COVID-19 infection: epidemiological, clinical, and radiological expression among adult population

Background High-resolution computed tomography (HRCT) has proved to be an important diagnostic tool throughout the COVID-19 pandemic outbreaks. Increasing number of the infected personnel and shortage of real-time transcriptase polymerase chain reaction (RT-PCR) as well as its lower sensitivity made the CT a backbone in diagnosis, assessment of severity, and follow-up of the cases. Results Two hundred forty patients were evaluated retrospectively for clinical, laboratory, and radiological expression in COVID-19 infection. One hundred eighty-six non-severe cases with home isolation and outpatient treatment and 54 severe cases needed hospitalization and oxygen support. Significant difference between both groups was encountered regarding the age, male gender, > 38° fever, dyspnea, chest pain, hypertension, ≤ 93 oxygen saturation, intensive care unit (ICU) admission, elevated D-dimer, high serum ferritin and troponin levels, and high CT-severity score (CT-SS) of the severe group. CT-SS showed a negative correlation with O2 saturation and patients’ outcome (r − 0.73/p 0.001 and r − 0.56/p 0.001, respectively). Bilateral peripherally distributed ground glass opacities (GGOs) were the commonest imaging feature similar to the literature. Conclusion Older age, male gender, smoking, hypertension, low O2 saturation, increased CT score, high serum ferritin, and high D-dimer level are the most significant risk factors for severe COVID-19 pneumonia. Follow-up of the recovered severe cases is recommended to depict possible post COVID-19 lung fibrosis.

COVID-19 infection with emphasis on computed tomography (CT) in screening, diagnosis, and follow-up of COVID-19 pneumonia [6][7][8][9]. High-resolution computed tomography (HRCT) is considered a backbone tool in management of the disease [10]. The purpose of the current study was to correlate the clinical expression of the disease and the HRCT findings among adults.

Cases
This retrospective study included 240 participants from 25 March 2020 till 5 July 2020. One hundred forty were males (58.3%) and 100 were females (41.7%). Age range was 18-85 years with mean ± SD = 45.82 ± 16.74. Clinical, laboratory, and radiological evaluation occurred within the first 5 days of the onset of the symptoms. The Institutional Research Ethics committee has approved the study, and a written informed consent was obtained from each patient.

Epidemiological and clinical points of view
The patients were included according to the following: (1) epidemiological background, traveling to areas with case reports or exposure to a confirmed case within 14 days prior to the onset of symptoms; (2) clinical and laboratory manifestations, the patients underwent complete history taking, general and local examination, laboratory tests including complete blood count (CBC), C-reactive protein (CRP), serum ferritin, D-dimer, and liver and kidney function tests; (3) imaging criteria for COVID-19 pneumonia; (4) real-time transcriptase polymerase chain reaction (RT-PCR) of the nasopharyngeal swab for 188 cases.

Image acquisition and analysis
HRCT of the chest was done using a 160 slice Multi-Detector Toshiba CT Aquilion Prime scanner. Patients were in supine position with head first. Image acquisition parameters were 100 kV, 250 mAs, FOV = 400 × 460 mm, slice thickness 1.0 mm, and inter-slice gap 1.0 mm. The images were reviewed on VITREA workstation for interpretation.

Follow-up CT
Eighteen cases underwent follow-up after discharge (about 5 weeks from the onset of the illness) due to recurrent dyspnea, and their CT showed strands of fibrosis as in Fig. 3.

Statistical analysis
The descriptive statistics are mean, standard deviation, and median for continuous data. The statistics for categorical variables are counts and percentages. Student's t test and Mann-Whitney U test were performed for continuous variables, and the χ 2 test and Fisher exact test were used for categorical variables. Z test was used to   compare two sample proportions. Spearman's test was used to analyze the correlation between measurement data and ordinal variables while the Pearson correlation was used to evaluate the linear relationship between two continuous variables. Multivariable binary logistic regression analyses were used to assess the association between age, gender, smoking history, O 2 saturation, CT score, CBC, serum ferritin and D-dimer level, and the dependent variable of severity of disease. The odds ratio (OR) along with the 95% CI were reported. Odds ratio (OR) is a measure of association between exposure and an outcome. The OR represents the odds that an outcome will occur given a particular exposure, compared to the odds of the outcome occurring in the absence of that exposure. A P value of less than .05 was regarded as statistically significant. All statistical analyses were performed using SPSS 20.0 for Windows (SPSS, Inc, Chicago, IL).

