Correction: The Evaluation of Health Care Services for Children and Adolescents With Post-COVID-19 Condition: Protocol for a Prospective Longitudinal Study.

[This corrects the article DOI: 10.2196/41010.].

The Evaluation of Health Care Services for Children and Adolescents With Post-COVID-19 Condition: Protocol for a Prospective Longitudinal Study.

BACKGROUND: Some children and adolescents suffer from late effects of a SARS-CoV-2 infection despite a frequently mild course of the disease. Nevertheless, extensive care for post-COVID-19 condition, also known as post-COVID-19 syndrome, in children and young people is not yet available. A comprehensive care network, Post-COVID Kids Bavaria (PoCo), for children and adolescents with post-COVID-19 condition has been set up as a model project in Bavaria, Germany. OBJECTIVE: The aim of this study is to evaluate the health care services provided within this network structure of care for children and adolescents with post-COVID-19 condition in a pre-post study design. METHODS: We have already recruited 117 children and adolescents aged up to 17 years with post-COVID-19 condition who were diagnosed and treated in 16 participating outpatient clinics. Health care use, treatment satisfaction, patient-reported outcomes related to health-related quality of life (the primary endpoint), fatigue, postexertional malaise, and mental health are being assessed at different time points (at baseline and after 4 weeks, 3 months, and 6 months) using routine data, interviews, and self-report questionnaires. RESULTS: The study recruitment process ran from April 2022 until December 2022. Interim analyses will be carried out. A full analysis of the data will be conducted after follow-up assessment is completed, and the results will be published. CONCLUSIONS: The results will contribute to the evaluation of therapeutic services provided for post-COVID-19 condition in children and adolescents, and avenues for optimizing care may be identified. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/41010.

Autoantibodies against SUMO1-DHX35 in long-COVID.

Long COVID is a collection of symptoms as a late sequelae of SARS-CoV-2 infection. It often includes mental symptoms such as cognitive symptoms, persisting loss of smell and taste, in addition to exertional dyspnea. A role of various autoantibodies (autoAbs) has been postulated in long-COVID and is being further investigated. With the goal of identifying potentially unknown autoAbs, we screened plasma of patients with long COVID on in-house post-translationally modified protein macroarrays including citrullinated, SUMOylated and acetylated membranes. SUMO1ylated isoform DEAD/H (Asp-Glu-Ala-Asp/His) box helicase 35 (SUMO1-DHX35) was identified as only candidate antigen. In adult patients with long COVID, IgG autoAbs against SUMO1-DHX35 of IgG class were found in seven of 71 (9.8%) plasma samples, of IgM and IgG class in one of 69 (1.4%) samples, not in 200 healthy adult controls, not in 442 healthy children, and 146 children after SARS-CoV-2 infection. All autoAb-positive seven patients were female. AutoAb titers ranged between 200 to up to 400 By point mutagenesis and expression of FLAG-tagged mutants of DHX35 in HEK293 cells, and subsequent SUMOylation of purified constructs, lysine 53 was identified as a unique, never yet identified, SUMOylation site. The autoAbs had no reactivity against the non-SUMO1ylated mutant (K53R) of DHX35. To summarize, autoAbs against SUMO1-DHX35 were identified in adult female patients with long-COVID. Further studies are needed to verify the frequency of occurrence. The function of DHX35 has not yet been determined and there is no available information in relation to disease implication. The molecular mechanism causing the SUMOylation, the potential functional consequences of this post-translational modification on DHX35, and a potential pathogenicity of the autoAbs against SUMO1-DHX35 in COVID-19 and other possible contexts remain to be elucidated.

[Parental intention to vaccinate their children against COVID-19]. / COVID-19-Impfintention von Eltern bezogen auf ihre Kinder.

