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A systematic review and meta-analysis were performed to evaluate the virus-specific T-cell response after COVID-19 mRNA vaccination, using the QuantiFERON SARS-CoV-2 interferon-γ release assay. A search was conducted (June 8, 2023) in the PUBMED, SCOPUS, and medRxiv databases, to identify studies reporting the QuantiFERON SARS-CoV-2 (Starter (two antigen tubes) or Starter + Extended Pack (three antigen tubes), cut-off ≥ 0.15 IU/mL) positivity rate (PR) in immunocompetent adults, following the administration of two or three COVID-19 mRNA vaccine doses. Study quality was evaluated with the Critical Appraisal Skills Programme Tool. A meta-analysis was conducted using a random-effects model. Heterogeneity and publication bias were assessed. Eleven eligible studies (with 5–73 vaccinated immunocompetent participants) were identified. For COVID-19-naïve participants, ≤ 3 months after the second dose, the pooled PR (random-effects model) was 86 (95% confidence interval (95% CI) 78–95%). Comparing the Starter vs. the Starter + Extended Pack, a significant difference in PRs was detected (80.6% vs. 100% p-value < 0.001). At 3–6 and >6 months after the second dose and ≥ 3 months after the third dose, the pooled PRs were 59% (95% CI 45–72%), 79% (95% CI 66–92%), and 66% (95% CI 50–82%), respectively. For convalescent participants, ≥ 6 months after the third dose, the pooled PR was 81% (95% CI 67–95%). Limitations include heterogeneity and a small number of studies, at some timepoints. In conclusion, following the second or third COVID-19 mRNA vaccine dose, QuantiFERON SARS-CoV-2 detected positive responses in a certain percentage of the vaccinees, possibly because of waning immunity, reduced assay sensitivity, or lack of T-cell response induction in some vaccinees. The detection of positive responses was higher when the Starter + Extended Pack was used. PROSPERO Registration Number: CRD42023431315. [ABSTRACT FROM AUTHOR]

Background/Objectives: Multisystem Inflammatory Syndrome in Children (MIS-C) is a post-infectious complication of COVID-19. MIS-C has overlapping features with other pediatric inflammatory disorders including Kawasaki Disease (KD), Macrophage Activation Syndrome (MAS), Toxic Shock Syndrome and sepsis. The exact mechanisms responsible for the clinical overlap between MIS-C and these conditions remain unclear, and biomarkers that could distinguish MIS-C from its clinical mimics are lacking. This study aimed to provide an overview of how proteomic methods, like Mass Spectrometry (MS) and affinity-based proteomics, can offer a detailed understanding of pathophysiology and aid in the diagnosis and prognosis of MIS-C. Methods: A narrative review of relevant studies published up to July 2024 was conducted. Results: We identified 15 studies and summarized their key proteomic findings. These studies investigated the serum or plasma proteome of MIS-C patients using MS, Proximity Extension, or Aptamer-based assays. The studies associated the proteomic profile of MIS-C with laboratory and clinical parameters and/or compared it with that of other diseases including acute COVID-19, KD, MAS, pediatric rheumatic diseases, sepsis and myocarditis or pericarditis following COVID-19 mRNA immunization. Depending on the method and the control group, different proteins were increased or decreased in the MIS-C group. The limitations and challenges in MIS-C proteomic research are also discussed, and future research recommendations are provided. Conclusions: Although proteomics appear to be a promising approach for understanding the pathogenesis and uncovering candidate biomarkers in MIS-C, proteomic studies are still needed to recognize and validate biomarkers that could accurately discriminate MIS-C from its clinical mimics. [ABSTRACT FROM AUTHOR]

Background/Objectives: Multisystem Inflammatory Syndrome in children (MIS-C) is a rare but severe post-infectious complication of COVID-19 that often requires admission to the Pediatric Intensive Care Unit (PICU). The present study aimed to compare the demographic, clinical, and laboratory characteristics of children diagnosed with MIS-C who were admitted to the PICU and those who did not require PICU admission. Methods: Children diagnosed with MIS-C from September 2020 to April 2023 were included in this case-control study. Demographic, clinical, and laboratory data were collected from medical records. Results: Fifty children with MIS-C were included in the study [median (IQR) age: 7.5 (4.3, 11.4) years, 28/50 (56%) males]. Twenty-two (22/50, 44%) children required admission to the PICU. In the multivariate regression analysis, hepatic (OR: 12.89, 95%CI: 1.35–123.41, p-value = 0.03) and cardiological involvement (OR: 34.55, 95%CI: 2.2–541.91, p-value = 0.01) were significantly associated with hospitalization at the PICU. Regarding the laboratory and imaging parameters during the first 48 h from admission, D-dimer levels higher than 4 μg/mL and decreased Left Ventricular Ejection Fraction (LVEF) were associated with an increased risk of PICU admission (OR: 7.95, 95%CI: 1.48–42.78, p-value = 0.02 and OR = 1.28, 95%CI: 1.07–1.53, p-value = 0.01). Children who were admitted to the PICU were more likely to develop complications during their hospitalization (10/22, 45.5% vs. 3/28, 10.7%, p-value = 0.005) and were hospitalized for more days than children in the pediatric ward (median length of stay (IQR): 20 (15, 28) days vs. 8.5 (6, 14) days, p-value < 0.001). Conclusions: The findings of this study indicate that cardiovascular and hepatic involvement and increased D-dimer levels in children with MIS-C might be associated with admission to the PICU. [ABSTRACT FROM AUTHOR]

This is a SARS-CoV-2 seroepidemiological study in a pediatric population (0–16 years) during the BA.5 Omicron predominance period in the Athens metropolitan area. Serum samples were tested for SARS-CoV-2 nucleocapsid antibodies (Abs-N), representing natural infection during three periods of BA.5 predominance: 1 May 2022–31 August 2022 (period A), 1 September 2022–31 December 2022 (period B), and July 2023 (period C). Εpidemiological data were also collected. Additionally, in period C, Abs-N-seronegative samples were tested for SARS-CoV-2 spike antibodies (Abs-S). A total of 878 children were tested (males: 52.6%), with a median age (IQR) of 96 (36–156) months; the number of cases of seropositivity during the three periods were as follows: A: 292/417 (70%), B: 288/356 (80.9%), and C: 89/105 (84.8%), with p < 0.001. SARS-CoV-2 seropositivity increased from period A to C for children 0–1 year (p = 0.044), >1–4 years (p = 0.028), and >6–12 years (p = 0.003). Children > 6–12 years had the highest seropositivity rates in all periods (A: 77.3%, B: 91.4%, and C: 95.8%). A significant correlation of monthly median Abs-N titers with monthly seropositivity rates was detected (rs: 0.812, p = 0.008). During period C, 12/105 (11.4%) Abs-S-seropositive and Abs-N-seronegative samples were detected and total seropositivity was estimated at 96.2% (101/105). The findings of this study indicate a high SARS-CoV-2 exposure rate of children during the BA.5 predominance period and suggest that in future seroepidemiological studies, both antibodies should be tested in Abs-N-seronegative populations. [ABSTRACT FROM AUTHOR]