Multisystem inflammatory syndrome in a neonate with severe hemophilia - a diagnostic challenge in COVID times: a case report.

BACKGROUND: Multisystem Inflammatory Syndrome in Neonates (MIS-N) can occur following antenatal COVID- 19 infection in the mother. Here we report a rare case of a neonate with Hemophilia A and MIS-N. CASE PRESENTATION: A 2-day-old baby presented with an intramuscular hematoma, neonatal seizures, and isolated activated partial thromboplastin time (APTT) prolongation. The neurosonogram showed a subdural hematoma. A diagnosis of Hemophilia A was made and was confirmed by factor 8 assay and genetic analysis. Supportive measures and Factor 8 replacement was initiated. A rising trend of inflammatory markers and an ongoing need for mechanical ventilation were noted. As there was a history of COVID-19 in the mother in the third trimester, MIS-N was diagnosed. The baby was treated with intravenous immunoglobulin (IVIG) and steroids, and there was an improvement in the clinical and laboratory markers. However, the baby developed seizures on day 16. There was an increase in the subdural hemorrhage and a further rise in inflammatory markers. A craniostomy and hematoma evacuation was done and the baby improved. CONCLUSION: The concurrent occurrence of hemophilia A with intracranial bleed, and MIS-N in a neonate is a diagnostic challenge. It is important to have a high index of suspicion to ensure timely diagnosis and treatment of MIS-N in this pandemic era.

Clinical Profile and Short-Term Outcome of SARS-CoV-2-Infected Neonates from a Government Medical College in West Bengal, India.

INTRODUCTION: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has led to a terrifying global pandemic. The presentations in neonates are varied with less case severity compared to adults. AIM: To describe the clinical and laboratory features and outcomes of neonates admitted with SARS-CoV-2 infection during the second surge of COVID-19 pandemic in a Government Medical College, West Bengal, India. MATERIALS AND METHODS: It is a hospital-based observational cross-sectional study conducted in the newborn unit of Burdwan Medical College and Hospital between 1 April 2021 and 31 July 2021 including all SARS-CoV-2 Real time RT-PCR (Reverse transcriptase polymerase chain reaction) positive neonates. The demographic, clinical and laboratory characteristics of all the neonates and their outcomes were documented and analysed. RESULTS: Twenty-two neonates were found to be SARS-CoV-2 RT-PCR positive out of which 9 (40.9%) were found to be asymptomatic and 6 (27.27%) required neonatal intensive care unit admissions. Among the symptomatic neonates, most common presentations were respiratory distress (40.9%) and gastrointestinal manifestations (40.9%). Eight (36.36%) neonates required respiratory support. Three (13.6%) neonates had pneumonia of which one had right middle lobe collapse. Laboratory parameters were nonspecific except for the two (9%) cases of multisystem inflammatory syndrome in neonates. High-resolution computed tomography findings in two cases were suggestive of SARS-CoV-2 infection-induced changes. Two (9%) neonates died of which one was likely due to SARS-CoV-2 infection. CONCLUSION: Neonates with SARS-CoV-2 infection are mostly asymptomatic. However, clinicians must be vigilant as atypical presentations such as consolidation, collapse, meningitis or multisystem inflammatory syndrome may occur.

SARS-CoV-2 infection in neonates is rare with varied presentations ranging from asymptomatic neonates to a few presenting with multiorgan failure. The disease severity and case fatality are much less than in adults. We studied the clinical and laboratory features and outcomes of 22 neonates with SARS-CoV-2 infection during the second surge of COVID-19 pandemic. While nine (40.9%) neonates were asymptomatic, six (27.27%) required NICU admission. Pneumonia is a rare presentation in neonates but severe COVID-19 pneumonia resulting in consolidation and lobar collapse requiring positive pressure ventilation is a possibility. Multisystem inflammatory syndrome in neonates is also a clinical entity probably as a result of hyperinflammatory syndrome due to transplacental transfer of antibodies. They require rigorous treatment, close monitoring and regular follow-ups. Amniotic fluid, placental or cord blood testing is essential to ascertain the definite mode of transmission in these neonates.

VAERS Vasculitis Adverse Events Retrospective Study: Etiology Model of Immune Complexes Activating Fc Receptors in Kawasaki Disease and Multisystem Inflammatory Syndromes.

