In our study, we evaluated diagnostic accuracy of low-dose chest CT in adults suspected of COVID-19 to be referred from the emergency department to general wards. Due to the low prevalence of COVID-19 in our study population, negative chest CT allowed to rule out COVID-19 with high certainty. Both typical and nonspecific CT features of COVID-19 identified participants with SARS-CoV-2 infection that would have been missed by RT-PCR test alone.
When COVID-19 prevalence is low, and thus, diagnostic strategy of SNOUT should be adopted, even the RT-PCR test, despite its comparatively low sensitivity [6], may achieve an acceptable negative predictive value to exclude COVID-19. However, costs of false negative results associated with SARS-CoV-2 transmission are high. Concomitant low dose chest CT in adults admitted to emergency departments for a variety of reasons who have symptoms and/or previous contact to SARS-CoV-2 infected individuals may cover the lack of sensitivity and provide a more reliable negative predictive value along with reasonable radiation exposure.
As reported earlier, chest CT is able to identify COVID-19 in participants without respiratory symptoms [12, 13]. In turn, a recent meta-analysis reported on only 8.4% of normal CT findings in COVID-19 patients [14]. However, previous studies found false negative CT results particularly during the first four days after symptom onset [15, 16] and neither RT-PCR test nor chest CT can detect incubating SARS-CoV-2 infection. The SNOUT rule is not applicable where prevalence is high. A previous study in Chinese regions with COVID-19 prevalence of 85% by RT-PCR found a chest CT sensitivity of 93% resulting in a NPV of only 42% [17].
Two participants of our study who were diagnosed COVID-19 negative by chest-CT had positive AB test results and thus were classified as “false negatives”. In one of these participants, respiratory symptoms started 3 weeks before chest CT, and AB test was conducted 5 weeks after symptom onset. In this participant, pulmonary emphysema might have superimposed typical COVID-19 patterns on CT. Even an infection after chest CT cannot be excluded. In the second false negative participant, AB test was conducted 15 days after onset of fever and weakness. As serum conversion occurs at the earliest 7 days, but more reliably 14 days from symptom onset,[18] in this participant, COVID-19 might have been overcome or present without pneumonia at the day of symptom onset and chest CT.
Specificity of chest CT was considerably lower than known from RT-PCR tests. Thus, chest CT does not appear appropriate for screening or as first line diagnostic test to “rule in” COVID-19. Previous studies reported on specificity that ranges from 25 to 100% [3–5, 17]. However, typical CT imaging features including bilateral and multi-lobar distribution of ground-glass opacity with or without crazy paving pattern and fibrous strips were consistent with previous reports and thus may be considered as characteristic of COVID-19 [14, 19, 20]. However, at a low prevalence, positive predictive value of chest CT is only moderate. Broad distribution of COVID-19 severity and high frequency of different severe alternative diagnosis in the clinical setting of the university hospital emergency department may also have contributed to an increased frequency of false positives. Moreover, in particular in flue seasons with high influenza prevalence there probably will be more false positive chest CT results. Thus, performance of radiologists [5] to distinguish COVID-19 from other viral infections will be crucial.
Our study has limitations. First, due to social lockdown, instituted by the German government and the accompanied considerably reduced COVID-19 incidence, we decided to prematurely terminate recruitment. Therefore, number of participants did not achieve the targeted sample size and precision of endpoints remained low. In addition, only around half of the participants who underwent chest CT were assessed by AB test. In these participants, the RT-PCR result alone applied as reference standard. Furthermore, both reference standards have limitations. Sensitivity of RT-PCR depends on the viral load that differs according to the time of sampling, to the specimen, specimen handling, and even among individual participants [7]. Detection of specific antibodies is insufficient to permit a conclusion on the exact time of infection. In participants with positive AB test result, it is therefore uncertain whether a confirmed SARS-CoV-2 infection was present or already overcome at the time of chest CT. Finally, we did not collect data on dysgeusia and anosmia because these symptoms were not known to be typical for COVID-19 at the time of inclusion.