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Background: SARS-CoV-2 infection can lead to a potentially life-threatening condition known as SARS-CoV-2-associated multisystem inflammatory syndrome in children (MIS-C), which differs from the severe lung disease and thrombotic complications commonly seen in adults. Recently, similar cases have been identified in adults, characterized by a clinical multisystem inflammatory syndrome referred to as MIS-A, which can emerge as a late and severe complication of SARS-CoV-2 infection. Case Presentation: We report two cases of MIS-A that were recently admitted to our hospital. Both patients developed a severe multisystem inflammatory syndrome despite experiencing only mild SARS-CoV-2 infection. Key clinical features in both cases included significant systemic inflammation, prominent cardiac involvement, and thrombocytopenia. Prior SARS-CoV-2 infection was confirmed through serological testing. Treatment protocols for MIS-C, including steroids and immunoglobulins, proved effective for both patients. Conclusions: Clinicians should remain vigilant for MIS-A in the context of ongoing SARS-CoV-2 infection worldwide. This infection, even when presenting with mild or no symptoms, can progress to a life-threatening hyperinflammatory syndrome with cardiac implications if not promptly recognized and treated. [ABSTRACT FROM AUTHOR]

ImportanceMultisystem inflammatory syndrome in adults (MIS-A) is a poorly understood complication of SARS-CoV-2 infection with significant morbidity and mortality.ObjectiveIdentify clinical, immunological, and histopathologic features of MIS-A to improve understanding of the pathophysiology and approach to treatment.DesignThree cases of MIS-A following SARS-CoV-2 infection were clinically identified between October 2021 - March 2022 using the U.S. Centers for Disease Control and Prevention diagnostic criteria. Clinical, laboratory, imaging, and tissue data were assessed.FindingsAll three patients developed acute onset cardiogenic shock and demonstrated elevated inflammatory biomarkers at the time of hospital admission that resolved over time. One case co-occurred with new onset Type 1 diabetes and sepsis. Retrospective analysis of myocardial tissue from one case identified SARS-CoV-2 RNA. All three patients fully recovered with standard of care interventions plus immunomodulatory therapy that included intravenous immunoglobulin, corticosteroids, and in two cases, anakinra.ConclusionMIS-A is a severe post-acute sequela of COVID-19 characterized by systemic elevation of inflammatory biomarkers. In this series of three cases, we find that although clinical courses and co-existent diseases vary, even severe presentations have potential for full recovery with prompt recognition and treatment. In addition to cardiogenic shock, glucose intolerance, unmasking of autoimmune disease, and sepsis can be features of MIS-A, and SARS-CoV-2 myocarditis can lead to a similar clinical syndrome.

Multisystem Inflammatory Syndrome in Adults (MIS-A) is a rare complication after COVID-19 that mainly occurs in young adults. Patients typically present with unremitting fever, rash, conjunctivitis, neurological signs, shock, gastrointestinal symptoms and thrombocytopenia. Reported cases are scarce. Here we describe three new cases.It is unclear to what extent MIS-A has a genetic basis, or whether MIS-A patients can be safely vaccinated after a case of MIS was reported after vaccination (termed MIS-V). We describe a monozygotic twin who was vaccinated without complications, suggesting no strict genetic basis for MIS-V. Furthermore, we report only the second case of MIS-A-related coronary aneurysm, which fully resolved upon regular treatment.With the majority of young adults living in low resources settings, we suggest more focus on clinical parameters to support a MIS-A diagnosis. We report the first two patients of North-African descent. Currently, MIS-A may be an underappreciated complication of COVID-19 due to the lack of reports in non-Caucasian populations.

Objectives Design Methods Results Conclusion Increasing evidence has supported the mutual relationship between suicidal motivations and personality pathology, especially in adolescence. Distinctive aspects of personality functioning can explain the tendency to resort to suicidal ideation and behaviours, which, in turn, may play a specific role in exacerbating severe impairments in self‐regulation mechanisms that underlie personality pathology.This study illustrates, through two clinical cases, the clinical utility of using the Psychodynamic Diagnostic Manual – Second Edition (PDM‐2) to better understand distinct pathways of suicidal processes.Two adolescents, named Luis and Gael, who attempted suicide multiple times were assessed using the Psychodiagnostic Chart Adolescent (PDC‐A) of the PDM‐2 to evaluate their mental functioning, emerging personality styles or syndromes, and symptom patterns. They were interviewed using the Motivational Interview for Suicidality in Adolescence (MIS‐A) to identify the motivations underpinning their suicidal behaviour.The results showed that Luis presented a narcissistic personality characterized by the need to deny his vulnerabilities through suicidal fantasies as a form of escape, while Gael presented a borderline personality characterized by the use of suicide attempts to express her inner and unspeakable pain.The study seems to support the reciprocal interconnections between personality functioning and suicidal motivations that should be better identified to plan tailored and more effective interventions. [ABSTRACT FROM AUTHOR]

Abstract Within 6 months of the coronavirus pandemic, a new disease entity associated with a multisystem hyperinflammation syndrome as a result of a previous infection with the SARS-CoV-2 virus is increasingly being identified in children termed Multisystem Inflammatory Syndrome in Children (MIS-C) and more recently in adults(MIS-A). Due to its clinical similarity with Kawasaki Disease, some institutions have used intravenous immunoglobulins and steroids as first line agents in the management of the disease. We seek to find how effective intravenous immunoglobulin therapy is across these two disease entities. A comprehensive English literature search was conducted across PubMed, MEDLINE, and EMBASE databases using the keywords multisystem inflammatory syndrome in children/adults and treatment. All major online libraries concerning the diagnosis and treatment of MIS-C and MIS-A were searched. Relevant papers were read, reviewed, and analyzed. The use of intravenous immunoglobulins (IVIG) and steroids for the treatment of multisystemic inflammatory syndrome in children(MIS-C) is well established and recommended by multiple pediatric governing institutions. However, there is still no optimal treatment guideline or consensus on the use of IVIG in adults. The use of IVIG in both the child and adult populations may lower the risk of treatment failure and the need for adjunctive immunomodulatory therapy. Despite the promising results of IVIG use for the management of MIS-C and MIS-A, considering the pathophysiological differences between MIS-C and MIS-A, healthcare professionals need to further assess the differences in disease risk and treatment. The optimal dose, frequency, and duration of treatment are still unknown, more research is needed to establish treatment guidelines.