BACKGROUND: With the start of the vaccination campaign, a new phase in the management of the coronavirus pandemic has begun. Approval and recommendation for COVID-19 vaccination of children followed gradually; to date (4 October 2022), vaccination for children under five years of age has not been approved in Germany. AIM OF THE STUDY: The aim was to investigate how parents' intention to vaccinate their children against COVID-19 developed from May 2020 to February 2021 (from the first to the second wave of the COVID-19 pandemic) and to analyse the determinants of the intention to vaccinate. METHODS: In May 2020, 612 families participating with their children aged 1.5-6 years in the KUNO Kids Health Study completed an online survey (participation rate 51%), and 507 completed the second survey in February 2021. Determinants of the intention to vaccinate were analysed for both time points using univariable and multivariable logistic regression models. RESULTS: While 51% of parents reported wanting their children vaccinated against COVID-19 in May 2020, this proportion decreased to 41% by February 2021. At least at one of the two time points, health literacy and perceived competence regarding protective measures against the virus were significantly positively associated with higher vaccination intentions, while belonging to a risk group and the perception that the political measures were exaggerated were associated with lower vaccination intentions. DISCUSSION: Parents' intention to have their children vaccinated against COVID-19 was low and decreased further from the first to the second wave of the coronavirus pandemic. Attitudinal and competence-related determinants were important at both time points and could be targeted in a future vaccination campaign addressing parents of younger children.

Analysis of COVID-19 Infection Chains in a School Setting: Data From a School-Based rRT-PCR-Gargle Pool Test System.

BACKGROUND: School testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was implemented in some countries to monitor and prevent SARS-CoV-2 transmissions. Here, we analyze infection chains in primary schools and household members of infected students based on systematic real-time reverse-transcriptase polymerase-chain-reaction (rRT-PCR)-gargle pool testing. METHODS: Students and school staff (N = 4300) of all 38 primary schools in the rural county of Cham, Germany, were tested twice per week with a gargle pool rRT-PCR system from April to July of 2021. Infection chains of all 8 positive cases identified by school testing were followed up. RESULTS: In total, 8 positive cases were found by gargle pool PCR testing based on 96,764 school tests. While no transmissions occurred in the school setting, 20 of 27 household members of the 8 cases tested positive. The overall attack rate was 74.1% in families. CONCLUSIONS: No school outbreaks occurred during the study period. All cases but 1 were initially picked up by school testing. No transmission from school to families was observed.

Focusing on severe infections with the respiratory syncytial virus (RSV) in adults: Risk factors, symptomatology and clinical course compared to influenza A / B and the original SARS-CoV-2 strain.

BACKGROUND: The role and impact of RSV in the adult population is not well understood and comparative data of RSV infection, influenza A/B and SARS-CoV-2 in the elderly hospitalized for respiratory infections is limited. METHODS: In a retrospective, monocentric study we analyzed data of adult patients with respiratory infections tested positive by PCR for RSV, Influenza A/B and SARS-CoV-2 over a four-year period from 2017 to 2020. Symptoms on admission, laboratory results, and risk factors were assessed, and the clinical course and outcomes were studied. RESULTS: A total of 1541 patients hospitalized with respiratory disease and PCR positive for one of the 4 viruses were enrolled in the study. RSV was the second most prevalent virus before the COVID-19 pandemic and RSV patients represent the oldest group in this study with an average age of 75 years. Neither clinical nor laboratory characteristics differ clearly between RSV, Influenza A / B and SARS-CoV-2 infections. Up to 85% of patients had risk factors, with COPD and kidney disease found particularly frequently in RSV infections. Hospital stay was 12.66 days for RSV patients and thus significantly longer than for influenza A / B (10.88 and 8.86, respectively, p < 0.001), but shorter than for SARS-CoV-2 (17.87 days, p < 0.001). The risk for ICU admission and the rate of mechanical ventilation were also higher for RSV than for influenza A (OR 1.69 (p = 0.020) and 1.59 (p = 0.050)) and influenza B: (1.98 (p = 0.018) and 2.33 (p < 0.001)), but lower than for SARS-CoV-2 (0.65 (p < 0.001) and 0.59 (p = 0.035)). The risk of hospital mortality for RSV was increased compared with influenza A (1.55 (p = 0.050)) and influenza B (1.42 (p = 0.262)), but lower compared to SARs-CoV-2 (0.37 (p < 0.001). CONCLUSION: RSV infections in elderly are frequent and more severe than those with influenza A/B. While the impact of SARS-CoV-2 most likely decreased in the elderly population due to vaccination, RSV can be expected to continue to be problematic for elderly patients, especially those with comorbidities and thus, more awareness on the disastrous impact of RSV in this age group is urgently needed.

