SARS-CoV-2 viral clearance and viral load kinetics in young children (1-6 years) compared to adults: Results of a longitudinal study in Germany.

Objective: To investigate SARS-COV-2 viral clearance and viral load kinetics in the course of infection in children aged 1-6 years in comparison with adults. Methods: Prospective cohort study of infected daycare children and staff and their close contacts in households from 11/2020 to 06/2021. Adult participants took upper respiratory tract specimen from themselves and/or their children, for PCR tests on SARS-CoV-2. Data on symptoms and exposure were used to determine the date of probable infection for each participant. We determined (a) viral clearance, and (b) viral load dynamics over time. Samples were taken from day 4-6 to day 16-18 after diagnosis of the index case in the respective daycare group (5 samples per participant). Results: We included 40 children (1-6 years) and 67 adults (18-77 years) with SARS-CoV-2 infection. Samples were available at a mean of 4.3 points of time per participant. Among the participants, the 12-day study period fell in different periods within the individual course of infection, ranging from day 5-17 to day 15-26 after assumed infection.Children reached viral clearance at a median of 20 days after assumed infection (95% CI 17-21 days, Kaplan-Meier Analysis), adults at 23 days (95% CI 20-25 days, difference not significant). In both children and adults, viral load decreased over time with trajectories of the mean viral load not being statistically different between groups. Kaplan-Meier calculations show that from day 15 (95% CI 13-15), 50% of all participants had a viral load <1 million copies/ml, i.e. were no longer infectious or negative. Conclusion: Children aged 1-6 and adults infected with SARS-CoV-2 (wild type and Alpha variant) did not differ significantly in terms of viral load kinetics and time needed to clear the virus. Therefore, containment measures are important also in the daycare settings as long as the pandemic continues.

[Symptoms of SARS-CoV-2 infections in children of day care age]. / Symptomatik einer akuten SARS-CoV-2-Infektion bei Kindern im Kita-Alter.

Background: The symptoms of SARS-CoV­2 infections in children are mostly mild; however, the symptoms are highly variable. There are only a few studies on non-hospitalized children. The clinical picture described in hospitalized children cannot be transferred to non-hospitalized children and the frequency of certain symptoms in children may thus be overestimated. Furthermore, most studies include a broad age group (up to 18 years). The symptoms of younger children have so far been described in less detail. Objective: The paper aims to describe the frequency of COVID-19 symptoms in younger children (1-6 years old). Data of the two modules COALA (Corona: Anlassbezogene Untersuchungen in Kitas) and CATS (Corona-KiTa surveillance) of the Corona-KiTa study are evaluated and the results of the two studies are compared and discussed against the background of the different methodologies. In the COALA study, the type and frequency of symptoms of children infected with SARS-CoV­2 are evaluated and compared to symptoms of children who tested negative for SARS-CoV­2. Symptom frequencies of SARS-CoV­2 infected children of the COALA study are compared with data collected from surveillance data (CATS). Material and methods: The COALA study investigated 30 SARS-CoV­2 outbreaks in day care centers where at least 1 SARS-CoV­2 case was reported between October 2020 and June 2021. Using a prospective study design, day care children who were infected with SARS-CoV­2 and their contact persons were studied over a period of 12 days (including regular SARS-CoV­2 testing, retrospective interviews and daily symptom reporting). The results from the COALA study were compared with data from COVID-19 surveillance cases (CATS) for the same age group and time period. In Germany, SARS-CoV­2 cases are reported to the local health authorities by physicians and laboratories. When reporting cases symptoms can be reported as well. Results: From the COALA study, interview and reported symptom data were available for 289 children from the participating day care centers. Of 39 children with a SARS-CoV­2 infection (wild-type, α­variant), 64% had at least 1 symptom; of the children who tested negative for SARS-CoV­2, 40% had at least 1 symptom. In both groups, rhinitis was the most common symptom (36% vs. 25%, n. s.). From the surveillance data (CATS), clinical information was available for 84,371 SARS-CoV­2 positive children; fever was most common (27%) along with rhinitis (26%). Severe symptoms such as dyspnea were rarely reported in the outbreak investigations and in the surveillance data (3% and 1%, respectively). Conclusion: Day care-aged children infected with SARS-CoV­2 usually have mild or asymptomatic courses. Their symptoms are similar to those of children who tested negative for SARS-CoV­2 from the same day care centers; thus, the observed COVID-19 symptoms are nonspecific. Combining data from the two modules is useful: findings from a very large database, as provided by the surveillance data, are complemented by findings from day care center outbreaks, where detailed prospective data on infected children can be compared with those of children who tested negative for SARS-CoV­2.