Background: Vasculitis diseases include Kawasaki disease (KD), Kawasaki disease shock syndrome (KDSS), Multisystem Inflammatory Syndrome (MIS), Henoch–Schönlein purpura (HS), or IgA vasculitis, and additional vasculitis diseases. These diseases are often preceded by infections or immunizations. Disease incidence rates are higher in children than in adults. These diseases have been extensively studied, but understanding of the disease etiology remains to be established. Objective: Many studies have failed to demonstrate an association between vasculitis diseases and vaccination; this study examines possible associations. Methods: Herein, the Vaccine Adverse Event Reporting System (VAERS) database is retrospectively examined for associations between vasculitis diseases and immunizations. Results: For some vaccines, the number of rare cases of KD, MIS, and HS are higher than the background rates. These rare cases are predicted to occur in individuals with (1) genetic risk factors with (2) antibody titer levels above the primary immune response level. Herein, the model of humoral immune response antibodies bound to antigens (pathogen or vaccine) creating immune complexes is proposed. These immune complexes are proposed to bind Fc receptors on immune cells and platelets, resulting in cell activation and the release of inflammatory molecules including histamine and serotonin. Immune complexes and inflammatory molecules including serotonin and histamine likely trigger vasculitis. Elevated serotonin and possibly histamine drive initial vasoconstrictions, disrupting blood flow. Increased blood flow pressure from cardiac capillary vasoconstrictions is predicted to trigger coronary artery aneurysms (CAA) or lesions (CAL) in some patients. For KDSS and MIS patients, these cardiac capillary vasoconstrictions are predicted to result in ischemia followed by ventricular dysfunction. Ongoing ischemia can result in long-term cardiac damage. Cases associated with pathogens are likely to have persistent infections triggering disease onset. Conclusion: The proposed model of immune complexes driving disease initial disease etiology by Fc receptor activation of immune cells and platelets, resulting in elevated histamine and serotonin levels, is testable and is consistent with disease symptoms and current treatments. [ABSTRACT FROM AUTHOR]

Multisystem inflammatory syndrome after COVID-19 (MIS-A) is a consequence of an abnormal inflammatory response after COVID-19 resolution. Current criteria for diagnosis consist of the involvement of several organ systems. We present two cases, one in an immunosuppressed kidney transplant recipient and one in a patient on hemodialysis currently not on immunosuppression. The different clinical presentations and disease development may indicate that the current criteria for MIS-A diagnosis may be inadequate for immunosuppressed patients, as chronic immunosuppression may alter disease presentation. Both patients were treated with corticosteroids and intravenous immunoglobulins, and in both cases the treatment resulted in a prompt resolution of symptoms and stabilization of inflammatory parameters. [ABSTRACT FROM AUTHOR]

Background The diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–associated multisystem inflammatory syndrome in adults (MIS-A) requires distinguishing it from acute coronavirus disease 2019 (COVID-19) and may affect clinical management. Methods In this retrospective cohort study, we applied the US Centers for Disease Control and Prevention case definition to identify adults hospitalized with MIS-A at 6 academic medical centers from 1 March 2020 to 31 December 2021. Patients MIS-A were matched by age group, sex, site, and admission date at a 1:2 ratio to patients hospitalized with acute symptomatic COVID-19. Conditional logistic regression was used to compare demographic characteristics, presenting symptoms, laboratory and imaging results, treatments administered, and outcomes between cohorts. Results Through medical record review of 10 223 patients hospitalized with SARS-CoV-2–associated illness, we identified 53 MIS-A cases. Compared with 106 matched patients with COVID-19, those with MIS-A were more likely to be non-Hispanic black and less likely to be non-Hispanic white. They more likely had laboratory-confirmed COVID-19 ≥14 days before hospitalization, more likely had positive in-hospital SARS-CoV-2 serologic testing, and more often presented with gastrointestinal symptoms and chest pain. They were less likely to have underlying medical conditions and to present with cough and dyspnea. On admission, patients with MIS-A had higher neutrophil-to-lymphocyte ratio and higher levels of C-reactive protein, ferritin, procalcitonin, and D-dimer than patients with COVID-19. They also had longer hospitalization and more likely required intensive care admission, invasive mechanical ventilation, and vasopressors. The mortality rate was 6% in both cohorts. Conclusions Compared with patients with acute symptomatic COVID-19, adults with MIS-A more often manifest certain symptoms and laboratory findings early during hospitalization. These features may facilitate diagnosis and management. [ABSTRACT FROM AUTHOR]

The SARS-CoV2 pandemic is the most significant global health emergency of the last century. While the pathophysiology of SARS-CoV2 is understood, the early and long-term outcomes of natural infection are increasingly being recognised. Multisystem inflammatory syndrome (MIS) represents a manifestation of the extreme immune dysfunction that SARS-CoV2 infection heralds and has been described in both children (MIS-C) and adults (MIS-A). Here, we discuss current knowledge of MIS-A and the vast questions that remain unanswered.

Abstract Background SARS-CoV-2 may trigger both vasculitis and arrhythmias as part of a multisystem inflammatory syndrome described in children as well as in adults following COVID-19 infection with only minor respiratory symptoms. The syndrome denotes a severe dysfunction of one or more extra-pulmonary organ systems, with symptom onset approximately 2–5 weeks after the COVID-19 infection. In the present case, a seemingly intractable ventricular tachycardia preceded by SARS-CoV2 infection was only managed following the diagnosis and management of aortitis. Case presentation A 69-year-old woman was hospitalized due to syncope, following a mild COVID-19 infection. She presented with paroxysmal atrial fibrillation and intermittent ventricular tachycardia interpreted as a septum-triggered bundle branch reentry ventricular tachycardia, unaffected by amiodaron, lidocaine and adenosine. A CT-scan revealed inflammation of the aortic arch, extending into the aortic root. In the following days, the tachycardia progressed to ventricular storm with intermittent third-degree AV block. A temporary pacemaker was implanted, and radiofrequency ablation was performed to both sides of the ventricular septum after which the ventricular tachycardia was non-inducible. Following supplemental prednisolone treatment, cardiac symptoms and arrythmia subsided, but recurred after tapering. Long-term prednisolone treatment was therefore initiated with no relapse in the following 14 months. Conclusion We present a rare case of aortitis complicated with life-threatening ventricular tachycardia presided by Covid-19 infection without major respiratory symptoms. Given a known normal AV conduction prior to the COVID-19 infection, it seems likely that the ensuing aortitis in turn affected the septal myocardium, enabling the reentry tachycardia. Generally, bundle branch reentry tachycardia is best treated with radiofrequency ablation, but if it is due to aortitis with myocardial affection, long-term anti-inflammatory treatment is mandatory to prevent relapse and assure arrhythmia control. Our case highlights importance to recognize the existence of the multisystem inflammatory syndrome in adults (MIS-A) following COVID-19 infection in patients with alarming cardiovascular symptoms. The case shows that the early use of an CT-scan was crucial for both proper diagnosis and treatment option.

