A Review on the Novel Coronavirus and Its Effects on Children

BACKGROUND: The outbreak of the new coronavirus was first reported in China and then spread to other parts of the world. The number of people infected with the virus is significantly increasing, making the disease an international concern. AIM: The present study aimed to investigate the coronavirus and its effects on children. MATERIALS AND METHODS: In the present study, search engines, and scientific databases of Google Scholar, Science Direct, PubMed, Medline, and Cochrane were searched to examine the effect of coronavirus on children. To collect information, keywords were also searched in the databases. RESULTS: In spite of contradictory results, among the children, those under 5 years old are the high-risk group. CONCLUSION: Some researchers believe that the virus shows fewer symptoms in children. However, the immune system of infants under six months develops pneumonia in rare cases

Predictive Value of Risk Factors for Chronic Idiopathic Thrombocytopenic Purpura in Patients with Acute Type of Disease

BACKGROUND: Immune thrombocytopenic purpura (ITP) is an autoimmune disease in which autoantibodies react with platelet surface antigens and results in mild to severe thrombocytopenia due to decreased platelet count or inhibition of platelet production. Given the relatively high prevalence of ITP among children and the lack of standard diagnostic testing for the diagnosis of chronic disease, this study evaluated the predictive value of risk factors for chronic ITP in hospitalized patients. METHODS: This prospective cohort study was performed on 65 children with ITP who referred to Ali Asghar and Rasool Akram Hospitals in Tehran, Iran, during the years 2017 and 2018. Relationships between different risk factors, including age of diagnosis, gender, white cell count, primary platelet count, mean platelet volume (MPV), history and type of the previous patient infection, FCG gene mutation, and type of FCG mutation with a chronic disease incidence were investigated using multiple logistic regression model. RESULTS: Of 65 patients, 31 (47.69%) were male and 34 (52.31%) were female included in the study. Twenty-eight patients (43.08%) had acute ITP and 37 (56.92%) had chronic ITP. Frequency of FCG gene mutation in patients with chronic and acute type ITP was 16.36% and 7.27%, respectively (p = 0.51). No association was found between the history of the previous infection and its type with the chronic incidence of ITP. The multiple logistic regression model showed that three factors, including the absolute number of lymphocytes, age of diagnosis, and primary white blood cells (WBC) count were directly linked to chronic ITP. Furthermore, three factors of platelet, sex, and MPV were indirectly related to chronic ITP. In addition, the absolute number of lymphocytes, age of diagnosis and primary WBC count were significantly associated with chronic ITP. The receiver operating characteristic analysis showed that the cutoff rate of these factors was 0.31. Further analysis of these risk factors in comparison with the gold standard demonstrated that the diagnostic sensitivity and specificity of these risk factors for chronic ITP were 73.08% and their specificity was 88.57%, indicating the high importance and predictive power of these risk factors. CONCLUSIONS: According to the results of this study, for the first time in Iran, six risk factors, including the absolute number of lymphocytes, age at diagnosis, sex, MPV level, platelet level at time of diagnosis, and primary WBC count were considered as the most important risk factors affecting the incidence of chronic ITP. Of course, more comprehensive studies can definitely lead to more comprehensive models

Gastrointestinal bleeding in a newborn infant with congenital factor X deficiency and COVID-19—A common clinical feature between a rare disorder and a new, common infection

