Correlation between Chest CT Severity Scores and the Clinical Parameters of Adult Patients with COVID-19 Pneumonia

Purpose Our aim is to correlate the clinical condition of patients with COVID-19 infection with the 25-point CT severity score by Chang et al. (devised for assessment of ARDS in patients with SARS in 2005). Materials and Methods Data of consecutive symptomatic patients who were suspected to have COVID-19 infection and presented to our hospital were collected from March to April 2020. All patients underwent two consecutive RT-PCR tests and had a noncontrast HRCT scan done at presentation. From the original cohort of 1062 patients, 160 patients were excluded leaving a total number of 902 patients. Results The mean age was 44.2 ± 11.9 years (85.3% males, 14.7% females). CT severity score was found to be positively correlated with lymphopenia, increased serum CRP, d-dimer, and ferritin levels (p < 0.0001). The oxygen requirements and length of hospital stay were increasing with the increase in scan severity. Conclusion The 25-point CT severity score correlates well with the COVID-19 clinical severity. Our data suggest that chest CT scoring system can aid in predicting COVID-19 disease outcome and significantly correlates with lab tests and oxygen requirements.


Introduction
is an infection that has widely and rapidly spread all over the world and became a pandemic with significant impacts upon the sociopolitical milieu and healthcare delivery systems [1]. e clinical presentations vary from asymptomatic carriers to patients requiring assisted ventilatory support, and ICU admissions with increased mortality made it an unusual and unprecedented challenge [2,3]. e nasopharyngeal swab RT-PCR test has been the diagnostic test used as the standard of reference for disease confirmation [4]. e test is a powerful tool; however, there is a small but significant proportion of false-negative results reported [5].
A noncontrast high-resolution CT chest imaging plays a pivotal and essential role in the early disease detection, particularly in patients with false-negative RT-PCR results, as well as in managing and monitoring the course of disease [6]. Moreover, the disease severity can be ascertained from the imaging findings, significantly supporting the clinicians in their clinical judgment and ensuring effective and timely management [7]. Prognosis can also be affected by the severity of the disease in the critically ill patients allowing appropriate selection of early involvement of the intensive care [8,9].
Multiple studies have explored the pulmonary involvement on the chest CT images using both visual and software quantitative assessments [10,11]. To our knowledge, ours is the first comprehensive study to describe the correlation of chest CT severity scores and the clinical picture of patients with COVID-19 disease in the Gulf and Arab region. Our study correlates the CT severity score with the clinical severity of the patients who were confirmed to have COVID-19 disease using the 25-point visual quantitative assessment.

Data Collection.
Ethical approval was obtained from Institutional Review Board (IRB) and Department of Health (DOH), Abu Dhabi, United Arab Emirates (UAE). e informed consent was waved off as per the ethics committee. We collected clinical and laboratory data for analysis, derived from an electronic medical record system, from March to April 2020 of patients who were suspected to have COVID-19 infection and underwent a chest HRCT scan. e results for the chest HRCT images were collected and evaluated using the Picture Archiving and Communication Systems (PACS).

HRCT Image
Analysis. Two radiologists with more than 8 years of experience evaluated the images to determine the disease severity score in each patient. e scans were first assessed whether negative or positive for typical findings of COVID-19 pneumonia (bilateral, multilobe, posterior peripheral ground-glass opacities) as defined by the RSNA Consensus statement [7,12]. Severity then was assessed using the following scoring system which depends on the visual assessment of each lobe involved [13][14][15] (Figure 1) (see Tables 1 and 2).

Statistical Analysis.
e analysis was performed using SPSS 21.0. Descriptive statistics of patients' demographics, clinical, and laboratory results were reported as numbers and relative frequencies. Frequencies of CT scores were calculated and compared with other clinical variables. e Pearson correlation coefficient test was used for correlations, and p value less than 0.05 was defined statistically significant.

Baseline Information.
Our population included 1,062 consecutive patients who were suspected to have COVID-19 infection. Infection with SARS-CoV-2 was confirmed from a nasopharyngeal swab using the U-TOP COVID-19 Detection Kit (Seasun Biomaterials Inc., Daejeon, Korea), which is a reverse transcriptase-polymerase chain reaction (RT-PCR) test that has received Emergency Use Authorization (EUA) from the US Food and Drug Administration (FDA). RT-PCR testing was performed using Clinical Laboratory Improvement Amendments (CLIAs) diagnostic standards according to current testing guidelines [16]. All patients underwent two consecutive RT-PCR tests and had a HRCT scan done. 160 patients were excluded from the study as per the following exclusion criteria: patients less than 18 years old, patients with negative RT-PCT results, discharge to another facility leading to lost follow-up, suboptimal HRCT scan due to significant motion artefacts, or CT with atypical findings for COVID-19 pneumonia.