SARS-CoV-2 Detection Limits in Swab and Gargle Samples by Comparing Antigen and RT-qPCR Testing

Background: Antigen tests for SARS-CoV-2 testing are rapid and inexpensive but usually have lower sensitivity than RT-qPCR and are only validated for nasopharyngeal/throat swabs;the latter are considered the gold standard in terms of material collection but are not tolerated by patients with frequent sampling. The present study, therefore, investigates the extent to which SARS-CoV-2 antigen testing is comparable to RT-qPCR from an easily obtained gargle solution compared to nasopharyngeal swabs. Methods: The performance of a high-quality POC fluorescence immune antigen test in single nasal swab samples and gargle samples compared to RT-qPCR was investigated (total n = 620 samples (gargle samples = 309, and nasal swabs = 311)). Findings: In our setting, the detection of SARS-CoV2 with an antigen test was reliable up to a Ct value of 30 for single nasal swab samples and was reduced to Ct:20 for single gargle samples. The overall antigen-test sensitivity is 83.92% (swab samples) and 75.72% (gargle samples). Interpretation: Antigen tests showed reliable results up to a detection limit of Ct: 30 with only nasal swab samples but not gargle samples. If the use of gargle samples is preferred due to their advantages, such as painless testing, easy handling, and the lack of a need to involve trained personnel for sample taking, reliable results can only be achieved with RT-qPCR.

Time Trend in SARS-CoV-2 Seropositivity, Surveillance Detection- and Infection Fatality Ratio until Spring 2021 in the Tirschenreuth County-Results from a Population-Based Longitudinal Study in Germany.

Herein, we provide results from a prospective population-based longitudinal follow-up (FU) SARS-CoV-2 serosurveillance study in Tirschenreuth, the county which was hit hardest in Germany in spring 2020 and early 2021. Of 4203 individuals aged 14 years or older enrolled at baseline (BL, June 2020), 3546 participated at FU1 (November 2020) and 3391 at FU2 (April 2021). Key metrics comprising standardized seroprevalence, surveillance detection ratio (SDR), infection fatality ratio (IFR) and success of the vaccination campaign were derived using the Roche N- and S-Elecsys anti-SARS-CoV-2 test together with a self-administered questionnaire. N-seropositivity at BL was 9.2% (1st wave). While we observed a low new seropositivity between BL and FU1 (0.9%), the combined 2nd and 3rd wave accounted for 6.1% new N-seropositives between FU1 and FU2 (ever seropositives at FU2: 15.4%). The SDR decreased from 5.4 (BL) to 1.1 (FU2) highlighting the success of massively increased testing in the population. The IFR based on a combination of serology and registration data resulted in 3.3% between November 2020 and April 2021 compared to 2.3% until June 2020. Although IFRs were consistently higher at FU2 compared to BL across age-groups, highest among individuals aged 70+ (18.3% versus 10.7%, respectively), observed differences were within statistical uncertainty bounds. While municipalities with senior care homes showed a higher IFR at BL (3.0% with senior care home vs. 0.7% w/o), this effect diminished at FU2 (3.4% vs. 2.9%). In April 2021 (FU2), vaccination rate in the elderly was high (>77.4%, age-group 80+).

Autoantibodies against interleukin-1 receptor antagonist in multisystem inflammatory syndrome in children: a multicentre, retrospective, cohort study.

