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1.
J Emerg Med ; 62(1): 28-37, 2022 01.
Article in English | MEDLINE | ID: covidwho-2180429

ABSTRACT

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a newly recognized condition affecting children with recent infection or exposure to coronavirus disease 2019 (COVID-19). MIS-C has symptoms that affect multiple organs systems, with some clinical features resembling Kawasaki disease (KD) and toxic shock syndrome (TSS). OBJECTIVE OF THE REVIEW: Our goal was to review the current literature and describe the evaluation and treatment algorithms for children suspected of having MIS-C who present to the emergency department. DISCUSSION: MIS-C has a wide clinical spectrum and diagnosis is based on a combination of both clinical and laboratory findings. The exact mechanism of immune dysregulation of MIS-C is not well understood. Physical findings may evolve and do not necessarily appear at the same time. Gastrointestinal, cardiac, inflammatory, and coagulopathy manifestations and dysfunction are seen frequently in MIS-C. CONCLUSIONS: The diagnosis of MIS-C is based on clinical presentation and specific laboratory findings. In the emergency setting, a high level of suspicion for MIS-C is required in patients exposed to COVID-19. Early diagnosis and prompt initiation of therapy offer the best chance for optimal outcomes.


Subject(s)
COVID-19 , Mucocutaneous Lymph Node Syndrome , COVID-19/complications , Child , Humans , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/etiology
2.
Intern Med ; 61(16): 2527-2532, 2022 Aug 15.
Article in English | MEDLINE | ID: covidwho-1885353

ABSTRACT

We herein report a case of multisystem inflammatory syndrome in adults (MIS-A) complicated with Kikuchi-Fujimoto disease (KFD). A previously healthy 41-year-old man presented with painful swelling of the cervical lymph nodes, fever, diarrhea, conjunctivitis, edema, and hypotension one month after the onset of asymptomatic coronavirus disease 2019. Laboratory investigations revealed an elevation of CRP, and echocardiography indicated diastolic dysfunction. We diagnosed the patient to have MIS-A. Histopathology of the lymph nodes showed necrotizing lymphadenitis. After the initiation of hydrocortisone and diuretics, his symptoms resolved immediately. This case suggested that post-viral immune dysregulation in MIS-A could play a role in the etiology of KFD.


Subject(s)
COVID-19 , Connective Tissue Diseases , Histiocytic Necrotizing Lymphadenitis , Adult , COVID-19/complications , Connective Tissue Diseases/complications , Histiocytic Necrotizing Lymphadenitis/complications , Histiocytic Necrotizing Lymphadenitis/diagnosis , Humans , Lymph Nodes/pathology , Male , Systemic Inflammatory Response Syndrome/complications , Systemic Inflammatory Response Syndrome/diagnosis
3.
Intern Med J ; 52(8): 1423-1428, 2022 08.
Article in English | MEDLINE | ID: covidwho-1990262

ABSTRACT

We report two cases of middle-aged men who presented with clinical features that satisfied the diagnostic criteria for multisystem inflammatory syndrome in adults (MIS-A). Both patients were treated for toxic shock syndrome and MIS-A and have recovered. The purpose of this article is to communicate our experience and challenges of assessing and treating this condition and to raise awareness of the condition.


Subject(s)
COVID-19 , Shock, Septic , Adult , Humans , Male , Middle Aged , Shock, Septic/diagnosis , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/therapy
8.
Ann Ital Chir ; 112022 Oct 24.
Article in English | MEDLINE | ID: covidwho-2101707

ABSTRACT

AIM: As more data about coronavirus disease-2019 (COVID-19) has been gathered it has become evident that children who have had or have been exposed to COVID-19 can develop a rare complication; multisystem inflammatory syndrome in children (MIS-C). We report the case of a 9-year-old boy, who was brought to the emergency room with suspected acute abdomen and was diagnosed with MIS-C. METHODS: The patient had had a positive molecular test for COVID-19, 25 days earlier and fever that started 4 days prior to presentation, He tested negative for COVID on arrival at the emergency room. After physical examination, and diagnostic tests were performed the differential diagnosis included appendiceal inflammation and MIS-C. Surgical exploration was performed laparoscopically. RESULTS: The immune morphological picture was reactive lymphogranular hyperplasia. Postoperatively the abdominal symptoms improved rapidly but the patient developed diffuse erythema as well as some cardiovascular and neurological disturbances. The patient was discharged on postoperative day 14 in good general condition with a diagnosis of MIS-C. CONCLUSIONS: In patients with a recent positive COVID test and mainly gastroenterological manifestations surgical exploration is necessary in order to prevent delayed diagnosis and inadequate/inappropriate treatment. KEY WORDS: Acute abdomen, COVID-19, MIS-C, Gastrointestinal symptoms.


