The pandemic spread of corona virus from China to Italy has represented a major problem due to overwhelming transmission and severity of disease, which is a potential threat to the health care system due to the limited availability of hospital resources, especially with regard to intensive care units [14]. The purpose of this study was to assess the potential role of chest CT for the early detection of COVID–19 and to explore its role in patient management in an adult Italian population admitted to the Emergency Department with suspected pneumonia.
We comprehensively evaluated and analyzed the CT findings of 314 patient admitted to the Emergency Department of our Regional hub Hospital in Rome, Italy. Using RT-PCR from nasopharyngeal swab test results as a reference, as mentioned in the results section, we classified as COVID–19 patients with negative RT-PCR results and as COVID–19 patients with positive RT-PCR results.
Nasopharyngeal swab test is a widely used method to confirm COVID–19 infection, and it is recommended by WHO guidelines, which state that a clinically suspected case is confirmed only in the presence of a positive RT-PCR result [5]. Despite specificity, swab tests only have limited sensitivity and negative predictive value and are not suitable to assess disease severity [4, 15, 16]. Moreover, results of swab tests are available with a lag of several hours. In our study mean turnaround time for swab results was 10 hours, while suspected patients must remain in isolation, hospitalized and mostly under clinical surveillance.
Chest CT is considered the routine imaging modality for diagnosis and for monitoring the care of patients with COVID–19 pneumonia, especially in an emergency setting where timing is crucial for early identification of diseased patients and the separation of disease-free patients from suspected disease, in order to reduce human-to-human transmission [9]. Our results showed a substantial agreement between RT-PCR results and CT findings (p<0.000001), as well as an almost perfect agreement between the two readers.
In patients COVID–19 + (n = 162) we observed a total of 147 cases classified as CT positive, according to findings interpretation. In this group, mixed GGO and consolidation pattern with peripheral and bilateral distribution, multifocal or diffuse abnormalities localized in both upper and lower lung, in association with interlobular septal thickening, bronchial wall thickening and air bronchogram, showed higher frequency (Fig.3). Unlike previous studies that show prevalence of GGO pattern at the early CT scan, the mixed GGO and consolidation was the most common pattern in our study [17]. This may be due to the fact that in Italy paucisymptomatic patients have mostly been managed at home by general practitioners; and only if patients worsen, they are sent to the Emergency Department. Most of our COVID population reached the hospital 7–15 days after onset of symptoms. For the same reason, in our study the most common distribution is both peripheral and centrolobular because during the second week the disease can spread and involve even the central regions [18]. CT features of COVID–19 pneumonia are similar to other common viral pneumonia [7]. However, according to other studies [19], we observed that spatial distribution, as well as attenuation pattern, could be suggestive for COVID–19 pneumonia [18, 20].
Despite substantial agreement, we also had some discrepancies between CT and RT-PCR.
In 15 cases RT-PCR showed positive results in spite of CT negative. In this subgroup: one patient showed a lobar uniform consolidation strongly suggestive of lobar pneumonia (i.e.: as seen in streptococcus pneumonia) and was interpreted as bacterial pneumonia (Fig.4); one patient had neoplastic history and his lung alterations were interpreted as metastatic involvement with lymphangitic carcinomatosis; four patients showed only a single and subtle opacity that was considered an atypical CT finding, not suggestive for COVID–19 pneumonia. In the remaining 9 patients, both radiologists found no parenchymal abnormalities (normal chest CT). Anyhow, in these 9 patients, chest CT ruled out the presence of pulmonary involvement in an emergency context and allows clinicians to treat them conservatively. Most were discharged under strict “active surveillance”. Thus, chest CT even when negative, had importantly affected clinical management in suspected infected patients. Hence a normal CT scan in the presence of a positive swab test could be a good prognostic indicator of absence of pulmonary involvement. A secondary hypothesis to explain why a normal CT scan could be found associated to a positive swab is that the CT scan has been performed too early, before the development of pulmonary involvement, because frequency of CT findings is dependent on infection time course [21]. In fact, early reports have stated that initial imaging might show normal findings in 15% of individuals, so a normal chest imaging examination does not exclude the infection [7]. Moreover, in a study conducted in China during the first 2 months of outbreak, no CR or CT abnormality was found in 17.9% patients with non-severe disease and in 2.9% patients with severe disease [22]. A better understanding of the spectrum of the disease is needed, since the same study revealed that in 8.9% of the patients, 19-nCov infection was detected before the development of viral pneumonia or viral pneumonia did not develop.
In 24 cases with negative swab tests (COVID), CT findings were consistent with COVID–19 pneumonia (CT Positive). Among this subgroup, one patient had pneumonia from another cause (Klebsiella Pneumoniae), and two patients had chronic bronchitis with disventilatory alterations of lung parenchyma, mimicking bilateral ground glass opacities (Fig.5). Lung infections or inflammatory conditions can share some findings with COVID–19 pneumonia and correct interpretation of those has probably been mistaken in a context of pandemic spread where most patients with fever and respiratory symptoms are expected to be affected by COVID–19.
