Multiorgan Inflammatory Syndrome in Adults MIS-A Post SARS-CoV-2 Infection: A Novel Clinical Enigma.

BACKGROUND: Multisystem inflammatory syndrome in adults (MIS-A) is an emergent heterogenous clinical syndrome seen in the convalescent phase of COVID-19 infection. MIS in children (MIS-C) is a rare but severe post-COVID-19 illness that has been recognized by the WHO and the Centre for Disease Control and Prevention (CDC). It introduced a similar illness in adults based on multiple case series, identified as MIS-A. OBJECTIVE: We present four rare cases of multiorgan inflammatory syndrome in adults (MI-A) presented in Goa Medical College (Tertiary Medical Institute). We would like to highlight the diversity of presentation of symptoms with a significant history of previous covid infection, laboratory abnormalities, the clinical course of the disease, treatment strategies, and response and follow-up findings. We seek to highlight the emergence of a serious clinical entity that can be fatal if not diagnosed or treated promptly. MATERIALS AND METHODS: This was a descriptive study conducted in Goa Medical College from June 2021 to November 2021. A systematic search in the Department of General Medicine, the Department of Medical Records, and data from ICU, ITU, and critical covid wards were collected. RESULTS AND CONCLUSION: A total of four cases fulfilling the criteria for MIS-A as per MMWR (CDC 2020)were included, ranging from the age group of 29-70 years. All had features of severe systemic inflammatory response with multiple organ dysfunction and elevated proinflammatory markers. All four patients had a recent history of (mild) COVID-19 infection. Hence, in the current pandemic scenario, MIS-A should be considered as a possible diagnosis in patients with recent COVID infection presenting with MODS, when the obvious septic cause is excluded through thorough clinical, physical, serological, laboratory, and radiological investigations. However, the presence of a past covid infection may not be an absolute criterion due to mild symptoms of the primary covid infection which usually go unnoticed resulting in nontesting.

Multisystemic Inflammatory Syndrome in Children and Kawasaki Disease: Parallels in Pathogenesis and Treatment.

PURPOSE OF REVIEW: Since it first appeared, multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) has been compared to Kawasaki disease (KD). Although there were early parallels between MIS-C and KD, key differences emerged over time. Here, we aim to compare the pathogenesis, clinical presentation, treatment, and outcomes of MIS-C and KD. RECENT FINDINGS: In this article, we review and compare MIS-C and KD, highlighting differentiating features. We discuss the epidemiological and immunological factors along with clinical and laboratory features which discern MIS-C from KD. We also compare treatment and our understanding of long-term outcomes. Though parallels exist between MIS-C and KD, distinguishing the two is important for clinical management of patients, counseling about natural history, and determining long-term monitoring. While both MIS-C and KD are characterized by profound inflammation and inflammatory vasculopathy, further study is needed to determine whether they are distinct immunopathogenic disorders.

Cardiac Outcome of Children With SARS-CoV-2 Related Multisystem Inflammatory Syndrome.

OBJECTIVE: To study the cardiac outcomes of patients with multisystem inflammatory syndrome in children (MIS-C) after 6-month of diagnosis. METHODS: This review of hospital records was conducted on MIS-C patients (aged <21 year) who completed a six-month follow up. The baseline demographic, clinical, laboratory, and treatment characteristics during the acute phase, and echocardiographic findings during follow-up were collected. RESULTS: 116 patients (61.2% male, median age 7 years) with MIS-C were included in the study. At the time of admission, cardiac abnormalities were present in 70.7% of MIS-C patients, and the most common cardiac abnormalities were valve failure (50.9%), followed by ventricular dysfunction (39.7%), and pericardial effusion (23.3%). Six month after diagnosis, cardiac abnormalities were found in 10.3% of patients, and patients had lower rates of ventricular dysfunction (P<0.001), valve failure (P<0.001), pericardial effusion (P<0.001), and coronary involvement (P<0.001) as composed to the baseline. Intravenous immunoglobulin (IVIG) and steroid treatment significantly reduced the odds of occurrence of ventricular dysfunction (P=0.002), valve failure (P=0.004), and low ejection fraction (P=0.002) in comparison to IVIG treatment. CONCLUSION: While most MIS-C patients had abnormal echocardiographic findings at admission, only 10.3% of patients had cardiac abnormalities during follow up.

Multisystem Inflammatory Syndrome in Children and Kawasaki Disease: A Spectrum of Postinfectious Hyperinflammatory Disease.

Kawasaki disease and multisystem inflammatory syndrome in children are hyperinflammatory conditions that share similar emerging pathophysiology hypotheses, clinical features, treatment strategies, and outcomes. Although both conditions have key differences, growing evidence suggests that both conditions might be closely related on a larger spectrum of postinfectious autoimmune responses.

