Analysis of Clinical and Radiologic Parameters in Children Diagnosed with COVID-19 Infection at Admission and Discharge

COVID-19, also known as Coronavirus Disease 2019, was first discovered in December 2019 in Wuhan, China (1). The World Health Organization (WHO) designated this novel coronavirus as severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) on February 12, 2020. On January 30, 2021, the WHO declared COVID-19 a global public health emergency (2, 3). The spread of SARS-CoV-2, a single-stranded RNA virus, has been rapid worldwide, with a high level of transmissibility (4). Currently, SARS-CoV-2 has affected more than 222 countries. World Health Organization reports indicate that as of March 10, 2024, there have been 774,889,074 confirmed cases of COVID-19 worldwide, resulting in 7,038,623 deaths (https://covid19.who.int/).

In Iran, as of November 26, 2023, a total of 155,460,000 vaccine doses have been administered. Despite vaccination efforts, from January 3, 2020, to April 28, 2024, the COVID-19 pandemic has led to over 7,627,186 confirmed cases and more than 146,811 deaths (https://covid19.who.int/region/emro/country/ir). The primary modes of transmission for SARS-CoV-2 are through respiratory droplets and contact (5).

COVID-19 infection affects all organ systems, including the gastrointestinal tract, neurological system, cardiovascular system, hepatocellular system, pulmonary system, urinary system, and immune system (6, 7). All age groups can be affected by SARS-CoV-2, with older adults (people over 50), immunocompromised individuals, and patients with chronic diseases being the most vulnerable to severe infections (8, 9).

World Health Organization classifies COVID-19 infections as mild, severe, or critical based on clinical symptoms (10, 11). Infants and children generally experience lower rates of COVID-19 infection, with up to 45% either being asymptomatic carriers or having a moderate clinical course of the disease. Children with underlying medical conditions may develop severe COVID-19 infections (12).

The inflammatory response significantly influences the progression of COVID-19, with disease severity and mortality often indicated by hematological and inflammatory parameters (13, 14). Neutrophil-to-monocyte ratio (NMR), lymphocyte count, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), platelet-to-lymphocyte ratio (PLR), D-dimer, white blood cell count (WBC), ferritin, fibrinogen, procalcitonin, and levels of various inflammatory cytokines are commonly considered prognostic indicators of COVID-19 severity (15, 16). According to Abdulla et al., patients with severe illness exhibit significant differences in serum levels of IL-6, CRP, and S-ferritin compared to those with mild or moderate illness (11). Yuan et al. demonstrated that severe and critically ill patients often present with lower lymphocyte counts, reduced red blood cells and hemoglobin, and decreased levels of immunoglobulin G antibodies specific to SARS-CoV-2. They also noted elevated levels of D-dimer, fibrinogen, WBC count, neutrophil count, IL-6, CRP, procalcitonin, ESR, ferritin, and LDH in patients with severe or critical illness (14). Alkan et al. found that hospitalized children with COVID-19 frequently have elevated WBC, lymphocyte, and platelet counts, as well as higher RDW, CRP, procalcitonin, D-dimer, and lymphocyte-to-monocyte ratio values (12).

Recognizing the risk factors for severe prognosis in COVID-19 patients is crucial, especially given the absence of standardized treatments and medications (17).

In the present study, we conducted a retrospective cross-sectional study to investigate the role of hematological parameters in assessing the severity of COVID-19 infection among children admitted to Mofid Children's Hospital, Tehran, Iran.

The present study focused on analyzing and summarizing the clinical parameters in children diagnosed with COVID-19 infection at admission and discharge. Our analysis of the patients' basic characteristics at admission revealed that 92.9% of patients had a fever. Additionally, 74% of patients showed an increase in both blood pressure and respiratory rate, and 74.8% of patients had elevated levels of neutrophils. According to previously published studies, typical symptoms of COVID-19 infection include fever, cough, dyspnea, malaise, fatigue, and sputum production (1, 18-20). Results from hematology tests showed that 51.7%, 67.4%, 69.3%, and 53.6% of patients had elevated levels of ESR, CRP, creatinine, and ferritin, respectively. Among the liver function tests, 98.2% of patients were found to have high levels of ALP enzyme.

Our analysis of hematological parameters before discharge from the hospital revealed that 23.3%, 74.7%, 25.3%, and 50% of patients had high levels of WBC, HB, PLT, and creatinine, respectively. Moreover, 85.7% of patients had a normal level of MCV, and 54.3% of patients had a high percentage of lymphocytes.

Several studies have examined the clinical and laboratory parameters of COVID-19 since December 2019. Alkan et al. analyzed hematological parameters and inflammatory markers in children with COVID-19 infection, finding lymphocytosis as the main hematological abnormality. Their study also noted elevated levels of WBC, lymphocytes, PLT, RDW, CRP, procalcitonin, D-dimer, and lymphocyte-to-monocyte ratio in hospitalized patients (12). Akbeyaz et al. identified cough, fever, and vomiting as common clinical symptoms in children with COVID-19, reporting that patients infected with the Omicron variant had lower hemoglobin and lymphocyte levels but higher D-dimer, INR, prothrombin time, and activated partial thromboplastin time (21). Saleh et al. from Saudi Arabia reported fever as the most frequent clinical symptom among COVID-19 patients (22).