Results
A total of 240 cases diagnosed as COVID-19 infection (188 underwent RT-PCR and 113 cases were positive representing 60.1%) were included. The patients were divided into two subgroups severe and non-severe cases whether the case needed ventilatory oxygen support at time of presentation. This was according to the 2019 clinical practice guideline from the Infectious Diseases Society of America and the American Thoracic Society for diagnosis and treatment of adults with communityacquired pneumonia [13].
In the analysis of the symptoms that belong to both groups, loss of taste and smell, sore throat, and runny nose were significantly common in non-severe cases (p < 0.0001 for all). On the other hand, dyspnea, chest pain, and expectoration were significantly common among severe cases (p < 0.0001, 0.008, and < 0.0001 respectively). Regarding the associated co-morbidities, systemic hypertension and cerebrovascular compromise were significantly encountered among severe cases (p 0.002 and 0.008 respectively) ( Table 1).
According to the laboratory results, serum ferritin, Ddimer, and troponin levels were significantly higher in severe patients compared to the non-severe ones (p 0.002, 0.001, and < 0.0001 respectively) ( Table 2).
Regarding CT findings, involvement of both lungs has been reported in 188 cases (78.3%), 48 cases (20%) showed unilateral lung affection, and 4 cases (1.7%) elicited normal lungs. According to lesion location either peripheral involving the outer third or central involving the inner two thirds, 140 cases (58.3%) showed peripheral lung lesions, 8 cases (3.3%) with central lesions, and 88 cases (36.7%) presented peripheral and central lesions as well.
The commonest pattern encountered on CT was the ground glass opacities (GGOs) representing 96.7%, followed by consolidations with 39.2%. Air bronchogram was the commonest special CT sign recorded in 92 cases (38.3%), and the least sign was reverse halo sign in 18 cases (7.5%) ( Table 3).
Regarding the imaging findings, the non-severe cases showed significant frequency of unilateral pulmonary affection, central location of the lesions, unilobar and bilobar affection, ground glass opacities and septal lines as well as the crazy paving patterns, reverse halo as a special imaging sign, and lower CT severity scores as illustrated in Table 3. CT-SS ranged from 0 to 25 with mean ± SD 12.22 ± 6.02. It showed significant negative correlation with O 2 saturation and outcome of the patients (r − 0.73/p 0.001 and r − 0.56/p 0.001 respectively) ( Table 4

and Figs. 4 and 5).
Multivariate regression analysis of the most relevant risk factors for severity among patients with COVID-19 revealed that older age, male gender, smoking, hypertension, low O 2 saturation, increased CT score, high serum ferritin, and high D-dimer level are the most significant risk factors (Table 5).
Few patients (9/240) whom were confirmed by RT-PCR had extra-pulmonary manifestations as follows: two cases were diagnosed as myocarditis after normal diagnostic coronary catheterization, three cases had dural venous sinus thrombosis on brain magnetic resonance venography (MRV), two patients with acute lower limb ischemia by Doppler study and CT angiography (a case of complete occlusion of peroneal artery and another one with anterior tibial artery occlusion), and two patients with acute infarction of middle cerebral artery territory.

Discussion
By the end of 2019, many cases with a novel febrile chest infection had been reported in Wuhan City, China. Clinical and CT imaging share characteristic findings. Our study has depended primarily on the HRCT to screen cases with clinical and epidemiological data suspicious for COVID-19 infection even with negative or unavailable RT-PCR testing. It has met the recent WHO guidelines [14]. The current study did not depend primarily on RT-PCR. This was supported by Bai et al. [15] who stated that CT chest had higher sensitivity in relation to RT-PCR, yet the obstacle was to differentiate between COVID-19 pneumonia and other viral pneumonia as well as the organizing pneumonia. Fang et al. [16] has reported 98% sensitivity for CT chest compared to 71% for RT-PCR.
Like Wu et al. [17], high fever and dyspnea as a symptom of lower respiratory tract involvement were significantly higher in patients belonged to the severe group compared to the upper respiratory tract symptoms.
On analysis of the imaging features, the bilateral multi-lobar affection with peripheral distribution was the commonest interpreting finding, and GGOs were the most encountered pattern; other reported patterns were consolidations and crazy paving as well as the septal lines. Similar outcome was stated by many studies [6,[18][19][20][21][22][23].
In agreement with Zhao et al. [25] who concluded that old age, diffuse pulmonary affection, and more lesions' extent as well as the presence of pleural effusion were significantly frequent among emergency cases compared to the non-emergency cases, there was no significant difference between both groups regarding the gender in their study.
Older age, male sex, smoking, low O 2 saturation, increased CT score, and high serum ferritin and high Ddimer level are the most significant risk factors; similar outcome has been reported by Li et al. [26] and Wu et al. [17] Hypertension as co-morbidity was an established risk factor for severity and poor patients' outcome, similarly with Guan et al. [27], Wu et al. [17], Li et al. [26], and Zhang et al. [28]. As it is known that ACE2 is a vital regulator for cardiac functions, thus it may explain the high frequency of severe COVID-19 pneumonia among the hypertensive patients. The current study elicited a strong negative correlation between the oxygen saturation and the CT-SS (r − 0.73/p 0.001), and this was different from the weak negative correlation reported by Wang et al. [29] (p < 0.05 and r − 0.446). There were significant correlations between the degree of pulmonary affection by COVID-19 infection and the main clinical symptoms and laboratory results, and this was in concordance with Wu et al. [30]. The current study agreed with Zhao et al. [31] who recommended clinical correlation with CT findings.
The globally disseminated COVID-19 infection outbreak is better to be aborted by the recommended protective measures.

Limitation of the study
The shortage of RT-PCR to include all cases was the main limitation. Other issues included somehow variable duration from the onset of the symptoms and seeking medical advice and investigations. Besides no hospitalbased electronic registry with self-recording of the comorbidities.

Conclusion
Regarding the current global pandemic of coronavirus infection, HRCT chest is the modality of choice for detecting COVID-19 pneumonia. It tells the clinicians about  severity using the severity score in interpretation. Older age, male sex, smoking, hypertension, low O 2 saturation, increased CT score, high serum ferritin, and high D-dimer level are the most significant risk factors and correlated with poor patients' outcome and mortality.

Recommendations
We recommend follow-up for the recovered cases to assess probable subsequent pulmonary fibrosis, also to pay attention to extra-pulmonary manifestations of COVID-19 infection, and to wait for larger scale studies to increase the awareness and knowledge about the disease and to strengthen the statistical analyses.