Multi-inflammatory Syndrome In Children Research Articles

Changing paradigm of scrub typhus infection in children: A study from a tertiary care center of Eastern India

Background: Scrub typhus, a zoonotic disease, is transmitted to humans by the bite of larval trombiculid mite. Keeping in view the morbidity and mortality associated with undiagnosed cases (due to both lack of specific diagnostic tests and ignorance about the disease), the disease deserves a special mention. Aims and Objectives: The aims and objectives of the study were to assess complications and atypical manifestations of scrub typhus fever in this subpopulation and to assess the prognosis of patients presenting with atypical manifestations/complications. Materials and Methods: This is a longitudinal observational study on the basis of clinical and laboratory evidence at Department of Pediatrics, Calcutta-National-Medical College and Hospital, Kolkata, West Bengal, from March 2021 to February 2022. Children between >28 days and <12 years with atypical manifestations of scrub typhus who were scrub immunoglobulin (Ig)M positive (Serum and/or cerebrospinal fluid) were included in the study. Results: Of the 120 scrub typhus IgM-positive patients admitted in 1 year, complications present in 35%. These patients developed encephalitis, encephalomyelitis, neurological deficits, myocarditis, disseminated intravascular coagulation, acute kidney injury, atypical pneumonia, acute respiratory distress syndrome, acute encephalitis syndrome (23.8%), myocarditis with/without heart failure (14.3%), and multi-inflammatory syndrome in children with/without severe acute respiratory syndrome coronavirus 2 IgG (14.2%). There is a statistically significant association between the duration of fever at admission and pediatric intensive care unit (PICU) admission, the longer the fever duration at admission, the higher the rate of complications and thus PICU admission. Conclusion: Scrub typhus infection has expanded its various forms, presenting in various atypical manifestations alongside the common clinical features. Multiple cases of multiorgan involvement in the form of multi-inflammatory syndrome and hemophagocytic lymphohistiocytosis have been reported in the background of COVID-19 infection, alongside a significant percentage of scrub typhus infection reported in infancy. Thus, early detection is important to start intervention.

Enhanced CD95 and interleukin 18 signalling accompany T cell receptor Vβ21.3+ activation in multi-inflammatory syndrome in children

Multisystem inflammatory syndrome in children is a post-infectious presentation SARS-CoV-2 associated with expansion of the T cell receptor Vβ21.3+ T-cell subgroup. Here we apply muti-single cell omics to compare the inflammatory process in children with acute respiratory COVID-19 and those presenting with non SARS-CoV-2 infections in children. Here we show that in Multi-Inflammatory Syndrome in Children (MIS-C), the natural killer cell and monocyte population demonstrate heightened CD95 (Fas) and Interleuking 18 receptor expression. Additionally, TCR Vβ21.3+ CD4+ T-cells exhibit skewed differentiation towards T helper 1, 17 and regulatory T cells, with increased expression of the co-stimulation receptors ICOS, CD28 and interleukin 18 receptor. We observe no functional evidence for NLRP3 inflammasome pathway overactivation, though MIS-C monocytes show elevated active caspase 8. This, coupled with raised IL18 mRNA expression in CD16- NK cells on single cell RNA sequencing analysis, suggests interleukin 18 and CD95 signalling may trigger activation of TCR Vβ21.3+ T-cells in MIS-C, driven by increased IL-18 production from activated monocytes and CD16- Natural Killer cells.

