Systematic review and meta‐analysis on the serological, immunological, and cardiac parameters of the multisystem inflammatory syndrome (MIS‐C) associated with SARS‐CoV‐2 infection

Esslami, Golnaz Ghazizadeh; Mamishi, Setareh; Pourakbari, Babak; Mahmoudi, Shima

doi:10.1002/jmv.28927

Cited by 5 publications

(2 citation statements)

References 62 publications

(85 reference statements)

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“…Limited data are available regarding SARS-CoV-2 serological response dynamics in pediatric patients with COVID-19, and there are substantial gaps in our understanding of the immune response in children ( Bohn et al, 2023 ). A recent meta-analysis estimated the combined prevalence of positive SARS-CoV-2 IgM and IgG antibody tests in MIS-C to be 39% and 81%, respectively ( Ghazizadeh Esslami et al, 2023 ). However, there is a scarcity of reports in pediatrics, particularly those employing a prospective or longitudinal design regarding SARS-CoV-2 serological response dynamics.…”

Section: Introductionmentioning

confidence: 99%

Post-discharge follow-up of pediatric COVID-19 patients: insights into serological dynamics

Mahmoudi,

Pourakbari,

Shahbabaie

et al. 2024

Front. Microbiol.

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IntroductionLimited data are available regarding SARS-CoV-2 serological response dynamics in pediatric patients with COVID-19, contributing to gaps in our understanding of the immune response in this population. This study aimed to investigate SARS-CoV-2 IgG seropositivity in patients diagnosed with COVID-19 during hospitalization and 2–4 weeks after discharge.MethodsA cohort of patients, consisting of 31 individuals with confirmed acute COVID-19 infection and 27 diagnosed with Multisystem Inflammatory Syndrome in Children (MIS-C), was enrolled in the study. Follow-up clinic appointments were scheduled for 2–4 weeks post-discharge. During admission and follow-up, blood samples were collected from each patient for laboratory analysis. Anti-nucleoprotein SARS-CoV-2 IgG levels were determined using the Enzyme-Linked Immunosorbent Assay (ELISA) method.ResultsIn this study, a cohort of 58 patients was examined. At admission, 52% (n = 14) of MIS-C patients and 10% (n = 3) of acute COVID-19 patients had positive SARS-CoV-2 IgG test. Only 48 cases were referred to the hospital, and follow-up data was available for 20 cases with MIS-C and 28 cases with acute COVID-19. All patients (n = 15) who initially tested positive for SARS-CoV-2 IgG at admission remained positive serology during follow-up (100%). Among the 33 patients who initially tested negative, 12 (37.5%) showed a positive serology result during follow-up, while 21 (62.5%) remained negative. Within this subgroup, 11 cases (44%) were diagnosed with acute COVID-19, and one patient (12.5%) presented with MIS-C. Fourteen cases with acute COVID-19 infection (56%) and seven cases with MIS-C (87.5%) consistently showed negative serology results throughout the study. During follow-up, the median lymphocyte count demonstrated a significant difference, with 0.96 × 109 cells per L (IQR: 0.75–3.0 × 109 cells per L) in the SARS-CoV-2 IgG-negative group and 2.9 × 109 cells per L (IQR = 1.33–7.22 × 109 cells per L) in the SARS-CoV-2 IgG-positive group (p-value = 0.03). Patients who demonstrated seropositivity during the follow-up were associated with a notably severe disease (p-value = 0.028).ConclusionOur study highlights the dynamic nature of SARS-CoV-2 IgG antibody responses in pediatric patients with COVID-19 infection. We observed a notable increase in seropositivity rates during follow-up. Furthermore, patients who were seropositive at follow-up demonstrated a severe disease course and lower lymphocyte counts compared to those with persistently negative serology. Our findings underscore the importance of longitudinal serological monitoring in understanding disease progression and immune response dynamics in pediatric COVID-19 cases.

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Section: Introductionmentioning

confidence: 99%

Post-discharge follow-up of pediatric COVID-19 patients: insights into serological dynamics

Mahmoudi,

Pourakbari,

Shahbabaie

et al. 2024

Front. Microbiol.

