As the novel coronavirus disease (COVID-19) rapidly spreads throughout the world, suspected COVID-19 cases with consecutive negative RT-PCR results deserve high attention in the disease control and patient management.(4) According to the current diagnostic criterion, viral nucleic acid test via RT-PCR is the “gold standard” for the confirmation of COVID-19. However, given the limited number and time consuming process of RT-PCR kits in some medical centers and the possibility of false negative results via RT-PCR, clinicians and radiologists probably encounter and interpret suspected COVID-19 cases without timely viral nucleic acid test or with negative result.(7, 15, 16) Actually, COVID-19 is contagious even in incubation period regardless of the RT-PCR result.(3, 6) To avoid over-dependence on RT-PCR results, clinical and imaging analysis of suspected COVID-19 cases is particularly important. Chest CT is supposed to be a more sensitive method in detecting COVID-19 than RT-PCR.(14-16) In this study, we reviewed the clinical and chest CT characteristics of a cluster of patients with SARS-CoV-2 exposure history and fever and/or respiratory symptoms but without positive RT-PCR results for COVID-19. The typical chest CT manifestation of suspected COVID-19 cases may help medical institutions to isolate and treat patients at early stage.
Without positive RT-PCR results, the enrolled suspected COVID-19 cases still showed some according laboratory features including normal or reduced counts of lymphocytes at early stage, elevated C-reactive protein and D-dimers in the majority of patients. Together with the exposure history and clinical symptoms, suspected COVID-19 cases were determined. In practice, chest CT was the routine method to detect the pulmonary abnormality of suspected cases. In this study, all of the patients presented ground glass opacity (GGO) and over half of the patients had consolidation and reticular/ interlobular septal thickening at the initial scan. This result was in accordance to earlier investigations with confirmed COVID-19. GGO, consolidation and interstitial abnormality were the most common findings of either confirmed or suspected COVID-19 patients.(9, 10, 17-19) As the time interval between initial CT scan and symptom onset were various, the pattern of CT manifestation were different as well. The 3 kinds of lesions were often mixed and tended to present simultaneously, especially in patients with extensive involvement. In patients with just symptom onset, focal GGO was the common findings on chest CT.(11-14) Additionally, pulmonary involvement was always characterized by a tendency of bilateral multiple lobes involvement and a predominant distribution in peripheral and lower parts of the lung.(10, 17) Our results demonstrated that the CT score of right lower lobe was significantly higher than right upper lobe, indicating more extensive involvement of lower lobe. Meanwhile, some other radiologic signs such as mediastinal lymphadenopathy were not present in this series of patients and pleural effusion was found in only one patient at initial CT scan. Based on the typical chest CT findings, clinicians and radiologists would be more confident to distinguish a suspected COVID-19 from other pulmonary infection.
Despite of lack of supportive RT-PCR results, serial CT imaging of suspected COVID-19 patients could reveal the evolution of the disease and help to monitor disease changes. A total of 70 CT scans was evaluated using a CT score system for the extent of the pulmonary involvement in suspected COVID-19 patients during the follow-up. According to the changes of extent and pattern of pulmonary lesions, most patients showed an improvement from the peak level of the disease, except for 2 deceased cases. The extent of disease on CT scans increased markedly from the first week to the second week after symptom onset, then decreased gradually during the third week and after. The time course of suspected COVID-19 on chest CT was similar to previous investigations on confirmed cases. The peak level of the disease emerged at the second week after symptom onset. (11, 14) In this cluster of CT scans, the general CT scores after the second showed no marked decrease because some patients did not fully improve during follow-up. In the progressing stage, besides of the enlarged pulmonary lesions, the pattern of lung lesions became more complex including more extensive consolidation and reticular/interlobular septal thickening, and other signs such as reversed halo sign emerged. The findings were largely similar to earlier radiologic investigative effort on confirmed COVID-19 patients.(9, 13) In the improving stage, some patients showed almost complete disappearance of GGO, consolidation and interstitial abnormality, while others showed incomplete absorption of these lesions possibly due to the insufficient observation period. In some cases, the pulmonary lesions on follow-up CT scans could presented as shifting from one location to another or “wane and wax”. This might be due to the treatment during progressing stage. The evolution of extent and pattern of lung lesions on chest CT had some features and could be used to evaluate the condition of suspected COVID-19 patients.
We acknowledged several limitations in this study. Firstly, the small sample size could not represent all conditions of suspected COVID-19 and larger sampled studies would be needed to understand the natural history of the disease. Secondly, not all the radiological outcomes of each individual were observed in this study because of limited period, further studies on prognosis would be more helpful for patient management. Thirdly, the possible medical intervention before in-patient of some patients might affect the interpretation of CT images.
In conclusion, our investigative effort demonstrated that the GGO, consolidation and interstitial abnormality with predominantly bilateral and peripheral distribution was the most common pattern for suspected COVID-19 patients with negative RT- PCR results. Most cases showed a recovering process from suspected COVID-19 on chest CT, despite of 2 deceased cases. The CT score system showed most extensive pulmonary involvement at second week after symptom onset. In the progressing stage, increased extent of mixed pulmonary lesions was found on chest CT. In the improving stage, gradual absorption of pulmonary lesions was the common finding. In some cases, the pulmonary lesions on follow-up CT scans could presented as shifting from one location to another or “wane and wax”, which might be due to the treatment during progressing stage. Considering the exposure history, clinical symptoms and laboratory results, for patients with typical CT findings of viral pneumonia, even if the viral nucleic acid test via RT-PCR is negative, clinicians and radiologists should also be alerted and take appropriate preventive measures.