Copyright Claims: This review is an intellectual property of the authors and of the Institute of Clinical Epidemiology, National Institutes of Health-UP Manila and Asia-Pacific Center for Evidence Based Healthcare Inc.

BACKGROUND

Current COVID-19 radiological literature is dominated by Chest CT which is more sensitive than chest x-ray. Chest CT is often used as a first line diagnostic exam and in some hospitals, a CT scan suite has been dedicated for suspected COVID 19 patients. This may not be feasible in many centers. Added demand is likewise placed on health facilities because of disinfection protocol requirement after each procedure. In British and Italian hospitals, Chest x-ray has been used as part of the initial diagnostic triage tool because of its ready availability and faster results compared with reverse transcription-polymerase chain reaction (RT-PCR).

The reported radiologic findings of the chest x-ray of COVID-19 patients are limited. This rapid review describes the percentage of normal and abnormal chest x-ray findings, the frequency of chest x-ray abnormalities among confirmed COVID-19 patients and correlates the chest x-ray appearances with RT-PCR.

Should Chest X-ray be used in Diagnosing COVID-19?

METHODS

Eligibility and Information Sources

Studies were included if they reported on the diagnostic accuracy of chest x-ray in determining individuals with COVID-19 or reported on at least one chest x-ray finding in patients with COVID-19. Eligible studies were identified using Pubmed, EBSCO (CINAHL Plus with full-text, Medline, Medline Complete), and Science Direct. Age and year restrictions were not used. Only articles with full-text reports written in English were included in the review.

Search Strategy

These Boolean terms and three (3) sets of keywords were used:

•Keywords 1: “Coronavirus Infections” [Mesh} OR “Coronavirus” [Mesh] OR coronavirus OR novel coronavirus OR NCOV or“COVID-19”[Supplementary Concept} OR covid19 OR covid 19 OR covid-19 OR “severe acute respiratory syndrome coronavirus 2” [Supplementary Concept] OR severe acute respiratory syndrome coronavirus 2 OR SARS2 OR SARS 2 OR SARS COV2 OR SARS COV 2 OR SARS-COV-2

•Keywords 2: chest x-ray OR chest x-ray OR Mass chest x-ray OR Mass chest x-ray

•Keywords 3: Cough OR flu OR acute respiratory syndrome OR respiratory distress syndrome OR severe acute respiratory syndrome OR SARS virus

Study Selection

The two reviewers independently searched the electronic databases using keywords with Boolean terms and the guidelines set by internationally-recognized societies. They independently screened the titles and abstracts of potentially relevant studies. The reviewers retrieved the full-text report of relevant articles. Disagreements on included studies in the review were resolved through discussions.

Critical Appraisal Tools and Data Extraction

Process

The National Health and Medical Research Council Hierarchy for diagnostic studies were used in classifying included articles. The two reviewers independently reviewed the articles using these critical appraisal tools:

1. The Joanna Briggs Institute (JBI) critical appraisal tool of checklist for case series and the JBI critical appraisal tool of checklist for cross-sectional studies. These tools were developed by the JBI Scientific Committee following an extensive peer review.1

2.The Center for Evidence-Based Medicine critical appraisal tool for Systematic Reviews. This tool has scores for over six questions. Numerous questions are similar to the Critical Appraisal Skills Program critical appraisal tool.1

The two reviewers independently extracted the data using a designed data abstraction tool. Data were extracted on authors, year, the country where the study originated, characteristics of the study population, sample size, eligibility criteria, protocol and chest x-ray equipment used, and results.

RESULTS

Study selection

The number of hits was comparable between the two reviewers revealing unlikelihood of missing important studies. The titles and abstracts were considered by the two reviewers fitting the set inclusion criteria. Ten out of the 295 potentially relevant articles were included in the rapid review (Appendix A).

Levels of evidence

One meta-analysis, seven cross-sectional and two case series studies have reported on the chest x-ray findings of adults who tested positive for RT-PCR. The ACR, CAR, CSTR, and the British Society of Thoracic Imaging and Fleischner Society published recommendations on the use of chest x-ray.

There was moderate agreement (kappa= 0.66) between the two reviewers. The disagreements were secondary to the assessor’s reliability in interpreting the chest x-ray results.

