SARS-CoV-2 Seroepidemiology and Antibody Levels in Children during BA.5 Predominance Period.

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.

Longitudinal Cardiac Evaluation of Children with Multisystem Inflammatory Syndrome (MIS-C) Following COVID-19 by Conventional and Speckle-Tracking Echocardiography.

Multisystem inflammatory syndrome in children (MIS-C), is a rare but severe, hyperinflammatory complication of COVID-19, in which cardiovascular abnormalities are frequently detected. In this prospective study, we describe the echocardiographic findings in patients with MIS-C, with the use of conventional Echocardiography and Speckle-Tracking Echocardiography (STE) with Left Ventricular (LV) Global Longitudinal Strain (GLS) analysis, in the acute and follow-up phase. In total, 25 MIS-C patients [64% females, mean (± SD) age: 8.3 (± 3.72) years] were included. In the acute phase, median (IQR) Troponin and NT-proBNP and mean heart rate, were 8.07 (14.52) pg/mL, 2875.00 (7713.00) pg/mL, and 102.87 (± 22.96) bpm, respectively. Median (IQR) LV Ejection Fraction (LVEF) was 66 (8)% and LVEF impairment was detected in 2/25 (8%) patients. On follow-up (mean time interval:9.50 ± 4.59 months), heart rate was significantly lower, with a mean value of 90.00 (± 14.56) bpm (p-value = 0.017). Median (IQR) LVEF was 66.00 (6.70)% (p-value = 0.345) and all 25 participants had normal LVEF. In 14/25 patients, additional LV-GLS analysis was performed. During the acute phase, mean LV-GLS was - 18.02 (± 4.40)%. LV-GLS was abnormal in 6/14 patients (42.9%) and among them, only one patient had reduced LVEF. On follow-up (median (IQR) time interval:6.93 (3.66) months), mean LV-GLS was -20.31 (± 1.91)% (p-value = 0.07) and in 1/14 patient (7.1%), the LV-GLS impairment persisted. In conclusion, in the acute and follow-up phase, we detected abnormal LV-GLS values in some patients, in the presence of normal LVEF, indicating that STE-GLS is a valuable tool for identifying subclinical myocardial injury in MIS-C.

The Soluble Urokinase Plasminogen Activator Receptor as a Severity Biomarker in Children With Acute COVID-19 or Multisystem Inflammatory Syndrome.

BACKGROUND: Elevated soluble urokinase plasminogen activator receptor (suPAR) has been associated with a poor prognosis in serious infections. The aim of this study was to evaluate the clinical value of suPAR in children with acute coronavirus disease 2019 (COVID-19) or multisystem inflammatory syndrome (MIS-C). METHODS: Serum suPAR was measured using the suPARnostic AUTO Flex enzyme-linked immunosorbent assay in hospitalized children with COVID-19, MIS-C, bacterial pneumonia, and healthy controls. RESULTS: A total of 211 children with a mean (±SD) age of 6.9 ± 4.96 years were tested; with COVID-19: 59 (28%), MIS-C: 36 (17%), pneumonia: 78 (37%) and healthy controls: 38 (18%). In the acute phase, the levels of suPAR (mean ± SD) were: MIS-C: 8.11 ± 2.80 ng/mL, COVID-19: 4.91 ± 1.90 ng/mL, pneumonia: 4.25 ± 1.44 ng/mL and controls: 2.09 ± 0.47 ng/mL ( P < 0.001). Children with acute COVID-19 and a severe or moderate clinical presentation had higher values than those with mild symptoms: 5.79 ± 1.58 versus 5.40 ± 1.94 versus 3.19 ± 0.73 ng/mL, respectively ( P < 0.001). In the MIS-C group, children hospitalized in the intensive care unit and in need of mechanical ventilation had higher suPAR than those who were not admitted to an intensive care unit: 9.32 ± 3.06 versus 7.13 ± 2.19 ng/mL, respectively ( P = 0.023). In children with COVID-19 or MIS-C, a correlation was detected between suPAR values and length of hospitalization ( rs = 0.418, P < 0.001). CONCLUSIONS: The findings suggest that suPAR may be a valuable biomarker of disease severity in children with COVID-19 or MIS-C. This could facilitate the identification of children in need of intensive anti-inflammatory treatment, as it has been shown in adults with severe COVID-19.

Kinetics of SARS-CoV-2 Spike Antibodies after the Second and Third Dose of the BNT162b2 COVID-19 Vaccine and Association with Epidemiological Characteristics and Breakthrough Infection in a Cohort Study of Healthcare Workers.