Background: Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious complication of infection with SARS-CoV-2. A possible involvement of pathogenetically relevant autoantibodies has been discussed. Recently, neutralising autoantibodies against inflammatory receptor antagonists progranulin and interleukin-1 receptor antagonist (IL-1Ra) were found in adult patients with critical COVID-19. The aim of this study was to investigate the role of such autoantibodies in MIS-C. Methods: In this multicentre, retrospective, cohort study, plasma and serum samples were collected from patients (0-18 years) with MIS-C (as per WHO criteria) treated at five clinical centres in Germany and Spain. As controls, we included plasma or serum samples from children with Kawasaki disease, children with inactive systemic juvenile idiopathic arthritis, and children with suspected growth retardation (non-inflammatory control) across four clinical centres in Germany and Spain (all aged ≤18 years). Serum samples from the CoKiBa trial were used as two further control groups, from healthy children (negative for SARS-CoV-2 antibodies) and children with previous mild or asymptomatic COVID-19 (aged ≤17 years). MIS-C and control samples were analysed for autoantibodies against IL-1Ra and progranulin, and for IL-1Ra concentrations, by ELISA. Biochemical analysis of plasma IL-1Ra was performed with native Western blots and isoelectric focusing. Functional activity of the autoantibodies was examined by an in vitro IL-1ß-signalling reporter assay. Findings: Serum and plasma samples were collected between March 6, 2011, and June 2, 2021. Autoantibodies against IL-1Ra could be detected in 13 (62%) of 21 patients with MIS-C (11 girls and ten boys), but not in children with Kawasaki disease (n=24; nine girls and 15 boys), asymptomatic or mild COVID-19 (n=146; 72 girls and 74 boys), inactive systemic juvenile idiopathic arthritis (n=10; five girls and five boys), suspected growth retardation (n=33; 13 girls and 20 boys), or in healthy controls (n=462; 230 girls and 232 boys). Anti-IL-1Ra antibodies in patients with MIS-C belonged exclusively to the IgG1 subclass, except in one patient who had additional IL-1Ra-specific IgM antibodies. Autoantibodies against progranulin were only detected in one (5%) patient with MIS-C. In patients with MIS-C who were positive for anti-IL-1Ra antibodies, free plasma IL-1Ra concentrations were reduced, and immune-complexes of IL-1Ra were detected. Notably, an additional, hyperphosphorylated, transiently occurring atypical isoform of IL-1Ra was observed in all patients with MIS-C who were positive for anti-IL-1Ra antibodies. Anti-IL-1Ra antibodies impaired IL-1Ra function in reporter cell assays, resulting in amplified IL-1ß signalling. Interpretation: Anti-IL-1Ra autoantibodies were observed in a high proportion of patients with MIS-C and were specific to these patients. Generation of these autoantibodies might be triggered by an atypical, hyperphosphorylated isoform of IL-1Ra. These autoantibodies impair IL-1Ra bioactivity and might thus contribute to increased IL-1ß-signalling in MIS-C. Funding: NanoBioMed fund of the University of Saarland, José Carreras Center for Immuno and Gene Therapy, Dr Rolf M Schwiete Stiftung, Staatskanzlei Saarland, German Heart Foundation, Charity of the Blue Sisters, Bavarian Ministry of Health, the Center for Interdisciplinary Clinical Research at University Hospital Münster, EU Horizon 2020.

Families' Worries during the First and Second COVID-19 Wave in Germany: Longitudinal Study in Two Population-Based Cohorts.