Fever of Unknown Origin in Children: The Challenge of History Taking

A fever of unknown origin (FUO) in children is usually described as a fever of at least 8 days duration with no apparent diagnosis after initial investigations, including taking medical history and preliminary laboratory assessment. Infectious diseases are the most common cause of FUO, followed by rheumatologic and neoplastic conditions. In this report, we present a case of a 15-year-old Caucasian boy with a silent past medical history, who presented at our Pediatric ER department with a three-day history of fever, fatigue, and abdominal pain with diarrhoea. Initial laboratory testing and microbiological work-up were non-significant. At hospital admission, a broad infectious diagnostic work-up was pursued, including serologies and polymerase-chain-reaction (PCR) for CMV, EBV, HAV, Parvovirus, Toxoplasma gondii and Adenovirus, all negative. Given mild splenomegaly and linfadenopathy, systemic Juvenile Idiopathic Arthritis (s-JIA) was suspected, as well as Multi-inflammatory Syndrome in Children (MIS-C), but the patient did not meet their main diagnostic criteria. Malignancy was ruled out by a negative bone marrow fine-needle aspiration cytology and whole-body PET-CT scan. On hospital day 8, Brucella was identified on a new set of blood cultures and a combined antibiotic therapy was started with IV Gentamicin plus per os Doxycycline. The patient’s general conditions rapidly improved, and both fever and diarrhoea resolved. A reassessment of the patient’s medical history before discharge revealed exposure to unpasteurized soft cheese in the weeks prior to the onset of symptoms. This case underlines the importance of taking a complete medical history, as well as a full diagnostic work-up to unveil unusual infectious etiologies behind FUO. After the preliminary negative microbiological tests, a connective tissue disease was ruled out (i.e. lack of cutaneous or articular involvement), as well as malignancy, which led to a closer evaluation for infection and the diagnosis of Brucellosis.

RNAseq-based transcriptomics of treatment-naïve multi-inflammatory syndrome in children (MIS-C) demonstrates predominant activation of matrisome, innate and humoral immune pathways.

MIS-C is a rare, highly inflammatory state resembling incomplete Kawasaki disease, temporarily associated with COVID-19. The pathogenesis is not completely known. RNAseq was carried out on whole blood of six treatment-naïve MIS-C patients. This was compared against RNAseq transcriptomics data of five healthy controls (HC), four Kawasaki Disease (KD) and seven systemic Juvenile Idiopathic Arthritis (sJIA). Using PCA, MIS-C clustered separately from HC, KD and sJIA. Amongst the top 50 significant genes in the three comparisons with HC, KD, and sJIA, common genes were: TMCC2, ITGA2B, DMTN, GFI1B, PF4, QSER1, GRAP2, TUBB1. DSEA revealed that maximum number of hits for overexpressed pathways was for NABA matrisome activation when MIS-C was compared against HC. Cytokine stimulated cellular activation pathways, specifically IL-10 were downregulated. MIS-C had more activated pathways of neutrophil degranulation and acquired immune activation but less of coagulation system or heat-shock system involvement as compared to KD. As compared to sJIA, humoral immune response and complements were activated. Matrisome activation was higher, with increased cell-cell interaction and ECM signalling. This analysis revealed novel insights into the pathogenesis of MIS-C, including the potential role of matrisomes, humoral immune system and down-regulated interleukin-10 pathways.

Emerging findings for the assessment and treatment of pediatric deep neck abscesses.

The purpose of this review is to summarize new literature regarding the description, diagnosis, and treatment of pediatric deep neck abscesses. Providers should include multi-inflammatory syndrome in children (MIS-C) in a differential diagnosis in children suspected of having a retropharyngeal abscess. MRI may guide the proper management of children with deep neck abscesses by more accurately detecting free fluid compared to computed tomography imaging. Factors that may predict the need for surgical management include elevations in white blood cell counts and abscess size more than 3 cm. However, future investigation is necessary to establish consistent guidelines. Medical management is effective in many children, with a new study indicating success using a combination of cefotaxime and rifampicin. Anatomical and age-related risk factors predispose children to the development of deep neck abscesses. Findings from recent studies may aid providers in making an accurate diagnosis and providing proper medical or surgical management of children with these infections.

Evaluation of patients presenting with febrile seizures in an Iranian referral hospital: emphasis on the frequency of meningitis and co-infections

