The footprint of SARS-COV-2 infection in neonatal late sepsis.

BACKGROUND: Predicting and finding the viral agents responsible for neonatal late-sepsis has always been challenging. METHOD: In this cross-sectional study, which has been done from September 2020 to December 2022, 145 hospitalized neonates suspected to late-onset sepsis alongside routine sepsis workup, were also evaluated for severe acute respiratory syndrome-coronavirus-2 (SARS-COV-2) infection, by nasopharyngeal real-time polymerase chain reaction (RT-PCR) or serological tests. RESULT: 145 neonates including 81 girls and 64 boys with a mean age of 12.3 ± 5.9 days and an average hospitalization stay of 23.1 ± 15.4 days were enrolled in the study. While 76.6% of them had negative bacterial culture, 63 patients (43.4%) showed evidence of SARS-COV-2 infection in RT-PCR or serology tests. None of the underlying factors including gender, age, and laboratory investigation had a significant relationship with SARS-COV-2 infection. Similarly, the outcomes of death and length of hospitalization were not different between the two groups with positive and negative SARS-COV-2 RT-PCR (P < 0.05). There was only a significant relationship between radiological changes including reticulonodular pattern, consolidation, pleural effusion, and different types of infiltrations and SARS-COV2 infection. CONCLUSION: Considering the widespread of coronavirus disease 2019 (COVID-19) in newborns, it seems logical to investigate the SARS-COV-2 infection in late-sepsis.

Multisystem inflammatory syndrome in children (MIS-C) post-COVID-19 in Iran: clinical profile, cardiac features, and outcomes.

BACKGROUND: In April 2020, an association between multisystem inflammatory syndromes (MIS-C) was observed in children with severe acute respiratory syndrome coronavirus infection (SARS-CoV-2). Most patients had heart involvement alone, and most patients had pericardial effusion. This study aimed to express and emphasize cardiac involvement in pediatric patients with respiratory symptoms who were diagnosed with COVID-19. METHODS: This study was conducted in July 2021 in Kerman province, Southeastern Iran, during a notable surge in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. The study included 904 pediatric patients diagnosed with COVID-19. Data collection involved a comprehensive assessment of clinical symptoms and manifestations. Patients with fever lasting more than five days were admitted to the hospital. Echocardiography was utilized for cardiac involvement diagnosis, with 47 patients undergoing this diagnostic procedure. RESULTS: Of the 904 patients, most of them had high fevers (74%). Fifty-five patients had a fever for more than five days and were hospitalized. Of the 47 patients who underwent echocardiography, 45 (81%) had heart involvement. In 75% of patients, pericardial effusion was the only cardiac involvement. Patients with pericardial effusion were treated with dexamethasone up to 3 mg every 8 h for 72 h. CONCLUSIONS: MIS-C has a wide range of clinical symptoms. In cases where the fever is prolonged and there are gastrointestinal symptoms, physicians have clinical suspicion to diagnose this syndrome. Most cases of pericardial effusion are alone and improve with treatment with glucocorticosteroids.

Assessment of the Effect of Sub-Cutaneous Adalimumab on Prognosis of COVID-19 Patients: a Non-Randomized Pilot Clinical Trial Study in Iran.

BACKGROUND: Adalimumab is an anti-inflammatory medicine used to treat a variety of disorders, although its effectiveness in improving the clinical status of COVID-19 patients is debatable. The goal was to evaluate the efficacy of adalimumab as an alternate treatment in COVID-19 patients. METHODS: This non-randomized pilot clinical trial study included 18 patients with severe COVID-19 status hospitalized at the Afzalipour Hospital in Kerman from February 2022 to March 2022. Patients were divided into two groups: nine patients in the control group received dexamethasone, remdesivir, and heparin in addition to supportive therapies. The case group also included nine patients who received adalimumab injection (CinnoRA®, CinnaGen, Iran) in addition to the treatment administered to the control group. RESULTS: Although the effect of adalimumab injection on clinical factors, including mechanical ventilation required, the number of days oxygen needed, the length of stay in the intensive care unit (ICU), and saturation of peripheral oxygen (SpO2) level and respiratory rate (RR), were not significantly different between groups, the intra-group SpO2 level before and after receiving oxygen was significantly different in the case group (p ≤ 0.001 and p = 0.002). In addition, laboratory tests for lactate dehydrogenase (LDH) and C-reactive protein (CRP) revealed no statistically significant differences between the two groups. Nonetheless, a positive intra-group effect of the medication was detected on these two parameters. No short-term side effects of drug injection were observed. CONCLUSIONS: This study demonstrated the efficacy of adalimumab as an alternate medication for improving SpO2, LDH, and CRP levels in COVID-19 patients.

