key: cord-1052118-hktp8vie
authors: Sasaki, Hisashi; Kawano, Shuichi; Ota, Shinichiro; Taniguchi, Hiroaki; Kodama, Tatsuya; Obinata, Hirofumi; Tamura, Kaku; Ito, Toshimitsu; Uwabe, Yasuhide
title: Efficacy of Chest Radiography as a Primary Care Triage Tool in Severe Coronavirus Disease
date: 2021-07-17
journal: Intern Med
DOI: 10.2169/internalmedicine.5205-20
sha: 99c986d4d7aa075c199eec6254ac158f967c39a9
doc_id: 1052118
cord_uid: hktp8vie

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 has spread globally, and it is important to utilize medical resources properly, especially in critically ill patients. We investigated the validity of chest radiography as a tool for predicting aggravation in coronavirus disease (COVID-19) cases. METHODS: A total of 104 laboratory-confirmed COVID-19 cases were referred from the cruise ship “Diamond Princess” to the Self-Defense Forces Central Hospital in Japan from February 11 to 25, 2020. Fifty-nine symptomatic patients were selected. Chest radiography was performed upon hospitalization; subsequently, patients were categorized into the positive radiograph (Group A) and negative radiograph (Group B) groups. Radiographic findings were analyzed with a six-point semiquantitative score. Group A was further classified into two additional subgroups: patients who required oxygen therapy during their clinical courses (Group C) and patients who did not (Group D). Clinical records, laboratory data, and radiological findings were collected for an analysis. RESULTS: Among 59 patients, 34 were men with a median age of 60 years old. Groups A, B, C, and D consisted of 33, 26, 12, and 21 patients, respectively. The number of patients requiring oxygen administration was significantly larger in Group A than in Group B. The consolidation score on chest radiographs was significantly higher in Group C than in Group D. When chest radiographs showed consolidation in more than two lung fields, the positive likelihood ratio of deterioration was 10.6. CONCLUSIONS: Chest radiography is a simple and easy-to-use clinic-level triage tool for predicting the severity of COVID-19 and may contribute to the allocation of medical resources.

Coronavirus disease (COVID-19) is a global threat due to its high infectivity and transmissibility from human to human (1) . As infections spread rapidly around the world, the World Health Organization (WHO) declared it a pandemic on March 11, 2020 (2) . Underlying factors, such as hypertension, diabetes, an older age, and high levels of lactate dehydrogenase (LDH) and D-dimer, have been reported as risk factors of deterioration (3) (4) (5) . According to a report from China, the mortality rate of COVID-19 is 2.3% (6) . The same report also states that the majority of patients are asymptomatic. Therefore, it has become a pressing issue to be able to diagnose disease severity accurately in order to treat patients at appropriate medical institutions and to prevent medical collapse.

Although chest computed tomography (CT) may be useful in assessing the severity of COVID-19 (7, 8) , the use of chest CT as a routine test for making a definitive diagnosis is still controversial because of its low negative predictive value (9) as well as from the perspective of high radiation exposure. Furthermore, chest CT is not always available, especially at primary care-level clinics. As the volume of pa- Figure 1 . Method of calculating the six-point semiquantitative score. Lung fields are separated into six areas. GGA is in the right middle and lower lung fields; consequently, the GGA score is calculated as two points (A). Consolidation is in the upper and middle lung fields; consequently, the score is calculated as 2 points (B) tients increases, the initial tool for assessment should be simpler and more convenient. Chest radiography is a simple and convenient tool generally used for assessing lung lesions and can be applied more readily than CT at the clinic level. However, its usefulness is not verified.

We therefore investigated the correlation between disease severity and radiological findings in COVID-19 cases and tested the efficacy of chest radiography as a simple screening tool for predicting patient deterioration.

This is a retrospective review of 104 laboratory-confirmed COVID-19 cases referred from the cruise ship "Diamond Princess" to the Self Defense Forces Central Hospital in Japan. All cases were enrolled from February 11 to 25, 2020.