ImportanceMultisystem inflammatory syndrome in adults (MIS-A) is a poorly understood complication of SARS-CoV-2 infection with significant morbidity and mortality.ObjectiveIdentify clinical, immunological, and histopathologic features of MIS-A to improve understanding of the pathophysiology and approach to treatment.DesignThree cases of MIS-A following SARS-CoV-2 infection were clinically identified between October 2021 – March 2022 using the U.S. Centers for Disease Control and Prevention diagnostic criteria. Clinical, laboratory, imaging, and tissue data were assessed.FindingsAll three patients developed acute onset cardiogenic shock and demonstrated elevated inflammatory biomarkers at the time of hospital admission that resolved over time. One case co-occurred with new onset Type 1 diabetes and sepsis. Retrospective analysis of myocardial tissue from one case identified SARS-CoV-2 RNA. All three patients fully recovered with standard of care interventions plus immunomodulatory therapy that included intravenous immunoglobulin, corticosteroids, and in two cases, anakinra.ConclusionMIS-A is a severe post-acute sequela of COVID-19 characterized by systemic elevation of inflammatory biomarkers. In this series of three cases, we find that although clinical courses and co-existent diseases vary, even severe presentations have potential for full recovery with prompt recognition and treatment. In addition to cardiogenic shock, glucose intolerance, unmasking of autoimmune disease, and sepsis can be features of MIS-A, and SARS-CoV-2 myocarditis can lead to a similar clinical syndrome.

Key Clinical Message: Our case report demonstrates extremely uncommon data associated with MIS‐A, such as cholestatic jaundice, anemia, and quickly progressing pneumonia. IVIG and pulse steroid medications are the best treatments for improving clinical outcomes. We report a case of multiple organ dysfunctions due to MIS‐A in an adult with a history of suspected COVID‐19. Our case demonstrates extremely uncommon data associated with MIS‐A, such as cholestatic jaundice, anemia, and quickly progressing pneumonia. IVIG and pulse steroid medications are the best treatments for improving clinical outcomes. [ABSTRACT FROM AUTHOR]

Each injection of any known vaccine results in a strong expression of pro-inflammatory cytokines. This is the result of the innate immune system activation, without which no adaptive response to the injection of vaccines is possible. Unfortunately, the degree of inflammation produced by COVID-19 mRNA vaccines is variable, probably depending on genetic background and previous immune experiences, which through epigenetic modifications could have made the innate immune system of each individual tolerant or reactive to subsequent immune stimulations.We hypothesize that we can move from a limited pro-inflammatory condition to conditions of increasing expression of pro-inflammatory cytokines that can culminate in multisystem hyperinflammatory syndromes following COVID-19 mRNA vaccines (MIS-V). We have graphically represented this idea in a hypothetical inflammatory pyramid (IP) and we have correlated the time factor to the degree of inflammation produced after the injection of vaccines. Furthermore, we have placed the clinical manifestations within this hypothetical IP, correlating them to the degree of inflammation produced. Surprisingly, excluding the possible presence of an early MIS-V, the time factor and the complexity of clinical manifestations are correlated to the increasing degree of inflammation: symptoms, heart disease and syndromes (MIS-V). [ABSTRACT FROM AUTHOR]

We observed multisystem inflammatory syndrome in 2 older adults in the United States who had received mRNA coronavirus disease vaccine soon after natural infection. We identified 5 similar cases from the Vaccine Adverse Events Reporting System. The timing of vaccination soon after natural infection might have an adverse effect on the occurrence of vaccine-related systemic inflammatory disorders.

Multisystem inflammatory syndrome in adults (MIS-A) is an uncommon but severe and still understudied post-infectious complication of COVID-19. Clinically, the disease manifests itself most often 2–6 weeks after overcoming the infection. Young and middle-aged patients are especially affected. The clinical picture of the disease is very diverse. The dominant symptoms are mainly fever and myalgia, usually accompanied by various, especially extrapulmonary, manifestations. Cardiac damage (often in the form of cardiogenic shock) and significantly increased inflammatory parameters are often associated with MIS-A, while respiratory symptoms, including hypoxia, are less frequent. Due to the seriousness of the disease and the possibility of rapid progression, the basis of a successful treatment of the patient is early diagnosis, based mainly on anamnesis (overcoming the disease of COVID-19 in the recent past) and clinical symptoms, which often imitate other severe conditions such as, e.g., sepsis, septic shock, or toxic shock syndrome. Because of the danger of missing the treatment, it is necessary to initiate it immediately after the suspicion of MIS-A is expressed, without waiting for the results of microbiological and serological examinations. The cornerstone of pharmacological therapy is the administration of corticosteroids and intravenous immunoglobulins, to which the majority of patients clinically react. In this article, the authors describe the case report of a 21-year-old patient admitted to the Clinic of Infectology and Travel Medicine for febrility up to 40.5 °C, myalgia, arthralgia, headache, vomiting, and diarrhea three weeks after overcoming COVID-19. However, as part of the routine differential diagnosis of fevers (imaging and laboratory examinations), their cause was not clarified. Due to the overall worsening of the condition, the patient was transferred to the ICU with suspicion of developing MIS-A (he met all clinical and laboratory criteria). Given the above, reserve antibiotics, intravenous corticosteroids, and immunoglobulins were added to the treatment due to the risk of missing them, with a good clinical and laboratory effect. After stabilizing the condition and adjusting the laboratory parameters, the patient was transferred to a standard bed and sent home. [ABSTRACT FROM AUTHOR]

The SARS-CoV2 pandemic is the most significant global health emergency of the last century. While the pathophysiology of SARS-CoV2 is understood, the early and long-term outcomes of natural infection are increasingly being recognised. Multisystem inflammatory syndrome (MIS) represents a manifestation of the extreme immune dysfunction that SARS-CoV2 infection heralds and has been described in both children (MIS-C) and adults (MIS-A). Here, we discuss current knowledge of MIS-A and the vast questions that remain unanswered. [ABSTRACT FROM AUTHOR]

Despite surviving a SARS-CoV-2 infection, some individuals experience an intense post-infectious Multisystem Inflammatory Syndrome (MIS) of uncertain etiology. Children with this syndrome (MIS-C) can experience a Kawasaki-like disease, but mechanisms in adults (MIS-A) are not clearly defined. Here we utilize a deep phenotyping approach to examine immunologic responses in an individual with MIS-A. Results are contextualized to healthy, convalescent, and acute COVID-19 patients. The findings reveal systemic inflammatory changes involving novel neutrophil and B-cell subsets, autoantibodies, complement, and hypercoagulability that are linked to systemic vascular dysfunction. This deep patient profiling generates new mechanistic insight into this rare clinical entity and provides potential insight into other post-infectious syndromes. [ABSTRACT FROM AUTHOR]

