Programmed Cell Death Protein-1 Regulation in Response to SARS-CoV-2 in Paediatric Multisystem Inflammatory Syndrome Temporally Associated with SARS-CoV-2: A Prospective Cohort Study.

The role of programmed death cell protein 1 (PD-1) has already been described in a range of various diseases, including COVID-19. This study provides new, innovative data, related to the expression of PD-1 and the risk of Paediatric Inflammatory Multisystem Syndrome, temporally associated with SARS-CoV-2 infection (PIMS-TS)-a rare, but potentially life-threatening complication of COVID-19. In this study, we evaluated the expression of PD-1 protein in patients with PIMS. Blood samples were taken from patients at the time of diagnosis (n = 33), after 6 weeks (n = 33), 3 months (n = 24), 6 months (n = 24) and 12 months (n = 8). The immunophenotypes were evaluated in flow cytometry. The control group consisted of 35 healthy children with negative SARS-CoV-2 antigen/PCR test, who were asymptomatic and had no history of allergic, autoimmune or oncological diseases. The associations between immunophenotypes, biochemical findings and clinical data were analysed. Significant increases in the expression of PD-1 for CD4+ and CD8+ T cells, compared to the control group, were observed in the day of admission, with a gradual decrease during the first weeks from initiation of treatment. This study sheds new light on the pathogenesis of PIMS-TS, emphasizing the role of PD-1 protein. Future research is essential for early risk prediction in SARS-CoV-2 patients and for devising effective clinical prevention and management strategies.

Inflammatory and Autoimmune Aspects of Multisystem Inflammatory Syndrome in Children (MIS-C): A Prospective Cohort Study.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a potentially life-threatening complication of COVID-19. The pathophysiological mechanisms leading to severe disease are poorly understood. This study leveraged clinical samples from a well-characterized cohort of children hospitalized with COVID-19 or MIS-C to compare immune-mediated biomarkers. Our objective was to identify selected immune molecules that could explain, in part, why certain SARS-CoV-2-infected children developed MIS-C. We hypothesized that type-2 helper T cell-mediated inflammation can elicit autoantibodies, which may account for some of the differences observed between the moderate-severe COVID-19 (COVID+) and MIS-C cohort. We enumerated blood leukocytes and measured levels of selected serum cytokines, chemokines, antibodies to COVID-19 antigens, and autoantibodies in children presenting to an academic medical center in Connecticut, United States. The neutrophil/lymphocyte and eosinophil/lymphocyte ratios were significantly higher in those in the MIS-C versus COVID+ cohort. IgM and IgA, but not IgG antibodies to SARS-CoV-2 receptor binding domain were significantly higher in the MIS-C cohort than the COVID+ cohort. The serum levels of certain type-2 cytokines (interleukin (IL)-4, IL-5, IL-6, IL-8, IL-10, IL-13, and IL-33) were significantly higher in children with MIS-C compared to the COVID+ and SARS-CoV-2-negative cohorts. IgG autoantibodies to brain antigens and pentraxin were higher in children with MIS-C compared to SARS-CoV-19-negative controls, and children with MIS-C had higher levels of IgG anti-contactin-associated protein-like 2 (caspr2) compared to the COVID+ and SARS-CoV-19-negative controls. We speculate that autoimmune responses in certain COVID-19 patients may induce pathophysiological changes that lead to MIS-C. The triggers of autoimmunity and factors accounting for type-2 inflammation require further investigation.

Dynamics of multisystem inflammatory syndrome in children associated to COVID-19 in Chile: Epidemiologic trends during pandemic, before and after children vaccination.

