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1.
Pediatrics ; 149(1)2022 01 01.
Article in English | MEDLINE | ID: covidwho-1595609

ABSTRACT

A 9-year-old girl presented to her primary care pediatrician via telemedicine during the initial months of the coronavirus disease 2019 pandemic because of 4 days of warmth perceived by her mother, decreased energy, and a new rash on her upper extremities. After 10 additional days of documented fever >38°C, worsening fatigue, and 1 day of nausea, vomiting, and diarrhea, she was allowed to schedule an in-person visit with her pediatrician after testing negative for severe acute respiratory syndrome coronavirus 2. She appeared ill on arrival to clinic, and her pediatrician recommended evaluation in an emergency department. Her initial laboratory testing revealed nonspecific elevation in several inflammatory markers and leukopenia, and she responded well to intravenous hydration. Over the next 2 weeks, her fever persisted, constitutional symptoms worsened, and she developed progressively painful cervical lymphadenopathy and pancytopenia. She was evaluated in clinic by several specialists and eventually was urged to present to the emergency department again, at which time she was admitted to the PICU. After consulting additional specialists and waiting for laboratory results, the team reached a definitive diagnosis and initiated therapy; however, she experienced rapid clinical decline shortly thereafter. The specialists who assisted with identification of the underlying etiology of her symptoms were able to work together to manage the subsequent complications.


Subject(s)
Exanthema , Fever , Intensive Care Units, Pediatric , Lupus Erythematosus, Systemic/diagnosis , Telemedicine , COVID-19/complications , COVID-19/diagnosis , Child , Disease Progression , Exanthema/diagnosis , Exanthema/etiology , Female , Fever/etiology , Histiocytic Necrotizing Lymphadenitis/diagnosis , Humans , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/complications , Lymphadenopathy/diagnosis , Lymphadenopathy/etiology , Pancytopenia/diagnosis , Symptom Assessment , Systemic Inflammatory Response Syndrome/diagnosis
3.
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
4.
Front Immunol ; 12: 723654, 2021.
Article in English | MEDLINE | ID: covidwho-1504010

ABSTRACT

With the appearance of the SARS-CoV-2 virus in December 2019, all countries in the world have implemented different strategies to prevent its spread and to intensively search for effective treatments. Initially, severe cases of the disease were considered in adult patients; however, cases of older school-age children and adolescents who presented fever, hypotension, severe abdominal pain and cardiac dysfunction, positive for SARS-CoV-2 infection, have been reported, with increased pro-inflammatory cytokines and tissue damage, condition denominated multisystemic inflammatory syndrome (MIS-C); The emerging data from patients with MIS-C have suggested unique characteristics in the immunological response and also clinical similarities with other inflammatory syndromes, which can support as a reference in the search for molecular mechanisms involved in MIS-C. We here in propose that oxidative stress (OE) may play a very important role in the pathophysiology of MIS-C, such as occurs in Kawasaki disease (KD), severe COVID-19 in adults and other processes with characteristics of vascular damage similar to MIS- C, for which we review the available information that can be correlated with possible redox mechanisms.


Subject(s)
COVID-19/complications , Oxidative Stress , SARS-CoV-2/pathogenicity , Systemic Inflammatory Response Syndrome/physiopathology , Adolescent , COVID-19/diagnosis , COVID-19/immunology , COVID-19/physiopathology , Child , Cytokines/immunology , Humans , Inflammation , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/immunology
5.
Front Immunol ; 12: 738073, 2021.
Article in English | MEDLINE | ID: covidwho-1497076

ABSTRACT

The mechanisms underlying the immune remodeling and severity response in coronavirus disease 2019 (COVID-19) are yet to be fully elucidated. Our comprehensive integrative analyses of single-cell RNA sequencing (scRNAseq) data from four published studies, in patients with mild/moderate and severe infections, indicate a robust expansion and mobilization of the innate immune response and highlight mechanisms by which low-density neutrophils and megakaryocytes play a crucial role in the cross talk between lymphoid and myeloid lineages. We also document a marked reduction of several lymphoid cell types, particularly natural killer cells, mucosal-associated invariant T (MAIT) cells, and gamma-delta T (γδT) cells, and a robust expansion and extensive heterogeneity within plasmablasts, especially in severe COVID-19 patients. We confirm the changes in cellular abundances for certain immune cell types within a new patient cohort. While the cellular heterogeneity in COVID-19 extends across cells in both lineages, we consistently observe certain subsets respond more potently to interferon type I (IFN-I) and display increased cellular abundances across the spectrum of severity, as compared with healthy subjects. However, we identify these expanded subsets to have a more muted response to IFN-I within severe disease compared to non-severe disease. Our analyses further highlight an increased aggregation potential of the myeloid subsets, particularly monocytes, in COVID-19. Finally, we provide detailed mechanistic insights into the interaction between lymphoid and myeloid lineages, which contributes to the multisystemic phenotype of COVID-19, distinguishing severe from non-severe responses.


