Sex differences in symptoms following the administration of BNT162b2 mRNA Covid-19 Vaccine in Children below 5 Years of age in Germany (CoVacU5): a retrospective cohort study (preprint)

Background Sex differences exist not only in the efficacy but also in adverse event rates of many vaccines. Here we compared the safety of BNT162b2 vaccine administered off-label in female and male children younger than 5 years in Germany. Methods This is a retrospective cohort study, in which we performed a post-hoc analysis of a dataset collected through an authentication-based survey of individuals having registered children aged 0-<5 years for vaccination against SARS-CoV-2 in six private practices and/or two lay person-initiated vaccination campaigns. We analyzed the safety profiles of the first 3 doses of 3-10g BNT162b2. Primary outcome was comparison in frequencies of 4 common post-vaccination symptom categories such as local, general, musculoskeletal symptoms and fever. Data were analyzed according to sex in bivariate analyses and regression models adjusting for age, weight, and dosage. Interaction between sex and BNT162b2 dosage was assessed. An active-comparator analysis was applied to compare post-vaccination symptoms after BNT162b2 versus non-SARS-CoV-2 vaccines. Results The dataset for the present analysis consisted of 7801 participants including 3842 females (49%) and 3977 males (51%) with an age of 3 years (median, interquartile: 2 years). Among individuals receiving 3g BNT162b2, no sex differences were noted, but after a first dose of 5 or 10g BNT162b2, local injection-site symptoms were more prevalent in girls compared to boys. In logistic regression, female sex was associated with higher odds of local symptoms, odds ratio (OR) of 1.33 (95% confidence interval [CI]: 1.15-1.55, p<0.05) and general symptoms with OR 1.21 (95% CI: 1.01-1.44, p<0.05). Following non-BNT162b2 childhood vaccinations, female sex was associated with a lower odds of post-vaccination musculoskeletal symptoms (OR: 0.29, 95% CI: 0.11-0.82, p<0.05). An active comparator analysis between BNT162b2 and non-SARS-CoV-2 vaccinations revealed that female sex positively influenced the association between BNT162b2 vaccine type and musculoskeletal symptoms. Conclusions Sex differences exist in post-vaccination symptoms after BNT162b2 administration even in young children. These are of importance for the conception of approval studies, for post-vaccination monitoring and for future vaccination strategies. (German Clinical Trials Register ID: DRKS00028759).

Vaccine effectiveness of BNT162b2 mRNA Covid-19 Vaccine in Children below 5 Years in German Primary Care (preprint)

Background Despite the approval of BNT162b2 mRNA vaccine for children aged 6 months to 4 years by the European Medicines Agency (EMA) and the Federal Drug Administration (FDA) in 2022, no data on vaccine effectiveness (VE) of BNT162b2 are available in this age group. We here report on the VE of BNT162b2 during an Omicron BA.1-2 dominant period. Methods An authentication-based retrospective survey was performed between April 14th 2022 and May 9th 2022 in individuals that had registered children for off-label SARS-CoV-2 vaccination in Germany. We used Cox regression to estimate relative VE of two BNT162b2 doses, with the period between first and second vaccine dose as reference period (24.8+-0.6 days) and >=7 days after Dose 2 to before Dose 3 as post-vaccination period (59.5+-23.6 days). Results The present analysis included 4615 children aged 2.8+-1.2 years (mean+-standard deviation) who had received their first dose of BNT162b2 on January 1st 2022 or thereafter. VE was substantial for protection from any SARS-CoV-2 infection (VE: 53.1% [95% confidence interval (CI): 36.3-69.6%], p<0.001), symptomatic SARS-CoV-2 infections (VE: 57.5% [95% CI: 40.8-74.2%], p<0.001), and SARS-CoV-2 infections leading to medication use (VE: 66.2% [95% CI: 43.7-88.7%], p<0.001). Differences in dosage of BNT162b2 yielded no change in VE. Conclusion This study offers a first industry-independent insight in the potential VE of two doses of the BNT162b2 vaccine in children aged below 5 years, as currently only immunogenicity data by the manufacturer Pfizer/BioNTech are available. Limitations include the retrospective study design, and that the reported VE does not necessarily correspond to currently circulating SARS-CoV-2 variants.