BACKGROUND: Multisystem inflammatory syndrome associated to Covid-19 (MIS-C) is one of the most severe outcomes of SARS-CoV-2 in children. Covid-19 vaccines were successfully implemented in Chile for the pediatric population since 2021, using both mRNA and inactivated platforms. Effectiveness against MIS-C has been reported for mRNA vaccines. The aim of this study was to describe the epidemiologic trend of MIS-C in Chile during Covid-19 pandemic, both before and after the availability of vaccination for children. MATERIALS AND METHODS: Analytic study of MIS-C cases from April 2020 to December 2022. Epidemiological data, SARS-CoV-2 variants and vaccination uptake information were obtained from the Epidemiology Department-Ministry of Health, Institute of Public Health and the National Immunization Program, respectively. RESULTS: 496 cases of MIS-C were reported, 58 % males. Median age was 5 years and most frequent age-cohorts were 6-11 and 0-2 years old with a 33 % each. After the introduction of the Covid-19 vaccine, most cases occurred in children aged 0-2 years. Incidence rates were 3.8, 5.4 and 1.7 per 100,000 inhabitants in 2020, 2021 and 2022, respectively. 97 % of cases (481) occurred in unvaccinated subjects. On those previously vaccinated (15), all but one case occurred in children receiving the inactivated vaccine. No association among circulating variants and incidence was observed. Incidence rate reduction (IRR) comparison between 2020 and 2021-2022 periods was 0.72 (CI 95 % 0.65-0.81, p < 0.05) overall; 0.86 for 0-2 years (CI 95 %:0.71-1; p = 0.12); 0.88 for 3-5 years (CI 95 %:0.69-1.11; p = 0.28); 0.61 for 6-11 years (CI 95 %: 0.50-0.75; p < 0.05); and 0.64 for 12-17 years (CI 95 %:0.47-0.89; p < 0.05), consistent with vaccination uptake during the studied period: 63 % for 3-5 years, 91 % for 6-11 years, and 99 % for 12-17 years. CONCLUSIONS: A decline of MIS-C incidence and a shift to younger, unvaccinated population overtime was observed. IRR decreased in age-cohorts which achieved high vaccination rates.

A case of TAFRO syndrome after vaccination, successfully treated with cyclosporine.

BACKGROUND: TAFRO syndrome is a rare disorder that causes thrombocytopenia, generalized oedema, fever, organ enlargement, and renal impairment. Few reports have suggested an association with vaccines, and few cases have undergone renal biopsy. TAFRO syndrome is often severe and fatal, and its cause is unknown. We report a case of TAFRO syndrome that occurred after vaccination with the coronavirus disease 2019 (COVID-19) vaccine. CASE PRESENTATION: An 82-year-old woman received two doses of the BNT162b2 mRNA vaccine 3 weeks apart. Two weeks later, she was admitted to the hospital with oedema, accompanied with renal failure and thrombocytopenia. After close examination, she was diagnosed with TAFRO syndrome. She was treated with steroids, cyclosporine, and thrombopoietin receptor agonists. The patient was discharged after several months in remission. CONCLUSIONS: Although an incident of TAFRO syndrome after COVID-19 vaccination has been previously reported, this is a rare case in which the patient went into remission and was discharged. A renal biopsy was also performed in this case, which was consistent with previous reports. The favorable treatment course for TAFRO syndrome provides valuable insights.

Rocky Mountain Spotted Fever Mimicking Multisystem Inflammatory Syndrome in Hospitalized Children, Sonora, Mexico.

We describe 5 children who had Rocky Mountain spotted fever (RMSF) and manifested clinical symptoms similar to multisystem inflammatory syndrome in Sonora, Mexico, where RMSF is hyperendemic. Physicians should consider RMSF in differential diagnoses of hospitalized patients with multisystem inflammatory syndrome to prevent illness and death caused by rickettsial disease.

[Hyperinflammatory immune response syndrome PIMS-TS]. / «Nachwehen¼: Hyperinflammatorisches Immunreaktionssyndrom PIMS-TS.

INTRODUCTION: PIMS-TS is a rare hyperinflammatory immune response syndrome, usually occurring two to six weeks after SARS-CoV-2 infection, which mainly affects schoolchildren and is often associated with the need for intensive care (2). The most common clinical signs are high fever, gastrointestinal symptoms such as abdominal pain, vomiting and diarrhea, cardiovascular dysfunction (impaired LVEF, hypotension, shock) and neurological symptoms such as headache and encephalopathy (1, 2, 4). The definition criteria include various clinical and laboratory parameters, which vary slightly depending on the authors (4, 6, 7). With intensive care treatment with circulatory support and administration of methylprednisolone, mortality and long-term consequences remain low.

Are we overdiagnosing multisystem inflammatory syndrome in children (MIS-C)? A case series of children with bacterial infection mimicking MIS-C.

