Multi-Inflammatory Syndrome in Children: A View into Immune Pathogenesis from a Laboratory Perspective

Abstract Background Multi-inflammatory syndrome in children (MIS-C) is a novel and rare inflammatory disorder associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in school-age children. Reports in the past year have suggested a multi-system pathophysiology characterized by hyperinflammation, gastrointestinal distress, and cardiovascular complications. Clinical laboratory investigations, including routine blood testing for inflammatory (e.g., CRP, ferritin) and cardiac (e.g., troponin, brain natriuretic peptides) markers have provided insight into potential drivers of disease pathogenesis, highlighting the role of the laboratory in the differential diagnosis of patients presenting with similar conditions (e.g., Kawasaki Disease, Macrophage Activating Syndrome). Content While few studies have applied high-dimensional immune profiling to further characterize underlying MIS-C pathophysiology, much remains unknown regarding predisposing risk factors, etiology, and long-term impact of disease onset. The extent of autoimmune involvement is also unclear. In the current review, we summarize and critically evaluate available literature on potential pathogenic mechanisms underlying MIS-C onset and discuss the current and anticipated value of various laboratory testing paradigms in MIS-C diagnosis and monitoring. Summary From initial reports, it is clear that MIS-C has unique inflammatory signatures involving both adaptive and innate systems. Certain cytokines, inflammatory markers, and cardiac markers assist in the differentiation of MIS-C from other hyperinflammatory conditions. However, there are still major gaps in our understanding of MIS-C pathogenesis, including T cell, B cell, and innate response. It is essential that researchers not only continue to decipher initial pathogenesis but also monitor long-term health outcomes, particularly given observed presence of circulating autoantibodies with unknown impact.

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Sinus bradycardia as the initial manifestation of multisystem inflammatory syndrome in children

European Heart Journal ◽

10.1093/eurheartj/ehab724.0412 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

K Gonzalez ◽

I Mendoza Britto ◽

M Mateu ◽

E Marcano ◽

J De Izaguirre ◽

...

Keyword(s):

Clinical Laboratory ◽

Sinus Bradycardia ◽

Case Series ◽

Intravenous Immunoglobulins ◽

Cardiovascular Complications ◽

Laboratory Evaluation ◽

Initial Manifestation ◽

Funding Sources ◽

Coronary Abnormalities ◽

Inflammatory Syndrome

Abstract Background While cardiovascular complications, including arrhythmias are now a recognized manifestation of Multisystem inflammatory syndrome in children (MIS-C), there are no reports of primary bradycardia preceding the clinical presentation. We sought to describe a case series of sinus bradycardia as an initial manifestation of MIS-C. Methods We included a series of 10 consecutive patients with confirmed COVID-19 who met WHO and CDC criteria for MIS-C, who developed sinus bradycardia with a heart rate measured in the awake state that was below the normal range for age for children, as an initial manifestation of the disease, in a prospective observational multicenter study. Patients underwent clinical, laboratory evaluation, ECG, Holter, telemetry, echocardiogram, chest X Ray, and a chest CT scan. Results Of the 10 patients included, 6 were male, with a mean age of 6.52±5.35 years, range 4 months to 14 years. All cases were Hispanic. Bradycardia was transient and did not merit treatment. Coronary abnormalities were noted in 6 cases; 4 patients had mild coronary ectasia; 9 patients had pericardial effusion with no evidence of tamponade. All patients had a mild clinical course; none had shock, heart failure, the need for mechanical ventilation, or died. All blood markers (Troponin, BNP, Platelet count, C-reactive protein, D-dimer, Ferritin) returned to normal levels by discharge/follow-up with a favorable outcome including resolution of coronary dilatation in all but 2 in which aneurysm persisted. Treatment All patients received steroids and low-weight-molecular heparin 10 patients, 8 aspirin and 8 intravenous immunoglobulins. Conclusion Sinus bradycardia may be the initial manifestation of MIS-C, usually transient and mild. Physicians should be aware of this presentation. FUNDunding Acknowledgement Type of funding sources: None. Kid, MIS-C. Bradycardia/Atrial Rhythm

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Abstract 15069: Long Term Heart Failure Risk in Zika Myocarditis

Circulation ◽

10.1161/circ.142.suppl_3.15069 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

ivan mendoza ◽

Karina Gonzalez ◽

Jose I Medina ◽

Igor Morr ◽

Yolimar Meza ◽

...

