COVID-19 Chest Manifestation on CT Scan and Associated Risk Factors for Developing Pulmonary Fibrosis

Purpose: This retrospective study describes the imaging findings on chest computed tomography (CT) scans of coronavirus disease 2019 (COVID-19) patients as well as the prevalence of pulmonary fibrosis and the potential risk factors for the disease. Methods: One of the major COVID-19 centers in the western province of Saudi Arabia, the King Abdullah Medical Complex in Jeddah, was the site of this study. All adult COVID-19 patients who got a CT chest scan between January 2020 and April 2022 were included in the trial. The imaging findings and pulmonary severity scores (PSS) were obtained from the patients' CT chest. Patients were divided into two groups according to the evidence of fibrotic-like lung changes; clinical and radiological data between the two groups were subsequently compared. Data from the patients' electronic records was collected. Results: The average patient age was 56.4 years, and most (73.5%) patients were men. Two-thirds of the patients had comorbidities (69.1%). CT scans revealed that diffuse lung infiltration is reported in 61% of cases, followed by lower lobes in 19.9%. Ground glass opacity (94.1%), consolidation (76.5%), septal thickening, and/or reticulation (24.4%) were the main chest findings during the initial CT scan. Fibrotic-like lung changes were developed in 9.6% of patients. Patients known to have a positive history of hypertension (p-value = 0.031) and coronary artery disease (CAD) (p-value = 0.011) were found to be significantly more likely to develop lung fibrosis. The patients’ pneumonia severity score was significantly higher among the lung fibrotic patients (p-value = 0.026). Also, patients who were diagnosed with pulmonary fibrosis stayed longer in the hospital (p-value 0.001). Sex and age did not correlate significantly with risk of lung fibrosis. Conclusion: Pulmonary fibrosis was observed in 9.6% of COVID-19 patients. A close follow-up of patients with severe pneumonia, prolonged hospitalization, and pre-existing CAD and hypertension was necessary, as pulmonary fibrosis was more likely to occur as a result of these factors. There is a need for a thorough, long-term investigation with a large sample size.


Introduction
On December 31, 2019, the World Health Organization (WHO) became aware of cases from Wuhan City, China, suffering from respiratory illnesses of unknown origin.The situation progressed and was declared a pandemic on March 12, 2020 [1].
The standard method of diagnosing coronavirus disease 2019 (COVID- 19) is real-time reverse-transcription polymerase chain reaction (RT-PCR) [2].But according to recent research, RT-PCR is only 60-71% sensitive for aiding in the detection of COVID-19 [3,4].On the other hand, chest CT has been demonstrated to be sensitive to COVID-19 at the time of initial presentation, with a range of 56-98% [3,4].
Acute respiratory distress syndrome (ARDS) can complicate 14% of COVID-19 cases; however, the majority of COVID-19-infected patients exhibit only very mild symptoms, such as a dry cough, fever, and loss of taste or smell [5].Although COVID-19 is a systemic disease because it can impact multiple organs, it is primarily a respiratory condition [6].
Even though it has been stated that the majority of COVID-19 cases will fully recover after the infection, a number of recent studies suggest that roughly 70-80% of patients will continue to experience a variety of short-or long-term post-infectious complications, especially in severe COVID-19 cases [7,8].The more severe and often described COVID-19 consequence is pulmonary fibrosis, with the precise incidence of this sequela among COVID-19 survivors and its connection to the viral disease yet to be fully determined [9].Although by early 2022 the pandemic was controlled in most countries and precautionary measures were lifted, we believe it is necessary to study, understand, document, and compare data from COVID-19 patients in our region with those published in different countries and regions.This study describes the chest findings on CT scans of COVID-19 patients as well as the prevalence of pulmonary fibrosis and the potential risk factors for the disease.

Materials And Methods
This was a retrospective study conducted in a major COVID-19 center, the King Abdullah Medical Complex in Jeddah, in the western province of Saudi Arabia.The study comprised all adult COVID-19 patients who underwent a CT chest scan between January 2020 and April 2022.Patients who had a CT chest scan either at the initial presentation and/or at follow-up were included in this study.Patients who did not have RT-PCR done or who were less than 18 years old were excluded.A total of 136 patients were finally included in the current study.The study was approved by the Institute Review Board of the Ministry of Health/Directorate of Health Affairs in Jeddah (approval number: A01463).

Chest CT protocol
All the patients were imaged with a multi-detector HiSpeed Dual CT scanner (GE HealthCare Technologies, Inc., Chicago, Illinois, United States) using the following parameters: 120 kVp, 150 mA, 0.625-5 mm collimation, 0.9 pitch, and image reconstruction with slice thickness, 2.5 mm/interval.All scans were from the upper thoracic inlet to the inferior costophrenic angle.The patient was supine and at full inspiration during scans.We reviewed the CT chest available at initial and/or follow-up visits for each patient.

Image evaluation
Two radiologists, each with 10 years of experience, reviewed the chest CTs of the COVID-19 patients.The initial and follow-up CT chest images were assessed and compared for the presence of the following features: ground glass opacity, consolidations, septal thickening and/or reticulation, linear bands, thickening of the bronchial wall, nodules, bronchiectasis, pulmonary embolism, and pneumomediastinum, among others.A predominant pattern of chest findings distribution and lung lobe involvement was documented.The PSS and classification were obtained, as described by Chung et al. [1].The PSS was computed using CT chest scans by adding the scores from each of the five lobes, with each lobe's score being determined independently.PSS ranges from 0 to 20 and a score from 0 to 4 was assigned to each lobe.The extrapulmonary findings and complications of COVID-19 were also recorded.
Patients were divided into two groups according to the evidence of fibrotic-like lung changes on their CT images: (i) the fibrosis group and (ii) the non-fibrosis group.Pulmonary fibrosis on chest CT imaging was defined as a combination of findings, including parenchymal bands, irregular septal thickening, reticulation, and traction bronchiectasis [10].Clinical and radiological data between the two groups were subsequently compared.

