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1.
Cardiol Young ; 32(1): 138-141, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1655373

ABSTRACT

A 17-year-old adolescent with severe multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease-2019 developed reduced left ventricular function and left ventricular thrombus. With treatment, his condition improved and the thrombus was dissolved. This case illustrates the risk of severe intra-cardiac thrombotic complications in patients with MIS-C.


Subject(s)
COVID-19 , Thrombosis , Adolescent , COVID-19/complications , Child , Humans , SARS-CoV-2 , Systemic Inflammatory Response Syndrome , Thrombosis/diagnosis , Thrombosis/etiology
2.
Pediatr Nephrol ; 36(9): 2627-2638, 2021 09.
Article in English | MEDLINE | ID: covidwho-1520348

ABSTRACT

BACKGROUND AND OBJECTIVES: COVID-19 is responsible for the 2019 novel coronavirus disease pandemic. Despite the vast research about the adult population, there has been little data collected on acute kidney injury (AKI) epidemiology, associated risk factors, treatments, and mortality in pediatric COVID-19 patients admitted to the ICU. AKI is a severe complication of COVID-19 among children and adolescents. METHODS: A comprehensive literature search was conducted in PubMed/MEDLINE and Cochrane Center Trials to find all published literature related to AKI in COVID-19 patients, including incidence and outcomes. RESULTS: Twenty-four studies reporting the outcomes of interest were included. Across all studies, the overall sample size of COVID positive children was 1,247 and the median age of this population was 9.1 years old. Among COVID positive pediatric patients, there was an AKI incidence of 30.51%, with only 0.56% of these patients receiving KRT. The mortality was 2.55% among all COVID positive pediatric patients. The incidence of multisystem inflammatory syndrome in children (MIS-C) among COVID positive patients was 74.29%. CONCLUSION: AKI has shown to be a negative prognostic factor in adult patients with COVID-19 and now also in the pediatric cohort with high incidence and mortality rates. Additionally, our findings show a strong comparison in epidemiology between adult and pediatric COVID-19 patients; however, they need to be confirmed with additional data and studies.


Subject(s)
Acute Kidney Injury/epidemiology , COVID-19/complications , Intensive Care Units/statistics & numerical data , Renal Replacement Therapy/statistics & numerical data , Systemic Inflammatory Response Syndrome/complications , Acute Kidney Injury/immunology , Acute Kidney Injury/therapy , Acute Kidney Injury/virology , Adult , Age Factors , COVID-19/diagnosis , COVID-19/immunology , COVID-19/mortality , Child , Hospital Mortality , Humans , Incidence , Pandemics/statistics & numerical data , Risk Factors , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/immunology , Systemic Inflammatory Response Syndrome/mortality
3.
Can J Cardiol ; 37(10): 1619-1628, 2021 10.
Article in English | MEDLINE | ID: covidwho-1474413

ABSTRACT

BACKGROUND: The emergence of increasing reports worldwide of a severe inflammatory process and shock in pediatric patients resembling Kawasaki disease (KD)-and, more specifically, Kawasaki disease shock syndrome (KDSS)-prompted us to explore KDSS in a preamble of a systematic comparison between the 2 conditions. METHODS: We completed a systematic review of KDSS and performed a meta-analysis comparison between reported KDSS cases and KD controls. RESULTS: A total of 10 case-control series were included in the meta-analysis. Patients with KDSS were older (38.4 ± 30.6 vs 21.9 ± 19.5 months; P < 0.001) compared with standard KD with equal sex distribution and completeness of clinical diagnostic criteria. KDSS present higher C-reactive protein (59.4 ± 29.2 mg/dL vs 20.8 ± 14.8 mg/dL; P < 0.001), lower albumin (2.7 ± 0.5 g/dL vs 3.3 ± 0.5 g/dL; P < 0.01), and lower platelets (255 ± 149 109/L vs 394 ± 132 109/L; P < 0.001) but only borderline higher white blood cells (P = 0.06). Differences in alanine transaminase, aspartate aminotransferase, and erythrocyte sedimentation rate were nonsignificant. The odds of intravenous immunoglobulin resistance (44.4% vs 9.6%; (P < 0.001) and the hospital length of stay (10.9 ± 5.8 vs 5.0 ± 3.0 days; P < 0.001) were higher in KDSS, as were the odds of coronary-artery abnormalities (33.9% vs 8.6%; P < 0.001). CONCLUSIONS: This first meta-analysis on KDSS vs KD represents a basis for future works on KDSS and opens the opportunity for future multicentre studies in the search of causal relationships between presenting elements and the eventual complications of KDSS. The similarities between SARS-CoV-2 multisystem inflammatory syndrome in children and KDSS open new horizons to the understanding of the etiology and pathophysiology related to KDSS.