Background: SARS-CoV-2 may trigger both vasculitis and arrhythmias as part of a multisystem inflammatory syndrome described in children as well as in adults following COVID-19 infection with only minor respiratory symptoms. The syndrome denotes a severe dysfunction of one or more extra-pulmonary organ systems, with symptom onset approximately 2–5 weeks after the COVID-19 infection. In the present case, a seemingly intractable ventricular tachycardia preceded by SARS-CoV2 infection was only managed following the diagnosis and management of aortitis. Case presentation: A 69-year-old woman was hospitalized due to syncope, following a mild COVID-19 infection. She presented with paroxysmal atrial fibrillation and intermittent ventricular tachycardia interpreted as a septum-triggered bundle branch reentry ventricular tachycardia, unaffected by amiodaron, lidocaine and adenosine. A CT-scan revealed inflammation of the aortic arch, extending into the aortic root. In the following days, the tachycardia progressed to ventricular storm with intermittent third-degree AV block. A temporary pacemaker was implanted, and radiofrequency ablation was performed to both sides of the ventricular septum after which the ventricular tachycardia was non-inducible. Following supplemental prednisolone treatment, cardiac symptoms and arrythmia subsided, but recurred after tapering. Long-term prednisolone treatment was therefore initiated with no relapse in the following 14 months. Conclusion: We present a rare case of aortitis complicated with life-threatening ventricular tachycardia presided by Covid-19 infection without major respiratory symptoms. Given a known normal AV conduction prior to the COVID-19 infection, it seems likely that the ensuing aortitis in turn affected the septal myocardium, enabling the reentry tachycardia. Generally, bundle branch reentry tachycardia is best treated with radiofrequency ablation, but if it is due to aortitis with myocardial affection, long-term anti-inflammatory treatment is mandatory to prevent relapse and assure arrhythmia control. Our case highlights importance to recognize the existence of the multisystem inflammatory syndrome in adults (MIS-A) following COVID-19 infection in patients with alarming cardiovascular symptoms. The case shows that the early use of an CT-scan was crucial for both proper diagnosis and treatment option. [ABSTRACT FROM AUTHOR]

Kawasaki disease is an acute febrile disease with the vasculitis of small and medium vessels that mainly affects children under the age of five, usually occurring after a viral respiratory diseases. During the coronavirus disease-19 (COVID-19) pandemic, a significant increase was reported in the number of children with symptoms similar to Kawasaki disease, which is known as a multi-system inflammatory syndrome in children (MIS-C). A Kawasaki-like disease is rare in adults, especially in the context of COVID-19. We hereby present the case of A 41 year old female patient presented with complaints of bleeding from the gums and red and watery eyes, high fever, sore throat, weakness, and lethargy. She mentioned a recent contact with a COVID-19 patient. Covid-19 was confirmed by a positive reverse transcription polymerase chain reaction (RT-PCR) test. Other lab tests and clinical manifestations revealed inflammatory phenomena that fully complied with multi-system inflammatory syndrome in adults (MIS-A) criteria. The patient was treated with a possible diagnosis of MIS-A in the context of COVID-19 and was discharged in good general condition. COVID-19 rarely presents in adults without clear respiratory symptoms and in the form of multisystem inflammatory syndrome (MIS-A). Due to the possibility of irreversible complications, MIS-A requires special attention and early diagnosis and treatment. [ABSTRACT FROM AUTHOR]

ABSTRACT: Multisystem inflammatory syndrome in adults is a rare and life-threatening complication that follows natural COVID-19 infection and primarily affects young unvaccinated adults. This complication is seldom described following vaccination, which would have important implications for the vaccination timing and platform in this population. COVID-19 vaccines are extremely effective; however, the risk of rare adverse events needs to be balanced with the vaccination benefits.

Abstract Background The current coronavirus disease pandemic has brought recognition of multisystem inflammatory syndrome in adults as a de novo entity, temporally associated with severe acute respiratory syndrome coronavirus 2 viral infection in adults. Hypothesis about its true pathophysiology remains controversial. Case report The patient was a 22-year-old African American female presenting to the emergency department with fever, sore throat, and neck swelling for the past 3 days. During her initial emergency department visit, her blood pressure was stable at 110/57 mmHg, temperature of 39.4 °C, and heart rate of 150 beats per minute. While in the emergency department, she received broad-spectrum antibiotics (vancomycin and ceftriaxone) and 30 cc/kg bolus of normal saline. Originally, she was admitted to a telemetry floor. The following night, a rapid response code was called due to hypotension. At that time, her blood pressure was 80/57 mmHg. She appeared comfortable without signs of respiratory distress. She received intravenous fluids and vasopressors, and was transferred to the intensive care unit. The patient had reported a previous coronavirus disease infection a few weeks prior. She was diagnosed and treated for multisystem inflammatory syndrome in adults. Intravenous immunoglobulin infusion was initiated and completed on hospital day 5. She was weaned off vasopressors by day 6, and discharged home on day 11. Conclusion Our case report is an example of the presentation, diagnosis, and management of multisystem inflammatory syndrome. Our research into previous case reports illustrates the wide range of presentations, degree of end organ damage, and treatment modalities. This diagnosis needs to be considered in the presence of recent coronavirus disease infection with new-onset end organ failure, as prompt diagnosis and treatment is crucial for better outcomes.

Despite surviving a SARS-CoV-2 infection, some individuals experience an intense post-infectious Multisystem Inflammatory Syndrome (MIS) of uncertain etiology. Children with this syndrome (MIS-C) can experience a Kawasaki-like disease, but mechanisms in adults (MIS-A) are not clearly defined. Here we utilize a deep phenotyping approach to examine immunologic responses in an individual with MIS-A. Results are contextualized to healthy, convalescent, and acute COVID-19 patients. The findings reveal systemic inflammatory changes involving novel neutrophil and B-cell subsets, autoantibodies, complement, and hypercoagulability that are linked to systemic vascular dysfunction. This deep patient profiling generates new mechanistic insight into this rare clinical entity and provides potential insight into other post-infectious syndromes.

