FamilyCoviDD19: results of a cross-sectional study-long-term outcomes of infected and uninfected household members.

OBJECTIVE: In this study, we aimed to compare long-term physical and mental health outcome between SARS-CoV-2 infected and uninfected household members to differentiate between infection-related and pandemic-related outcomes after about two and a half years of the pandemic. Furthermore, possible differences in the outcome of adults and children and young people (CYP) were of interest. DESIGN: In a cross-sectional study design, we compared the long-term physical and mental health outcome of between infected and uninfected as well as between adult and CYP (household members). SETTING: The FamilyCoviDD19 study-a serology study in households-was initially conducted to evaluate virus transmission in a close contact setting focusing on households with children and adolescents in Germany. At least 1 year after initial infection in the respective households, a follow-up took place in which the prevalence and type of possible long-term consequences were surveyed on the basis of self-reported information on physical and mental health. PARTICIPANT: In this study, a total of 533 household members of 146 families participated and responded to our survey, including 296 (55.5%) adults and 237 (44.5%) CYP. RESULT: The difference in frequency of reported symptoms between infected and uninfected individuals was very moderate, suggesting that the vast majority of reported symptoms were not attributable to a previous SARS-CoV-2 infection. However, regardless of age and infection status, this study showed overall high rates of self-reported symptoms with CYP having fewer long-term sequelae than adults one year after infection. Furthermore, over 50% of those reporting symptoms were not affected in their daily life, with CYPs reporting an even lower percentage compared with adults. CONCLUSION: CYP are at reduced risk not only to develop symptomatic infection or severe disease courses (previous analyses) but also to develop infection-associated long-term sequelae (this study). Independent of infection CYP reported high rates of neurocognitive, pain, somatic and mood symptoms, which makes the influence of the pandemic itself-including pandemic control measures-decisive.

Subjective Perception of Recovery and Measured Olfactory Function in COVID-19 Patients.

This cross-sectional study aimed to investigate self-rated olfactory dysfunction in relation to measured olfactory function after partial or complete subjective recovery in individuals with a history of coronavirus disease 2019 (COVID-19) infection. A total of 186 individuals (aged 5-62 years) with a history of COVID-19 infection were included. Visual analogue scale (VAS) ratings for olfactory function (before, during, and after infection) and age-appropriate psychophysical olfactory test scores (odor threshold and odor identification: "Sniffin' Sticks" for adults and both "Sniffin' Sticks" and "U-Sniff" for children) were determined. Participants were assigned to four "age groups" and three "recovery classes" (incomplete recovery, complete recovery, no smell loss). Surprisingly, there were no significant differences in odor threshold and adult identification scores between the "recovery classes". However, children with "incomplete recovery" had lower identification scores than those with "complete recovery" (p = 0.033) and those with "no smell loss" (p = 0.022). The pediatric age groups had significantly higher VAS ratings during and after COVID-19 compared to older participants. Older individuals experienced greater magnitude of changes in their sense of smell after COVID-19 infection, but those with parosmia were 3.5 times more likely to report "incomplete recovery" of olfaction after COVID-19. The general prognosis for olfactory recovery after COVID-19 is good but appears to be particularly confounded by the presence of parosmia, leading patients to subjectively report incomplete olfactory recovery. Although it is of high significance to monitor recovery using validated psychophysical olfactory tests, subjective measures of olfaction help provide specific insight, especially for qualitative olfactory dysfunction.

Pediatric ICU Admissions After Adolescent Suicide Attempts During the Pandemic.

BACKGROUND AND OBJECTIVES: The worldwide severe acute respiratory syndrome coronavirus 2 pandemic challenges adolescents' mental health. In this study, we aim to compare the number of pediatric ICU (PICU) admissions after suicide attempts during the first German lockdown and one year later during a second, prolonged lockdown with prepandemic years. METHODS: A retrospective multicenter study was conducted among 27 German PICUs. Cases <18 years admitted to the PICU because of accidents or injuries between March 16 and May 31 of 2017 to 2021 were identified based on International Classification of Diseases, 10th Revision codes (German modification) and patient data entered into a database. This study is a subset analysis on suicide attempts in adolescents aged 12 to 17.9 years. The Federal Statistics Office was queried for data on fatal suicides, which were available only for 2020 in adolescents aged 10 to 17.9 years. RESULTS: Total admissions and suicide attempts declined during the first lockdown in 2020 (standardized morbidity ratio 0.74 (95% confidence interval; 0.58-0.92) and 0.69 (0.43-1.04), respectively) and increased in 2021 (standardized morbidity ratio 2.14 [1.86-2.45] and 2.84 [2.29-3.49], respectively). Fatal suicide rates remained stable between 2017 to 2019 and 2020 (1.57 vs 1.48 per 100 000 adolescent years) with monthly numbers showing no clear trend during the course of 2020. CONCLUSIONS: This study shows a strong increase in serious suicide attempts among adolescents during the course of the pandemic in Germany. More research is needed to understand the relation between pandemic prevention measures and suicidal ideation to help implement mental health support for adolescents.