Subject(s)
COVID-19/immunology , Killer Cells, Natural/immunology , Mucosal-Associated Invariant T Cells/immunology , Neutrophils/immunology , SARS-CoV-2/physiology , Systemic Inflammatory Response Syndrome/immunology , T-Lymphocytes/immunology , COVID-19/diagnosis , Cell Differentiation , Cell Proliferation , Humans , Immunity, Innate , Interferon Type I/metabolism , Lymphopoiesis , Receptors, Antigen, T-Cell, gamma-delta/metabolism , Sequence Analysis, RNA , Single-Cell Analysis , Systemic Inflammatory Response Syndrome/diagnosis , T-Lymphocytes/metabolism , Thrombopoiesis
6.
Clin Dermatol ; 39(2): 329-333, 2021.
Article in English | MEDLINE | ID: covidwho-1491848

ABSTRACT

Multisystem inflammatory syndrome in children (MIS-C) affects a small percentage of pediatric patients infected with COVID-19 and is characterized by fever, laboratory evidence of inflammation, multisystem involvement, and severe illness necessitating hospitalization. Skin findings are often present in these patients, and when initially compared with Kawasaki disease, they likely represent distinct phenomena and overall remain poorly characterized. In this retrospective review of 34 case reports and series, we identified cutaneous manifestations documented in 417 of 736 patients (57%) with MIS-C associated with COVID-19. "Rash" was the sole descriptor of skin findings in nearly half of patients. Case reports and smaller case series provided more detail, outlining a broad range of lesion morphologies (polymorphic, maculopapular, morbilliform, erythrodermic, urticarial, reticular, petechial, purpuric) in variable anatomic distribution. More thorough descriptions of dermatologic manifestations in patients with MIS-C are warranted to better characterize this syndrome, as they may lend important insight into pathogenic mechanisms of disease.


Subject(s)
COVID-19/complications , Skin Diseases/etiology , Systemic Inflammatory Response Syndrome/complications , COVID-19/diagnosis , Child , Humans , Retrospective Studies , Systemic Inflammatory Response Syndrome/diagnosis
7.
BMC Cardiovasc Disord ; 21(1): 522, 2021 10 29.
Article in English | MEDLINE | ID: covidwho-1486551

ABSTRACT

BACKGROUND: With the high prevalence of COVID-19 infections worldwide, the multisystem inflammatory syndrome in adults (MIS-A) is becoming an increasingly recognized entity. This syndrome presents in patients several weeks after infection with COVID-19 and is associated with thrombosis, elevated inflammatory markers, hemodynamic compromise and cardiac dysfunction. Treatment is often with steroids and intravenous immunoglobulin (IVIg). The pathologic basis of myocardial injury in MIS-A, however, is not well characterized. In our case report, we obtained endomyocardial biopsy that revealed a pattern of myocardial injury similar to that found in COVID-19 cardiac specimens. CASE PRESENTATION: A 26-year-old male presented with fevers, chills, headache, nausea, vomiting, and diarrhea 5 weeks after his COVID-19 infection. His SARS-CoV-2 PCR was negative and IgG was positive, consistent with prior infection. He was found to be in cardiogenic shock with biventricular failure, requiring inotropes and diuretics. Given concern for acute fulminant myocarditis, an endomyocardial biopsy (EMB) was performed, showing an inflammatory infiltrate consisting predominantly of interstitial macrophages with scant T lymphocytes. The histologic pattern was similar to that of cardiac specimens from COVID-19 patients, helping rule out myocarditis as the prevailing diagnosis. His case was complicated by persistent hypoxemia, and a computed tomography scan revealed pulmonary emboli. He received IVIg, steroids, and anticoagulation with rapid recovery of biventricular function. CONCLUSIONS: MIS-A should be considered as the diagnosis in patients presenting several weeks after COVID-19 infection with severe inflammation and multi-organ involvement. In our case, EMB facilitated identification of MIS-A and guided therapy. The patient's biventricular function recovered with IVIg and steroids.