Abstract Aim Multisystem inflammatory syndrome in adults (MIS‐A) is a hyperinflammatory multisystem condition associated with coronavirus disease (COVID‐19). Critically ill COVID‐19 patients may develop multiorgan damage and elevated inflammatory responses, thus making it difficult to differentiate between progression to organ damage due to COVID‐19 itself or MIS‐A. This study aimed to explore the characteristics and complications of MIS‐A in critical COVID‐19 patients. Methods The Japan Extracorporeal Membrane Oxygenation (ECMO) Network and ICU Collaboration Network developed a web‐based database system called the CRoss Intensive Care Unit Searchable Information System (CRISIS) to monitor critical COVID‐19 patients throughout Japan. We retrospectively identified patients with MIS‐A among critical COVID‐19 patients enrolled from March 2020 to December 2021, using CRISIS. Our MIS‐A definition required patients to be at least 18 years of age, have laboratory evidence of inflammation, severe dysfunction of at least two extrapulmonary organ systems, and no plausible alternative diagnoses. Results Of the 1052 patients, 26 (2.5%) were diagnosed with MIS‐A. The MIS‐A patients had a higher likelihood of using ECMO (13% vs. 46%, p

Background Multisystem inflammatory syndrome in adults (MIS-A) is a severe condition temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods In this retrospective cohort study, we applied the US Centers for Disease Control and Prevention (CDC) case definition to identify diagnosed and undiagnosed MIS-A cases among adults discharged during April 2020–January 2021 from 4 Atlanta, Georgia hospitals affiliated with a single medical center. Non–MIS-A coronavirus disease 2019 (COVID-19) hospitalizations were identified using International Classification of Diseases, Tenth Revision, Clinical Modification encounter code U07.1. We calculated the ratio of MIS-A to COVID-19 hospitalizations, compared demographic characteristics of the 2 cohorts, and described clinical characteristics of MIS-A patients. Results We identified 11 MIS-A cases, none of which were diagnosed by the treatment team, and 5755 COVID-19 hospitalizations (ratio 1:523). Compared with patients with COVID-19, patients with MIS-A were more likely to be younger than 50 years (72.7% vs 26.1%, P <.01) and to be non-Hispanic Black (81.8% vs 50.0%, P =.04). Ten patients with MIS-A (90.9%) had at least 1 underlying medical condition. Two MIS-A patients (18.2%) had a previous episode of laboratory-confirmed COVID-19, occurring 37 and 55 days prior to admission. All MIS-A patients developed left ventricular systolic dysfunction. None had documented mucocutaneous involvement. All required intensive care, all received systemic corticosteroids, 8 (72.7%) required mechanical ventilation, 2 (18.2%) required mechanical cardiovascular circulatory support, and none received intravenous immunoglobulin. Two (18.2%) died or were discharged to hospice. Conclusions MIS-A is a severe but likely underrecognized complication of SARS-CoV-2 infection. Improved recognition of MIS-A is needed to quantify its burden and identify populations at highest risk. [ABSTRACT FROM AUTHOR]

Abstract Background Adult patients with coronavirus disease present primarily with respiratory symptoms, but children and some adults may display a more systemic inflammatory syndrome with rash, fever, mucosal changes, and elevated inflammatory biomarkers. Case presentation Here, we report the case of a 29-year-old Hispanic patient presenting with significant rash and multisystem inflammation. We describe his clinical course, review dermatological manifestations of coronavirus disease, and summarize the pathophysiology of coronavirus disease-associated multisystem inflammation. Conclusion This case should alert physicians to the atypical nature of presenting rash with minimal respiratory symptoms in coronavirus disease.

Objectives: The aim of this study was to add to the descriptive data pertaining to the epidemiology, presentation, and clinical course of multisystem inflammatory syndrome (MIS) temporally associated with coronavirus disease 2019 in adults and adolescents from low- and middle-income countries.Methods: Patients presenting to the adult wards (14 years and older) of three academic hospitals in South Africa, who were diagnosed with MIS between August 1, 2020 and May 31, 2021, were reviewed retrospectively. The presentation, laboratory and radiographic findings, and clinical course are described.Results: Eleven cases of MIS were reported, four in adolescents (14–19 years) and seven in adults (≥19 years). Fever was universal. Gastrointestinal symptoms (90.9%), cardiorespiratory abnormalities (90.9%), and mucocutaneous findings (72.7%) were prominent. Echocardiography in 10/11 patients (90.9%) showed a median left ventricular ejection fraction of 26.3% (interquartile range 21.9–33.6%). All patients required high care admission and 72.7% required inotropic support. Glucocorticoids were initiated in all cases and 72.7% received intravenous immunoglobulin.Conclusions: This constitutes the largest multicentre review of adults and adolescents with MIS in Africa. MIS may be overlooked in resource-limited settings, and heightened suspicion is needed in patients with multi-organ dysfunction, especially where repeated investigations for other aetiologies are negative.

Le syndrome inflammatoire multisystémique de l’enfant (MIS-C) est l’une des principales répercussions de la maladie à coronavirus 2019 (COVID-19) qui a été décrite dans la littérature depuis le début de la pandémie. Bien que le MIS-C concerne les enfants, des cas ayant des caractéristiques cliniques semblables ont récemment été décrits chez les adultes. Une description des caractéristiques épidémiologiques et cliniques du syndrome inflammatoire multisystémique de l’adulte (MIS-A) est un point de départ pour une meilleure connaissance et compréhension de cette maladie émergente. Nous avons recensé neuf cas de MIS-A dans la littérature, cinq aux États-Unis, deux en France et deux au Royaume-Uni. Les descriptions de cas ont révélé des similitudes dans les caractéristiques cliniques, y compris l’occurrence au cours de la phase post-aiguë de la maladie, la fièvre, les symptômes digestifs, des atteintes cardiaques et des marqueurs inflammatoires élevés. Tous les patients ont été hospitalisés, trois ont dû être admis à l’unité de soins intensifs et un est décédé. Les traitements les plus courants étaient l’immunoglobuline intraveineuse, la prednisolone et l’aspirine. Ces résultats suggèrent que le MIS-A est une grave complication de la COVID-19 qui peut entraîner la mort. D’autres études visant à améliorer notre compréhension de la pathogenèse du MIS-A, qui contribueront à améliorer les décisions de traitement et à prévenir les séquelles ou la mort.

Multisystem inflammatory disease in children (MIS-C) is one of the severe presentations of the coronavirus disease 2019 (COVID-19) that has been described in the literature since the beginning of the pandemic. Although MIS-C refers to children, cases with similar clinical characteristics have been recently described in adults. A description of the epidemiologic and clinical characteristics of multisystem inflammatory disease in adults (MIS-A) is a starting point for better knowledge and understanding of this emerging disease. We identified nine case reports of MIS-A in the literature, five from the United States, two from France and two from the United Kingdom. The case descriptions revealed similarities in clinical features, including occurrence during post-acute disease phase, fever, digestive symptoms, cardiac involvement and elevated inflammatory markers. All the patients were hospitalized, three required admission to the intensive care unit and one died. The most common treatments were intravenous immunoglobulin, prednisolone and aspirin. These findings suggest that MIS-A is a severe complication of COVID-19 disease that can lead to death. Further studies to improve our understanding of the pathogenesis of MIS-A, which will help improve treatment decisions and prevent sequelae or death.

