Clinical and laboratory features of SARS-CoV-2 variants across multiple rounds of pandemic waves in hospitalized children in an Iranian referral hospital.

BACKGROUND: Since the onset of the COVID-19 pandemic, SARS-CoV-2 has evolved into independent new forms, variants of concern (VOCs). While epidemiological data showed increased transmissibility of VOCs, their impact on clinical outcomes is less clear. This study aimed to investigate the differences between the clinical and laboratory features of children infected with VOCs. METHODS: This study included all cases with SARS-CoV-2-positive nasopharyngeal swabs obtained from patients referred to Children's Medical Center (CMC), an Iranian referral hospital, between July 2021 and March 2022. The inclusion criteria for this study included all patients, regardless of age, who had a positive test anywhere in the hospital setting. Exclusion criteria for the study included those whose data was obtained from non-hospital outpatient settings, or referred from another hospital. The SARS-CoV-2 genome area encoding the S1 domain was amplified and sequenced. The type of variant in each sample was identified based on the mutations in the S1 gene. Demographic characteristics, clinical data, and laboratory findings were collected from the patient's medical records. RESULTS: This study included 87 pediatric cases with confirmed COVID-19, with a median age of 3.5 years (IQR: 1-8.12). Data from sequencing reveals the type of variants as 5 (5.7%) alpha, 53 (60.9%) Delta, and 29 (33.3%) Omicron. The incidence of seizure was higher in patients with Alpha and Omicron infection compared to the Delta group. A higher incidence of diarrhea was reported in Alpha-infected patients, and a higher risk of disease severity, distress, and myalgia was associated with Delta infection. CONCLUSION: Laboratory parameters did not mostly differ among the patients infected with Alpha, Delta, and Omicron. However, these variants may manifest different clinical features. Further studies with larger sample sizes are required to fully understand the clinical manifestations of each variant.

Association of body mass index with COVID-19 outcome in a pediatric tertiary referral hospital in Iran

Background One of the challenging risk factors for severe COVID-19 infection is obesity and high body mass index (BMI). In this study we assessed the association between BMI and outcomes of hospitalized pediatric patients with COVID-19 in Iran. Method This retrospective cross-sectional study was performed in the biggest referral pediatric hospital in Tehran from March 7 to August 17, 2020. All hospitalized children ≺18 years of age with laboratory-confirmed COVID-19 were included in the study. We evaluated the association of BMI with COVID-19 outcomes (death, severity of clinical course, oxygen therapy, intensive care unit [ICU] admission, ventilator requirement). The secondary objectives were investigating the association of gender, underlying comorbidity, and patient age with COVID-19 outcomes. The limits for obesity, overweight, and underweight were set at BMI >95 percentile, 85≤ BMI ≤ 95, and BMI<5 percentile, respectively. Results In total, 189 confirmed pediatric cases of COVID-19 (0.1–17 years) with a mean age of 6.4±4.7 years were included. Overall, 18.5% of the patients were obese and 33% were underweight. We found that BMI had no significant relation with COVID outcomes in pediatric cases but after subgrouping the participants, underlying comorbidities and lower BMI in previously ill children were independently associated with a poor clinical outcome of COVID-19. In addition, the previously ill children with higher BMI percentiles were at a relatively lower risk of ICU admission (95% CI: 0.971–0.998, OR: 0.98, p=0.025) and better clinical course of COVID-19 (95% CI: 0.970–0.996, OR: 0.98, p=0.009). The BMI percentile had a statistically significant direct relationship with age (Spearman correlation coefficient= 0.26, p<0.001). When we separated the children with underlying comorbidity, the BMI percentile was significantly lower (p<0.001) in comparison to the previously healthy children. Conclusion Based on our results, obesity is not related to COVID-19 outcomes in pediatric patients, but after controlling for confounding effects, underweight in children with underlying comorbidities was more likely to be associated with a poor prognosis of COVID-19.

Children with SARS-CoV-2 infection during the novel coronaviral disease (COVID-19) outbreak in Iran: an alarming concern for severity and mortality of the disease.