Subject(s)
Abdomen, Acute , COVID-19 , Child , Male , Humans , COVID-19/complications , Abdomen, Acute/etiology , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/etiology , Emergency Service, Hospital
9.
PLoS Pathog ; 18(11): e1010915, 2022 11.
Article in English | MEDLINE | ID: covidwho-2098780

ABSTRACT

The clinical presentation of MIS-C overlaps with other infectious/non-infectious diseases such as acute COVID-19, Kawasaki disease, acute dengue, enteric fever, and systemic lupus erythematosus. We examined the ex-vivo cellular parameters with the aim of distinguishing MIS-C from other syndromes with overlapping clinical presentations. MIS-C children differed from children with non-MIS-C conditions by having increased numbers of naïve CD8+ T cells, naïve, immature and atypical memory B cells and diminished numbers of transitional memory, stem cell memory, central and effector memory CD4+ and CD8+ T cells, classical, activated memory B and plasma cells and monocyte (intermediate and non-classical) and dendritic cell (plasmacytoid and myeloid) subsets. All of the above alterations were significantly reversed at 6-9 months post-recovery in MIS-C. Thus, MIS-C is characterized by a distinct cellular signature that distinguishes it from other syndromes with overlapping clinical presentations. Trial Registration: ClinicalTrials.gov clinicaltrial.gov. No: NCT04844242.


Subject(s)
COVID-19 , Lupus Erythematosus, Systemic , Child , Humans , CD8-Positive T-Lymphocytes , Systemic Inflammatory Response Syndrome/diagnosis
10.
Curr Allergy Asthma Rep ; 22(5): 53-60, 2022 05.
Article in English | MEDLINE | ID: covidwho-2094770

ABSTRACT

PURPOSE OF REVIEW: The novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has developed into a pandemic. A unique challenge of this pandemic has been the emergence of multisystem inflammatory syndrome in children (MIS-C), a rare post-infectious hyperinflammatory disorder associated with SARS-CoV-2. This syndrome is characterized by overwhelming systemic inflammation, fever, hypotension, and cardiac dysfunction. This disorder may also have features overlapping with Kawasaki disease (KD), macrophage activation syndrome (MAS), and toxic shock syndrome (TSS). The goal of this review is to outline the presenting features, presumed immunopathogenesis, management, and outcomes of patients with MIS-C. RECENT FINDINGS: Patients with MIS-C present with characteristics that fall within a wide clinical spectrum. Main features include fever, gastrointestinal symptoms such as abdominal pain and diarrhea, and cardiac complications such as myocarditis and coronary artery aneurysms, although various other features have been reported. Younger children may present with features of Kawasaki-like disease, and older children are often admitted to the intensive care unit with cardiogenic shock. Current treatment guidelines recommend intravenous immunoglobulins (IVIG) and glucocorticoids, with utilization of biologics in refractory cases. Fortunately, the majority of patients recover, with resolution of the systemic inflammation and cardiac abnormalities. Mortality from MIS-C is rare. This review provides an overview of the presenting features, proposed pathogenesis, suggested therapies, and outcomes of MIS-C. Clinicians must have a high clinical suspicion for this disorder in children who have had recent COVID-19 infection or exposure and present with a significant inflammatory response. Understanding of this disorder continues to evolve, and prompt diagnosis and treatment allow for the best possible outcome for patients with MIS-C.