INTRODUCTION: Multisystem inflammatory syndrome in children (MIS-C) is a serious hyperinflammatory condition associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Usually, the diagnosis of MIS-C is made by criteria defined by international organizations, which include specific clinical features, laboratory findings, and evidence of SARS-CoV-2 infection. We hereby present a case series of three children. The objective of this case series, involving chart review of medical records of children admitted with MIS-C, is to emphasize that the features of MIS-C may overlap with other conditions. CASE PRESENTATION: Three children were presented with MIS-C based on World Health Organization (WHO) criteria and given treatment for the same. However, due to persistent symptoms, they were further worked up and diagnosed to have underlying bacterial infections which included liver abscess, enteric fever, or urinary tract infection. CONCLUSIONS: The criteria for MIS-C may overlap with other conditions, particularly bacterial infection that may lead to overdiagnosis of MIS-C. Therefore, one should be very careful in making an MIS-C diagnosis and other differential diagnoses should be considered when the symptoms persist or worsen.

Should aortic stiffness parameters be used in MIS-C patient follow-up?

We evaluated the short- and long-term effects of multisystem inflammatory syndrome in children (MIS-C) on their cardiovascular system. The study population consisted of 38 MIS-C patients and 55 control patients. Standard echocardiographic measurements and aortic stiffness parameters were compared between the two groups at different time points. During the standard echocardiographic examination at the time of diagnosis, mitral valve insufficiency was detected in 42% of the cases, left ventricular systolic dysfunction in 36%, aortic valve insufficiency in 3%, tricuspid valve insufficiency in 13%, and coronary artery dilatation in 31%. The ejection fraction, pulse pressure of the experimental group were significantly lower than the control group (p < 0.01, p = 0.045, respectively). When aortic stiffness parameters were compared, it was seen that the parameters increased in the experimental group and the difference was significant for aortic distensibility. (p = 0.105, p = 0.029 respectively). When comparing the experimental group's results at diagnosis and at the sixth month, there was a decrease in aortic stiffness parameters at the sixth month compared to the time of diagnosis, but the difference wasn't significant (p = 0.514, p = 0.334). However, no statistically significant difference was detected when comparing the aortic distensibility results of the experimental group with the control group at the sixth month (p = 0.667). Our results showed that many pathological echocardiographic findings detected at diagnosis in MIS-C patients returned to normal within six months. Therefore, we believe that the cardiovascular follow-up period of MIS-C cases should be at least six months.

[Cardiovascular manifestations in pediatric multisystem inflammatory syndrome associated with COVID-19 in a tertiary care pediatric center in Mexico City]. / Alteraciones cardiovasculares en el síndrome inflamatorio multisistémico pediátrico asociado a COVID-19 en un hospital pediátrico de tercer nivel de la Ciudad de México.

Objective: The objective is to expose the cardiovascular alterations in patients diagnosed with pediatric inflammatory multisystem syndrome (PIMS) associated with COVID-19 during the SARS-CoV-2 pandemic, in order to understand the disease, its evolution, and optimal management upon diagnosis. Method: Retrospective, observational, cross-sectional analytical study of patients diagnosed with PIMS according to the criteria of the World Health Organization at the National Institute of Pediatrics, from March 2020 to December 2021. Results: During the study period, 77 patients with PIMS were diagnosed. The results showed correlation between the shock state and alteration of laboratory markers (platelets 144217.29 ± 139321.6 µL [p < 0.001], procalcitonin 27.37 ± 38.37 ng/ml [p = 0.05] and ferritin 1937.87 ± 2562.63 [p < 0.001]). The ventricular function in patients with shock was significantly lower compared to those without shock (49.6 ± 9.1% vs. 58.1 ± 8.4 %; t-Student p < 0.001), as well as injury to the left coronary artery (p = 0.02). There is a correlation between NT-proBNP and ventricular dysfunction (Kruskal-Wallis p = 0.007). Statistical significance was found in the association between death, elevation of inflammatory markers and ventricular dysfunction (p < 0.001). Conclusions: The cardiovascular alterations observed, in order of frequency, were pericardial effusion (25.7%), myocarditis (15%), mild ventricular dysfunction (13.5%) and small coronary aneurysm with predominance of the left coronary artery and the anterior descending one.

