Search

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: The immunological pathways that cause Multisystem Inflammatory Syndrome after SARS-CoV-2 infection in children (MIS-C) remain under investigation. Methods: The aim of this study was to prospectively compare the T-cell cytokine expression profile in unvaccinated children with acute MIS-C (MISC_A) before immunosuppression, convalescent MIS-C (one month after syndrome onset, MISC_C), convalescent COVID-19 (one month after hospitalization), and in healthy, unvaccinated controls. The intracellular expression of IL-4, IL-2, IL-17, IFNγ, TNF-α and Granzyme B, and the post SARS-CoV-2-Spike antigenic mix stimulation of T-cell subsets was analyzed by 13-color flow cytometry. Results: Twenty children with a median age (IQR) of 11.5 (7.25–14) years were included in the study. From the comparison of the flow cytometry analysis of the 14 markers of MISC_A with the other three groups (MISC_C, post-COVID-19 and controls), significant differences were identified as follows: 1. CD4+IL-17+/million CD3+: 293.0(256.4–870.9) vs. 50.7(8.4–140.5); p-value: 0.03, vs. 96.7(89.2–135.4); p-value: 0.03 and vs. 8.7(0.0–82.4); p-value: 0.03, respectively; 2. CD8+IL-17+/million CD3+: 335.2(225.8–429.9) vs. 78.0(31.9–128.9) vs. 84.1(0.0–204.6) vs. 33.2(0.0–114.6); p-value: 0.05, respectively; 3. CD8+IFNγ+/million CD3+: 162.2(91.6–273.4) vs. 41.5(0.0–77.4); p-value: 0.03 vs. 30.3(0.0–92.8); p-value: 0.08, respectively. Conclusions: In children presenting with MIS-C one month after COVID-19 infection, T cells were found to be polarized towards IL-17 and IFNγ production compared to those with uncomplicated convalescent COVID-19, a finding that could provide possible immunological biomarkers for MIS-C detection. [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/Objective: Secreted frizzled-related protein 5 (Sfrp5) is an anti-inflammatory adipokine that has been implicated in the pathophysiology of obesity and its metabolic complications. Despite the fact that numerous studies have been carried out in adults, limited data on Sfrp5 exist for youth, especially in relation to overweight and obesity. Methods: In our study, we assessed the concentrations of Sfrp5, total oxidative (TOS) and antioxidative (TAS) status, high-sensitivity C-reactive protein (hs-CRP), and several cytokines (IL-1α, IL-1β, IL-2, IL-6, IL-8, IL-12, TNF-α) in 120 children and adolescents (mean age ± SE: 11.48 ± 0.25 years; 48 prepubertal, 72 pubertal; 74 males and 46 females) before and 1 year after the implementation of a personalized, structured, lifestyle intervention program of healthy diet, sleep, and physical exercise. Results: Based on the body mass index (BMI), participants were categorized as having morbid obesity (n = 63, 52.5%), obesity (n = 21, 17.5%), overweight (n = 22, 18.33%), or normal BMIs (n = 14, 11.67%), based on the International Obesity Task Force (IOTF) cut-off points. Following the 1-year lifestyle intervention program, a significant improvement in anthropometric measurements (BMI, BMI-z score, diastolic blood pressure, WHR, and WHtR), body-composition parameters, hepatic enzymes, lipid profile, inflammation markers, and the insulin-sensitivity profile (HbA1C, HOMA index) was observed in all subjects. Sfrp5 decreased in subjects with obesity (p < 0.01); however, it increased significantly (p < 0.05) in patients with morbid obesity. Linear regression analysis indicates that TNF-α and systolic blood pressure were the best positive predictors and hs-CRP was the best negative predictor for Sfpr5 concentration at initial assessment and glucose concentration for ΔSfrp5, while TNF-α and TAS were the best positive predictors for Sfpr5 concentration at annual assessment. Conclusions: These results indicate that Sfrp5 is associated with severe obesity and is increased following weight loss in children and adolescents with morbid obesity. It is also related to metabolic homeostasis, as well as inflammation and oxidative status. [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]

Group A rotavirus (RVA), which causes acute gastroenteritis (AGE) in children worldwide, is categorized mainly based on VP7 (genotype G) and VP4 (genotype P) genes. Genotypes that circulate at <1% are considered unusual. Important genes also include VP6 (genotype I) and NSP4 (genotype E). VP6 establishes the group and affects immunogenicity, while NSP4, as an enterotoxin, is responsible for the clinical symptoms. The aim of this study was to genotype the VP6 and NSP4 genes and molecularly characterize the NSP4 and VP6 genes of unusual RVA. Unusual RVA strains extracted from fecal samples of children ≤16 years with AGE were genotyped in VP6 and NSP4 genes with Sanger sequencing. In a 15‐year period (2007–2021), 54.8% (34/62) of unusual RVA were successfully I and E genotyped. Three different I and E genotypes were identified; I2 (73.5%, 25/34) and E2 (35.3%, 12/34) were the most common. E3 genotype was detected from 2017 onwards. The uncommon combination of I2‐E3 was found in 26.5% (9/34) of the strains and G3‐P[9]‐I2‐E3 remained the most frequent G‐P‐I‐E combination (20.6%, 7/34). Children infected with RVA E2 strains had a statistically higher frequency of dehydration (50%) than those infected with RVA E3 strains (p = 0.019). Multiple substitutions were detected in NSP4, but their functional effect remains unknown. The result indicates the genetic diversity of RVA strains. Continuous surveillance of the RVA based on the whole genome will provide better knowledge of its evolution. [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]

SARS-CoV-2 infection is associated with respiratory complications, especially during the acute phase. We report an unusual case of an adolescent boy who presented with cough, dyspnea and unilaterally absent breath sounds on auscultation. Two weeks prior to the admission, the patient reported lowgrade fever and mild cough. A rapid SARS-CoV-2 antigen test was positive. On admission, the child tested positive for SARS-CoV-2 with polymerase chain reaction (PCR). The diagnosis of spontaneous pneumothorax was confirmed by a chest X-ray. A chest tube was inserted, and symptoms gradually resolved. This case report highlights that SARS-CoV-2 infection may cause serious respiratory complications in children, even after the resolution of acute infection. [ABSTRACT FROM AUTHOR]