Subject(s)
COVID-19/complications , Mucocutaneous Lymph Node Syndrome , Systemic Inflammatory Response Syndrome , COVID-19/blood , COVID-19/diagnosis , Child, Preschool , Diagnosis, Differential , Humans , Mucocutaneous Lymph Node Syndrome/blood , Mucocutaneous Lymph Node Syndrome/diagnosis , Outcome Assessment, Health Care , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/etiology , Systemic Inflammatory Response Syndrome/therapy
4.
Clin Rheumatol ; 40(10): 4179-4189, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1384475

ABSTRACT

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a new clinical condition characterized by signs of inflammation and multiorgan dysfunction due to cytokine storm associated with SARS-CoV-2. The clinical spectrum of MIS-C ranges from mild to severe, and even to mortal multisystem involvement. To guide clinicians, we evaluated detailed demographic characteristics, clinical features, laboratory findings, and outcomes of MIS-C cases. METHODS: We performed a retrospective study of patients with MIS-C who were managed in the Department of Pediatric Infectious Disease in the Selcuk University Faculty of Medicine, Konya, Turkey. MIS-C patients were divided into three clinical severity groups (mild, moderate, and severe) and separated into three age groups (< 5 years, 5-10 years, > 10 years). We compared the characteristics of MIS-C cases according to the severity of the disease and by age groups. RESULT: Thirty-six children with MIS-C were evaluated (52.8% male, median age of 7.8 years). A clinical spectrum overlapping with Kawasaki disease (KD) was the most common presentation (69.4%) in all age groups. The most common clinical symptoms were fever (100%), mucocutaneous rash (69.4%), and gastrointestinal symptoms (66.6%). There was no statistically significant difference in echocardiographic abnormality between KD-like and the other clinical spectra (p > 0.05). All life-threatening rhythm disturbances were observed in severe cases. No patients died. CONCLUSION: It is important to increase the awareness of physicians about the MIS-C disease, which can present with different combinations of different systemic findings, so that patients can be diagnosed and treated in a timely manner. Key Points • A single tertiary centre study shows that children with MIS-C can present with different clinic spectra other than Kawasaki diseases. • Electrocardiographic and echocardiographic evaluation is important in early diagnosis of children with MIS-C. • Pro-BNP can be used as a screening test in the emergency room for children with prolonged and unexplained fever for determine early cardiac involvement of MIS-C. • The lack of require biological agents and favourable outcomes in children with MIS-C may be related with administration of steroid therapy with IVIG in early stage of disease.


Subject(s)
COVID-19 , Child , Child, Preschool , Female , Humans , Male , Retrospective Studies , SARS-CoV-2 , Systemic Inflammatory Response Syndrome , Turkey/epidemiology
5.
J Pediatr ; 229: 33-40, 2021 02.
Article in English | MEDLINE | ID: covidwho-1382573

ABSTRACT

OBJECTIVE: To describe the similarities and differences in the evaluation and treatment of multisystem inflammatory syndrome in children (MIS-C) at hospitals in the US. STUDY DESIGN: We conducted a cross-sectional survey from June 16 to July 16, 2020, of US children's hospitals regarding protocols for management of patients with MIS-C. Elements included characteristics of the hospital, clinical definition of MIS-C, evaluation, treatment, and follow-up. We summarized key findings and compared results from centers in which >5 patients had been treated vs those in which ≤5 patients had been treated. RESULTS: In all, 40 centers of varying size and experience with MIS-C participated in this protocol survey. Overall, 21 of 40 centers required only 1 day of fever for MIS-C to be considered. In the evaluation of patients, there was often a tiered approach. Intravenous immunoglobulin was the most widely recommended medication to treat MIS-C (98% of centers). Corticosteroids were listed in 93% of protocols primarily for moderate or severe cases. Aspirin was commonly recommended for mild cases, whereas heparin or low molecular weight heparin were to be used primarily in severe cases. In severe cases, anakinra and vasopressors frequently were recommended; 39 of 40 centers recommended follow-up with cardiology. There were similar findings between centers in which >5 patients vs ≤5 patients had been managed. Supplemental materials containing hospital protocols are provided. CONCLUSIONS: There are many similarities yet key differences between hospital protocols for MIS-C. These findings can help healthcare providers learn from others regarding options for managing MIS-C.