IntroductionFebrile seizures are one of the most common diseases that physicians encounter in pediatric emergency departments. Two important aspects of managing patients presenting with a febrile seizure are meningitis exclusion and co-infection investigation. This study was designed to determine any infection that occurs concomitantly with a febrile seizure episode and also to assess the frequency of meningitis among children presenting with febrile seizures.MethodsThis retrospective cross-sectional study was conducted at the Children’s Medical Center, an Iranian pediatric referral hospital. All patients aged 6 months to 5 years presenting with febrile seizures from 2020 to 2021 were included. Patients’ data were collected from the medical report files. The presence of respiratory, gastrointestinal, and urinary infections was evaluated. Moreover, the detection of SARS-CoV-2 using reverse transcription polymerase chain reaction (RT-PCR) was performed for suspicious cases.The results of urine and stool analysis, as well as blood, urine, and stool cultures were checked. The frequency of lumbar puncture (LP) performance and its results were studied. The relationship between white blood cells (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein in meningitis was evaluated.ResultsA total of 290 patients were referred to the Children’s Medical Center, Tehran, Iran, due to fever and seizures. The mean age of the patients was 21.5 ± 13.0 months, and 134 (46.2%) were female. Out of 290 patients, 17% presented with respiratory infections. Nasopharyngeal SARS-CoV-2 RT-PCR was requested for 50 patients (17%), of which nine (3%) were reported positive and two patients had multi-inflammatory syndrome in children (MIS-C). Fever without local signs, gastroenteritis, and urinary tract infections were found in 40%, 19%, and 14% of the patients, respectively. LP was requested for 97 participants (33.4%) to evaluate central nervous system infection, of which 22 cases were suggestive of aseptic meningitis. Among laboratory tests, leukocytosis was significantly related to aseptic meningitis (odds ratio = 11.1, 95% CI = 3.0- 41.5). The blood culture testing result was positive in seven patients; all of them were due to skin contamination.ConclusionEvaluation of patients for possible meningitis is necessary for febrile seizure management. Although the prevalence of bacterial meningitis in these patients is not high, according to this study and other studies conducted in Iran, aseptic meningitis, especially after Measles, Mumps, and Rubella (MMR) vaccination should be considered. Leukocytosis and increased CRP can predict the occurrence of aseptic meningitis in these patients. However, further studies with a larger sample size are highly recommended. Moreover, during the COVID-19 pandemic, it is recommended to pay attention to an acute COVID-19 infection or evidence of MIS-C in children with fever and seizure.

Multi-Inflammatory Syndrome in Children (MIS-C) in 2023: Is It Time to Forget about It?

Multisystem inflammatory syndrome in children (MIS-C) is defined as a clinically serious condition requiring hospitalization involving fever, multi-system organ dysfunction, and an increase in inflammatory biomarkers. The syndrome was originally described as a post-infectious complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which usually causes COVID-19. During the COVID-19 pandemic, not only did the virus undergo mutations but vaccines against SARS-CoV-2 were also developed. Both these conditions led to a decrease in the incidence of MIS-C. This narrative review summarizes the recent updates for MIS-C, particularly regarding the change in incidence, the link between the SARS-CoV-2 vaccine and MIS-C, and new updates of MIS-C treatments.

Multiplatform analyses reveal distinct drivers of systemic pathogenesis in adult versus pediatric severe acute COVID-19

The pathogenesis of multi-organ dysfunction associated with severe acute SARS-CoV-2 infection remains poorly understood. Endothelial damage and microvascular thrombosis have been identified as drivers of COVID-19 severity, yet the mechanisms underlying these processes remain elusive. Here we show alterations in fluid shear stress-responsive pathways in critically ill COVID-19 adults as compared to non-COVID critically ill adults using a multiomics approach. Mechanistic in-vitro studies, using microvasculature-on-chip devices, reveal that plasma from critically ill COVID-19 adults induces fibrinogen-dependent red blood cell aggregation that mechanically damages the microvascular glycocalyx. This mechanism appears unique to COVID-19, as plasma from non-COVID sepsis patients demonstrates greater red blood cell membrane stiffness but induces less significant alterations in overall blood rheology. Multiomics analyses in pediatric patients with acute COVID-19 or the post-infectious multi-inflammatory syndrome in children (MIS-C) demonstrate little overlap in plasma cytokine and metabolite changes compared to adult COVID-19 patients. Instead, pediatric acute COVID-19 and MIS-C patients show alterations strongly associated with cytokine upregulation. These findings link high fibrinogen and red blood cell aggregation with endotheliopathy in adult COVID-19 patients and highlight differences in the key mediators of pathogenesis between adult and pediatric populations.