Laboratory
Results. Lymphopenia was detected in 17 patients (8.4%) of the negative group, 55 patients (13.7%) of the mild group, 110 patients (35.6%) of the moderate group, and 31 patients (50.8%) of the severe group. When compared with disease phase, lymphopenia was found to be more significant among patients with more severe scans (p < 0.0001).
e oxygen requirement and CT severity scores were found to have statistically significant correlation (p < 0.0001, r � 0.529).
In terms of length of hospital stay, 190/902 patients (21.1%) with negative scans, 276 patients (30.6%) with mild scans, 160 (17.7%) patients with moderate, and 5 patients (0.6%) with severe findings were either discharged the same day or required hospital admission for <5 days.

Discussion
e WHO advised the use of chest imaging as part of diagnostic workup of COVID-19 disease whenever RT-PCR testing is not available, in case of delayed test results or when there is a clinical suspicion of COVID-19 with initial negative RT-PCR testing. Clinicians should work hand in hand with the radiologists in order to make the proper choice of imaging modality [17].
CT scan can be a useful tool in evaluating the individual disease burden [18]. e quantitative severity can be assessed using a visual method (as in our study) or software that determines the percentage of affected lung volumes using the deep learning algorithms [10,19,20].
In our study, and due to unavailability of the software, we used the visual assessment of each of the 5 lung lobes. e severities were further classified based on the total cumulative severity score.
Our population revealed a relatively young age (mean 44.2 years) with male predilection. is can be explained by the particular characteristics of the population in the UAE, with prevalence of young male immigrant workers [21].
Severe disease was mostly seen in males (93.4%). Studies suggest that such distribution can be attributed to many factors like disparity in behavior and the possible protective effect of estrogen [22]. e most severe disease and the highest mortality rates were found in the 50-to 59-year age group. is can be affected by different factors like the stage of the pandemic when the study was carried, presence of patients' comorbidities, maturity and preparation of the healthcare system, and existence of elderly nursing homes services where disease can spread faster [23].
A number of existing literature suggested that the presence of risk factors, particularly hypertension, diabetes, lung, and coronary artery diseases, carries a poor prognosis, with even worse outcome when multiple risk factors are present [24,25]. Although in our study we did not find a statically significant correlation between the presence of risk factors and CT severity scores, there was however a significant correlation (P < 0.0001) between the ICU admission and presence of risk factors (Figure 4).
Lymphopenia correlated well with the increasing CT severity score. e presence of lymphopenia can be related to the inflammatory cytokine storm. Decreased T cell counts, particularly CD8+, has been observed in severe cases [26].
Furthermore, our results showed that the serum CRP level had significant correlation with CT severity. Studies have also suggested that early treatment at early disease stage can be considered using CRP as a predictive marker for likelihood of disease progression [27]. Similarly, serum ferritin is a vital mediator of immune dysregulation, and its level was closely linked to the severity of the disease [28]. D-dimer likewise can be used as a prognostic indicator, where higher levels are seen  [29,30]. As expected, and found in our data, oxygen requirements increase with the increasing CT severity. e progressive increase in oxygen requirement can be due to the direct damage of the lung by the virus causing inflammatory changes in alveolar wall that limit oxygen exchange, leading to acute respiratory distress, pulmonary fibrosis, and eventually death. Moreover, significant pulmonary thromboembolic effects were also found on autopsies from patients who died from COVID-19 disease [31][32][33].
Concerning the length of hospital stay for patients with COVID-19 disease, a systematic review done by Rees et al. has suggested that LOS varies depending on multiple factors such as admission and discharge criteria, bed demand and availability, and different timing within the pandemic [34]. Death rate in our cohort was significantly increased among patients with severe CT findings, as noted in other studies [35].
ere are several limitations in this study: first, the need for a larger multicenter cohort to increase the accuracy of the findings and second, the fact that the assessment of disease severity on CT scans can be subjective. is was reduced by involving two experienced readers to reach a consensus. Finally, the other factors that might contribute to the disease outcome such as lifestyle and relying on self-reporting/ underreporting of the comorbidities should be considered.
In conclusion, CT scans can have a pivotal role in assisting physicians in the management plan and work as an indicator for disease severity and possible outcome. CT severity score is positively correlated with inflammatory lab markers, length of hospital stays, and oxygen requirement in patients with COVID-19 infection. However, more research is needed to further clarify the value of chest CT for prognostication in COVID-19 disease, including correlation with patient outcome.

COVID-19:
Coronavirus disease CRP: C-reactive protein CT: Computed tomography GGO: Ground-glass opacity HRCT: High-resolution computed tomography PACS: Picture archiving and communication systems RT-PCR: Reverse transcription polymerase chain reaction WHO: World Health Organization.

Data Availability
Data are available on request through institutional review board (medical.research@doh.gov.ae).

Conflicts of Interest
e authors declare that there are no conflicts of interest.