COVID-19 in children and adolescents: MIS(-C)-taken diagnoses.

Multisystem inflammatory syndrome in children (MIS-C) is an inflammatory condition associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is characterized by fever, gastro-intestinal symptoms, cardiovascular complications, conjunctivitis, skin involvement, elevated inflammatory markers, and coagulation abnormalities. The current ongoing COVID-19 pandemic causes an increased alertness to MIS-C. In combination with the heterogeneous clinical spectrum, this could potentially lead to diagnostic blindness, misdiagnosis of MIS-C, and overtreatment with expensive IVIG treatment. This report demonstrates the challenge of accurately distinguishing MIS-C from other more common inflammatory pediatric diseases, and the need to act with caution to avoid misdiagnoses in the current pandemic. We present a case series of 11 patients suspected of MIS-C based on the current definitions. Three of them were eventually diagnosed with a different disease. CONCLUSION: Current definitions and diagnostic criteria lack specificity which potentially leads to misdiagnosis and overtreatment of MIS-C. We emphasize the need to act with caution in order to avoid MIS(-C)-taken diagnoses in the current pandemic. WHAT IS KNOWN: • A pediatric multisystem inflammatory disease associated with SARS-CoV-2 has been described (MIS-C). • There are three definitions being used for MIS-C, all including fever for at least 24 h, laboratory evidence of inflammation, clinically severe illness with multi-organ (≥ 2) involvement, and no alternative plausible diagnosis. WHAT IS NEW: • MIS-C has a heterogeneous clinical spectrum without distinctive features compared to more common childhood diseases. Current definitions and diagnostic criteria for MIS-C lack specificity which leads to misdiagnosis and overtreatment. • Amid the current excessive attention to COVID-19 and MIS-C, pediatricians should remain vigilant to avoid mistaken diagnoses.

Multisystemic Inflammatory Syndrome in Neonates: A Systematic Review.

INTRODUCTION: Multisystem inflammatory syndrome in neonates (MIS-N) related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has increasingly been reported worldwide amid the spread of the SARS-CoV-2 pandemic. METHODS: We searched PubMed, EMBASE, and CINAHL and preprint servers (BioRxiv.org and MedRxiv.org) using a specified strategy integrating Medical Subject Headings terms and keywords until October 20, 2021. Our aim was to systematically review demographic profiles, clinical features, laboratory parameters, complications, treatments, and outcomes of neonates with MIS-N. Studies were selected when fulfilling the inclusion criteria. Articles were included if they fulfilled the World Health Organization (WHO), Centers for Disease Control (CDC) definitions of MIS-C, or our proposed definition. RESULTS: Sixteen reports of MIS-N including 47 neonates meeting MIS-N criteria were identified. Presentation included cardiovascular compromise (77%), respiratory involvement (55%), and fever in (36%). Eighty-three percent of patients received steroids, and 76% received immunoglobulin. Respiratory support was provided to 60% of patients and inotropes to 45% of patients. Five (11%) neonates died. CONCLUSION: The common presentation of MIS-N included cardiorespiratory compromise with the possibility of high mortality. Neonates with MIS-N related to SARS-CoV-2 may be at higher risk of adverse outcomes.

SARS-CoV-2 Infection and COVID-19 in Children.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is common in children, and clinical manifestations can vary depending on age, underlying disease, and vaccination status. Most children will have asymptomatic or mild infection, but certain baseline characteristics can increase the risk of moderate to severe disease. The following article will provide an overview of the clinical manifestations of coronavirus disease 2019 in children, including the post-infectious phenomenon called multisystem inflammatory syndrome in children. Currently available treatment and prophylaxis strategies will be outlined, with the caveat that new therapeutics and clinical efficacy data are constantly on the horizon.

Multisystem Inflammatory Syndrome in Children.

Multisystem inflammatory disease in children (MIS-C) is a condition typically seen 3 to 6 weeks after acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Believed to be a postinfection hyperinflammatory response, the clinical manifestation of this viral sequelae can vary significantly in severity and symptomatic presentation. Clinical prodrome includes persistent fever and dysfunction of at least two organ systems. Often developing after asymptomatic or mildly symptomatic coronavirus disease 2019 (COVID-19) infection, MIS-C is a diagnosis of exclusion that requires evaluation for other infectious or noninfectious etiology for symptoms. Vital sign instability, including fever, tachycardia, and hypotension; laboratory studies demonstrating elevated inflammatory markers and elevated cardiac markers; and positive SARS-CoV-2 polymerase chain reaction, SARS-CoV-2 antibodies, or exposure to someone with confirmed COVID-19 infection 4 to 6 weeks before clinical presentation are used to diagnose this condition. Skin and mucosal involvement, gastrointestinal symptoms, and neurologic manifestations are also commonly seen. An echocardiogram is indicated to evaluate for cardiac dysfunction, including but not limited to coronary artery enlargement, left ventricular dysfunction, arrythmias, or atrioventricular block. [Pediatr Ann. 2023;52(3):e114-e121.].