Subject(s)
COVID-19/therapy , Clinical Protocols , Practice Patterns, Physicians'/statistics & numerical data , Systemic Inflammatory Response Syndrome/therapy , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Anticoagulants/therapeutic use , Antirheumatic Agents/therapeutic use , Aspirin/therapeutic use , COVID-19/diagnosis , Child , Cross-Sectional Studies , Glucocorticoids/therapeutic use , Heparin/therapeutic use , Hospitals , Humans , Immunoglobulins, Intravenous , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Surveys and Questionnaires , Systemic Inflammatory Response Syndrome/diagnosis , United States/epidemiology , Vasoconstrictor Agents/therapeutic use
6.
Pediatrics ; 148(3)2021 09.
Article in English | MEDLINE | ID: covidwho-1378143

ABSTRACT

Multisystem inflammatory syndrome in children (MIS-C) is a serious, sometimes life-threatening late complication of coronavirus disease 2019 (COVID-19) with multiorgan involvement and evidence of immune activation. The pathogenesis of MIS-C is not known, nor is the pathogenesis of the severe organ damage that is the hallmark of MIS-C. Human herpesvirus 6 (HHV-6), the virus responsible for roseola, is a ubiquitous herpesvirus that causes close to universal infection by the age of 3 years. HHV-6 remains latent for life and can be activated during inflammatory states, by other viruses, and by host cell apoptosis. HHV-6 has been associated with end-organ diseases, including hepatitis, carditis, and encephalitis. In addition, ∼1% of people have inherited chromosomally integrated human herpesvirus 6 (iciHHV-6), which is HHV-6 that has been integrated into chromosomal telomeric regions and is transmitted through the germ line. iciHHV-6 can be reactivated and has been associated with altered immune responses. We report here a case of MIS-C in which an initial high HHV-6 DNA polymerase chain reaction viral load assay prompted testing for iciHHV-6, which yielded a positive result. Additional research may be warranted to determine if iciHHV-6 is commonly observed in patients with MIS-C and, if so, whether it may play a part in MIS-C pathogenesis.


Subject(s)
COVID-19/virology , Herpesvirus 6, Human , Roseolovirus Infections/virology , Systemic Inflammatory Response Syndrome/virology , COVID-19 Nucleic Acid Testing , Child , DNA, Viral/isolation & purification , Herpesvirus 6, Human/genetics , Herpesvirus 6, Human/isolation & purification , Humans , Male , Polymerase Chain Reaction , Telomere/virology , Viral Load , Virus Latency
7.
J Pediatric Infect Dis Soc ; 10(6): 714-721, 2021 Aug 14.
Article in English | MEDLINE | ID: covidwho-1358467

ABSTRACT

BACKGROUND: Children with coronavirus disease-2019 (COVID-19) have a milder clinical course than adults. We describe the spectrum of cardiovascular manifestations during a COVID-19 outbreak in Emilia-Romagna, Italy. METHODS: A cross-sectional multicenter study was performed, including all patients diagnosed with Kawasaki disease (KD), myocarditis, and multisystem inflammatory syndrome in children (MIS-C) from February to April 2020. KD patients were compared with those diagnosed before the epidemic. RESULTS: KD: 8 patients (6/8 boys, all negative for severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2]): complete presentation in 5/8, 7/8 immunoglobulin (IVIG) responders, and 3/8 showed transient coronary lesions (CALs). Myocarditis: one 5-year-old girl negative for SARS-CoV-2 and positive for parvovirus B19. She responded to IVIG. MIS-C: 4 SARS-CoV-2-positive boys (3 patients with positive swab and serology and 1 patient with negative swab and positive serology): 3 presented myocardial dysfunction and pericardial effusion, and 1 developed multicoronary aneurysms and hyperinflammation; all responded to treatment. The fourth boy had mitral and aortic regurgitation that rapidly regressed after steroids. CONCLUSIONS: KD, myocarditis, and MIS-C were distinguishable cardiovascular manifestations. KD did not show a more aggressive form compared with previous years: coronary involvement was frequent but always transient. MIS-C and myocarditis rapidly responded to treatment without cardiac sequelae despite high markers of myocardial injury at the onset, suggesting a myocardial depression due to systemic inflammation rather than focal necrosis. Evidence of actual or previous SARS-CoV-2 infection was documented only in patients with MIS-C.