Rodriguez-Morales et al. (2020) study did not include imaging as a keyword in searching the evidence for chest x-ray as diagnostic tool for COVID-19.2 Three out of the six cross-sectional studies did not report on:

a.The history (i.e., travel history, past medical history) of COVID-19 patients.(3,11-12)

b.Co-morbidities (i.e. hypertension, diabetes, chronic obstructive pulmonary disease, malignancy, chronic liver disease) present in COVID-19 patients.(3,11-12)

Five out of the seven cross-sectional studies did not report on the standard protocol used in chest x-ray.4–8 The history, presence of confounders, and standard chest x-ray protocol could have influenced the reported abnormal chest x-ray findings.

Descriptions of included studies

The seven cross-sectional and two case series studies reported the chest x-ray findings of 1,268 COVID-19 patients. There were 1,225 males and 885 females whose ages range from 16 to 96 years old. Cough and fever were common presenting symptoms of patients with COVID-19.3–7,9  Three studies focused only on critically ill patients5-6, 9 while one study was conducted in an ambulatory care setting.11 Wong et al. (2020) reported higher sensitivity (Sns) of baseline RT-PCR (Sns=91%) compared to chest x-ray (Sns = 69%).3 Table 1 shows majority of the studies were done in China.

The meta-analysis by Rodriguez-Morales et al. (2020) which included 19 observational studies and 39 case reports was based on the chest x-ray findings among 760 COVID-19 from 14 countries (i.e., China, Australia, South Korea, Germany France, Australia Taiwan, Vietnam Canada, Japan, Nepal, Thailand, United States of America. Mean age was 52 years (46-58) with males comprising 56%.2 Rodriguez-Morales et al. (2020) did not analyze the nine primary studies included in this rapid review.

Table 2 presents that ground-glass opacities and bilateral pneumonia were the common abnormalities found

on chest x-rays. Only two studies reported progress of lung abnormalities on chest-x-rays. Three studies graded severity of findings.

DISCUSSION

The diagnosis of COVID-19 is suspected based on symptoms of pneumonia, history of recent travel to countries with known sustained community transmission, or exposure to a known patient. RT-PCR because of its high sensitivity and specificity is considered the reference standard in

diagnosing COVID-19. RT-PCR has high sensitivity and specificity identifying SARS-CoV-2 as the causative agent. The combination of clinical features and RT-PCR is important for diagnosing patients presenting with early COVID-19 symptoms.13

Radiological examination, as a routine imaging tool for pneumonia diagnosis, may be important in the early detection and treatment of patients affected by COVID-19. Radiological examinations are easy to perform, producing rapid diagnosis. Wong et al. (2020) reported abnormalities in chest imaging preceded RT-PCR diagnosis of COVID-19.3

Chest CT is more sensitive than chest x-ray in determining COVID-19. In a systematic review and meta- analysis, the pooled positive rate of CT imaging was 89.76 % and 90.35% when only including thin section CT.17 However, Chest CT is more expensive and may not be readily available. Its routine use is impractical due to the required cleaning and decontamination procedure. Chest x-ray is a widely available assessment tool in hospital and ambulatory centers and allows a relatively rapid cleaning of equipment and turn- over between patients

The proportion of patients with abnormal baseline chest x-ray findings ranged from 33% to 100%. The different rates may be due to research design and patient selection for imaging. The published studies varied from case reports, case series, and cross-sectional studies. Patients included also had different clinical presentations, severity of respiratory symptoms ranging from those with mild

disease to those who developed severe disease and acute respiratory distress syndrome (ARDS). Asthma and Chronic obstructive pulmonary disease (COPD), known predictors of poor outcome were seen in 9 % -14% 5-6 & and 1% - 33% 2,4-9 of cases, respectively in articles which reported co- morbidities. Setting of the studies were outpatient urgent care, to hospitals and intensive care units. Most of the reports had baseline imaging done upon admission with median (range): 4 (2-15) days from symptom onset. The timing of radiography is important as some patients with normal baseline chest x-rays developed abnormalities on follow-up radiographs.3 Imaging findings may change throughout the disease course. Correlation with signs, medical history, and demographic characteristics with normal and abnormal chest x-ray findings of patients with COVID-19 have not been adequately explored.

The most common chest x-ray features in patients with COVID-19 are ground-glass opacity and consolidation. Infection involves mostly bilateral lungs and the lower lobes. No abnormalities were detected in 5- 67%. Early reports have stated that initial imaging might show normal findings in 15-20% of individuals. A normal chest imaging examination does not exclude presence of infection.14

The reported imaging features in COVID-19 have significant overlap with Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) in terms of the presence of peripheral multifocal airspace opacities (ground glass opacities, consolidation, or both).

