Predictors of the chest CT score in COVID-19 patients: a cross-sectional study

Background Since the COVID-19 outbreak, pulmonary involvement was one of the most significant concerns in assessing patients. In the current study, we evaluated patient’s signs, symptoms, and laboratory data on the first visit to predict the severity of pulmonary involvement and their outcome regarding their initial findings. Methods All referred patients to the COVID-19 clinic of a tertiary referral university hospital were evaluated from April to August 2020. Four hundred seventy-eight COVID-19 patients with positive real-time reverse-transcriptase-polymerase chain reaction (RT-PCR) or highly suggestive symptoms with computed tomography (CT) imaging results with typical findings of COVID-19 were enrolled in the study. The clinical features, initial laboratory, CT findings, and short-term outcomes (ICU admission, mortality, length of hospitalization, and recovery time) were recorded. In addition, the severity of pulmonary involvement was assessed using a semi-quantitative scoring system (0–25). Results Among 478 participants in this study, 353 (73.6%) were admitted to the hospital, and 42 (8.7%) patients were admitted to the ICU. Myalgia (60.4%), fever (59.4%), and dyspnea (57.9%) were the most common symptoms of participants at the first visit. A review of chest CT scans showed that Ground Glass Opacity (GGO) (58.5%) and consolidation (20.7%) were the most patterns of lung lesions. Among initial clinical and laboratory findings, anosmia (P = 0.01), respiratory rate (RR) with a cut point of 25 (P = 0.001), C-reactive protein (CRP) with a cut point of 90 (P = 0.002), white Blood Cell (WBC) with a cut point of 10,000 (P = 0.009), and SpO2 with a cut point of 93 (P = 0.04) was associated with higher chest CT score. Lung involvement and consolidation lesions on chest CT scans were also associated with a more extended hospitalization and recovery period. Conclusions Initial assessment of COVID-19 patients, including symptoms, vital signs, and routine laboratory tests, can predict the severity of lung involvement and unfavorable outcomes.

Person-to-person transmission of SARS-CoV-2 occurs with respiratory droplets from an infected person to others. Viral shedding may occur 1-2 days before the onset of symptoms and may continue for 1-2 weeks in mild to moderate cases or go beyond two weeks in severe cases [5,6]. Symptoms usually appear between 2 and 14 days after exposure; The common initial symptoms of COVID-19 are fever, cough, fatigue, and dyspnea [7,8], with more specific symptoms, including loss of taste and smell [6]. SARS-CoV-2 targets multiple organs, including respiratory, cardiac, and renal systems causing pneumonia and respiratory failure in patients [9,10]. In addition, systemic inflammatory response syndrome and cytokine storm contribute to multi-organ failure and coagulopathy in critical patients with COVID-19 [11,12].
Computed tomography (CT) is the most sensitive tool for diagnosing COVID-19, and several radiological patterns are seen in different phases of disease [13,14]. Among different patterns of chest CT scan, groundglass opacities (GGO) and mixed GGO with consolidation is reported as the most common patterns in COVID-19 patients [15]. Although definite diagnosis relies on real-time reverse-transcriptase-polymerase chain reaction (RT-PCR) [16], chest CT is a valuable modality to measure the extent of lung involvement and propose a treatment plan.
Initial assessment of COVID-19 patients is essential for further management. In this study, we assessed the patient's signs, symptoms, laboratory tests, and imaging findings to identify which initial clinical and laboratory findings may predict the severity of lung involvement and, accordingly, short-term outcome.

Study design and participants
The study protocol and consent notes were reviewed and approved by the ethics board of our institute (approval code: TUMS.VCR.REC.1399.138). This study is a crosssectional, observational, single-center study conducted between April and August 2020 at a tertiary medical center. All referred patients to the COVID-19 clinic of Imam Khomeini Hospital, university hospital, were evaluated for eligibility of participation in the study. Patients with mild, moderate, or severe clinical symptoms suggestive of COVID-19 who had positive RT-PCR (226, 47.2%) confirming COVID-19 or suggestive chest CT scan (252, 52.8%) were included after signing a written informed consent form. Patients with history of previous lung diseases excluded from study. Four physicians did the patient examination and data registration, and five medical residents followed up with the patients through telephone calls. Both hospitalized (after discharge) and outpatient participants were followed weekly through telephone calls until symptoms resolved. Treatment regimens were based on the latest version of the national protocol of COVID-19.Hydroxychloroquine was used as the primary therapeutic option in the outpatient setting; hydroxychloroquine, lopinavir/ritonavir (Kaletra), atazanavir (nonboosted with ritonavir or cobicistat) were administered for hospitalized patients, and in case of severe hypoxemia (not attaining SpO2 of > 88% with reservoir mask), corticosteroid was given.