Subject(s)
COVID-19 , Cardiovascular Diseases , Adolescent , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Child , Cross-Sectional Studies , Female , Humans , Male , SARS-CoV-2 , Systemic Inflammatory Response Syndrome
8.
J Pediatric Infect Dis Soc ; 10(6): 706-713, 2021 Aug 14.
Article in English | MEDLINE | ID: covidwho-1358465

ABSTRACT

BACKGROUND: Recently, cases of multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) have been reported worldwide. Negative polymerase chain reaction (RT-PCR) testing associated with positive serology in most of the cases suggests a postinfectious syndrome. Because the pathophysiology of this syndrome is still poorly understood, extensive virological and immunological investigations are needed. METHODS: We report a series of 4 pediatric patients admitted to Geneva University Hospitals with persistent fever and laboratory evidence of inflammation meeting the published definition of MIS-C related to COVID-19, to whom an extensive virological and immunological workup was performed. RESULTS: RT-PCRs on multiple anatomical compartments were negative, whereas anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin A (IgA) and immunoglobulin G (IgG) were strongly positive by enzyme-linked immunosorbent assay and immunofluorescence. Both pseudoneutralization and full virus neutralization assays showed the presence of neutralizing antibodies in all children, confirming a recent infection with SARS-CoV-2. The analyses of cytokine profiles revealed an elevation in all cytokines, as reported in adults with severe COVID-19. Although differing in clinical presentation, some features of MIS-C show phenotypic overlap with hemophagocytic lymphohistiocytosis (HLH). In contrast to patients with primary HLH, our patients showed normal perforin expression and natural killer (NK) cell degranulation. The levels of soluble interleukin (IL)-2 receptor (sIL-2R) correlated with the severity of disease, reflecting recent T-cell activation. CONCLUSION: Our findings suggest that MIS-C related to COVID-19 is caused by a postinfectious inflammatory syndrome associated with an elevation in all cytokines, and markers of recent T-cell activation (sIL-2R) occurring despite a strong and specific humoral response to SARS-CoV-2. Further functional and genetic analyses are essential to better understand the mechanisms of host-pathogen interactions.


Subject(s)
COVID-19 , Antibodies, Neutralizing , Child , Humans , SARS-CoV-2 , Systemic Inflammatory Response Syndrome
9.
Lancet Child Adolesc Health ; 5(7): 473-482, 2021 07.
Article in English | MEDLINE | ID: covidwho-1349610

