Some patients with positive chest CT findings may present with negative results of real-time reverse-transcription polymerase chain reaction (RT-PCR) tests for coronavirus disease 2019 (COVID-19). In this study, the authors present chest CT findings from five patients with COVID-19 infection who had initial negative RT-PCR results. All five patients had typical imaging findings, including ground-glass opacity (five patients) and/or mixed ground-glass opacity and mixed consolidation (two patients). After isolation for presumed COVID-19 pneumonia, all patients were eventually confirmed to have COVID-19 infection by means of repeated swab tests. A combination of repeated swab tests and CT scanning may be helpful for individuals with a high clinical suspicion of COVID-19 infection but negative findings at RT-PCR screening.

Summary In patients at high risk for coronavirus disease 2019 (COVID-19) infection, chest CT evidence of viral pneumonia may precede positive reverse-transcription polymerase chain reaction test results.

Key Results ■ Five patients infected with coronavirus disease 2019 presented with initial negative results at reverse-transcription polymerase chain reaction testing but had a positive CT finding.

■ All patients had typical imaging findings, such as ground-glass opacity (five patients, 100%) or mixed ground-glass opacity and mixed consolidation (two patients, 40%); the mean CT involvement score was 6.8, and the median CT involvement score was 4 (highest CT involvement score, 14; lowest CT involvement score, 2).

Introduction

In December 2019, an outbreak of coronavirus disease 2019 (COVID-19) pneumonia began in Wuhan (Hubei, China) and spread rapidly (1). Without a therapeutic vaccine or specific antiviral drugs, early detection and isolation become essential against COVID-19. The use of chest CT as a screening tool for patients suspected of having COVID-19 is not well understood. In our experience, some patients with likely COVID-19 infection may have negative results at initial reverse-transcription polymerase chain reaction (RT-PCR) testing. Reasons for false-negative RT-PCR results may include insufficient cellular material for detection and improper extraction of nucleic acid from clinical materials.

The purpose of this study was to describe CT imaging features in five patients with initial negative or weakly positive RT-PCR results but with high suspicion of COVID-19 infection.

Materials and Methods

This study was approved by the medical ethical committee (approval number: 2020002), which waived the requirement for patients’ informed consent referring to the Council for International Organizations of Medical Sciences guideline. J.L. had full access to all data in the study and had final responsibility for the decision to submit for publication.

Clinical Evaluation

Data from patients with laboratory-confirmed COVID-19 infection with initial negative RT-PCR results in the Radiology Quality Control Center database (Hunan Province) were collected. Diagnosis of COVID-19 was determined according to the following three methods: isolation of COVID-19 or at least two positive results with real-time RT-PCR assay for COVID-19 or a genetic sequence that matches COVID-19. From 167 laboratory-confirmed cases, a total of five patients (one woman, four men; age range, 25–66 years) who underwent CT scanning from three cities in Hunan Province, China, were included in this study. Three patients were evaluated in Changsha, one in Changde, and one in Xiangtan.

Available clinical history, laboratory results, and epidemic characteristics were collected. According to the COVID-19 guideline (trial version 5) (2), disease severity was categorized into four groups: mild, common, severe, and fatal. All patients underwent CT scanning on the same day when the initial mouth swab test was performed.

Image Interpretation

Two thoracic radiologists (X.X. and W.Z. with 10 years of experience) blinded to the clinical data reviewed the CT images independently and resolved discrepancies by consensus. All images were viewed with both lung (width, 1500 HU; level, −700 HU) and mediastinal (width, 350 HU; level, 40 HU) settings. The presence or absence of nine image features was recorded: ground-glass opacities (GGOs), consolidation, mixed GGO and consolidation, traction bronchiectasis, bronchial wall thickening, reticulation, subpleural bands, vascular enlargement, and lesion distribution. The detailed definitions of these features were as described by Ajlan et al (3). We divided each lung into three zones: upper (above the carina), middle (below the carina up to the inferior pulmonary vein), and lower (below the inferior pulmonary vein) (4). A semiquantitative score was assigned for each lung zone, as follows: score 0, 0% involvement; score 1, less than 25% involvement; score 2, 25% to less than 50% involvement; score 3, 50% to less than 75% involvement; and score 4, 75% or greater involvement. There were six lung zones per patient; the maximum score was 4 × 6 zones, resulting in a score of 24.

Results

Of the 167 patients evaluated, five (3%) initially had negative RT-PCR results but positive chest CT findings with a pattern consistent with viral pneumonia (Fig 1). After positive CT findings, all patients were isolated for presumed COVID-19 pneumonia. Repeat swab testing and RT-PCR tests for COVID-19 infection were performed in all patients. In seven of the 167 patients (4%), CT findings were initially negative while RT-PCR results were positive. In 155 of the 167 patients (93%), both RT-PCR and CT results were concordant for COVID-19 infection. Of the five patients with negative RT-PCR results and positive CT findings at initial presentation, the median CT involvement score was 4. The highest CT involvement score was 14, and the lowest was 2.

Figure 1: Patient flowchart. Of 167 patients screened, five (3%) had negative reverse-transcription polymerase chain reaction (RT-PCR) results and chest CT findings compatible with coronavirus 2019 pneumonia. Figure 1: Download as PowerPointOpen in Image Viewer

The description of five patients with positive CT findings and negative RT-PCR results are as follows.