Analysis of two choir outbreaks acting in concert to characterize long- range transmission risks through SARS-CoV-2, Berlin, Germany, 2020.

BACKGROUND: Superspreading events are important drivers of the SARS-CoV-2 pandemic and long-range (LR) transmission is believed to play a major role. We investigated two choir outbreaks with different attack rates (AR) to analyze the contribution of LR transmission and highlight important measures for prevention. METHODS: We conducted two retrospective cohort studies and obtained demographic, clinical, laboratory and contact data, performed SARS-CoV-2 serology, whole genome sequencing (WGS), calculated LR transmission probabilities, measured particle emissions of selected choir members, and calculated particle air concentrations and inhalation doses. RESULTS: We included 65 (84%) and 42 (100%) members of choirs 1 and 2, respectively, of whom 58 (89%) and 10 (24%) became cases. WGS confirmed strain identity in both choirs. Both primary cases transmitted presymptomatically. Particle emission rate when singing was 7 times higher compared to talking. In choir 1, the median concentration of primary cases' emitted particles in the room was estimated to be 8 times higher, exposure at least 30 minutes longer and room volume smaller than in choir 2, resulting in markedly different estimated probabilities for LR transmission (mode: 90% vs. 16%, 95% CI: 80-95% vs. 6-36%). According to a risk model, the first transmission in choir 1 occurred likely after 8 minutes of singing. CONCLUSIONS: The attack rate of the two choirs differed significantly reflecting the differences in LR transmission risks. The pooled proportion of cases due to LR transmission was substantial (81%; 55/68 cases) and was facilitated by likely highly infectious primary cases, high particle emission rates, and indoor rehearsing for an extended time. Even in large rooms, singing of an infectious person may lead to secondary infections through LR exposure within minutes. In the context of indoor gatherings without mask-wearing and waning or insufficient immunity, these results highlight the ongoing importance of non-pharmaceutical interventions wherever aerosols can accumulate.

Delta and Omicron: protective measures and SARS-CoV-2 infections in day care centres in Germany in the 4th and 5th wave of the pandemic 2021/2022.

BACKGROUND: During the five waves of the SARS-CoV-2 pandemic so far, German early childhood education and care (ECEC) centres implemented various protective measures, such as wearing a face mask, fixed children-staff groups or regular ventilation. In addition, parents and ECEC staff were increasingly vaccinated throughout 2021. During the 4th wave, variant of concern (VOC) Delta-driven transmission indicators reached record values at the end of 2021. Those values were even exceeded in the 5th wave at the beginning of 2022 when Omicron dominated. We examine which factors facilitated or prevented infection with SARS-CoV-2 in ECEC centres, and if these differed between different phases within wave 4 (Delta) and 5 (Omicron). METHODS: Since August 2020, a weekly online survey among approximately 8000 ECEC managers has been conducted, monitoring both incident SARS-CoV-2 infections and protective measures taken. We included data from calendar week 26/2021 to 05/2022. We estimate the probability of any infections and the number of SARS-CoV-2 infections in children, parents and staff using random-effect-within-between (REWB) panel models for binomial and count data. RESULTS: While children, parents and staff of ECEC centres with a high proportion of children from families with low socioeconomic status (SES) have a higher risk of infections in the beginning of wave 4 (OR up to 1.99 [1.56; 2.56]), this effect diminishes for children and parents with rising incidences. Protective measures, such as wearing face masks, tend to have more extensive effects with rising incidences in wave 5 (IRR up to 0.87 [0.8; 0.93]). Further, the protective effect of vaccination against infection among staff is decreasing from wave 4 to wave 5 (OR 0.3 [0.16; 0.55] to OR 0.95, [0.84; 1.07, n.s.]). The degree of transmission from staff to child and from staff to parent is decreasing from wave 4 to wave 5, while transmission from child to staff seems to increase. CONCLUSION: While Omicron seems to affect children and parents from ECEC centres with families with all SES levels more equally than Delta, the protective effect of vaccination against infection is decreasing and the effect of protective measures like face masks becomes increasingly important. In order to prevent massive closures of ECEC centres due to infection of staff, protective measures should be strictly adhered to, especially to protect staff in centres with a high proportion of children from families with low socioeconomic status.