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. [ABSTRACT FROM AUTHOR]

Background: Extrapulmonary multisystemic manifestations in children were recognized, early in the pandemic, Multisystem Inflammatory Syndrome in Children (MIS-C). Of late, similar manifestations have been reported in adults (Multisystem Inflammatory Syndrome in adults - MIS-A) in too. As new variants of SARS-CoV 2 emerge and fade away, MIS-A needs to be recognized at the most opportune time. Besides, we hypothesize that MIS-A may also co-exist with other tropical infections to further confuse diagnostic scenario. Methodology: A series of five cases of MIS-A is presented. Their demographic, comorbidities, and clinical data were noted. Besides, the clinical and laboratory parameters of patients with and without tropical infections were compared. Results: Patients presented with diverse heterogenous clinical manifestations. The cardiovascular, hematological, and abdominal systems were most commonly involved along with high inflammatory markers. Three of our patients in the present series had tropical infections along with MIS-A. There was no statistically significant difference between clinical manifestations and laboratory parameters among MIS-A patients with and without tropical infections. All the five patients improved on treatment and were discharged home. Conclusions: A high index of suspicion is required to diagnose MIS-A, especially in tropical areas where background rate of other infections is also high. Moreover, these tropical infections may co-occur along with MIS-A, further confusing the diverse heterogenous clinical presentations. Patients with MIS-A may be critically ill, but outcomes are good if lifesaving immunosuppressive therapy is initiated on time. [ABSTRACT FROM AUTHOR]

Since the identification of SARS-CoV-2, a multisystem inflammatory syndrome (MIS-C) that appears in children after COVID-19 disease and mimics Kawasaki disease was reported in the UK in April 2020, while it is associated with Covid-19 in adults. Multisystem inflammatory syndrome (MIS-A) was reported in June 2020. MIS-A patients have been reported to be up to 50 years of age in the literature and are more likely to have some underlying health condition and have recently had an identifiable respiratory disease compared to MIS-C. On the other hand, MIS-A patients and MIS-C patients have many overlapping clinical features, but the severity of cardiac dysfunction, incidence of thrombosis, and MIS-A mortality may be higher in MIS-A. While it is clear that neutrophilia, lymphopenia, and thrombocytopenia are common in MIS-C/A, these features, together with elevations in troponin and BNP/NT-proBNP, have been considered measures of disease activity. [ABSTRACT FROM AUTHOR]

Background Multisystem inflammatory syndrome in adults (MIS-A) was reported in association with the coronavirus disease 2019 (COVID-19) pandemic. MIS-A was included in the list of adverse events to be monitored as part of the emergency use authorizations issued for COVID-19 vaccines. Methods Reports of MIS-A patients received by the Centers for Disease Control and Prevention (CDC) after COVID-19 vaccines became available were assessed. Data collected on the patients included clinical and demographic characteristics and their vaccine status. The Vaccine Adverse Events Reporting System (VAERS) was also reviewed for possible cases of MIS-A. Results From 14 December 2020 to 30 April 2021, 20 patients who met the case definition for MIS-A were reported to CDC. Their median age was 35 years (range, 21–66 years), and 13 (65%) were male. Overall, 16 (80%) patients had a preceding COVID-19-like illness a median of 26 days (range 11–78 days) before MIS-A onset. All 20 patients had laboratory evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Seven MIS-A patients (35%) received COVID-19 vaccine a median of 10 days (range, 6–45 days) before MIS-A onset; 3 patients received a second dose of COVID-19 vaccine 4, 17, and 22 days before MIS-A onset. Patients with MIS-A predominantly had gastrointestinal and cardiac manifestations and hypotension or shock. Conclusions Although 7 patients were reported to have received COVID-19 vaccine, all had evidence of prior SARS-CoV-2 infection. Given the widespread use of COVID-19 vaccines, the lack of reporting of MIS-A associated with vaccination alone, without evidence of underlying SARS-CoV-2 infection, is reassuring. [ABSTRACT FROM AUTHOR]

Multisystem inflammatory syndrome in adults (MIS-A) is a rare condition that develops after coronavirus disease 2019 (COVID-19). We present two young adult male patients, aged 25 and 24 years, who admitted to our outpatient clinic with high fever, redness in the eyes, diarrhea, and maculopapular rash four weeks after after clinically mild COVID-19 infection. Echocardiography showed global hypokinesia in both cases. Therefore, the history of COVID-19 should be questioned, and the patient should be evaluated for possible MIS-A, especially when new heart failure is detected during the pandemic. [ABSTRACT FROM AUTHOR]

Multisystem inflammatory syndrome (MIS) triggered by a recent SARS-Cov-2 infection has been recognised worldwide. Although predominantly affecting children (MIS-C), similar presentations have been reported among adults (MIS-A). A retrospective case series describing four critically ill patients with MIS-C/A diagnosed between January and April 2021 at Sahlgrenska University Hospital, Gothenburg, Sweden. Clinical presentation, laboratory and radiological findings, treatment and outcome are reported. Cases occurred in previously healthy patients with a history of laboratory-confirmed mild SARS-CoV-2 infection four to seven weeks earlier. The median age was 24 years (range 19–43) and 3/4 were male. All fulfilled suggested MIS-C/A criteria according to the US Centre for Disease Control and all required care at an intensive care unit. Treatment was initiated with intravenous immunoglobulin, interleukin-1-receptor antagonists, and pulse steroids in 3/4 cases which resulted in rapid clinical improvement. No severe complications were noticed in any case during a three-month follow-up period. MIS-C/A should be considered, irrespective of age, in patients with fever, hyperinflammation and multiple organ system involvements emerging weeks after COVID-19. Previously suggested treatment regimens for MIS-C seem to be applicable also for MIS-A. [ABSTRACT FROM AUTHOR]

Infection with SARS-CoV-2 may trigger a delayed hyperinflammatory illness in children called paediatric multisystem inflammatory syndrome temporally associated with COVID-19 (PIMS-TS). A similar syndrome is increasingly recognised in adults termed multisystem inflammatory syndrome in adults (MIS-A) and may present acutely to medical or surgical specialties with severe symptoms, such as acute abdominal pain or cardiogenic shock. No national guidelines exist in the UK for the management of MIS-A and there is limited evidence to guide treatment plans. We undertook a national Delphi process to elicit opinions from experts in hyperinflammation about the diagnosis and management of MIS-A with the dual aim of improving recognition and producing a management guideline. Colleagues in paediatrics successfully initiated a national consensus management document that facilitated regional multidisciplinary referral and follow-up pathways for children with PIMS-TS, and we propose a similar system be developed for adult patients across the UK. This would facilitate better recognition and treatment of MIS-A across the multiple specialties to which it may present as well as enable follow-up with specialty services post-discharge. [ABSTRACT FROM AUTHOR]