BACKGROUND: The rapid worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections led to public health crises globally and the number of pediatric patients with Coronavirus Disease 2019 (COVID-19) is still rising. The aim of this study was to describe the epidemiological, clinical, laboratory, and imaging features of hospitalized patients with COVID-19 at an Iranian referral pediatrics hospital and to compare these parameters between hospitalized patients with and without severe disease, multisystem inflammatory syndrome in children (MIS-C) and children with acute COVID-19, as well as deceased and discharged cases. METHODS: This study included hospitalized children and adolescents (≤ 18 years) with suspected COVID-19 who had positive results for SARS-CoV-2. RESULTS: Among the 262 patients with suspected COVID-19, 142 confirmed COVID-19 cases were included in the study. A total of 11 children were diagnosed as MIS-C. The majority of the cases with MIS-C were male, (n = 9, 82%) which is significantly higher than children (n = 61, 47%) with acute COVID-19 (P = 0.03). Fifty patients (35%) were shown to have a more severe form of COVID-19. Ninety percent of the cases (n = 45) with severe COVID-19 had comorbidities that was significantly higher than cases with non-severe or mild disease (n = 41, 45%; P < 0.0001). A mortality rate of 10% was reported (n = 14). Ninety-three percent of the deceased cases (n = 13) had comorbidities that were significantly higher than discharged patients (n = 73, 57%; P = 0.009). CONCLUSION: The increasing number of children with severe COVID-19 is cause for great concern. Underlying diseases, mainly cardiovascular diseases, cancer, and malignancies, are associated with greater risk of development of severe COVID-19 and even death in children. On the other hand, pediatric patients with MIS-C usually develop a milder form of the disease. However, evaluation specific immunological responses in children to explore the delayed inflammatory syndrome are highly recommended.

COVID-19 infection in children with underlying malignancies in Iran.

OBJECTIVES: Although coronavirus disease 2019 (COVID-19) prognosis is mostly good in pediatric patients with no underlying diseases, there are a few reports on children with oncological underlying malignancies. This study aimed to describe the clinical and laboratory features of 20 children with COVID-19 who had underlying malignancies in an Iranian referral pediatrics hospital. METHODS: All children under 15-year-old of age with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive real-time polymerase chain reaction (PCR) and presence of an underlying malignancy were included in the study. RESULTS: In this study, among 20 patients, 11 were male (55%). The mean age of the patients was 6.0 ± 4.1 years. Twelve patients (60%) had acute lymphocytic leukemia, two had acute myeloid leukemia (10%), and six had solid organ tumors (30%). The most common symptoms were fever (65%) and cough (65%). We reported severe pneumonia in seven hospitalized patients (35%) and three patients (20%) required intensive care unit admission and mechanical ventilation. Procalcitonin was normal in 73% of the cases (11 out of 15), but it was highly elevated in four cases (27%). Five patients (25%) had positive blood cultures and a mortality of 20% was reported. CONCLUSIONS: This is the largest study on SARS-CoV-2 infected pediatric patients with underlying malignancies in Iran. Since the risk of exposure to SARS-CoV-2 and even death in children with malignancy, either in the hospital or community setting during the pandemic is high, special precautions to reduce the risk of transmission are highly suggested.

Clinical Effects of COVID-19 on Hematopoietic Stem Cell Transplant Outcomes in Pediatric Patients.

Coronavirus disease 2019 is the third zoonotic acute respiratory disease after SARS virus and Middle East respiratory syndrome. Most cases are mild in healthy children. In contrast, the infection is more severe in patients with underlying health conditions. Because there are few posttransplant reports in hematopoietic stem celltransplant patients, here we described COVID19 infection in 4 confirmed cases among pediatric hematopoietic stem cell transplant recipients: 3 boys and 1 girl with a median age of 6 years. Three patients presented with symptoms of lower respiratory tract disease, whereas 1 patient presented with extrapulmonary symptoms without fever or pulmonary involvement. All of the patients were on immunosuppressivedrugs, ie, 1patientforgraft-versus-hostdisease prophylaxis and 3 patients for graft-versus-host disease treatment.Thosewhowerediagnosedwith active graftversus-hostdisease requiredmechanical ventilationand intensive care. Two patients died from multiple organ dysfunction and resistant coinfection, and 1 patient developed pulmonary hypertension and mild cardiomegaly and remained at the hospital for more than 2 months, whereas the patient with no graft-versus-host disease was discharged and recovered. Our findings showed that COVID-19 infection among hematopoietic stem cell transplant recipients may be more severe and associatedwithlong-termhospitalization and complications. Active graft-versus-hostdisease, coinfections, and long-term use of immunosuppressive agents are risk factors for poor outcomes.