Chest CT protocols and interpretation
All chest CT scans were performed on either lightspeed 64-detector CT (GE Healthcare) or the 16-slice (Siemens SOMATOM Emotion) MDCT scanner with patients in Keywords: COVID-19, Computed tomography, Outcome, Recovery, Chest CT score the supine position at full inspiration breath-hold. The leading scanning parameters were as follows: 120 kVp tube voltage; 50-150 mAs tube current; 0.75 s tube rotation time; 0.5-0.75 s gantry rotation time; 2-3-mm section thickness; and 0.6-2 mm beam collimation.
The visual chest CT interpretation was performed using a single, experienced (10 years) thoracic radiologist. The radiologist was blinded to clinical and laboratory data of participants and reviewed on both lung and mediastinal window settings. The presence of CT features including (a) predominant pattern of lesions: groundglass opacification (GGO), consolidation, or mixed GGO and consolidation; (b) dominant distribution of lesions: central, peripheral, diffuse, or peri-broncho vascular; (c) shape of lesions: round, elongated, wedged, or confluent; (d) additional findings: crazy paving pattern, reverse-halo sign, interlobular septal thickening, linear opacities combined, air bronchogram sign, tree in bud, adjacent pleural thickening, pleural effusion, pericardial effusion, lymphadenopathy, and pulmonary emphysema, was reported as defined in Fleischner Society Glossary of terms for Thoracic Imaging [17].

Statistical analysis
The statistical analysis was performed using SPSS version 16 (SPSS Inc. Chicago, IL). Continuous variables were presented as mean (standard deviation), and categorical variables as frequency and percentages. Variables were tested for normality using Kolmogorov-Smirnov test. Normally distributed continuous variables were analyzed using the independent sample t-test; otherwise, the Mann-Whitney U test was used. A Chi-square test was employed for nominal variables. P values less than 0.05 were considered statistically significant.
Demographics, initial signs, symptoms, and laboratory data of all participants are listed (Table 1).
Further analysis showed consolidation on chest CT scan had a significant association with initial lower SpO2 (P = 0.001), higher risk of ICU admission (P = 0.005), extended hospitalization (P = 0.003), and longer recovery time (P = 0.008) ( Table 4).

Discussion
As treatment protocols are based on the extent of lung involvement, assessing the severity of pulmonary involvement is crucial in determining the treatment plan for COVID-19 infected patients. Chest CT scan is not available everywhere, and its usage is sometimes limited, especially in pregnant patients. Therefore, physicians need prompt assessment according to patient's initial signs and symptoms and routine laboratory tests for timely management. In the current study, we assessed clinical and laboratory findings on the first visit to predict the extent of lung involvement in COVID-19 patients. We found that patients with anosmia, lower SpO2 (< 93), and higher respiratory rate (> 25 per minute), WBC count (> 10,000 cells/mm3), CRP (> 90 mg/Liter) had higher total CT scores. Besides, consolidation opacities as the worst lung lesions were more commonly detected in patients with lower initial SpO2 or admitted to ICU. Moreover, patients with consolidation on their chest CT scan experienced extended hospitalization (≥ 15) and recovery period (≥ 15). A higher chest CT score was also associated with more extended hospitalization and recovery time.

