key: cord-034689-se1hdn61
authors: Smith, David L.; Grenier, John-Paul; Batte, Catherine; Spieler, Bradley
title: A Characteristic Chest Radiographic Pattern in the Setting of COVID-19 Pandemic
date: 2020-09-03
journal: Radiol Cardiothorac Imaging
DOI: 10.1148/ryct.2020200280
sha: 
doc_id: 34689
cord_uid: se1hdn61

BACKGROUND: Compared with chest CT, there is a relative paucity of data regarding the role of the chest radiograph (CXR) in the diagnosis of COVID-19. PURPOSE: To determine the utility of CXR in aiding clinical diagnosis of COVID-19, utilizing RT-PCR as the standard of comparison. MATERIALS AND METHODS: A retrospective study was performed of persons under investigation (PUIs) for COVID-19 presenting to our institution during the exponential growth phase of the COVID-19 outbreak in New Orleans, USA (March 13 – 25, 2020). 376 in-hospital CXR exams for 366 individual patients were reviewed along with concurrent RT-PCR tests. Two experienced radiologists categorized each CXR as characteristic, nonspecific, or negative in appearance for COVID-19, utilizing well-documented COVID-19 imaging patterns. CXR categorization was compared against RT-PCR results to determine the utility of CXR in diagnosing COVID-19. RESULTS: There were 178/366 male (49%) and 188/366 female (51%) patients with a mean age of 52.7 years (range 17 to 98 years). 37/376 CXR exams (10%) exhibited the characteristic COVID-19 appearance; 215/376 (57%) exhibited the nonspecific appearance; and 124/376 (33%) were considered negative for a pulmonary abnormality. Of the 376 RT-PCR tests evaluated, 200/376 (53%) were positive and 176/376 (47%) were negative. RT-PCR tests took an average of 2.5 ± 0.7 days to result. Sensitivity and specificity for correctly identifying COVID-19 with a characteristic CXR pattern were 15.5% (31/200) and 96.6% (170/176), with PPV and NPV 83.8% (31/37) and 50.1% (170/339), respectively. CONCLUSION: The presence of patchy and/or confluent, bandlike ground glass opacity or consolidation in a peripheral and mid-to-lower lung zone distribution on a chest radiograph obtained in the setting of pandemic COVID-19 is highly suggestive of SARS-CoV-2 infection and should be used in conjunction with clinical judgement to make a diagnosis.

To date, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as 2019-nCoV, has infected millions of patients and claimed over 200,000 lives globally, and these numbers continue to grow rapidly [1] . The utility of thoracic computed tomography (CT) for diagnosing pneumonia associated with coronavirus disease 2019 (COVID-19), the disease caused by SARS-CoV-2, has been a focus worldwide with ample literature originating in particular from experts in China, the United States, and Europe, where specific CT patterns have been recognized in affected patients [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] . Nonetheless, leading radiologic societies have discouraged the use of CT as a screening tool [5, 6, 13] with reverse-transcription polymerase chain reaction (RT-PCR) testing considered to be the gold standard for COVID-19 diagnostic screening [14] [15] [16] . Rather, these societies recommend CT use be reserved for management of COVID-19 patients with worsening and/or severe respiratory symptoms, in particular for those in a hospital setting or those having special indications for CT [6, 13] . These recommendations coupled with additional concerns regarding CT, including risks associated with patient transport and scanner decontamination, have undoubtedly led to fewer CT examinations for persons under investigation for COVID-19 [13, 17] . Chest radiography (CXR), on the other hand, has I n p r e s s been widely used in these patients who usually present with respiratory symptoms [18] ; yet, much less has been written about CXR with respect to COVID-19. We have observed a CXR pattern in patients during the exponential growth phase of the COVID-19 outbreak in New Orleans, USA [19] which is in accordance with the most commonly recognized CT features of COVID-19 in recent literature [2, 7, 9, 10, 12, [20] [21] [22] [23] [24] [25] [26] [27] . These observations may be useful for patient triage or may assist in discharge and quarantine planning where rapid and highly sensitive and specific testing is lacking.

Our institutional review board (IRB) approved this study (IRB# 20-838) and deemed it to be Health Insurance Portability and Accountability Act (HIPAA) compliant. We performed a retrospective database query within our institution's electronic medical record system for all patients who had undergone COVID-19 RT-PCR testing utilizing the United States Center for Disease Control (CDC) assay between March 13 and March 26, 2020. These dates represent the period of upswing and exponential growth of COVID-19 incidence in New Orleans. The query returned 383 RT-PCR tests performed on 373 patients, with 10 patients receiving repeat RT-PCR and CXR (which were treated as unique entries for the purpose of data analysis). Six cases were excluded for lack of corresponding CXR and one case was excluded for an 'inconclusive' RT-PCR result, with a final total of 376 coincident CXR and PCR tests evaluated for 366 individual patients. Therefore, our case count represents 366 CXR and PCR tests acquired upon presentation at our institution (one set of tests for each of the patients in our study) plus 10 sets of CXR/PCR for patients counted above but who also received repeat tests later in their hospital course. Gender, age, chief complaint (Table 1) , and BMI were also collected for the cohort.