Empyema thoracic in a neonate co-infected with SARS-CoV-2 and staphylococcus arouse successfully treated with fibrinolysis: a brief report.

BACKGROUND: Empyema as a rare cause of respiratory distress in neonatal period has not yet been reported after Corona virus disease 2019 (COVID-19) and even rarely in the context of bacterial infections is age group. CASE PRESENTATION: The first neonate of quadruplets, resulting from Cesarean-Section of a 30-year-old mother without a history of previous illness, born at 34 weeks of gestation with a birth weight of 1600 gram. All four newborns were hospitalized; while the first one underwent nasal continuous positive airway pressure (N-CPAP) with a positive end-expiratory pressure of 6 and fractional inspired oxygen of 0.6, due to respiratory distress, noting a respiratory score of five out of 12.She was resuscitated one hour later due to bradycardia and underwent ventilator support. She received a single dose of pulmonary surfactant, intravenous paracetamol, and phenobarbital due to respiratory distress syndrome, Pectus Ductus Arteriosus, and unilateral clonic movements, respectively. In the lack of positive blood culture, she extubated two days later and breast-feeding was started. On day eight, she underwent high flow nasal cannula. On day 12, she suddenly developed respiratory distress, mottling, and abdominal distension, leading to N-CPAP and re-evaluation. The nasopharyngeal sampling for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) real time Polymerase chain reaction and the blood culture for staphylococcus aurous became positive. A large volume pleural effusion including septa and loculation in right hemi-thorax on chest computerized tomography scan and ultrasound was seen, necessitating to thoracotomy, which was not possible due to her general condition. Remdesivir was started and antibiotics changed to a more broad-spectrum coverage. Chest tube was inserted and Alteplase was injected for three consecutive days with beneficial effects. She had no problem for six-month follow up. CONCLUSION: This was a case of empyema thoracic in the context of SARS-CoV-2 and Staphylococcus arouses co-infection. In our experience, it can be treated by chest drainage and fibrinolysis in neonatal period.

Finding positive SARS-CoV-2 RT-PCR in cerebrospinal fluid of two pediatric patients with severe COVID-19: a brief case report.

BACKGROUND: There is growing evidence of nervous system involvement and related complaints in children with coronavirus disease 2019 (COVID-19). However, it seems that attempts to track of the virus in the nervous system have so far been unsuccessful. CASE PRESENTATION: Here we describe two pediatric cases of severe COVID-19 who had positive cerebrospinal fluid (CSF) and nasopharyngeal polymerase chain reaction (PCR) tests for severe acute respiratory syndrome coronavirus disease 2019 (SARS-CoV-2). A 36-month-old girl who presented with fever, diarrhea, mild left ventricular dysfunction and bizarre movements, and a five-month-old boy who presented with fever, watery diarrhea, severe dehydration, mottling, and two episodes of seizure. Their CSF analyses and cultures were normal. They admitted in intensive care unit (ICU) for near four days and discharged after ten days without any complaint. CONCLUSION: This is one of the first reports of the presence of coronavirus in the central nervous system in COVID-19 pediatric patients, emphasizing the neurotropism and neuroinvasion characteristics of the virus.

A dual H-type tracheoesophageal fistula; why not being repaired simultaneously? A case report and review of literature.