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“…A SARS-CoV-2 infection primarily causes symptoms similar to the common flu, with patients presenting with fever, respiratory disorder and myalgia [1][2][3][4][5]. Soon, it was discovered that SARS-CoV-2 also affects the immune system by triggering hyper-inflammatory reactions, which eventually may cause a systemic illness called Multisystemic inflammatory syndrome in children, i.e., "MIS-C" [6][7][8][9][10]. However, vaccination against SARS-CoV-2 shows potential interactions with the immune system that may, in rare cases, cause similar disorders of autoimmune reactions and disorders [11,12].…”

Section: Introductionmentioning

confidence: 99%

“Multisystem Inflammatory Syndrome in Children”-Like Disease after COVID-19 Vaccination (MIS-V) with Potential Significance of Functional Active Autoantibodies Targeting G-Protein-Coupled Receptors (GPCR-fAAb) for Pathophysiology and Therapy

Schmidt,

Hébert,

Wallukat

et al. 2023

Children

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Background: An infection with SARS-CoV-2 can trigger a systemic disorder by pathological autoimmune processes. A certain type of this dysregulation is known as Multisystemic inflammatory syndrome in children (MIS-C). However, similar symptoms may occur and have been described as Multisystemic inflammatory syndrome after SARS-CoV-2 Vaccination (MIS-V) following vaccination against SARS-CoV-2. We report the case of a 12-year-old boy who was identified with MIS-C symptoms without previous SARS-CoV-2 infection after receiving two doses of the Pfizer–BioNTech COVID-19 vaccine approximately one month prior to the onset of symptoms. He showed polyserositis, severe gastrointestinal symptoms and, consequently, a manifestation of a multiorgan failure. IgG antibodies against spike proteins of SARS-CoV-2 were detected, indicating a successful vaccination, while SARS-CoV-2 Nucleocapsid protein antibodies and SARS-CoV-2 PCR were not detected. Several functional, active autoantibodies against G-protein-coupled receptors (GPCR-fAAb), previously associated with Long COVID disease, were detected in a cardiomyocyte bioassay. Immunosuppression with steroids was initiated. Due to side effects, treatment with steroids and later interleukin 1 receptor antagonists had to be terminated. Instead, immunoadsorption was performed and continued with tacrolimus and mycophenolic acid therapy, leading to improvement and discharge after 79 days. GPCR-fAAb decreased during therapy and remained negative after clinical curing and under continued immunosuppressive therapy with tacrolimus and mycophenolic acid. Follow-up of the patient showed him in good condition after one year. Conclusions: Infection with SARS-CoV-2 shows a broad and severe variety of symptoms, partly due to autoimmune dysregulation, which, in some instances, can lead to multiorgan failure. Despite its rarity, post-vaccine MIS-C-like disease may develop into a serious condition triggered by autoimmune dysregulation. The evidence of circulating GPCR-fAAb and their disappearance after therapy suggests a link of GPCR-fAAb to the clinical manifestations. Thus, we hypothesize a potential role of GPCR-fAAb in pathophysiology and their potential importance for the therapy of MIS-C or MIS-V. However, this observation needs further investigation to prove a causative correlation.

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Diagnostic value of D-dimer in differentiating multisystem inflammatory syndrome in Children (MIS-C) from Kawasaki disease: systematic literature review and meta-analysis

Lippi,

Mattiuzzi,

Favaloro

2024

Diagnosis

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Coronavirus disease 2019 (COVID-19) is frequently associated with thrombo inflammation, which can predispose to developing of life-threatening conditions in children such as the multisystem inflammatory syndrome (MIS-C) and Kawasaki disease. Because of the consistent overlap in pathogenesis and symptoms, identifying laboratory tests that may aid in the differential diagnosis of these pathologies becomes crucial. We performed an electronic search in PubMed, Web of Science and Scopus, without date or language restrictions, to identify all possible studies reporting D-dimer values in separate cohorts of children with MIS-C or Kawasaki disease. Three multicenter cohort studies were included in our analysis, totaling 487 patients (270 with MIS-C and 217 with Kawasaki disease). In this meta-analysis, significantly higher D-dimer values were found in MIS-C compared to Kawasaki disease in all three studies, yielding an SMD of 1.5 (95 % CI, 1.3–1.7) mg/L. Thus, very high D-dimer values early in the course of disease should raise the clinical suspicion of MIS-C rather than Kawasaki disease. Further studies should be planned to identify harmonized D-dimer diagnostic thresholds that may help discriminate these conditions.

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Systematic review and meta‐analysis on the serological, immunological, and cardiac parameters of the multisystem inflammatory syndrome (MIS‐C) associated with SARS‐CoV‐2 infection

Cited by 5 publications

References 62 publications

Post-discharge follow-up of pediatric COVID-19 patients: insights into serological dynamics

Post-discharge follow-up of pediatric COVID-19 patients: insights into serological dynamics

“Multisystem Inflammatory Syndrome in Children”-Like Disease after COVID-19 Vaccination (MIS-V) with Potential Significance of Functional Active Autoantibodies Targeting G-Protein-Coupled Receptors (GPCR-fAAb) for Pathophysiology and Therapy

Diagnostic value of D-dimer in differentiating multisystem inflammatory syndrome in Children (MIS-C) from Kawasaki disease: systematic literature review and meta-analysis

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