This article aims at studying different pulmonary changes that occurred during COVID-19 pneumonia using serial CT scans and exploring more knowledge about the natural history of the disease process. This knowledge is important during the fight against COVID-19 infection which reflects on the morbidity and mortality rates. We studied 125 patients who underwent a total of 293 CT studies (average 2.34 CT study/patient). We divided the CT studies into 4 stages according to the timing of CT after the onset of the symptoms. We assessed different CT features and CT patterns as well as the CT severity score during different stages and recorded the patients’ complications as well as the oxygen saturation during different stages. We found an overall progression of the disease features, extension, and severity over time to reach the peak at the 3rd stage (8-14 days after the onset of symptoms) when the highest incidence of complications and the lowest level of oxygen saturation occurred. This was followed by the regression of these signs during the 4th stage (15-21 days from the onset of symptoms).
Most of the patients enrolled in this study were males (64.8%). Francone M et al. found a higher incidence of COVID-19 between the male gender in their study population (64.6%) and this was very close to our result [13]. Male patients represented 60% of the sample population in the study done by Xiong Y et al. [4]. This was controversial to Salvati L et al. who studied the relation of gender to the incidence, severity, and mortality of COVID-19 and concluded almost equal distribution of the disease between males and females. Although, some difference was found regarding the severity and mortality of the disease being more common in males [14].
Dyspnea and fever were the commonest presenting symptoms found in our sample size (66.4% and 55.2% incidence respectively). Fever was found as one of the most common presenting symptoms [4, 15].
In this study, GGO was the commonest CT feature all through the disease and it showed a gradual rise to reach the peak about 4-7 days from the onset of symptoms, then gradually declined during the last stage. During the last stage, GGO had a higher incidence than the initial stage. This was consistent with Wang Y et al. who found GGO to be the commonest CT features during their study, persisted till the late stage, and became the last finding to resolve [10]. Also, this agreed with Pan F et al. who noticed a progression in the GGOs till the peak stage (9-13 after the onset of symptoms) where most of the GGOs were replaced by consolidations, and this finding was almost similar to our study. Also, they observed extensive GGOs during the absorption stage (> 14 days after the onset of symptoms) as the sequel of consolidation absorption [11].
The incidence of consolidation and crazy paving showed a gradual rise to reach its peak at the 3rd stage (8-14 days after the onset of symptoms) (63.4%) and this was in parallel to the highest incidence of complications as well as the lowest oxygen saturation level at the same stage. Therefore, we can consider the consolidation as a CT sign of severity and prediction of complications. Pan F et al.’ study agreed with this, as they noticed consolidation changes in 90% of the patients at the 3rd stage which was also the peak [11]. Liang T et al. also showed a progressive increase in the incidence of consolidation that resolved gradually after 2 weeks from the onset of symptoms [16]. Wang Y et al. hypothesized that consolidation during this stage was due to organizing pneumonia which had the potential to progress to fibrosis and mandated the increase in steroid therapy [10]. Liu et al. studied 73 patients and found that consolidation was the commonest CT feature in patients with severe infection [17]. Liu N et al. also found that consolidation was the commonest feature during the follow-up study (81%) and gradually decreased during further follow-up [18].
Fibrosis was not seen in all cases particularly in the early stages. Yet, its incidence increased in the late stage (4th stage) 15-21 days from the onset of the symptoms, when most of the features, CT severity, and oxygen saturation improved. Therefore, we could consider the appearance of fibrosis as a sign of healing and resolution of the disease. This was consistent with Wang Y et al. and Liang et al. who found a higher incidence of fibrosis in the late stage in their studies and also confirmed it as a sign of resolution of the disease process [10, 16]. Xiong Y et al. studied 42 patients with initial and follow-up CT done at 4.5 and 11.6 days respectively after the onset of symptoms and concluded that the incidence of fibrosis almost doubled from 36% in the initial CT to 74% in the follow-up CT [4].
According to our study, there was a gradual progression of the pulmonary opacities, an increase in crazy paving and consolidation, and consequently mixed attenuation pattern through the course of the disease to reach the peak at the 3rd stage and then dropped in the 4th stage. Moreover, mixed attenuation with predominant consolidation was commoner than mixed attenuation pattern with predominant GGO during the 3rd stage. These were keeping with other few studies [10, 13, 16]. Also in complicated cases, we noticed a higher incidence of mixed attenuation patterns with predominant consolidation during different stages of the disease rendering it a CT sign of severity.
Different CT scoring systems were used to assess the disease severity, some of them depended on the assessment of the disease extension whatever the pattern of the disease, while others depended on both the disease extension as well as the pattern of CT features [10, 11, 16, 19, 20]. We used a simple CT scoring similar to the one used by Francone M and Pan F et al. [11, 13] which depended on the extension of the disease. It was simple, rapid, and had less inter-observer variability.
In our study, we noticed more lobar affection, and hence worse CT severity score, during the disease which peaked at the 3rd stage (8-14 days from the onset of the symptoms). Xiong et al. compared the affected lobes during the initial and follow-up CT (average 7 days interval) and found a significant increase in the number of the affected lobes from 3.7 ± 1.6 in initial CT to 4.4 ± 1.2 in follow-up CT [4]. Our results agreed with Pan F et al. who found the peak of CT score and several lobes involved in stage 3 (9-13 days from the onset of symptoms) and the peak CT score was 7 ± 4 compared to 7.1 ± 5.1 in our study [11]. Also, Liang T et al. noticed the peak of CT score occurred at days 11-14 during follow-up. However, the score was 5.3 ± 3.3 which was lower than our study [16].
Furthermore, we detected the highest CT severity score in complicated cases during the 2nd and 3rd stages (12.66 and 10.21 respectively) and this was in line with Liu N et al. who found a higher CT score in patients with severe COVID-19 infection compared to patients with moderate disease form and the peak CT score in severe cases was 12.1 during the second follow-up (average 13 days after the onset of symptoms) [18].
Oxygen saturation was considered one of the main important parameters that indicated disease severity and progression. We noticed an inverse relationship between the CT severity and the level of oxygen saturation, as the higher the CT severity score was, the lower the level of oxygen saturation. The lowest level of oxygen saturation noticed in our study was at the 3rd stage and this could be explained by the highest incidence of mixed attenuation pattern with predominant consolidation at this stage. Moreover, the progressive development of fibrosis came in parallel with more disease extension, higher numbers of lobar involvement, and higher CT severity score. This was compatible with Wang K et al. who studied 114 confirmed cases with COVID-19 pneumonia and found an inverse correlation between CT and SpO2 [21]. Also, Dia H et al. found a drop in SpO2 level with the progression of the disease and also noticed that more diffuse parenchymal involvement, consolidation, and fibrosis explained the severity of pulmonary dysfunction [22].
Limitation
The limitations of our study were being a retrospective. Hence, all patients underwent their CT studies according to the clinical condition and not at a regular fixed interval. We did not divide our patients into subgroups depending on the clinical severity which required more researches to acquire more data about the disease progression between different clinical groups. Moreover, long-duration follow-up is needed for more understanding of long term effects and pulmonary changes.