COVID-19 in transplant recipient children: An Iranian referral hospital-based study.

To our knowledge, there is still very limited information on the severity, mortality, laboratory, and radiologic findings of COVID-19 infection in transplant patients, particularly children. In this study, we report and analyze 7 transplant recipients with laboratory-confirmed COVID-19 infection. The median age was 7.5 years (IQR: 31month-10 years), and 71% of the patients were male. All cases presented with a fever. The median duration of fever before admission was 2 days (IQR:1-8 days). Five patients (71%) experienced cough and dyspnea. Lymphocytopenia (Median of 0.6 (IQR: 0.14-2.0× 109 cells per L) and thrombocytopenia (Median of 65 (IQR: 49-201× 109 cells per L) were the most common CBC findings (both seen in 5 out of the 7 patients. Among 4 of the patients who underwent CT scans, 2 had ground glass opacity and consolidations. The mean number of lobe involvement in our patients was 3(0-5), and 75% of the cases showed bilateral lung involvement in the imaging. In 4 patients (51%) the disease course manifested severely, and 2 patients are now deceased (28.6%). In conclusion, immunocompromised pediatric subgroups may experience higher rates of disease severity and mortality in comparison with the immunocompetent pediatric population.

Giant intracardiac thrombosis in an infant with leukaemia and prolonged COVID-19 viral RNA shedding: a case report.

BACKGROUND: COVID-19 can induce thrombotic disease both in the venous and arterial circulations, as a result of inflammation, platelet activation, endothelial dysfunction, and stasis. Although several studies have described the coagulation abnormalities and thrombosis in adult patients with COVID-19, there is limited data in children. Here, we present an 18-month-old boy with a prolonged SARS-CoV-2 RNA shedding and chronic right atrial and superior vena cava (SVC) thrombosis. CASE PRESENTATION: An 18-month-old boy with acute lymphoblastic leukemia (ALL) (pre-B cell ALL) and a history of chemotherapy was referred to our center due to intermittent fever with unknown origin. a positive nasopharyngeal PCR for COVID-19 was reported and stayed positive for eight consecutive weeks The high-resolution computed tomography (HRCT) showed no sign of pulmonary embolism. Initial echocardiography indicated a semilunar thrombotic mass extending from right SVC into the right atrium without coronary or myocardial involvement. Enoxaparin was administered with continuous monitoring of the level of anti-Xa activity. The serial echocardiographic studies found a slow but continuous reduction in the mass size. CONCLUSIONS: Our case shows that, as already described in adult patients, clinically relevant thrombosis can complicate the course of pediatric patients as well. In view of the specific and milder manifestations of COVID-19 in children, these complications may pose considerable diagnostic and therapeutic challenges.

SARS-CoV-2 RNAaemia in children: An Iranian referral hospital-based study.

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is generally detected in nasopharyngeal swabs, viral RNA can be found in other samples including blood. Recently, associations between SARS-CoV-2 RNAaemia and disease severity and mortality have been reported in adults, while no reports are available in pediatric patients with coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the mortality, severity, clinical, and laboratory findings of SARS-CoV-2 RNA detection in blood in 96 pediatric patients with confirmed COVID-19. Among all patients, 6 (6%) had SARS-CoV-2 RNAaemia. Out of the six patients with SARS-CoV-2 RNAaemia, four (67%) had a severe form of the disease, and two out of the 6 patients with SARS-CoV-2 RNAaemia passed away (33%). Our results show that the symptoms more commonly found in the cases of COVID-19 in the study (fever, cough, tachypnea, and vomiting), were found at a higher percentage in the patients with SARS-CoV-2 RNAaemia. Creatine phosphokinase and magnesium tests showed significant differences between the positive and negative SARS-CoV-2 RNAaemia groups. Among all laboratory tests, magnesium and creatine phosphokinase could better predict SARS-CoV-2 RNAemia with area under the curve  levels of 0.808 and 0.748, respectively. In conclusion, 67% of individuals with SARS-CoV-2 RNAaemia showed a severe COVID-19 and one-third of the patients with SARS-CoV-2 RNAaemia passed away. Our findings suggest that magnesium and creatine phosphokinase might be considered as markers to estimate the SARS-CoV-2 RNAaemia.