Cavitation, pleural effusion, and lymphadenopathy are infrequently found in all coronaviruses. Early bilateral involvement however is unique in the imaging characteristics of COVID-19 in contrast to unilateral involvement in the early stages of SARS and the Middle East respiratory syndrome.15,16

Viral pneumonia and bacterial pneumonia have limited radiography cues to differentiate them. Chest x-ray features suggesting bacterial etiology include alveolar infiltrates, lobar consolidation, nodular densities, and pleural effusion. In contrast, interstitial infiltrates with patchy and bilateral distribution are more common in viral pneumonia, including COVID-19.17In a cohort of 456 patients with pneumonia, the presence of ground-glass opacity was an independent predictor of viral pneumonia (OR 4.68 R 4.68; 95% CI, 2.48–8.89). The sensitivity, specificity, positive- and negative-predictive values (PPV and NPV) of ground- glass opacity were 43, 84, 40, and 86%, respectively.18 Since no radiographic finding is pathognomonic for COVID-19 pneumonia, it is suspected based on essential cues in the history and viral-like clinical presentation.

Our report has important limitations. Not all patients in the included papers had a chest x-ray. Variations in clinical decision-making by health care providers, existing hospital protocols, and patient symptoms and presentation may have influenced the availability of chest x-rays among patients confirmed to have COVID- 19. Studies did not assess for radiologist’s interrater reliability. Studies,

however, highlighted the findings reported for COVID-19 patients in a clinical setting with variability in chest x-ray assessment. We limited the analysis to initial chest – ray findings to examine the value of chest radiography in the early diagnosis of COVID-19. Progression of findings on follow-up imaging, when performed, was not described.

Despite the limitations, the paper has value in helping clinicians realize the value as well as shortcomings of chest radiographs in the diagnosis and management of patients during the COVID-19 pandemic.

RECOMMENDATIONS FROM OTHER GUIDELINES

ACR Recommendation for the Use of Chest Radiography and Computed (CT) for Suspected COVID-19 Infection19

•The Center for Disease Control and Prevention (CDC) does not recommend a chest x-ray or CT to diagnose COVID-19. Viral testing remains to be the only specific method of diagnosis.

•Confirmation with a viral test is required even if radiologic findings are suggestive of COVID-19 on chest x-ray or CT.

•Generally, the findings on chest imaging in COVID-19 are not specific and overlap with other infections, including influenza, HINI, SARS, and MERS.

Should Chest X-ray be used in Diagnosing COVID-19?

The CAR and the CSTR Recommendations on COVID-19 Management in Imaging Departments March 25, 2020-version 220

•The Center for Disease Control and Prevention (CDC) does not recommend a chest x-ray or CT to diagnose COVID-19. Viral testing remains to be the only specific method of diagnosis.

•Confirmation with a viral test is required even if radiologic findings are suggestive of COVID-19 on chest x-ray or CT.

•Generally, the findings on chest imaging on COVID-19 are not specific and overlap with other infections.

•Imaging should only be conducted in those COVID-19 patients were imaging impacts the management of the condition.

•Emergency department of hospitals, ambulatory care

facilities, or long term home care may consider deploying portable radiography units such as chest x-ray, as these are considered medical necessities. Using portable radiography units prevents the need to bring patients into radiography rooms. The surfaces of these units are easily cleaned. These minimize the spread of infections in large healthcare institutions.

British Society of Thoracic Imaging Statement, Clinical Radiology21

•Disease severity and timing of imaging appear to impact the rates of normal baseline imaging. In non- severe disease, up to 18 % of patients had normal initial chest x-ray or CT

•Chest x-ray typically shows patch or diffuse asymmetric airspace opacities, similar to other causes of coronavirus pneumonia

The Role of Chest Imaging in Patient Management During the COVID-19 Pandemic: A Multinational Consensus Statement from the Fleischner Society22

•Imaging is not routinely indicated as a screening test for COVID-19 in asymptomatic individuals

•Imaging is not indicated for patients with mild features of COVID-19 unless they are at risk for disease progression

•Imaging is indicated for patients with moderate to severe features of COVID-19 regardless of COVID-19 test results

•Imaging is indicated for patients with COVID-19 and evidence of worsening respiratory status

•In a resource-constrained environment where access to CT is limited, a chest x-ray may be preferred for patients with COVID-19 unless with a worsening respiratory feature, where CT is needed.