Objetivo: Exponer las alteraciones cardiovasculares en los pacientes diagnosticados con síndrome inflamatorio multisistémico pediátrico (PIMS) asociado a COVID-19 durante la pandemia por SARS-CoV-2 con el fin de comprender la enfermedad, su evolución y el manejo óptimo al diagnóstico. Método: Estudio retrospectivo, observacional, transversal y analítico de pacientes con diagnóstico de PIMS de acuerdo con los criterios de la Organización Mundial de la Salud en el Instituto Nacional de Pediatría, de marzo de 2020 a diciembre de 2021. Resultados: Durante el periodo de estudio se diagnosticaron 77 pacientes con PIMS. Los resultados demostraron una correlación entre el estado de choque y la alteración de los marcadores de laboratorio (plaquetas 144217.29 ± 139321.6 µl [p < 0.001], procalcitonina 27.37 ± 38.37 ng/ml [p = 0.05] y ferritina 1937.87 ± 2562.63 [p < 0.001]). La función ventricular en los pacientes con choque se registró significativamente menor en comparación con aquellos sin choque (49.6 ± 9.1 % vs. 58.1 ± 8.4 %; t de Student p < 0.001), así como lesión en la arteria coronaria izquierda (p = 0.02). Existe una correlación entre el NT-proBNP y la disfunción ventricular (Kruskal-Wallis p = 0.007). Se encontró significancia estadística en la asociación entre fallecimiento, elevación de los marcadores inflamatorios y disfunción ventricular (p < 0.001). Conclusiones: Las alteraciones cardiovasculares observadas fueron, en orden de frecuencia, derrame pericárdico (25.7%), miocarditis (15%), disfunción ventricular leve (13.5%) y aneurisma pequeño coronario con predominio de la arteria coronaria izquierda y la descendente anterior.

Diagnostic markers of acute encephalitis syndrome and COVID-associated multisystem inflammatory syndrome in children from Southern India.

Acute encephalitis syndrome (AES) in children poses a significant public health challenge in India. This study aims to explore the utility of host inflammatory mediators and neurofilament (NfL) levels in distinguishing etiologies, assessing disease severity, and predicting outcomes in AES. We assessed 12 mediators in serum (n = 58) and 11 in cerebrospinal fluid (CSF) (n = 42) from 62 children with AES due to scrub typhus, viral etiologies, and COVID-associated multisystem inflammatory syndrome (MIS-C) in Southern India. Additionally, NfL levels in serum (n = 20) and CSF (n = 18) were examined. Clinical data, including Glasgow coma scale (GCS) and Liverpool outcome scores, were recorded. Examining serum and CSF markers in the three AES etiology groups revealed notable distinctions, with scrub typhus differing significantly from viral and MIS-C causes. Viral causes had elevated serum CCL11 and CCL2 compared with scrub typhus, while MIS-C cases showed higher HGF levels than scrub typhus. However, CSF analysis showed a distinct pattern with the scrub typhus group exhibiting elevated levels of IL-1RA, IL-1ß, and TNF compared with MIS-C, and lower CCL2 levels compared with the viral group. Modeling the characteristic features, we identified that age ≥3 years with serum CCL11 < 180 pg/mL effectively distinguished scrub typhus from other AES causes. Elevated serum CCL11, HGF, and IL-6:IL-10 ratio were associated with poor outcomes (p = 0.038, 0.005, 0.02). Positive CSF and serum NfL correlation, and negative GCS and serum NfL correlation were observed. Median NfL levels were higher in children with abnormal admission GCS and poor outcomes. Measuring immune mediators and brain injury markers in AES provides valuable diagnostic insights, with the potential to facilitate rapid diagnosis and prognosis. The correlation between CSF and serum NfL, along with distinctive serum cytokine profiles across various etiologies, indicates the adequacy of blood samples alone for assessment and monitoring. The association of elevated levels of CCL11, HGF, and an increased IL-6:IL-10 ratio with adverse outcomes suggests promising avenues for therapeutic exploration, warranting further investigation.

COVID-19 and cardiac complications: Myocarditis and multisystem inflammatory syndrome in children.

Coronavirus is an important pathogen causing disease in humans and animals. At the end of 2019, an investigation into an increase in pneumonia cases in Wuhan, Hubei Province, China, found that the cause was a new coronavirus. This disease, which spread rapidly across China and caused an outbreak worldwide, resulted in a pandemic. Although this virus has previously been referred to as 2019-nCoV, which causes coronavirus disease 2019 (COVID-19), later it was named severe acute respiratory syndrome coronavirus 2. Children were usually asymptomatic and rarely severely affected. In April 2020, reports from the United Kingdom indicated that children may have Kawasaki disease or a clinical condition similar to toxic shock syndrome. This clinical picture was later defined as multisystem inflammatory syndrome in children. Since then, similarly affected children as well as cases with other cardiac complications have been reported in other parts of the world. In this review, we aimed to evaluate COVID-19 in terms of cardiac involvement by reviewing the literature.