Two board certified radiologists with greater than 10 years' experience interpreting chest radiographs, blinded to RT-PCR results, independently assessed 376 portable anteroposterior (AP) or upright posteroanterior (PA) chest radiographs in 366 patients ( Fig. 1 ) obtained on the day of testing or immediately prior to that date. Patients with radiographs performed more than 2 days prior to RT-PCR testing were excluded. Readers assigned one of three patterns: characteristic, nonspecific, and negative ( Table 2) . A subsequent consensus read was performed to address discrepancies between the two readers. The characteristic COVID-19 pattern ( Fig. 2-4) was defined in accordance with the prevailingly accepted chest imaging findings of COVID-19 in recent literature [2, 12, 20, 24, 25, [27] [28] [29] including the presence of bilateral "patchy" or "confluent, bandlike" ground glass opacity or consolidation in a peripheral and mid-to-lower lung zone distribution. If the CXR showed a pleuropulmonary abnormality other than the above description, it was assigned to the nonspecific category. Nonspecific radiographs were grouped according to type of abnormality (mass-like, upper lung zone predominant, diffuse, ill-defined bibasilar, focal/unilateral, effusion). A radiograph without any perceived pleuropulmonary abnormality was labeled negative (Table 3) .

Statistical analysis was performed using Microsoft Excel software (Microsoft Corporation.

[2018]. Microsoft Excel). CXR characterizations were compared to RT-PCR tests, considered the gold standard. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated on consensus reads. Inter-reader agreement was assessed using Cohen kappa coefficient.

The clinical characteristics of the 366 patients at the time of RT-PCR testing include: 178/366 male (49%) and 188/366 female (51%) patients, with a mean age of 52.7 years (range 17 to 98 years). Average patient BMI was 32.0 ± 9.7 kg/m 2 . Various clinical indications for the exams in question are listed in Table 3 subject that had a negative RT-PCR result with either a negative or nonspecific CXR. A false positive (FP) therefore was a subject considered to have a characteristic appearance on CXR but had a negative RT-PCR result. False negative(s) (FN) were subjects considered to be either nonspecific or normal in appearance on CXR but had a positive RT-PCR, FN=169. The achieved high specificity (96.6%) of this study is attributed to the high number of TNs, 170, and relatively few FPs, 6. We attribute these numbers to a very strict definition of a positive, characteristic radiographic appearance for COVID-19. Given this narrow classification, our study has few FPs as well as few TPs, 6 and 31 respectively. As a result, our study's specificity should be considered in conjunction with our PPV (83.8%).

The chest radiograph, while low in sensitivity, can be highly suggestive COVID-19 in patients whose radiographs exhibit characteristic COVID-19 findings, when used in concert with clinical factors. While not a substitute for RT-PCR or chest CT, CXR could provide rapid, cost-effective diagnosis of COVID-19 in a subset of infected patients (estimated at 15 out of 100 in our cohort), during the COVID-19 pandemic. The utility of this technique is described in the context of known disadvantages of RT-PCR, considered the gold standard in COVID-19 diagnosis, and Chest CT, which is currently not recommended for COVID-19 diagnosis [13] . Moreover, it is important to note that the observed specificity of radiographic findings in this study is significantly influenced by the prevalence of COVID-19 in the community and would only serve to guide management in the context of a pandemic.

Variable RT-PCR sensitivities have been reported, ranging from 30-91% [28, 31] . This may be the result of relatively lower viral loads in individuals who are asymptomatic or experience only mild symptoms. Furthermore, tests performed when symptoms were resolving also resulted in false negatives [14, 32, 33] . These low sensitivities result in false negative tests, potentially leading to patient discharge without appropriate planning and creating the potential of community transmission of disease by patients incorrectly "cleared" by the health care system. Second, RT-PCR testing has been difficult to obtain, especially in the earliest days of the COVID-19 outbreak in New Orleans. Because of a dearth of tests and testing supplies, only the highest pretest-probability patients were tested, while others were diagnosed clinically. As we know now and suspected then, many more patients were infected than tested [19] . Initially, RT-PCR assays and kits from United States Center for Disease Control (CDC) were utilized. Later, other tests with varying sensitivities and specificities became available. In this study we relied With CT usage in persons under investigation (PUIs) for COVID-19 being largely dissuaded [6, 13] , there is an opportunity for the ubiquitous chest radiograph to be useful. While CXRs of most PUIs are either negative or reveal nonspecific abnormalities (Fig. 5) , there is a characteristic pattern of opacity that can aid in diagnosis. That pattern corresponds to a subset of patients with the typical pattern discussed in the joint statement on reporting by the American College of Radiology (ACR), Radiological Society of North America (RSNA), and Society of Thoracic Radiology (STR) [5] . The characteristic pattern, therefore, indicates an idiosyncratic distribution of acute lung injury and/or organizing pneumonia which is more clearly illustrated on CT.

