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

PURPOSE: Despite the need to generate valid and reliable estimates of protection levels 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Long COVID in pediatrics-epidemiology, diagnosis, and management.

This review summarizes current knowledge on post-acute sequelae of COVID-19 (PASC) and post-COVID-19 condition (PCC) in children and adolescents. A literature review was performed to synthesize information from clinical studies, expert opinions, and guidelines. PASC also termed Long COVID - at any age comprise a plethora of unspecific symptoms present later than 4 weeks after confirmed or probable infection with severe respiratory syndrome corona virus type 2 (SARS-CoV-2), without another medical explanation. PCC in children and adolescents was defined by the WHO as PASC occurring within 3 months of acute coronavirus disease 2019 (COVID-19), lasting at least 2 months, and limiting daily activities. Pediatric PASC mostly manifest after mild courses of COVID-19 and in the majority of cases remit after few months. However, symptoms can last for more than 1 year and may result in significant disability. Frequent symptoms include fatigue, exertion intolerance, and anxiety. Some patients present with postural tachycardia syndrome (PoTS), and a small number of cases fulfill the clinical criteria of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). To date, no diagnostic marker has been established, and differential diagnostics remains challenging. Therapeutic approaches include appropriate self-management as well as the palliation of symptoms by non-pharmaceutical and pharmaceutical strategies.    Conclusion: PASC in pediatrics present with heterogenous severity and duration. A stepped, interdisciplinary, and individualized approach is essential for appropriate clinical management. Current health care structures have to be adapted, and research was extended to meet the medical and psychosocial needs of young people with PASC or similar conditions. What is Known: • Post-acute sequelae of coronavirus 2019 (COVID-19) (PASC) - also termed Long COVID - in children and adolescents can lead to activity limitation and reduced quality of life. • PASC belongs to a large group of similar post-acute infection syndromes (PAIS). Specific biomarkers and causal treatment options are not yet available. What is New: • In February 2023, a case definition for post COVID-19 condition (PCC) in children and adolescents was provided by the World Health Organization (WHO), indicating PASC with duration of at least 2 months and limitation of daily activities. PCC can present as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). • Interdisciplinary collaborations are necessary and have been established worldwide to offer harmonized, multimodal approaches to diagnosis and management of PASC/PCC in children and adolescents.

Intelligent image-based deformation-assisted cell sorting with molecular specificity.

Although label-free cell sorting is desirable for providing pristine cells for further analysis or use, current approaches lack molecular specificity and speed. Here, we combine real-time fluorescence and deformability cytometry with sorting based on standing surface acoustic waves and transfer molecular specificity to image-based sorting using an efficient deep neural network. In addition to general performance, we demonstrate the utility of this method by sorting neutrophils from whole blood without labels.

SARS-CoV-2 sero-immunity and quality of life in children and adolescents in relation to infections and vaccinations: the IMMUNEBRIDGE KIDS cross-sectional study, 2022.

PURPOSE: The study evaluates the effects on sero-immunity, health status and quality of life of children and adolescents after the upsurge of the Omicron variant in Germany. METHODS: This multicenter cross-sectional study (IMMUNEBRIDGE Kids) was conducted within the German Network University Medicine (NUM) from July to October 2022. SARS-CoV-2- antibodies were measured and data on SARS-CoV-2 infections, vaccinations, health and socioeconomic factors as well as caregiver-reported evaluation on their children's health and psychological status were assessed. RESULTS: 497 children aged 2-17 years were included. Three groups were analyzed: 183 pre-schoolchildren aged 2-4 years, 176 schoolchildren aged 5-11 years and 138 adolescents aged 12-18 years. Positive antibodies against the S- or N-antigen of SARS-CoV-2 were detected in 86.5% of all participants (70.0% [128/183] of pre-schoolchildren, 94.3% of schoolchildren [166/176] and 98.6% of adolescents [136/138]). Among all children, 40.4% (201/497) were vaccinated against COVID-19 (pre-schoolchildren 4.4% [8/183], schoolchildren 44.3% [78/176] and adolescents 83.3% [115/138]). SARS-CoV-2 seroprevalence was lowest in pre-school. Health status and quality of life reported by the parents were very positive at the time of the survey (Summer 2022). CONCLUSION: Age-related differences on SARS-CoV-2 sero-immunity could mainly be explained by differences in vaccination rates based on the official German vaccination recommendations as well as differences in SARS-CoV-2 infection rates in the different age groups. Health status and quality of life of almost all children were very good independent of SARS-CoV-2 infection and/or vaccination. TRIAL REGISTRATION: German Registry for Clinical Trials Identifier Würzburg: DRKS00025546 (registration: 11.09.2021), Bochum: DRKS00022434 (registration:07.08.2020), Dresden: DRKS 00022455 (registration: 23.07.2020).

