COVID-19 is a new highly contagious infectious disease that causes lower respiratory inflammation; it starts by alveolar hyaline membrane injury or interstitial edema which appears on CT as GGO then progresses to alveolar filling with exudate which is the consolidation after which an autoimmune reaction begins by activation of both humeral and cellular immunity mediated by virus-specific B and T cells causing the formation of pro-inflammatory cytokines which are the cause of interlobular septal thickening, giving rise to first crazy paving then lung fibrosis [12].
The clinical picture of the disease is diverse ranging from asymptomatic or subclinical forms to critically ill patients with acute respiratory distress syndrome [ARDS] or multi-organ failure which can occur as short as 9 days from the onset of symptoms [9], so not only diagnosis of the disease is mandatory but also monitoring the clinical course of the disease is of paramount importance to triage patients who are in need of urgent intensive medical care. Extension of pulmonary affection is easily assessed by chest CT but this is not suitable for critically ill patients, so a laboratory biomarker of disease progression is needed and here comes the role of LDH and ferritin.
LDH is an enzyme that converts lactate to pyruvate in the process of tissue breaking down, so patients with severe COVID-19 pneumonia shows an increase in the serum LDH [13]; also, ferritin is increased because it is secreted either by the macrophages that produce cytokines and account for the main immune cells present in lung parenchyma or by cytokines themselves such as interleukin-6 [14].
From 250 cases with confirmed RT-PCR for COVID-19, 185 [74%] patients were symptomatizing from which 22/185 [11.2%] showed normal chest CT; this was in agreement with Yang and Yan [15] who reported 11.8% [symptomatizing patient showing normal chest CT] while Bernheim et al. [16] showed 56%; this big difference in the percentage between the current study/Yang and Yan [15] and Bernheim et al. [16] could be explained that the latter study was done only within the first 2 days from onset of symptoms in contrary to our study and Yang and Yan that were done within 1 week.
Thirty-seven [14.8%] patients were asymptomatic and showed positive chest CT findings; this clinical-radiological discrepancy was evident in previous studies like Chung et al. [17] which showed 14% while Inui et al. [18] which reported 39.2%; this was explained by a lot of theories, like those patients were exposed to COVID-19 virus before and hence developed immunity leading to a subclinical presentation, or they are having a recent infection and in the recovery period with subsiding of symptoms at the time of chest CT done but an absence of clear clinical history of infection and lacking CT features of healing COVID-19 pneumonia weaken this theory, and the only logical explanation is that there is a time interval between chest CT manifestation and developing symptoms with the former begins first but this hypothesis needs to be more investigated [17, 18]; unfortunately, in the current study, none of those patients was followed up to see if they have developed symptoms or not.
Regarding the comparison between gender and different stages of COVID-19 pulmonary affection, there was no gender difference in the mild stage while in the moderate stage males represented 64.6% almost double of the females who were 35.4% while in the severe stage males were 85% compared to only 14.3% for females; this result was in concordance with Jin et al. [19] and Hiroki et al. [20] with the latter stating that male gender may be a predictor of a more severe form of COVID-19.
Regarding the age, there was a statistically significant correlation between older age and severity of chest CT manifestations as no patient in the severe stage was under 30 years while there was no difference between 31 and 50 years group and 51–82 years group showing 47.6% and 52.4%, respectively; this was in agreement with the US Centers for Disease Control and Prevention reporting that 8 in 10 COVID-19-related deaths have been among people aged 65 years or over [21].
Regarding the distribution of lung manifestations, unilateral lung affection was only observed in 24/200 [12%] while bilaterally was seen in 176/200 [88%], and that was in agreement with almost all previous publications [7,8,9, 16, 17].
Peripheral involvement was seen in 62/200 [31%] and broncho-vascular in 4/200 [2%], while both peripheral and broncho-vascular involvement was the highest percentage being 134/200 [67%]; this finding was in agreement with Wang et al. [8] who reported 56.4% both peripheral and broncho-vascular distribution. On the contrary, Shi et al. [9] reported more percentage of peripheral distribution 54% compared to 44% diffuse, and this can be explained that this study included a small number of patients, only 81 patients with some of which were asymptomatic.
Regarding the pattern of chest CT pulmonary affection in different stages, GGO was the highest percentage accounting for 191/487 [39.2%], followed by consolidation 152/487 [31.2%], then fibrosis 74/487 [15.2%], and CP 67/487 [13.7%], with lymph node only seen in 3/487 [0.6%]; these findings were in agreement with Song et al. [22].
Since the outbreak of the COVID-19 pandemic, many studies showed that the inflammatory cytokine storm is the main cause of complication of COVID-19 pneumonia leading to acute respiratory stress syndrome and multi-organ failure and even death, so laboratory detection of increased serum inflammatory markers is mandatory in order to provide those patients early proper treatment [23].
In the current study, there was a statistically high significance between increased levels of both serum ferritin and LDH in correlation with CT staging, where ferritin was increased in 18.4% in the mild stage, 63% in the moderate, and 100% in the severe stage; these findings were in agreement with Lin et al. [24] who reported that patients with severe COVID-19 pneumonia showed higher levels of serum ferritin than the non-severe patients using a multivariate logistic regression analysis showing that the serum ferritin level was an independent risk factor for disease severity.
LDH was increased in 39.4%, 92.3%, and 100% mild, moderate, and severe stages, respectively, and this was in concordance with Wu et al. [13] who reported that the higher LDH levels were found in patients with severe COVID-19. All the ICU patients showed a marked increase reaching up to more than four times the normal; these results were in agreement with the pooled study done by Henry et al. [25] who stated that increased LDH was associated with significantly increased odds of severe COVID-19 in both case-control studies and retrospective studies.
In spite that CT scoring is a subjective method for assessing the severity of COVID-19 pneumonia, it correlates well with the clinical manifestations and laboratory findings of the disease [26] helping to triage patients and reserving health care resources so only the ones with severe lung affection could be closely monitored in order to provide early aggressive treatment; in the current study, comparing the CT score for patients admitted to ICU and patients who were treated either in the hospital or at home, all the patients in ICU were in severe stage with CT scores ranging from 21 to 23, and this was in agreement with the study of 236 patients done by Colombi et al. [27] who reported a positive correlation between the extent of CT lung manifestations and intensive care unit admission or death. Also, Francone et al. [25] reported that CT score was significantly higher in critical COVID-19 patients ranging from 15 to 24 with 20.3±3 [mean value ± SD] than in the mild stage range 0–19 with 8.7±4 [mean value ± SD].
This study has limitations as none of the patients was in the pediatric age group; the study included only patients within the first week of onset of symptoms or positive RT-PCR, so late chest manifestations of the disease could not be investigated; also, there was no follow-up of cases that were asymptomatic with positive chest CT findings to find out if they developed symptoms or not or the patients that were symptomatic and with negative chest CT findings to see if they developed imaging manifestations or not, but this could be explained that the time of the study was at the peak period of the disease with a large number of cases and limited health care resources.