Subject(s)
Anticoagulants/administration & dosage , COVID-19 , Myocarditis/diagnosis , Shock, Cardiogenic , Systemic Inflammatory Response Syndrome , Adult , Biopsy/methods , COVID-19/complications , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/immunology , COVID-19/physiopathology , Cardiotonic Agents/administration & dosage , Diagnosis, Differential , Diuretics/administration & dosage , Electrocardiography/methods , Humans , Immunoglobulins, Intravenous/administration & dosage , Male , Myocardium/pathology , Radiography, Thoracic/methods , SARS-CoV-2 , Shock, Cardiogenic/diagnosis , Shock, Cardiogenic/drug therapy , Shock, Cardiogenic/etiology , Shock, Cardiogenic/physiopathology , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/drug therapy , Systemic Inflammatory Response Syndrome/physiopathology , Treatment Outcome
8.
Viruses ; 13(10)2021 10 07.
Article in English | MEDLINE | ID: covidwho-1463839

ABSTRACT

SARS-CoV-2 infection in children can trigger cardiovascular manifestations potentially requiring an intensive treatment and defining a new entity named Multisystem Inflammatory Syndrome in Children (MIS-C), whose features partially overlap with Kawasaki Disease (KD). A cross-sectional study including all diagnoses of MIS-C and KD from April 2020 to May 2021 in our metropolitan area was conducted evaluating clinical, laboratory (including immunological response, cytokines, and markers of myocardial damage), and cardiac (coronary and non-coronary) features at onset of the diseases. Evolution of ventricular dysfunction, valve regurgitations, and coronary lesions was documented. The severity of the disease was also considered based on the need for inotropic support and ICU admission. Twenty-four MIS-C were diagnosed (14 boys, median age 82 months): 13/24 cases (54.17%) presented left ventricular dysfunction, 12/24 (50%) required inotropic support, and 10/24 (41.67%) developed coronary anomalies (CALs). All patients received steroids and IVIG at a median time of 5 days (IQR1:4, IQR3:6.5) from onset of fever and heart function normalized 6 days (IQR1: 5, IQR3: 7) after therapy, while CALs persisted in one. One patient (12.5%) required infliximab because of refractory disease and still presented CALs 18 days after therapy. During the same study period, 15 KD were diagnosed: none had ventricular dysfunction, while 7/15 (46.67%) developed CALs. Three out of 15 patients (20%) still presented CALs 46 days from onset. Compared to KD, MIS-C pts have significantly higher IL8 and similar lymphocytes subpopulations. Despite a more severe presentation and initial cardiac findings compared to KD, the myocardial injury in MIS-C has a rapid response to immunomodulatory treatment (median time 6 days), in terms of ventricular function, valve regurgitations, and troponin. Incidence of CALs is similar at onset, but it tends to regress in most of the cases of MIS-C differently than in KD where CALs persist in up to 40% in the subacute stage after treatment.


Subject(s)
COVID-19/complications , COVID-19/pathology , Mucocutaneous Lymph Node Syndrome/pathology , Myocardium/pathology , Systemic Inflammatory Response Syndrome/pathology , Ventricular Dysfunction, Left/pathology , Adolescent , COVID-19/diagnosis , COVID-19/epidemiology , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Infant , Infant, Newborn , Interleukin-10/blood , Interleukin-8/blood , Italy/epidemiology , Male , Mucocutaneous Lymph Node Syndrome/diagnosis , Prospective Studies , SARS-CoV-2/metabolism , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/epidemiology , Ventricular Dysfunction, Left/virology
9.
Nat Immunol ; 22(11): 1452-1464, 2021 11.
Article in English | MEDLINE | ID: covidwho-1454797