To prospectively study the kinetics of immune responses after immunization with the BNT162b2 mRNA COVID-19 vaccine and their association with epidemiological parameters and breakthrough infection (BI), we measured total (TAbs-WT) and neutralizing antibodies against wild-type (NAbs-WT) and Omicron (NAbs-O) SARS-CoV-2 spike proteins in healthcare workers (HCWs) after the second (4 and 8 months) and third dose (1 and 8 months). Vaccinated HCWs (n = 486), with a median age (IQR) of 49 years (38-56), were included in this prospective cohort study. BI was observed 4 and 8 months after the second dose in 8/486 (1.6%) and 15/486 (3.1%) HCWs, respectively, and 1 and 8 months after the third dose in 17/486 (3.5%) and 152/486 (31.3%) HCWs, respectively. A comparison of immune responses 1 month after the third dose in vaccinated HCWs without a BI or with a BI in the next 7 months did not detect any statistically significant differences in the TAbs-WT (median (IQR): 16,611.0 (13,011.0) U/mL vs. 17,572.5 (14,501.0) U/mL, p = 0.529) and NAbs-WT (median (IQR): 96.5% (1.7) vs. 96.7% (1.9), p = 0.555). After infection, HCWs with a BI had significantly increased TAbs-WT levels at all time points compared to healthy HCWs. The findings of the present study indicate that antibody levels after three doses of the BNT162b2 vaccine are not directly associated with the possibility of a BI.

Epidemiological study of unusual rotavirus strains and molecular characterization of emerging P[14] strains isolated from children with acute gastroenteritis during a 15-year period.

Rotavirus group A (RVA) is characterized by molecular and epidemiological diversity. To date, 42 G and 58 P RVA genotypes have been identified, some of which, like P[14], have a zoonotic origin. In this study, we describe the epidemiology of unusual RVA genotypes and the molecular characteristics of P[14] strains. Fecal samples from children ≤ 16 years of age with acute gastroenteritis (AGE) who were hospitalized during 2007-2021 in Greece were tested for RVA by immunochromatography. Positive RVA samples were G and P genotyped, and part of the VP7 and VP4 genes were sequenced by the Sanger method. Epidemiological data were also recorded. Phylogenetic analysis of P[14] was performed using MEGA 11 software. Sixty-two (1.4%) out of 4427 children with RVA AGE were infected with an unusual G (G6/G8/G10) or P (P[6]/P[9]/P[10]/P[11]/P[14]) genotype. Their median (IQR) age was 18.7 (37.3) months, and 67.7% (42/62) were males. None of the children were vaccinated against RVA. P[9] (28/62; 45.2%) was the most common unusual genotype, followed by P[14] (12/62; 19.4%). In the last two years, during the period of the COVID-19 pandemic, an emergence of P[14] was observed (5/12, 41.6%) after an 8-year absence. The highest prevalence of P[14] infection was seen in the spring (91.7%). The combinations G8P[14] (41.7%), G6P[14] (41.7%), and G4P[14] (16.6%) were also detected. Phylogenetic analysis showed a potential evolutionary relationship of three human RVA P[14] strains to a fox strain from Croatia. These findings suggest a possible zoonotic origin of P[14] and interspecies transmission between nondomestic animals and humans, which may lead to new RVA genotypes with unknown severity.

Evaluation of T cell responses with the QuantiFERON SARS-CoV-2 assay in individuals with 3 doses of BNT162b2 vaccine, SARS-CoV-2 infection, or hybrid immunity.

Cellular immunity after SARS-CoV-2 infection or immunization may be important for long-lasting protection against severe COVID-19 disease. We investigated cellular immune responses after SARS-CoV-2 infection and/or vaccination with an interferon-γ release assay (QuantiFERON, QFN), in parallel, with humoral immunity assessment. We recruited 41 participants: unvaccinated convalescent children and adults and vaccinated uninfected or vaccinated convalescent adults. All vaccinated adults had received three doses of the BNT162b2 COVID-19 vaccine at 6.2 to 10.9 months prior to their inclusion to the study. All the unvaccinated participants were tested negative with QFN. Regarding the vaccinated population, 50% (8/16) of the vaccinated uninfected adults and 57.1% (8/14) of the vaccinated convalescent adults were tested positive. QFN did not detect T cell responses in unvaccinated individuals and in a significant number of vaccinated individuals. Further comparative studies with different immunoassays are required to elucidate whether this is the result of waning immunity or low sensitivity of the assay.