This study aimed to compare worries related to the Coronavirus disease 2019 (COVID-19) in families with young children in two regions in Germany differently affected by the pandemic (Regensburg in Southeast Germany, Leipzig in Eastern Germany) during the first and the second waves of the COVID-19 pandemic. 720 parents participating in the KUNO Kids health study in Regensburg (n = 507) or the LIFE Child study in Leipzig (n = 213) answered questions regarding COVID-19-related worries and trust in anti-pandemic policy measures during the first wave (spring 2020) and during the second wave (winter 2020/2021) of the pandemic. Ordinal mixed-effects models were performed to assess differences depending on region and time, adjusting for education and migration background. Participants worried most about the general economic situation and their family and least about their own health or financial situation. Worries about oneself, family, friends, hometown, and country were stronger during the second than during the first wave. In regional comparisons, worries about family, friends, and hometown increased more pronouncedly from wave 1 to wave 2 in Leipzig (OR ranging from 2.67 (95% CI 1.71-4.19) to 3.01 (95% CI 1.93-4.71), all p < 0.001) than in Regensburg (OR ranging from to 1.38 (95% CI 1.08-1.78) to 1.72 (95% CI 1.33-2.21), all p < 0.05), running parallel with the increase in SARS-CoV-2 infections. Trust in anti-pandemic policy measures, in contrast, decreased significantly between wave 1 and wave 2, with a stronger decrease in Regensburg (OR = 0.30 (95% CI 0.22-0.39), p < 0.001) than in Leipzig (OR = 0.91 (95% CI 0.59-1.41), n.s.). The degree of families' COVID-19-related worries differs by region and time, which might be related to differences in infection rates and public interest. Regional differences should be taken into account when developing communication strategies and policy measures during the COVID-19 pandemic.

How to Implement Safe, Efficient and Cost-Effective SARS-CoV-2 Testing in Urban and Rural Schools within One Month

(1) Background: With vaccination and new variants of SARS-CoV-2 on the horizon, efficient testing in schools may enable prevention of mass infection outbreaks, keeping schools safe places and buying time until decisions on feasibility and the necessity of vaccination in children and youth are made. We established, in the course of the WICOVIR (Where Is the COrona VIRus) study, that gargle-based pool-PCR testing offers a feasible, efficient, and safe testing system for schools in Germany when applied by central university laboratories. (2) Objectives: We evaluated whether this approach can be implemented in different rural and urban settings. (3) Methods: We assessed the arrangements required for successful implementation of the WICOVIR approach in a variety of settings in terms of transport logistics, data transfer and pre-existing laboratory set-up, as well as the time required to establish the set-up. (4) Results: We found that once regulatory issues have been overcome, all challenges pertaining to logistics, data transfer, and laboratory testing on different platforms can be solved within one month. Pooling and depooling of samples down to the individual test result were achievable within one working day in all settings. Local involvement of the community and decentralized set-ups were keys for success. (5) Conclusion: The WICOVIR gargle-based pool-PCR system is so robust and simple that it can be implemented within one month in all settings now or in future pandemics.

Results of WICOVIR Gargle Pool PCR Testing in German Schools Based on the First 100,000 Tests.

Background: Opening schools and keeping children safe from SARS-CoV-2 infections at the same time is urgently needed to protect children from direct and indirect consequences of the COVID-19 pandemic. To achieve this goal, a safe, efficient, and cost-effective SARS-CoV-2 testing system for schools in addition to standard hygiene measures is necessary. Methods: We implemented the screening WICOVIR concept for schools in the southeast of Germany, which is based on gargling at home, pooling of samples in schools, and assessment of SARS-CoV-2 by pool rRT-PCR, performed decentralized in numerous participating laboratories. Depooling was performed if pools were positive, and results were transmitted with software specifically developed for the project within a day. Here, we report the results after the first 13 weeks in the project. Findings: We developed and implemented the proof-of-concept test system within a pilot phase of 7 weeks based on almost 17,000 participants. After 6 weeks in the main phase of the project, we performed >100,000 tests in total, analyzed in 7,896 pools, identifying 19 cases in >100 participating schools. On average, positive children showed an individual CT value of 31 when identified in the pools. Up to 30 samples were pooled (mean 13) in general, based on school classes and attached school staff. All three participating laboratories detected positive samples reliably with their previously established rRT-PCR standard protocols. When self-administered antigen tests were performed concomitantly in positive cases, only one of these eight tests was positive, and when antigen tests performed after positive pool rRT-PCR results were already known were included, 3 out of 11 truly positive tests were also identified by antigen testing. After 3 weeks of repetitive WICOVIR testing twice weekly, the detection rate of positive children in that cohort decreased significantly from 0.042 to 0.012 (p = 0.008). Interpretation: Repeated gargle pool rRT-PCR testing can be implemented quickly in schools. It is an effective, valid, and well-received test system for schools, superior to antigen tests in sensitivity, acceptance, and costs.