Patient 1: A 62-year-old man with recent travel history to Wuhan, China, the epicenter of the COVID-19 outbreak (5), was admitted to the hospital with a fever and mild cough of 6 days duration. Chest CT showed multifocal GGO and parenchyma consolidation, predominantly involving subpleural regions of both lungs (Fig 2). The CT involvement score was 14. During isolation for presumed COVID-19 pneumonia, the patient became dyspneic and developed type I respiratory failure 5 days after admission. The second swab test for COVID-19 was positive 5 days after CT scanning.

Figure 2: Chest CT images in patient 1. A–D, CT images obtained at different levels of lung, from apex to basal segment, show bilateral multifocal ground-glass opacities (GGOs) and mixed GGO and consolidation lesions. Traction bronchiectasis (arrow in B) and vascular enlargement (arrow in D) are also shown. Figure 2: Download as PowerPointOpen in Image Viewer

Patient 2: A 60-year-old man with a fever of 39°C was referred for hospital evaluation. His wife had been previously diagnosed with COVID-19 pneumonia. His CT images showed multifocal GGO and mixed consolidation that mostly appeared at the peripheral area of the lung (Fig 3). The CT involvement score was 11. The first swab test was negative, and the patient was quarantined at home. Over the next week, multiple swab tests returned negative results, but his symptoms remained. On day 8, the swab test was positive, and the patient was hospitalized for further treatment.

Figure 3: Chest CT images in patient 2. A–D, CT images obtained at different levels of lung, from apex to basal segment, show multifocal ground-glass opacity and mixed consolidation that mostly appeared at peripheral area of both lungs. CT involvement score was 11. Figure 3: Download as PowerPointOpen in Image Viewer

Patient 3: A 25-year-old woman presented with cough, dizziness, and debility but no fever. Her RT-PCR results were weakly positive on the first swab test. Both her parents were diagnosed with COVID-19 pneumonia. She was quarantined at home. A second mouth swab test conducted the next day was negative, but a CT examination at that time showed bilateral subpleural GGO indicating viral pneumonia (Fig 4). The CT involvement score was 4. Two days after CT examination, the third swab test result was positive for COVID-19, confirming CT results.

Figure 4: Chest CT images in patient 3. A–D, CT images obtained at different levels of lung, from apex to basal segment, show bilateral subpleural bandlike areas of ground-glass opacity compatible with viral pneumonia. Figure 4: Download as PowerPointOpen in Image Viewer

Patient 4: A 66-year-old man with ongoing fever was admitted to the hospital. His social history was positive for close contact with an individual confirmed to have COVID-19 pneumonia. A swab test and RT-PCR for COVID-19 were negative. CT scanning was performed at the same time and showed patchy GGOs in the subpleural regions of both lungs, suggesting viral pneumonia. The CT involvement score was 3. The patient was kept under observation and home isolation. During the period of isolation (2 days after chest CT scanning), the swab test turned positive, confirming prior CT results.

Patient 5: A 29-year-old man with ongoing fever was admitted to the hospital. He had traveled to Wuhan during the COVID-19 outbreak. A swab test and CT scanning were performed. The CT images showed multifocal mixed GGO and parenchyma consolidation involving the subpleural regions of both lungs, which are suspicious for viral pneumonia. The CT involvement score was 2. Two RT-PCR tests were both negative, and the patient was kept in home isolation. A third swab test was positive 8 days after CT scanning. The patient was hospitalized for isolated treatment.

Discussion

According to clinical data obtained from the Radiology Quality Control Center in Hunan Province, we evaluated radiologic characteristics of five patients with confirmed coronavirus disease 2019 (COVID-19) infection and negative or weakly positive results at initial reverse-transcription polymerase chain reaction testing. All patients presented with characteristic radiologic features of COVID-19 pneumonia from the first CT scan and then were confirmed by positive repeat swab tests during the isolated observation or treatment. Review of these five cases suggested that typical CT findings can help early screening of suspected cases and may help predict severe complications such as acute respiratory diseases.

According to current diagnostic criteria, laboratory examinations, such as swab tests, have become a standard and formative assessment for the diagnosis of COVID-19 infection (2). However, the current laboratory test is time consuming, and a shortage of supply test kits may not meet the needs of a growing infected population. RT-PCR testing for COVID-19 may be falsely negative due to laboratory error or insufficient viral material in the specimen.

Previous radiologic studies showed that the majority of cases had similar features on CT images, such as ground-glass opacity (GGO) or mixed GGO and consolidation. Coronavirus disease 2019 (COVID-19) pneumonia is likely to have a peripheral distribution with bilateral, multifocal lower-lung involvement (6–8). In the context of typical clinical presentation and exposure to other individuals with COVID-19, CT features of viral pneumonia may be strongly suspicious for COVID-19 infection despite negative reverse-transcription polymerase chain reaction results. In these cases, repeat swab testing and patient isolation should be considered.

Author Contributions

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Author contributions: Guarantor of integrity of entire study, J.L.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; agrees to ensure any questions related to the work are appropriately resolved, all authors; literature research, all authors; clinical studies, X.X., W.Z., C.Z., J.L.; experimental studies, X.X., Z.Z., W.Z., F.W., J.L.; statistical analysis, X.X., W.Z., J.L.; and manuscript editing, X.X., W.Z., C.Z., F.W., J.L.