Estimates of protection against SARS-CoV-2 infection and severe COVID-19 in Germany before the 2022/2023 winter season - the IMMUNEBRIDGE project (preprint)

Despite the need to generate valid and reliable estimates of protection against SARS-CoV-2 infection and severe course of COVID-19 for the German population in summer 2022, there was a lack of systematically collected population-based data allowing for the assessment of the protection level in real-time. In the IMMUNEBRIDGE project, we harmonised data and biosamples for nine population-/hospital-based studies (total number of participants n=33,637) to provide estimates for protection levels against SARS-CoV-2 infection and severe COVID-19 between June and November 2022. Based on evidence synthesis, we formed a combined endpoint of protection levels based on the number of self-reported infections/vaccinations in combination with nucleocapsid/spike antibody responses ("confirmed exposures"). Four confirmed exposures represented the highest protection level, and no exposure represented the lowest. Most participants were seropositive against the spike antigen; 37% of the participants [≥]79 years had less than four confirmed exposures (highest level of protection) and 5% less than three. In the subgroup of participants with comorbidities, 46-56% had less than four confirmed exposures. We found major heterogeneity across federal states, with 4%-28% of participants having less than three confirmed exposures. Using serological analyses, literature synthesis and infection dynamics during the survey period, we observed moderate to high levels of protection against severe COVID-19, whereas the protection against SARS-CoV-2 infection was low across all age groups. We found relevant protection gaps in the oldest age group and amongst individuals with comorbidities, indicating a need for additional protective measures in these groups.

Burden of Pediatric SARS-CoV-2 Hospitalizations during the Omicron Wave in Germany (preprint)

(1) Background: When the Omicron variant of SARS-CoV-2 first emerged in Germany in January 2022, data on related disease severity among children and adolescents was not yet available. Given Omicron’s high transmissibility, the ability to assess its impact on admission and hospitalization rates in children’s hospitals is critical for the purpose of understanding the scope of its burden on the German health care system. (2) Methods: From January 24, 2022 to July 31, 2022, SARS-CoV-2 cases admitted to German pediatric hospitals were monitored via a national, clinician-led reporting system (CLRS) established by the German Society for Pediatric Infectious Diseases (DGPI). Cases treated on general wards and intensive care units, as well as patient age and need for respiratory support were recorded. (3) Results: From January to July 2022, a median of 1.7 cases (range 0.4–3) per reporting pediatric hospital per day were hospitalized on general wards, whereas a median of 0.1 cases (range 0–0.4 cases) were on intensive care units. Of all hospitalized patients, 4.2% received respiratory support. (4) Conclusions: Despite the high incidence rates documented in connection with the Omicron variant in early 2022, the number of pediatric hospital admissions, and especially the number of cases with need for intensive care treatment and respiratory support due to a symptomatic SARS-CoV-2 infection, remained relatively low. Higher Omicron incidence rates had only a modest impact on SARS-CoV-2-related admissions and hospitalization in German children’s hospitals.

Comparison of Pediatric Inflammatory Multisystem Syndrome temporarily-associated with SARS-CoV-2 and Kawasaki Disease: Results from a nationwide German registry 2020-2021 (preprint)

The connection between Pediatric Inflammatory Multisystem Syndrome (PIMS) and Kawasaki Disease (KD) is not yet fully understood. Using the same national registry, clinical features and outcome of children hospitalized in Germany, and Innsbruck (Austria) were compared. Reported to the registry were 395 PIMS and 69 KD hospitalized patients. Patient age in PIMS cases was higher than in KD cases (median 7 [IQR 4–11] vs. 3 [IQR 1–4] years). A majority of both PIMS and KD patients were male and without comorbidities. PIMS patients more frequently presented with organ dysfunction, with the gastrointestinal (80%), cardiovascular (74%), and respiratory (52%) systems being most commonly affected. By contrast, KD patients more often displayed dermatological (99% vs. 68%) and mucosal changes (94% vs. 64%), plus cervical lymph node swelling (51% vs. 34%). Intensive care admission (48% vs. 19%), pulmonary support (32% vs. 10%), and use of inotropes/vasodilators (28% vs. 3%) were higher among PIMS cases. No patients died. Upon patient discharge, potentially irreversible sequelae – mainly cardiovascular – were reported (7% PIMS vs. 12% KD). Despite differences in age distribution and disease severity, PIMS and KD cases shared many common clinical and prognostic characteristics. This supports the hypothesis that the two entities represent a syndrome continuum.

