Changes in behavior and quality of life in German young children during the COVID-19 pandemic-results from the COVID kids bavaria study.

Introduction: The COVID-19 pandemic with its containment measures such as closures of schools and daycare facilities led to numerous restrictions in daily life, putting developmental opportunities and health-related quality of life in children at risk. However, studies show that not every family was impacted equally by the pandemic and that this exceptional health and societal situation reinforced pre-existing health inequalities among the vulnerable. Our study aimed at analyzing changes in behavior and health-related quality of life of children attending elementary schools and daycare facilities in Bavaria, Germany in spring 2021. We also sought to identify associated factors contributing to inequalities in quality of life. Methods: Data from a multi-center, open cohort study ("COVID Kids Bavaria") conducted in 101 childcare facilities and 69 elementary schools across all electoral districts of Bavaria were analyzed. Children attending these educational settings (aged 3-10 years) were eligible for participation in a survey on changes in behavior and health-related quality of life. The KINDLR questionnaire (based on children's self-report and parental report) was administered about one year after the onset of the pandemic (spring 2021). Descriptive and logistic regression analyses and comparisons to pre-pandemic KiGGS (German Health Interview and Examination Survey for Children and Adolescents) data were undertaken. Results: Among respondents, a high percentage of parents reported changes in their children's eating and sleeping behavior, sports and outdoor activities as well as altered screen time. Health-related quality of life in KINDLR analyses compared to pre-pandemic population averages were lower in all age groups (for 3-6-year-old KINDLR-total score: COVID Kids Bavaria MD 74.78 ± 10.57 vs KiGGS data 80.0 ± 8.1; 7-10 years-old KINDLR-total score: COVID Kids Bavaria MD 73.88 ± 12.03 vs KiGGS data 79.30 ± 9.0). No significant differences were detected with regard to associated factors, namely type of institution, sex of the child, migration background, household size and parental education. Conclusion: These findings suggest a relevant impact of the COVID-19 pandemic on children's behavior and health-related quality of life one year after the onset of the pandemic. Further analyses in large-scale longitudinal studies are needed to determine the effects of specific pandemic or crisis associated factors contributing to health inequalities.

Association between IgG responses against the nucleocapsid proteins of alphacoronaviruses and COVID-19 severity.

Understanding immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial to contain the COVID-19 pandemic. Using a multiplex approach, serum IgG responses against the whole SARS-CoV-2 proteome and the nucleocapsid proteins of endemic human coronaviruses (HCoVs) were measured in SARS-CoV-2-infected donors and healthy controls. COVID-19 severity strongly correlated with IgG responses against the nucleocapsid (N) of SARS-CoV-2 and possibly with the number of viral antigens targeted. Furthermore, a strong correlation between COVID-19 severity and serum responses against N of endemic alpha- but not betacoronaviruses was detected. This correlation was neither caused by cross-reactivity of antibodies, nor by a general boosting effect of SARS-CoV-2 infection on pre-existing humoral immunity. These findings raise the prospect of a potential disease progression marker for COVID-19 severity that allows for early stratification of infected individuals.

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

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

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

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

Post-COVID Syndrome.

BACKGROUND: As defined by the WHO, the term post-COVID syndrome (PCS) embraces a group of symptoms that can occur following the acute phase of a SARS-CoV-2 infection and as a consequence thereof. PCS is found mainly in adults, less frequently in children and adolescents. It can develop both in patients who initially had only mild symptoms or none at all and in those who had a severe course of coronavirus disease 2019 (COVID-19). METHODS: The data presented here were derived from a systematic literature review. RESULTS: PCS occurs in up to 15% of unvaccinated adults infected with SARS-CoV-2. The prevalence has decreased in the most recent phase of the pandemic and is lower after vaccination. The pathogenesis of PCS has not yet been fully elucidated. Virustriggered inflammation, autoimmunity, endothelial damage (to blood vessels), and persistence of virus are thought to be causative. Owing to the broad viral tropism, different organs are involved and the symptoms vary. To date, there are hardly any evidence-based recommendations for definitive diagnosis of PCS or its treatment. CONCLUSION: The gaps in our knowledge mean that better documentation of the prevalence of PCS is necessary to compile the data on which early detection, diagnosis, and treatment can be based. To ensure the best possible care of patients with PCS, regional PCS centers and networks embracing existing structures from all healthcare system sectors and providers should be set up and structured diagnosis and treatment algorithms should be established. Given the sometimes serious consequences of PCS for those affected, it seems advisable to keep the number of SARS-CoV-2 infections low by protective measures tailored to the prevailing pandemic situation.