Symptoms, SARS-CoV-2 Antibodies, and Neutralization Capacity in a Cross Sectional-Population of German Children.

Background: Children and youth are affected rather mildly in the acute phase of COVID-19 and thus, SARS-CoV-2 infection infection may easily be overlooked. In the light of current discussions on the vaccinations of children it seems necessary to better identify children who are immune against SARS-CoV-2 due to a previous infection and to better understand COVID-19 related immune reactions in children. Methods: In a cross-sectional design, children aged 1-17 were recruited through primary care pediatricians for the study (a) randomly, if they had an appointment for a regular health check-up or (b) if parents and children volunteered and actively wanted to participate in the study. Symptoms were recorded and two antibody tests were performed in parallel directed against S (in house test) and N (Roche Elecsys) viral proteins. In children with antibody response in either test, neutralization activity was determined. Results: We identified antibodies against SARS-CoV-2 in 162 of 2,832 eligible children (5.7%) between end of May and end of July 2020 in three, in part strongly affected regions of Bavaria in the first wave of the pandemic. Approximately 60% of antibody positive children (n = 97) showed high levels (>97th percentile) of antibodies against N-protein, and for the S-protein, similar results were found. Sufficient neutralizing activity was detected for only 135 antibody positive children (86%), irrespective of age and sex. Initial COVID-19 symptoms were unspecific in children except for the loss of smell and taste and unrelated to antibody responses or neutralization capacity. Approximately 30% of PCR positive children did not show seroconversion in our small subsample in which PCR tests were performed. Conclusions: Symptoms of SARS-CoV-2 infections are unspecific in children and antibody responses show a dichotomous structure with strong responses in many and no detectable antibodies in PCR positive children and missing neutralization activity in a relevant proportion of the young population.

Feasibility of a surveillance programme based on gargle samples and pool testing to prevent SARS-CoV-2 outbreaks in schools.

School closures have a negative impact on physical and mental well-being, and education, of children and adolescents. A surveillance programme to detect asymptomatic SARS-CoV-2 infection could allow schools to remain open, while protecting the vulnerable. We assessed the feasibility of a programme employing gargle samples and pool testing of individually extracted RNA using rRT-qPCR in a primary and a secondary school in Germany, based on programme logistics and acceptance. Twice a week, five participants per class were selected to provide samples, using an algorithm weighted by a risk-based priority score to increase likelihood of case detection. The positive response rate was 54.8% (550 of 1003 pupils). Logistics evaluation revealed the rate-limiting steps: completing the regular pre-test questionnaire and handing in the samples. Acceptance questionnaire responses indicated strong support for research into developing a surveillance programme and a positive evaluation of gargle tests. Participation was voluntary. As not all pupils participated, individual reminders could lead to participant identification. School-wide implementation of the programme for infection monitoring purposes would enable reminders to be given to all school pupils to address these steps, without compromising participant anonymity. Such a programme would provide a feasible means to monitor asymptomatic respiratory tract infection in schools.

Performance evaluation of the Roche Elecsys Anti-SARS-CoV-2 S immunoassay.