In the remaining 21 cases we observed highly suggestive CT findings for COVID–19 pneumonia, though negative RT-PCR results. This was not confirmed in all patients because 6 patients had positive swab test results in following repeated samples, thus in this subgroup of patients CT scan actually allowed an early diagnosis (Fig.6). Since repeated swab tests are performed after 24 hours from first one, and if the latter is still negative, a third is performed the following day and so on, CT scans can give remarkable diagnostic anticipation. This is in accordance with previous experiences and it is already known that some patients with positive chest CT findings may at first present negative swab test, thus repeated sampling may be required in patients with high clinical suspicion and positive CT findings [23]. Our experience confirms that when swab tests are negative, the possibility of a false-negative result should be considered in the context of a patient’s recent exposures and the presence of clinical and radiological signs and symptoms consistent with 2019-nCoV infection. For this reason, in case of epidemiological anamnesis and CT findings suggestive for COVID–19, repeated swab test and patient isolation should be considered [24, 25]. Reasons for false negative RT-PCR may include insufficient cellular material for detection and improper extraction of nucleic acid from clinical materials [26].
Finally, as demonstrated in the correlation analysis, we found that chest CT considered “CT positive” and specific CT findings mentioned in the result section, significantly correlated with oxygenation impairment, expressed by PaO2/FIO2 ratio. While most people with COVID–19 develop only mild or uncomplicated illness, approximately 14% develop severe disease that requires hospitalization and oxygen support, and 5% require admission to an intensive care unit [27]. In latter cases, COVID–19 can be complicated by the acute respiratory distress syndrome (ARDS) [28]. A draft definition accepted worldwide proposed 3 mutually exclusive categories of ARDS based on degree of hypoxemia: mild (PaO2/FIO2 ≤ 300 mm Hg), moderate (PaO2/FIO2 ≤ 200 mm Hg), and severe (PaO2/FIO2 ≤ 100 mm Hg) [29]. As oxigenation impairment increases, several therapeutic options must be considered, like high-flow nasal oxygen in mild-moderate ARDS or endotracheal intubation and mechanical ventilation in severe cases [30].
Our study confirmed a strong correlation between swab test and chest CT findings for diagnosing or ruling out COVID–19 pneumonia and a strong relationship between clinical variables likehypoxemia and CT findings in patients considered CT positive. Hence our results suggest the creation of a flow-chart for managing patients admitted to the Emergency Department with suspected infection from 2019-nCov.
Patients with negative CT scan can be early discharged and isolated at home considering the low likelihood of a positive swab test and the very unlikely development of pulmonary problems. CT may help for screening out patients with suspected disease, especially patients with an initial negative RT-PCR screening result [23]. However, it must always be kept in mind that low sensitivity and negative predicted value of chest CT in early patients limits its role as an effective standalone tool to rule out COVID–19 [21]. Conversely, patients with positive CT scan reached an early diagnosis compared to the results of the RT-PCR results which can lag at least 8 hours. Although CT imaging has a certain turnaround time, nucleic acid and gene sequencing detection require a relatively longer time compared to CT. Therefore, chest CT represents a valuable tool in identifying patients with 2019-nCov infections at an early stage, when clinical symptoms may be unspecific or sparse [19]. Thus, for the timely and accurate diagnosis of COVID–19, CT can quickly identify suspected patients and significantly help in isolating the source of infection, cutting off the route of transmission, and avoiding further spread [26].
The above described management improves clinical decision making, especially in the emergency setting where it’s of paramount importance to stratify outpatients in suspected or non-suspected cases, while waiting for the RT-PCR results [31]. A management strategy based on CT results and clinical condition has already been used during the COVID–19 epidemic in China, when 10567 patients were diagnosed as clinical diagnosed cases. This designation has been used in Hubei Province. In these cases, no RT-PCR test was performed but diagnosis was made based on typical symptoms, exposure history, and chest CT manifestations consistent with COVID–19 pneumonia. Under this criteria, 10567 cases were diagnosed and isolated. This strategy quarantined a large number of suspected people and protected the healthy people to a major extent [14].
Our study has limitations. An intrinsic limit of a cohort of patients admitted to the Emergency Department is a large inhomogeneity, since the time of disease onset was unknown, depending on different incubation times. Moreover, disease severity was different among patients depending on previous clinical conditions that can affect lung pathology. According to the limited duration of this study (3 weeks), we still don’t have long term follow up data which could clarify if the small amount of normal chest CTs in the presence of positive swab tests were indicative of a preclinical lung disease or were to be considered as false positive swab tests.
In conclusion, our study shows how chest CT is a vital component in the early detection of COVID–19 pneumonia in a pandemic. Chest CT is also extremely useful in patients management in an Emergency Department because it can reliably identify suspected patients and significantly help in isolating the infected ones, cutting off the route of transmission and avoiding further spread of infection.