Symptomatic patients were categorized into two groups (A and B) depending on chest radiographic abnormalities. On the premise that people who visit primary care clinics generally have some symptoms, asymptomatic patients and patients who lacked chest radiographs were excluded from the analysis. Symptomatic patients with radiographic abnormalities (positive radiograph) that seemed to be caused by COVID-19 were allocated to Group A, and those without radiographic abnormalities (negative radiograph) were allocated to Group B. Group A was also further classified into two subgroups depending on oxygen administration: patients who required oxygen therapy during their clinical courses (Group C) and patients who did not (Group D). The symptoms were a fever (>37.5°C), general malaise, headache, nasal discharge, sore throat, cough, muscle pain, joint pain, diarrhea, nausea and vomiting, abdominal pain, and dyspnea. Regardless of radiographic abnormalities, all cases were defined as severe or mild depending on oxygen administration.

Patient information, including clinical records, laboratory findings, and radiographs, were collected and reviewed from the electronic medical records in our hospital.

Fifty-nine patients underwent chest radiography after admission. The examination protocol was standing position (post anterior) or supine position (anterior post). Two pulmonologists interpreted the chest radiographs of the 59 patients. Among the patients with positive findings on chest radiographs (Group A), radiological findings were classified according to their distribution and characteristics. A sixpoint semiquantitative score was used for the analysis. The distribution of chest radiographic abnormalities was sorted according to six affected lung fields (right upper field, right middle field, right lower field, left upper field, left middle field, and left lower field), and the abnormalities were classified into two common radiological manifestations [groundglass attenuation (GGA) and consolidation]. GGA and consolidation of each lung field on chest radiographs were scored separately. If there were two localized consolidations in the same lung field, the score was one. If GGA straddled two lung fields, the score was two. GGA and consolidation were scored independently regardless of their size and number. Fig. 1 shows the scoring method and examples.

Data were statistically analyzed with the GraphPad Prism 8.4 software program (Graph Pad Software, San Diego, USA). Continuous variables were expressed as the mean± standard deviation (SD) or median with interquartile range (IQR), and groups were compared using Student's t-test and the Mann-Whitney U-test for parametric and non-parametric data, respectively, as well as using the chi-squared test. The sensitivity and specificity were calculated by a receiver op- erating characteristic (ROC) curve to predict the severity of the disease based on the findings on chest radiographs. A two-sided p-value of less than 0.05 was considered statistically significant.

The Institutional Review Board at the Self-Defense Forces Central Hospital approved this study (Approval number 01011), and all patients provided their written informed consent for the publication of their innominate data.

Of the 59 patients, 34 (58%) were men with a median age of 60 years old. Fig. 2 shows the patient recruitment flowchart and breakdown. Thirty-three symptomatic patients (56%) had abnormal radiological findings (Group A) on their chest radiographs, and 26 symptomatic patients (44%) had no abnormal findings (Group B). Twelve patients from Group A (36%) required oxygen therapy during hospitalization (Group C), and the remaining 21 (Group D) (64%) did not require oxygen therapy. Table 1 shows the characteristics of the symptomatic patients. There were significant differences in the age, fever incidence, and muscle pain between Group A and Group B. Table 2 shows the laboratory findings of symptomatic patients. Blood urea nitrogen (BUN), LDH, serum albumin, Creactive-protein (CRP), white blood cell (WBC) counts, and lymphocyte counts showed statistically significant differ-ences between Groups A and B. The 6-point semiquantitative score of consolidation was significantly higher in Group C than in Group D (p<0.05). In contrast, there were no significant differences in GGA scores between Groups C and D (Table 3) . Twelve patients (36%) from Group A required oxygen administration through their clinical courses, whereas only 1 patient (3%) from Group B required oxygen therapy (Table 4) . Of the 13 patients who required oxygen therapy, 8 (62%) were men, and the mean age was 70 years old. Five of the 13 patients received high-flow nasal oxygen therapy, and 1 patient was treated by mechanical ventilation with tracheal intubation. The area under the ROC curve was used to predict the disease severity based on chest radiography. Consolidation had an area under the curve of 0.816 [95% confidence interval (CI), 0.648-0.983; p=0.002] (Fig. 3) . When chest radiographs showed consolidation in more than 2 lung fields, the sensitivity and specificity were 50% (95% CI, 25.4-74.6%) and 95% (95% CI, 77.3-99.7%), respectively. The positive likelihood ratio of severity was 10.6. Fig. 4 shows representative chest radiographs before and after treatment in a patient who required oxygen therapy.