ABSTRACT

BACKGROUND: Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) is a new, rare, post-infectious complication of SARS-CoV-2 infection in children. We aimed to describe the 6-month outcomes of PIMS-TS. METHODS: This retrospective cohort study comprised children (aged <18 years) who fulfilled the UK Royal College of Paediatrics and Child Health (RCPCH) diagnostic criteria for PIMS-TS and were admitted to Great Ormond Street Hospital (London, UK) between April 4 and Sept 1, 2020. Patients were followed up by a multidisciplinary team of specialists at 6 weeks and 6 months after admission. Biochemical and functional outcomes were analysed. FINDINGS: 46 children were included in this study. The median age at presentation was 10·2 years (IQR 8·8-13·3), 30 (65%) patients were male and 16 (35%) were female, 37 (80%) were from minority ethnic groups, and eight (17%) had pre-existing comorbidities. All patients had elevated markers of systemic inflammation at baseline. None of the patients died. By 6 months, systemic inflammation was resolved in all but one patient. 38 (90%) of 42 patients who had positive SARS-CoV-2 IgG antibodies within 6 weeks of admission remained seropositive at 6 months. Echocardiograms were normal in 44 (96%) of 46 patients by 6 months, and gastrointestinal symptoms that were reported in 45 (98%) of 46 patients at onset were present in six (13%) of 46 patients at 6 months. Renal, haematological, and otolaryngological findings largely resolved by 6 months. Although minor abnormalities were identified on neurological examination in 24 (52%) of 46 patients at 6 weeks and in 18 (39%) of 46 at 6 months, we found minimal functional impairment at 6 months (median Expanded Disability Status Scale score 0 [IQR 0-1]). Median manual muscle test-8 scores improved from 53 (IQR 43-64) during hospital admission to 80 (IQR 68-80) at 6 months, but 18 (45%) of 40 patients showed 6-min walk test results below the third centile for their age or sex at 6 months. PedsQL responses revealed severe emotional difficulties at 6 months (seven [18%] of 38 by parental report and eight [22%] of 38 by self report). 45 (98%) of 46 patients were back in full-time education (virtually or face to face) by 6 months. INTERPRETATION: Despite initial severe illness, few organ-specific sequelae were observed at 6 months. Ongoing concerns requiring physical re-conditioning and mental health support remained, and physiotherapy assessments revealed persisting poor exercise tolerance. Longer-term follow-up will help define the extended natural history of PIMS-TS. FUNDING: None.


Subject(s)
COVID-19/epidemiology , Outcome Assessment, Health Care , Systemic Inflammatory Response Syndrome/epidemiology , Adolescent , Child , Cohort Studies , Female , Follow-Up Studies , Hospitals, Pediatric , Humans , Male , Retrospective Studies , United Kingdom/epidemiology
10.
BMJ Case Rep ; 14(4)2021 Apr 22.
Article in English | MEDLINE | ID: covidwho-1198276

ABSTRACT

This case demonstrates pneumatosis intestinalis and small bowel perforation in a paediatric patient with multisystem inflammatory syndrome in children (MIS-C). Our patient presented with fever, abdominal pain and shortness of breath. She progressed to haemodynamic failure and small bowel perforation approximately 1 week after admission. Patients with suspected or confirmed MIS-C should be monitored closely for abdominal catastrophe, especially when critically ill in the intensive care unit.


Subject(s)
Intestinal Perforation , Pneumatosis Cystoides Intestinalis , Systemic Inflammatory Response Syndrome/complications , Child , Female , Humans , Intestinal Perforation/diagnostic imaging , Intestinal Perforation/etiology , Pneumatosis Cystoides Intestinalis/diagnostic imaging , Pneumatosis Cystoides Intestinalis/etiology
11.
Ital J Pediatr ; 47(1): 119, 2021 Jun 02.
Article in English | MEDLINE | ID: covidwho-1319490

ABSTRACT

BACKGROUND: SARS-CoV-2 infection in children is often non severe and in the majority of cases does not require long term hospitalization, nevertheless it is burdened with social issues and managing difficulties. To our knowledge there is no literature on telephonic follow up in pediatric patients with positive PCR for SARS-CoV-2 on rhino-pharyngeal swab after discharge. The aim of the study is to describe our experience in a telephonic follow up which can allow early and safe discharge from hospital while keeping the patients under close clinical monitoring. MATERIALS AND METHODS: Sixty-five children were admitted for SARS-CoV-2 infection at Bambino Gesù Pediatric Hospital COVID Center from 16th March to 3rd July. We monitored through a telephonic follow-up, using a specific survey, the patients discharged still presenting a positive PCR for SARS-CoV-2. We checked if any symptoms occurred at home until recovery, defined as two consecutive negative PCR for SARS-CoV-2 on rhino-pharyngeal swabs. RESULTS: During the follow up 7 patients had mild and self-limited symptoms related to SARS-CoV-2 infection, while 2 patients were re-hospitalized. One patient had Multisystem Inflammatory Syndrome in Children (MIS-C), the other patient had an increase in troponin and D-dimers. We also monitored the average time of viral shedding, resulting in a median duration of 28 days. CONCLUSION: Our experience describes the daily telephonic follow up as safe in pediatric patients discharged with positive PCR. As a matter of fact it could avoid long term hospitalization and allow to promptly re-hospitalize children with major complications such as MIS-C.