Comparing SARS-CoV-2 variants among children and adolescents in Germany: relative risk of COVID-19-related hospitalization, ICU admission and mortality.

PURPOSE: SARS-CoV-2 infections cause COVID-19 and have a wide spectrum of morbidity. Severe disease courses among children are rare. To date, data on the variability of morbidity in relation to variant of concern (VOC) in children has been sparse and inconclusive. We compare the clinical severity of SARS-CoV-2 infection among children and adolescents in Germany during the Wildtype and Alpha combined, Delta and Omicron phases of the COVID-19 pandemic. METHODS: Comparing risk of COVID-19-related hospitalization, intensive care unit (ICU) admission and death due to COVID-19 in children and adolescents, we used: (1) a multi-center seroprevalence study (SARS-CoV-2-KIDS study); (2) a nationwide registry of pediatric patients hospitalized with SARS-CoV-2 infections; and (3) compulsory national reporting for RT-PCR-confirmed SARS-CoV-2 infections in Germany. RESULTS: During the Delta predominant phase, risk of COVID-19-related hospitalization among all SARS-CoV-2 seropositive children was 3.35, ICU admission 1.19 and fatality 0.09 per 10,000; hence about halved for hospitalization and ICU admission and unchanged for deaths as compared to the Wildtype- and Alpha-dominant period. The relative risk for COVID-19-related hospitalization and ICU admission compared to the alpha period decreased during Delta [0.60 (95% CI 0.54; 0.67) and 0.51 (95% CI 0.42; 0.61)] and Omicron [0.27 (95% CI 0.24; 0.30) and 0.06 (95% CI 0.05; 0.08)] period except for the < 5-year-olds. The rate of case fatalities decreased slightly during Delta, and substantially during Omicron phase. CONCLUSION: Morbidity caused by SARS-CoV-2 infections among children and adolescents in Germany decreased over the course of the COVID-19 pandemic, as different VOCs) emerged.

Post-COVID-19 condition in the German working population: A cross-sectional study of 200k registered stem cell donors.

BACKGROUND: The SARS-CoV-2 pandemic has strained health systems worldwide, and infection numbers continue to rise. While previous data have already shown that many patients suffer from symptoms for months after an acute infection, data on risk factors and long-term outcomes are incomplete, particularly for the working population. OBJECTIVES: We aimed to provide information on the prevalence of post COVID-19 conditions in a subset of the German working-age population (18-61 years old) and to analyze risk-factors. METHODS: We conducted an online survey with a health questionnaire among registered potential stem cell donors with or without a self-reported history of PCR-confirmed SARS-CoV-2 infection. Logistic regression models were used to examine the risks of severity of acute infection, sex, age, body mass index, diabetes mellitus and arterial hypertension medication on post COVID-19 symptoms. RESULTS: 199,377 donors reported evaluable survey questionnaires: 12,609 cases had a history of SARS-CoV-2 infection and 186,768 controls had none. Overall, cases reported physical, cognitive and psychological complaints more frequently compared to controls. Increased rates of complaints persisted throughout 15 months post infection, e.g. 28.4/19.3% of cases/controls reported fatigue (p<0.0001) and 9.5/3.6% of cases/controls reported loss of concentration (p<0.0001). No significant differences were observed in the frequency of reported symptoms between three- and 15-months post-infection. Multivariate analysis revealed a strong influence of the severity of the acute SARS-CoV-2 infection episode and age on the risk for post-COVID-19 conditions. CONCLUSION: We report the prevalence of post-COVID-19 conditions in mainly unvaccinated individuals with SARS-CoV-2 infections between February 2020 and August 2021. Severity of the acute course and age were major risk factors. Vaccinations may reduce the risk of post-COVID-19 conditions by reducing the risk for severe infections. This article is protected by copyright. All rights reserved.

