Clinical, Laboratory, and Imaging Features of COVID-19 in a Cohort of Patients: Cross-Sectional Comparative Study

Background: The clinical, laboratory, and imaging features of COVID-19 disease are variable. Multiple factors can affect the disease progression and outcome. Objective: This study aimed to analyze the clinical, laboratory, and imaging features of COVID-19 in Jordan. Methods: Clinical, laboratory, and imaging data were collected for 557 confirmed COVID-19 patients admitted to Prince Hamzah Hospital (PHH), Jordan. Analysis was performed using appropriate statistical tests with SPSS version 24. Results: Of the 557 COVID-19 polymerase chain reaction (PCR)-positive cases admitted to PHH, the mean age was 34.4 years (SD 18.95 years; range 5 weeks to 87 years), 86.0% (479/557) were male, 41% (29/70) were blood group A+, and 57.1% (93/163) were overweight or obese. Significant past medical history was documented in 25.9% (144/557), significant surgical history in 12.6% (70/557), current smoking in 14.9% (83/557), and pregnancy in 0.5% (3/557). The mean duration of hospitalization was 16.4 (SD 9.3; range 5 to 70) days; 52.6% (293/557) were asymptomatic, and 12.9% (72/557) had more than 5 symptoms, with generalized malaise and dry cough the most common symptoms. Only 2.5% (14/557) had a respiratory rate over 25 breaths/minute, and 1.8% (10/557) had an oxygen saturation below 85%. Laboratory investigations showed a wide range of abnormalities, with lymphocytosis and elevated C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and D-dimer the most common abnormalities. Ground glass opacity was the most common imaging finding. Men had a significantly higher frequency of symptoms, incidence of smoking, reduced hemoglobin, increased monocyte %, elevated creatinine levels, and intensive care unit admissions compared with women (P<.05). Hospitalization duration was associated with increased age, male gender, symptom score, history of smoking, elevated systolic blood pressure, elevated respiratory rate, and elevated monocyte %, CRP, ESR, creatinine, and D-dimer (P<.05). Conclusions: Most COVID-19 cases admitted to PHH were asymptomatic. Variabilities in symptoms, signs, laboratory results, and imaging findings should be noted. Increased age, male gender, smoking history, and elevated inflammatory markers were significantly associated with longer duration of hospitalization. (JMIR Public Health Surveill 2021;7(9):e28005) doi: 10.2196/28005 JMIR Public Health Surveill 2021 | vol. 7 | iss. 9 | e28005 | p. 1 https://publichealth.jmir.org/2021/9/e28005 (page number not for citation purposes) Qaisieh et al JMIR PUBLIC HEALTH AND SURVEILLANCE


Introduction
In December 2019, an outbreak of pneumonia of unknown etiology was identified in Wuhan city, China [1]. Later, it was found that the causative pathogen was severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) [1]. The routes of transmission of this virus are mainly droplets and direct contact with patients, and the main source of the disease at present is patients with COVID-19 [2]. On March 11, 2020, the World Health Organization declared COVID-19 a pandemic due to its exponential spread all over the globe [3].
X-ray imaging studies showed that bilateral involvement is more common than unilateral, and the most common lesion is a ground glass appearance followed by consolidation [4]. Computed tomography (CT) scans also confirmed these findings [9]. The most prevalent laboratory findings are decreased albumin, high C-reactive protein (CRP), lymphopenia, increased platelets, increased lactate dehydrogenase, and a high erythrocyte sedimentation rate (ESR) [10].
Although the prevalence of COVID-19 is equal between men and women, the disease is more severe in men [11]. Some studies attributed this to a higher expression of angiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV2, in men than in women in pathological conditions [12]. Furthermore, it has been found that ACE2 expression is higher in current and ex-smokers, and smoking is more common in men than in women. Thus, the disease is more severe in men [13]. Patients with hypertension or chronic obstructive pulmonary disease (COPD) tend to have more severe COVID-19 disease. Children have less severe disease than adults, and these differences are possibly due to having different expression levels of ACE2 receptors [14]. While this disease involves mainly the respiratory tract, different organ systems can become involved.
Researchers have dug into massive gene expression datasets to show that other potential target cells that also produce ACE2 and TMPRSS2 are scattered throughout the body, which could explain the systemic nature of this disease [14]. While multiple studies have reported greater disease severity and mortality in men infected with COVID-19, no comparative studies have been conducted regarding the differences in clinical, laboratory, and imaging findings according to gender [11][12][13]15].
The first case of COVID-19 in Jordan was registered on March 2, 2020 in a Jordanian citizen who came back from Italy [16], and the number of cases as of December 12, 2020 exceeded 250,000 [3, 16,17]. Even though there is a tremendous number of studies worldwide regarding COVID-19 patients' clinical features, laboratory findings, and imaging findings, there are only a few in our region (the Middle East), and no study has yet been done in Jordan. Clinical, laboratory, and imaging findings are widely variable according to geographic location, disease severity, SARS-CoV2 strains, population demographics, immunity, and other factors [2,10]. The aim of this study was to describe the clinical manifestations, laboratory findings, and imaging findings of COVID-19 patients in Jordan with an emphasis on gender-related differences.