BACKGROUND: Vasculitis diseases include Kawasaki disease (KD), Kawasaki disease shock syndrome (KDSS), Multisystem Inflammatory Syndrome (MIS), Henoch-Schönlein purpura (HS), or IgA vasculitis, and additional vasculitis diseases. These diseases are often preceded by infections or immunizations. Disease incidence rates are higher in children than in adults. These diseases have been extensively studied, but understanding of the disease etiology remains to be established. OBJECTIVE: Many studies have failed to demonstrate an association between vasculitis diseases and vaccination; this study examines possible associations. METHODS: Herein, the Vaccine Adverse Event Reporting System (VAERS) database is retrospectively examined for associations between vasculitis diseases and immunizations. RESULTS: For some vaccines, the number of rare cases of KD, MIS, and HS are higher than the background rates. These rare cases are predicted to occur in individuals with (1) genetic risk factors with (2) antibody titer levels above the primary immune response level. Herein, the model of humoral immune response antibodies bound to antigens (pathogen or vaccine) creating immune complexes is proposed. These immune complexes are proposed to bind Fc receptors on immune cells and platelets, resulting in cell activation and the release of inflammatory molecules including histamine and serotonin. Immune complexes and inflammatory molecules including serotonin and histamine likely trigger vasculitis. Elevated serotonin and possibly histamine drive initial vasoconstrictions, disrupting blood flow. Increased blood flow pressure from cardiac capillary vasoconstrictions is predicted to trigger coronary artery aneurysms (CAA) or lesions (CAL) in some patients. For KDSS and MIS patients, these cardiac capillary vasoconstrictions are predicted to result in ischemia followed by ventricular dysfunction. Ongoing ischemia can result in long-term cardiac damage. Cases associated with pathogens are likely to have persistent infections triggering disease onset. CONCLUSION: The proposed model of immune complexes driving disease initial disease etiology by Fc receptor activation of immune cells and platelets, resulting in elevated histamine and serotonin levels, is testable and is consistent with disease symptoms and current treatments.

Early Outcome of Multisystem Inflammatory Syndrome in Neonates Diagnosed following Prenatal Maternal COVID-19 Infection: A Three-Case Series.

BACKGROUND: The aim of this case series report is to evaluate the characteristics of multisystem inflammatory syndrome (MIS) in neonates following prenatal maternal COVID-19 infection. METHODS: We present a case series of three newborns (≤28 days of age) diagnosed with MIS due to the vertical transmission of SARS-CoV2 infection and admitted from 1 January 2021 to 1 June 2023. The inclusion criteria were negative RT-PCR-SARS-CoV-2 test in infants, initial negative IgM-SARS-CoV-2 in infants followed by the emergence of positive IgG-SARS-CoV-2 antibodies in infants and maternal COVID-19 infection in the third trimester of pregnancy. Patients enrolled in this case series were admitted due to acute febrile illnesses. RESULTS: All three cases occurred in patients born at a mean gestational age of 39 weeks and who were appropriate for gestational age. The mean age at admission was 18.3 days. Fibrinogen (>400 mg/dL) and ferritin (>120 mg/dL) were elevated above the upper normal limit. Elevated levels of myocardial biomarkers (D-dimers, N-terminal pro b-type natriuretic peptide troponin T and creatine phosphokinase myocardial band) were recorded, with normal heart function evaluated using echocardiography. All three patients were treated with antibiotics; one received intravenous immunoglobulin. A 4-week follow-up was completed in two patients when their myocardial biomarkers and ferritin were still elevated but lower compared with previous examinations. D-dimers levels were normalized in 2/3 patients. CONCLUSIONS: Subclinical myocarditis was diagnosed as an early outcome in infants with MIS diagnosed postnatally due to the vertical transmission of SARS-CoV2 infection and may represent a new challenge for pediatricians in the pandemic era.

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.

Multisystem inflammatory syndromeneonates (MIS-N) associated with acute kidney injury: A case report.

A late preterm presented with multisystem involvement (respiratory failure, shock, acute kidney injury). Initially, the baby was managed with mechanical ventilation, inotropic support, antibiotics, fluid restriction and furosemide infusion. Despite conservative management for 12 h, urine output, metabolic status and renal function did not improve; peritoneal dialysis was therefore commenced. Intravenous immunoglobulin and methylprednisolone were introduced. Respiratory failure, shock and acute kidney injury (AKI) then resolved. The baby's condition gradually improved, and he was discharged after 19 days. On follow up, he was gaining weight satisfactorily, with no sequalae. Atypical presentation of multisystem involvement in the form of AKI should not be missed since it is treatable with definitive and supportive care and has a favorable outcome.

Multi-System Inflammatory Syndrome in Neonate (MIS-N) presenting as Bowel Obstruction: A case report

Background@#Since the start of SARS-CoV-2 pandemic, a post-infection hyperinflammatory process in children with features similar to Kawasaki disease, termed multisystem inflammatory syndrome in children (MIS-C),1 was identified. Thousands of MIS-C cases have already been reported worldwide.2 As possible cases of MIS-C in neonates were increasingly identified, multisystem inflammatory syndrome in neonates (MIS-N) as a distinct entity was proposed as neonates may not manifest all the typical features described in older children. @*Case Presentation@#We describe the case of a previously well term neonate with sudden signs of bowel obstruction who later had multisystem involvement (cardiac, gastrointestinal, and hematologic). The baby was born to a 23-yearold multigravida with an unremarkable prenatal history except for COVID-19 infection during her 34th week age of gestation. The mother presented with mild respiratory symptoms and resolved with supportive management. Our patient was born stable, then had sudden manifestations of feeding intolerance on the 16th day of life and upon work-up had moderate anemia, elevated inflammatory and cardiac markers, ileus, and dilatation of proximal left coronary artery. RT-PCR for SARS-CoV2 was negative. The baby was managed with intravenous immunoglobulin (IVIG) and steroids, with rapid clinical and laboratory parameters improvement thereafter. @*Conclusion@#MIS-N is still evolving as a disease entity with no clear, directed guidance yet on diagnosis and management. Management is extrapolated from treatment of MIS-C. Additional case reports and series are warranted to increase awareness and enable better understanding of the disease pathology among clinicians for timely investigation, diagnosis, and management.