BACKGROUND: H-type Tracheoesophageal Fistula (TEF) is a particular type of congenital esophageal anomalies, in which patients present with non-specific symptoms that can result in delayed diagnosis. Here, we report two pediatric cases with a rarer variant called ?dual H-type TEFË®. CASE PRESENTATION: We present two cases of H-type TEF. The first was a 45-day-old boy with feeding problem and cyanosis while feeding, and the second was a three-month-old girl with cough and choking after feeding from the first day of birth. In both cases, two separate TEFs were detected during diagnostic evaluation by flexible bronchoscopy. Both were repaired simultaneously through a cervical incision. The first patient deteriorated 13 days after the surgery, disturbancing in acid-base balance and expired unfortunately. CONCLUSION: Hence, it is necessary to consider the possibility of double TEF in any newly diagnosed H-type TEF.

Sigmoid colon perforation in a SARS-CoV-2 positive neonate: a uniqueness report and a brief review.

BACKGROUND: Despite the relative prevalence of small bowel and proximal colon perforation in the neonatal period, recto-sigmoid perforation is extremely rare. Full-term neonates experience intestinal perforation less frequently than premature infants. Here we report a neonate with sigmoid perforation and simultaneous Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. CASE PRESENTATION: A 2550 g female neonate born at 38-weeks' gestation from a coronavirus disease-2019 (COVID-19) infected mother by cesarean section. Despite a good Apgar score in the first and fifth minutes, she was admitted to the neonatal intensive care unit with grunting and mild respiratory distress. She underwent antibiotics and oxygen by head box resulting in an Oxygen Saturation rate of 94%. The patients' respiratory distress decreased during the second day, resulting once breastfeeding without tolerance. While she passed meconium in the first 2 days, she developed abdominal distention on day 3. The nasopharyngeal SARS-CoV-2 real-time polymerase chain reaction (RT-PCR) was performed with positive results. Surgical consultation was requested and a thoraco-abdominal X-Ray was performed at this stage, which suspected to be a gastrointestinal perforation. Due to clinical deterioration and persistent abdominal distention, a contrast study was performed with water-soluble contrast, which confirmed intestinal perforation. However, the surgical exploration revealed perforation of the sigmoid colon at the posterior segment. The patient underwent antibiotic therapy, abdominal lavage, and colostomy, immediately. She was discharged in good condition approximately 14-days later. CONCLUSION: To our knowledge, this is the first report of sigmoid colon perforation in a term neonate following COVID-19.

Is neonatal phototherapy associated with a greater risk of childhood cancers?

BACKGROUND: Neonatal phototherapy (NNPT) has long been used as an effective and relatively safe method of treating neonatal hyperbilirubinemia. Considering the subsequent evidence of long-term impacts of NNPT such as malignancies, this study was conducted to evaluate the relationship between NNPT and childhood cancers. METHODS: This case-control study assessed 116 children up to 4 years old with every kind of cancer referred to the Oncology department of Afzalipour hospital, Kerman, Iran, from 2011 to 18. Moreover, 116 pediatric patients without cancer hospitalized at the same Center were included after sex and age matching as the control group. The history of phototherapy and its duration were evaluated in these two groups. RESULTS: We found no association between the NNPT and malignancies in children. However, high intensive phototherapy was higher historically among affected cancerous patients than in non-cancerous cases without any statistically significant difference (25% vs 19%; P = 0.26). Maternal educational level and history of maternal infection during pregnancy, which initially appeared to be two factors associated with malignancy in single variable regression analyses, were not significant based on the adjusted models. CONCLUSIONS: The results did not show a positive correlation between NNPT and childhood cancers, which may partly be due to the relatively small sample size of the study. However, some other evidence is worrisome enough that NNPT should not be considered risk-free. Additional multi-centric studies should be undertaken to specify that phototherapy is really safe.

Mixed Connective Tissue Disease (MCTD) in a Girl with Lower Extremities Edema: A Brief Report.

