Early temporal changes on CT chest in patients with COVID-19 pneumonia

Introduction: Computed tomography (CT) scan of the chest helps in the evaluation, prognostication, and follow-up of patients with Corona virus disease-19 (COVID-19) pneumonia. Objectives: To study the early temporal evolution of findings on CT chest in patients with COVID-19 pneumonia at 6 weeks follow up. Material and methods: A retrospective analysis was performed on 40 patients with confirmed COVID-19 pneumonia who underwent baseline chest CT scans followed by a repeat scan at six weeks. Patients were quantitatively assessed using an objective CT severity score and qualitatively assessed using imaging parameters like consolidation, ground glass opacities (GGOs), parenchymal bands, septal thickening, nodules and crazy paving pattern. Results: Mean age of our study population was 58.5 ± 10.2 years with 80% being males. The baseline CT scan revealed a total median CT severity score interquartile range (IQR) of 16/25 (range: 14-20) while the follow-up scan after six weeks revealed a median score (IQR) of 14/25 (range: 8-19). This difference was statistically significant (p=0.04). The difference in CT severity scores of bilateral upper lobes was statistically significant (p=0.04 on right side and p=0.009 on left side); however, the difference in scores of bilateral lower lobes was not statistically significant (p>0.05). The common imaging patterns on baseline imaging were GGO (97.5%), consolidation (85%), septal thickening (85%), parenchymal bands (60%) and nodules (32.5%), which showed an interval resolution in the follow-up CT scan. Conclusion: Most of the patients with COVID-19 pneumonia showed interval resolution of lung findings seen on short-term follow-up CT scan.


Introduction
Coronavirus disease-19 (COVID-19) has been a major crisis globally and been declared as a pandemic on 11th March 2020.As on January 2023, the disease has claimed millions of lives globally [1].Computed tomography (CT) scan of the chest has been instrumental in assessment of severity of illness and for prognostication and management of the disease [2][3][4].
COVID-19 pneumonia exhibits a wide spectrum of clinical courses.While many patients experience significant resolution of the disease and its aftereffects, others may develop persistent lung abnormalities on imaging, experience lingering symptoms, and even suffer from functional limitations [5].
A comprehensive understanding of the temporal evolution of lung abnormalities observed on short-term chest CT scans in patients with COVID-19 pneumonia, particularly during the early disease course, is hindered by the paucity of available data.This knowledge gap is further exacerbated by the limited research conducted within the South Asian populations.Our study, conducted at a tertiary care hospital in India, explores the early temporal evolution of CT chest findings in patients with COVID-19 pneumonia, specifically focusing on changes between baseline and the 6-week follow-up scan.

Study design and sample
This study employed a retrospective design and received approval from the Institutional Ethical Committee.(reference no.IEC-INT/2023/study-1258).Need for informed consent was waived by the institutional ethical (Key words: COVID pneumonia, post COVID, CT scan in COVID, early temporal changes in COVID)

Original article
committee in view of retrospective nature of the study.We searched our database for the keywords 'COVID pneumonia' and 'post COVID' from October, 2020 to December, 2020.The study included patients who had COVID-19 confirmed by a positive reverse transcriptasepolymerase chain reaction (RT-PCR) test and moderate or severe illness during the initial phase of the disease.We included only patients who underwent two CT scans: a baseline scan and a follow-up scan six weeks later, with a permissible one-week window on either side.Patients aged less than 18 years, those with pre-existing lung parenchymal diseases and those who had undergone only one CT scan or if the repeat CT scan done earlier than five weeks or later than seven weeks were excluded from the study.A total of 40 cases were included after exclusion.Clinical profile of the study subjects was obtained from the hospital health records.

CT Acquisition and Protocol
CT scan acquisition was done on a 256 slice CT scan machine (Philips Brilliance iCT) in the department of Radiodiagnosis and Imaging, PGIMER.The CT scan was done in supine position.The imaging sections taken from apices of lung to the domes of diaphragm.The CT scans were acquired at kilo voltage peak (kVp) of 120 kVp with application of automated exposure control (AEC) modulated tube current.High resolution CT (HRCT) images were subsequently reconstructed into 1 mm sections at 0.5 mm increment.

Image interpretation and analysis
Each patient underwent two CT scans, a baseline CT scan, and a follow-up CT scan.Both the scans were independently reviewed by two different radiologists (UD with 13 years of experience and AD with 5 years of experience respectively) who were blinded to the clinical data.The disagreements were resolved by mutual consensus.
Qualitative parameters for assessment were presence or absence of imaging patterns in COVID-19 pneumonia such as consolidation, ground glass opacities (GGOs), parenchymal bands, interlobular septal thickening, nodules, and halo sign.

Statistical Analysis
Analysis was done using IBM SPSS statistics (version 22.0).The categorical variables in our study have been reported as counts and percentages.Normality of quantitative data (data for lobes) was checked by the Kolmogorov Smirnov test.The data which was normally distributed was represented as mean ± SD.Skewed data was represented as range with median and interquartile range (IQR).Spearman correlation coefficient was also calculated to look for relationship among different variables (quantitative data).For time related variables of skewed data Wilcoxon Signed rank test was applied.McNemar test was carried out for comparison of variables of baseline data with follow up variables.Interobserver variability was checked and evaluated according to the standard classification for k (kappa) with k = 0.81-1.00suggesting a perfect agreement.A p-value of less than 0.05 was considered statistically significant.