Subject(s)
COVID-19/therapy , Continuity of Patient Care , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , Telephone , Adolescent , Biomarkers/blood , COVID-19/epidemiology , COVID-19 Testing , Child , Child, Preschool , Female , Humans , Infant , Italy/epidemiology , Male , Patient Discharge , Pneumonia, Viral/virology , SARS-CoV-2 , Virus Shedding
12.
Am J Emerg Med ; 49: 148-152, 2021 11.
Article in English | MEDLINE | ID: covidwho-1316366

ABSTRACT

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a dangerous pediatric complication of COVID-19. OBJECTIVE: The purpose of this review article is to provide a summary of the diagnosis and management of MIS-C with a focus on management in the acute care setting. DISCUSSION: MIS-C is an inflammatory syndrome which can affect nearly any organ system. The most common symptoms are fever and gastrointestinal symptoms, though neurologic and dermatologic findings are also well-described. The diagnosis includes a combination of clinical and laboratory testing. Patients with MIS-C will often have elevated inflammatory markers and may have an abnormal electrocardiogram or echocardiogram. Initial treatment involves resuscitation with careful assessment for cardiac versus vasodilatory shock using point-of-care ultrasound. Treatment should include intravenous immunoglobulin, anticoagulation, and consideration of corticosteroids. Interleukin-1 and/or interleukin-6 blockade may be considered for refractory cases. Aspirin is recommended if there is thrombocytosis or Kawasaki disease-like features on echocardiogram. Patients will generally require admission to an intensive care unit. CONCLUSION: MIS-C is a condition associated with morbidity and mortality that is increasingly recognized as a potential complication in pediatric patients with COVID-19. It is important for emergency clinicians to know how to diagnose and treat this disorder.


Subject(s)
COVID-19/complications , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/therapy , Adolescent , Adrenal Cortex Hormones/therapeutic use , Aspirin/therapeutic use , COVID-19/diagnosis , COVID-19/mortality , COVID-19/therapy , Child , Child, Preschool , Emergency Service, Hospital , Humans , Immunoglobulins, Intravenous , Infant , Infant, Newborn , Point-of-Care Systems , Resuscitation , SARS-CoV-2 , Shock/physiopathology , Systemic Inflammatory Response Syndrome/mortality , Ultrasonography
13.
J Clin Invest ; 131(14)2021 07 15.
Article in English | MEDLINE | ID: covidwho-1311202

ABSTRACT

BACKGROUNDWeeks after SARS-CoV-2 infection or exposure, some children develop a severe, life-threatening illness called multisystem inflammatory syndrome in children (MIS-C). Gastrointestinal (GI) symptoms are common in patients with MIS-C, and a severe hyperinflammatory response ensues with potential for cardiac complications. The cause of MIS-C has not been identified to date.METHODSHere, we analyzed biospecimens from 100 children: 19 with MIS-C, 26 with acute COVID-19, and 55 controls. Stools were assessed for SARS-CoV-2 by reverse transcription PCR (RT-PCR), and plasma was examined for markers of breakdown of mucosal barrier integrity, including zonulin. Ultrasensitive antigen detection was used to probe for SARS-CoV-2 antigenemia in plasma, and immune responses were characterized. As a proof of concept, we treated a patient with MIS-C with larazotide, a zonulin antagonist, and monitored the effect on antigenemia and the patient's clinical response.RESULTSWe showed that in children with MIS-C, a prolonged presence of SARS-CoV-2 in the GI tract led to the release of zonulin, a biomarker of intestinal permeability, with subsequent trafficking of SARS-CoV-2 antigens into the bloodstream, leading to hyperinflammation. The patient with MIS-C treated with larazotide had a coinciding decrease in plasma SARS-CoV-2 spike antigen levels and inflammatory markers and a resultant clinical improvement above that achieved with currently available treatments.CONCLUSIONThese mechanistic data on MIS-C pathogenesis provide insight into targets for diagnosing, treating, and preventing MIS-C, which are urgently needed for this increasingly common severe COVID-19-related disease in children.