The novel coronavirus SARS-CoV-2, which has similarities to the 2002–2003 severe acute respiratory syndrome coronavirus known as SARS-CoV-1, causes the infectious disease designated COVID-19 by the World Health Organization (Coronavirus Disease 2019). Although the first reports indicated that activity of the virus is centered in the lungs, it was soon acknowledged that SARS-CoV-2 causes a multisystem disease. Indeed, this new pathogen causes a variety of syndromes, including asymptomatic disease; mild disease; moderate disease; a severe form that requires hospitalization, intensive care, and mechanical ventilation; multisystem inflammatory disease; and a condition called long COVID or postacute sequelae of SARS-CoV-2 infection. Some of these syndromes resemble previously described disorders, including those with no confirmed etiology, such as Kawasaki disease. After recognition of a distinct multisystem inflammatory syndrome in children, followed by a similar syndrome in adults, various multisystem syndromes occurring during the pandemic associated or related to SARS-CoV-2 began to be identified. A typical pattern of cytokine and chemokine dysregulation occurs in these complex syndromes; however, the disorders have distinct immunological determinants that may help to differentiate them. This review discusses the origins of the different trajectories of the inflammatory syndromes related to SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has brought attention to a newly identified syndrome of multisystem inflammation. This potentially fatal complication of the disease was initially observed in children and later in adults. It affects primarily unvaccinated patients and may manifest within a timeframe of 2-12 weeks following infection. Soluble urokinase plasminogen activator receptor (suPAR), a novel biomarker, highlights the severity of inflammation and the degree of immune system activation. Herein, we report a case of a patient with multisystem inflammatory syndrome in adults (MIS-A) and markedly elevated suPAR levels, successfully treated with interleukin-1 (IL-1) receptor antagonist. A 59-year-old female was admitted to our hospital due to febrile illness (up to 40°C) with chills, vomiting, non-bloody diarrhea, and abdominal pain for four days prior to her admission. She tested positive for SARS-CoV-2 12 weeks before her presentation. During hospitalization, the patient deteriorated clinically with multiorgan involvement and hemodynamically instability, with concomitant markedly elevated inflammatory markers. Extensive workup with high suPAR levels led to post-COVID-19 MIS-A diagnosis, and treatment with dexamethasone and an interleukin-1 receptor antagonist (IL-1ra), anakinra, was administered. The subcutaneous injection of anakinra effectively and safely deterred MIS-A. Further research is needed to investigate the role of interleukin-1 inhibitors for the management of this potentially life-threatening condition., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Christaki et al.)

Introduction and aim. Multisystem inflammatory syndrome in adults (MIS-A) is a rare severe illness which is related to prior SARS-CoV2 infection in individuals>=21 years old. The condition was described few months after recognition of similar entity in children known as MIS-C (United Kingdom, April, 2020). The diagnosis of MIS-A is based on clinical symptoms andevidence of inflammation in laboratory markers. It is characterized by extrapulmonary organ dysfunction (cardiovascular, gastrointestinal), general symptoms such as fever, malaise, rash and deviations in blood tests (elevated level of ferritin, procalcitonin, CRP, IL-6, D-Dimer) with a previous or current SARS-CoV-2 infection. The purpose of this study is to present the syndrome on the basis of a clinical case example, to show the course of the disease, its symptoms and the result of applied treatment. Description of the case. The following case describes the clinical history, diagnostic process and applied treatment of 37-year old female patient who was admitted urgently to the hospital with a suspicion of sepsis originating from pharynx. The final diagnosis -- MIS-A was settled after performing a broad panel of tests. Clinical picture was non- characteristic. The patient was successfully treated with steroids. Conclusion. MIS-A is a rare clinical entity linked with SARS-CoV-2 infection. The symptoms manifest from multiple organ systems and the diagnostic process may be challenging. The illness can be successfully treated with steroids. [ABSTRACT FROM AUTHOR]

The introduction of coronavirus 2019 (COVID-19) vaccination has been an integral force in stopping the spread of COVID-19 across the globe. While reported side effects of vaccination have predominantly been mild, in the last year reports have emerged of myocarditis following the BNT162b2 (Pfizer-BioNtech) and mRNA-1273 (Moderna) vaccinations. The adolescent and young adult population have been the population most reported, with over 1000 cases under review by the Centers for Disease Control (CDC) since April 2021. Here we report a case of a previously healthy 21-year-old male who developed Multisystem Inflammatory Syndrome in Adults (MIS-A) and following the second dose of the Pfizer-BioNtech vaccine. The young male initially presented with fever, leukocytosis with high neutrophil-lymphocyte ratio, severe cardiac illness, and positive COVID-19 nucleocapsid serology, consistent with MIS-A diagnosis. His case was complicated by cardiogenic shock, requiring brief venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. While this report does not detract from the overwhelming benefit of vaccination from COVID-19, clinicians should be aware of this possible relationship in the future.

COVID-19 vaccines are generally proven safe in all population and are highly recommended. However, rare adverse events have been reported. We hereby present a case of an 18-year-old man who presented to emergency department with fever, meningitis like symptoms, shortness of breath, chest pain, skin rash, and extreme fatigue. He had cardiac manifestations including hypotension, elevated troponin, and reduced ejection fraction. High inflammatory markers were also noted. He was initially worked up for and treated as a possible infectious etiology, but the microbiological studies were negative and there was no response to treatment. Since he had recently received booster dose of Pfizer-BioNTech COVID-19 vaccination three weeks prior to onset of symptoms, a possibility of Multisystem inflammatory syndrome in children (MIS-C) was made. His presentation fulfilled all the diagnostic criteria. The possibility for MIS-C being related to vaccination was proposed after relevant serological tests showed that the antibodies, he had were due to COVID-19 vaccine, not to a prior infection. After he received appropriate immunomodulatory treatment (IVIG and methylprednisolone) as per the guideline, he showed marked clinical improvement. Our case report highlights the need to consider MIS-C as a potential differential in young patients who present with unexplained multisystem illness with increased inflammatory markers and negative microbiologic work-up. MIS-C can be secondary to COVID-19 vaccination as well as to prior COVID-19 infection

Background: The current coronavirus disease pandemic has brought recognition of multisystem inflammatory syndrome in adults as a de novo entity, temporally associated with severe acute respiratory syndrome coronavirus 2 viral infection in adults. Hypothesis about its true pathophysiology remains controversial. Case report: The patient was a 22-year-old African American female presenting to the emergency department with fever, sore throat, and neck swelling for the past 3 days. During her initial emergency department visit, her blood pressure was stable at 110/57 mmHg, temperature of 39.4 °C, and heart rate of 150 beats per minute. While in the emergency department, she received broad-spectrum antibiotics (vancomycin and ceftriaxone) and 30 cc/kg bolus of normal saline. Originally, she was admitted to a telemetry floor. The following night, a rapid response code was called due to hypotension. At that time, her blood pressure was 80/57 mmHg. She appeared comfortable without signs of respiratory distress. She received intravenous fluids and vasopressors, and was transferred to the intensive care unit. The patient had reported a previous coronavirus disease infection a few weeks prior. She was diagnosed and treated for multisystem inflammatory syndrome in adults. Intravenous immunoglobulin infusion was initiated and completed on hospital day 5. She was weaned off vasopressors by day 6, and discharged home on day 11. Conclusion: Our case report is an example of the presentation, diagnosis, and management of multisystem inflammatory syndrome. Our research into previous case reports illustrates the wide range of presentations, degree of end organ damage, and treatment modalities. This diagnosis needs to be considered in the presence of recent coronavirus disease infection with new-onset end organ failure, as prompt diagnosis and treatment is crucial for better outcomes. [ABSTRACT FROM AUTHOR]

