Hierarchisierung von Risikofaktoren für schwere COVID-19-Erkrankungsverläufe im Kontext der COVID-19-Schutzimpfungen

Angesichts der derzeitigen Impfstoffknappheit geht mit den bundesweiten Schutzimpfungen gegen COVID-19 die Notwendigkeit einer Priorisierung bestimmter Bevölkerungsgruppen einher. Basierend auf den Empfehlungen der STIKO sollen zunächst Personen mit besonders hohem Risiko für schwere oder tödliche COVID-19-Verläufe oder beruflicher Exposition geimpft werden. Diese Empfehlungen stützen sich überwiegend auf internationale Studien - für den deutschen Versorgungskontext steht nur begrenzt Evidenz zur Bedeutung relevanter Risikofaktoren für einen schweren COVID-19-Verlauf zur Verfügung. Das Ziel der im Epidemiologischen Bulletin 19/2021 vorgestellten Studie war es, die Relevanz ausgewählter Vorerkrankungen für einen schweren COVID-19-Verlauf in der in Deutschland lebenden Bevölkerung empirisch zu überprüfen, Erkrankungen hinsichtlich ihres Risikos für einen schweren COVID-19-Verlauf zu ordnen und damit eine einfache, im Versorgungsalltag unkompliziert umsetzbare und dabei möglichst effektive Grundlage für die Impfrangfolge in der ambulanten ärztlichen Versorgung bilden

Systematic classification of micromixers

This work is a systematic classification of passive micromixers according to their performance. The basis is the introduction of an efficiency measure which relates both mixing quality and pressure drop. This measure is then applied to data from several experimental characterizations. It is found that micromixers can be classified into two groups: inertial micromixers with a strong increase in performance above a critical flow rate and mixers based on lamination with a continuous change of the efficiency with growing Reynolds number. This classification is achieved by analysis of the mixing performance rather than describing the mixing principle

Hierarchisierung von Risikofaktoren für schwere COVID-19-Erkrankungsverläufe im Kontext der COVID-19-Schutzimpfungen

Angesichts der derzeitigen Impfstoffknappheit geht mit den bundesweiten Schutzimpfungen gegen COVID-19 die Notwendigkeit einer Priorisierung bestimmter Bevölkerungsgruppen einher. Basierend auf den Empfehlungen der STIKO sollen zunächst Personen mit besonders hohem Risiko für schwere oder tödliche COVID-19-Verläufe oder beruflicher Exposition geimpft werden. Diese Empfehlungen stützen sich überwiegend auf internationale Studien - für den deutschen Versorgungskontext steht nur begrenzt Evidenz zur Bedeutung relevanter Risikofaktoren für einen schweren COVID-19-Verlauf zur Verfügung. Das Ziel der im Epidemiologischen Bulletin 19/2021 vorgestellten Studie war es, die Relevanz ausgewählter Vorerkrankungen für einen schweren COVID-19-Verlauf in der in Deutschland lebenden Bevölkerung empirisch zu überprüfen, Erkrankungen hinsichtlich ihres Risikos für einen schweren COVID-19-Verlauf zu ordnen und damit eine einfache, im Versorgungsalltag unkompliziert umsetzbare und dabei möglichst effektive Grundlage für die Impfrangfolge in der ambulanten ärztlichen Versorgung bilden

Post COVID-19 associated morbidity in children, adolescents, and adults: A matched cohort study including more than 157,000 individuals with COVID-19 in Germany