BACKGROUND: Mixed Connective Tissue Disease (MCTD) is a rare condition in children, characterized by a high titer of anti-ribonucleoprotein-U1 (anti-U1 RNP) antibodies, often presenting with overlapping features of two or more rheumatologic disorders, including juvenile idiopathic arthritis (JIA), systemic lupus erythematous (SLE), systemic sclerosis (SSc), and juvenile dermatomyositis/polymyositis (JDM/PM). CASE PRESENTATION: We report the case of an 8-year-old girl with a history of fever, hair loss, lower extremities edema, weakness, oral aphthous ulcers, and a high titer of anti-U1 RNP antibodies, which is consistent with the diagnosis of MCTD. The patient received immunomodulator drugs, and her disease went into remission. CONCLUSION: Diagnosing MCTD in pediatric patients can be challenging. It should be considered especially in cases with recurrent muscular weakness or pain, lupus-like manifestations, and edema. Moreover, serum anti-U1 RNP testing can be a helpful diagnostic tool.

Investigating the comparative effect of vitamin D level with the type of complications in Henoch Schönlein purpura and Kawasaki disease.

INTRODUCTION AND OBJECTIVES: Henoch Schönlein purpura (HSP) and Kawasaki disease (KD) are two main inflammatory diseases among childhood vasculitis. Considering the anti-inflammatory effects of 25-hydroxyvitamin D3, we decided to investigate the association of serum 25-hydroxy vitamin D3 level with the type and severity of these conditions. MATERIALS AND METHODS: The present study was performed as a historical cohort of 254 affected children with KD and HSP vasculitis. The required data were extracted, using a researcher-made questionnaire from patients' electronic file, and then they were analyzed after collecting information of the patients. RESULTS: In HSP group, 54% of participants were boys. Similarly, in KD group, boys were more affected than girls. The comparative 25-hydroxyvitamin vitamin D3 level in HSP patients with and without renal involvement (P=0.02), hematuria (P=0.14), and in two groups with and without heart disease, and also with and without coronary artery dilatation in KD patients (P<0.001) were significant. DISCUSSION AND CONCLUSIONS: The findings showed that insufficient level of vitamin D3 were significantly associated with the exacerbation of complications of both diseases, and therefore it seems that vitamin D deficiency can be an effective predictive factor of severity in HSP and KD patients.

Correlation between antiphospholipid antibodies and renal involvement in children with Henoch-Schönlein purpura: A cross-sectional study.

Background: Renal involvement is the most damaging long-term complication of Immunoglobulin-A (IgA) vasculitis. In the lack of a definite predictive biomarker for renal involvement, antiphospholipid antibodies (aPL) have been proposed in recent years. Methods: In this prospective cohort of 48 pediatric patients who were admitted with IgA vasculitis from September 2015 to June 2017, two serum samples were taken 12 weeks apart to detect Anti-Phospholipid antibodies. All patients were followed-up for renal involvement for six months. Results: Renal involvement occurred in 14 out of 48 patients with IgA vasculitis (29.16%). APLs were positive in nine out of 14 patients with IgA vasculitis and renal involvement (64.28%), in contrast to only six out of 34 patients with IgA vasculitis without renal involvement (17.64%). The presence of aPL antibodies was statistically associated with renal involvement (P=0.002). Although, the relationship between both sex (P=0.025) and age (P=0.046) with aPL positivity was statistically significant, performing a modified logistic regression test, the odds ratio was significant between the groups with and without renal involvement only in term of age and aPL positivity). Conclusion: The presence of aPL antibodies was statistically associated with renal involvement. We found a significant relationship between the age and aPL positivity. Hence, we need multicenter, more extensive cohort studies to reach a better and more accurate conclusion on the relationship between serum aPLs and renal involvement in IgA vasculitis patients.

Multisystem Inflammatory Syndrome in a Newborn (MIS-N): Clinical Evidence and Neurodevelopmental Outcome.