Effects of Coronavirus Disease 2019 (COVID-19) on Peripheral Blood Lymphocytes and Their Subsets in Children: Imbalanced CD4+/CD8+ T Cell Ratio and Disease Severity.

Introduction: While pathogenesis in COVID-19 is not fully known and the effects between SARS-CoV-2 and the immune system are complicated, it is known that lymphopenia, hyper-inflammatory responses, and cytokines play an important role in the pathology of COVID-19. While some hematological abnormalities have been described among the laboratory features of COVID-19, there have not been studies reported on lymphocyte subset analyses in children. The aim of this study was to describe lymphocyte subsets in pediatric patients with mild/moderate or severe COVID-19. Methods: The subjects in the study were children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia confirmed with the real-time RT-PCR. The subjects were admitted to the Children's Medical Center, affiliated with the Tehran University of Medical Sciences, between March 7th and June 10th of 2020. The complete blood counts and lymphocyte subpopulations were analyzed for each patient. Results: The study included 55 hospitalized patients with confirmed SARS-CoV-2 infection (34 patients (62%) with an observed mild/moderate case of the disease and 21 patients (38%) with severedisease). Lymphocyte counts were found to be lower in patients with a severe case (mean ± SD 1.6 ± 0.9 in the severe group vs. 2.3 ± 2.2 in the mild group). Compared to the group with mild/moderate pneumonia, children with severe pneumonia had an increased count of CD8+ T cell and a lower percentage of CD4+ T cell. However, the differences between the groups were negligible. Interestingly, the severe group had a lower CD4+/CD8+ T cell ratio compared to the mild group (1.1 ± 0.47 vs. 1.4 ± 0.8, p-value: 0.063). CD4+/CD8+ T cell ratio <2, 1.5, and 1 was found in 48 (87%), 40 (73%), and 19 cases (35%). All of the seven cases in which the subject passed (13%) had CD4+/CD8+ T cell ratio of <2, 86% had CD4+/CD8+ T cell ratio of <1.5, and 29% had CD4+/CD8+ T cell ratio of <1. Conclusion: The CD4+/CD8+ T cell ratio was lower in patients with severe COVID-19 compared to those with mild/moderate form of disease. However, although a decline in CD4+/CD8+ ratio may serve as a useful metric in analyzing of the derangement in immune responses in patients with severe COVID-19, further study with larger sample sizes is highly recommended.

COVID-19 and congenital heart disease: a case series of nine children.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is the current pandemic disease without any vaccine or efficient treatment to rescue the patients. Underlying diseases predispose the patients to a more severe disease and to a higher mortality rate. However, little evidence exists about COVID-19 outcomes in the pediatric population with congenital heart disease (CHD). Here, we report nine children with COVID-19 and concomitant CHD. METHODS: Our study included nine children with COVID-19 and concomitant CHD who were admitted to Children Medical Center Hospital during March and April 2020. The patients were classified based on the final outcome (death), and their clinical sign and symptoms, type of CHD, and drugs administered were compared. RESULTS: Among the nine patients, two died and we compared different characteristics, laboratory results and clinical findings of these cases based on the mortality. The deceased patients had severe types of CHD, worse arterial blood gases, severe clinical symptoms, higher mean level of partial thromboplastin time and C-reactive protein, and required more medications. CONCLUSIONS: The present study showed that the general consideration of mild COVID-19 in children does not include patients with CHD and that it is necessary to pay greater attention to children with CHD to determine guidelines for treatment of COVID-19 in these children. Owing to the scarcity of CHD and COVID-19, we reported only nine cases. However, further studies are highly required in this regard.

Multisystem inflammatory syndrome associated with SARS-CoV-2 infection in 45 children: a first report from Iran.