SARS-CoV-2 variants and the risk of Pediatric Inflammatory Multisystem Syndrome temporally associated with SARS-CoV-2 in children in Germany (preprint)

Purpose: To investigate the risk of Pediatric Inflammatory Multisystem Syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in children depending on periods with different dominant variants of concern (VOC) of SARS-CoV-2.Methods: The risk of developing PIMS-TS in three phases of the pandemic with different VOC (Alpha, Delta, and Omicron) was calculated using data of rtPCR confirmed SARS-CoV-2 infections extracted from the German statutory notification system and reports of cases with PIMS-TS captured by a national, prospective registry. Overall and age group-specific rate ratios of PIMS-TS rates in the different observation periods, using the Alpha period as the baseline, were calculated.Results: The rate of PIMS-TS changed significantly over time. During April-August 2021, with dominant VOC Alpha_B.1.1.7, the PIMS-TS rate was 6.19 (95% confidence intervals (95% CI) 5.17, 7.20), decreased to 1.68 (95% CI 1.49, 1.87) in August 2021 to January 2022 with Delta_AY and to 0.89 (95% CI 0.79, 1.00) in January-April 2022 with Omicron_BA as dominant VOC. This corresponds to a decrease in PIMS-TS rate of 73% (rate ratio 0.271, 95% CI 0.222; 0.332) and 86% (rate ratio 0.048, 95% CI 0.037; 0.062), respectively, compared to the Alpha period. Rate ratios were almost identical for all age groups.Conclusion: The data strongly suggest a relation of the risk for PIMS-TS to the prevailing VOC with the highest risk related to Alpha_B.1.1.7 and the lowest with Omicron_BA. Uniformity of the decrease across age groups does not suggest a major role for vaccination on the risk of PIMS-TS in infected children.

FamilyCoviDD19 Study: Lower SARS-CoV-2 transmission in children and adolescents compared to adults (preprint)

In the COVID-19 pandemic, children were considered to play a major role in SARS-CoV-2 transmission similar to influenza. Thus, mitigation measures have been focused on children, impacting their everyday life severely. However, infectivity in this age group regarding SARS-CoV-2 is not yet clarified. We performed a serology study in households with confirmed SARS-CoV-2 infection to evaluate virus transmission with focus on children and adolescents. Between January and July 2021, 341 minors and 650 adults from 300 households with a confirmed index case participated in the FamilyCoviDD19-study including serological assessment for SARS-CoV-2 antibodies and a questionnaire on demographics, recent and ongoing symptoms, hygiene measures and comorbidities. 45 (16.3%) of all index cases were < 18 years old. Thereof, 55.6% reported COVID-19 associated symptoms, while nearly all adult index cases were symptomatic (94.8%). There was significantly less virus transmission by children and adolescents compared to adult index cases with a secondary attack rate of 0.29 vs. 0.54. With the caveat that the results do not necessarily apply to the Delta and Omicron variants, we conclude that children and adolescents are less susceptible for SARS-CoV-2 infection, more frequently show an asymptomatic course of disease and are less infective than adults.

Safety of the BNT162b2 mRNA COVID-19 Vaccine in Children below 5 Years in Germany (CoVacU5): An Investigator-initiated Retrospective Cohort Study (preprint)

Background The safety of SARS-CoV-2 vaccines is unknown in children aged <5 years. Here, we retrospectively evaluated the safety of BNT162b2 vaccine used off-label in children of this age group in Germany. Methods An investigator-initiated retrospective cohort study (CoVacU5) included parents or caregivers having children aged <5 years registered for SARS-CoV-2 vaccination in outpatient care facilities in Germany. Reported short-term safety data of 1-3 doses of 3-10ug BNT162b2 in children aged 0 to <60 months are presented. Co-primary outcomes were the frequencies of 11 categories of symptoms post-vaccination with bivariate analyses and regression models adjusting for age, sex, weight and height. On-label non-SARS-CoV-2 vaccines served as controls in an active-comparator design. Results The study included 7806 representing a 41% response rate of 19,000 registered children. 338 children received the first dose of BNT162b2 at age 0-<12 months, n=1272 at age 12-24 months and n=5629 at age [≥]24 to <60 months. A 10ug dosage was more frequently associated with injection-site symptoms compared to lower dosages. The probability of any symptoms (OR: 1.62 [95% confidence interval (CI): 1.36-1.94]), injection-site, musculoskeletal, dermatological or otolaryngological symptom categories were modestly elevated after BNT12b2 compared to non-SARS-CoV-2 vaccines, whereas the probabilities of general symptoms (OR: 0.74 [95% CI: 0.64-0.85]) and fever (OR: 0.43 [95% CI: 0.35-0.51]) were lower after BNT162b2. Symptoms requiring hospitalization (n=10) were reported only at BNT162b2 dosages higher than 3ug. Conclusions The symptoms reported after BNT162b2 administration were overall comparable to on-label non-SARS-CoV-2 vaccines in this cohort of children aged <5 years.

