Clinical findings and laboratory parameters associated with CO-RADS classification in children with COVID-19

Abstract

Background

The aim of this study was to determine whether there are proven associations between CO-RADS categorizations and clinical and laboratory findings in children diagnosed with COVID-19 infection.

Methods

This is a retrospective observational study that includes the clinical and radiological data of pediatric patients who were admitted to both Minia University Hospital and Minia Insurance Hospital with a confirmed diagnosis of COVID-19, detected via reverse transcriptase PCR (RT-PCR) from nasopharyngeal swabs obtained between June 2022 and February 2023. Patients were divided into 5 groups based on the severity of involvement in chest CT.

Results

This study involved a total of 62 children who were confirmed to have COVID-19 infection. The most commonly observed symptoms in these children were fever (91.9%), shortness of breath (88.7%), and cough (87.1%). In addition, vomiting (24.2%), diarrhea (12.9%), impaired consciousness (11.2%), and convulsions (9.7%) were also reported. Significant differences were observed between CO-RADS classes in relation to patient gender, severity of respiratory distress, presence of cough, occurrence of diarrhea, elevated LDH levels, and prognosis.

Conclusion

The CO-RADS classification exhibited positive correlations with inflammatory biomarkers such as total leucocytic count, LDH, D-dimer, serum ferritin, and AST. Conversely, the CO-RADS classification showed negative correlations with ionized calcium levels, hemoglobin, and platelet count.

Background

Coronavirus disease 2019 (COVID-19) is a respiratory illness caused by the SARS-CoV-2 virus. The initial case of COVID-19 infection was documented in Wuhan, China, towards the end of December 2019. Since then, it has rapidly spread, leading to a global pandemic [1].

Compared to adults, children with COVID-19 may be asymptomatic or have minor clinical symptoms. Children account for an estimated 1 to 5% of patients diagnosed with COVID-19 [2]. However, cases of severe disease or the post-infectious multisystem hyperinflammatory state known as multisystem inflammatory syndrome in children (MIS-C) have been documented [3].

Egypt was among the countries affected by the global spread, and the first case was documented on February 14, 2020 [4]. As of May 1, 2020, the number of confirmed cases was 5895, representing a mortality rate of 6.9%. Although children were affected, the overall incidence rate was less than 10%. Additionally, healthcare workers accounted for 11% of all confirmed cases [5].

The confirmation of COVID-19 involves the utilization of reverse transcriptase PCR (RT-PCR) test, which isolates the viral RNA from patients through a nasopharyngeal swab [6]. In middle-income countries, there is a need for additional laboratory and radiological testing to improve the accuracy of detecting COVID-19 as this test is expensive.

High-resolution chest CT is a crucial tool for early detection of COVID-19 in patients with false-negative RT-PCR results and for determining disease severity [7].

The objective of this study was to assess the relationship between coronavirus disease 2019 (COVID-19) Reporting and Data System (CO-RADS) classification and the clinical and laboratory findings in children who have been diagnosed with COVID-19.

Methods

This is a retrospective observational cross-sectional study that includes the clinical and radiological data of pediatric patients who were admitted to both Minia University Hospital and Minia Insurance Hospital with a confirmed diagnosis of COVID-19, detected via RT-PCR from nasopharyngeal swabs obtained between June 2022 and February 2023. Patients were divided into 5 groups based on the severity of involvement in chest CT.

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional Review Board and Medical Ethics Committee, Faculty of Medicine, Al-Azhar University (Assiut) (MSR/AZ.AST./PED025/22/218/4/2023). The need for informed consent was waived by the ethics committee of the Faculty of Medicine because of the retrospective nature of the study.

Inclusion criteria were all children aged from 1 month to 18 years who had positive COVID-19 infection. Children with missing data and those with preexisting chronic lung disease that may interfere with the interpretation of chest CT were excluded from the study.

Data collection

We reviewed the electronic medical records of the patients and extracted the following data:

• Demographic and clinical data included the following: age, gender, presenting symptoms, degree of respiratory distress (RD) (I: tachypnea, II: accessory muscle use, III: grunting, IV: cyanosis), associated comorbidities, outcome.

