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      Welche Rolle spielen Kinder in Schulen und Kindertagesstätten bei der Übertragung von SARS-CoV-2? – Eine evidenzbasierte Perspektive Translated title: What role do children in school and kindergarten settings play in transmitting SARS-CoV-2? An evidence-based perspective

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          Abstract

          Sind Kinder und Jugendliche relevante Vektoren für die Übertragung von SARS-CoV-2? Und welche Rolle spielt es, wenn sie eine Schule oder Kindertagesstätte besuchen? Diese Fragen konnten zu Beginn der Pandemie nur unzureichend beantwortet werden. So wurden weltweit Schulen und Kinderbetreuungseinrichtungen geschlossen, um die Verbreitung von SARS-CoV‑2 einzudämmen. Inzwischen ist die Rolle von Kindern im Gesamtgeschehen der Pandemie jedoch klarer. Die Rate von SARS-CoV-2-Infektionen bei Kindern unter 10 Jahren war im Jahr 2020 deutlich niedriger als die bei Erwachsenen. Zudem zeigte sich bei Kindern ein deutlich milderer Verlauf der Erkrankung.

          Analysen zu Ausbrüchen an Schulen und Kinderbetreuungseinrichtungen kamen mehrheitlich zu dem Ergebnis, dass die Weitergabe des Virus in den Einrichtungen zwar stattfindet, jedoch das Infektionsgeschehen insgesamt nicht maßgeblich beeinflusst. Trotz dieser Erkenntnisse hält die deutsche Politik Schulschließungen weiterhin für einen integralen Baustein der Pandemiebekämpfung, wohingegen viele Fachgesellschaften, wie die Deutsche Gesellschaft für Pädiatrische Infektiologie e. V. (DGPI), betonen, dass es sich um das letzte Mittel in der Bekämpfung der Pandemie handeln sollte. Diese Botschaft hat auch eine evidenzbasierte und auf interdisziplinärem Expertenkonsens aufgebaute S3-Leitlinie, die bereits Anfang Februar 2021 klare Empfehlungen für Zeiten hoher Inzidenzen in der Gesamtbevölkerung ausgesprochen hat, die Schulschließungen nur noch in Ausnahmefällen für notwendig erachten.

          In diesem Artikel möchten wir die Datenlage mit Stand Juni 2021 zu diesem Thema darlegen, einen Blick in die Zukunft wagen und diskutieren, unter welchen Umständen ein regulärer Präsenzunterricht gelingen kann, ohne das Risiko einer unkontrollierten Ausbreitung von SARS-CoV‑2 in Kauf nehmen zu müssen.

          Translated abstract

          Are children and adolescents relevant disease vectors when it comes to the transmission of SARS-CoV-2? Moreover, do they play a role as relevant disease vectors in a school or kindergarten setting? These questions could not be sufficiently answered at the beginning of the pandemic. Consequently, schools and childcare facilities were closed to stop the spread of SARS-CoV‑2. Over the past few months, researchers have gained a more detailed understanding of the overall pandemic situation. The SARS-CoV‑2 infection rate in children below 10 years of age in 2020 has been substantially lower than in adults. In addition, it showed that children had a milder course of disease.

          Although a majority of the analyses performed in schools and childcare facilities revealed that the virus is transmitted in these facilities, these transmissions did not, however, have a considerable influence on the overall rate of new infections. Despite these findings, German politicians continue to advocate for the closure of childcare facilities, including schools, to fight the pandemic, whereas many specialist societies such as the German Society for Pediatric Infectious Diseases (DGPI) have emphasized that such closures should be the measure of last resort in combating the pandemic. The same message is also conveyed by a German evidence-based S3 guideline established by an interdisciplinary expert group that had already put forward clear recommendations for high incidences in the general population at the beginning of February 2021, indicating that school closures were only required in exceptional cases.

          In this article, we would like to outline the situation based on the currently available data, try to predict the future, and discuss the circumstances necessary to realize normal classroom teaching without accepting the risk of an uncontrolled spread of SARS-CoV‑2.

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          Viral dynamics in mild and severe cases of COVID-19