Extending the German Corona Consensus Dataset (GECCO) to the immunization, pediatrics, and cardiology domains (preprint)

Background The COVID-19 pandemic has spurred large-scale, inter-institutional research efforts. To enable these efforts, the German Corona Consensus (GECCO) dataset has been developed previously as a harmonized, interoperable collection of the most relevant data elements for COVID-19-related patient research. As GECCO has been developed as a compact core dataset across all medical fields, the focused research within particular medical domains demanded the definition of extension modules that include those data elements that are most relevant to the research performed in these individual medical specialties. Main body We created GECCO extension modules for the immunization, pediatrics , and cardiology domains with respect to the pandemic requests. The data elements included in each of these modules were selected in a consensus-based process by working groups of medical experts from the respective specialty to ensure that the contents are aligned with the research needs of the specialty. The selected data elements were mapped to international standardized vocabularies and data exchange specifications were created using HL7 FHIR profiles on the appropriate resources. All steps were performed in close interdisciplinary collaboration between medical domain experts, medical information scientists and FHIR developers. The profiles and vocabulary mappings were syntactically and semantically validated in a two-stage process. In that way, we defined dataset specifications for a total number of 23 ( immunization ), 59 ( pediatrics ), and 50 ( cardiology ) data elements that augment the GECCO core dataset. We created and published implementation guides and example implementations as well as dataset annotations for each extension module. Conclusions We here present extension modules for the GECCO core dataset that contain data elements most relevant to COVID-19-related patient research in immunization, pediatrics and cardiology . These extension modules were defined in an interdisciplinary, iterative, consensus-based approach that may serve as a blueprint for the development of further dataset definitions and GECCO extension modules. The here developed GECCO extension modules provide a standardized and harmonized definition of specialty-related datasets that can help to enable inter-institutional and cross-country COVID-19 research in these specialties.

Risk of Hospitalization, severe disease, and mortality due to COVID-19 and PIMS-TS in children with SARS-CoV-2 infection in Germany (preprint)

Background: Although children and adolescents have a lower burden of SARS-CoV-2-associated disease as compared to adults, assessing absolute risk among children remains difficult due to a high rate of undetected cases. However, without more accurate case numbers, reliable risk analyses are impossible. Methods: We combine data from three sources - a national seroprevalence study (the SARS-CoV-2 KIDS study), the German statutory notification system and a nationwide registry on children and adolescents hospitalized with either SARS-CoV-2 or Pediatric Inflammatory Multisystem Syndrome (PIMS-TS) - in order to provide reliable estimates on childrens hospitalization, intensive care admission and death due to COVID-19 and PIMS-TS. Results: While the overall hospitalization rate associated with SARS-CoV-2 infection was 35.9 per 10,000 children, ICU admission rate was 1.7 per 10,000 and case fatality was 0.09 per 10,000. Children without comorbidities were found to be significantly less likely to suffer from a severe or fatal disease course. The lowest risk was observed in children aged 5-11 without comorbidities. In this group, the ICU admission rate was 0.2 per 10,000 and case fatality could not be calculated, due to an absence of cases. The overall PIMS-TS rate was 1 per 4,000 SARS-CoV-2 infections, the majority being children without comorbidities. Conclusion: Overall, the SARS-CoV-2-associated burden of a severe disease course or death in children and adolescents is low. This seems particularly the case for 5-11-year-old children without comorbidities. By contrast, PIMS-TS plays a major role in overall disease burden among all pediatric age groups.