Symptomatik einer akuten SARS-CoV-2-Infektion bei Kindern im Kita-Alter Symptoms of SARS-CoV-2 infections in children of day care age

Hintergrund Die Symptomatik einer pädiatrischen SARS-CoV-2-Infektion ist sehr variabel. Es gibt nur wenige Studien zu nichthospitalisierten Kindern bzw. Kindern im Kita-Alter. Ziel der Arbeit Die Arbeit soll die Häufigkeit verschiedener COVID-19-Symptome bei ein- bis 6‑jährigen Kindern beschreiben. Sie führt dazu Daten aus 2 Modulen der Corona-KiTa-Studie zusammen: 1) das Modul „COALA“ – Corona: Anlassbezogene Untersuchungen in Kitas und 2) das Modul „CATS“ – Corona KiTa Surveillance (Meldedaten). Material und Methoden In COALA wurden die Infektionsgeschehen in 30 Kitas, in denen ein SARS-CoV-2-Fall gemeldet wurde, untersucht (Oktober 2020 bis Juni 2021). Kita-Kinder wurden prospektiv über 12 Tage beobachtet (SARS-CoV-2-Tests, Symptomtagebuch). Die Ergebnisse wurden mit den Symptomangaben der deutschlandweit gemeldeten SARS-CoV-2-Fälle (Meldedaten) verglichen. Ergebnisse Aus den teilnehmenden Kitas liegen für 289 Kinder Angaben vor. Von 39 Kindern mit SARS-CoV‑2 (Wildtyp, α‑Variante) hatten 64 % mindestens ein Symptom, von den nicht mit SARS-CoV‑2 infizierten Kindern 40 %. In beiden Gruppen war Schnupfen das häufigste Symptom (36 % vs. 25 %, n. s.). Aus den Meldedaten liegen für 84.371 Kinder klinische Informationen vor, Fieber war am häufigsten (27 %), neben Schnupfen (26 %). Schwere Beschwerden wie z. B. Atemnot wurden in den Ausbruchsuntersuchungen und in den Meldedaten nur selten angegeben (3 % bzw. 1 %). Schlussfolgerung Kinder im Kita-Alter haben meist milde bzw. asymptomatische Verläufe einer SARS-CoV-2-Infektion. Ihre Symptome ähneln denjenigen von nicht mit SARS-CoV‑2 infizierten Kindern aus denselben Kitas. Es erscheint sinnvoll, Erkenntnisse aus den Meldedaten durch Ausbruchsuntersuchungen zu ergänzen, um methodische Limitationen der einzelnen Vorgehensweisen auszugleichen. Zusatzmaterial online Die Online-Version dieses Beitrags (10.1007/s00112-022-01640-3) enthält eine weitere Tabelle, die Symptome bei symptomatischen SARS-CoV-2-Fällen von Kindern im Alter von einem bis 6 Jahren in der COALA-Stichprobe und in den Meldedaten gegenüberstellt.

Transmission of SARS-CoV-2 among children and staff in German daycare centres.

In daycare centres, the close contact of children with other children and employees favours the transmission of infections. The majority of children <6 years attend daycare programmes in Germany, but the role of daycare centres in the SARS-CoV-2 pandemic is unclear. We investigated the transmission risk in daycare centres and the spread of SARS-CoV-2 to associated households. 30 daycare groups with at least one recent laboratory-confirmed SARS-CoV-2 case were enrolled in the study (10/2020-06/2021). Close contact persons within daycare and households were examined over a 12-day period (repeated SARS-CoV-2 PCR tests, genetic sequencing of viruses, symptom diary). Households were interviewed to gain comprehensive information on each outbreak. We determined primary cases for all daycare groups. The number of secondary cases varied considerably between daycare groups. The pooled secondary attack rate (SAR) across all 30 daycare centres was 9.6%. The SAR tended to be higher when the Alpha variant was detected (15.9% vs. 5.1% with evidence of wild type). The household SAR was 53.3%. Exposed daycare children were less likely to get infected with SARS-CoV-2 than employees (7.7% vs. 15.5%). Containment measures in daycare programmes are critical to reduce SARS-CoV-2 transmission, especially to avoid spread to associated households.