Multi-inflammatory syndrome in children (MIS-C) associated with COVID-19: a nursing perspective experience report from a high-income tertiary paediatric hospital context

BackgroundIn the midst of the COVID-19 coronavirus pandemic, a new disease that affects children has arisen called multisystem inflammatory syndrome in children (MIS-C). Several research articles focusing on its medical aspects have been published, but very few have focused on nursing care. The aim of this study was therefore to describe the nursing status of children suffering from MIS-C and the experiences of registered nurses (RNs) in caring for these children in paediatric hospital inpatient care.Methods The study design includes both quantitative nursing clinical record data and qualitative interview data. Quantitative data from the clinical records were analysed using descriptive statistics. Qualitative data analysis of the interviews was conducted using both deductive and inductive approaches with content analysis.ResultsIn total, 47 clinical records from children with MIS-C were investigated during January–March 2021. The mean age of the children was 8.8 years. Boys were more affected than girls. Challenges in children’s nursing status were related to circulation (fever and swelling), nutrition (great thirst and loss of appetite), pain, and psychosocial situations. When caring for children with MIS-C, nurses experienced “frustration over uncertainty of care”, “children’s illbeing” and “unavoidable procedures”.ConclusionThis study contributes knowledge to the ongoing nursing care of children suffering from MIS-C. The results show many different areas of nursing focus, which challenges nurses and other disciplines within paediatric hospital care. One important factor when caring for these children was the use of a central venous line early in the care process, which improved the quality of care. Moreover, the care of children suffering from MIS-C demands resources and time from healthcare professionals, especially RNs, to meet caring needs and reduce illbeing.

A Case of ‘Multi-Inflammatory Syndrome in Children’ Complicated with Cardiogenic Shock

SARS Cov-2 infection causes Multi-Inflammatory Syndrome in Children (MIS-C), a serious condition that affects children. We report an 18-year-old Turkish male who was diagnosed with MIS-C and successfully treated. He was diagnosed with MIS-C and required invasive mechanical ventilation due to cardiogenic shock, after what he recovered. With a high temperature, rash, and conjunctival hyperemia, the patient was taken to the emergency department. He had no symptomatic COVID-19 in his medical history, although he had had contact with a COVID-19 positive patient in the near past. Physical examination revealed an erythematous maculopapular rash on the back and neck, as well as hepatosplenomegaly. SARS-CoV-2 IgM and IgG positivity were detected in the rapid antibody test. Following the procedure, rectal bleeding and tachypnea developed. Inflammation indicators and pro-BNP levels both increased. With echocardiogenic examination, the ejection fraction decreased from 50-55 percent to 35%. He needed invasive mechanical ventilation. As a result, the case was classified as MIS-C with predominant cardiac and gastrointestinal involvement. The patient was discharged after a successful multidisciplinary approach. Although COVID-19 infection in children and adolescents is asymptomatic or minimally symptomatic, clinicians should be aware of post-infection autoimmune complications.

1096. Riding the Waves: Infection by SARS-CoV-2 Variants in Solid Organ Transplant Recipients at Texas Children’s Hospital