Post COVID-19 in children, adolescents, and adults: results of a matched cohort study including more than 150,000 individuals with COVID-19 (preprint)

Background: Long-term health sequelae of the coronavirus disease 2019 (COVID-19) are a major public health concern. However, evidence on post-acute COVID-19 syndrome (post COVID-19) is still limited, particularly for children and adolescents. Utilizing comprehensive healthcare data on more than 45 percent of the German population from January 2019 through December 2020, we investigated post COVID-19 in children/adolescents and adults. Methods: From a total of 38 million individuals, we identified all patients with laboratory confirmed diagnosis of COVID-19 through June 30, 2020. A control cohort was assigned using 1:5 exact matching on age, sex, and propensity score matching on prevalent medical conditions. COVID-19 and control cohorts were followed for incident morbidity outcomes documented at least three months after the date of COVID-19 diagnosis, which was used as the index date for both groups. Overall, 96 pre-defined outcomes were aggregated into 13 diagnosis/symptom complexes and three domains (physical health, mental health, physical/mental overlap domain). We used Poisson regression to estimate incidence rate ratios (IRRs) with 95%-confidence intervals (95%-CI). Results: The study population included 157,134 individuals (11,950 children/adolescents and 145,184 adults) with confirmed COVID-19. COVID-19 and control cohort were well-balanced regarding covariates. For all health outcomes combined, incidence rates (IRs) in the COVID-19 cohort were significantly higher than those in the control cohort in both children/adolescents (IRR=1.30, 95%-CI=[1.25-1.35], IR COVID-19=436.91, IR Control=335.98) and adults (IRR=1.33, 95%-CI=[1.31-1.34], IR COVID-19=615.82, IR Control=464.15). The relative magnitude of increased documented morbidity was similar for the physical, mental, and physical/mental overlap domain. In the COVID-19 cohort, incidence rates were significantly higher in all 13 diagnosis/symptom complexes in adults and in ten diagnosis/symptom complexes in children/adolescents. IRR estimates were similar for the age groups 0-11 and 12-17. Incidence rates in children/adolescents were consistently lower than those in adults. Among the specific outcomes with the highest IRR and an incidence rate of at least 1/100 person-years in the COVID-19 cohort in children and adolescents were malaise/fatigue/exhaustion (IRR=2.28, 95%-CI=[1.71-3.06], IR COVID-19=12.58, IR Control=5.51), cough (IRR=1.74, 95%-CI=[1.48-2.04], IR COVID-19=36.56, IR Control=21.06), and throat/chest pain (IRR=1.72, 95%-CI=[1.39-2.12], IR COVID-19=20.01, IR Control=11.66). In adults, these included dysgeusia (IRR=6.69, 95%-CI=[5.88-7.60], IR COVID-19=12.42, IR Control=1.86), fever (IRR=3.33, 95%-CI=[3.01-3.68], IR COVID-19=11.53, IR Control=3.46), and dyspnea (IRR=2.88, 95%-CI=[2.74-3.02], IR COVID-19=43.91, IR Control=15.27). Conclusions: This large, matched cohort study indicates substantial new-onset post COVID-19 morbidity in pediatric and adult populations based on routine health care documentation. Further investigation is required to assess the persistence and long-term health impact of post COVID-19 conditions, especially in children and adolescents.

Risk factors for hospitalization, disease severity and mortality in children and adolescents with COVID-19: Results from a nationwide German registry (preprint)