Comparison of hematological parameters during admission and discharge from the hospital revealed significantly higher PLT and neutrophil levels at discharge compared to admission, while creatinine levels were significantly lower upon discharge.

Several studies have examined changes in hematologic parameters during COVID-19. A systematic review conducted by Waleed et al. in Pakistan revealed that patients with COVID-19 infection exhibited increased levels of neutrophils, lactate dehydrogenase, serum ferritin, interleukins (IL-6, IL-2, IL-7), CRP, procalcitonin, TNF-α, D-dimer, and fibrinogen degradation products. Additionally, their study reported decreased levels of thrombocytes and lymphocytes in these patients (13). In another study, Abdulla et al. investigated the relationship between changes in hematological parameters and disease severity in COVID-19 patients. They found that lymphocyte counts decreased in severely ill patients compared to those with mild and moderate symptoms. Moreover, severely ill patients exhibited significantly increased serum levels of IL-6, CRP, and ferritin (11). Bozkurt et al. identified higher body mass index and lower albumin levels as factors associated with postpartum progression of COVID-19 (23). Yuan et al. conducted a study to assess changes in hematological and immunological parameters in COVID-19 patients, revealing that severe and critically ill patients had significantly elevated levels of D-dimer, fibrinogen, WBC count, neutrophil count, IL-6, CRP, procalcitonin, ESR, ferritin, and lactate dehydrogenase (14). A study by Mermutluoğlu et al. in Turkey indicated that COVID-19 patients had elevated levels of mean platelet volume (MPV), neutrophil-to-lymphocyte ratio (NLR), and PLR (15). Matin et al. found that patients with severe COVID-19 infection had lower lymphocyte counts and increased NLR levels compared to non-severe patients (24). Qin et al., in a systematic review and meta-analysis, investigated immune dysfunction parameters in COVID-19 patients, noting significantly increased levels of cytokines such as IL-1β, IL-1Ra, IL-2R, IL-4, IL-6, IL-8, IL-10, IL-18, TNF-α, IFN-γ, IgA, IgG, CD4+ T/CD8+ T cell ratio, WBC, neutrophils, PLT, ESR, CRP, ferritin, serum amyloid A, D-dimer, and LDH in severely ill patients or non-survivors (25). In contrast, Uzel et al. found no statistically significant differences in blood parameters between COVID-19 patients with mild or severe clinical symptoms (26).

In this study, we investigated the correlation between hematological parameters, ICU hospitalization, and duration of hospital stay. Our findings revealed that increased pulse rate, respiratory rate, MCV, RDW, PT, and ESR were associated with ICU admission. Additionally, patients admitted to ICUs had lower SPO₂ percentages compared to those not admitted. In Iran, Sadeghi et al. demonstrated that initial admission SPO₂, hematocrit (HCT), CRP levels, and myalgia predict ICU admission (27). Moradinia et al., also from Iran, identified age, cough, blood oxygen levels, and diastolic blood pressure as factors associated with ICU hospitalization in COVID-19 patients (28). Candelli et al. reported from Italy that blood type A, PaO₂/FiO₂ ratio, LDH, lactate levels, dyspnea, and SpO₂ were significantly linked to ICU admission in COVID-19 patients (29). A study by Hergens et al. in Sweden found that hypertension, obesity, and type II diabetes were all risk factors for ICU admission with COVID-19 (30). Kurniyanto et al. in Indonesia highlighted age ≥ 60 years, obesity, shortness of breath, leukocyte count > 10,000/L, SPO₂ < 95%, and moderate-severe COVID-19 as strongly associated with ICU referral (20).

We also found that patients hospitalized for more than a week showed increased pulse rate, respiratory rate, ESR, neutrophil percentage, and lymphocyte percentage. Furthermore, these patients had hemoglobin levels above 10 and RDW levels above 13. Mermutluoğlu et al. from Turkey identified a positive correlation between hospitalization duration and fifth-day D-dimer and ferritin levels. They also noted a negative relationship between hospitalization duration and lymphocyte counts on admission day and the fifth day, suggesting that elevated ferritin and D-dimer levels and decreased lymphocyte counts may prolong hospital stays for COVID-19 patients (15). Alkan et al. reported a positive correlation between elevated WBC and procalcitonin levels and hospitalization in children with COVID-19 infections (12). Saleh et al.'s study in Saudi Arabia found that blood group A, hypertension, age < 14 years, and respiratory symptoms were significantly associated with admission to the pediatric intensive care unit (PICU). Their results also indicated that higher levels of factor VIII and fibrinogen were linked to longer hospital stays (22).

However, our study has several limitations: (1) A significant number of patients' clinical information at discharge was inaccessible, preventing a comprehensive analysis of all parameters; (2) Patients were not categorized based on the severity of their illness, limiting our ability to analyze differences between mild and severe COVID-19 cases; and (3) We lacked access to data on treatment outcomes and mortality rates related to COVID-19.