Subject(s)
COVID-19 , Adolescent , COVID-19/complications , COVID-19/therapy , Child , Humans , Pandemics , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/complications , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/therapy
11.
Indian Pediatr ; 59(7): 563-569, 2022 07 15.
Article in English | MEDLINE | ID: covidwho-2092961

ABSTRACT

BACKGROUND: With wide clinical spectrum, multisystem inflammatory syndrome associated with coronavirus disease 2019 (COVID-19) in children (MIS-C) is a relatively novel condition occurring weeks to months' post SARS-CoV-2 infection. The aim was to systematically review data on clinical features, laboratory parameters and therapeutics of MIS-C from India. Methods: This systematic review was done as per the PRISMA guidelines, and quality assessment was done using NIH tool for case-series. A systematic search through databases yielded studies whose data was pooled to calculate the mean frequencies with standard deviation using GraphPad software. RESULTS: Screening of 2548 articles published till December, 2021, yielded 11 case-series. World Health Organization case definition was used widely. There was a slight preponderance of males (57%), median (IQR) age was 7 (6,7) years, 63% (n=305) required intensive care unit admissions, and mortality rate was 10% (n=261). Clinical features included fever, mucocutaneous features (72%), and gastrointestinal problems (62%) in majority. Widely used treatment was corticosteroids (76%) and intravenous immunoglobulin (62%) with other options depending on patient's state. An increased level of inflammatory markers and derangement in other parameters corroborated with disease status. Kawasaki disease like features, not reported in many studies, ranged from 4-76% of patients. CONCLUSION: MIS-C presents with a wide spectrum clinical features, increased inflammatory markers and managed as per the disease course and presentation. Future studies monitoring the long-term effects of MIS-C are recommended.


Subject(s)
COVID-19 , Mucocutaneous Lymph Node Syndrome , Biomarkers , COVID-19/complications , COVID-19/epidemiology , Child , Humans , Male , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/epidemiology
12.
J Korean Med Sci ; 37(41): e299, 2022 Oct 24.
Article in English | MEDLINE | ID: covidwho-2089756

ABSTRACT

Multisystem inflammatory syndrome in children and adults (MIS-C/A) was rarely reported as a complication of coronavirus disease 2019 (COVID-19) and potential adverse events following COVID-19 vaccination. Recently, the case definition of MIS-C/A was developed by the Brighton Collaboration Network. However, only a limited number of adult patients with MIS-A following immunization have been reported, and there is still little evidence for adequate treatment. A 57-year-old man presented with fever, headache, vomiting, and hypotension 24 days after receiving the second COVID-19 vaccination with the Pfizer-BioNTech vaccine. According to the Brighton Collaboration Case Definition, the patient met a definitive case of MIS-A after vaccination (level 1 of diagnostic certainty). After administration of medium-dose prednisolone (20 mg/d) with colchicine (1.2 mg/d), all symptoms and signs improved rapidly. The dose of prednisolone was gradually tapered from the third week, and the patient confirmed a full recovery without medication after 8 weeks. This is the first report showing that low-dose steroids in combination with colchicine may be an effective treatment option for MIS-A after vaccination.


Subject(s)
COVID-19 , Humans , Male , Middle Aged , Colchicine/therapeutic use , COVID-19/drug therapy , COVID-19 Vaccines/adverse effects , Prednisolone/therapeutic use , RNA, Messenger , Steroids , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/drug therapy , Systemic Inflammatory Response Syndrome/etiology , Vaccination/adverse effects
13.
PLoS One ; 17(10): e0274289, 2022.
Article in English | MEDLINE | ID: covidwho-2089402

ABSTRACT

While the majority of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) display mild or no symptoms, rare individuals develop severe disease presenting with multisystem inflammatory syndrome (MIS-C). The reason for variable clinical manifestations is not understood. Here, we carried out TCR sequencing and conducted comparative analyses of TCR repertoires between children with MIS-C (n = 12) and mild (n = 8) COVID-19. We compared these repertoires with unexposed individuals (samples collected pre-COVID-19 pandemic: n = 8) and with the Adaptive Biotechnologies MIRA dataset, which includes over 135,000 high-confidence SARS-CoV-2-specific TCRs. We show that the repertoires of children with MIS-C are characterised by the expansion of TRBV11-2 chains with high junctional and CDR3 diversity. Moreover, the CDR3 sequences of TRBV11-2 clones shift away from SARS-CoV-2 specific T cell clones, resulting in distorted TCR repertoires. In conclusion, our study reports that CDR3-independent expansion of TRBV11-2+ cells, lacking SARS-CoV-2 specificity, defines MIS-C in children.