Seroprevalence of SARS-CoV-2 in German secondary schools from October 2020 to July 2021: a longitudinal study.

PURPOSE: To quantify the number of SARS-CoV-2 infections in students and teachers in 14 Secondary schools in eastern Saxony, Germany. Seroprevalence of SARS-CoV-2 antibodies in study population. Number of undetected cases. METHODS: Serial seroprevalence study. RESULTS: The role of educational settings in the SARS-CoV-2 Pandemic is still controversial. Seroprevalence increases from 0.8 to 5.9% from October to December when schools remained open and to 12.2% in March/April during a strict lockdown with closed schools. The ratio of undetected to detected cases decreased from 0.76 to 0.44 during the study period. CONCLUSION: During the second and third wave of the pandemic in Germany, students and teachers are not overrepresented in SARS-CoV-2 infections. The percentage of undetected cases is moderate and decreases over time. The risk of contracting SARS-CoV-2 within the household is higher than contracting it in educational settings making school closures rather ineffective in terms of pandemic control measures or individual risk reduction in children and adolescents. TRIAL REGISTRATION: DRKS00022455 (July 23rd, 2020).

Impact of the First COVID Lockdown on Accident- and Injury-Related Pediatric Intensive Care Admissions in Germany-A Multicenter Study.

Children's and adolescents' lives drastically changed during COVID lockdowns worldwide. To compare accident- and injury-related admissions to pediatric intensive care units (PICU) during the first German COVID lockdown with previous years, we conducted a retrospective multicenter study among 37 PICUs (21.5% of German PICU capacities). A total of 1444 admissions after accidents or injuries during the first lockdown period and matched periods of 2017-2019 were reported and standardized morbidity ratios (SMR) were calculated. Total PICU admissions due to accidents/injuries declined from an average of 366 to 346 (SMR 0.95 (CI 0.85-1.05)). Admissions with trauma increased from 196 to 212 (1.07 (0.93-1.23). Traffic accidents and school/kindergarten accidents decreased (0.77 (0.57-1.02 and 0.26 (0.05-0.75)), whereas household and leisure accidents increased (1.33 (1.06-1.66) and 1.34 (1.06-1.67)). Less neurosurgeries and more visceral surgeries were performed (0.69 (0.38-1.16) and 2.09 (1.19-3.39)). Non-accidental non-suicidal injuries declined (0.73 (0.42-1.17)). Suicide attempts increased in adolescent boys (1.38 (0.51-3.02)), but decreased in adolescent girls (0.56 (0.32-0.79)). In summary, changed trauma mechanisms entailed different surgeries compared to previous years. We found no evidence for an increase in child abuse cases requiring intensive care. The increase in suicide attempts among boys demands investigation.

Comparison of mental health outcomes in seropositive and seronegative adolescents during the COVID19 pandemic.

Post-COVID19 complications such as pediatric inflammatory multisystem syndrome (PIMS) and Long-COVID19 move increasingly into focus, potentially causing more harm in young adolescents than the acute infection. To better understand the symptoms of long-term mental health outcomes in adolescents and distinguish infection-associated symptoms from pandemic-associated symptoms, we conducted a 12 question Long-COVID19 survey. Using this survey, we compared the responses on neurocognitive, general pain and mood symptoms from seropositive and seronegative adolescents in a cross-sectional study design. Since May 2020, students grade 8-12 in fourteen secondary schools in Eastern Saxony were enrolled in the SchoolCovid19 study. Serostatus was assessed regularly in all participants. In March/April 2021, 1560 students with a median age of 15 years participated at the regular study visit after re-opening of the schools in mid-March and responded to our Long-COVID19 survey as part of this visit. 1365 (88%) students were seronegative, 188 (12%) were seropositive. Each symptom asked in the Long-COVID19 survey was present in at least 35% of the students within the last seven days before the survey. With the exception of seropositive students being less sad, there was no significant difference comparing the reported symptoms between seropositive students and seronegative students. 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 emphasizes on the impact of pandemic-associated symptoms regarding the well-being and mental health of young adolescents.Clinical Trial Registration: 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=DRKS00022455.

Prevalence and Transmission of Severe Acute Respiratory Syndrome Coronavirus Type 2 in Childcare Facilities: A Longitudinal Study.