Abstract Background Texas Children’s Hospital is the largest pediatric solid organ transplant (SOT) program in the US, performing heart, kidney, liver, and lung transplants. Limited data exist about SARS-CoV-2 infection (COVID-19) in the pediatric SOT population. We evaluated the impact of different SARS-CoV-2 variants in a cohort of PCR positive SOT recipients. Methods SOT recipients with a positive SARS-CoV-2 PCR test from 3/1/2020 to 2/28/2022 were included in the cohort. The study period was divided into 3 eras based on the predominant circulating variant of SARS-CoV-2: 3/20-6/21 original strain/Alpha, 7/21-11/21 Delta, and 12/21-2/22 Omicron variants. Retrospective medical record review was performed; Chi-squared and Fischer exact test were used to compare groups. Results A total of 269 of 1031 (26%) SOT recipients tested positive for SARS-CoV-2 during the study period. By organ, 87/335 (26%) heart, 57/224 (25%) kidney, 92/405 (23%) liver, and 25/67 (37%) lung recipients had COVID-19 infection. By era, there were 99 (37%) original strain/ Alpha, 65 (24%) Delta, and 105 (39%) Omicron. The patients’ median age was 12.72 years (IQR 6.6, 15.1) with a minority of recipients being female (42%). Common comorbidities included hypertension (50%), obesity (13%), diabetes (10%), and chronic kidney disease (10%); 34% had no comorbidities aside from chronic immunosuppression post-transplant. Overall, 80% of recipients were symptomatic (Figure 1), and 50 (19%) required hospitalization. Hospitalization rates were highest (29%) during Delta, compared with 18% for original/Alpha and 13% for Omicron (p=0.02) eras. Need for respiratory support, ICU admission, and all-cause mortality did not vary by era (Table 1). Three SOT recipients (2 original/Alpha and 1 Delta) were diagnosed with multi-inflammatory syndrome in children (MIS-C). Conclusion Our study suggests that pediatric SOT recipients have a high risk for hospitalization and short-term complications with COVID-19; Omicron appears to cause less severe disease, including MIS-C. Additional studies are needed to understand long-term complications of COVID-19 in SOT recipients. Disclosures Elizabeth A. Moulton, MD, PhD, Pfizer: Grant/Research Support Flor M. Munoz, MD, MSc, Gilead: Grant/Research Support|Moderna: DSMB|Pfizer: DSMB.

Unilateral Acute Parotitis

Background: Severe acute respiratory virus coronavirus-2 infection or coronavirus disease (COVID) is categorized into acute illness and late multiinflammatory syndrome in children (MISC). This has recently been challenged with recognition of presentations with mucocutaneous-enteric symptoms that display considerable overlap between the two. We recognized a similar overlap of manifestations when encountered the three cases of fever associated with unilateral parotitis. Clinical Description: The three patients were of different age groups ranging from 2 months to 7 years of age, all of whom presented with fever, unilateral swelling of face and neck consistent with the region of the parotid gland, and absence of other localizing symptoms or abnormalities on examination. All of them were positive for COVID antibodies, had negative COVID real-time polymerase chain reaction test, did not satisfy the diagnostic criteria of MISC, but had raised inflammatory markers. Since the workup for other common causes of acute parotitis was negative, a clinical diagnosis of post-COVID immune-mediated acute parotitis was kept. Management: All the three patients were managed with systemic steroids (oral or parenteral) and showed complete resolution of symptoms and normalization of laboratory parameters within a few days, a therapeutic response in alignment with an immune-mediated phenomenon. Conclusion: Acute unilateral parotitis with pyrexia may be a hitherto unreported late post-COVID manifestation that is immune mediated and shows an excellent therapeutic response to a short course of steroids.

Parametric Mapping Cardiac Magnetic Resonance Imaging for the Diagnosis of Myocarditis in Children in the Era of COVID-19 and MIS-C.

Myocarditis comprises many clinical presentations ranging from asymptomatic to sudden cardiac death. The history, physical examination, cardiac biomarkers, inflammatory markers, and electrocardiogram are usually helpful in the initial assessment of suspected acute myocarditis. Echocardiography is the primary tool to detect ventricular wall motion abnormalities, pericardial effusion, valvular regurgitation, and impaired function. The advancement of cardiac magnetic resonance (CMR) imaging has been helpful in clinical practice for diagnosing myocarditis. A recent Scientific Statement by the American Heart Association suggested CMR as a confirmatory test to diagnose acute myocarditis in children. However, standard CMR parametric mapping parameters for diagnosing myocarditis are unavailable in pediatric patients for consistency and reliability in the interpretation. The present review highlights the unmet clinical needs for standard CMR parametric criteria for diagnosing acute and chronic myocarditis in children and differentiating dilated chronic myocarditis phenotype from idiopathic dilated cardiomyopathy. Of particular relevance to today’s practice, we also assess the potential and limitations of CMR to diagnose acute myocarditis in children exposed to severe acute respiratory syndrome coronavirus-2 infections. The latter section will discuss the multi-inflammatory syndrome in children (MIS-C) and mRNA coronavirus disease 19 vaccine-associated myocarditis.