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 adults. TRIAL REGISTRATION: ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT05074953.

Post COVID and Apheresis - Where are we Standing?

A continual increase in cases of Long/Post COVID constitutes a medical and socioeconomic challenge to health systems around the globe. While the true extent of this problem cannot yet be fully evaluated, recent data suggest that up to 20% of people with confirmed SARS-CoV-2 suffer from clinically relevant symptoms of Long/Post COVID several weeks to months after the acute phase. The clinical presentation is highly variable with the main symptoms being chronic fatigue, dyspnea, and cognitive symptoms. Extracorporeal apheresis has been suggested to alleviate symptoms of Post/COVID. Thus, numerous patients are currently treated with apheresis. However, at present there is no data from randomized controlled trials available to confirm the efficacy. Therefore, physicians rely on the experience of practitioners and centers performing this treatment. Here, we summarize clinical experience on extracorporeal apheresis in patients with Post/COVID from centers across Germany.

SARS-CoV-2 in pediatric cancer: a systematic review.

The outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019 in Wuhan challenges pediatric oncologists in an unexpected way. We provide a comprehensive overview, which systematically summarizes and grades evidence (QoE) on SARS-CoV-2 infections in pediatric cancer patients at 1.5 years of pandemic. A systematic literature search in PubMed combined with an additional exploratory literature review in other international databases was conducted to identify studies on children (aged < 18 years) with a malignant disease and COVID-19 infections. In total, 45 reports on 1003 pediatric cancer patients with SARS-CoV-2 infections were identified out of 1397 reports analyzed. The clinical course of COVID-19 was reported mild or moderate in 358 patients (41.7%), whereas 11.1% of patients showed severe COVID-19. In 12.7% of patients, chemotherapy was postponed, whereas 19% of patients with different underlying malignancies received chemotherapy during SARS-CoV-2 infection. Twenty-five patients with SARS-CoV-2 infections died, potentially related to COVID-19. CONCLUSION: Despite a favorable COVID-19 outcome in most pediatric cancer patients, the morbidity is reported higher than in children without comorbidities. However, no severe COVID-19 complications were associated to the continuation of chemotherapy in some cohort studies and reports on two patients. Therefore, the risk of cancer progress or relapse due to interruption of chemotherapy has carefully to be weighed against the risk of severe COVID-19 disease with potentially fatal outcome. WHAT IS KNOWN: • Most of pediatric patients with malignant diseases show an asymptomatic, mild or moderate clinical course of SARS-CoV-2 infection. • Current need for a basis for decision-making, whether to stop or interrupt cancer treatment in a patient infected with SARS-CoV-2, and when to continue chemotherapy. WHAT IS NEW: • Review results comprising over 1000 pediatric COVID-19 cancer patients confirm mild courses of SARS-CoV-2 infection in most patients but also show the attributable mortality is at least 10 times higher compared to reports on hospitalized children without comorbidities. • Review identifies that chemotherapy was continued despite SARS-CoV-2 positivity in 18% of patients with individual chemotherapy modification according to the clinical course of SARS-CoV-2 infection and existing comorbidities. On this basis, no severe COVID-19 complications were associated to the continuation of chemotherapy in several cohort studies and two case reports.

Real-time fluorescence and deformability cytometry.

The throughput of cell mechanical characterization has recently approached that of conventional flow cytometers. However, this very sensitive, label-free approach still lacks the specificity of molecular markers. Here we developed an approach that combines real-time 1D-imaging fluorescence and deformability cytometry in one instrument (RT-FDC), thus opening many new research avenues. We demonstrated its utility by using subcellular fluorescence localization to identify mitotic cells and test for mechanical changes in those cells in an RNA interference screen.

Proteomic, biomechanical and functional analyses define neutrophil heterogeneity in systemic lupus erythematosus.