SARS-CoV-2 Transmissibility Within Day Care Centers-Study Protocol of a Prospective Analysis of Outbreaks in Germany.

Introduction: Until today, the role of children in the transmission dynamics of SARS-CoV-2 and the development of the COVID-19 pandemic seems to be dynamic and is not finally resolved. The primary aim of this study is to investigate the transmission dynamics of SARS-CoV-2 in child day care centers and connected households as well as transmission-related indicators and clinical symptoms among children and adults. Methods and Analysis: COALA ("Corona outbreak-related examinations in day care centers") is a day care center- and household-based study with a case-ascertained study design. Based on day care centers with at least one reported case of SARS-CoV-2, we include one- to six-year-old children and staff of the affected group in the day care center as well as their respective households. We visit each child's and adult's household. During the home visit we take from each household member a combined mouth and nose swab as well as a saliva sample for analysis of SARS-CoV-2-RNA by real-time reverse transcription polymerase chain reaction (real-time RT-PCR) and a capillary blood sample for a retrospective assessment of an earlier SARS-CoV-2 infection. Furthermore, information on health status, socio-demographics and COVID-19 protective measures are collected via a short telephone interview in the subsequent days. In the following 12 days, household members (or parents for their children) self-collect the same respiratory samples as described above every 3 days and a stool sample for children once. COVID-19 symptoms are documented daily in a symptom diary. Approximately 35 days after testing the index case, every participant who tested positive for SARS-CoV-2 during the study is re-visited at home for another capillary blood sample and a standardized interview. The analysis includes secondary attack rates, by age of primary case, both in the day care center and in households, as well as viral shedding dynamics, including the beginning of shedding relative to symptom onset and viral clearance. Discussion: The results contribute to a better understanding of the epidemiological and virological transmission-related indicators of SARS-CoV-2 among young children, as compared to adults and the interplay between day care and households.

SARS-CoV-2 Aerosol Transmission Indoors: A Closer Look at Viral Load, Infectivity, the Effectiveness of Preventive Measures and a Simple Approach for Practical Recommendations.

There is uncertainty about the viral loads of infectious individuals required to transmit COVID-19 via aerosol. In addition, there is a lack of both quantification of the influencing parameters on airborne transmission and simple-to-use models for assessing the risk of infection in practice, which furthermore quantify the influence of non-medical preventive measures. In this study, a dose-response model was adopted to analyze 25 documented outbreaks at infection rates of 4-100%. We show that infection was only possible if the viral load was higher than 108 viral copies/mL. Based on mathematical simplifications of our approach to predict the probable situational attack rate (PARs) of a group of persons in a room, and valid assumptions, we provide simplified equations to calculate, among others, the maximum possible number of persons and the person-related virus-free air supply flow necessary to keep the number of newly infected persons to less than one. A comparison of different preventive measures revealed that testing contributes the most to the joint protective effect, besides wearing masks and increasing ventilation. In addition, we conclude that absolute volume flow rate or person-related volume flow rate are more intuitive parameters for evaluating ventilation for infection prevention than air exchange rate.

[SARS-CoV-2 incidence, transmission, and containment measures in daycare centers during the COVID-19 pandemic-findings from the Corona Daycare Study]. / Infektionsgeschehen und Eindämmungsmaßnahmen in Kitas während der COVID-19-Pandemie ­ Erkenntnisse aus der Corona-KiTa-Studie.