One Virus, Two Diseases: Evaluation of Clinical and Immunological Differences in Covid-19 and Multisystem Inflammatory Syndrome Cases.

Objectives: This study aims to uncover early detection markers through the immunological analysis of children diagnosed with multisystem inflammatory syndrome (MIS-C) and coronavirus disease-2019 (COVID-19). Methods: We retrospectively analyzed immunological data from thirty-three MIS-C patients and an equivalent number of patients under the age of 18 with a positive polymerase chain reaction (PCR) test for COVID-19. These individuals were admitted to Ondokuz Mayis University between November 2020 and February 2021. In total, the study group consisted of 66 patients and an additional 10 healthy controls. Results: Lymphopenia, thrombocytopenia, anemia, and neutrophilia, along with elevated levels of ferritin, D-dimer, and C-reactive protein, were more pronounced in MIS-C patients (p<0.001). No significant disparities were found in serum IgG, A, M, and E concentrations. Notably, there was an increased proportion of B cells (p<0.001), an inversion of the CD4/CD8 ratio, and a marked presence of CD3+CD38+HLA-DR+active T cells (p=0.009) in the MIS-C cohort. Conclusion: In the early diagnosis of MIS-C, lymphopenia, increase in B cells, reversal of CD4/CD8 ratio, and demonstration of CD3+CD38+HLA-DR+active T cells may be helpful.

The role of malnutrition on outcomes of multisystem inflammatory syndrome in children (MIS-C) due to COVID-19.

BACKGROUND: Malnutrition increases the complications and mortality in critically-ill children. We performed a retrospective analysis to define the impact of malnutrition on the outcomes of multisystem inflammatory syndrome in children (MIS-C) due to COVID-19. METHODS: Patients with MIS-C were evaluated for demographic features, anthropometric parameters, clinical findings and outcomes. Patients with z scores of body mass index (> 5 years) and weight-for-age (< 5 years) < -2 were considered malnourished. Sarcopenia was defined by total psoas muscle area (tPMA), calculated on abdominal computed tomography (CT) at the level of L3 and L4 vertebrae. The z scores <- 2 for tPMA were considered sarcopenia. The results of patients with and without malnutrition were compared. RESULTS: Twenty-seven patients were included. Forty-four percent (n=12) of patients had malnutrition. Malnutrition was classified as mild to moderate (1/3), severe (1/3) and overweight (1/3). Eighty-two % of cases had acute malnutrition. Among MIS-C symptom criteria, rash was significantly higher in children with malnutrition (p<0.05). Laboratory investigations showed higher ferritin levels in patients with malnutrition (p<0.05). The median tPMA and sarcopenia were significantly higher in patients with malnutrition when compared to patients without malnutrition (42% vs 7%, p<0.05). The oral feeding time, complication rates, and length of hospital stay were similar in both groups (p>0.05). CONCLUSION: Children with MIS-C already had mild to severe malnutrition at admission. Rash and higher ferritin levels were more common in patients with malnutrition. In addition to anthropometric parameters, sarcopenia calculated using tPMA can be used to predict malnutrition in critically-ill children.

Cardiovascular involvement in children with COVID-19 temporally related multisystem inflammatory syndrome (MIS-C): can cardiac magnetic resonance arrive to the heart of the problem?

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) shows a significant overlap of symptoms with other hyper-inflammatory diseases such as Kawasaki disease (KD), but the real difference of the two conditions is still matter of debate. Coronary artery lesions (CAL) are the most relevant complication in KD. Nonetheless, CAL, myocarditis, pericarditis, arrhythmia are the main cardiovascular complications in MIS-C. A close clinical assessment is mandatory, both at the diagnosis and during the follow-up, by ECG and echocardiography. Cardiac magnetic resonance (MRI) adds important data to ultrasound findings. However, cardiac MRI studies in MIS-C are limited to a small number of cohorts. METHODS: We enrolled 20 children (age:1-16 years; 11 F; 9 M) with cardiac involvement secondary to MIS-C, all evaluated by cardiac MRI. RESULTS: 8 children showed pathological cardiac MRI: 2 showed pericardial effusion; 2 showed myocardial oedema; 1 showed aortic insufficiency; 3 showed delayed enhancement (one for acute myocarditis with oedema; 2 for myocardial fibrosis). Delayed enhancement was reduced significantly 5.6-9 months after the first MRI evaluation. 25% of patients with pathological MRI had CAL associated with valvular insufficiency of 2 valves. 17% of patients with normal MRI had CAL, associated with valvular insufficiency of 1 valve in 1 patient. The correlations between haematological, clinical, cardiologic parameters, treatment, did not reach the statistical significance. 4 patients were treated with anakinra. Among those, 2 patients showed a normal cardiac MRI. Cardiac lesions resolved in all the patients during the follow-up. Some patients with pathological cardiac MRI could not underwent a control with MRI, for the low compliance. However, echocardiography and ECG, documented the resolution of the pathological data in these cases. CONCLUSIONS: A higher risk of CAL was documented in patients with an association of other cardiac lesions. Cardiac MRI is difficult to perform routinely; however, it is useful for evaluating the acute myocardial damage and the outcome of patients with MIS-C.