Clinical examination
Patient data including age, gender, nationality, and comorbidities, including diabetes, hypertension, CAD, chronic renal disease, chronic lung disease, and obesity were obtained from the electronic medical records.Data on hospital stays, ICU admissions, and mortalities was also collected.The presenting signs and symptoms of COVID-19 patients were also recorded.

Statistical analysis
The mean and standard deviation were used to describe continuous measured variables, and the metric variables that showed statistical normality assumption violations were described with medians and the interquartile range (IQR).The categorically measured variables were described using percentages and frequencies.The multiple response dichotomy analysis was used to describe the variables with more than one option, like the patients' main CT scan findings.The relationship between categorically measured variables was evaluated using the Chi-squared test of independence.The non-parametric Mann-Whitney U test was used to assess the statistical significance of metric variable differences across the levels of binary and categorically measured factors and variables.The multivariable logistic binary regression analysis was used to assess the statistically significant predictors of the patients' odds of lung fibrosis at admission and follow-up CT scan findings.The association between the predictor variables in the logistic regression analysis was expressed as a multivariate-adjusted odds ratio (OR) with its associated 95% confidence intervals (CIs).The IBM SPSS Statistics for Windows, Version 21.0 (Released 2012; IBM Corp., Armonk, New York, United States) was used for the statistical data analysis, and the alpha significance level was considered at the 0.05 level.

Initial CT, n (%) Follow-up CT, n (%)
Main  Fibrotic-like lung changes were developed in 13 out of 136 patients (9.6%).Sex and age did not correlate significantly with the risk of lung fibrosis.However, patients aged ≥ 56 years were found to be significantly more likely to develop lung fibrosis compared to people in other age groups (p-value = 0.013).Patients known to have a positive history of hypertension and CAD were found to be significantly more likely to develop lung fibrosis compared to those not known to have hypertension or CAD (p-value = 0.031 and pvalue = 0.011, respectively).PSS was significantly higher among the lung fibrotic patients (median = 13) compared to those who had no lung fibrotic changes (median score = 10) (p-value = 0.026).The patients who were diagnosed with lung fibrosis stayed longer in the hospital (median HLOS = 44 days) compared to those patients who had no lung fibrosis (median HLOS = 18 days) (p-value = 0.001) (Table 4).

TABLE 4: Correlation between COVID-19 patients' characteristics and presence of lung fibrosis
Data given as frequency (percentage) except in age and hospital length of stay, which are given in mean (SD) and median (IQR), respectively.

COVID-19: coronavirus disease 2019; IQR: interquartile range
Regression was applied to the COVID-19 patients' odds of CT-evidenced lung fibrosis.The patients with a known history of CAD were found to be significantly more inclined (7.17 times more) to have positive evidence of lung fibrotic changes with COVID-19 disease compared to the patients not known to have CAD (p-value = 0.02) (Table 5).

Discussion
The results of the present study are similar to those of the 58 patients in the study by Caruso et al. [11], where consolidation was observed in 42 patients (72%), and ground-glass opacity in 58 patients (100%).Our findings, however, contradict the findings by Zhu et al. [12] and Chung et al. [1], which found a lower prevalence of ground glass opacities.Of the 21 patients in Chung et al., 12 patients (57%) showed groundglass opacities and six patients (29%) showed consolidation [1].Of the 31 patients in Zhu et al., only 15 (47%) developed ground glass opacities [12].
Interestingly, bilateral involvement was much lower in the current study (27.2%) versus (76%) in Chung et al. [1] and (91%) in Zhu et al. [12].Moreover, in prior reports that evaluated CT patterns in COVID-19 patients, there were tendencies for the lung disease to have a basilar and subpleural distribution without a definite lobar or craniocaudal distribution [1,[11][12][13].Our study showed diffuse and peripheral infiltration to be the most common patterns of involvement.
A strong association between fibrotic lung disorders and CAD was documented in non-COVID-19 patients [29].Numerous studies have shown a link between chronic obstructive pulmonary disease (COPD) and PCPF, but no conclusive evidence of an association with CAD has been reported [16][17]23].According to the current study findings, the most significant comorbidity, which has a strong correlation with PCPF, is CAD.As in earlier investigations, we also discovered a significant association between hypertension and PCPF [16][17]23].
There are various limitations to the current study.First, the study employed a single-center retrospective design.Second, the sample size was also quite small.Third, a longer follow-up is needed to ascertain if the fibrotic abnormalities were temporary or permanent and whether they cured, stabilized, or worsened with time.

Conclusions
Pulmonary fibrosis was observed in 9.6% of COVID-19 patients.A close follow-up of patients with severe pneumonia, prolonged hospitalization, and pre-existing CAD and hypertension was necessary, as pulmonary fibrosis was more likely to occur as a result of these factors.There is a need for a thorough, long-term investigation with a large sample size.
Health/Directorate of Health Affairs in Jeddah Institute Review Board issued approval A01463 via review according to KACST (GCP) regulations.Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue.Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work.Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work.Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

TABLE 2 : Presenting symptoms and radiological characteristics of the patients included in the study
Data presented as frequency and percentage except in Pneumonia Severity Score, which is given in median (interquartile range (IQR))