BACKGROUND: Daycare centers are of substantial sociopolitical and pedagogical relevance; at the same time, the close contact of children in daycare groups among each other and with employees favors the transmission of infections. In the COVID-19 pandemic, questions arose about how infection events occur in daycare centers, what role daycare children play in the pandemic, and what protective and hygienic measures are implemented in daycare centers. From 06/2020 to 12/2021, we conducted the "Corona Day Care Study," in which we address pedagogical and infection epidemiological topics in a joint approach. METHODS: In the study, data are collected from different sources. Official reporting data as well as weekly data from daycare centers in the so-called KiTa Register are continuously evaluated. In addition, SARS-CoV­2 outbreaks in daycare centers are investigated on site by repeated sample collection and interviews. RESULTS: SARS-CoV­2 infection incidence in daycare centers or in daycare-aged children was very dynamic from 03/2020 to 05/2021. In the second and third pandemic waves, the number of SARS-CoV­2 outbreaks in daycare centers rose sharply, accompanied by a substantial increase in daycare and group closures. Most recently, the proportion of affected children in outbreaks increased steadily. However, preliminary examinations of SARS-CoV­2 outbreaks (n = 28) revealed that, on average, only a fraction of daycare contact persons (6.8%) were infected by child index cases. Transmission frequencies differed markedly between the individual daycare centers. DISCUSSION: The combination of regularly collected reporting and survey data as well as outbreak investigations allows a multilayered monitoring and understanding of infection events in daycare centers; its findings could be incorporated into recommendations for public health measures.

Factors preventing SARS-CoV-2 transmission during unintentional exposure in a GP practice: a cohort study of patient contacts; Germany, 2020.

Two general practitioners (GPs) with SARS-CoV-2 infection provided in-person patient care to patients of their joint medical practice before and after symptom onset, up until SARS-CoV-2 laboratory confirmation. Through active contact tracing, the local public health authorities recruited the cohort of patients that had contact with either GP in their putative infectious period. In this cohort of patient contacts, we assess the frequency and determinants of SARS-CoV-2-transmission from GPs to patients. We calculated incidence rate ratios (IRR) to explore the type of contact as an explanatory variable for COVID-19 cases. Among the cohort of 83 patient contacts, we identified 22 (27%) COVID-19 cases including 17 (21%) possible, three (4%) probable and two (2%) confirmed cases. All 22 cases had contact with a GP when the GP did not wear a mask, and/or when contact was ≥10 min. Importantly, patients who had contact <10 min with a GP wearing a facemask were at reduced risk (IRR 0.21; 95% CI 0.01-0.99) of COVID-19. This outbreak investigation adds to the body of evidence in supporting current guidelines on measures at preventing the transmission of SARS-CoV-2 in an outpatient setting.

SARS-CoV-2 variant B.1.1.7 susceptibility and infectiousness of children and adults deduced from investigations of childcare centre outbreaks, Germany, 2021.

We investigated three SARS-CoV-2 variant B.1.1.7 childcare centre and related household outbreaks. Despite group cohorting, cases occurred in almost all groups, i.e. also among persons without close contact. Children's secondary attack rates (SAR) were similar to adults (childcare centres: 23% vs 30%; p = 0.15; households: 32% vs 39%; p = 0.27); child- and adult-induced household outbreaks also led to similar SAR. With the advent of B.1.1.7, susceptibility and infectiousness of children and adults seem to converge. Public health measures should be revisited accordingly.

[Measures to cope with the COVID-19 pandemic in Germany: nonpharmaceutical and pharmaceutical interventions]. / Maßnahmen zur Bewältigung der COVID-19-Pandemie in Deutschland: nichtpharmakologische und pharmakologische Ansätze.

When the emerging novel SARS-CoV­2 virus first appeared in December 2019, neither specific therapeutic options nor vaccinations were available. The role of nonpharmaceutical interventions (NPIs) became of central importance. At the Robert Koch Institute, a multilayer strategy consisting of population-based and individual preventive measures to control the pandemic was developed, which built upon existing influenza pandemic plans as well as generic plans. This paper explains the recommended NPIs and illustrates the pharmaceutical approaches developed in parallel.Among others, general contact bans, providing material for infection prevention and control, ban of events, closing educational institutions, and restricting travel are counted among population-based measures. Additional individual preventive measures are necessary, e.g., keeping a minimum distance, reducing contacts, and wearing a mouth-nose covering as well as quarantine and isolation. Measures within the health system are based on recommendations of the Commission on Hospital Hygiene and Infection Protection (Kommission für Krankenhaushygiene und Infektionsprävention (KRINKO)) and specified and implemented by professional societies. Since November 2020, an antiviral therapy with remdesivir and treatment with the glucocorticoid dexamethasone have been available as pharmaceutical interventions. Monoclonal antibodies are at this time not approved. Therapeutic anticoagulation is recommended.Recommendations are constantly adapted to the increasing knowledge on the pathogen and its means of transmission. A challenge is to strengthen the trust of the population. Many measures have to be applied on an individual basis in order to work together.