Subject(s)
COVID-19/etiology , COVID-19/physiopathology , Haptoglobins/physiology , Intestinal Mucosa/physiopathology , Protein Precursors/physiology , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/etiology , Systemic Inflammatory Response Syndrome/physiopathology , Adolescent , Antigens, Viral/blood , Biomarkers/blood , COVID-19/virology , Case-Control Studies , Child , Child, Preschool , Female , Haptoglobins/antagonists & inhibitors , Humans , Infant , Infant, Newborn , Intestinal Mucosa/drug effects , Intestinal Mucosa/virology , Male , Oligopeptides/pharmacology , Permeability/drug effects , Proof of Concept Study , Protein Precursors/antagonists & inhibitors , Protein Precursors/blood , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/blood , Spike Glycoprotein, Coronavirus/immunology , Systemic Inflammatory Response Syndrome/virology , Young Adult
15.
Arthritis Rheumatol ; 73(7): 1341-1342, 2021 07.
Article in English | MEDLINE | ID: covidwho-1290413

Subject(s)
Anticoagulants , COVID-19 , Humans
16.
Int J Clin Pract ; 75(9): e14471, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1285028

ABSTRACT

OBJECTIVE: Although the initial reports of COVID-19 cases in children described that children were largely protected from severe manifestations, clusters of paediatric cases of severe systemic hyperinflammation and shock related to severe acute respiratory syndrome coronavirus 2 infection began to be reported in the latter half of April 2020. A novel syndrome called "multisystem inflammatory syndrome in children" (MIS-C) shares common clinical features with other well-defined syndromes, including Kawasaki disease, toxic shock syndrome and secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome. Our objective was to develop a protocol for the evaluation, treatment and follow-up of patients with MIS-C. METHODS: The protocol was developed by a multidisciplinary team. We convened a multidisciplinary working group with representation from the departments of paediatric critical care, cardiology, rheumatology, surgery, gastroenterology, haematology, immunology, infectious disease and neurology. Our protocol and recommendations were based on the literature and our experiences with multisystem inflammatory syndrome in children. After an agreement was reached and the protocol was implemented, revisions were made on the basis of expert feedback. CONCLUSION: Children may experience acute cardiac decompensation or other organ system failure due to this severe inflammatory condition. Therefore, patients with severe symptoms of MIS-C should be managed in a paediatric intensive care setting, as rapid clinical deterioration may occur. Therapeutic approaches for MIS-C should be tailored depending on the patients' phenotypes. Plasmapheresis may be useful as a standard treatment to control hypercytokinemia in cases of MIS-C with severe symptoms. Long-term follow-up of patients with cardiac involvement is required to identify any sequelae of MIS-C.


Subject(s)
COVID-19 , Algorithms , Child , Humans , SARS-CoV-2 , Syndrome , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/therapy
17.
N Engl J Med ; 385(1): 23-34, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1270704

ABSTRACT

BACKGROUND: The assessment of real-world effectiveness of immunomodulatory medications for multisystem inflammatory syndrome in children (MIS-C) may guide therapy. METHODS: We analyzed surveillance data on inpatients younger than 21 years of age who had MIS-C and were admitted to 1 of 58 U.S. hospitals between March 15 and October 31, 2020. The effectiveness of initial immunomodulatory therapy (day 0, indicating the first day any such therapy for MIS-C was given) with intravenous immune globulin (IVIG) plus glucocorticoids, as compared with IVIG alone, was evaluated with propensity-score matching and inverse probability weighting, with adjustment for baseline MIS-C severity and demographic characteristics. The primary outcome was cardiovascular dysfunction (a composite of left ventricular dysfunction or shock resulting in the use of vasopressors) on or after day 2. Secondary outcomes included the components of the primary outcome, the receipt of adjunctive treatment (glucocorticoids in patients not already receiving glucocorticoids on day 0, a biologic, or a second dose of IVIG) on or after day 1, and persistent or recurrent fever on or after day 2. RESULTS: A total of 518 patients with MIS-C (median age, 8.7 years) received at least one immunomodulatory therapy; 75% had been previously healthy, and 9 died. In the propensity-score-matched analysis, initial treatment with IVIG plus glucocorticoids (103 patients) was associated with a lower risk of cardiovascular dysfunction on or after day 2 than IVIG alone (103 patients) (17% vs. 31%; risk ratio, 0.56; 95% confidence interval [CI], 0.34 to 0.94). The risks of the components of the composite outcome were also lower among those who received IVIG plus glucocorticoids: left ventricular dysfunction occurred in 8% and 17% of the patients, respectively (risk ratio, 0.46; 95% CI, 0.19 to 1.15), and shock resulting in vasopressor use in 13% and 24% (risk ratio, 0.54; 95% CI, 0.29 to 1.00). The use of adjunctive therapy was lower among patients who received IVIG plus glucocorticoids than among those who received IVIG alone (34% vs. 70%; risk ratio, 0.49; 95% CI, 0.36 to 0.65), but the risk of fever was unaffected (31% and 40%, respectively; risk ratio, 0.78; 95% CI, 0.53 to 1.13). The inverse-probability-weighted analysis confirmed the results of the propensity-score-matched analysis. CONCLUSIONS: Among children and adolescents with MIS-C, initial treatment with IVIG plus glucocorticoids was associated with a lower risk of new or persistent cardiovascular dysfunction than IVIG alone. (Funded by the Centers for Disease Control and Prevention.).


