SARS-CoV-2 seroprevalence among children in Latvia : a cross-sectional study

Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.Coronavirus disease 2019 (COVID-19) is a major global health concern. In contrast to adults, the course of the disease has been observed to be mild or even asymptomatic in children. It is therefore both clinically and epidemiologically important to measure the seroprevalence in children and adolescents to discern the overall morbidity of the disease and to compare these findings with similar data collected globally. We conducted a cross-sectional study between March and July of 2022 at the Children Clinical University Hospital in Riga, Latvia, to evaluate the seroprevalence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Participants aged 0 to 18 years were enrolled during hospitalization for reasons other than COVID19. The levels of SARS-CoV-2 spike protein and nucleocapsid antibodies were measured in blood samples. The possibility of transplacental antibody transport was evaluated by directly interviewing the mothers of participants aged 18 months and younger. Various demographic and epidemiological risk factors and their association with seroprevalence were analyzed. Positive SARSCoV-2 nucleocapsid antibodies were designated the main criterion for seropositivity. Of 200 enrolled children, 173 were found to be seropositive, resulting in an overall seroprevalence of 86.5%. The highest seroprevalence was detected in children and adolescents aged 12 to 18 years. With the progression of the COVID-19 pandemic, the seroprevalence in children has increased significantly. We found that almost 1-third of seropositive children in our study population were unaware of being previously infected with SARS-CoV-2 due to an asymptomatic course of the disease. Our study findings pertaining to high seropositivity among children and adolescents might be beneficial for public authorities to adapt epidemiological strategies and prevention measures. The high seroprevalence rate reported here and in many other populations around the world suggests that COVID-19 will likely become one of the many seasonal viral infections.publishersversionPeer reviewe

Impact of infection on proteome-wide glycosylation revealed by distinct signatures for bacterial and viral pathogens

Funding Information: This research, part of the PERFORM project, has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 668303 . The samples collected previously were funded by: the European Seventh Framework Programme for Research and Technological Development ( FP7 ) under EUCLIDS Grant Agreement No. 279185 . Funding Information: This research, part of the PERFORM project, has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No. 668303. The samples collected previously were funded by: the European Seventh Framework Programme for Research and Technological Development (FP7) under EUCLIDS Grant Agreement No. 279185. We would like to thank all the patients and the healthy controls for donating their blood for the EUCLIDS, IRIS, and Westra studies. We would like to thank the Radboud Consortium for Glycoscience for their advice for data interpretation. We also thank the PERFORM consortium (see supplemental material for all participants) for their collaboration and fruitful discussions. Conceptualization, E.W. H.W. and M.J.; Methodology, E.W. M.D. H.W. and M.J.; Investigation, E.W.; Software, A.S. and H.W.; Formal Analysis, E.W. and H.W.; Visualization, E.W. and H.W.; Resources, M.F. L.H. N.K. R.P. M.K. V.W. J.H. and F.M.; Writing – Original Draft, E.W. and M.J.; Writing – Review & Editing, E.W. J.G. A.S. M.F. L.H. N.K. R.P. M.D. M.K. V.W. J.H. F.M. M.L. R.G. A.G. D.L. H.W. and M.J.; Funding Acquisition, M.J. R.G. and M.L.; Supervision, H.W. D.L. and M.J. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research. Publisher Copyright: © 2023 The Author(s)Mechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an innovative glycoproteomics method to study the systemic proteome-wide glycosylation in response to infection. The protein site-specific glycosylation was characterized in plasma derived from well-defined controls and patients. We found 3862 unique features, of which we identified 463 distinct intact glycopeptides, that could be mapped to more than 30 different proteins. Statistical analyses were used to derive a glycopeptide signature that enabled significant differentiation between patients with a bacterial or viral infection. Furthermore, supported by a machine learning algorithm, we demonstrated the ability to identify the causative pathogens based on the distinctive host blood plasma glycopeptide signatures. These results illustrate that glycoproteomics holds enormous potential as an innovative approach to improve the interpretation of relevant biological changes in response to infection.Peer reviewe

A multi-platform approach to identify a blood-based host protein signature for distinguishing between bacterial and viral infections in febrile children (PERFORM) : a multi-cohort machine learning study

Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.BACKGROUND: Differentiating between self-resolving viral infections and bacterial infections in children who are febrile is a common challenge, causing difficulties in identifying which individuals require antibiotics. Studying the host response to infection can provide useful insights and can lead to the identification of biomarkers of infection with diagnostic potential. This study aimed to identify host protein biomarkers for future development into an accurate, rapid point-of-care test that can distinguish between bacterial and viral infections, by recruiting children presenting to health-care settings with fever or a history of fever in the previous 72 h. METHODS: In this multi-cohort machine learning study, patient data were taken from EUCLIDS, the Swiss Pediatric Sepsis study, the GENDRES study, and the PERFORM study, which were all based in Europe. We generated three high-dimensional proteomic datasets (SomaScan and two via liquid chromatography tandem mass spectrometry, referred to as MS-A and MS-B) using targeted and untargeted platforms (SomaScan and liquid chromatography mass spectrometry). Protein biomarkers were then shortlisted using differential abundance analysis, feature selection using forward selection-partial least squares (FS-PLS; 100 iterations), along with a literature search. Identified proteins were tested with Luminex and ELISA and iterative FS-PLS was done again (25 iterations) on the Luminex results alone, and the Luminex and ELISA results together. A sparse protein signature for distinguishing between bacterial and viral infections was identified from the selected proteins. The performance of this signature was finally tested using Luminex assays and by calculating disease risk scores. FINDINGS: 376 children provided serum or plasma samples for use in the discovery of protein biomarkers. 79 serum samples were collected for the generation of the SomaScan dataset, 147 plasma samples for the MS-A dataset, and 150 plasma samples for the MS-B dataset. Differential abundance analysis, and the first round of feature selection using FS-PLS identified 35 protein biomarker candidates, of which 13 had commercial ELISA or Luminex tests available. 16 proteins with ELISA or Luminex tests available were identified by literature review. Further evaluation via Luminex and ELISA and the second round of feature selection using FS-PLS revealed a six-protein signature: three of the included proteins are elevated in bacterial infections (SELE, NGAL, and IFN-γ), and three are elevated in viral infections (IL18, NCAM1, and LG3BP). Performance testing of the signature using Luminex assays revealed area under the receiver operating characteristic curve values between 89·4% and 93·6%. INTERPRETATION: This study has led to the identification of a protein signature that could be ultimately developed into a blood-based point-of-care diagnostic test for rapidly diagnosing bacterial and viral infections in febrile children. Such a test has the potential to greatly improve care of children who are febrile, ensuring that the correct individuals receive antibiotics. FUNDING: European Union's Horizon 2020 research and innovation programme, the European Union's Seventh Framework Programme (EUCLIDS), Imperial Biomedical Research Centre of the National Institute for Health Research, the Wellcome Trust and Medical Research Foundation, Instituto de Salud Carlos III, Consorcio Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Grupos de Refeencia Competitiva, Swiss State Secretariat for Education, Research and Innovation.Peer reviewe

Guideline adherence in febrile children below 3 months visiting European Emergency Departments : an observational multicenter study

Funding Information: This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 848196. The Research was supported by the National Institute for Health Research Biomedical Research Centres at Imperial College London, Newcastle Hospitals NHS Foundation Trust and Newcastle University. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. For the remaining authors, no sources of funding were declared. The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Publisher Copyright: © 2022, The Author(s).Febrile children below 3 months have a higher risk of serious bacterial infections, which often leads to extensive diagnostics and treatment. There is practice variation in management due to differences in guidelines and their usage and adherence. We aimed to assess whether management in febrile children below 3 months attending European Emergency Departments (EDs) was according to the guidelines for fever. This study is part of the MOFICHE study, which is an observational multicenter study including routine data of febrile children (0–18 years) attending twelve EDs in eight European countries. In febrile children below 3 months (excluding bronchiolitis), we analyzed actual management compared to the guidelines for fever. Ten EDs applied the (adapted) NICE guideline, and two EDs applied local guidelines. Management included diagnostic tests, antibiotic treatment, and admission. We included 913 children with a median age of 1.7 months (IQR 1.0–2.3). Management per ED varied as follows: use of diagnostic tests 14–83%, antibiotic treatment 23–54%, admission 34–86%. Adherence to the guideline was 43% (374/868) for blood cultures, 29% (144/491) for lumbar punctures, 55% (270/492) for antibiotic prescriptions, and 67% (573/859) for admission. Full adherence to these four management components occurred in 15% (132/868, range 0–38%), partial adherence occurred in 56% (484/868, range 35–77%). Conclusion: There is large practice variation in management. The guideline adherence was limited, but highest for admission which implies a cautious approach. Future studies should focus on guideline revision including new biomarkers in order to optimize management in young febrile children.What is Known:• Febrile children below 3 months have a higher risk of serious bacterial infections, which often leads to extensive diagnostics and treatment.• There is practice variation in management of young febrile children due to differences in guidelines and their usage and adherence.What is New:• Full guideline adherence is limited, whereas partial guideline adherence is moderate in febrile children below 3 months across Europe.• Guideline revision including new biomarkers is needed to improve management in young febrile children.publishersversionPeer reviewe

Emergency medical services utilisation among febrile children attending emergency departments across Europe : an observational multicentre study