Due to the aforementioned limitations of RT-PCR and current recommendations against routine use of CT, recognition of the characteristic CXR pattern used in conjunction with clinical judgment may allow clinicians to diagnose COVID-19. However, the main hurdle in using our approach to the characteristic COVID-19 CXR is the associated low sensitivity. Wong et al reported a sensitivity, as it pertains to the diagnostic ability of baseline CXR compared to RT-I n p r e s s PCR in detecting COVID-19, to be 69% and 91% respectively [28]. Our calculated sensitivity was 15.3%. We attribute this discordance to stark differences in image evaluation between our studies. The image evaluation in the work of Wong et al was based upon a scoring system for the evaluation of pulmonary edema, the radiographic assessment of lung edema (RALE) score [40] . As such, readers identified areas of lung consolidation/opacity and rendered a severity score. The study's baseline CXR sensitivity was then calculated based on a score of greater than "zero" which was denoted as an absence of pulmonary opacification or consolidation, such that any opacification/consolidation (even if singular in one lung) was considered positive [28].

In our design, a CXR was considered positive only if a characteristic pattern was seen, necessitating the presence of bilateral opacity/consolidation in a peripheral and mid-to-lower lung zone distribution. This stricter inclusion criterion resulted in far less TPs and a high number of FNs for our study, yielding a low sensitivity but a higher specificity. It cannot be overstated that calculated specificity is undoubtedly shaped by the plenitude of COVID-19 in our patient population at the time of this study and therefore should be used for guidance of patient management only in the setting of such a pandemic.

Statistical analysis of our data also revealed 6 false positive CXR results. A few issues may generate false positive results while utilizing our approach. First, false positive CXR interpretations may be a reflection of the variability of RT-PCR sensitivities, as discussed above. Furthermore, the pattern of disease we have labeled as characteristic of COVID-19 can be seen in other pathologic conditions. The differential diagnosis list includes chronic eosinophilic pneumonia (CEP), nonspecific interstitial pneumonia (NSIP), organizing pneumonia (OP), and acute lung injury, including diffuse alveolar damage (DAD), among others [42, 43] . These histologic diagnoses, in turn, may result from any number of insults, including autoimmune disease, drug toxicity, viruses other than SARS-CoV-2, etc. We do not propose, therefore, that the characteristic pattern herein should always suggest COVID-19 positivity-the pattern may be seen in other conditions. Nevertheless, this pattern is quite uncommon outside of the setting of pandemic; the corresponding author appreciated several characteristic cases per day in late March and early April 2020 and can only recall a few such cases in the previous ten years of his career. With the particulars of recall bias set aside, we believe it is fair to say that in the setting of pandemic COVID-19, the characteristic pattern notable on chest radiographs should be highly suggestive of SARS CoV-2 infection, and that patient triage and disposition should be informed by that suggestion. At times when serologic testing is deficient in number or quality, or when resulting times are inconveniently long, CXR provides a useful diagnostic tool.

Our study has limitations as discussed in detail above. These limitations include variability in timing between CXR and RT-PCR; the broad scope of the nonspecific category and narrow scope of the characteristic category; uncertainty in RT-PCR sensitivity; and variability in image quality and technique. Future work would address many of these limitations. Sensitivity and specificity of CXR results could be correlated with BMI, breast tissue, and technique, to address the potential confounder of inconsistent image quality. Re-analysis of CXR images utilizing either a scoring system or a 4-tiered rather than a 3-tiered categorization system may offer improved sensitivity in an "intermediate" category defined between characteristic and I n p r e s s nonspecific. Finally, as more information regarding the LA OPH RT-PCR test emerges and RT-PCR sensitivities and specificities become better known, and as RT-PCR tests continue to improve, CXR results could be correlated with newer and more sensitive RT-PCR tests which could decrease FP CXR results and increase TN CXR results.

The presence of bilateral "patchy" and/or "confluent, bandlike" ground glass opacity or consolidation in a peripheral and mid-to-lower lung zone distribution on a chest radiograph obtained in the setting of pandemic COVID-19 is highly suggestive of SARS-CoV-2 infection and should be used in conjunction with clinical judgement to make a diagnosis, especially when rapid and reliable serologic testing is lacking.

DLS is the guarantor of this manuscript. JPG and CB had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Lessons from the frontline of the covid-19 outbreak -The BMJ I n p r e s s 

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I n p r e s s 

Bilateral "patchy" and/or "confluent, bandlike" ground glass opacity or consolidation in a peripheral and mid-to-lower lung zone distribution

Any pleuropulmonary abnormality other than the above

No perceived pleuropulmonary abnormality I n p r e s s . Characteristic CXR of a 63-year-old female presenting with dyspnea and fever. Chest radiographic findings include bilateral "patchy" and "confluent, bandlike" ground glass and consolidative opacity in a peripheral, mid-to-lower lung zone distribution (arrows). Figure 3 : Characteristic CXR of a 41-year-old female presenting with cough and fever. Chest radiographic findings include bilateral "patchy" and "confluent, bandlike" ground glass and consolidative opacity in a peripheral, mid-to-lower lung zone distribution (arrows).