Study Population
A total of 557 confirmed COVID-19 cases admitted to Prince Hamzah Hospital (PHH) during the period from March 1, 2020 to August 1, 2020 were recruited prospectively to this study after giving formal voluntary consent, and they were followed daily for clinical, paraclinical, and outcome parameters. All COVID-19 cases were confirmed by at least one positive COVID-19 reverse transcription (RT)-PCR test performed by an accredited referral lab. All COVID-19 recovery cases were confirmed by complete clinical and laboratory resolution, including 2 negative COVID-19 RT-PCR tests within 2 days. The government of Jordan had a policy at the time of the study to admit all COVID-19-positive patients to the hospital for isolation regardless of symptom severity.
The study protocol was approved by the institutional review board (IRB) at the Hashemite University (No: 1∕5∕2019∕2020) and the Jordanian Ministry of Health/PHH IRB (No: 1/1631).

Demographic, Clinical, and Laboratory Data From COVID-19 Patients in Jordan
Confirmed COVID-19 patients' demographics; clinical, social, and medical history; and laboratory and imaging data were obtained directly from patients, relatives, or medical records of patients admitted to PHH, Amman, Jordan (the main COVID-19 isolation and management center in Jordan). Data were recorded on the first day of admission and daily during follow-ups. Demographic data included age, gender, weight, height, BMI, and blood group. Clinical data included symptoms reported by patients, vital signs, medical and surgical history, and duration of hospitalization. Laboratory data included all laboratory tests performed for patients during their admission. Imaging data assessed by an accredited radiology specialist were extracted for the 135 patients who had imaging studies (questionnaire in

Radiological Features of COVID-19
The following radiological data were obtained for 135 COVID-19 patients. CT scan studies of the chest showed that the most common appearance of infiltrates was ground glass opacity (44/135, 32.6%), followed by broncho-alveolar consolidation ( Table 4).