BACKGROUND: Although coronavirus disease-2019 (COVID-19) seems to be milder in children than in adults, children may exhibit severe multisystemic involvement, supported by growing evidence of this incidence in neonates. This case report aimed to demonstrate an inflammatory response syndrome in a full-term neonate born from a 35-old-year woman infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). CASE PRESENTATION: A full-term neonate girl with uneventful perinatal history was admitted with mild tachypnea at the first hour of birth and gradually worsened, resulting in subsequent ventilator support on the second day. The nasal SARS-CoV-2 real-time polymerase chain reaction (RT-PCR) test was positive in several cessations from the time of admission until the tenth day. She revealed cardiomegaly, a diffuse opacification of lungs in the chest radiograph, both side ventricular hypertrophy, valvular regurgitation, and severe pulmonary hypertension on echocardiography. She underwent treatment with surfactant, antibiotics, paracetamol, inotropes, and sildenafil, with beneficial effects. In the lack of a positive fluid culture, she developed necrotizing enterocolitis, transaminitis, and a generalized rash on day six. Furthermore, her mild brain edema that occurred on the second day developed into hydrocephaly. The patient was considered MIS-N and successfully treated with methylprednisolone pulse and intravenous immunoglobulin. She was discharged after 29 days and followed for eight months with persistent mild hydrocephalous and possible evidence of cerebral palsy. CONCLUSION: We conclude that maternal exposure to COVID-19 may potentially be associated with multisystem inflammation in the early neonatal period. However, this condition is relatively rare. Immunomodulatory agents may be beneficial in this condition.

What Kept Back on the Mirror of COVID-19-Related Acute Transverse Myelitis? A Genetic Background!

COVID-19-associated acute transverse myelitis (ATM) cases have been reported worldwide. Nevertheless, Iran, Italy, and the USA are the most affected countries, witnessing the possibility that genetic factors might be associated with this susceptibility. The genetic variants of the coronavirus-2 entry mechanisms and host innate immune response-related genes like interferons, interleukins, Toll-like receptors, human leukocyte antigens, blood groups, and some risk loci may be accountable. This study describes the compatibility of the geographical distribution between ATM and the Neanderthal core haplotype that confers risk for severe COVID-19 and some possible culprit genes.

Why COVID-19 is less frequent and severe in children: a narrative review.

BACKGROUND: Despite the streaks of severity, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection is, in general, less frequent and severe in children than in adults. We searched for causal evidence of this mystery. DATA SOURCES: An extensive search strategy was designed to identify papers on coronavirus disease 2019 (COVID-19). We searched Ovid MEDLINE, PubMed, EMBASE databases, and Cochrane library and carried out a review on the causes of this dilemma. RESULTS: Our searches produced 81 relevant articles. The review showed that children accounted for a lower percentage of reported cases, and they also experienced less severe illness courses. Some potential explanations, including the tendency to engage the upper airway, the different expression in both receptors of angiotensin-converting enzyme and renin-angiotensin system, a less vigorous immune response, the lower levels of interleukin (IL)-6, IL-10, myeloperoxidase, and P-selectin and a higher intracellular adhesion molecule-1, a potential protective role of lymphocytes, and also lung infiltrations might have protective roles in the immune system-respiratory tract interactions. Finally, what have shed light on this under representation comes from two studies that revealed high-titer immunoglobulin-G antibodies against respiratory syncytial virus and mycoplasma pneumonia, may carry out cross-protection against SARS-CoV-2 infection, just like what suggested about the vaccines. CONCLUSIONS: These results require an in-depth look. Properties of the immune system including a less vigorous adaptive system beside a preliminary potent innate response and a trained immunity alongside a healthier respiratory system, and their interactions, might protect children against SARS-CoV-2 infection. However, further studies are needed to explore other possible causes of this enigma.

Acute transverse myelitis of childhood due to novel coronavirus disease 2019: The first pediatric case report and review of literature.