Predictors of severe lung involvement
In line with previous studies, our results showed that higher initial WBC and CRP are associated with more severe cases of COVID-19 patients, as WBC > 1000 cell/ mm3 and CRP > 90 mg/L were associated with higher chest CT scores. Similar to our findings, Salvatore et al. reported hospitalized and critical COVID-19 patients had higher CRP, leukocyte count, neutrophils, LDH, D-dimer, and troponin [19]. Zhang et al. also reported that chest CT score positively associated with WBC count, CRP, ESR, procalcitonin, and abnormal coagulation function [20].
Among several clinical symptoms on the first visit, just anosmia was associated with extended pulmonary involvement. A literature review did not show any previous report of extended lung involvement in patients with anosmia, and our study is the first to report this correlation. Association of anosmia and pulmonary involvement can be justified by the roll ofchemokines, as previous reports defined CXCL10 contribution in both cytokine storm of COVID-19 patients causing acute respiratory distress syndrome (ARDS) and demyelination process of the olfactory nerve causing anosmia [21].
Several clinical signs of patients on the first visit, including higher RR and lower SpO2, were associated with higher total chest CT scores. Lower SpO2 was also associated with consolidation opacities as the most severe lesion of COVID-19 in chest CT scan. In line with our findings, Kunwei Li et al. also showed that patients with RR ≥ 30 times/min, and SpO2 ≤ 93% as categorized in severe type patients, had significantly higher total chest CT scores than common type patients [22]. Another study also confirmed that severe/critical patients with respiratory rate ≥ 30 times/min and SpO2 of 93% or less in a resting state had higher total CT scores than ordinary COVID-19 patients [23]. Aalinezhad [24] and Osman [25] et al. also reported higher chest CT score    is inversely associated with O2 saturation. Furthermore, a multicenter cohort study demonstrated that consolidation in upper lungs on the initial chest CT of COVID-19 patients was associated with increased odds of adverse endpoints, including SpO2 < 93% and partial arterial pressure of oxygen less than 60 mm Hg on room air [26].

Chest CT predictors of unfavorable outcomes
We found that ICU admission, more extended hospitalization, and recovery period were associated with higher total CT scores and consolidation opacities in chest CT of these patients. Similarly, a previous study showed a higher pulmonary score ≥ of 8 accompanied by age ≥ 53, and SpO 2 ≤ 91 predicts ICU admission and mortality [27]. Deepak Nagra et al. also reported a higher lung opacification score is a reliable predictor of ICU admission for COVID-19 patients [28]. Another study on baseline chest CT scans and clinical and laboratory data of 72 patients admitted with COVID-19 pneumonia showed lung severity score > was associated with a significantly lower recovery rate and discharge and extended hospitalization in patients admitted for COVID-19 pneumonia [29]. Similar to our findings, Ahlstrand et al. previously reported that chest CT score at hospital admission correlates closely with hospital length of stay and ICU admission [30]. CT severity score combined with age and history of at least one underlying disease had 79.7% sensitivity and 65.5% specificity in predicting the adverse outcomes in a previous study [31]. Initial assessment of patients in the clinic determines the treatment plan, so we assessed lung involvement based on initial signs, symptoms, and laboratory tests. Taken together, we found that patients with anosmia, higher respiratory rate, WBC count, or CRP, and lower SpO2 had extended pulmonary involvement of COVID-19 pneumonia, which can cause adverse outcomes, including more extended hospitalization and recovery period. Hence, those patients should be prioritized for greater attention and intensive care.

Limitations
As recovery time was defined as a subjective statement of patients, this could have resulted in a conclusion error; inviting the patients to the clinic for evaluation could have been more precise to confirm recovery. In addition, in this study, we assessed just the presence of symptoms, not their severity; we recommend further studies assessing the severity of symptoms and their correlation with lung involvement or adverse outcomes.

Conclusion
Extended lung involvement of COVID-19 pneumonia can be predicted in clinics with patient's initial symptoms, vital signs, and laboratory tests, including anosmia, low SpO2, high RR, WBC, and CRP. Therefore, these patients should be considered high-risk patients for further medical planning.

Availability of data and materials
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations
Ethics approval and consent to participate Study protocols and patients consent forms were reviewed and approved by the ethics committee of Tehran University of Medical Sciences (approval code: TUMS.VCR.REC.1399.138). All patients signed an informed consent form before entering the study.

Consent for publication
Not applicable.