OBJECTIVES: Low-density granulocytes (LDGs) are a distinct subset of proinflammatory and vasculopathic neutrophils expanded in systemic lupus erythematosus (SLE). Neutrophil trafficking and immune function are intimately linked to cellular biophysical properties. This study used proteomic, biomechanical and functional analyses to further define neutrophil heterogeneity in the context of SLE. METHODS: Proteomic/phosphoproteomic analyses were performed in healthy control (HC) normal density neutrophils (NDNs), SLE NDNs and autologous SLE LDGs. The biophysical properties of these neutrophil subsets were analysed by real-time deformability cytometry and lattice light-sheet microscopy. A two-dimensional endothelial flow system and a three-dimensional microfluidic microvasculature mimetic (MMM) were used to decouple the contributions of cell surface mediators and biophysical properties to neutrophil trafficking, respectively. RESULTS: Proteomic and phosphoproteomic differences were detected between HC and SLE neutrophils and between SLE NDNs and LDGs. Increased abundance of type 1 interferon-regulated proteins and differential phosphorylation of proteins associated with cytoskeletal organisation were identified in SLE LDGs relative to SLE NDNs. The cell surface of SLE LDGs was rougher than in SLE and HC NDNs, suggesting membrane perturbances. While SLE LDGs did not display increased binding to endothelial cells in the two-dimensional assay, they were increasingly retained/trapped in the narrow channels of the lung MMM. CONCLUSIONS: Modulation of the neutrophil proteome and distinct changes in biophysical properties are observed alongside differences in neutrophil trafficking. SLE LDGs may be increasingly retained in microvasculature networks, which has important pathogenic implications in the context of lupus organ damage and small vessel vasculopathy.

The mechanics of myeloid cells.

The effects of cell size, shape and deformability on cellular function have long been a topic of interest. Recently, mechanical phenotyping technologies capable of analysing large numbers of cells in real time have become available. This has important implications for biology and medicine, especially haemato-oncology and immunology, as immune cell mechanical phenotyping, immunologic function, and malignant cell transformation are closely linked and potentially exploitable to develop new diagnostics and therapeutics. In this review, we introduce the technologies used to analyse cellular mechanical properties and review emerging findings following the advent of high throughput deformability cytometry. We largely focus on cells from the myeloid lineage, which are derived from the bone marrow and include macrophages, granulocytes and erythrocytes. We highlight advances in mechanical phenotyping of cells in suspension that are revealing novel signatures of human blood diseases and providing new insights into pathogenesis of these diseases. The contributions of mechanical phenotyping of cells in suspension to our understanding of drug mechanisms, identification of novel therapeutics and monitoring of treatment efficacy particularly in instances of haematologic diseases are reviewed, and we suggest emerging topics of study to explore as high throughput deformability cytometers become prevalent in laboratories across the globe.

Long-term, single-center surveillance of non-invasive group A streptococcal (GAS) infections, emm types and emm clusters.

Group A streptococci (GAS) are among the most frequent pathogens in children. Many epidemiological studies focus on specific GAS infections (such as tonsillopharyngitis or invasive disease), on GAS carriers or on post-streptococcal sequelae. By comparison, reports on regional GAS characteristics, particularly circulating non-invasive GAS in Europe, are rare. In a monocentric study, all GAS isolated from pediatric patients at a tertiary care hospital over a 6-year period (2006-2012) were characterized. GAS emm types and clusters were determined. Associated patient data were analyzed. Five hundred sixty-six GAS strains were collected. GAS tonsillopharyngitis was most common (71.6%), followed by pyoderma (6.0%), otitis media (3.7%), perineal dermatitis (3.4%), and invasive infections (1.4%). Colonizing strains represented 13.6% of GAS. GAS emm12 was most prevalent among invasive and non-invasive isolates. Emm1, emm4, emm28, and emm89 were the most frequent non-invasive GAS strains. The emm E4 cluster was most common, followed by the A-C4, A-C3, and E1. Among the GAS infections, different emm types and clusters were identified, e.g., emm4 was more common among patients with scarlet fever. Three new emm subtypes were characterized: emm29.13, emm36.7, and emm75.5. This comprehensive review of a large, local GAS cohort points to the differences between and similarities among GAS genotypes and disease manifestations, while minimizing regional variations. Considerable deviation from previous epidemiological findings is described, especially regarding the frequent detection of emm1 and emm89 in non-invasive GAS infections. Periodic updates on molecular and epidemiological GAS characteristics are needed to track the multifaceted pathogenic potential of GAS.

Survival of Group A Streptococcus (GAS) is Enhanced Under Desiccated Culture Conditions.