• Laboratory test results: complete blood count (CBC), D-dimer, ferritin, C-reactive protein (CRP), lactate dehydrogenase (LDH), blood urea, serum creatinine, aspartate transaminase (AST), alanine transaminase (ALT), serum electrolytes (Na, K, ionized Ca).

• Chest CT scan was performed using a GE Bright Speed 16-slice spiral CT. Scanning slice thickness 10 mm, slice interval 10 mm. Chest CT scan findings with an assessment of CO-RADS grades: (CO-RADS 1, normal chest CT or noninfectious findings, CO-RADS 2 low suspicion level, typical for infections other than COVID-19, CO-RADS 3, equivocal, features compatible with COVID-19 and other diseases, CO-RADS 4, high suspicion level for COVID-19, CO-RADS 5, very high suspicion level, typical for COVID-19, CO-RADS 6, RT-PCR positive for SARS-CoV-2) [8]. The radiologists interpreted all CTs and were blinded to the clinical symptoms or laboratory findings of the patients.

Statistical analysis

Data were collected, revised, and entered into a master spreadsheet using Microsoft Excel 2013. The Statistical Package for Social Science (SPSS) version 23 was used for statistical analysis. Qualitative data were presented as numbers and percentages. Normally distributed quantitative were presented as mean and standard deviation, while abnormally distributed quantitative data were presented as median and interquartile range (IQR). The categorical data was analyzed using the chi-square test. Spearman’s correlation was used to detect the correlation between the CO-RADS classification and the laboratory parameters. The statistical significance level was set at p < 0.05.

Results

Patient characteristics

This study included 62 patients with confirmed COVID-19 infection by RT-PCR test (Fig. 1). Of the 62 patients, 61.3% were male. The median age of patients was 24 months (IQR, 5.0–96.0 months). Patients younger than 1 year accounted for 37.1% (Table 1).

Fig. 1

Flow chart of the studied patients

Table 1 Demographic characteristics and clinical manifestations of the patients

The most commonly observed symptoms at presentation were fever (91.9%), shortness of breath (88.7%), and cough (87.1%). Vomiting (24.2%), diarrhea (12.9%), impaired consciousness (11.2%), and convulsions (9.7%) were also reported, as shown in Table 1. Regarding RD, 12.9% of patients experienced grade IV RD, 16.1% had grade I RD, 32.3% had grade II RD, and 38.7% had grade III RD.

Comorbidities were identified in 22 patients (35.5%). Vasculitis was present in three patients (4.8%), while congenital diseases such as congenital heart defects and congenital biliary atresia were found in seven patients (11.2%). Additional comorbidities included asthma, cerebral palsy, chronic renal failure, central nervous system (CNS) infections, diabetic ketoacidosis, intracranial hemorrhage, pleural effusion, pericardial effusion, and dilated right coronary artery (RCA), as shown in (Fig. 2).

Fig. 2

Line chart demonstrates the associated comorbidities in children with COVID-19 as percentages

Laboratory investigations

In the current study, most laboratory findings were unremarkable, except for the median lymphocyte levels, which mostly decreased (2.40 × 10⁹/L). Conversely, there was an increase noted in the median count of neutrophils, neutrophil/lymphocyte ratio, CRP, D-dimer, ferritin, and Na (5.0 × 109/L, 2.53, 20.0 mg/L, 1.0 U/L, 190.0 µg/L, and 143.5 mEq/L, respectively). Eighteen (46.8%) patients had mild to moderate lymphopenia (1500–3000), while 29.0% of patients had severe lymphopenia Other laboratory parameters such as hemoglobin, platelets, blood urea, serum creatinine, AST, ALT, ionized calcium, and LDH were mostly normal (Table 2).

Table 2 Laboratory characteristics of the studied patients

Radiological characteristics

Most cases were CO-RADS III (41.9%), followed by CO-RAD II and IV with 19.4% and 22.6%, respectively. In addition, we found significant differences in gender (p = 0.031), RD severity (p < 0.001), and outcome (p < 0.001) between CO-RADS groups 1, 2, 3, 4, and 5 (Table 3).