Subject(s)
COVID-19/drug therapy , Glucocorticoids/therapeutic use , Immunoglobulins, Intravenous/therapeutic use , Systemic Inflammatory Response Syndrome/drug therapy , Ventricular Dysfunction, Left/prevention & control , Adolescent , COVID-19/complications , COVID-19/immunology , COVID-19/mortality , Child , Child, Preschool , Cohort Studies , Combined Modality Therapy , Drug Therapy, Combination , Female , Hospitalization , Humans , Immunomodulation , Infant , Logistic Models , Male , Propensity Score , Public Health Surveillance , Shock/etiology , Shock/prevention & control , Systemic Inflammatory Response Syndrome/complications , Systemic Inflammatory Response Syndrome/immunology , Systemic Inflammatory Response Syndrome/mortality , Treatment Outcome , Ventricular Dysfunction, Left/etiology , Young Adult
18.
Pan Afr Med J ; 38: 174, 2021.
Article in English | MEDLINE | ID: covidwho-1173703

ABSTRACT

Since late April 2020, a syndrome now termed Multisystem Inflammatory Syndrome in Children (MIS-C) has been seen in children and adolescents in association with COVID-19 infection. The definition of MIS-C involves fever, organ dysfunction and laboratory confirmation of inflammation in the context of laboratory or epidemiological evidence of SARS-CoV-2 infection in a patient under 21 years of age. Notably, cases are now being identified in adults termed Multisystem Inflammatory syndrome in Adults (MIS-A). Few cases have been reported in sub-Saharan Africa. We report a case of a young African male presenting with a maculopapular rash, persistent fever, elevation in inflammatory markers and a sudden, significant deterioration in cardiac function resulting in cardiogenic shock. The patient responded to intravenous steroids, intravenous immunoglobulin and background inotropic support. The recognition of this disease entity proves even more crucial now amidst the ongoing global wave of COVID-19 infection. It is paramount to identify these patients early, leading to prompt treatment avoiding further morbidity and mortality.


Subject(s)
COVID-19/diagnosis , Shock, Cardiogenic/diagnosis , Systemic Inflammatory Response Syndrome/diagnosis , Adolescent , Africa South of the Sahara , COVID-19/physiopathology , COVID-19/therapy , Humans , Immunoglobulins, Intravenous/administration & dosage , Male , Shock, Cardiogenic/virology , Steroids/administration & dosage , Systemic Inflammatory Response Syndrome/physiopathology , Systemic Inflammatory Response Syndrome/therapy
20.
J Pediatric Infect Dis Soc ; 10(5): 669-673, 2021 May 28.
Article in English | MEDLINE | ID: covidwho-1262143

ABSTRACT

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) antibody responses in children remain poorly characterized. Here, we show that pediatric patients with multisystem inflammatory syndrome in children (MIS-C) possess higher SARS-CoV-2 spike immunoglobulin G (IgG) titers compared with those with severe coronavirus disease 2019, likely reflecting a longer time since the onset of infection in MIS-C patients.


Subject(s)
Antibodies, Viral/immunology , Antibody Formation , COVID-19/immunology , Spike Glycoprotein, Coronavirus/immunology , Systemic Inflammatory Response Syndrome/immunology , COVID-19 Serological Testing , Child , Female , Humans , Immunoglobulin A/immunology , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Male , SARS-CoV-2 , Severity of Illness Index
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