Association of SARS-CoV-2 Seropositivity With Myalgic Encephalomyelitis and/or Chronic Fatigue Syndrome Among Children and Adolescents in Germany.

Importance: During the COVID-19 pandemic, a reduction in quality of life and physical and mental health among children and adolescents has been reported that may be associated with SARS-CoV-2 infection and/or containment measures. Objective: To assess the association of SARS-CoV-2 seropositivity with symptoms that may be related to myalgic encephalomyelitis and/or chronic fatigue syndrome (ME/CFS) among children and adolescents. Design, Setting, and Participants: This substudy of the cross-sectional SARS-CoV-2 seroprevalence surveys in Germany (SARS-CoV-2 KIDS) was performed in 9 pediatric hospitals from May 1 to October 31, 2021. Pediatric patients were recruited during an inpatient or outpatient visit regardless of the purpose of the visit. Parental questionnaires and serum samples were collected during clinically indicated blood draws. The parental questionnaire on demographic and clinical information was extended by items according to the DePaul Symptom Questionnaire, a pediatric screening tool for ME/CFS in epidemiological studies in patients aged 5 to 17 years. Exposures: Seropositivity was determined by SARS-CoV-2 IgG antibodies in serum samples using enzyme-linked immunosorbent assays. Main Outcomes and Measures: Key symptoms of ME/CFS were evaluated separately or as clustered ME/CFS symptoms according to the DePaul Symptom Questionnaire, including fatigue. Results: Among 634 participants (294 male [46.4%] and 340 female [53.6%]; median age, 11.5 [IQR, 8-14] years), 198 (31.2%) reported clustered ME/CFS symptoms, including 40 of 100 SARS-CoV-2-seropositive (40.0%) and 158 of 534 SARS-CoV-2-seronegative (29.6%) children and adolescents. After adjustment for sex, age group, and preexisting disease, the risk ratio for reporting clustered ME/CFS symptoms decreased from 1.35 (95% CI, 1.03-1.78) to 1.18 (95% CI, 0.90-1.53) and for substantial fatigue from 2.45 (95% CI, 1.24-4.84) to 2.08 (95% CI, 1.05-4.13). Confinement to children and adolescents with unknown previous SARS-CoV-2 infection status (n = 610) yielded lower adjusted risks for all symptoms except joint pain ME/CFS-related symptoms. The adjusted risk ratio was 1.08 (95% CI, 0.80-1.46) for reporting clustered ME/CFS symptoms and 1.43 (95% CI, 0.63-3.23) for fatigue. Conclusions and Relevance: These findings suggest that the risk of ME/CFS in children and adolescents owing to SARS-CoV-2 infection may be very small. Recall bias may contribute to risk estimates of long COVID-19 symptoms in children. Extensive lockdowns must be considered as an alternative explanation for complex unspecific symptoms during the COVID-19 pandemic.