Proteomic mapping identifies serum marker signatures associated with MIS-C specific hyperinflammation and cardiovascular manifestation.

Multisystem inflammatory syndrome in children (MIS-C) shares several clinical and immunological features with Kawasaki Disease (KD) and pediatric hyperinflammation, but the immuno-phenotypic overlap among these clinical mimics is still incompletely understood. Here we analyzed serum samples from treatment-naïve patients with MIS-C (n = 31) and KD (n = 11), pediatric hyperinflammation (n = 13) and healthy controls (HC, n = 10) by proximity extension assay (PEA) to profile 184 blood biomarkers. Collectively, immunophenotypic overlap between MIS-C and hyperinflammation exceeds overlap with KD. Overexpression of IL-17A in MIS-C and KD could best separate these conditions from hyperinflammatory conditions, while those were hallmarked by overabundance of adenosin deaminase and IL-18. Depletion in serum TNF-related subfamily member 9 (TNFRSF9) and apoptosis inducing ligand (TRAIL) linked with cardiovascular manifestations and myocarditis in MIS-C. Altogether, our analysis highlights important differences in molecular marker signatures also across different MIS-C and KD cohorts and suggests several previously unidentified molecular associations in context of cardiovascular inflammation.

Immunoregulatory natural killer cells.

This review discusses a broader scope of functional roles for NK cells. Despite the well-known cytolytic and inflammatory roles of NK cells against tumors and pathogenic diseases, extensive evidence demonstrates certain subsets of NK cells have defacto immunoregulatory effects and have a role in inducing anergy or lysis of antigen-activated T cells and regulating several autoimmune diseases. Furthermore, recent evidence suggests certain subsets of immunoregulatory NK cells can cause anergy or lysis of antigen-activated T cells to regulate hyperinflammatory diseases, including multisystem inflammatory syndrome. Several pathogens induce T cell and NK cell exhaustion and/or suppression, which impair the immune system's control of the replication speed of virulent pathogens and tumors and result in extensive antigens and antigen-antibody immune complexes, potentially inducing to some extent a Type III hypersensitivity immune reaction. The Type III hypersensitivity immune reaction induces immune cell secretion of proteinases, which can cleave specific proteins to create autoantigens which activate T cells to initiate autoimmune and/or hyperinflammatory diseases. Furthermore, pathogen induced NK cell exhaustion and/or suppression will inhibit NK cells which would have induced the anergy or lysis of activated T cells to regulate autoimmune and hyperinflammatory diseases. Autoimmune and hyperinflammatory diseases can be consequences of the dual lymphocyte exhaustion and/or suppression effects during infections, by creating autoimmune and/or hyperinflammatory diseases, while also impairing immunoregulatory lymphocytes which otherwise would have regulated these diseases.

Cytokine storm in Chikungunya: Can we call it multisystem inflammatory syndrome associated with Chikungunya? / Tormenta de citoquinas en Chikungunya. ¿Podemos llamarla Síndrome inflamatorio multisistémico asociado a Chikungunya?