The present study investigated the correlation between radiographic findings and the severity of symptomatic COVID-19, which was considered the typical model for walk-in cases. The severity, age, underlying disease, inci- The p values indicate differences between patients in Groups A and B patients. Continuous variables were expressed as mean±SD. Groups were compared using unpaired t-tests. p<0.05 was considered statistically significant. SD: standard deviation, BUN: blood urea nitrogen, AST: aspartate aminotransferase, ALT: alanine aminotransferase, γ-GTP: γ-glutamyltransferase, LDH: lactate dehydrogenase, CRP: C-reactedprotein, WBC: white blood cells, APTT: activated partial thromboplastin time Comparison of six-point semiquantitative score between patients who required oxygen during their clinical courses (group C) and patients who did not (group D) with abnormal chest X-ray findings. Continuous variables were expressed as mean standard deviation (SD). Groups were compared using the Mann Whitney U-test or chi-squared tests. p value <0.05 was considered statistically significant. GGA: ground glass attenuation Groups were compared using chi-squared tests. p<0.05 was considered statistically significant.

dence of a fever (>37.5°C), levels of LDH and CRP, and leukocyte and lymphocyte counts have been reported as risk factors (3) (4) (5) . These factors are consistent with those in previous reports.

Our results imply that the GGA score at the initial chest radiographic examination has a limited effect on the need for oxygen administration. In contrast, the consolidation score was significantly associated with the presence or absence of oxygen administration. Specifically, our study suggests that there may be a risk of aggravation if chest radiographs show consolidation in two or more lung fields. Patients diagnosed with COVID-19 may be less likely to progress to a severe disease state if their initial chest radiograph findings are normal or show only GGA. The typical CT finding in COVID-19 is patchy GGA in the peripheral area, and when it deteriorates, consolidations are found and increase in number (10, 11) . Consolidations are easily detectable, unlike GGA, on chest radiographs, even for doctors who are not familiar with chest radiography. In other words, patients at potential risk for deterioration may have chest radiographs that show easily identifiable abnormalities com-pared to those in mild cases. Chest radiography is simpler to administer and has a lower radiation exposure than CT. Furthermore, primary care physicians can perform radiography easily at clinics, unlike CT (12) .

Several limitations associated with the present study war- rant mention. First, this was a retrospective review, and the number of patients analyzed was small. Second, the enrolled patients were mostly elderly people, and the data of young people are not shown. However, given the evidence that being elderly is an important risk factor of disease progression, the disproportional age distribution in the sample may be acceptable. Third, we were unable to strictly distinguish similar respiratory diseases, such as interstitial lung diseases, microbial superinvasion with influenza, mycoplasma, and other types of bacterial pneumonia, from COVID-19. Some of the patients with a positive polymerase chain reaction (PCR) test and an abnormal chest radiograph may not have had true lung lesions due to COVID-19. Finally, the radiographic results may not reflect the exact clinical status of patients due to variations in the timing of chest radiography in each patient. It is important to avoid overlooking the timing of aggravation by comprehensively considering risk factors for aggravation, such as underlying diseases, other than chest radiographic findings.

Chest radiography can be an easy-to-use primary care triage tool for COVID-19 patients, which can lead to the appropriate consumption of medical resources and may prevent medical disruption. We hope that our results will be of use to all healthcare providers who are currently struggling around the world with the management of COVID-19.

The authors state that they have no Conflict of Interest (COI).

Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

World Health Organization declares global emergency: a review of the 2019 novel coronavirus (COVID-19)

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

History in a crisis -lessons for Covid-19

Clinical characteristics of coronavirus disease 2019 in China

Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72,314 cases from the Chinese Center for Disease Control and Prevention

Coronavirus disease 2019 (COVID-19): role of chest CT in diagnosis and management

Relation between chest CT findings and clinical conditions of coronavirus disease (COVID-19) pneumonia: a multicenter study

Radiological Society of North America expert consensus statement on reporting chest CT findings related to COVID-19. Endorsed by the Society of Thoracic Radiology, the American College of Radiology, and RSNA -secondary publication

CT imaging features of 2019 novel coronavirus (2019-nCoV)

Correlation of chest CT and RT-PCR testing in coronavirus disease 2019 (COVID-19) in China: a report of 1014 cases

Interpretation of plain chest roentgenogram

The Internal Medicine is an Open Access journal distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. To view the details of this license

We thank everyone involved in the COVID-19 management and treatment team from the Self-Defense Forces Central Hospital in Japan and members who were assembled from other institutes of the Japan Self-Defense Forces. In particular, we thank Dr. Sakiko Tabata