Multisystem inflammatory syndrome in adults (MIS-A) is a hyperinflammatory illness related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The characteristics of patients with this syndrome and the frequency with which it occurs among patients hospitalised after SARS-CoV-2 infection are unclear. Using the Centers for Disease Control and Prevention case definition for MIS-A, we created ICD-10-CM code and laboratory criteria to identify potential MIS-A patients in the Premier Healthcare Database Special COVID-19 Release, a database containing patient-level information on hospital discharges across the United States. Modified MIS-A criteria were applied to hospitalisations with discharge from March to December 2020. The proportion of hospitalisations meeting electronic health record criteria for MIS-A and descriptive statistics for patients in the potential MIS-A cohort were calculated. Of 34 515 SARS-CoV-2-related hospitalisations with complete clinical and laboratory data, 53 met modified criteria for MIS-A (0.15%). The median age was 62 years (IQR 52–74). Most patients met the severe cardiac illness criterion through either myocarditis (66.0%) or new-onset heart failure (35.8%). A total of 79.2% of patients required ICU admission, while 43.4% of patients in the cohort died. MIS-A appears to be a rare but severe outcome of SARS-CoV-2 infection. Additional studies are needed to investigate how this syndrome differs from severe coronavirus disease 2019 (COVID-19) in adults. [ABSTRACT FROM AUTHOR]

Background Multisystem inflammatory syndrome in adults (MIS-A) is a rare but potentially life-threatening condition that may occur during or in the weeks following severe acute respiratory syndrome coronavirus-2 infection. To date, only case reports and small case series have described typical findings and management of patients with MIS-A. The prevalence of MIS-A is largely unknown due to the lack of data. Case summary A 30-year-old male patient presented to the emergency department with new-onset of fever, chest discomfort, macular exanthema, abdominal pain, mild dyspnoea, and coughing. The patient reported a mildly symptomatic recent coronavirus disease-19 (COVID-19). Significantly increased markers of inflammation and a modest increase of cardiac troponin were found upon laboratory work-up at admission. Despite broad-spectrum antibiotics, the patient's clinical status deteriorated continuously. Cardiac work-up, including echocardiography, coronary angiography, and cardiac magnetic resonance imaging, was done and signs of acute myocarditis with mildly reduced left ventricular systolic function were found. The complex multi-organ symptom constellation facilitated the diagnosis of MIS-A following COVID-19 infection. Besides aspirin, intravenous, continuous hydrocortisone treatment was initiated, resulting in a prompt improvement of symptoms and clinical findings. Discussion We report a case of successfully treated MIS-A in the context of COVID-19, which further adds to the existing literature on this rare but clinically significant condition. Our case highlights the necessity of an interdisciplinary approach to correctly diagnose this complex, multi-organ disease and enable fast and appropriate management of these high-risk patients. [ABSTRACT FROM AUTHOR]

Each injection of any known vaccine results in a strong expression of pro-inflammatory cytokines. This is the result of the innate immune system activation, without which no adaptive response to the injection of vaccines is possible. Unfortunately, the degree of inflammation produced by COVID-19 mRNA vaccines is variable, probably depending on genetic background and previous immune experiences, which through epigenetic modifications could have made the innate immune system of each individual tolerant or reactive to subsequent immune stimulations.We hypothesize that we can move from a limited pro-inflammatory condition to conditions of increasing expression of pro-inflammatory cytokines that can culminate in multisystem hyperinflammatory syndromes following COVID-19 mRNA vaccines (MIS-V). We have graphically represented this idea in a hypothetical inflammatory pyramid (IP) and we have correlated the time factor to the degree of inflammation produced after the injection of vaccines. Furthermore, we have placed the clinical manifestations within this hypothetical IP, correlating them to the degree of inflammation produced. Surprisingly, excluding the possible presence of an early MIS-V, the time factor and the complexity of clinical manifestations are correlated to the increasing degree of inflammation: symptoms, heart disease and syndromes (MIS-V).

A 26-year-old otherwise healthy man died of fulminant myocarditis. Nasopharyngeal specimens collected premortem tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Histopathological evaluation of the heart showed myocardial necrosis surrounded by cytotoxic T-cells and tissue-repair macrophages. Myocardial T-cell receptor (TCR) sequencing revealed hyper-dominant clones with highly similar sequences to TCRs that are specific for SARS-CoV-2 epitopes. SARS-CoV-2 RNA was detected in the gut, supporting a diagnosis of multisystem inflammatory syndrome in adults (MIS-A). Molecular targets of MIS-associated inflammation are not known. Our data indicate that SARS-CoV-2 antigens selected high-frequency T-cell clones that mediated fatal myocarditis.

Abstract Multisystem Inflammatory Syndrome is a rare and novel clinical presentation described during the evolving COVID‐19 pandemic. The condition is usually presenting as a sepsis‐like syndrome leading to secondary multi‐organ dysfunction post–COVID‐19 infection. Although the syndrome has been mainly described in children, rare adults' form has been similarly described. We are describing a 37‐year‐old female patient presented with fever and neck pain after 1 month of a mild SARS‐CoV‐2 infection course and 10 days post her second COVID‐19 vaccine. Examination demonstrated fever, hypotension, and hypoxemia, in addition to multiple tender cervical lymph nodes. Initial laboratory workup showed evidence of significant inflammation with raised markers, including C‐reactive protein, ferritin, and interleukin‐6. Extensive evaluation to rule out active infection was done, and all return negative, including repeat SARS‐CoV‐2 test. Furthermore, cardiac evaluation showed moderately reduced systolic ventricular function. Despite all negative test and supportive measures, the patient continued to deteriorate requiring critical care admission for ionotropic support, non‐invasive ventilation in addition to presumptive broad‐spectrum antimicrobial management. There was no significant improvement with supportive care until the presentation of multisystem involvement on in the context of a recent history of COVID 19 and negative infective screen was raised. The diagnosis of multisystem inflammatory syndrome‐adult form (MIS‐A) was embraced, and the patient was commenced on methylprednisolone leading to a dramatic resolution of symptoms both clinically and biochemically with stabilization of vital functions allowing for safe outcomes.