Severe Multi-inflammatory Syndrome in Children Temporally Related to COVID 19-Clinical Course, Laboratory Profile and Outcomes from a North Indian PICU.

Objective: We describe the trajectory of clinical course, laboratory markers and outcomes in children with severe multi-inflammatory syndrome temporally related to COVID-19 (MIS-C) admitted to our pediatric intensive care unit (PICU). Methods: This was a prospective case series of children admitted to PICU between May 1, 2020 and January 31, 2021, fulfilling the case definition of MIS-C published by World Health Organization (WHO) or Centers for Disease Control and Prevention (CDC). We analyzed demographic, clinical, laboratory data and echocardiographic findings. We also plotted the variation in trends between survivors and nonsurvivors. Results: Of the 34 critically ill children referred to PICU with diagnosis of MIS-C only 17 fulfilled the WHO/CDC classification of MIS-C, rest were MISC mimickers albeit other tropical infections. Median age at admission was 4 years (range 1y 6 mo-8 years). Fever, rash and conjunctival redness were most prominent symptoms. Myocardial involvement was seen in 70.5% while 76.4% developed shock; Invasive mechanical ventilation was required in 64.7% cases. Inflammatory markers showed a downward trend such as-median C- reactive protein (mg/L) had a serial reduction in levels-from (median/IQR) 210 (132.60, 246.90) at admission to 52.3 (42, 120) on Day 3. Median Ferritin (ng/ml) (n = 12) was 690 (203, 1324), serum LDH (IU/L) (n = 12) was 505 (229.5, 1032) and Mean D-dimer (ng/ml) (n = 7) was 5093.85 (1991.65), suggestive of hyperinflammatory syndrome. Twelve patients received intravenous immune globulin, with adjunctive steroid therapy used in two third of the cases. Six children died, 4 of them were under-5 years of age. Tocilizumab was prescribed in two children with high vasotrope inotrope score (VIS), cardiogenic shock and oxygenation index more than 15, both survived. Conclusions: Severe MIS-C has a heterogenous presentation, local or regional outbreaks of prevalent infectious diseases often lead to confusion and overdiagnosis. Higher proportion of mortality was seen in Under -5 children with MISC. Shock-like presentation, presence of myocardial dysfunction or nonsurvivor status is associated with higher trend of inflammatory markers and more profound multi-organ dysfunction. If disease progresses rapidly despite first line therapy (IvIg and steroids), use of Tocilizumab should be considered-as a rescue therapy under resource limitations in the absence of extracorporeal support.

Serum homocysteine level in pediatric patients with COVID-19 and its correlation with the disease severity.

BackgroundThrombosis and embolism are possible complications in coronavirus disease 2019 (COVID)‐19‐positive pediatric patients. Although the risk is lesser in children than it is in adults, it does exist during acute infection and multi‐inflammatory syndrome in children. Biomarkers such asd‐dimer, prothrombin time, and fibrinogen degradation products are ineffective at detecting disease severity. Homocysteine (Hcy) is a prothrombotic factor that has been reported to be higher in adult COVID‐19 patients, leading to speculation that it could be used as a biomarker for disease severity.PurposeTo detect the correlation between serum total homocysteine (tHcy) level and the severity of COVID‐19 in pediatrics.MethodsA cross‐sectional study was conducted on 40 children with COVID‐19 and 40 healthy control subjects. Serum tHcy was measured by enzyme‐linked immunosorbent assay and correlated with the clinical, laboratory, and radiological parameters of the patients.ResultsThe median serum tHcy level in COVID‐19 patients was 27.5 (interquartile range [IQR]: 23–31.75) μmol/L, while that in the controls was 1.8 (IQR: 1.6–1.875) μmol/L. There was a statistically significant increase in the tHcy level in cases compared to controls (p < 0.001). There was a statistically significant positive correlation between serum tHcy and d‐dimer, ferritin, alanine transaminase, aspartate transaminase, blood urea nitrogen, and a highly significant positive correlation between tHcy and COVID‐19 reporting and data system score, pediatric intensive care unit admission, and the disease severity classification.ConclusionHcy could be a biomarker of importance in predicting the severity of COVID‐19 in pediatrics.