Keyword(s):

Heart Failure ◽

Acute Phase ◽

Clinical Laboratory ◽

Acute Myocarditis ◽

Disease Onset ◽

Cardiac Resynchronization ◽

Laboratory Evaluation ◽

Cardiac Complications

Introduction: It has been estimated that up to a billion people worldwide could be exposed to Zika re-emergence including North America. Zika was considered the worst outbreak of the century before COVID-19. There are only few reports of cardiac complications and the long-term risk of heart failure (HF) is unknown. This is the objective of this study. Methods: We included 19 patients who developed acute myocarditis within one week of symptomatic Zika, in a prospective observational multi-center study. Patients underwent clinical, laboratory evaluation including Zika confirmation, ECG, echocardiogram, Holter, cardiac MRI, coronary arteriography (2). Patient follow-up examinations were performed at 2, 6,12, 24, 36 and 48 months. Results: Of the 19 patients, 12 (63%) were female with a mean age of 49 ± 17 years with a median follow-up of 3 years. Nine patients (47%) developed acute HF; 8 (42%) with reduced ejection fraction (HFrEF) and one with preserved EF (HFrEF) and moderate to severe pericardial effusion. Two cases died suddenly in the first week of Zika onset, both with HFrEF. Treatment included sacubitril /valsartan, or ace-inhibitors, SGLT2 inhibitors, beta-blockers, aldosterone-blockers, cardiovascular rehabilitation, and in one case cardiac resynchronization therapy plus implanted defibrillator. There was no new HF onset after the acute phase of the disease. Myocarditis resolved in 10 (56%) patients. Persistent atrial and ventricular arrhythmia with normal EF observed in 5 (26%) of cases. Altogether, characteristic features of dilated cardiomyopathy that developed in 7 patients (36, 8%); 2 (11%) of them died. Conclusion: Almost half of the patients with Zika myocarditis developed acute HF during the first week of disease onset, none of the patients developed HF after the acute phase. A 3-year mortality rate of 10,5 % was observed.

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Severe ileocecal inflammatory syndrome in adult patients with cystic fibrosis

Zeitschrift für Gastroenterologie ◽

10.1055/a-0829-7050 ◽

2019 ◽

Vol 57 (03) ◽

pp. 312-316 ◽

Cited By ~ 2

Author(s):

Robert Henker ◽

Annett Oltmanns ◽

Alexandra Wald ◽

Jan Tuennemann ◽

Sabine Opitz ◽

...

Keyword(s):

Cystic Fibrosis ◽

Adult Patients ◽

Ileocecal Resection ◽

Inflammatory Disorder ◽

Ileocecal Region ◽

Distal Intestinal Obstruction Syndrome ◽

Fibrosing Colonopathy ◽

Inflammatory Syndrome ◽

Distal Intestinal Obstruction

AbstractThe relevance of gastrointestinal manifestations of cystic fibrosis (CF) is increasing due to an improved life expectancy. We report on 2 adult patients with prior lung transplantation who presented with a severe inflammatory disorder of the ileocecal region. One patient underwent ileocecal resection; the second patient died after emergency surgery for intestinal perforation. Both cases did not show typical signs of CF-related distal intestinal obstruction syndrome or extensive fibrosing colonopathy. However, the clinical and histopathological findings revealed CF-induced inflammatory alterations of the intestinal mucosa. Thus, these cases illustrate a further CF-related bowel disorder, which can be especially relevant in long-term CF survivors.

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New Onset of Hepatic Steatosis Post-Severe Multisystem Inflammatory Syndrome in Children (MIS-C): A Case Report

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18136961 ◽

2021 ◽

Vol 18 (13) ◽

pp. 6961

Author(s):

Rossella Sica ◽

Serena Pennoni ◽

Laura Penta ◽

Giuseppe Di Cara ◽

Alberto Verrotti

Keyword(s):

Hepatic Steatosis ◽

Clinical Laboratory ◽

Long Term Outcomes ◽

Significant Past Medical History ◽

Long Term Follow Up ◽

Inflammatory Syndrome ◽

Management Challenge ◽

New Onset

The emergence of Multisystem Inflammatory Syndrome (MIS-C) following SARS-CoV-2 infection in children and adolescents provided a new diagnostic and management challenge as there is limited knowledge about this condition and its natural history. In existing literature on MIS-C, there are currently no data about long-term outcomes. We report the case of a 14-year-old boy, with no significant past medical history, who presented a condition of multiorgan dysfunction due to MIS-C, after a SARS CoV-2 infection, and subsequent clinical-laboratory signs of hepatic steatosis at short-term follow-up. The case suggests how hepatic steatosis may be a possible sequela following SARS-CoV-2 infection, MIS-C and its medical treatment. Therefore, a close and long-term follow-up is needed to establish the pathophysiology and the evolution of this condition in patients following MIS-C.