Associations Between Age, Gender, BMI, Hospitalization Duration and COVID-19 Clinical, Laboratory, Imaging Data
Men had a significantly higher frequency of having symptoms (symptom score) than women (244/479, 51.0% vs 19/78, 24.4%, P=.004). Furthermore, generalized malaise, diarrhea, chills/rigors, dry cough, rhinorrhea, and fever were significantly more frequent in men than in women (P≤.05). Mean heart rate and frequency of elevated heart rate were significantly higher in men than in women (P=.02). Past medical, past surgical, allergy, and smoking history were significantly higher in men than in women (P≤.001). Hemoglobin, hematocrit, monocyte %, basophile %, and creatinine levels were significantly higher in men than in women (P<.05), while ESR, alkaline phosphatase (ALP), and D-dimer levels were significantly higher in women than in men (P≤.05). Hospitalization duration and intensive care unit (ICU) admissions were significantly higher in men than in women (P=.000); 7 men and 1 woman were admitted to the ICU, and 2 men died. Table 6 shows the associations between age, gender, BMI, and hospitalization duration in relation to symptoms and signs, laboratory data, and imaging findings. Increased age was significantly associated with a higher frequency of symptoms (symptom score; P=.03); increased frequency of generalized malaise, headache, loss of smell, diarrhea, loss of taste, rhinorrhea, wet and dry cough, shortness of breath, chest pain, and palpitations; higher frequency of significant past medical, past surgical, and smoking history; and increased blood pressure, lower oxygen saturation, and higher BMI (P≤.05). Furthermore, increased age was significantly associated with elevated CRP, ESR, urea, creatinine, ALT, and ALP levels and positive imaging findings (P≤.05; Table 6). Higher BMI was associated with increased age; higher symptom score; elevated blood pressure, CRP, ESR, creatinine, ALT, and ALP levels; and positive imaging findings (P≤.05; Table 6). Hospitalization duration was positively associated with increased age, male gender, higher symptom score, history of smoking, significant past medical and surgical histories, elevated systolic blood pressure, elevated respiratory rate, lower oxygen saturation, elevated monocyte %, elevated CRP and ESR, increased creatinine, and elevated D-dimer (P<0.05; Table 6).