          Coronavirus disease 2019 (COVID-19) is a new pandemic disease. We previously reported that the viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) peaks within the first week of disease onset.1, 2 Findings from Feb, 2020, indicated that the clinical spectrum of this disease can be very heterogeneous. 3 Here, we report the viral RNA shedding patterns observed in patients with mild and severe COVID-19. 76 patients admitted to the First Affiliated Hospital of Nanchang University (Nanchang, China) from Jan 21 to Feb 4, 2020, were included in the study. All patients were confirmed to have COVID-19 at the time of admission by RT-PCR. The viral loads of their nasopharyngeal swab samples were estimated with the DCt method (Ctsample – Ctref). Patients who had any of the following features at the time of, or after, admission were classified as severe cases: (1) respiratory distress (≥30 breaths per min); (2) oxygen saturation at rest ≤93%; (3) ratio of partial pressure of arterial oxygen to fractional concentration of oxygen inspired air ≤300 mm Hg; or (4) severe disease complications (eg, respiratory failure, requirement of mechanical ventilation, septic shock, or non-respiratory organ failure). 46 (61%) individuals were classified as mild cases and 30 (39%) were classified as severe cases. The basic demographic data and initial clinical symptoms of these patients are shown in the appendix. Parameters did not differ significantly between the groups, except that patients in the severe group were significantly older than those in the mild group, as expected. 4 No patient died from the infection. 23 (77%) of 30 severe cases received intensive care unit (ICU) treatment, whereas none of the mild cases required ICU treatment. We noted that the DCt values of severe cases were significantly lower than those of mild cases at the time of admission (appendix). Nasopharyngeal swabs from both the left and right nasal cavities of the same patient were kept in a sample collection tube containing 3 mL of standard viral transport medium. All samples were collected according to WHO guidelines. 5 The mean viral load of severe cases was around 60 times higher than that of mild cases, suggesting that higher viral loads might be associated with severe clinical outcomes. We further stratified these data according to the day of disease onset at the time of sampling. The DCt values of severe cases remained significantly lower for the first 12 days after onset than those of corresponding mild cases (figure A ). We also studied serial samples from 21 mild and ten severe cases (figure B). Mild cases were found to have an early viral clearance, with 90% of these patients repeatedly testing negative on RT-PCR by day 10 post-onset. By contrast, all severe cases still tested positive at or beyond day 10 post-onset. Overall, our data indicate that, similar to SARS in 2002–03, 6 patients with severe COVID-19 tend to have a high viral load and a long virus-shedding period. This finding suggests that the viral load of SARS-CoV-2 might be a useful marker for assessing disease severity and prognosis. Figure Viral dynamics in patients with mild and severe COVID-19 (A) DCT values (Ctsample-Ctref) from patients with mild and severe COVID-19 at different stages of disease onset. Median, quartile 1, and quartile 3 are shown. (B) DCT values of serial samples from patients with mild and severe COVID-19. COVID-19=coronavirus disease 2019. *p<0·005.
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            Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data

            Background Following the emergency use authorisation of the Pfizer–BioNTech mRNA COVID-19 vaccine BNT162b2 (international non-proprietary name tozinameran) in Israel, the Ministry of Health (MoH) launched a campaign to immunise the 6·5 million residents of Israel aged 16 years and older. We estimated the real-world effectiveness of two doses of BNT162b2 against a range of SARS-CoV-2 outcomes and to evaluate the nationwide public-health impact following the widespread introduction of the vaccine. Methods We used national surveillance data from the first 4 months of the nationwide vaccination campaign to ascertain incident cases of laboratory-confirmed SARS-CoV-2 infections and outcomes, as well as vaccine uptake in residents of Israel aged 16 years and older. Vaccine effectiveness against SARS-CoV-2 outcomes (asymptomatic infection, symptomatic infection, and COVID-19-related hospitalisation, severe or critical hospitalisation, and death) was calculated on the basis of incidence rates in fully vaccinated individuals (defined as those for whom 7 days had passed since receiving the second dose of vaccine) compared with rates in unvaccinated individuals (who had not received any doses of the vaccine), with use of a negative binomial regression model adjusted for age group (16–24, 25–34, 35–44, 45–54, 55–64, 65–74, 75–84, and ≥85 years), sex, and calendar week. The proportion of spike gene target failures on PCR test among a nationwide convenience-sample of SARS-CoV-2-positive specimens was used to estimate the prevelance of the B.1.1.7 variant. Findings During the analysis period (Jan 24 to April 3, 2021), there were 232 268 SARS-CoV-2 infections, 7694 COVID-19 hospitalisations, 4481 severe or critical COVID-19 hospitalisations, and 1113 COVID-19 deaths in people aged 16 years or older. By April 3, 2021, 4 714 932 (72·1%) of 6 538 911 people aged 16 years and older were fully vaccinated with two doses of BNT162b2. Adjusted estimates of vaccine effectiveness at 7 days or longer after the second dose were 95·3% (95% CI 94·9–95·7; incidence rate 91·5 per 100 000 person-days in unvaccinated vs 3·1 per 100 000 person-days in fully vaccinated individuals) against SARS-CoV-2 infection, 91·5% (90·7–92·2; 40·9 vs 1·8 per 100 000 person-days) against asymptomatic SARS-CoV-2 infection, 97·0% (96·7–97·2; 32·5 vs 0·8 per 100 000 person-days) against symptomatic COVID-19, 97·2% (96·8–97·5; 4·6 vs 0·3 per 100 000 person-days) against COVID-19-related hospitalisation, 97·5% (97·1–97·8; 2·7 vs 0·2 per 100 000 person-days) against severe or critical COVID-19-related hospitalisation, and 96·7% (96·0–97·3; 0·6 vs 0·1 per 100 000 person-days) against COVID-19-related death. In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined. 8006 of 8472 samples tested showed a spike gene target failure, giving an estimated prevalence of the B.1.1.7 variant of 94·5% among SARS-CoV-2 infections. Interpretation Two doses of BNT162b2 are highly effective across all age groups (≥16 years, including older adults aged ≥85 years) in preventing symptomatic and asymptomatic SARS-CoV-2 infections and COVID-19-related hospitalisations, severe disease, and death, including those caused by the B.1.1.7 SARS-CoV-2 variant. There were marked and sustained declines in SARS-CoV-2 incidence corresponding to increasing vaccine coverage. These findings suggest that COVID-19 vaccination can help to control the pandemic. Funding None.
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              Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: A living systematic review and meta-analysis