Subject(s)
COVID-19 , Connective Tissue Diseases , Child , Humans , SARS-CoV-2 , COVID-19/genetics , Pandemics , Receptors, Antigen, T-Cell/genetics , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/genetics
15.
Medicina (Kaunas) ; 58(11)2022 Oct 24.
Article in English | MEDLINE | ID: covidwho-2081854

ABSTRACT

Multisystem Inflammatory Syndrome (MIS) is a rare but increasingly recognized complication of SARS-CoV-2 infection, usually presenting 2 to 6 weeks after the onset of COVID-19 infection symptoms and affecting mainly children. However, there have been reported several cases of a similar multisystem inflammatory syndrome in adults (MIS-A). We describe the case of a previously healthy 28-year-old male who presented with a clinical profile with multiorgan involvement within four weeks after confirmed SARS-CoV-2 infection, suggestive for multisystem inflammatory syndrome (MIS-A). The clinical presentation included persistent high grade of fever, gastrointestinal and mucocutaneous lesions, lymphadenopathy, elevated cardiac and inflammatory biomarkers, cytopenia and shock. This case report illustrates the wide range of presentations, diagnosis, and treatment modalities of multisystem inflammatory syndrome. The pathophysiology and the mechanisms by which SARS-CoV-2 triggers an abnormal immune response leading to MIS remain poorly understood. Better characterization of MIS-A and early recognition of MIS is important because it is associated with high mortality if left untreated.


Subject(s)
COVID-19 , Child , Male , Young Adult , Humans , Adult , COVID-19/complications , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/etiology
16.
Ital J Pediatr ; 47(1): 191, 2021 Sep 18.
Article in English | MEDLINE | ID: covidwho-2079518

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
18.
Clin Infect Dis ; 75(8): 1351-1358, 2022 Oct 12.
Article in English | MEDLINE | ID: covidwho-2062875

ABSTRACT

BACKGROUND: Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens in blood has high sensitivity in adults with acute coronavirus disease 2019 (COVID-19), but sensitivity in pediatric patients is unclear. Recent data suggest that persistent SARS-CoV-2 spike antigenemia may contribute to multisystem inflammatory syndrome in children (MIS-C). We quantified SARS-CoV-2 nucleocapsid (N) and spike (S) antigens in blood of pediatric patients with either acute COVID-19 or MIS-C using ultrasensitive immunoassays (Meso Scale Discovery). METHODS: Plasma was collected from inpatients (<21 years) enrolled across 15 hospitals in 15 US states. Acute COVID-19 patients (n = 36) had a range of disease severity and positive nasopharyngeal SARS-CoV-2 RT-PCR within 24 hours of blood collection. Patients with MIS-C (n = 53) met CDC criteria and tested positive for SARS-CoV-2 (RT-PCR or serology). Controls were patients pre-COVID-19 (n = 67) or within 24 hours of negative RT-PCR (n = 43). RESULTS: Specificities of N and S assays were 95-97% and 100%, respectively. In acute COVID-19 patients, N/S plasma assays had 89%/64% sensitivity; sensitivities in patients with concurrent nasopharyngeal swab cycle threshold (Ct) ≤35 were 93%/63%. Antigen concentrations ranged from 1.28-3844 pg/mL (N) and 1.65-1071 pg/mL (S) and correlated with disease severity. In MIS-C, antigens were detected in 3/53 (5.7%) samples (3 N-positive: 1.7, 1.9, 121.1 pg/mL; 1 S-positive: 2.3 pg/mL); the patient with highest N had positive nasopharyngeal RT-PCR (Ct 22.3) concurrent with blood draw. CONCLUSIONS: Ultrasensitive blood SARS-CoV-2 antigen measurement has high diagnostic yield in children with acute COVID-19. Antigens were undetectable in most MIS-C patients, suggesting that persistent antigenemia is not a common contributor to MIS-C pathogenesis.


