Although RT-PCR test is considered the gold standard for definitive diagnosis, it has limitations such as detection sensitivity of COVID-19, long waiting time for results, staff experience, varying test protocols between countries, and quality differences of kits. Serial RT-PCR tests are performed to avoid these limitations, but this prolongs the diagnostic time. In addition, insufficient test kit resources can prevent retesting. Studies comparing the diagnostic accuracy of RT-PCR tests and CT findings in COVID-19 disease reported that the RT-PCR test may show false-negative results; the sensitivity of the test varies between 50 and 83%. Moreover, some studies suggest that the sensitivity of CT findings is higher than that of RT-PCRs [17,18,19]. In a study conducted by Xie et al. with 167 patients, it has been reported that all 5 patients with negative RT-PCR and positive CT at initial presentation were in direct contact with COVID-19 patients or that there were COVID-19 patients in their family. In the repeated RT-PCR tests, the positivity time varying between 2 and 8 days was detected in these patients [20].
In a study by Ai et al., 1014 patients were examined and CT findings were detected in 308 patients with negative RT-PCR results. Bilateral lung lesions consisting of ground glass opacities and consolidations were detected in lung CT of these 308 patients. For patients with a follow-up RT-PCR test, the mean interval between the initial negative to positive RT-PCR results is reported as 4–8 days. In this study, when RT-PCR results were taken as the reference standard, the sensitivity, specificity, and accuracy of chest CT in demonstrating COVID-19 infection were found to be 97%, 25%, and 68%, respectively [21].
In this retrospective study, we compared the clinical symptoms and CT findings of RT-PCR (+) and RT-PCR (N) patients. Both groups showed similar symptoms with fever and cough being the most frequent symptoms.
In our study, 80% of patients confirmed to have COVID-19 with RT-PCR assays showed positive findings at chest CT and typical CT findings were present in all patients with negative RT-PCR tests. In their review of 45 studies involving 4410 patients, Ojha et al. reported that the most common lesion patterns were GGO, consolidation, and GGO + consolidation (mixed) [22]. These findings were mostly observed in bilateral, peripheral, and lower lobe distributions. Similar results have been reported in different studies, and other CT findings such as crazy-paving pattern, halo and reversed halo sign, air bubble sign, subpleural curvilinear line, air bronchogram, airway changes, and fibrous stripe formations have been described [13, 14, 15]. Similar to these findings in the literature, GGO, GGO + consolidation, and consolidation were the most common lesion patterns in both groups examined in our study. Other findings identified were less frequent in both groups, and fibrous stripes were mostly seen on follow-up CTs at 1 and 2 months. Moreover, in accordance with the literature, bilateral, peripheral, and lower lobe lesion distributions were more frequent.
The COVID-19 literature reports that GGOs generally appear in follow-up CTs within the first 5 days after symptom onset, and the peak level is reached approximately 6–14 days after the onset of symptoms (GGO + consolidation). After 14 days, the consolidations regress more significantly, and resolution or fibrosis occurs toward the fourth week [22,23,24]. In our study of patients who underwent the same treatment protocol, resorption of the consolidations and a significant decrease in GGOs were detected in both groups in the first- and second-month follow-up CTs, and new fibrotic changes were observed in some patients. These findings were similar in both groups. Follow-up CT images were completely normal in 16 patients.
Our study identified 26 asymptomatic patients with CT findings. The frequency and distribution of lesion patterns in these patients of both groups were consistent with typical findings in the literature. Similar and lower viral loads have been reported in asymptomatic patients compared to symptomatic patients in previous studies [25, 26, 27]. There are insufficient data on the contagiousness of asymptomatic individuals and CT scanning may be helpful for the decision of isolation in clinically highly suspected asymptomatic RT-PCR (−) cases.
In studies examining the presence of ACE2 protein in samples taken from different tissues, high ACE2 protein expression in type 1 and type 2 alveolar epithelial cells but low expression in the cytoplasm of bronchial epithelial cells were observed. ACE2 protein was not detected in the nasal and oral mucosa or the surface epithelial cells of the nasopharynx. A study showed that BAL and tracheal aspirate samples had the highest viral load [28]. The upper respiratory tract’s positive RT-PCR test results may have been caused by the lower respiratory tract [29]. In individual patients, COVID-19 disease shows different viral load kinetics; thus, sampling timing, test quality, and disease progression have a significant impact on RT-PCR test results [30].
In this study, the laboratory findings, clinical symptoms, CT findings, and changes in CT findings after treatment were similar for COVID-19 patients and RT-PCR (−) patients with clinically suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Specifically, the frequencies, types, distributions, and distribution patterns of lesions on CT scans were similar in both groups.
In our study, no positivity was observed in the repeat tests of patients in the RT-PCR (−) group, and therefore the diagnosis of COVID-19 could not be made definitively. However, all patients in this group had contact with the COVID-19 patient or a recent history of travel abroad, and all of these patients also had typical CT findings. For these reasons, these patients are highly suspicious of COVID-19 disease. RT-PCR test may not be positive in these patients due to reasons such as incomplete sampling techniques, variations in viral load, sampling time after contact, late transfer to the laboratory, and kit sensitivity.
This study has some limitations. First of all, the sensitivity of RT-PCR test kits may be low. Second, tracheal aspirate and BAL sampling could not be performed in RT-PCR (−) patients due to high transmission risk. According to various studies with larger study populations, BAL samples of patients with negative nasopharyngeal PCR results should be re-tested. Third, the number of patients with follow-up CT scans was small.