ABSTRACT

There is limited understanding of the viral antibody fingerprint following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children. Herein, SARS-CoV-2 proteome-wide immunoprofiling of children with mild/moderate or severe coronavirus disease 2019 (COVID-19) versus multisystem inflammatory syndrome in children versus hospitalized control patients revealed differential cytokine responses, IgM/IgG/IgA epitope diversity, antibody binding and avidity. Apart from spike and nucleocapsid, IgG/IgA recognized epitopes in nonstructural protein (NSP) 2, NSP3, NSP12-NSP14 and open reading frame (ORF) 3a-ORF9. Peptides representing epitopes in NSP12, ORF3a and ORF8 demonstrated SARS-CoV-2 serodiagnosis. Antibody-binding kinetics with 24 SARS-CoV-2 proteins revealed antibody parameters that distinguish children with mild/moderate versus severe COVID-19 or multisystem inflammatory syndrome in children. Antibody avidity to prefusion spike correlated with decreased illness severity and served as a clinical disease indicator. The fusion peptide and heptad repeat 2 region induced SARS-CoV-2-neutralizing antibodies in rabbits. Thus, we identified SARS-CoV-2 antibody signatures in children associated with disease severity and delineate promising serodiagnostic and virus neutralization targets. These findings might guide the design of serodiagnostic assays, prognostic algorithms, therapeutics and vaccines in this important but understudied population.


Subject(s)
COVID-19 Serological Testing/methods , COVID-19/complications , COVID-19/immunology , SARS-CoV-2/immunology , Systemic Inflammatory Response Syndrome/immunology , Adolescent , Antibodies, Neutralizing/metabolism , Antibodies, Viral/metabolism , COVID-19/diagnosis , Child , Child, Preschool , Disease Progression , Epitopes/metabolism , Female , Hospitalization , Humans , Immunity, Humoral , Immunoglobulin A/metabolism , Immunoglobulin G/metabolism , Immunoglobulin M/metabolism , Male , Prognosis , Proteome , Severity of Illness Index , Systemic Inflammatory Response Syndrome/diagnosis
10.
BMJ Case Rep ; 14(10)2021 Oct 01.
Article in English | MEDLINE | ID: covidwho-1447983

ABSTRACT

Multisystem inflammatory syndrome in adults (MIS-A) is an uncommon and under-recognised postinfectious manifestation that presents 4-6 weeks after COVID-19 infection. Patients affected tend to be young or middle-aged, from ethnic minority backgrounds and previously healthy. In addition to high fever and myalgia, there are a myriad of extrapulmonary symptoms and signs, including cardiac, gastrointestinal, neurological and dermatological involvement. Cardiovascular shock and markedly raised inflammatory markers are prominent features, while significant hypoxia is uncommon. Patients respond well to corticosteroid therapy, but failure of clinicians to recognise this recently identified phenomenon, which can mimic common conditions including sepsis, could delay diagnosis and treatment. Here we present a case of MIS-A in an adult woman, compare her presentation and management with other similar case reports, and reflect on how clinicians can learn from our experiences.


Subject(s)
COVID-19 , Adult , Female , Humans , Middle Aged , Minority Groups , SARS-CoV-2 , Syndrome , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/etiology
11.
Ital J Pediatr ; 47(1): 191, 2021 Sep 18.
Article in English | MEDLINE | ID: covidwho-1413462

ABSTRACT

BACKGROUND: Presently, it is known that, even if less frequently than in adults, children can develop a severe new coronavirus disease 2019 (COVID-19). Children with the SARS-CoV-2 infection can have neurological signs and symptoms of disease more frequently than previously thought, revealing the involvement of the central nervous system, the peripheral nervous system, or both. Aim of this manuscript is to highlight the neurologic complications associated with SARS-CoV-2 among pediatric patients with COVID-19, suggesting when to monitor carefully neurologic development. MAIN FINDINGS: Children with a severe chronic underlying disease, infants and toddlers and those who develop the so-called multisystem inflammatory syndrome (MIS-C) are those with the highest incidence of neurological complications. Fortunately, in most of the cases, neurological manifestations, mainly represented by headache and anosmia, are mild and transient and do not significantly complicate the COVID-19 course. However, in some cases, very severe clinical problems associated with relevant alterations of neuroimaging, electroencephalography, nerve conduction studies and electromyography findings can develop. Generally, almost all the children with COVID-19 and neurological manifestations till now described have made a complete recovery, although in some cases this has occurred after several weeks of treatment. Moreover, COVID-19 infection during pregnancy has been found associated with an increased risk of obstetric complications that can lead to neurological acute and long-term manifestations in neonates. CONCLUSIONS: Based on data showing the neurologic impact of COVID-19 in pediatric age, we suggest monitoring neurological development a few months after healing in pediatric patients who have presented MIS-C, seizures or other neurological manifestations and in children of pregnant women with COVID-19 in order to detect overt and subtle deficits.