APPLICATION IN CLINICAL PRACTICE

Because chest radiography is not sensitive for the detec- tion of ground-glass opacity (GGO) and may demonstrate

normal findings in the early stage of infection, it is not recommended for the diagnosis, nor is the preferred imaging modality for COVID-19. The Fleischner Society has come up with guidance on the utility of imaging within three scenarios representing varying patient risk factors, community conditions, and healthcare environment. Based on the consensus statement, a chest x-ray may be done on patients with moderate to severe COVID-19 features in a resource-constrained setting with limited or delayed access to RT-PCR COVID-19 testing or CT scan. A presumptive diagnosis can be made if imaging reveals features of COVID-19, which may facilitate rapid triage, infection control, and clinical management.

CONCLUSION

Bilateral ground-glass opacities and consolidation in the periphery, which are non-specific, are the most common abnormalities reported among COVID-19 patients. The sensitivity of the chest x-ray is affected by the time of imaging with illness onset and severity of symptoms. The chest x-ray is not as sensitive as RT-PCR in diagnosing COVID-19.

Declaration of conflict of interest

No conflict of interest.

REFERENCES

1.International Centre for Allied Health Evidence. University of South Australia Critical Appraisal Tools. Critical Appraisal Tools [Internet]. May 13, 2020 [cited 2020 May 13]. Available from: https://www.unisa.edu.au/research/Health-Research/Research/ Allied-Health-Evidence/Resources/CAT/

2.Rodriguez-Morales AJ, Cardona-Ospina JA, Gutiérrez-Ocampo E, Villamizar-Peña R, Holguin-Rivera Y, Escalera-Antezana JP, et al. Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis. Travel Med Infect Dis. 2020 Mar-Apr; 43:101623. doi:10.1016/j.tmaid.2020.101623

3.Wong HYF, Lam HYS, Fong AHT, Leung ST, Chin TWY, Lo CSY, et al. Frequency and distribution of chest radiographic findings in patients positive for COVID-19. Radiology. 2020 Aug;296(2):E72-E78. doi:10.1148/radiol.2020201160

4.Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr; 382(18):1708-1720. doi:10.1056/NEJMoa2002032

5.Bhatraju PK, Ghassemieh BJ, Nichols M, Kim R, Jerome KR, Nalla AK, et al. Covid-19 in Critically Ill Patients in the Seattle Region

— Case Series. N Engl J Med. 2020 May; 382(21):2012-2022. doi:10.1056/NEJMoa2004500

6.Arentz M, Yim E, Klaff L, Lokhandwala S, Riedo FX, Chong M, et al. Characteristics and Outcomes of 21 Critically Ill Patients With COVID-19 in Washington State. JAMA. 2020 Apr; 323(16): 1612-1614. doi:10.1001/jama.2020.4326

7.Ng M-Y, Lee EY, Yang J, Yang F, Li X, Wang H, et al. Imaging Profile of the COVID-19 Infection: Radiologic Findings and Literature Review. Radiology Cardiothoracic Imaging. 2020;2(1):e200034. doi:10.1148/ryct.2020200034

8.Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Feb; 395(10223):507-513. doi:10.1016/S0140-6736(20)30211-7.

9. Albarello F, Pianura E, Di Stefano F, Cristofaro M, Petrone A, Marchioni L, et al. 2019-novel Coronavirus severe adult respiratory distress syndrome in two cases in Italy: An uncommon radiological presentation. Int J Infect Dis. 2020 Apr; 93:192-197. doi:10.1016/ j.ijid.2020.02.043

10.Yoon SH, Lee KH, Kim JY, Lee YK, Ko H, Kim KH, et al. Chest Radiographic and CT Findings of the 2019 Novel Coronavirus Disease (COVID-19): Analysis of Nine Patients Treated in Korea. Korean J Radiol. 2020 Apr; 21(4):494-500. doi:10.3348/kjr.2020.0132

11.Weinstock MB, Echenique A, Russell JW, Leib A, Miller JA, Cohen DJ, et al. Chest x-ray findings in 636 ambulatory patients with COVID-19 presenting to an urgent care center: a normal chest x-ray is no guarantee. J Urgent Care Med. 2020; 14(7):13-18.