Dear Editors, Congenital factor X (FX) deficiency is an extremely rare, bleeding disorder with an estimated incidence of one per 1 million. Patients with severe FX deficiency (FX:C < 1%) demonstrate a wide spectrum of serious clinical presentations, including hemarthrosis, hematoma, gastrointestinal (GI) bleeding, intracranial hemorrhage (ICH), and umbilical cord bleeding.1 In fact, severe FX deficiency, with a high rate of life‐threatening bleeding, is the second‐most severe, rare coagulation factor deficiency (RCFD) after FXIII deficiency.1, 2 Although homozygotes are at risk of severe bleeding, heterozygotes usually are asymptomatic, but postsurgical bleeding or bleeding after childbirth may occur.1, 2 Other risk factors can increase the risk of bleeding in FX deficiency, and coronavirus disease 2019 (COVID‐19), a new medical challenge, could affect the patient's bleeding or thrombotic tendency.3 COVID‐19, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) presents an enormous challenge for everyone, especially for those with underlying risk factors such as cardiovascular disease, diabetes, obesity, and renal failure. Age and male sex are other risk factors.4 Limited data are available regarding the effect of COVID‐19 on patients with congenital bleeding disorders (CBDs), particularly RCFDs.5 It has been shown that hypercoagulability‐related adverse consequences are less common among patients with CBDs, at least in those with moderate‐to‐severe deficiency, but further studies, including our ongoing work on a large number of patients, are required.5 Although there are several reports of newborns among infected pregnant mothers, this is the first report of such a case in an RCFD. This case report may help medical professionals to better manage similar cases. A 19‐year‐old pregnant woman was infected with SARS‐CoV‐2 early in the 9th month of pregnancy. Reverse transcriptase‐polymerase chain reaction (RT‐PCR) confirmed the infection. The patient had been in close contact with family members with confirmed COVID‐19. The patient had cough and fever. Due to the mild presentation, she was given Azithromycin and advised to isolate herself at home. The symptoms resolved within 14 days. At end of her 9th month, three days prior to the planned cesarean section, she was rechecked for SARS‐CoV‐2 infection; her RT‐PCR was negative. She successfully underwent cesarean section without complications and delivered a healthy full‐term baby. Therefore, mother and newborn discharged the following morning. In the evening, the baby experienced bloody vomiting and was hospitalized for further assessment, which showed GI bleeding. At admission, laboratory tests showed a positive C‐reactive protein (CRP) (qualitative), a low hemoglobin level, and prolonged prothrombin time (PT), and activated partial thromboplastin time (APTT) (Table 1). He was hospitalized in the neonate intensive care unit (NICU) for 10 days. Due to the risk of SARS‐CoV‐2 infection, on the third day after admission he was tested by RT‐PCR, which was positive. The neonate received 30 mL frozen plasma (FFP) six times over 10 days, which resolved the GI bleeding. Tranexamic acid (TXA) was administered at a dose of 10 mg/kg every 8 hours. Due to lack of COVID‐19 symptoms, he did not receive any special treatment for the disorder. After 10‐day hospitalization in the NICU, the neonate was sent to an isolation room for 5 days, during which his condition stabilized, after which he was discharged in stable condition. He has had no complications during the past two months after discharge. Since the child's father and two other first‐degree family members have severe FX deficiency, and the parents of the baby are closely related, the mother and the baby were checked for FX deficiency. Routine coagulation tests, and FX:C assay performed by STA Compact automatic coagulometer (Stago, Paris, France), revealed a severe deficiency in the baby, and a mild deficiency, compatible with heterozygote FX deficiency, in the mother (Table 1). Table 1. Laboratory characteristics of mother and baby with factor X deficiency and COVID‐19 Test Proband (2nd day after birth) Proband (7th day after birth) Proband (2 months after hospital discharge) Mother (about 3 1/2 months after SARS‐CoV‐2 infection) WBC × 109/L 14.2 (8‐24)b 9.43 (5‐21) 10.79 (6‐18) 8.7 (3.6‐10.6) RBC × 109/L 2.5 (4.36‐5.96) 2.78 (4.2‐5.8) 3.50 (3.4‐5) 4.41 (3.8‐5.2) Hb (g/dL) 8.2 (16.4‐20.8) 9.2 (15.2‐20.4) 10.2 (10.6‐16.4) 13.6 (12‐15) HCT (%) 24.6 (48‐68) 27 (50‐64) 29.2 (32‐50) 41.4 (35‐49) Lymphocyte × 109/L 6.4 (1.3‐11) 4.3 (1.2‐11.3) 8.21 (2.5‐13) 2.22 (1‐3.2) Neutrophil × 109/L 4.9 (2.6‐17) 2.9 (1.5‐12.6) 1.85 (1.2‐8.1) 5.75 (1.7‐7.5) Platelet × 109/L 370 (150‐450) 331 (150‐450) 334 (150‐450) 276 (150‐450) PT (sec) >60 (PTC: 12.6) 90 (PTC: 12.6) >60 (PTC: 10) 13 (PTC: 10) APTT (sec) >120 (APTTC: 31) 100 (APTTC: 30) >120 (APTTC: 32) 37 (APTTC: 32) CRP (Quantitative) Trace Negative NC NC FX:C level NC NC <1% (50%‐150%) 40% (50%‐150%) Abbreviations: APTT, activated partial thromboplastin time; APTTC, APTT control; CRP, C‐reactive