Paraguay is currently facing a new outbreak of Chikungunya virus. This report summarizes two severe cases of Chikungunya (CHIKV) infection, confirmed by real-time reverse transcription polymerase chain reaction. We present the cases of patients with acute CHIKV infection and multisystem involvement, with fever, rash, abdominal pain, vomiting, myocarditis, and coronary artery anomalies, very similar to the cases described in MIS-C related to SARS-CoV-2 during the COVID-19 Pandemic. Both patients received IVIG and methylprednisolone, with good clinical response. In this setting of cytokine storm in Chikungunya, can we call it “Multisystem inflammatory syndrome associated with Chikungunya”?.(AU)

Paraguay se enfrenta actualmente a un nuevo brote del virus Chikungunya. Este informe resume dos casos graves de infección por Chikungunya (CHIKV), confirmados mediante reacción en cadena de la polimerasa con transcripción inversa en tiempo real. Presentamos los casos de pacientes con infección aguda por CHIKV y afectación multisistémica, con fiebre, erupción cutánea, dolor abdominal, vómitos, miocarditis y anomalías de las arterias coronarias, muy similares a los casos descritos en síndrome inflamatorio multisistémico relacionado con el SARS-CoV-2 durante la pandemia de COVID-19. Ambos pacientes recibieron IGIV y metilprednisolona, con buena respuesta clínica. En este escenario de tormenta de citoquinas en Chikungunya, ¿podemos llamarla «síndrome inflamatorio multisistémico asociado a Chikungunya»?.(AU)

Multisystem Inflammatory Syndrome in Adults-Related Unstable Angina With Coronary Aneurysm in a Young Female: A Case Report.

Multisystem inflammatory syndrome in adults (MIS-A) is a systemic inflammatory disease associated with COVID-19 and follows coronary artery aneurysms similar to Kawasaki disease. In many cases, it is improved by treatments such as high-dose steroids or intravenous immunoglobulin (IVIg). However, the role of untreated coronary artery aneurysms leading to future stenosis remains unknown. Untreated MIS-A may potentially lead to the formation of coronary aneurysms. In cases of COVID-19 where young adults present with angina-like symptoms, an evaluation for angina is considered. Herein, we report a case of a 27-year-old female who developed unstable angina with coronary artery aneurysms six months after COVID-19 infection. She required surgery for unstable angina, which resulted in an improvement in chest pain. Coronary artery lesions are considered to be related to MIS-A, and treatment was conducted in accordance with that for Kawasaki disease. Currently, the pathological differences and prognosis between MIS-A and Kawasaki disease remain unclear, but the elucidation of the conditions is warranted in the future.

Vitamin D Supplementation in Neonatal and Infant MIS-C Following COVID-19 Infection.

To date, the SARS-CoV-2 pandemic still represents a great clinical challenge worldwide, and effective anti-COVID-19 drugs are limited. For this reason, nutritional supplements have been investigated as adjuvant therapeutic approaches in disease management. Among such supplements, vitamin D has gained great interest, due to its immunomodulatory and anti-inflammatory actions both in adult and pediatric populations. Even if there is conflicting evidence about its prevention and/or mitigation effectiveness in SARS-CoV-2 infection, several studies demonstrated a strict correlation between hypovitaminosis D and disease severity in acute COVID-19 and MIS-C (multisystem inflammatory syndrome in children). This narrative review offers a resume of the state of the art about vitamin D's role in immunity and its clinical use in the context of the current pandemic, specially focusing on pediatric manifestations and MIS-C. It seems biologically reasonable that interventions aimed at normalizing circulating vitamin D levels could be beneficial. To help clinicians in establishing the correct prophylaxis and/or supportive therapy with vitamin D, well-designed and adequately statistically powered clinical trials involving both adult and pediatric populations are needed. Moreover, this review will also discuss the few other nutraceuticals evaluated in this context.

A case report on multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 infection.

Key Clinical Message: Early recognition and treatment of Multisystem Inflammatory Syndrome in Children (MIS-C) within the context of COVID-19 infection is crucial for improved outcomes. Prompt intervention with IVIG and steroids leads to significant improvement in a severe case of MIS-C. Clinicians should be vigilant for MIS-C symptoms and initiate timely management. Abstract: We report a case involving a fourteen-year-old male with COVID-19 infection who developed multisystem inflammatory disease. A previously healthy child presented with a history of 10 days of fever and cough, along with diarrhea, and vomiting for 3 days. His COVID-19 infection was confirmed through Polymerase Chain Reaction (PCR), and the laboratory values were remarkable for high levels of C-reactive protein, D-dimers, B-type natriuretic peptide (BNP), and troponin I. He developed circulatory shock on the second day of the presentation and needed inotropic support. Steroids and intravenous immunoglobulin (IVIG) were started in light of Multisystem Inflammatory Syndrome in Children (MIS-C), which improved his condition. Thus, during the management of COVID-19 infection, early detection and a careful clinical characterization for MIS-C are essential.