Subject(s)
COVID-19/complications , Nervous System Diseases/virology , Pregnancy Complications, Infectious/virology , Systemic Inflammatory Response Syndrome/virology , COVID-19/diagnosis , COVID-19/virology , Child , Child, Preschool , Comorbidity , Female , Humans , Infant , Infant, Newborn , Male , Nervous System Diseases/diagnosis , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Risk Factors , SARS-CoV-2 , Seizures/virology , Systemic Inflammatory Response Syndrome/diagnosis
12.
Sci Rep ; 11(1): 13840, 2021 07 05.
Article in English | MEDLINE | ID: covidwho-1383121

ABSTRACT

To characterize the new SARS-Co-V-2 related multisystem inflammatory syndrome in children (MIS-C) among Israeli children and to compare it with Kawasaki disease (KD). We compared, in two medical centers, the clinical and laboratory characteristics of MIS-C, KD and an intermediate group, which met the case definitions of both conditions. MIS-C patients were older, were more likely to be hypotensive, to have significant gastrointestinal symptoms, lymphopenia and thrombocytopenia and to have non-coronary abnormal findings in their echocardiogram. Lymphopenia was an independent predictor of MIS-C. Most of our MIS-C patients responded promptly to corticosteroid therapy. KD incidence in both centers was similar in 2019 and 2020. Although there is clinical overlap between KD and MIS-C, these are separate entities. Lymphopenia clearly differentiates between these entities. MIS-C patients may benefit from corticosteroids as first-line therapy.


Subject(s)
COVID-19/complications , COVID-19/pathology , Lymphopenia/pathology , Mucocutaneous Lymph Node Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/diagnosis , Adolescent , Adrenal Cortex Hormones/therapeutic use , Adult , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/virology , Child , Child, Preschool , Diagnosis, Differential , Female , Humans , Lymphopenia/diagnosis , Male , Mucocutaneous Lymph Node Syndrome/drug therapy , Mucocutaneous Lymph Node Syndrome/pathology , Mucocutaneous Lymph Node Syndrome/virology , Risk Factors , SARS-CoV-2/pathogenicity , Systemic Inflammatory Response Syndrome/drug therapy , Systemic Inflammatory Response Syndrome/pathology , Systemic Inflammatory Response Syndrome/virology , Young Adult
13.
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
14.
Semin Pediatr Neurol ; 40: 100922, 2021 12.
Article in English | MEDLINE | ID: covidwho-1386629

ABSTRACT

Primary intracranial hypertension (PIH) is characterized by clinical signs of increased intracranial pressure, papilledema, elevated opening pressure, and absence of mass lesion, hydrocephalus, or meningeal enhancement on neuroimaging. Visual changes are a common presenting feature and if untreated there is risk of irreversible vision loss. There have been recent proposed changes to the criteria for PIH along with studies looking at the differences in imaging characteristics between adult and pediatric PIH. The presence of transverse sinus stenosis alone was highly sensitive and specific for pediatric PIH. The Idiopathic Intracranial Hypertension Treatment Trial was an adult, multicenter study that examined the use of acetazolamide and weight loss on the course of PIH. The study confirmed many previously held beliefs including the most common presenting symptom in PIH is headache. Most patients present with bilateral papilledema with 58.2% of patients having symmetric Frisen scale grading and within one grade in 92.8%. Although diplopia is a common reported symptom, very few have evidence of cranial nerve palsy. Male gender, high-grade papilledema, and decreased visual acuity at presentation are risk factors for treatment failure. Acetazolamide use is associated with mild metabolic acidosis. During acetazolamide treatment, monitoring for hypokalemia or aplastic anemia is not recommended. Monitoring transaminases in the titration phase of treatment should be considered due to a case of transaminitis and pancreatitis with elevated lipase. Newer case reports have also seen associations of secondary intracranial hypertension with concurrent COVID-19 infection and MIS-C.