Results
Mean age of our study population was 58.5 ± 10.2 years with 80% being males.Time to CT scan (from onset of symptoms) was 44.5 ± 5.4 days.The demographic details have been summarized in Table 1.We observed that patients had a relatively high median CT severity score (IQR) of 16/25 (range: 14/25-20/25) at the time of initial assessment.These patients on a follow up CT scan after six weeks showed a slight reduction in the score to a median (IQR) score of 14/25 (range: 9/25-19/25).However, this difference turned out to be statistically significant (p=0.04).Also, patients were symptomatically better and showed partial resolution of symptoms at 6 weeks follow up.The pattern of lung involvement in patients at baseline and follow-up showed a lower lobe predominant pattern in both group of patients.The right lower lobe has a median (IQR) score of 4/5 (range: 3/5-5/5) on baseline imaging and 3.5/5 (range: 2/5-5/5) on follow-up imaging.For left lower lobe, the median (IQR) score at baseline imaging was 4/5 (range: 3/5-5/5) and on follow-up imaging was 3/5 (range: 2/5-5/5); however, the differences were not statistically significant (p>0.05).On the other hand, median score for right upper lobe was 3/5 (range: 2/5-4/5) on baseline imaging and 2/5 (range: 1/5-3/5) on follow-up.For left upper lobe, baseline score was 3/5 (range: 2/5-4/5) and 2/5 (range: 1.75/5-3/5) on follow-up.The differences were statistically significant (p=0.04 on right side and p=0.009 on left side respectively).There was a near perfect agreement (with k = 0.81-1.00)between the two radiologists who interpreted the imaging.

Discussion
The emergence of COVID-19 in late 2019 presented a global health crisis.Characterized by respiratory illness, the virus can range from asymptomatic to life-threatening.Early diagnosis plays a crucial role in patient management and infection control.Chest CT scans, despite limitations like radiation exposure, emerged as a valuable tool in the initial stages of the pandemic.These scans offered high sensitivity in detecting lung abnormalities associated with COVID-19, even when traditional PCR testing might be negative.As the disease evolved and understanding of its long-term effects grew, radiology continued to play a central role.Follow-up CT scans are being used to assess the resolution of lung abnormalities and identify potential post-COVID complications, aiding in patient prognosis and treatment strategies [1][2][3][4][5].We aimed to study the early evolution of the imaging findings in patients with COVID-19 pneumonia.
Baseline chest CT scans in our study demonstrated a high prevalence of pulmonary parenchymal abnormalities in our patient cohort.GGOs emerged as the most prevalent finding (97.5%) followed by consolidation and interlobular septal thickening which were seen in 85% of the study population.Other major findings were parenchymal bands and crazy paving.Previous literatures [7,8] suggest a temporal evolution in COVID-19 pneumonia, progressing from focal ground-glass opacities (GGOs) in the very early stages to areas of patchy consolidation, then potentially multi-focal consolidation.This pattern typically resolves by the end of the third week, with a decrease in overall lung consolidation.
The mean time of baseline CT scan in our patients was around 27.5 days which fell in the dissipative stage of illness; however, GGO and consolidation were still the most common and florid findings followed by interlobular septal thickening, parenchymal bands and crazy paving.
The follow-up CT scan done after six weeks also showed GGO as the predominant pattern seen in almost 85% of the patients; however, significant resolution of consolidation was seen which was present only in about 15% of the patients.The changes which might suggest fibrotic component such as interlobular septal thickening, and parenchymal bands also showed significant interval resolution.Our findings were similar to the findings seen in studies done by You et al. [9] which showed that most common imaging findings on follow-up CT scan were GGO and sub-pleural parenchymal bands respectively.The study done by Zhou et al. [10] in this regard had also showed that 71% of the patients had some residual lung findings.In our study we saw that the resolution was significantly more (p<0.05) in bilateral upper lobes compared to the lower lobes which suggests that resolution starts taking place from top to bottom in the lungs.At the time of follow-up CT scan, most of our patients were symptomatically much better and most of them had been discharged from the hospital.Pleural effusion was observed in 18% of our patients at baseline CT scan and in about 6% on follow-up.This is in contrast to the study done by Chong et al. [11] which showed incidence of pleural effusion to be at approx.7% among various studies.The pathophysiology proposed for pleural effusion has been multi-system inflammatory response which is seen in critically sick patients.Thus, our study found that a significant portion of patients with COVID-19 pneumonia showed interval resolution of lung abnormalities on follow-up CT scans, which aligns with observations in previous literature [6,12,13].
Our study had a few limitations.The generalizability of our study may be limited by the relatively small sample size of 40 patients.While assessing early temporal changes was our primary goal, the lack of long-term follow-up CT scans (beyond six weeks) restricts our ability to comprehensively evaluate the disease's entire course.

Conclusion
Our findings are encouraging, demonstrating that a majority of patients experienced early temporal resolution of both lung abnormalities on follow-up CT scans and their initial symptoms.This suggests a positive recovery course for most patients in this study.Future research with larger patient cohorts and extended follow-up periods would be valuable to gain a more comprehensive understanding of COVID-19 pneumonia's long-term effects.

Figure 1 .
Figure 1.Bar diagram showing common imaging patterns of COVID-19 pneumonia on baseline CT (blue colour) and on follow-up CT scan (orange colour) at 6 weeks.

Figure 2 .
Figure 2. A 73-year-old male patient showing consolidation, inter-lobular septal thickening, few parenchymal bands respectively (A & C black circles), showing significant interval resolution on follow-up CT scan (B & D black circles) done after 6 weeks with only few GGO and interlobular septal thickening respectively.

Figure 3 .
Figure 3.A 50-year-old female patient showing extensive inter-lobular septal thickening, patchy GGOs (black arrows and black dotted circles) and patchy consolidation (elbow arrows) respectively (A & C), showing significant interval resolution on follow-up CT scan (B & D) done after 6 weeks with only subtle GGOs.

Table 1 . Demographic, clinical and laboratory details of the study subjects
Symptom onset to CT scan (mean) 44.5 ± 5.4 days