Association between IgG responses against the nucleocapsid proteins of alphacoronaviruses and COVID-19 severity

Understanding immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial to contain the COVID-19 pandemic. Using a multiplex approach, serum IgG responses against the whole SARS-CoV-2 proteome and the nucleocapsid proteins of endemic human coronaviruses (HCoVs) were measured in SARS-CoV-2-infected donors and healthy controls. COVID-19 severity strongly correlated with IgG responses against the nucleocapsid (N) of SARS-CoV-2 and possibly with the number of viral antigens targeted. Furthermore, a strong correlation between COVID-19 severity and serum responses against N of endemic alpha- but not betacoronaviruses was detected. This correlation was neither caused by cross-reactivity of antibodies, nor by a general boosting effect of SARS-CoV-2 infection on pre-existing humoral immunity. These findings raise the prospect of a potential disease progression marker for COVID-19 severity that allows for early stratification of infected individuals.

A prospective observational study of post-COVID-19 chronic fatigue syndrome following the first pandemic wave in Germany and biomarkers associated with symptom severity.

A subset of patients has long-lasting symptoms after mild to moderate Coronavirus disease 2019 (COVID-19). In a prospective observational cohort study, we analyze clinical and laboratory parameters in 42 post-COVID-19 syndrome patients (29 female/13 male, median age 36.5 years) with persistent moderate to severe fatigue and exertion intolerance six months following COVID-19. Further we evaluate an age- and sex-matched postinfectious non-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome cohort comparatively. Most post-COVID-19 syndrome patients are moderately to severely impaired in daily live. 19 post-COVID-19 syndrome patients fulfill the 2003 Canadian Consensus Criteria for myalgic encephalomyelitis/chronic fatigue syndrome. Disease severity and symptom burden is similar in post-COVID-19 syndrome/myalgic encephalomyelitis/chronic fatigue syndrome and non-COVID-19/myalgic encephalomyelitis/chronic fatigue syndrome patients. Hand grip strength is diminished in most patients compared to normal values in healthy. Association of hand grip strength with hemoglobin, interleukin 8 and C-reactive protein in post-COVID-19 syndrome/non-myalgic encephalomyelitis/chronic fatigue syndrome and with hemoglobin, N-terminal prohormone of brain natriuretic peptide, bilirubin, and ferritin in post-COVID-19 syndrome/myalgic encephalomyelitis/chronic fatigue syndrome may indicate low level inflammation and hypoperfusion as potential pathomechanisms.

Surveillance of Acute SARS-CoV-2 Infections in Elementary Schools and Daycare Facilities in Bavaria, Germany (09/2020-03/2021).

Introduction: Here we report our results of a multi-center, open cohort study ("COVID-Kids-Bavaria") investigating the distribution of acute SARS-CoV-2 infections among children and staff in 99 daycare facilities and 48 elementary schools in Bavaria, Germany. Materials and Methods: Overall, 2,568 children (1,337 school children, 1,231 preschool children) and 1,288 adults (466 teachers, 822 daycare staff) consented to participate in the study and were randomly tested in three consecutive phases (September/October 2020, November/December 2020, March 2021). In total, 7,062 throat swabs were analyzed for SARS-CoV-2 by commercial RT-PCR kits. Results: In phase I, only one daycare worker tested positive. In phase II, SARS-CoV-2 was detected in three daycare workers, two preschool children, and seven school children. In phase III, no sample tested positive. This corresponds to a positive test rate of 0.05% in phase I, 0.4% in phase II and 0% in phase III. Correlation of a positive PCR test result with the local-7-day incidence values showed a strong association of a 7-day-incidence of more than 100/100,000 as compared to <100/100,000 (OR = 10.3 [1.5-438], p < 0.005). After phase III, antibody testing was offered to 713 study participants in elementary schools. A seroprevalence rate of 7.7% (students) and 4.5% (teachers) was determined. Discussion: During the initial waves of the SARS-CoV-2 pandemic, the risk of a positive SARS-CoV-2 result correlated positively with the local 7-day incidence. Hence, the occurrence of SARS-CoV-2 infections were reflected in schools and daycare facilities. An increased risk of SARS-CoV-2 transmission in the setting of daycare and elementary schooling was unlikely.