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Perioperative hyperoxia — Long-term impact on cardiovascular complications after abdominal surgery, a post hoc analysis of the PROXI trial

International Journal of Cardiology ◽

10.1016/j.ijcard.2016.04.104 ◽

2016 ◽

Vol 215 ◽

pp. 238-243 ◽

Cited By ~ 38

Author(s):

Siv Fonnes ◽

Ismail Gögenur ◽

Edith Smed Søndergaard ◽

Volkert Dirk Siersma ◽

Lars Nannestad Jorgensen ◽

...

Keyword(s):

Abdominal Surgery ◽

Cardiovascular Complications ◽

Post Hoc Analysis ◽

Long Term Impact ◽

Post Hoc

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Mortality and Clinical Characteristics of Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 in critically ill patients: an observational multicenter study (MISCO STUDY)

10.21203/rs.3.rs-388266/v1 ◽

2021 ◽

Author(s):

Lorena Acevedo ◽

Byron Enrique Piñeres-Olave ◽

Laura Fernanda Niño-Serna ◽

Liliana Mazillo-Vega ◽

Ivan Jose Ardila Gómez ◽

...

Keyword(s):

Critically Ill ◽

Clinical Characteristics ◽

Clinical Laboratory ◽

Myocardial Dysfunction ◽

Cardiovascular Complications ◽

High Income ◽

Critically Ill Children ◽

Middle Income ◽

One Year ◽

Inflammatory Syndrome

Abstract Background The clinical presentation and severity of Multisystem Inflammatory Syndrome in Children associated with COVID-19 is widespread and presents a very low mortality rate in highincome countries. This research describes the clinical characteristics of MIS-C in critically ill children in middle-income countries compared to described series in high-income countries along with the factors associated with mortality and worse outcomes. Methods An observational cohort study was conducted in 14 PICUs in Colombia between April 01, 2020 and January 31, 2021. Patient´s age ranged between one month and 18 years and they met the requirements set forth by WHO for MIS-C. Results There were seventy-eight children in this study. The median age was seven years (IQR 1- 11), 18% (14/78) were under one year old, and 56% were male. Thirty-five percent (29/78) were obese or overweight. The PICU stay was six days (IQR 4-7), and 100% had a fever on admission lasting five days (IQR 3.7-6). Seventy percent (55/78) had diarrhea, and 87% (68/78) had shock or myocardial dysfunction (78%). Compared to the United Kingdom (UK) study, there were more children under the age of five (37% vs. 10%; p=0.004), and there was a higher frequency of obesity (29.5% vs. 10%; p=0.008). With regard to the US study, there was more lymphadenopathy (23% vs. 13%; p=0.02), diarrhea (70.5% vs. 53%; p=0.001), lymphopenia (64% vs. 35%; p=0.001), shock (87% vs. 35%; p=0.001), elevated troponin (51% vs. 31%; p=0.006) and elevated proBNP (82% vs 43%; p=0.001), as well as greater mortality (9% vs 1.8%; p=0.001). The group that did not survive had a longer duration of the disease until admission to the PICU (6 days vs. 5 days; p = 0.003), more frequency of ferritin above 500 ngr/mL (100% vs. 45%; p = 0.012) and more cardiovascular complications (100% vs. 54%; p = 0.019) compared to the group that survived. Conclusions Multisystem Inflammatory Syndrome in Children due to SARS-CoV-2 in critically ill children living in a middle-income country has some clinical, laboratory, and echocardiographic characteristics similar to those described in high-income countries. It was observed inflammatory response, and cardiovascular involvement were conditions that, added to the difficulties in accessing healthcare systems in countries with limited resources, may explain the higher mortality seen in these children.

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Crisis Phones - Suicide Prevention Versus Suggestion/Contagion Effects

Crisis ◽

10.1027/0227-5910/a000313 ◽

2015 ◽

Vol 36 (3) ◽

pp. 220-224 ◽

Cited By ~ 3

Author(s):

Steven Stack

Keyword(s):

Suicide Prevention ◽

Contagion Effects ◽

Long Term Impact

Abstract. Background: There has been no systematic work on the short- or long-term impact of the installation of crisis phones on suicides from bridges. The present study addresses this issue. Method: Data refer to 219 suicides from 1954 through 2013 on the Skyway Bridge in St. Petersburg, Florida. Six crisis phones with signs were installed in July 1999. Results: In the first decade after installation, the phones were used by 27 suicidal persons and credited with preventing 26 or 2.6 suicides a year. However, the net suicide count increased from 48 in the 13 years before installation of phones to 106 the following 13 years or by 4.5 additional suicides/year (t =3.512, p < .001). Conclusion: Although the phones prevented some suicides, there was a net increase after installation. The findings are interpreted with reference to suggestion/contagion effects including the emergence of a controversial bridge suicide blog.

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