The Elecsys® Anti-SARS-CoV-2 S immunoassay (Roche Diagnostics International Ltd, Rotkreuz, Switzerland) has been developed for the detection of antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein. We evaluated the assay performance using samples from seven sites in Germany, Austria, and Switzerland. For specificity and sensitivity analyses, 7880 presumed negative pre-pandemic samples and 827 SARS-CoV-2 PCR-confirmed single or sequential samples from 272 different patients were tested, respectively. The overall specificity and sensitivity (≥14 days post-PCR) for the Elecsys Anti-SARS-CoV-2 S immunoassay were 99.95% (95% confidence interval [CI]: 99.87-99.99; 7876/7880) and 97.92% (95% CI: 95.21-99.32; 235/240), respectively. The Elecsys Anti-SARS-CoV-2 S immunoassay had significantly higher specificity compared with the LIAISON® SARS-CoV-2 S1/S2 IgG (99.95% [2032/2033] vs 98.82% [2009/2033]), ADVIA Centaur® SARS-CoV-2 Total (100% [928/928] vs 86.96% [807/928]), ARCHITECT SARS-CoV-2 IgG (99.97% [2931/2932] vs 99.69% [2923/2932]), iFlash-SARS-CoV-2 IgM (100.00% [928/928] vs 99.57% [924/928]), and EUROIMMUN Anti-SARS-CoV-2 IgG (100.00% [903/903] vs 97.45% [880/903]) and IgA (100.00% [895/895] vs 95.75% [857/895]) assays. The Elecsys Anti-SARS-CoV-2 S immunoassay had significantly higher sensitivity (≥14 days post-PCR) compared with the ARCHITECT SARS-CoV-2 IgG (98.70% [76/77] vs 87.01% [67/77]), iFlash-SARS-CoV-2 IgG (100.00% [76/76] vs 93.42% [71/76]) and IgM (100.00% [76/76] vs 35.53% [27/76]), and EUROIMMUN Anti-SARS-CoV-2 IgG (98.26% [113/115] vs 93.91% [108/115]) assays. Therefore, the Elecsys Anti-SARS-CoV-2 S assay demonstrated a reliable performance across various sample populations for the detection of anti-S antibodies.

Pool Testing as a Strategy for Prevention of SARS-CoV-2 Outbreaks in Schools: Protocol for a Feasibility Study.

BACKGROUND: School closures are a widely implemented strategy for limiting infection spread in the current COVID-19 pandemic. The negative impact of school closures on children and young people is increasingly apparent, however. OBJECTIVE: We aim to evaluate the feasibility of an infection monitoring program in schools to enable targeted quarantining to replace school closures. The program is currently being implemented in two model schools in Magdeburg, Germany, within the framework of the Study of Coronavirus Outbreak Prevention in Magdeburg Schools (Studie zur Ausbruchsvermeidung von Corona an Magdeburger Schulen [STACAMA]). METHODS: Five pupils per class are pseudorandomly selected twice a week and asked to provide a gargle sample over a 16-week evaluation period. RNA is extracted from each sample individually in a laboratory and pooled according to school class for real-time reverse transcription polymerase chain reaction (rRT-PCR) analysis. Immediate individual sample testing will be carried out in the case of a positive pool test. Individual RNA extraction prior to pooling and application of rRT-PCR result in high test sensitivity. Testing will be performed in strict adherence to data protection standards. All participating pupils will receive a 16-digit study code, which they will be able to use to access their test. RESULTS: When the study commenced on December 2, 2020, 520 (52%) pupils and their families or guardians had consented to study participation. The study was suspended after four test rounds due to renewed school closures resulting from rising regional infection incidence. Testing resumed when schools reopened on March 8, 2021, at which time consent to participation was provided for 54% of pupils. We will quantitatively and qualitatively evaluate the logistics and acceptability of the program. CONCLUSIONS: The findings from this study should inform the design of infection surveillance programs in schools based on gargle samples and a PCR-based pool testing procedure, enabling the identification of aspects that may require adaptation before large-scale implementation. Our focus on each step of the logistics and on the experiences of families should enable a robust assessment of the feasibility of such an approach. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/28673.

Estimates and Determinants of SARS-Cov-2 Seroprevalence and Infection Fatality Ratio Using Latent Class Analysis: The Population-Based Tirschenreuth Study in the Hardest-Hit German County in Spring 2020.