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 approximately 46% of the German population, we investigated post-COVID-19-associated morbidity in children/adolescents and adults. Methods and findings: We used routine data from German statutory health insurance organizations covering the period between January 1, 2019 and December 31, 2020. The base population included all individuals insured for at least 1 day in 2020. Based on documented diagnoses, we identified individuals with polymerase chain reaction (PCR)-confirmed COVID-19 through June 30, 2020. A control cohort was assigned using 1:5 exact matching on age and sex, and propensity score matching on preexisting medical conditions. The date of COVID-19 diagnosis was used as index date for both cohorts, which were followed for incident morbidity outcomes documented in the second quarter after index date or later.Overall, 96 prespecified outcomes were aggregated into 13 diagnosis/symptom complexes and 3 domains (physical health, mental health, and physical/mental overlap domain). We used Poisson regression to estimate incidence rate ratios (IRRs) with 95% confidence intervals (95% CIs). The study population included 11,950 children/adolescents (48.1% female, 67.2% aged between 0 and 11 years) and 145,184 adults (60.2% female, 51.1% aged between 18 and 49 years). The mean follow-up time was 236 days (standard deviation (SD) = 44 days, range = 121 to 339 days) in children/adolescents and 254 days (SD = 36 days, range = 93 to 340 days) in adults. COVID-19 and control cohort were well balanced regarding covariates. The specific outcomes with the highest IRR and an incidence rate (IR) 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 to 3.06, p < 0.01, IR COVID-19: 12.58, IR Control: 5.51), cough (IRR: 1.74, 95% CI: 1.48 to 2.04, p < 0.01, IR COVID-19: 36.56, IR Control: 21.06), and throat/chest pain (IRR: 1.72, 95% CI: 1.39 to 2.12, p < 0.01, IR COVID-19: 20.01, IR Control: 11.66). In adults, these included disturbances of smell and taste (IRR: 6.69, 95% CI: 5.88 to 7.60, p < 0.01, IR COVID-19: 12.42, IR Control: 1.86), fever (IRR: 3.33, 95% CI: 3.01 to 3.68, p < 0.01, IR COVID-19: 11.53, IR Control: 3.46), and dyspnea (IRR: 2.88, 95% CI: 2.74 to 3.02, p < 0.01, IR COVID-19: 43.91, IR Control: 15.27). For all health outcomes combined, IRs per 1,000 person-years 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 to 1.35, p < 0.01, IR COVID-19: 436.91, IR Control: 335.98) and adults (IRR: 1.33, 95% CI: 1.31 to 1.34, p < 0.01, 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, IRs were significantly higher in all 13 diagnosis/symptom complexes in adults and in 10 diagnosis/symptom complexes in children/adolescents. IRR estimates were similar for age groups 0 to 11 and 12 to 17. IRs in children/adolescents were consistently lower than those in adults. Limitations of our study include potentially unmeasured confounding and detection bias. Conclusions: In this retrospective matched cohort study, we observed significant new onset morbidity in children, adolescents, and adults across 13 prespecified diagnosis/symptom complexes, following COVID-19 infection. These findings expand the existing available evidence on post-COVID-19 conditions in younger age groups and confirm previous findings in adult

Post-COVID-19-associated morbidity in children, adolescents, and adults: A matched cohort study including more than 157,000 individuals with COVID-19 in Germany

Roessler M, Tesch F, Batram M, et al. Post-COVID-19-associated morbidity in children, adolescents, and adults: A matched cohort study including more than 157,000 individuals with COVID-19 in Germany. PLoS Medicine. 2022;19(11): e1004122.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 approximately 46% of the German population, we investigated post-COVID-19-associated morbidity in children/adolescents and adults. Methods and findings We used routine data from German statutory health insurance organizations covering the period between January 1, 2019 and December 31, 2020. The base population included all individuals insured for at least 1 day in 2020. Based on documented diagnoses, we identified individuals with polymerase chain reaction (PCR)-confirmed COVID-19 through June 30, 2020. A control cohort was assigned using 1:5 exact matching on age and sex, and propensity score matching on preexisting medical conditions. The date of COVID-19 diagnosis was used as index date for both cohorts, which were followed for incident morbidity outcomes documented in the second quarter after index date or later.Overall, 96 prespecified outcomes were aggregated into 13 diagnosis/symptom complexes and 3 domains (physical health, mental health, and physical/mental overlap domain). We used Poisson regression to estimate incidence rate ratios (IRRs) with 95% confidence intervals (95% CIs). The study population included 11,950 children/adolescents (48.1% female, 67.2% aged between 0 and 11 years) and 145,184 adults (60.2% female, 51.1% aged between 18 and 49 years). The mean follow-up time was 236 days (standard deviation (SD) = 44 days, range = 121 to 339 days) in children/adolescents and 254 days (SD = 36 days, range = 93 to 340 days) in adults. COVID-19 and control cohort were well balanced regarding covariates. The specific outcomes with the highest IRR and an incidence rate (IR) 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 to 3.06, p < 0.01, IR COVID-19: 12.58, IR Control: 5.51), cough (IRR: 1.74, 95% CI: 1.48 to 2.04, p < 0.01, IR COVID-19: 36.56, IR Control: 21.06), and throat/ chest pain (IRR: 1.72, 95% CI: 1.39 to 2.12, p < 0.01, IR COVID-19: 20.01, IR Control: 11.66). In adults, these included disturbances of smell and taste (IRR: 6.69, 95% CI: 5.88 to 7.60, p < 0.01, IR COVID-19: 12.42, IR Control: 1.86), fever (IRR: 3.33, 95% CI: 3.01 to 3.68, p < 0.01, IR COVID-19: 11.53, IR Control: 3.46), and dyspnea (IRR: 2.88, 95% CI: 2.74 to 3.02, p < 0.01, IR COVID-19: 43.91, IR Control: 15.27). For all health outcomes combined, IRs per 1,000 person-years 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 to 1.35, p < 0.01, IR COVID-19: 436.91, IR Control: 335.98) and adults (IRR: 1.33, 95% CI: 1.31 to 1.34, p < 0.01, 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, IRs were significantly higher in all 13 diagnosis/symptom complexes in adults and in 10 diagnosis/symptom complexes in children/adolescents. IRR estimates were similar for age groups 0 to 11 and 12 to 17. IRs in children/adolescents were consistently lower than those in adults. Limitations of our study include potentially unmeasured confounding and detection bias. Conclusions In this retrospective matched cohort study, we observed significant new onset morbidity in children, adolescents, and adults across 13 prespecified diagnosis/symptom complexes, following COVID-19 infection. These findings expand the existing available evidence on post-COVID-19 conditions in younger age groups and confirm previous findings in adults. Author summary Why was this study done? Some patients with Coronavirus Disease 2019 (COVID-19) suffer from long-term health problems following the acute phase of COVID-19. Evidence on post-acute COVID-19 (post-COVID-19) syndrome is still limited, especially for children and adolescents. What did the researchers do and find? We used comprehensive healthcare data from a sample of almost half of the German population to investigate the risk of post-COVID-19 disease patterns in children, adolescents, and adults. We identified all patients with polymerase chain reaction (PCR)-confirmed diagnosis of COVID-19 (157,134 individuals in total, 11,950 children/adolescents and 145,184 adults) and matched them to a control cohort of individuals with identical age and sex, and similar preexisting medical conditions without COVID-19. We recorded medical conditions documented by a physician at least 3 months after the date of COVID-19 diagnosis and compared them to the matched controls without COVID-19. We observed increased rates of newly diagnosed physical and mental health problems in the COVID-19 group, compared to the control group, which differed according to age. What do these findings mean? Although healthcare utilization may differ between those who have suffered COVID-19 and those who have not, the results of our study indicate that people of all age groups (children, adolescents, and adults) are at risk of post-COVID-19 syndrome and that the spectrum of health problems differs between age groups