Subject(s)
Acetazolamide/administration & dosage , COVID-19/diagnosis , Carbonic Anhydrase Inhibitors/administration & dosage , Headache/diagnosis , Intracranial Hypertension , Papilledema/diagnosis , Vision Disorders/diagnosis , Weight Loss , Acetazolamide/adverse effects , Adolescent , Adult , COVID-19/complications , Carbonic Anhydrase Inhibitors/adverse effects , Child , Combined Modality Therapy , Diagnosis, Differential , Female , Headache/etiology , Humans , Intracranial Hypertension/complications , Intracranial Hypertension/diagnosis , Intracranial Hypertension/therapy , Magnetic Resonance Imaging , Male , Middle Aged , Multicenter Studies as Topic , Papilledema/etiology , Pseudotumor Cerebri/complications , Pseudotumor Cerebri/diagnosis , Pseudotumor Cerebri/etiology , Pseudotumor Cerebri/therapy , Randomized Controlled Trials as Topic , Systemic Inflammatory Response Syndrome/complications , Systemic Inflammatory Response Syndrome/diagnosis , Tomography, Optical Coherence , Vision Disorders/etiology , Young Adult
16.
Eur J Pediatr ; 180(5): 1581-1591, 2021 May.
Article in English | MEDLINE | ID: covidwho-1384440

ABSTRACT

This study was conducted to assess the clinical spectrum, management, and outcome of SARS-CoV-2-related multisystem inflammatory syndrome in children (MIS-C). We reviewed medical records of children with MIS-C diagnosis seen at the Children's Hospital of Michigan in Detroit between April and June 2020. Thirty-three children were identified including 22 who required critical care (group 1) and 11 with less intense inflammation (group 2). Children in group 1 were older (median 7.0 years) than those in group 2 (median 2.0 years). Abdominal pain was present in 68% of patients in group 1. Hypotension or shock was present in 17/22 patients in group 1. Thirteen (39.4%) had Kawasaki disease (KD)-like manifestations. Five developed coronary artery dilatation; All resolved on follow-up. Intravenous immunoglobulin (IVIG) was given to all patients in group 1 and 7/11 in group 2. Second-line therapy was needed in 13/22 (group 1) for persisting inflammation or myocardial dysfunction; 12 received infliximab. All patients recovered.Conclusion: MIS-C clinical manifestations may overlap with KD; however, MIS-C is likely a distinct inflammatory process characterized by reversible myocardial dysfunction and rarely coronary artery dilatation. Supportive care, IVIG, and second-line therapy with infliximab were associated with a favorable outcome. What is Known: • Multisystem inflammatory syndrome in children (MIS-C) manifestations include fever, gastrointestinal symptoms, shock, and occasional features of Kawasaki disease (KD). • Treatment includes immunomodulatory agents, most commonly IVIG and corticosteroids. What is New: • Spectrum of MIS-C varies from mild to severe inflammation and coronary artery dilatation occurred in 5/22 (23%) critically ill patients. • IVIG and infliximab therapy were associated with a favorable outcome including resolution of coronary dilatation; only 2/33 received corticosteroids.


Subject(s)
COVID-19/drug therapy , Infliximab/therapeutic use , Systemic Inflammatory Response Syndrome/drug therapy , Adolescent , COVID-19/diagnosis , Child , Child, Preschool , Female , Humans , Infant , Male , Mucocutaneous Lymph Node Syndrome/diagnosis , Mucocutaneous Lymph Node Syndrome/drug therapy , Systemic Inflammatory Response Syndrome/diagnosis
18.
J Crohns Colitis ; 15(4): 687-691, 2021 Apr 06.
Article in English | MEDLINE | ID: covidwho-1387845

ABSTRACT

Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 [PIMS-TS] is a newly described condition. It has a spectrum of presentations proposed to occur as part of a post-infectious immune response. We report the first case of PIMS-TS in a child on established anti-tumour necrosis factor alpha [anti-TNFα] therapy; a 10 year-old girl with ulcerative colitis treated with infliximab. The patient had 6 weeks of daily fever with mucocutaneous, gastrointestinal, renal, and haematological involvement. Biomarkers of hyperinflammation were present including: hyperferritinaemia [up to 691 µ/L; normal 15-80 µg/L], C-reactive protein [CRP] [ >100mg/L for  >10 days, normal 0-5 mg/L], erythrocyte sedimentation rate [ESR] consistently  >100mm/h [normal 0-15 mm/h], raised white cell count with neutrophilia, elevated D-dimer and lactate dehydrogenase [LDH], anaemia and Mott cells on bone marrow analysis. Extensive investigations for alternative diagnoses for pyrexia of unknown origin [PUO] were negative. The condition was refractory to treatment with intravenous immunoglobulin [IVIG] but improved within 24 h of high-dose methylprednisolone. Infliximab treatment followed and the patient has remained well at follow-up. Polymerase chain reaction [PCR] and serology for SARS-CoV-2 were negative. Current series report such negative findings in up to half of cases. The patient experienced a milder clinical phenotype without cardiac involvement, shock, or organ failure. Accepting the wide spectrum of PIMS-TS presentations, it is possible that previous anti-TNFα therapy may have attenuated the disease course. Given the uncertainty around therapeutic strategies for PIMS-TS, this case supports the need for further investigation into continuing infliximab as a treatment option for the condition.