Objective To characterize the clinical features of children and adolescents hospitalized with SARS-CoV-2 infections and to explore predictors for disease severity. Design Nationwide prospective observational cohort study. Setting Data collected from 169 out of 351 childrens hospitals in Germany between March 18, 2020 and April 30, 2021 and comparison with the Statutory Notification System. Participants 1,501 children and adolescents up to 19 years of age with laboratory confirmed SARS-CoV-2 infections who were admitted to childrens hospitals and subsequently reported to the COVID-19 registry of the German Pediatric Infectious Disease Society (DGPI). Main outcome measures Admission to intensive care, in-hospital. Results As compared to the information in the statutory notification system, up to 30% of all children and adolescents hospitalized in Germany during the study period were reported to the DGPI registry. Median age was three years (IQR, 0-12), with 36% of reported cases being infants. Although roughly half of patients in the registry were not admitted to the hospital due to their SARS-CoV-2 infection, 72% showed infection-related symptoms during hospitalization. Preexisting comorbidities were present in 28%, most commonly respiratory disorders, followed by neurological, neuromuscular, and cardiovascular diseases. Median length of hospitalization was five days (IQR 3-10). Only 20% of patients received a SARS-CoV-2-related therapy. Infants were less likely to require therapy as compared to older children. Overall, 111 children and adolescents were admitted to intensive care units (ICU). In a fully adjusted model, patient age, trisomy 21, coinfections and primary immunodeficiencies (PID) were significantly associated with intensive care treatment. In a bivariate analysis, pulmonary hypertension, cyanotic heart disease, status post (s/p) cardiac surgery, fatty liver disease, epilepsy and neuromuscular impairment were statistically significant risk factors for ICU admission. Conclusion Overall, a small proportion of children and adolescents was hospitalized in Germany during the first year of the pandemic. The majority of patients within our registry was not admitted due to COVID-19 suggesting an overestimation of the disease burden even in hospitalized children. Nevertheless, a large proportion of children and adolescents with confirmed COVID-19 reported in Germany could be captured. This allowed for detailed assessment of overall disease severity and underlying risk factors in our cohort. The main risk factors for COVID-19 disease associated intensive care treatment were older patient age, trisomy 21, PIDs and coinfection at the time of hospitalization. Trial registration Registry of hospitalized pediatric patients with SARS-CoV-2 infection (COVID-19), DRKS00021506

Mental Health of Adolescents in the Pandemic: Long-COVID-19 or Long-Pandemic Syndrome? (preprint)

Backround: Post-COVID19 complications such as pediatric inflammatory multisystem syndrome (PIMS) and Long-COVID19 move increasingly into focus, potentially causing more harm in this age group than the acute infection. To better understand the symptoms of long-COVID19 in adolescents and to distinguish infection-associated symptoms from pandemic-associated symptoms, we conducted a Long-COVID19 survey, comparing responses from seropositive and seronegative adolescents. To our knowledge, data of Long-COVID19 surveys with seronegative control groups have not been published yet.Methods: Since May 2020 students grade 8-12 in fourteen secondary schools in Eastern Saxony were enrolled in the SchoolCovid19 study. Seroprevalence was assessed via serial SARS-CoV-2 antibody testing in all participants. Furthermore, during the March/April 2021 study visit all participants were asked to complete a 12 question Long-COVID19 survey regarding the occurrence and frequency of difficulties concentrating, memory loss, listlessness, headache, abdominal pain, myalgia/ arthralgia, fatigue, insomnia and mood (sadness, anger, happiness and tenseness).Findings: 1560 students with a median age of 15 years participated in this study. 1365 (88%) were seronegative, 188 (12%) were seropositive. Each symptom was present in at least 35% of the students within the last seven days before the survey. However, there was no statistical difference comparing the reported symptoms between seropositive students and seronegative students. Whether the infection was known or unknown to the participant did not influence the prevalence of symptoms.Interpretation: The lack of differences comparing the reported symptoms between seropositive and seronegative students suggests that Long-COVID19 might be less common than previously thought and emphasizing the impact of pandemic-associated symptoms regarding the well-being and mental health of young adolescents.Trial Registration: Clinical trial number DRKS00022455. SchoolCoviDD19: Prospektive Erfassung der SARS-CoV-2 Seropositivität bei Schulkindern nach Ende der unterrichtsfreien Zeit aufgrund der Corona-Schutz-Verordnung (COVID- 19), DRKS00022455, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00022455Funding: This study was supported by a grant by the Federal State of Saxony. M.K.W. was supported by the Else Kröner-Fresenius Center for Digital Health (EKFZ), TU Dresden, Germany.Declaration of Interests: Reinhard Berner and Jakob P. Armann report grants from the Federal State of Saxony during the conduct of the study. The other authors have no conflicts of interest to disclose.Ethics Approval Statement: The SchoolCoviDD19 study was approved by the Ethics Committee of the Technische Universität (TU) Dresden (BO-EK-156042020).