A young adult with multisystem inflammatory syndrome (MIS-A) following COVID-19 infection: A case report

Recent reports have described a secondary Multi system Inflammatory Syndrome in adult (MIS-A)and its temporal association with COVID-19 infection. Here, we report the case of a 25-year-old male who presented with shock and multi organ failure. Three-week prior to present admission he developed an Influenza like illness, secondary to SARS-CoV2 infection as detected by a reverse-transcription polymerase chain reaction (RT-PCR). Three weeks later, patient had recurrence of fever associated with throat pain, neck swelling, and a rash followed by shock and multiorgan failure. Laboratory work revealed elevated inflammatory markers. His throat swab for SARS-CoV-2 by RT-PCR was negative and SARS-CoV-2 IgG antibody was reactive.In view of presentation like multi-inflammatory syndrome in children (MIS-C) a probable diagnosis of MIS-A was made. He was successfully treated with intravenous Immunoglobulin and pulse dose Methylprednisolone. This case highlights the need to remain vigilant for multisystem inflammatory syndromes in the COVID-19 affected patients.[

SARS-CoV-2 Interacts with Mucosal Dysbiosis to Cause the Wide Range of Disease Seen in Covid-19

Hypothesis: SARS-CoV-2 amplifies pre-existing dysbiosis induced mucosal inflammation and this can cause a severe systemic inflammatory disease. The microbial flora perturbation can persist long after the virus has been eliminated leading to a wide range of long Covid symptoms. Evidence: Dysbiosis induced mucosal inflammation increases with age and is strongly associated with the metabolic syndrome (obesity, type 2 diabetes mellitus, ischaemic heart disease, hypertension, and depression). These are risk factors for the conversion of mild to severe Covid-19. Certain common strains of Staphylococcus aureus, which is commonly carried in pharyngeal mucosa, can trigger a cytokine cascade as seen in severe Covid-19. Blood group A and vitamin D deficiency, which are risk factors for hospitalisation in Covid-19 are also associated with increased S. aureus pharyngeal carriage rates. Multi-inflammatory syndrome in children is a post Covid condition which resembles toxic shock syndrome and Kawasaki disease (the former is known to be caused by staphylococcal pyrogenic toxins). A number of studies have shown dysbiosis of the oral mucosa and rectal mucosa in patients who progress to severe Covid-19. The wide range of pathology seen during and following SARS-CoV-2 infection is more in keeping with dysbiosis induced inflammation (multiple pathogenic bacteria at multiple sites) than with an otherwise simple viral induced respiratory tract infection. Implication: Optimization of the microbial flora, prior to encountering the virus, could have reduced the severity of the pandemic. The consumption of fermented foods, especially yoghurt, holds the most promise for reducing dysbiosis induced mucosal inflammation and preventing a wide range of complications. Reduced mucosal inflammation brings not only health but also happiness in which oxytocin has a key role.

Clinical characteristics of multi-inflammatory syndrome in children associated with COVID 19 at the time of first contact with a primary care physician: an observational study

Background: MIS-C is a new clinical syndrome with many similarities with well-known common childhood illness. This present study aims to describe the clinical profile at the time of first contact with the primary care provider and to delineate it from other common illness.Methods: Retrospective observational study in a referral hospital, GMC Thrissur, Kerala. All 43 diagnosed cases during the study period were enrolled. Data was retrieved from the case sheets and reference letters. Data was analysed in Statistical package for social sciences (SPSS) 20 software.Results: 43 patients were diagnosed with MIS-C with a mean age at diagnosis was 7.3 years with a male preponderance. Fever was the universal symptom, gastrointestinal symptoms in 27 (62.7%), rash in 24 (55.8%), shock in 2 (4.6%), lymphadenopathy in 2, seizures in 2, altered sensorium in 1, palatal palsy in 1etc were the presenting symptoms. 12 (27.9%) of patients had no history of COVID 19 infection. The mean latency for MIS-C was 21 days (range 6-60 days). 17 (39.5%) patients developed shock later.Conclusions: The symptom triad of fever, rash and gastrointestinal symptoms was the common presenting symptom at the first contact. Fever was present in all children. One third of patients had no history of symptomatic covid 19. Shock was the presenting symptom only in 2 (4.6%), but subsequently 17 (39.5%) children developed shock within 5 days of onset of symptoms. High index of suspicion and vigilance should be maintained by the primary care provider for the timely diagnosis and referral to higher centre.