              Background There is disagreement about the level of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted a living systematic review and meta-analysis to address three questions: (1) Amongst people who become infected with SARS-CoV-2, what proportion does not experience symptoms at all during their infection? (2) Amongst people with SARS-CoV-2 infection who are asymptomatic when diagnosed, what proportion will develop symptoms later? (3) What proportion of SARS-CoV-2 transmission is accounted for by people who are either asymptomatic throughout infection or presymptomatic? Methods and findings We searched PubMed, Embase, bioRxiv, and medRxiv using a database of SARS-CoV-2 literature that is updated daily, on 25 March 2020, 20 April 2020, and 10 June 2020. Studies of people with SARS-CoV-2 diagnosed by reverse transcriptase PCR (RT-PCR) that documented follow-up and symptom status at the beginning and end of follow-up or modelling studies were included. One reviewer extracted data and a second verified the extraction, with disagreement resolved by discussion or a third reviewer. Risk of bias in empirical studies was assessed with an adapted checklist for case series, and the relevance and credibility of modelling studies were assessed using a published checklist. We included a total of 94 studies. The overall estimate of the proportion of people who become infected with SARS-CoV-2 and remain asymptomatic throughout infection was 20% (95% confidence interval [CI] 17–25) with a prediction interval of 3%–67% in 79 studies that addressed this review question. There was some evidence that biases in the selection of participants influence the estimate. In seven studies of defined populations screened for SARS-CoV-2 and then followed, 31% (95% CI 26%–37%, prediction interval 24%–38%) remained asymptomatic. The proportion of people that is presymptomatic could not be summarised, owing to heterogeneity. The secondary attack rate was lower in contacts of people with asymptomatic infection than those with symptomatic infection (relative risk 0.35, 95% CI 0.10–1.27). Modelling studies fit to data found a higher proportion of all SARS-CoV-2 infections resulting from transmission from presymptomatic individuals than from asymptomatic individuals. Limitations of the review include that most included studies were not designed to estimate the proportion of asymptomatic SARS-CoV-2 infections and were at risk of selection biases; we did not consider the possible impact of false negative RT-PCR results, which would underestimate the proportion of asymptomatic infections; and the database does not include all sources. Conclusions The findings of this living systematic review suggest that most people who become infected with SARS-CoV-2 will not remain asymptomatic throughout the course of the infection. The contribution of presymptomatic and asymptomatic infections to overall SARS-CoV-2 transmission means that combination prevention measures, with enhanced hand hygiene, masks, testing tracing, and isolation strategies and social distancing, will continue to be needed.
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                Author and article information

                Contributors
                anna.kern@med.uni-muenchen.de
                Journal
                Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz
                Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz
                Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                1436-9990
                1437-1588
                18 November 2021
                18 November 2021
                : 1-8
                Affiliations
                [1 ]GRID grid.411095.8, ISNI 0000 0004 0477 2585, Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, , LMU Klinikum, ; München, Deutschland
                [2 ]GRID grid.4488.0, ISNI 0000 0001 2111 7257, Klinik und Poliklinik für Kinder- und Jugendmedizin, Universitätsklinikum und Medizinische Fakultät Carl Gustav Carus, , TU Dresden, ; Dresden, Deutschland
                [3 ]GRID grid.488549.c, IKM Abt. Neuropädiatrie, Entwicklungsneurologie, Sozialpädiatrie, , Universitätsklinik für Kinder- und Jugendmedizin Tübingen, ; Tübingen, Deutschland
                [4 ]GRID grid.487225.e, ISNI 0000 0001 1945 4553, Bundeszentrale für gesundheitliche Aufklärung (BZgA), ; Köln, Deutschland
                [5 ]GRID grid.7700.0, ISNI 0000 0001 2190 4373, Mannheimer Institut für Public Health, , Universität Heidelberg, ; Mannheim, Deutschland
                Article
                3454
                10.1007/s00103-021-03454-2
                8600106
                34792612
                72f43292-28a4-4003-8cd6-6dd2f2fd92c6
                © The Author(s) 2021

                Open Access Dieser Artikel wird unter der Creative Commons Namensnennung 4.0 International Lizenz veröffentlicht, welche die Nutzung, Vervielfältigung, Bearbeitung, Verbreitung und Wiedergabe in jeglichem Medium und Format erlaubt, sofern Sie den/die ursprünglichen Autor(en) und die Quelle ordnungsgemäß nennen, einen Link zur Creative Commons Lizenz beifügen und angeben, ob Änderungen vorgenommen wurden.

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                History
                : 25 June 2021
                : 22 October 2021
                Funding
                Funded by: Universitätsklinik München (6933)
                Categories
                Leitthema

                covid-19,pandemie,kinder,vektor,schule,pandemic,children,disease vector,schools

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