Mental health of Adolescents in the Pandemic: Long-COVID19 or Long-Pandemic Syndrome? (preprint)

Backround Post-COVID19 complications such as pediatric inflammatory multisystem syndrome (PIMS) and Long-COVID19 move increasingly into focus, potentially causing more harm in this age group than the acute infection. To better understand the symptoms of long-COVID19 in adolescents and to distinguish infection-associated symptoms from pandemic-associated symptoms, we conducted a Long-COVID19 survey, comparing responses from seropositive and seronegative adolescents. To our knowledge, data of Long-COVID19 surveys with seronegative control groups have not been published yet. Methods Since May 2020 students grade 8-12 in fourteen secondary schools in Eastern Saxony were enrolled in the SchoolCovid19 study. Seroprevalence was assessed via serial SARS-CoV-2 antibody testing in all participants. Furthermore, during the March/April 2021 study visit all participants were asked to complete a 12 question Long-COVID19 survey regarding the occurrence and frequency of difficulties concentrating, memory loss, listlessness, headache, abdominal pain, myalgia/ arthralgia, fatigue, insomnia and mood (sadness, anger, happiness and tenseness). Findings 1560 students with a median age of 15 years participated in this study. 1365 (88%) were seronegative, 188 (12%) were seropositive. Each symptom was present in at least 35% of the students within the last seven days before the survey. However, there was no statistical difference comparing the reported symptoms between seropositive students and seronegative students. Whether the infection was known or unknown to the participant did not influence the prevalence of symptoms. Interpretation The lack of differences comparing the reported symptoms between seropositive and seronegative students suggests that Long-COVID19 might be less common than previously thought and emphasizing the impact of pandemic-associated symptoms regarding the well-being and mental health of young adolescents. Funding This study was supported by a grant by the Federal State of Saxony. M.K.W. was supported by the Else Kroener-Fresenius Center for Digital Health (EKFZ), TU Dresden, Germany.

Kinetics and seroprevalence of SARS-CoV-2 antibodies – a comparison of 3 different assays (preprint)

Purpose: Comparing seroprevalence and antibody kinetics in three different commercially available assays for SARS-CoV-2. Methods: Serostatus of COVID-19 patients was analyzed 5 months and 10 months after their infection, using three different assays: Diasorin LIAISON®, Euroimmun®, Abbott Diagnostics® ARCHITECT. Results: Seropositivity at baseline differed significantly depending on the assay (Diasorin 81%, Euroimmun 83%, Abbott 59%). At follow-up antibody levels detected in the Diasorin assay were stable, while there was a significant loss in seropositivity in the Euroimmun and Abbott assays. Conclusion: There are significant differences in SARS-CoV-2 antibody kinetics based on the specific assay used.Trial registration number, date of registration DRKS00022549, 29.07.2020 “retrospectively registered”

Prevalence and Transmission of SARS-CoV-2 in Childcare Facilities: A Longitudinal Study (preprint)

Objectives Previous data indicate that children might play a less crucial role in SARS-CoV-2 transmission than initially assumed. We conducted a study to gain further knowledge on prevalence, transmission and spread of SARS-CoV-2 among preschool children, their parents and caretakers. Methods Children, their parents and care givers in 14 childcare facilities in Dresden, Saxony/ Germany were invited to participate in the KiTaCoviDD19-study between July 2020 and January 2021. Seroprevalence of SARS-CoV-2 antibodies was assessed up to 4 times during the study period in all participating adults and personal characteristics as well as epidemiological information of personal SARS-CoV-2 history were obtained. Stool viral shedding of SARS-CoV-2 was analyzed every 2-4 weeks in all participating children. Results In total, 318 children, 299 parents and 233 childcare workers were enrolled. The percentage of seropositive adults and SARS-CoV-2 positive detected children rose considerably by January 2021. However, the rate of SARS-CoV-2 positive children was considerably lower than the rate of seropositive adults. Overall, we detected a maximum of three connected cases in children. About 50% of SARS-CoV-2 infections in children could not be connected to a secondary case within our study population. Conclusion The study could not provide evidence for a relevant asymptomatic (“silent”) spread of SARS-CoV-2 in childcare facilities, neither in a low nor a high prevalence setting. This finding adds to the evidence that childcare and educational settings do not play a crucial role in driving the SARS-CoV-2 pandemic. Table of Contents Summary This longitudinal study among children, parents and childcare workers provides further insight on SARS-CoV-2 prevalence and transmission within childcare facilities. What’s Known on This Subject Based on age distribution of SARS-CoV-2 infections and previous data of very limited spread of COVID-19 among primary and secondary schools there is reason to believe that children play a less crucial role in SARS-CoV-2 transmission than initially assumed. What This Study Adds Previously published studies focus mainly on SARS-CoV-2 transmission in schools. This longitudinal study provides information on prevalence, transmission and spread of SARS-CoV-2 within childcare facilities during low- and high-prevalence settings.