Streptococcus pyogenes or Group A Streptococcus (GAS) infections are the leading cause of bacterial tonsillopharyngitis. The bacterium can survive and persist within the human host for a long time as it is observed in up to 40% of the population who are considered as carriers. Recurrent tonsillopharyngitis is a particular problem in children which is caused either by relapses due to failed bacterial clearance or by reinfection. A prolonged survival in tonsillar crypts or on inanimate surfaces might be sources for reinfection. We therefore examined 64 clinical GAS isolates from children with tonsillopharyngitis for their long-term survival under either liquid or desiccated culture conditions. After 6 weeks, the overall GAS survival rate was 400-fold increased under desiccated culture conditions compared to liquid culture conditions, but varied depending on the emm-type between 20-fold (emm4) and 14000-fold (emm3). The survival rates of isolates from emm75 were significantly lower which is probably due to their production of hydrogen peroxide up to fatal doses. No hydrogen peroxide production could be detected for other emm-types. Furthermore, 11 isolates from patients with recurrent tonsillopharyngitis were compared to isolates of the same emm-type from patients with single episodes of tonsillopharyngitis. A significant elevated pH value and an increased survival rate for isolates from patients with recurrent infections were observed. In conclusion, significant differences in long-term survival of different GAS isolates as well as survival under desiccated culture conditions might contribute to both failed bacterial clearance and reinfection in patients with recurrent tonsillopharyngitis.

Hydrogen Peroxide Production of Group A Streptococci (GAS) is emm-Type Dependent and Increased at Low Temperatures.

Group A streptococcus (GAS) is an important human pathogen whose clinical isolates differ in their ability to produce hydrogen peroxide (H2O2). H2O2 is primarily produced by the enzyme lactate oxidase (LctO), an in depth in silico research revealed that all genome-sequenced GAS possess the required gene lctO. The importance of lctO for GAS is underlined by its highly conserved catabolite control element (cre box) as well as its perfect promotor sequence in comparison to the known consensus sequences of the Gram-positive model organism Bacillus subtilis. In this study, we provide further insight in the function and regulation of lactate oxidase by analyzing a large group of clinical GAS isolates. We found that H2O2 production increased over time in the late stationary phase; after 4 days of incubation, 5.4% of the isolates showed a positive result at 37 °C, while the rate increased to 16.4% at 20 °C. This correlation between H2O2 production and low temperatures suggests additional regulatory mechanisms for lctO besides catabolite control protein A (CcpA) and indicates that lctO might play a role for GAS energy metabolism at sub-body temperatures. Furthermore, we could identify that H2O2 production was different among clinical isolates; we could correlate H2O2 production to emm-types, indicating that emm-types 6 and 75 had the highest rate of H2O2 production. The emm-type- and temperature-dependent H2O2 production of clinical GAS isolates might contribute to their different survival strategies.

Mechanotransduction in neutrophil activation and deactivation.

Mechanotransduction refers to the processes through which cells sense mechanical stimuli by converting them to biochemical signals and, thus, eliciting specific cellular responses. Cells sense mechanical stimuli from their 3D environment, including the extracellular matrix, neighboring cells and other mechanical forces. Incidentally, the emerging concept of mechanical homeostasis,long term or chronic regulation of mechanical properties, seems to apply to neutrophils in a peculiar manner, owing to neutrophils' ability to dynamically switch between the activated/primed and deactivated/deprimed states. While neutrophil activation has been known for over a century, its deactivation is a relatively recent discovery. Even more intriguing is the reversibility of neutrophil activation and deactivation. We review and critically evaluate recent findings that suggest physiological roles for neutrophil activation and deactivation and discuss possible mechanisms by which mechanical stimuli can drive the oscillation of neutrophils between the activated and resting states. We highlight several molecules that have been identified in neutrophil mechanotransduction, including cell adhesion and transmembrane receptors, cytoskeletal and ion channel molecules. The physiological and pathophysiological implications of such mechanically induced signal transduction in neutrophils are highlighted as a basis for future work. This article is part of a Special Issue entitled: Mechanobiology.

Clinical practice guideline: tonsillitis II. Surgical management.