Table 3 Relationship of the CO-RADS category with clinical manifestations of the patients

According to the data presented in (Table 4), there was a positive correlation between the CO-RADS score and total leucocytic count, LDH, D-dimer, serum ferritin, and AST levels. Conversely, a negative correlation was observed with the hemoglobin level, platelet count, and ionized calcium level.

Table 4 Correlation of CO-RADS with other studied parameters

Discussion

The hospital admission of infants with COVID-19 was increasing in different waves of COVID-19. Małgorzata et al. reported that the number of hospitalized infants was significantly higher in 2021 than in 2020 (651 vs.289, respectively) and they attributed this rise in the number of infants by the increase in the percentage of comorbidities, especially prematurity [9].

In this study, infants were found to be the most susceptible to COVID-19 (37.1%), when compared to other age groups. This is consistent with the findings of Alshengeti et al. who observed that patients under the age of 1 year accounted for 43.4% of their study population, [10]. Additionally, Hsieh et al. reported that children under 1 year of age and those between 12 and 18 years constituted the largest proportion (23%) of the patients [11]. In contrast to our results, Dong et al. reported that children under 1 year of age constituted 17.6%, while most of the children (24.5%) were between the ages of 6 years to 10 years [12]. Also, Bayramoglu et al. reported that the age group 0–6 years was the least affected at 28.9%, followed by the age groups 6–12 years (33.3%) and 12–18 years (37.7%) [13].

The higher prevalence of COVID-19 infection in this age group might be attributed to their underdeveloped immune systems and narrower airways, in addition to the associated underlying conditions such as prematurity and congenital heart diseases which make them more susceptible to respiratory viral infections [14].

In terms of clinical presentation, fever, shortness of breath, and cough were the most common symptoms, which is consistent with previous reports [11, 15,16,17].

According to the CO-RADS classification, our results showed that 45 (72.6%) patients had a CO-RADS score of three or higher. This is consistent with the results of El-Sayed et al., who found that 16/26 (61.5%) patients had CO-RADS scores of three or more [18]. The increased percentage of abnormal chest CT findings may be related to the fact that the majority of our cases were patients with moderate to severe disease.

Bayramoglu et al. reported that CO-RADS scores over three were found in 11/37 (29.7%) of the patients which is in agreement with our findings [14]. However, they did not disclose whether the patients included in their study were inpatients or outpatients or whether any of the patients had chronic cardiac, pulmonary, or hepatic disease, which may explain the high percentage of normal CT chest findings.

The correlation between the gender of patients and the different CO-RADS grades is statistically significant. In this study, the male participants showed a higher percentage of CO-RADS I, II, III, and V compared to the female participants. Aydin et al. and Hamarat et al. suggested no gender-based differences in CO-RADS classification [19, 20]. The observation that males are more susceptible to respiratory tract infections than females could potentially clarify our results.

Furthermore, our findings revealed that the intensity of pulmonary involvement had a negative effect on the prognosis, with CO-RADS grades three and above exhibiting the highest mortality rates. Moreover, Aydin et al. found that patients who required ICU transfers and had lower oxygen saturation levels had higher CO-RADS grades [19].

We found that the severity of CO-RADS was positively correlated with TLC, LDH, D-dimer, and ferritin levels and negatively correlated with hemoglobin levels, platelet counts, and ionized calcium levels. It is expected that as lung tissue damage increases, the concentration of inflammatory biomarkers increases, while other markers decrease. Our results are consistent with previous meta-analyses and two additional studies that also reported that low hemoglobin levels and elevated TLC, D-dimer, fibrinogen, procalcitonin, and ferritin levels are associated with higher mortality and morbidity rates [21,22,23,24].

This study has some limitations: first. It was a retrospective study. Second, it included only patients with positive RT-PCR, so we were unable to assess the overall sensitivity of the CO-RADS classification among patients.

Conclusion

Infants aged below 1 year were discovered to exhibit the highest vulnerability to COVID-19. The CO-RADS classification displayed positive associations with inflammatory biomarkers like total leucocytic count, LDH, D-dimer, serum ferritin, and AST. Conversely, the CO-RADS classification exhibited negative associations with ionized calcium levels, hemoglobin, and platelet count.