Kinetics and seroprevalence of SARS-CoV-2 antibodies - a comparison of 3 different assays (preprint)

Purpose Comparing seroprevalence and antibody kinetics in three different commercially available assays for SARS-CoV-2. Methods Serostatus of COVID-19 patients was analyzed 5 months and 10 months after their infection, using three different assays: Diasorin LIAISON, Euroimmun, Abbott Diagnostics ARCHITECT. Results Seropositivity at baseline differed significantly depending on the assay (Diasorin 81%, Euroimmun 83%, Abbott 59%). At follow-up antibody levels detected in the Diasorin assay were stable, while there was a significant loss in seropositivity in the Euroimmun and Abbott assays. Conclusion There are significant differences in SARS-CoV-2 antibody kinetics based on the specific assay used.

Lower Household Transmission Rates of SARS-CoV-2 from Children Compared to Adults - Results from the FamilyCoviDD19-Study (preprint)

Background: While lockdown and social distancing measures effectively reduce transmission rates of SARS-CoV-2 in public spaces crowded indoor spaces remain a significant venue for SARS-CoV-2 transmission. Analyzing seroprevalence in households with confirmed index-cases we can assess transmissibility and risk factors associated with infectivity and susceptibility more accurately than PCR based studies.Methods: Households with a confirmed SARS-CoV-2 infected member in Dresden (Saxony, Germany) were invited to participate in the FamilyCoviDD19 study between June 2020 and January 2021. Personal history and characteristics of the households were obtained and seroprevalence of SARS-CoV-2 antibodies was assessed.Findings:150 households with 414 participating household-members were enrolled. 51% of all study participants were seropositive. The secondary attack rate (SAR) in households with an index-case < 18 years was 0·15 compared to 0·38 in households with an adult index-case. In 56% of the households there was no detectable transmission. Temporal separation and mask wearing reduced transmissions as well as the likelihood of all household members being seropositive significantly.Interpretation: Household transmissions are detected more frequently by seroprevalence than observed in PCR based studies. Children and adolescents are less likely to transmit the disease compared to adults. Temporal separation and mask wearing reduces transmission rates in households significantly.Trial Registration: clinical trial number DRKS00022564Funding Statement: This study was supported by a grant by the Federal State of Saxony.Declaration of Interests: Dr. Berner reports grants from Federal State of Saxony/Germany, during the conduct of the study; Dr. Dalpke reports grants from Federal State of Saxony, during the conduct of the study; Dr. Armann reports grants from Federal State of Saxony, during the conduct of the study; all other authors have nothing to disclose. Ethics Approval Statement: The investigation is part of the FamilyCoviDD19-study which was approved by the Ethics Committee of the Technische Universität (TU) Dresden (BO-EK 342072020).

Anti-SARS-CoV-2 IgG antibodies in adolescent students and their teachers in Saxony, Germany (SchoolCoviDD19): very low seropraevalence and transmission rates (preprint)

Background: School closures are part of the SARS-CoV-2 pandemic control measures in many countries, based on the assumption that children play a similar role in transmitting SARS-CoV-2 as they do in transmitting influenza. We therefore performed a SARS-CoV-2 seropraevalence-study in students and teachers to assess their role in the SARS-CoV-2 transmission. Methods: Students grade 8-11 and their teachers in 13 secondary schools in eastern Saxony, Germany, were invited to participate in the SchoolCoviDD19 study. Blood samples were collected between May 25th and June 30th, 2020. Anti-SARS-CoV-2 IgG were assed using chemiluminescence immunoassay technology and all samples with a positive or equivocal test result were re-tested with two additional serological tests. Findings: 1538 students and 507 teachers participated in this study. The seropraevalence for SARS-CoV-2 was 0.6%. Even in schools with reported Covid-19 cases before the Lockdown of March 13th no clusters could be identified. 23/24 participants with a household history of COVID-91 were seronegative. By using a combination of three different immunoassays we could exclude 16 participants with a positive or equivocal results after initial testing. Interpretation: Students and teachers do not play a crucial role in driving the SARS-CoV-2 pandemic in a low prevalence setting. Transmission in families occurs very infrequently, and the number of unreported cases is low in this age group, making school closures not appear appropriate as a strategy in this low prevalence settings. Funding: This study was supported by a grant from the state of Saxony