Surveillance of Acute SARS-CoV-2 Infections in Elementary Schools and Daycare Facilities in Bavaria, Germany (09/2020–03/2021)

Introduction Here we report our results of a multi-center, open cohort study (“COVID-Kids-Bavaria”) investigating the distribution of acute SARS-CoV-2 infections among children and staff in 99 daycare facilities and 48 elementary schools in Bavaria, Germany. Materials and Methods Overall, 2,568 children (1,337 school children, 1,231 preschool children) and 1,288 adults (466 teachers, 822 daycare staff) consented to participate in the study and were randomly tested in three consecutive phases (September/October 2020, November/December 2020, March 2021). In total, 7,062 throat swabs were analyzed for SARS-CoV-2 by commercial RT-PCR kits. Results In phase I, only one daycare worker tested positive. In phase II, SARS-CoV-2 was detected in three daycare workers, two preschool children, and seven school children. In phase III, no sample tested positive. This corresponds to a positive test rate of 0.05% in phase I, 0.4% in phase II and 0% in phase III. Correlation of a positive PCR test result with the local-7-day incidence values showed a strong association of a 7-day-incidence of more than 100/100,000 as compared to <100/100,000 (OR = 10.3 [1.5–438], p < 0.005). After phase III, antibody testing was offered to 713 study participants in elementary schools. A seroprevalence rate of 7.7% (students) and 4.5% (teachers) was determined. Discussion During the initial waves of the SARS-CoV-2 pandemic, the risk of a positive SARS-CoV-2 result correlated positively with the local 7-day incidence. Hence, the occurrence of SARS-CoV-2 infections were reflected in schools and daycare facilities. An increased risk of SARS-CoV-2 transmission in the setting of daycare and elementary schooling was unlikely.

[Recommendation for standardized medical care for children and adolescents with long COVID]. / Einheitliche Basisversorgung von Kindern und Jugendlichen mit Long COVID: Stellungnahme einer multidisziplinären Arbeitsgruppe der DGKJ-Konvent-Gesellschaften (Stand: Februar 2022).

This current consensus paper for long COVID complements the existing AWMF S1 guidelines for long COVID with a detailed overview on the various clinical aspects of long COVID in children and adolescents. Members of 19 different pediatric societies of the DGKJ convent and collaborating societies together provide expert-based recommendations for the clinical management of long COVID based on the currently available but limited academic evidence for long COVID in children and adolescents. It contains screening questions for long COVID and suggestions for a structured, standardized pediatric medical history and diagnostic evaluation for patients with suspected long COVID. A time and resource-saving questionnaire, which takes the clinical complexity of long COVID into account, is offered via the DGKJ and DGPI websites as well as additional questionnaires suggested for an advanced screening of specific neurocognitive and/or psychiatric symptoms including post-exertional malaise (PEM) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). According to the individual medical history as well as clinical signs and symptoms a step by step diagnostic procedure and a multidisciplinary therapeutic approach are recommended.

Cross-sectional seroprevalence surveys of SARS-CoV-2 antibodies in children in Germany, June 2020 to May 2021.

The rate of SARS-CoV-2 infections in children remains unclear due to many asymptomatic cases. We present a study of cross-sectional seroprevalence surveys of anti-SARS-CoV-2 IgG in 10,358 children recruited in paediatric hospitals across Germany from June 2020 to May 2021. Seropositivity increased from 2.0% (95% CI 1.6, 2.5) to 10.8% (95% CI 8.7, 12.9) in March 2021 with little change up to May 2021. Rates increased by migrant background (2.8%, 4.4% and 7.8% for no, one and two parents born outside Germany). Children under three were initially 3.6 (95% CI 2.3, 5.7) times more likely to be seropositive with levels equalising later. The ratio of seropositive cases per recalled infection decreased from 8.6 to 2.8. Since seropositivity exceeds the rate of recalled infections considerably, serologic testing may provide a more valid estimate of infections, which is required to assess both the spread and the risk for severe outcomes of SARS-CoV-2 infections.