Coronavirus Disease 2019 (COVID-19) Vaccination for Children: Position Statement of Indian Academy of Pediatrics Advisory Committee on Vaccination and Immunization Practices

JustificationData generated after the first wave has revealed that some children with Coronavirus 19 (COVID-19) can become seriously ill. Multi-inflammatory syndrome in children (MIS-C) and long COVID cause significant morbidity in children. Prolonged school closures and quarantine have played havoc with the psychosocial health of children. Many countries in the world have issued emergency use authorisation (EUA) of selected COVID-19 vaccines for use in children. In India, a Subject Expert Committee (SEC) has recommended the use of Covaxin (Bharat Biotech) for children from the ages of 2–18 years. The recommendation has been given to the Drugs Controller General of India (DCGI) for final approval.ObjectiveTo provide an evidence-based document to guide the pediatricians on the recommendation to administer COVID vaccines to children, as and when they are available for use.ProcessFormulation of key questions was done by the committee, followed by review of literature on epidemiology and burden of COVID-19 in children, review of the studies on COVID vaccines in children, and the IAP stand on COVID-19 vaccination in children. The available data was discussed in the ACVIP focused WhatsApp group followed by an online meeting on 24 October, 2021, wherein the document was discussed in detail and finalized.RecommendationsThe IAP supports the Government of India’s decision to extend the COVID-19 vaccination program to children between 2–18 years of age. Children with high-risk conditions may be immunized on a priority basis. The IAP and its members should be a partner with the Government of India, in the implementation of this program and the surveillance that is necessary following the roll-out.

471. Descriptive Analysis of Multiinflammatory Syndrome in Children (MIS-C) Secondary to COVID 19 Infection in a Predominantly Latino Population in Western Massachusetts

BackgroundCOVID-19 infection is usually mild in children. Progression to severe disease with multiple organ systems compromise described as Multi Inflammatory Syndrome in Children (MIS-C) is a rare occurrence believed to be immunologically mediated. Previous reports describe a possible link between children of Latino origin and high incidence of MIS-C in the US. 40% of the total population in Western Massachusetts is of Latino origin. MethodsRetrospective chart review of 30 children admitted to Baystate Medical Center in Springfield, Massachusetts from April 2020-June 2021 meeting Centers for Disease Control and Prevention (CDC) criteria for MIS-C. Demographics, laboratory data, and clinical outcomes including progression to Macrophage Activation Syndrome (MAS) were analyzed.Results60% of children were Hispanic. Mean age (9.1 yrs). Range (3m-20 yrs). COVID PCR positive (78%) and COVID Antibody positive (68%). The most common symptom was fever (96.8%) followed by gastrointestinal symptoms (84%). Respiratory symptoms (29%), dermatological manifestations (39%). Most common comorbidity, asthma (19%) followed by obesity (17%). Leukocytosis (47%), lymphopenia (45%), Anemia (55%), thrombocytopenia (20%), high CRP (90%), ferritinemia (57%), acute kidney injury (20%), elevated liver enzymes (53%), 52% children had electrocardiogram (EKG) abnormalities, 34% had abnormal echocardiograms, none displayed coronary artery dilation. Progression to MAS (20%). All patients were treated with intravenous immunoglobulin G, steroids, aspirin, and anakinra (IL1 receptor antagonist) if progression to MAS. All patients survived.ConclusionIn our population, gastrointestinal symptoms were predominant despite a high prevalence of asthma and obesity, previous reports of children with MIS-C describe predominance of respiratory manifestations. We did not encounter any coronary aneurysms during admission. Most children had positive PCR or Antibodies for COVID 19 and showed important abnormalities in multiple cell lines and inflammatory markers. More research is needed to fully understand ethnical risk factors associated with disease severity especially the risk of progression to MAS from MIS-C in children of Latino origin diagnosed with COVID 19 infection.Disclosures All Authors: No reported disclosures