Subject(s)
COVID-19 , Adult , Antigens, Viral , COVID-19/complications , COVID-19/diagnosis , Child , Humans , Immunoassay , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/diagnosis
19.
J Med Case Rep ; 16(1): 352, 2022 Oct 04.
Article in English | MEDLINE | ID: covidwho-2053961

ABSTRACT

BACKGROUND: As the coronavirus disease 2019 infections are still ongoing, there is an increasing number of case reports and case series with various manifestations of life-threatening multisystem inflammatory syndrome in children . Our case aims to remind all providers to scrutinize for clinical manifestations, including neurological symptoms, which may mimic aseptic meningitis. CASE PRESENTATION: A 5-year-old Albanian male child with obesity was admitted to the pediatric intensive care unit due to persistent fever, headache, vomiting, abdominal pain, mucocutaneous manifestations, and fatigue. Initial laboratory results revealed high level of inflammatory markers, including C-reactive protein of 156.8 mg/l, erythrocyte sedimentation rate of 100 mm/hour, procalcitonin of 13.84, leukocytosis with neutrophilia, and lymphopenia. Liver and renal functions, and capillary blood electrolytes (Na, K, Ca), were also altered. Cerebrospinal fluid was slightly turbid, with a white blood cell count of 128/mm3 (80% mononuclear cells and 20% polymorphonuclear), consistent with aseptic meningitis. The clinical presentation with prolonged fever, multiorgan dysfunction, and elevated inflammatory markers, with no plausible alternative diagnosis, matches the case definition of multisystem inflammatory syndrome in children. Combining corticosteroid methylprednisolone with intravenous immunoglobulin was effective. CONCLUSIONS: Apart from the most common presentation of multisystem organ dysfunction, neurological manifestations of multisystem inflammatory syndrome in children such as aseptic meningitis, may be present as an immune response post-viral to coronavirus disease 2019. Given the rapid deterioration of children with multisystem inflammatory syndrome, early treatment with immunoglobulins and corticosteroids should be considered.


Subject(s)
COVID-19 , Connective Tissue Diseases , Meningitis, Aseptic , C-Reactive Protein/analysis , COVID-19/complications , Child , Child, Preschool , Humans , Immunoglobulins, Intravenous/therapeutic use , Male , Meningitis, Aseptic/diagnosis , Meningitis, Aseptic/etiology , Methylprednisolone , Procalcitonin , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/complications , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/drug therapy
20.
Int J Immunopathol Pharmacol ; 36: 3946320221131981, 2022.
Article in English | MEDLINE | ID: covidwho-2053630

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection may present with some systemic lupus erythematosus (SLE) manifestations intermingled with Kawasaki disease features. These emerging presentations were dubbed under the umbrella term 'multisystem inflammatory syndrome in children (MIS-C)'. A one and half-year-old girl, admitted to Mansoura University Children's Hospital (MUCH) with fever, bad general condition, vomiting, widespread maculopapular, vasculitic rash, hands and feet oedema, oral ulceration, arthralgia and lymphadenopathy. Moreover, bicytopenia, positive antinuclear, anti-double-stranded DNA antibodies and low C3 qualified her as a case of juvenile SLE. Despite the child received the initial therapy of immunosuppressive medication, her general condition deteriorated with fever persistence and rash exacerbation. At that time, the skin of her hands and feet started to peel. Thus, an expanded study for other alternatives was obligatory; SARS-CoV-2 infection testing revealed positive IgG serology, and retesting for lupus autoantibodies turned negative. HRCT chest showed bilateral basal consolidation with ground-glass appearance. Furthermore, Echo exhibited coronary artery dilation with thrombus inside. This evolution raised the concern for COVID-related MIS-C syndrome. This report provides a model of COVID-19 heterogeneity with protean immune-related manifestations. This case has a unique presentation that necessities its description, in order to provide a nidus for future studies in this new entity.


Subject(s)
COVID-19 , Exanthema , Lupus Erythematosus, Systemic , Antibodies, Viral , Autoantibodies , COVID-19/complications , COVID-19/diagnosis , Child , DNA , Exanthema/etiology , Female , Fever , Humans , Immunoglobulin G , Infant , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/diagnosis , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/diagnosis
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