Einheitliche Basisversorgung von Kindern und Jugendlichen mit Long COVID : Stellungnahme einer multidisziplinären Arbeitsgruppe der DGKJ-Konvent-Gesellschaften (Stand: Februar 2022) Recommendation for standardized medical care for children and adolescents with long COVIDStatement of a multidisciplinary pediatric expert group of the DGKJ convent societies (status: February 2022)

Das vorliegende Konsensuspapier bietet in Ergänzung zur AWMF-S1-Leitlinie eine Übersicht über die verschiedenen klinischen Aspekte von Long COVID im Kindes- und Jugendalter. Es wurde von Vertreter:innen aus 19 Fachgesellschaften des DGKJ-Konvents und kooperierenden Fachgesellschaften erstellt und bietet Expertenempfehlungen für die Praxis auf Grundlage der bisherigen, noch geringen studienbasierten Evidenz zu Long COVID im Kindes- und Jugendalter. Es enthält Screeningfragen zu Long COVID sowie einen Vorschlag zur strukturierten, standardisierten pädiatrischen Anamnese und zur diagnostischen Evaluation bei V. a. Long COVID. Dazu werden ein zeit- und ressourcensparender Erfassungsbogen, der die Komplexität des Krankheitsbildes berücksichtigt, über die Internetseiten der DGKJ und DGPI zur Verfügung gestellt und weitere Fragebögen zur Abklärung von spezifischen neurokognitiven und/oder psychischen Störungen sowie post-exertioneller Malaise (PEM) und myalgischer Enzephalomyelitis/chronischem Fatigue-Syndrom (ME/CFS) benannt. Anhand der jeweiligen anamnestisch und klinisch ermittelten Hauptsymptome werden ein gestuftes, diagnostisches Vorgehen und eine multidisziplinäre Betreuung empfohlen. Zusatzmaterial online Die Online-Version dieses Beitrags (10.1007/s00112-021-01408-1) enthält weitere Tabellen mit Angaben zur erweiterten Diagnostik (Labor- und Funktionsdiagnostik, Bildgebung).

A cross-sectional investigation of psychosocial stress factors in German families with children aged 0-3 years during the COVID-19 pandemic: initial results of the CoronabaBY study.

BACKGROUND: Psychosocial stress during the COVID-19 pandemic is increasing particularly in parents. Although being specifically vulnerable to negative environmental exposures, research on psychosocial stress factors in infants' and toddlers' families during the pandemic is so far sparse. The CoronabaBY study investigates the perceived pandemic burden, parenting stress and parent and child mental health problems in families with children aged 0-3 years in Bavaria, Southern Germany. Further, the relationships between these psychosocial stressors are examined and sociodemographic characteristics that may be predictive of these factors will be explored. METHODS: Participants were cross-sectionally surveyed via smartphone app. Standardized questionnaires on perceived pandemic burden, parenting stress, parental symptoms of depression and anxiety, infants' crying, sleeping and feeding problems or toddlers' emotional and behavioral problems were applied. RESULTS: N = 991 parents (Mage = 33.7 years, SD = 4.5; 93.7% mothers, 91.5% born in Germany) with infants (n = 554; Mage = 5.9 months, SD = 3.0) or toddlers (n = 435; Mage = 25.9 months, SD = 6.5) participated in the first half-year of 2021. Sixty-five percent of the parents perceived a high pandemic burden, 37.7% experienced parenting stress and 24.1% showed affective symptoms (anxiety: 30.1%, depression: 18.5%). Feeding problems, crying/ sleeping problems and multiple regulatory problems were found in 34.8%, 26.2% and 13.5% of the infants, respectively. Amongst toddlers, 8.5% showed noticeable behavior and emotional problems. Children`s mental health problems correlated moderately with parenting stress and parental affective symptoms and weakly with perceived pandemic burden. A lower financial status, higher parental education and increasing child age were significant but weak predictors for higher parenting stress, affective symptoms and higher psychological problems in children. CONCLUSIONS: A majority of the surveyed families with infants and toddlers experience the pandemic as stressful. The main challenges are parental affective symptoms and limited resources for childcare due to parenting stress. Overall, infants and toddlers show similar levels of mental health problems when being compared to pre-pandemic studies, but staggered detrimental effects on children`s mental health might occur if the stressful conditions persist. This is already indicated by correlations between parental and child psychosocial stress factors.