CD83 expression is essential for Treg cell differentiation and stability

Foxp3-positive regulatory T cells (Tregs) are crucial for the maintenance of immune homeostasis and keep immune responses in check. Upon activation, Tregs are transferred into an effector state expressing transcripts essential for their suppressive activity, migration, and survival. However, it is not completely understood how different intrinsic and environmental factors control differentiation. Here, we present for the first time to our knowledge data suggesting that Treg-intrinsic expression of CD83 is essential for Treg differentiation upon activation. Interestingly, mice with Treg-intrinsic CD83 deficiency are characterized by a proinflammatory phenotype. Furthermore, the loss of CD83 expression by Tregs leads to the downregulation of Treg-specific differentiation markers and the induction of an inflammatory profile. In addition, Treg-specific conditional knockout mice showed aggravated autoimmunity and an impaired resolution of inflammation. Altogether, our results show that CD83 expression in Tregs is an essential factor for the development and function of effector Tregs upon activation. Since Tregs play a crucial role in the maintenance of immune tolerance and thus prevention of autoimmune disorders, our findings are also clinically relevant

SARS-CoV-2 infection triggers profibrotic macrophage responses and lung fibrosis.

COVID-19-induced "acute respiratory distress syndrome" (ARDS) is associated with prolonged respiratory failure and high mortality, but the mechanistic basis of lung injury remains incompletely understood. Here, we analyze pulmonary immune responses and lung pathology in two cohorts of patients with COVID-19 ARDS using functional single-cell genomics, immunohistology, and electron microscopy. We describe an accumulation of CD163-expressing monocyte-derived macrophages that acquired a profibrotic transcriptional phenotype during COVID-19 ARDS. Gene set enrichment and computational data integration revealed a significant similarity between COVID-19-associated macrophages and profibrotic macrophage populations identified in idiopathic pulmonary fibrosis. COVID-19 ARDS was associated with clinical, radiographic, histopathological, and ultrastructural hallmarks of pulmonary fibrosis. Exposure of human monocytes to SARS-CoV-2, but not influenza A virus or viral RNA analogs, was sufficient to induce a similar profibrotic phenotype in vitro. In conclusion, we demonstrate that SARS-CoV-2 triggers profibrotic macrophage responses and pronounced fibroproliferative ARDS