protein; Hb, hemoglobin; HCT, hematocrit; NC, Not checked; PT, prothrombin time; PTC, PT control; RBC, red blood cell; WBC, white blood cell. a Hematological test normal ranges are extracted from Rodak's Hematology: Clinical Principles and Applications, 5th Ed (2016). b Normal values are placed in parentheses. COVID‐19 is an emerging medical challenge that can present more difficulties for those with special conditions, such as pregnant women and newborns. Due to alterations in cellular immunity, pregnant women are more prone to infection by intracellular pathogens like viruses.6 The fetus is also highly susceptible to infection due to immaturity of the immune system.7 Furthermore, the mother's (heterozygote) congenital coagulopathy and that of her newborn (homozygote) were additional potential risk factors, because a disrupted coagulation system is a prominent feature of SARS‐CoV‐2 infection.8 To date, FX deficiency in a newborn has not been cited anywhere as a special condition requiring close attention in the case of SARS‐CoV‐2 infection. According to the few reports to date, SARS‐CoV‐2 infection is a risk factor for severe maternal morbidity. It is worth noting that most of those mothers were discharged without complications.9 From a clinical aspect, fever was the most common symptom (68%) at the time of admission.9 This was also observed in the affected woman of this study. SARS‐CoV‐2 infection can even affect the type of delivery. A systematic review of these women showed that about 92% of deliveries were by cesarean section, less than 10% being the usual vaginal delivery (7 of 85). Fetal distress was mentioned as the most common indication for cesarean section. Our patient underwent a planned cesarean section, due to her previous history. The delivery itself was uneventful, and a healthy baby was delivered, while among other reported cases, a number of complications have been noted.9 As with most other reports, the infant did not have any symptoms at the time of delivery and was discharged the day after birth.9 In a case series of 10 patients, various first clinical presentations were observed, including shortness of breath (n = 6), fever (n = 2), vomiting (n = 1), and rapid heart rate (n = 1).10 In the case at hand, bloody vomiting was the first clinical presentation. In the same case series, one died due to refractory shock, multiple organ failure (MOF), and disseminated intravascular coagulation (DIC). Another patient with severe presentation was managed by intravenous infusions of gamma globulin, platelets, and plasma, which was suggestive of the effectiveness of gamma globulin in severe cases. The author recommended early use of intravenous gamma globulin for passive immunization.10 GI bleeding in our case was successfully managed by administration of FFP and TXA. In addition to thrombotic complication, bleeding is not infrequent in patients affected by COVID‐19, with GI bleeding seemingly the most common hemorrhagic manifestation among adults. GI bleeding, with a frequency of 40%, was observed among neonates from affected mothers.3 On the other hand, GI bleeding is also a relatively common presentation among severely FX deficient patients.1, 2 In fact, GI bleeding can occur in children with severe FX deficiency within the first months of life. It seems that such patients are prone to experience severe bleeding, such as ICH, later in life, in the absence of an appropriate therapeutic strategy, most likely preventative regular secondary prophylaxis.1, 2 In one study of 102 patients with congenital FX deficiency, GI bleeding has been reported in 12% of symptomatic cases.1 In this case, with GI bleeding being a common presentation of SARS‐CoV‐2 infection and congenital FX deficiency, it cannot definitively be attributed to one or the other. Close monitoring of such cases is necessary to decrease related adverse consequences. Although it seems that COVID‐19 is less severe in adults with CBDs, it is a less‐known issue among children and newborns with CBDs. Further reports and studies could provide clarity. Due to their severe bleeding tendency, close monitoring of patients with severe congenital FX deficiency is mandatory, even without potential SARS‐CoV‐2 infection. And close monitoring of neonates with infected mothers is mandatory to prevent severe consequences. Patients with concomitant infection with SARS‐CoV‐2 require even more rigorous preventative and supportive care. ACKNOWLEDGEMENTS We highly appreciate Daisy Morant's valuable aid in improving the English Language of this manuscript. The study was supported and approved by Shahid Beheshti University of Medical Sciences. CONFLICT OF INTEREST The authors have no competing interests. AUTHOR CONTRIBUTIONS A. Dorgalaleh designed the work, performed laboratory analysis, and wrote the manuscript. F Ghazizadeh, M. Baghaipour, A. Dabbagh, Gh. Bahoush, and N Baghaipour performed clinical studies. Sh. Tabibian, M. Jazebi, N. Baghaipour, M. Bahraini, A. Fazeli, and F. Yousefi performed laboratory analysis. All the authors approved the submission