Can Multisystem Inflammatory Syndrome in Children Be Managed in the Outpatient Setting? An EHR-Based Cohort Study From the RECOVER Program.

Using electronic health record data combined with primary chart review, we identified seven children across nine participant pediatric medical centers with a diagnosis of Multisystem Inflammatory Syndrome in Children (MIS-C) managed exclusively as outpatients. These findings should raise awareness of mild presentations of MIS-C and the option of outpatient management.

Multisystem Inflammatory Syndrome.

The novel coronavirus (severe acute respiratory syndrome coronavirus-2), also referred to as coronavirus disease 2019, has caused a global pandemic that cost more than 900,000 deaths and affected nearly 80 million Americans since the start of the pandemic in early 2020. A majority of cases have primarily been reported in the adult population. Initially, lower morbidity and mortality rates were noted in children, compared with adults. However, some pediatric patients have been shown to develop a rare, but severe complication of severe acute respiratory syndrome coronavirus-2 infection, referred to as Multisystem Inflammatory Syndrome in Children. The condition has now been reported in adults as well. In this article, the origins, clinical features, pathogenesis, treatment, and latest literature on multisystem inflammatory syndrome are explored.

Pathogenesis, immunology, and immune-targeted management of the multisystem inflammatory syndrome in children (MIS-C) or pediatric inflammatory multisystem syndrome (PIMS): EAACI Position Paper.

Multisystem inflammatory syndrome in children (MIS-C) is a rare, but severe complication of coronavirus disease 2019 (COVID-19). It develops approximately 4 weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and involves hyperinflammation with multisystem injury, commonly progressing to shock. The exact pathomechanism of MIS-C is not known, but immunological dysregulation leading to cytokine storm plays a central role. In response to the emergence of MIS-C, the European Academy of Allergy and Clinical Immunology (EAACI) established a task force (TF) within the Immunology Section in May 2021. With the use of an online Delphi process, TF formulated clinical statements regarding immunological background of MIS-C, diagnosis, treatment, follow-up, and the role of COVID-19 vaccinations. MIS-C case definition is broad, and diagnosis is made based on clinical presentation. The immunological mechanism leading to MIS-C is unclear and depends on activating multiple pathways leading to hyperinflammation. Current management of MIS-C relies on supportive care in combination with immunosuppressive and/or immunomodulatory agents. The most frequently used agents are systemic steroids and intravenous immunoglobulin. Despite good overall short-term outcome, MIS-C patients should be followed-up at regular intervals after discharge, focusing on cardiac disease, organ damage, and inflammatory activity. COVID-19 vaccination is a safe and effective measure to prevent MIS-C. In anticipation of further research, we propose a convenient and clinically practical algorithm for managing MIS-C developed by the Immunology Section of the EAACI.

COVID-19 and children.

There has been substantial research on adult COVID-19 and how to treat it. But how do severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections afflict children? The COVID-19 pandemic has yielded many surprises, not least that children generally develop less severe disease than older adults, which is unusual for a respiratory disease. However, some children can develop serious complications from COVID-19, such as multisystem inflammatory syndrome in children (MIS-C) and Long Covid, even after mild or asymptomatic COVID-19. Why this occurs in some and not others is an important question. Moreover, when children do contract COVID-19, understanding their role in transmission, especially in schools and at home, is crucial to ensuring effective mitigation measures. Therefore, in addition to nonpharmaceutical interventions, such as improved ventilation, there is a strong case to vaccinate children so as to reduce possible long-term effects from infection and to decrease transmission. But questions remain about whether vaccination might skew immune responses to variants in the long term. As the experts discuss below, more is being learned about these important issues, but much more research is needed to understand the long-term effects of COVID-19 in children.

SARS-CoV-2 Sequelae and Postdischarge Health Care Visits Over 5 Months Follow-up Among Children Hospitalized for COVID-19 or MIS-C.

Although post-acute sequelae of COVID-19 among adult survivors has gained significant attention, data in children hospitalized for severe acute respiratory syndrome coronavirus 2 is limited. This study of commercially insured US children shows that those hospitalized with COVID-19 or multisystem inflammatory syndrome in children have a substantial burden of severe acute respiratory syndrome coronavirus 2 sequelae and associated health care visits postdischarge.

