X-ray sensitivity decreased when symptoms appeared  5 days before performing imaging technique with a value of only 37%, a specificity of 65% and overall diagnostic accuracy of 77%, while in case of a longer course of the disease the sensitivity increased up to 76% maintaining a good specificity (68%) with an overall suitable diagnostic accuracy (74%).

Moreover the subdivision of SARS-CoV-2 patients according to age ( and > 50 years) allows to establish that alveolar opacities with coarse linear shadows are more frequent in older patients in J o u r n a l P r e -p r o o f comparison to younger ones. On the other hand the diagnostic performance changes: in younger patients chest X-ray showed an excellent specificity (100%) and accuracy (88%), but a low sensitivity (47%), instead sensitivity slightly increased in older patients till about 60%, while specificity and accuracy barely decreased (82% and 71%, respectively), maybe due to the presence of others lung comorbidities.

In recent literature, few studies focused on chest X-ray, mainly evaluating the role of CT as a routine imaging modality for screening or diagnosis (11, 12, 13) . The Radiology Scientific Expert Panel suggests that, after CT imaging, the room downtime is typically between 30 minutes to 1 hour for room decontamination (14) , suggesting that chest X-ray may be considered to minimize the risk of cross-infection.

Following the aforementioned statement, we assumed that chest X-ray can achieve the potential role of a screening test in medical settings with high disease prevalence, according to its sensitivity.

In fact, in the emergency setting, the bedside chest X-ray is a key component of the diagnostic workup and should be considered as a useful diagnostic tool also to minimize the risk of cross-infection, because the surface of portable unit can be easily cleaned. In these patients, the use of CT means a huge burden for the radiology departments and a big challenge for continuous infection control.

The results in our series support the idea that the conventional radiographs can be considered an important diagnostic resource in patients suspected for SARS-CoV-2, thus being a useful diagnostic approach, especially in Countries where the access to CT is lacking Our study had some limitations. First of all, most of our patients did not undergo a CT scan examination of the lung, therefore some early radiological lung features may not be demonstrated.

It is well known that patients without infiltration observed on radiograph and with unsure diagnosis greatly benefited from CT scan, however, we weighed this consideration against the importance of urgent reporting. Furthermore, chest radiograph results not only induced diagnosis probability changes but also led to the immediate adjustment of patients' care. Finally, a single radiologist evaluated all images, and consequently, it was not possible to evaluate the agreement. J o u r n a l P r e -p r o o f Table 3 . Type and distribution of the lesions according to positivity or negativity to SARS-CoV-2

infection. The interstitial pattern is the more frequent imaging finding in SARS-CoV-2 patients. The distribution is typically bilateral, subpleural, and diffuse. No statistically significant difference was found between SARS-CoV-2 positive and negative patients. 

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We would like to thank all the radiographers that have dedicated their time and efforts to perform the several radiological SARS-CoV-2 examinations in the isolation wards during this time and the radiologist staff of hospitals to support that work.