The global coronavirus disease 2019 (COVID-19) pandemic appears to have some streaks of severity in pediatrics. These streaks include variable signs of respiratory distress, a new entity called multi-system inflammatory syndrome, and some evidences of neurological symptoms involving both central and peripheral nervous systems. Here, we described the first pediatric patient with COVID-19 who presented with acute transverse myelitis. An 11-year-old otherwise healthy girl presented to our clinic with acute onset of lower limbs paresis, urinary and fecal retention, alongside epigastric pain, and fever for 3 days. A neurological examination revealed a severe flaccid paraplegia in her lower limbs associated with a sensory level at T5. She was evaluated systematically for all probable causes of her symptoms, and finally, due to having a positive nasopharyngeal PCR test, she was considered to suffer from post-COVID-19 transverse myelitis. She underwent intravenous-immunoglobulin, methylprednisolone pulse, and other supportive cares without obvious results. Therefore, she underwent seven sessions of plasma exchange with little effects on muscle strength. The focal inflammation and injury of the spinal cord, otherwise known as transverse myelitis, have a wide array of potential etiologies. Transverse myelitis has been well documented to be the result of viral and bacterial infections. We believe our patient was not involved in a cytokine storm status due to good CRP, IL-6 and Ferritin levels. Albeit, we cannot certainly consider the patient to have a direct viral impactor involved in a late immunity process. To our knowledge, this is the first report of TM in the field of pediatrics occurred after COVID-19. Thus, this is critical to note that children can present with some severe types of COVID-19.

Post SARS-CoV-2 infection reactive arthritis: a brief report of two pediatric cases.

BACKGROUND: Although, preliminary reports of Severe Acute Respiratory Syndrome (SARS)-CoV-2 infection suggest that the infection causes a less severe illness in children, there is now growing evidence of other rare or even serious complications of disease. CASE PRESENTATION: During the recent COVID-19 pandemic in Kerman, Iran, two children (an 8 year-old boy and a 6 year-old girl) were referred to outpatient Clinic of Pediatric Rheumatology with complaints of limping. Both children had experienced fever and mild respiratory tract infection. At the beginning of the second week of infection, they developed joint effusion. They both tested positive for coronavirus infection and were therefore diagnosed with post Coronavirus reactive arthritis. Both children were treated successfully with rest and Non-Steroidal Anti-Inflammatory Drugs (NSAID). They did not have any medical problems in the two months fallow up. CONCLUSIONS: These two cases suggest that COVID-19 may be rheumatogenic. Highlighting the need for awareness of physicians, especially pediatricians, regarding the pathogenesis margins of this virus, as late presentations are of great importance.

A dermatopathic Juvenile Dermatomyositis; An Unexpected Case in Childhood.

Juvenile dermatomyositis (JDM) is a rare idiopathic inflammatory disease, which usually presents with skin rashes along with muscle weakness. We report a case of JDM in a 10- year-old girl with no skin manifestations presenting with progressive muscle weakness and fatigue. Further laboratory investigations, along with a muscle biopsy, confirmed the diagnosis of adermatopathic JDM. The patient was treated with intravenous immunoglobulin, corticosteroids, methotrexate, hydroxychloroquine, pamidronate, and rituximab. Following treatment, patients' symptoms subsided, and she gained normal muscular strength over a year.

Determination of diagnostic value (validity) leukocyte esterase (urine dipstick strip) in differentiating inflammatory arthritis from bacterial arthritis.

BACKGROUND: The current diagnostic cornerstone for septic arthritis contains gram stains, bacterial culture, and cell count with a differential of aspirated synovial fluid. Recently, a synovial leukocyte esterase (LE) test has been used for diagnosing septic arthritis. Since this test measures the esterase activity of leukocytes, there is always a dilemma for using this test in patients with inflammatory arthritis. METHODS: We collected the synovial fluid specimens as part of the general diagnostic protocol for patients suspected of Juvenile Idiopathic Arthritis (JIA) or Septic Arthritis (SA). Each group included 34 patients. We compared the result of the synovial LE test with the result of the culture of each patient. RESULTS: The mean ages of patients were 64.14 ± 31.27 and 50.88 ± 23.19 months in the JIA group and septic arthritis group, respectively. The LE test results were positive in 30 specimens, trace in 3 and negative in one in the first-time test and were positive in 31 specimens and trace in 3 in the second-time test, while it was negative in all patients with JIA. Hence, the sensitivity of the synovial LE test was 80.8%, the specificity, PPV, and NPV were 78.6, 70.0, 86.8% respectively based on a positive culture. CONCLUSION: The leukocyte esterase strip test can be used as a rapid, bedside method for diagnosing or excluding bacterial infections in different body fluids. The synovial LE test can be used as an accurate test to rapidly rule in or out an acute articular bacterial infection, even in patients with concurrent inflammatory arthritis.