Funding Information: This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 848196. CT received an additional funding from Stichting Erasmus Trustfonds. The Research was supported by the National Institute for Health Research Biomedical Research Centres at Imperial College London, Newcastle Hospitals NHS Foundation Trust, and Newcastle University. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. For the remaining authors, no sources of funding were declared. The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Publisher Copyright: © 2023, The Author(s).Children constitute 6–10% of all patients attending the emergency department (ED) by emergency medical services (EMS). However, discordant EMS use in children occurs in 37–61% with fever as an important risk factor. We aimed to describe EMS utilisation among febrile children attending European EDs. This study is part of an observational multicentre study assessing management and outcome in febrile children up to 18 years (MOFICHE) attending twelve EDs in eight European countries. Discordant EMS use was defined as the absence of markers of urgency including intermediate/high triage urgency, advanced diagnostics, treatment, and admission in children transferred by EMS. Multivariable logistic regression analyses were performed for the association between (1) EMS use and markers of urgency, and (2) patient characteristics and discordant EMS use after adjusting all analyses for the covariates age, gender, visiting hours, presenting symptoms, and ED setting. A total of 5464 (15%, range 0.1–42%) children attended the ED by EMS. Markers of urgency were more frequently present in the EMS group compared with the non-EMS group. Discordant EMS use occurred in 1601 children (29%, range 1–59%). Age and gender were not associated with discordant EMS use, whereas neurological symptoms were associated with less discordant EMS use (aOR 0.2, 95%CI 0.1–0.2), and attendance out of office hours was associated with more discordant EMS use (aOR 1.6, 95%CI 1.4–1.9). Settings with higher percentage of self-referrals to the ED had more discordant EMS use (p < 0.05). Conclusion: There is large practice variation in EMS use in febrile children attending European EDs. Markers of urgency were more frequently present in children in the EMS group. However, discordant EMS use occurred in 29%. Further research is needed on non-medical factors influencing discordant EMS use in febrile children across Europe, so that pre-emptive strategies can be implemented. What is Known: •Children constitute around 6–10% of all patients attending the emergency department by emergency medical services. •Discordant EMS use occurs in 37–61% of all children, with fever as most common presenting symptom for discordant EMS use in children. What is New: •There is large practice variation in EMS use among febrile children across Europe with discordance EMS use occurring in 29% (range 1–59%), which was associated with attendance during out of office hours and with settings with higher percentage of self-referrals to the ED. •Future research is needed focusing on non-medical factors (socioeconomic status, parental preferences and past experience, healthcare systems, referral pathways, out of hours services provision) that influence discordant EMS use in febrile children across Europe.Peer reviewe

Impact of infection on proteome-wide glycosylation revealed by distinct signatures for bacterial and viral pathogens

Mechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an innovative glycoproteomics method to study the systemic proteome-wide glycosylation in response to infection. The protein site-specific glycosylation was characterized in plasma derived from well-defined controls and patients. We found 3862 unique features, of which we identified 463 distinct intact glycopeptides, that could be mapped to more than 30 different proteins. Statistical analyses were used to derive a glycopeptide signature that enabled significant differentiation between patients with a bacterial or viral infection. Furthermore, supported by a machine learning algorithm, we demonstrated the ability to identify the causative pathogens based on the distinctive host blood plasma glycopeptide signatures. These results illustrate that glycoproteomics holds enormous potential as an innovative approach to improve the interpretation of relevant biological changes in response to infection

Emergency medical services utilisation among febrile children attending emergency departments across Europe: an observational multicentre study

Abstract Children constitute 6–10% of all patients attending the emergency department (ED) by emergency medical services (EMS). However, discordant EMS use in children occurs in 37–61% with fever as an important risk factor. We aimed to describe EMS utilisation among febrile children attending European EDs. This study is part of an observational multicentre study assessing management and outcome in febrile children up to 18 years (MOFICHE) attending twelve EDs in eight European countries. Discordant EMS use was defined as the absence of markers of urgency including intermediate/high triage urgency, advanced diagnostics, treatment, and admission in children transferred by EMS. Multivariable logistic regression analyses were performed for the association between (1) EMS use and markers of urgency, and (2) patient characteristics and discordant EMS use after adjusting all analyses for the covariates age, gender, visiting hours, presenting symptoms, and ED setting. A total of 5464 (15%, range 0.1–42%) children attended the ED by EMS. Markers of urgency were more frequently present in the EMS group compared with the non-EMS group. Discordant EMS use occurred in 1601 children (29%, range 1–59%). Age and gender were not associated with discordant EMS use, whereas neurological symptoms were associated with less discordant EMS use (aOR 0.2, 95%CI 0.1–0.2), and attendance out of office hours was associated with more discordant EMS use (aOR 1.6, 95%CI 1.4–1.9). Settings with higher percentage of self-referrals to the ED had more discordant EMS use (p &lt; 0.05).  Conclusion: There is large practice variation in EMS use in febrile children attending European EDs. Markers of urgency were more frequently present in children in the EMS group. However, discordant EMS use occurred in 29%. Further research is needed on non-medical factors influencing discordant EMS use in febrile children across Europe, so that pre-emptive strategies can be implemented. What is Known: •Children constitute around 6–10% of all patients attending the emergency department by emergency medical services. •Discordant EMS use occurs in 37–61% of all children, with fever as most common presenting symptom for discordant EMS use in children. What is New: •There is large practice variation in EMS use among febrile children across Europe with discordance EMS use occurring in 29% (range 1–59%), which was associated with attendance during out of office hours and with settings with higher percentage of self-referrals to the ED. •Future research is needed focusing on non-medical factors (socioeconomic status, parental preferences and past experience, healthcare systems, referral pathways, out of hours services provision) that influence discordant EMS use in febrile children across Europe. </jats:p