12.Cozzi D, Albanesi M, Cavigli E, Moroni C, Bindi A, Luvarà S, et al. Chest X-ray in new Coronavirus Disease 2019 (COVID-19) infection: findings and correlation with clinical outcome. Radiol Med. 2020 Aug; 125(8):730-737. doi:10.1007/s11547-020-01232-9

13.Tahamtan A, Ardebili A. Real-time RT-PCR in COVID-19 detection: issues affecting the results. Expert Rev Mol Diagn. 2020 May; 20(5):453-454. doi:10.1080/14737159.2020.1757437

14.Hosseiny M, Kooraki S, Gholamrezanezhad A, Reddy S, Myers L. Radiology Perspective of Coronavirus Disease 2019 (COVID-19): Lessons From Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome. Am J Roentgenol. 2020 May; 214(5):1078- 1082. doi:10.2214/AJR.20.22969

15.Das KM, Lee EY, Langer RD, Larsson SG. Middle East Respiratory Syndrome Coronavirus: What Does a Radiologist Need to Know? Am J Roentgenol. 2016 Jun; 206(6):1193-1201. doi:10.2214/ AJR.15.15363

16.Ooi GC, Daqing M. SARS: radiological features. Respirology. 2003 Nov; 8 Suppl(s1):S15-9. doi:10.1046/j.1440-1843.2003.00519.x

17.Freeman AM, Leigh Jr TR. Viral Pneumonia. In: StatPearls [Internet].

Treasure Island (FL): StatPearls Publishing; 2020 Jan. [cited 2020 Aug  24].  Available  from:  http://www.ncbi.nlm.nih.gov/books/ NBK513286/

18.Kim JE, Kim UJ, Kim HK, Cho SK, An JH, Kang SJ, et al. Predictors of viral pneumonia in patients with community-acquired pneumonia. PLoS ONE. 2014 Dec; 9(12):e114710. doi:10.1371/journal.pone. 0114710

19.ACR Recommendations for the use of Chest Radiography and Computed Tomography (CT) for Suspected COVID-19 Infection [Internet]. May 17, 2020 [cited 2020 May 17]. Available from: https://www.acr.org/Advocacy-and-Economics/ACR-Position- Statements/Recommendations-for-Chest-Radiography-and-CT- for-Suspected-COVID19-Infection

20.Canadian Association of Radiologists, Canadian Society of Thoracic

Radiology. The Canadian Association of Radiologists (CAR) and the Canadian Society on Thoracic Radiology (CSTR) Recommendations on COVID-19 Management in Imaging Departments [Internet]. [cited 2020 Apr 17]. Available from: https://car.ca/wp-content/ uploads/2020/03/CAR-CSTR-COVID-19-Recommendations- En.pdf

21.Nair A, Rodrigues JCL, Hare S, Edey A, Devaraj A, Jacob J, et al. A British Society of Thoracic Imaging statement: considerations in designing local imaging diagnostic algorithms for the COVID-19 pandemic. Clin Radiol. 2020 May; 75(5):329-334. doi:10.1016/

j.crad.2020.03.008	CJ, Haramati LB, Sverzellati N, Kanne
22. Rubin GD, Ryerson
JP, Raoof S, et al. The	Role of Chest Imaging in Patient Management

During the COVID-19 Pandemic. Chest. 2020 Jul;158(1):106-116. doi: 10.1016/j.chest.2020.04.003

APPENDICES

Appendix A. Search hits per database

	Search	Search Terms
	Number

1“Coronavirus Infections” [Mesh} OR “Coronavirus” [Mesh] OR coronavirus OR novel coronavirus OR NCOV or “COVID-19” [Supplementary Concept} OR covid19 OR covid 19 OR covid-19 OR “severe acute respiratory syndrome coronavirus 2” [Supplementary Concept] OR severe acute respiratory syndrome coronavirus 2 OR SARS2 OR SARS 2 OR SARS COV2 OR SARS COV 2 OR SARS-COV-2

	Pubmed	Hits EBSCO (CINAHL Plus	Science Direct
		with full-text, Medline,
	n=hits		n=hits
		Medline Complete) n=hits
	21,589	51,531	127,446

Appendix B. Critical appraisal by the two reviewers

Critical appraisal for systematic review

Criteria

1. What question (PICO) did the systematic review address?

Rodriguez-Morales et al.

(2020)

R1	R2
Y	Y

Criteria

1.Were the criteria for inclusion in the sample clearly defined?

Ng et al.		Wong et al.		Guan et al.		Bhatraju et al.		Arentz et al.		Weinstock et al.
(2020)7		(2020)3		(2020)4		(2020)5		(2020)6		(2020)
R1	R2	R1	R2	R1	R2	R1	R2	R1	R2	R1	R2
Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y