During the coronavirus disease 2019 (COVID-19) pandemic, a new phenomenon manifesting as a multisystem inflammatory syndrome in children (MIS-C) which has a similar clinical presentation to Kawasaki disease, toxic shock syndrome and severe sepsis has emerged. Although the number of MIS-C reports is increasing, rare reports in Asia is still available. To our knowledge, this study is the largest series of published MIS-C cases in Iran. We performed a retrospective study of all patients with case definition for MIS-C admitted to the three paediatric hospitals in Iran. All of these hospitals are located within the most active COVID-19 pandemic areas (Tehran, Qom and Mazandaran) in Iran. Demographic characteristics, clinical data, laboratory findings, imaging and echocardiographic findings, treatment and outcomes were collected. Between 7 March and 23 June 2020, 45 children were included in the study. The median age of children was 7 years (range between 10 months and 17 years). Common presenting symptoms include fever (91%), abdominal pain (58%), nausea/vomiting (51%), mucocutaneous rash (53%), conjunctivitis (51%) and hands and feet oedema (40%) with median duration of symptoms prior to presentation of 5 (interquartile range (IQR) 3, 7) days. Fifty-three percent of children showed lymphopaenia. Overall, the majority of cases at admission had markedly elevated inflammatory markers erythrocyte sedimentation rate (ESR) (95.5%) and C-reactive protein (CRP) (97%). Ferritin was abnormal in 11 out of 14 tested patients (73%), and it was highly elevated (>500 ng/ml) in 47% of cases. Median fibrinogen level was 210 (IQR 165, 291) mg/dl, D-dimer was 3909 (IQR 848, 4528) ng/ml and troponin was 0.6 (IQR 0.1, 26) ng/ml, respectively. Twenty out of 31 patients (64.5%) had hypoalbuminaemia. In addition, hyponatraemia was found in 64% of cases. Twenty-five patients (56%) presented with cardiac involvement and acute renal failure was observed in 13 cases (29%). Pleural, ascitic, ileitis and pericardial effusions were found in 18%, 11%, 4% and 2% of cases, respectively. In conclusion, this is a first large case series of hospitalised children who met criteria for MIS-C in Iran. There was a wide spectrum of presenting signs and symptoms; evidence of inflammation with abnormal values of CRP, ESR, D-dimer, ferritin and albumin; and multi-organ involvement.

The Coronavirus Disease 2019 (COVID-19) in Children: A Study in an Iranian Children's Referral Hospital.

BACKGROUND: Despite the worldwide spread of the coronavirus disease 2019 (COVID-19), the epidemiological and clinical patterns of the COVID-19 infection remain largely unclear, particularly among children. In this study, we explored the epidemiological characteristics, clinical patterns, and laboratory and imaging findings of pediatric patients with COVID-19. MATERIALS AND METHODS: From March 7 to March 30, 2020, there were a total of 35 patients who had confirmed COVID-19 infection by laboratory virus nucleic acid test (RT-PCR) assay with throat swab samples or typical chest CT manifestation compatible with COVID-19, in addition to a history of close contact with suspected or confirmed SARS-CoV-2 in family members. Information recorded included demographic data, medical history, exposure history, underlying comorbidities, symptoms, signs, laboratory findings and radiologic assessments, severity of disease, treatment, and mortality. RESULTS: The median age of the patients was 7.5 years (IQR=4-11; range=4 months to 15 years). A total of 63% were male. Cough was present in 80% of the patients, followed by fever (77%), nausea or vomiting (29%), diarrhea (26%), shortness of breath (29%), headache (20%), and myalgia (14%). Lymphopenia was present in 43% of the patients, thrombocytopenia in 9%, neutopenia in 8%, and leucopenia in 26%. We reported severe pneumonia in 40% of the hospitalized patients and 18 (51%) had underlying diseases. Of 35 patients, 11 had positive RT-PCR results (31%). The chest CT images of 24 patients (69%) suggested COVID-19, while their RT-PCR assays from throat swab samples were negative. CONCLUSION: This study demonstrates different clinical findings of pediatrics compared to the previous reports of children. Since a high rate of false negative RT-PCR test was observed, early detection of children with COVID-19 infection by CT is conducive to reasonable management and early treatment.