Two cases of multisystem inflammatory syndrome in adults: experience at a single centre in Sydney.

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.

Characteristics and Outcomes of Critically Ill Children With Multisystem Inflammatory Syndrome.

OBJECTIVES: To characterize the prevalence of pediatric critical illness from multisystem inflammatory syndrome in children (MIS-C) and to assess the influence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain on outcomes. DESIGN: Retrospective cohort study. SETTING: Database evaluation using the Virtual Pediatric Systems Database. PATIENTS: All children with MIS-C admitted to the PICU in 115 contributing hospitals between January 1, 2020, and June 30, 2021. MEASUREMENTS AND MAIN RESULTS: Of the 145,580 children admitted to the PICU during the study period, 1,338 children (0.9%) were admitted with MIS-C with the largest numbers of children admitted in quarter 1 (Q1) of 2021 ( n = 626). The original SARS-CoV-2 viral strain and the D614G Strain were the predominant strains through 2020, with Alpha B.1.1.7 predominating in Q1 and quarter 2 (Q2) of 2021. Overall, the median PICU length of stay (LOS) was 2.7 days (25-75% interquartile range [IQR], 1.6-4.7 d) with a median hospital LOS of 6.6 days (25-75% IQR, 4.7-9.3 d); 15.2% received mechanical ventilation with a median duration of mechanical ventilation of 3.1 days (25-75% IQR, 1.9-5.8 d), and there were 11 hospital deaths. During the study period, there was a significant decrease in the median PICU and hospital LOS and a decrease in the frequency of mechanical ventilation, with the most significant decrease occurring between quarter 3 and quarter 4 (Q4) of 2020. Children admitted to a PICU from the general care floor or from another ICU/step-down unit had longer PICU LOS than those admitted directly from an emergency department. CONCLUSIONS: Overall mortality from MIS-C was low, but the disease burden was high. There was a peak in MIS-C cases during Q1 of 2021, following a shift in viral strains in Q1 of 2021. However, an improvement in MIS-C outcomes starting in Q4 of 2020 suggests that viral strain was not the driving factor for outcomes in this population.

Multisystem Inflammatory Syndrome in Children (MIS-C).

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.

Multisystem inflammatory syndrome in children.

ABSTRACT: Multisystem inflammatory syndrome in children (MIS-C) is a potentially life-threatening syndrome that emerged soon after the start of the COVID-19 pandemic. This case report focuses on the general overview, case definition, epidemiology, pathogenesis, clinical findings, and management of MIS-C.

Clinico-Laboratory Profile, Intensive Care Needs and Short-Term Outcome of Multisystem Inflammatory Syndrome in Children (MIS-C): Experience during First and Second Waves from North India.

OBJECTIVES: To describe the clinico-laboratory profile, intensive care needs and outcome of multisystem inflammatory syndrome in children (MIS-C) during the first and second waves. METHODOLOGY: This retrospective study was conducted in the paediatric emergency and paediatric intensive care unit (PICU) of a tertiary care teaching hospital in North India involving 122 children with MIS-C admitted during the first wave (September 2020-January 2021, n = 40) and second wave (February 2021-September 2021, n = 82) of coronavirus disease 2019 (COVID-19). RESULTS: The median (interquartile range) age was 7 (4-10) years and 67% were boys. Common manifestations included fever (99%), abdominal symptoms (81%), rash (66%) and conjunctival injection (65%). Elevated C-reactive protein (97%), D-dimer (89%), procalcitonin (80%), IL-6 (78%), ferritin (56%), N-terminal pro B-type natriuretic peptide (84%) and positive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibody (81%) were common laboratory abnormalities. Cardiovascular manifestations included myocardial dysfunction (55%), shock (48%) and coronary artery changes (10%). The treatment included intensive care support (57%), non-invasive (33%) and invasive (18%) ventilation, vasoactive drugs (47%), intravenous immunoglobulin (IVIG) (83%), steroids (85%) and aspirin (87%). The mortality was 5% (n = 6). During the second wave, a significantly higher proportion had positive SARS-CoV-2 antibody, contact with COVID-19 and oral mucosal changes; lower markers of inflammation; lower proportion had lymphopenia, elevated IL-6 and ferritin; lower rates of shock, myocardial dysfunction and coronary artery changes; lesser need of PICU admission, fluid boluses, vasoactive drugs and IVIG; and shorter hospital stay. CONCLUSION: MIS-C is a febrile multisystemic disease characterized by hyperinflammation, cardiovascular involvement, temporal relationship to SARS-CoV-2 and good outcome with immunomodulation and intensive care. During the second wave, the severity of illness, degree of inflammation, intensive care needs, and requirement of immunomodulation were less as compared to the first wave.