SARS-CoV-2 infection fatality ratios (IFR) remain controversially discussed with implications for political measures. The German county of Tirschenreuth suffered a severe SARS-CoV-2 outbreak in spring 2020, with particularly high case fatality ratio (CFR). To estimate seroprevalence, underreported infections, and IFR for the Tirschenreuth population aged ≥14 years in June/July 2020, we conducted a population-based study including home visits for the elderly, and analyzed 4203 participants for SARS-CoV-2 antibodies via three antibody tests. Latent class analysis yielded 8.6% standardized county-wide seroprevalence, a factor of underreported infections of 5.0, and 2.5% overall IFR. Seroprevalence was two-fold higher among medical workers and one third among current smokers with similar proportions of registered infections. While seroprevalence did not show an age-trend, the factor of underreported infections was 12.2 in the young versus 1.7 for ≥85-year-old. Age-specific IFRs were <0.5% below 60 years of age, 1.0% for age 60-69, and 13.2% for age 70+. Senior care homes accounted for 45% of COVID-19-related deaths, reflected by an IFR of 7.5% among individuals aged 70+ and an overall IFR of 1.4% when excluding senior care home residents from our computation. Our data underscore senior care home infections as key determinant of IFR additionally to age, insufficient targeted testing in the young, and the need for further investigations on behavioral or molecular causes of the fewer infections among current smokers.

Parents' intention to get vaccinated and to have their child vaccinated against COVID-19: cross-sectional analyses using data from the KUNO-Kids health study.

A COVID-19 vaccine can be an important key for mitigating the spread of the pandemic, provided that it is accepted by a sufficient proportion of the population. This study investigated parents' intention to get vaccinated and to have one's child vaccinated against COVID-19. In May 2020, 612 parents participating with their child in the KUNO-Kids health study completed an online survey. Multivariable logistic regression models were calculated to analyze predictors of intention to vaccinate. Fifty-eight percent of parents intended to get vaccinated against COVID-19, and 51% intended to have their child vaccinated. Significant predictors for the intention to get vaccinated and for having the child vaccinated included stronger parental confidence in one's knowledge about prevention measures and lower beliefs that policy measures were exaggerated.Conclusion: COVID-19 vaccination hesitancy was considerable in our sample of parents in Germany. However, our study revealed some potentially modifiable factors which should be addressed by a comprehensive and tailored communication and education strategy. What is Known? • A COVID-19 vaccine can mitigate the spread of the pandemic. • Many parents are skeptical about vaccinations in general. What is New? • COVID-19 vaccination hesitancy was considerable in our sample of parents from Germany, not only for getting vaccinated but also for having the child vaccinated. • Negative parental attitudes regarding policy measures to contain the pandemic were associated with a lower intention to vaccinate.

Serum neurofilament light chain (sNfL) values in a large cross-sectional population of children with asymptomatic to moderate COVID-19.

BACKGROUND: Serum neurofilament light chain (sNfL) is an established biomarker of neuro-axonal damage in multiple neurological disorders. Raised sNfL levels have been reported in adults infected with pandemic coronavirus disease 2019 (COVID-19). Levels in children infected with COVID-19 have not as yet been reported. OBJECTIVE: To evaluate whether sNfL is elevated in children contracting COVID-19. METHODS: Between May 22 and July 22, 2020, a network of outpatient pediatricians in Bavaria, Germany, the Coronavirus antibody screening in children from Bavaria study network (CoKiBa), recruited healthy children into a cross-sectional study from two sources: an ongoing prevention program for 1-14 years, and referrals of 1-17 years consulting a pediatrician for possible infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We determined sNfL levels by single molecule array immunoassay and SARS-CoV-2 antibody status by two independent quantitative methods. RESULTS: Of the 2652 included children, 148 (5.6%) were SARS-CoV-2 antibody positive with asymptomatic to moderate COVID-19 infection. Neurological symptoms-headache, dizziness, muscle aches, or loss of smell and taste-were present in 47/148 cases (31.8%). Mean sNfL levels were 5.5 pg/ml (SD 2.9) in the total cohort, 5.1 (SD 2.1) pg/ml in the children with SARS-CoV-2 antibodies, and 5.5 (SD 3.0) pg/ml in those without. Multivariate regression analysis revealed age-but neither antibody status, antibody levels, nor clinical severity-as an independent predictor of sNfL. Follow-up of children with pediatric multisystem inflammatory syndrome (n = 14) showed no association with sNfL. CONCLUSIONS: In this population study, children with asymptomatic to moderate COVID-19 showed no neurochemical evidence of neuronal damage.