Neurologic Manifestations of Coronavirus Disease 2019 in Children: An Iranian Hospital-Based Study.

BACKGROUND: COVID-19 infection and its neurological manifestations were seen in children although less common than adults. The aim of this study was to determine the frequency of different types of neurologic findings of hospitalized children with COVID-19. ]. METHODS: This retrospective study was performed on hospitalized pediatric patients aged≤18 years with confirmed SARS-CoV-2 at Children's Medical Center Hospital. Neurological manifestations were defined as the presence of any of the following symptoms: seizure, altered mental status, behavioral/personality change, ataxia, stroke, muscle weakness, smell and taste dysfunctions, and focal neurological disorders. RESULTS: Fifty-four children with COVID-19 were admitted and their mean age was 6.94±4.06 years. Thirty-four of them (63%) were male. The most frequent neurological manifestation was seizure (19 [45%]) followed by muscle weakness (11 [26%]), loss of consciousness (10 [23%]), and focal neurological disorders (10 [23%]). Other neurological manifestations consisted of headache (n=7), movement disorders (n=6), behavioral/personality change (n=5), ataxia (n=3), and stroke (n=3). Twenty-nine percent of our patients had leukocytosis. A neutrophil count above 70% was seen in 31% of participants. Among our patients, 81% had a positive reverse-transcription polymerase chain reaction (RT-PCR) test for SARS-CoV-2. CONCLUSION: During the current pandemic outbreak, hospitalized children with COVID-19 should be evaluated for neurological signs because it is common among them and should not be under-estimated.

Alteration of Plasma Amino Acid Concentrations in Iranian Children with COVID-19.

COVID-19 is an acute viral disease that has so far infected more than 200 million and killed more than four million worldwide. It affects the immune system and other organs. Here, we investigated the level of free plasma amino acids in COVID-19 patients and compared them with non-COVID-19 subjects. We also compared amino acids levels in critically ill patients admitted to the intensive care unit (ICU) with non-ICU patients and expired and recovered patients. Twenty-six COVID-19 patients and 32 non-COVID-19 subjects were included in the study. The mean of glutamic acid, serine, glycine, threonine, phenylalanine, leucine, lysine, alanine, arginine, aspartic acid, and ornithine was significantly higher in cases than controls. In addition, the mean of glutamine was significantly lower in patients than controls (443.89 ± 254.31 vs. 651.73 ± 107.38, PV < 0.001). Low level of glutamine and isoleucine was seen in the majority of ICU and expired patients, respectively. Logistic regression analysis showed low level of isoleucine as a predictor variable in mortality (P = 0.02, EXP (B) = 16.5, and CI 95% = (1.48, -183.07)). There was a positive and significant relationship between some amino acids levels, serum liver enzymes, and sodium concentrations. There was also a significant but negative correlation between histidine levels, ESR, and ferritin. Phenylalanine had a highly positive relationship with serum procalcitonin in patients (R 2 = 0.534, PV = 0.015). Our studies have shown the alteration of plasma amino acids concentration in COVID-19 patients. These changes are more evident in critically ill and at-risk patients.

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.

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.