Immunoinformatic Analysis Reveals Antigenic Heterogeneity of Epstein-Barr Virus Is Immune-Driven.

Whole genome sequencing of Epstein-Barr virus (EBV) isolates from around the world has uncovered pervasive strain heterogeneity, but the forces driving strain diversification and the impact on immune recognition remained largely unknown. Using a data mining approach, we analyzed more than 300 T-cell epitopes in 168 published EBV strains. Polymorphisms were detected in approximately 65% of all CD8+ and 80% of all CD4+ T-cell epitopes and these numbers further increased when epitope flanking regions were included. Polymorphisms in CD8+ T-cell epitopes often involved MHC anchor residues and resulted in changes of the amino acid subgroup, suggesting that only a limited number of conserved T-cell epitopes may represent generic target antigens against different viral strains. Although considered the prototypic EBV strain, the rather low degree of overlap with most other viral strains implied that B95.8 may not represent the ideal reference strain for T-cell epitopes. Instead, a combinatorial library of consensus epitopes may provide better targets for diagnostic and therapeutic purposes when the infecting strain is unknown. Polymorphisms were significantly enriched in epitope versus non-epitope protein sequences, implicating immune selection in driving strain diversification. Remarkably, CD4+ T-cell epitopes in EBNA2, EBNA-LP, and the EBNA3 family appeared to be under negative selection pressure, hinting towards a beneficial role of immune responses against these latency type III antigens in virus biology. These findings validate this immunoinformatics approach for providing novel insight into immune targets and the intricate relationship of host defense and virus evolution that may also pertain to other pathogens.

[S1 Guideline Post-COVID/Long-COVID]. / S1-Leitlinie Post-COVID/Long-COVID.

The German Society of Pneumology initiated the AWMFS1 guideline Post-COVID/Long-COVID. In a broad interdisciplinary approach, this S1 guideline was designed based on the current state of knowledge.The clinical recommendation describes current post-COVID/long-COVID symptoms, diagnostic approaches, and therapies.In addition to the general and consensus introduction, a subject-specific approach was taken to summarize the current state of knowledge.The guideline has an expilcit practical claim and will be continuously developed and adapted by the author team based on the current increase in knowledge.

Swarm Learning for decentralized and confidential clinical machine learning.

Fast and reliable detection of patients with severe and heterogeneous illnesses is a major goal of precision medicine1,2. Patients with leukaemia can be identified using machine learning on the basis of their blood transcriptomes3. However, there is an increasing divide between what is technically possible and what is allowed, because of privacy legislation4,5. Here, to facilitate the integration of any medical data from any data owner worldwide without violating privacy laws, we introduce Swarm Learning-a decentralized machine-learning approach that unites edge computing, blockchain-based peer-to-peer networking and coordination while maintaining confidentiality without the need for a central coordinator, thereby going beyond federated learning. To illustrate the feasibility of using Swarm Learning to develop disease classifiers using distributed data, we chose four use cases of heterogeneous diseases (COVID-19, tuberculosis, leukaemia and lung pathologies). With more than 16,400 blood transcriptomes derived from 127 clinical studies with non-uniform distributions of cases and controls and substantial study biases, as well as more than 95,000 chest X-ray images, we show that Swarm Learning classifiers outperform those developed at individual sites. In addition, Swarm Learning completely fulfils local confidentiality regulations by design. We believe that this approach will notably accelerate the introduction of precision medicine.