OBJECTIVE: To evaluate the role of childcare facilities in the transmission of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) in a longitudinal study to gain further knowledge of SARS-CoV-2 prevalence, transmission, and spread among preschool children, their parents, and their caregivers. STUDY DESIGN: Children aged 1-6 years, their parents, and their caregivers 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 demographic characteristics, as well as epidemiologic information on personal SARS-CoV-2 history were obtained. Samples for stool virus shedding of SARS-CoV-2 were analyzed by polymerase chain reaction every 2-4 weeks in all participating children. RESULTS: In total, 318 children, 299 parents and 233 childcare workers were enrolled. By January 2021, 11% of the participating adults were found to be seropositive, whereas the percentage of children shedding SARS-CoV-2 was 6.8%. Overall, we detected 17 children with SARS-CoV-2 virus shedding in 8 different childcare facilities. In 4 facilities, there were a maximum of 3 connected cases in children. Approximately 50% of SARS-CoV-2 infections in the children could not be connected to a secondary case in our study population. CONCLUSIONS: This study does not provide evidence of relevant asymptomatic ("silent") spread of SARS-CoV-2 in childcare facilities in both low- and high-prevalence settings. Our findings add to the evidence that childcare and educational settings do not have a crucial role in driving the SARS-CoV-2 pandemic.

Kinetics and seroprevalence of SARS-CoV-2 antibodies: a comparison of 3 different assays.

Comparing seroprevalence and antibody kinetics in three different commercially available assays for SARS-CoV-2. 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. 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. There are significant differences in SARS-CoV-2 antibody kinetics based on the specific assay used.

Event-Driven Immunoprofiling Predicts Return of Disease Activity in Alemtuzumab-Treated Multiple Sclerosis.

Background: Alemtuzumab is a highly effective drug for the treatment of multiple sclerosis (MS), characterized by specific patterns of depletion and repopulation. As an induction-like treatment concept, two mandatory infusion courses can inhibit long-term disease activity in the majority of patients, and additional courses can successfully manage subsequent re-emergence of disease activity. Currently, there are no biomarkers to identify patients with re-emergent disease activity requiring retreatment. Methods: In this study, we systematically characterized 16 MS patients commencing alemtuzumab. Clinical parameters, MRI and detailed immunoprofiling were conducted every 3 months for up to 84 months. Results: Alemtuzumab led to significant decrease in clinical disease activity in all evaluated patients. Nine out of 16 patients presented with no evidence of disease activity (NEDA)-3 up to 84 months ("complete-responder"), while 7 patients demonstrated clinical or/and subclinical MRI disease activity and received alemutzumab retreatment ("partial-responder"). In both response categories, all T- and B-cell subsets were markedly depleted after alemtuzumab therapy. In particular, absolute numbers of Th1 and Th17 cells were markedly decreased and remained stable below baseline levels-this effect was particularly pronounced in complete-responders. While mean cell numbers did not differ significantly between groups, analysis of event-driven immunoprofiling demonstrated that absolute numbers of Th1 and Th17 cells showed a reproducible increase starting 6 months before relapse activity. This change appears to predict emergent disease activity when compared with stable disease. Conclusion: Studies with larger patient populations are needed to confirm that frequent immunoprofiling may assist in evaluating clinical decision-making of alemtuzumab retreatment.

Graves' disease after treatment with alemtuzumab for multiple sclerosis.

CONTEXT: Alemtuzumab, a humanized monoclonal antibody against CD52, is effective in the treatment of early relapsing-remitting multiple sclerosis (MS). Common adverse effects include an acute-phase reaction, infections and autoimmune diseases, including thyroid disorders. SETTING: Patients from two phase 3 trials (CARE MS 1 and 2, n=15) were studied in a clinical research center. PATIENTS: Five out of fifteen patients developed severe Graves' disease after a mean of 32 months following the first alemtuzumab treatment. MAIN OUTCOME MEASURES: Thyroid function tests and thyroid antibodies were assessed. In addition, endocrine tests and measurement of antibodies indicative of autoimmunity were performed. RESULTS: Of the five patients developing Graves' disease, four patients were initially treated with antithyroid drugs, whereas the fifth patient had mild and self-limiting hyperthyroidism. Of the four patients treated with antithyroid drugs, one is currently under medical treatment in a dose-reducing regimen, whereas three patients underwent near-total thyroidectomy 2, 12 and 16 months later. Two patients developed endocrine ophthalmopathy. Pituitary, adrenal and gonadal hormones were normal in all patients. While four out of five patients were positive for several other autoantibodies, none developed other autoimmune diseases. CONCLUSION: Since autoimmune thyroid disease is common after alemtuzumab treatment for MS, pretreatment screening and careful follow-up may allow for early diagnosis and treatment.