[Monitoring of COVID-19 by extending existing surveillance for acute respiratory infections]. / Überwachung von COVID-19 durch Erweiterung der etablierten Surveillance für Atemwegsinfektionen.

As part of the national influenza pandemic preparedness, surveillance systems have been established in Germany in addition to the mandatory notifications according to the Protection Against Infection Act. The aim of these systems is the description, analysis, and evaluation of the epidemiology of acute respiratory infections (ARIs), the identification of the circulating viruses, and the trend. Since the beginning of the COVID-19 pandemic, the systems have been expanded to enable monitoring of infections with SARS-CoV­2.Three systems are presented: GrippeWeb, the primary care sentinel Arbeitsgemeinschaft Influenza with its electronic reporting module SEEDARE, and the ICD-10-based hospital sentinel ICOSARI. With these systems, ARIs can be monitored at the population, outpatient, and inpatient levels. In combination with the monitoring of mortality, these systems provide important information on the frequency of different stages of disease severity in the population. In order to expand the systems to SARS-CoV­2, only a few adjustments were needed.As the case definitions for ARIs were preserved, historical baselines of the systems can still be used for comparison. All systems are structured in such a way that stable and established reference values are available for calculating weekly proportions and rates.This is an important addition to the mandatory reporting system of infectious diseases in Germany, which depends on the particular testing strategy, the number of tests performed, and on specific case definitions, which are adapted as required.The surveillance systems have proven to be feasible and efficient in the COVID-19 pandemic, even when compared internationally.

[Field investigations of SARS-CoV-2-outbreaks in Germany by the Robert Koch Institute, February-October 2020]. / Untersuchung von SARS-CoV-2-Ausbrüchen in Deutschland durch Feldteams des Robert Koch-Instituts, Februar­Oktober 2020.

The Robert Koch Institute (RKI) offers advice and assistance to local public health agencies on the investigation and management of outbreaks of infectious diseases. Specially trained experts conduct field investigations. During the COVID-19 pandemic, RKI experts participated in the investigation of outbreaks in residential buildings, physicians' offices, nursing homes, hospitals, and asylum seekers' facilities as well as at a night club and on a cruise ship.This report describes some of the field investigations conducted in Germany during the COVID-19 pandemic between February and October 2020. The investigations provided information on the properties of SARS-CoV­2 and its transmission as a basis for the recommendations on suitable prevention measures. The practical examples demonstrate the variety of support given as well as the opportunities to gather epidemiological evidence.In September 2020, the RKI established a new unit called the "Focal Point for the Public Health Service," which now coordinates and is expanding field support. In order to further support the public health system to improve its capability to react to and investigate outbreaks of infectious diseases, interdisciplinary training shall be intensified.

Analysis of Asymptomatic and Presymptomatic Transmission in SARS-CoV-2 Outbreak, Germany, 2020.

We determined secondary attack rates (SAR) among close contacts of 59 asymptomatic and symptomatic coronavirus disease case-patients by presymptomatic and symptomatic exposure. We observed no transmission from asymptomatic case-patients and highest SAR through presymptomatic exposure. Rapid quarantine of close contacts with or without symptoms is needed to prevent presymptomatic transmission.

Surveillance of COVID-19 school outbreaks, Germany, March to August 2020.

Mitigation of the coronavirus disease (COVID-19) pandemic in Germany included school closures in early March 2020. After reopening in April, preventive measures were taken in schools. We analysed national surveillance system data on COVID-19 school outbreaks during different time periods. After reopening, smaller outbreaks (average: 2.2/week) occurred despite low incidence in the general population. School closures might have a detrimental effect on children and should be applied only cautiously and in combination with other measures.