Imatinib Mesylate (Glivec) in Pediatric Chronic Myelogenous Leukemia

&quot;nIntroduction: Imatinib Mesylate is a selective inhibitor of TK and is considered now to be the frontline therapeutic agent during the chronic phase of CML. We have evaluated the efficacy of it on children with chronic-phase of CML. &quot;nPatients and Methods: In a clinical trial study over the past 3 years, 14 patients (8 females and 6 males, 2.5-14 years old) were admitted with a diagnosis of CML. Seven patients who were in the early chronic-phase and seven who were in the late chronic-phase suffered from hematological relapse while being treated with conventional therapy. All of them had positive BCR-ABL in peripheral blood and bone marrow. Glivec was given as an oral dose of 300mg/m2/d. Then, regular monitoring was done for hematological and cytogenetic response, toxic effects, disease progression and survival. &quot;nResults: All seven patients with newly- diagnosed CML and five previously treated patients attained complete and sustained hematological and cytogenetic remission in a follow-up period over 2 to 30 months (the mean was 22.5). One patient was taken off study because of drug intolerance. One patient in each group relapsed after initial response and died from progressive disease. Overall survival was 86%. No major side effects were noted and there was no drug- related mortality. &quot;nConclusion: Glivec has proved to be effective in inducing prolonged complete hematological and cytogenetic remission in newly- diagnosed as well as previously treated children with CML. One major problem is prolonged, unlimited and continued therapy which results in poor compliance as time goes by. In addition, in developing countries, high cost and suboptimal accessibility would make its routine use quite difficult

Pediatric Long-term follow up for renal disorders in ALL children by evaluating urine NGAL

Introduction: Recent Developments in cancer treatment could provide a better survival rate for Acute Lymphoblastic Leukemia (ALL) patients. Survivors faced different long term complication after treatment, for instance cardiac, neurologic and kidney complications. Assessment of the late complications could be useful in the optimization of treatment protocols. The objective of this study was to evaluate the late kidney complications, renal function in ALL patients after therapy.Material &amp; Methods: In this study, we used 46 children. The treatment preformed based on ICBFM protocol. The mean age at the start of the treatment was 53±23 and the mean follow up time was 48±11 months. The tubular damage in these patients was evaluated by urinary NGAL level and the renal function was assessed by GFR.Results: in this study 56.7% of the patients were male. The NGAL level shows abnormally high in 8.9% of patients and the mean urine NGAL was 63±113ng/mL. Also, the mean GFR at the time of the diagnosis and at the time of the start of the follow up were 102.8 ±25.6 mL/min/1.73 m2 and 93.6 ±29.1 mL/min/1.73 m2, respectively. The study indicated GFR were less than 60 mL/min/1.73 m2 in 13.3% of patients. Conclusion: this study indicated the long term follow up of the ALL survivors for kidney disorders are an important manner. The urinary NGAL level shows that 8.9% of the patients are tubular damage by using this treatment protocol. The study concluded that ICBFM protocol is a safe protocol with little long term damage.

IKZF1 Alteration in Pediatric B-Cell Acute Lymphoblastic Leukemia: a Single-Center Report on the Frequency of IKZF1 Deletions and Its Subtypes

Introduction:&nbsp; The most prevalent malignancy of childhood is B-cell acute lymphoblastic leukemia (B-ALL). Many genetic variations are causes of B-ALL. IKZF1 alterations are prevalent in childhood B-ALL cases, which are associated with a poor prognosis. This study examined seventy-two pediatric B-ALL patients for the frequency of IKZF1 alteration and types of IKZF1 deletions. Patients and Methods: In this study, we used bone marrow aspirate specimens at the stage of diagnosis in pediatric B–ALL patients. The diagnosis of B-ALL was performed following cytomorphology, cytochemistry, and immunophenotyping based on the 2016 World Health Organization guidelines. ALL translocations, including TCF3-PBX1 fusion, ETV6-RUNX1 fusion, BCR-ABL1 fusion, and KMT2A-AFF1 fusion, were performed on DNA specimens of all patients. IKZF1 status was checked with the SALSA MLPA P335 ALL-IKZF1 probemix Kit. Results: The common-B ALL subtype was detected in 64/72 (88.9%) patients. CD2 and CD13 aberrant expressions was found in 5/72 (6.9%) and 7/72 patients (9.7%), respectively. Molecular analysis for translocation revealed the frequency of ETV6-RUNX1 in 12/72 patients (16.7%) and BCR-ABL1 in 3/72 patients (4.2%). IKZF1 alterations were found in 13/72 (18%) patients, of which 10 (13.9%) patients had IKZF1 deletions. Three common types of IKZF1 deletions were found. Conclusion: The frequency of IKZF1 deletion in this study is similar to the results obtained in larger studies. The type of IKZF1 deletion related to poor outcomes has a higher frequency in this study. Because of the high relative prevalence of IKZF1 deletion, its determination is important for better risk stratification and prognosis in pediatric B-ALL patients