Principal Findings
Jordan has successfully managed to contain the first wave of the SARS-CoV2 virus by implementing early lockdowns. The lockdown began on March 18, 2020, when the number of known cases of the virus was less than 20. Jordan closed its borders on March 16, 2020 and kept arriving passengers in quarantine. Extensive contact tracing was carried out, and every person who tested positive for the virus was admitted to the hospital to control the spread of the virus [17]. Having all COVID-19-positive patients admitted to the hospital for isolation provided an opportunity to study the clinical and laboratory characteristics in patients with SARS-CoV2 viral infection in Jordan. PHH in Jordan was the main hospital designated to admit patients positive for the SARS-CoV2 virus. The patients were admitted regardless of their symptoms. In Jordan, most cases were in the age range of 21-40 years (34.1%), which is comparable to other studies [2,19]. Furthermore, a meta-analysis later in the pandemic by Pormohammad et al [4] had a mean age of 48 years for patients from studies around the world.
In this study, the younger age group (0-20 years old) represented about 29% of the cases, which was higher than the percentiles of young people infected in Saudi Arabia and China, where the percentages were about 15% [2,19]. More recently, in the United States, children under 18 years old represented 12% of all COVID-19 cases [20]. In South Korea, where all patients with positive tests were also admitted, only 9% of the patients were under 20 years of age, with the population under 24 years old representing about 24% of the nation's population [21]. The age group under 20 years old represents about 44% of the Jordanian population [18], and this is the most likely reason for this higher percentage of COVID-19 cases among the young. Also likely contributing to this is the fact that all patients with positive tests were admitted, and extensive contact tracing was carried out.
There were more men than women in this study (86% men), which is different from other studies that either showed a slightly increased percentage of male patients [4,19] or, in a more recent meta-analysis of 3 million patients, showed equal infection rates between the 2 sexes [22]. This difference is difficult to explain but could be caused by the fact that SARS-CoV2 infection was mainly contracted by travelers and men working in the trucking business who then spread the disease to their family members [16]. Regarding the symptoms of COVID-19 in this study, most patients were asymptomatic (52.6%), and among symptomatic patients, dry cough (21.7%) and generalized malaise (21.5%), followed by fever (19.4%), were the most prevalent symptoms. This is quite similar to other studies, including 2 meta-analyses that showed that fever and cough were the most common symptoms [10,23]. Less common symptoms such as headache (13.5%), rhinorrhea (10.2%), and diarrhea (10.2%) were reported at much higher percentages in this study [24]. This is most likely explained by the fact that all patients with SARS-CoV2 viral infection were admitted regardless of symptoms, whereas other studies mainly included patients hospitalized due to their symptoms.
In this study, only 13.1% of COVID-19 patients had lymphopenia, while 30% had lymphocytosis and 56.9% of patients had a normal lymphocyte count. This contrasts with most other studies that tended to show an association between lymphopenia and COVID-19 [4,10]. Some studies hypothesized that lymphopenia may correlate with disease severity, such that lymphocyte count could possibly be used as a prognostic factor for COVID-19 patients [25,26]. Since more than half of the patients in our study were asymptomatic, this may explain the low percentage of COVID-19 patients found to have lymphopenia.
Inflammatory markers in COVID-19 patients in our study, including CRP, ESR, and LDH, were inconsistent with the findings of 2 meta-analyses [4,10]. This is most likely due to the high percentage of asymptomatic (52.6%) patients in this study. This finding increases the possibility of a positive association between high inflammatory markers and the severity of COVID-19, as proposed by yet another meta-analysis [27]. Abnormal liver enzymes, including AST and ALT, were present at lower rates compared with the results found elsewhere [28].
The radiological data from CT and x-ray scans of 135 patients were collected and analyzed. The most common lesion detected by CT scan was ground glass appearance, and this is consistent with what was found in the meta-analysis done by Bao et al [9], but at a much lower rate than those authors found (32.6% vs 90.35%, respectively). Peripheral involvement was more common than central involvement, and posterior involvement was more common than anterior involvement. These findings are similar to what was found by another study [29]. Multilobar distribution was more common than unilobar distribution, and the lower lobes were more affected than the upper lobes. Other studies found similar results [30,31]. The majority of patients who underwent chest x-ray had normal results, while Wong et al [31] found that 69% of the patients had abnormal findings on their chest radiography. This may be related to the fact that the majority of the patients in our study were asymptomatic.
When comparing male patients to female patients admitted with SARS-CoV2 infection, it was noted that male patients were more symptomatic than female patients (51.0% vs 24.4%, P<.05). Men were also more likely to be admitted to ICUs. In a meta-analysis that compared around 3 million patients from around the world [22], men had higher rates of ICU admission and mortality as well. The reason for this difference in morbidity and mortality between the sexes may be due to differences in the adaptive and innate immune systems, as the adaptive immune system in women has a higher number of CD 4 T cells [32,33] and stronger CD 8 cytotoxic activity [34]. Women also have more B cells and antibody production [32,35]. The reason for these differences is due to X-linked genes that affect the immune response to viruses [15,35].
Age was associated with increased symptoms (P<.05) and abnormal lab results. This has been documented in many other studies [36,37]. Age is also related to increased comorbidities, and in 1 meta-analysis in which there was an attempt to control for comorbidities, age itself remained a weak risk factor [38]. In our study, having an increased BMI was associated with having more symptoms, and this finding is similar to other studies and meta-analyses [39,40].
This study is the first to address the clinical, laboratory, and radiological features of COVID-19 patients in Jordan, and it was conducted with 557 patients, a considerable number of participants. A downside of this study is that all of the participants were from 1 center (PHH). Also, the data regarding laboratory testing and imaging were incompletely collected.

Conclusions
This is the first study to describe in detail all the clinical, laboratory, and imaging findings of the first 557 confirmed COVID-19 patients admitted to PHH in Jordan. Most cases were asymptomatic, male, and overweight or obese. Generalized malaise and dry cough were the most common symptoms. Only 2.5% had a respiratory rate over 25 breaths/minute, and 2% had an oxygen saturation below 85%. Lymphocytosis and elevated CRP, ESR, and D-dimer were the most common laboratory abnormalities, while ground glass opacity was the most common imaging finding. Men had a significantly higher frequency of symptoms, smoking, abnormal laboratory findings, and ICU admissions compared to women. Hospitalization duration was positively correlated with increased age, male gender, symptom score, history of smoking, elevated systolic blood pressure, elevated respiratory rate, elevated monocyte %, and elevated CRP, ESR, creatinine, and D-dimer.