Subject(s)
COVID-19/diagnosis , Colitis, Ulcerative/drug therapy , Gastrointestinal Agents/therapeutic use , Infliximab/therapeutic use , Systemic Inflammatory Response Syndrome/diagnosis , COVID-19/complications , COVID-19/therapy , Child , Colitis, Ulcerative/complications , Female , Humans , Systemic Inflammatory Response Syndrome/complications , Systemic Inflammatory Response Syndrome/therapy
19.
MMWR Morb Mortal Wkly Rep ; 69(40): 1450-1456, 2020 Oct 09.
Article in English | MEDLINE | ID: covidwho-1389856

ABSTRACT

During the course of the coronavirus disease 2019 (COVID-19) pandemic, reports of a new multisystem inflammatory syndrome in children (MIS-C) have been increasing in Europe and the United States (1-3). Clinical features in children have varied but predominantly include shock, cardiac dysfunction, abdominal pain, and elevated inflammatory markers, including C-reactive protein (CRP), ferritin, D-dimer, and interleukin-6 (1). Since June 2020, several case reports have described a similar syndrome in adults; this review describes in detail nine patients reported to CDC, seven from published case reports, and summarizes the findings in 11 patients described in three case series in peer-reviewed journals (4-6). These 27 patients had cardiovascular, gastrointestinal, dermatologic, and neurologic symptoms without severe respiratory illness and concurrently received positive test results for SARS-CoV-2, the virus that causes COVID-19, by polymerase chain reaction (PCR) or antibody assays indicating recent infection. Reports of these patients highlight the recognition of an illness referred to here as multisystem inflammatory syndrome in adults (MIS-A), the heterogeneity of clinical signs and symptoms, and the role for antibody testing in identifying similar cases among adults. Clinicians and health departments should consider MIS-A in adults with compatible signs and symptoms. These patients might not have positive SARS-CoV-2 PCR or antigen test results, and antibody testing might be needed to confirm previous SARS-CoV-2 infection. Because of the temporal association between MIS-A and SARS-CoV-2 infections, interventions that prevent COVID-19 might prevent MIS-A. Further research is needed to understand the pathogenesis and long-term effects of this newly described condition.


Subject(s)
Coronavirus Infections/complications , Pneumonia, Viral/complications , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/virology , Adult , COVID-19 , Coronavirus Infections/epidemiology , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , United Kingdom/epidemiology , United States/epidemiology , Young Adult
20.
J Pediatric Infect Dis Soc ; 9(6): 781-784, 2020 Dec 31.
Article in English | MEDLINE | ID: covidwho-1387931

ABSTRACT

We describe an 8-week-old infant with severe gastrointestinal symptoms, significant hypoalbuminemia, and mild carditis following asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infant's symptoms, including their temporal appearance, were consistent with multisystem inflammatory syndrome in children (MIS-C). A unique finding on colonic histology which may shed light on the pathogenesis of MIS-C was identified. The patient improved significantly following several anti-inflammatory treatments. The lag between the presentation of MIS-C and initial SARS-CoV-2 exposure, which may often be asymptomatic, together with the young age of our patient, makes this a challenging diagnosis. Clinicians should be aware of this entity, even in the neonatal and infantile age groups, to facilitate timely identification and treatment.


Subject(s)
COVID-19/diagnosis , Systemic Inflammatory Response Syndrome/diagnosis , COVID-19/pathology , COVID-19/therapy , Colon/pathology , Female , Gastrointestinal Tract/pathology , Humans , Infant , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/pathology , Systemic Inflammatory Response Syndrome/therapy
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