In 2013, a total of 84,332 patients had undergone extracapsular tonsillectomies (TE) and 11,493 a tonsillotomy (TT) procedure in Germany. While the latter is increasingly performed, the number of the former is continually decreasing. However, a constant number of approximately 12,000 surgical procedures in terms of abscess-tonsillectomies or incision and drainage are annually performed in Germany to treat patients with a peritonsillar abscess. The purpose of this part of the clinical guideline is to provide clinicians in any setting with a clinically focused multi-disciplinary guidance through the surgical treatment options to reduce inappropriate variation in clinical care, improve clinical outcome and reduce harm. Surgical treatment options encompass intracapsular as well as extracapsular tonsil surgery and are related to three distinct entities: recurrent episodes of (1) acute tonsillitis, (2) peritonsillar abscess and (3) infectious mononucleosis. Conservative management of these entities is subject of part I of this guideline. (1) The quality of evidence for TE to resolve recurrent episodes of tonsillitis is moderate for children and low for adults. Conclusions concerning the efficacy of TE on the number of sore throat episodes per year are limited to 12 postoperative months in children and 5-6 months in adults. The impact of TE on the number of sore throat episodes per year in children is modest. Due to the heterogeneity of data, no firm conclusions on the effectiveness of TE in adults can be drawn. There is still an urgent need for further research to reliably estimate the value of TE compared to non-surgical therapy of tonsillitis/tonsillo-pharyngitis. The impact of TE on quality of life is considered as being positive, but further research is mandatory to establish appropriate inventories and standardized evaluation procedures, especially in children. In contrast to TE, TT or comparable procedures are characterized by a substantially lower postoperative morbidity in terms of pain and bleeding. Although tonsillar tissue remains along the capsule, the outcome appears not to differ from TE, at least in the pediatric population and young adults. Age and a history of tonsillitis are not a contraindication, abscess formation in the tonsillar remnants is an extremely rare finding. The volume of the tonsils should be graded according to Brodsky and a grade >1 is considered to be eligible for TT. The number of episodes during 12 months prior to presentation is crucial to indicate either TE or TT. While surgery is not indicated in patients with less than three episodes, a wait-and-see policy for 6 months is justified to include the potential of a spontaneous healing before surgery is considered. Six or more episodes appear to justify tonsil surgery. (2) Needle aspiration, incision and drainage, and abscess tonsillectomy are effective methods to treat patients with peritonsillar abscess. Compliance and ability of the patient to cooperate must be taken into account when choosing the surgical method. Simultaneous antibiotic therapy is recommended but still subject of scientific research. Abscess tonsillectomy should be preferred, if complications have occurred or if alternative therapeutic procedures had failed. Simultaneous TE of the contralateral side should only be performed when criteria for elective TE are matched or in cases of bilateral peritonsillar abscess. Needle aspiration or incision and drainage should be preferred if co-morbidities exist or an increased surgical risk or coagulation disorders are present. Recurrences of peritonsillar abscesses after needle aspiration or incision and drainage are rare. Interval TE should not be performed, the approach is not supported by contemporary clinical studies. (3) In patients with infectious mononucleosis TE should not be performed as a routine procedure for symptom control. TE is indicated in cases with clinically significant upper airway obstruction resulting from inflammatory tonsillar hyperplasia. If signs of a concomitant bacterial infection are not present, antibiotics should not be applied. Steroids may be administered for symptom relief.

Clinical practice guideline: tonsillitis I. Diagnostics and nonsurgical management.

More than 120,000 patients are treated annually in Germany to resolve repeated episodes of acute tonsillitis. Therapy is aiming at symptom regression, avoidance of complications, reduction in the number of disease-related absences in school or at work, increased cost-effectiveness and improved quality of life. The purpose of this part of the guideline is to provide clinicians in any setting with a clinically focused multi-disciplinary guidance through different conservative treatment options in order to reduce inappropriate variation in clinical care, improve clinical outcome and reduce harm. Surgical management in terms of intracapsular as well as extracapsular tonsillectomy (i.e. tonsillotomy) is the subject of part II of this guideline. To estimate the probability of tonsillitis caused by ß-hemolytic streptococci, a diagnostic scoring system according to Centor or McIsaac is suggested. If therapy is considered, a positive score of ≥3 should lead to pharyngeal swab or rapid test or culture in order to identify ß-hemolytic streptococci. Routinely performed blood tests for acute tonsillitis are not indicated. After acute streptococcal tonsillitis, there is no need to repeat a pharyngeal swab or any other routine blood tests, urine examinations or cardiological diagnostics such as ECG. The determination of the antistreptolysin O-titer (ASLO titer) and other antistreptococcal antibody titers do not have any value in relation to acute tonsillitis with or without pharyngitis and should not be performed. First-line therapy of ß-hemolytic streptococci consists of oral penicillin. Instead of phenoxymethylpenicillin-potassium (penicillin V potassium), also phenoxymethlpenicillin-benzathine with a clearly longer half-life can be used. Oral intake for 7 days of one of both the drugs is recommended. Alternative treatment with oral cephalosporins (e.g. cefadroxil, cefalexin) is indicated only in cases of penicillin failure, frequent recurrences, and whenever a more reliable eradication of ß-hemolytic streptococci is desirable. In cases of allergy or incompatibility of penicillin, cephalosporins or macrolides (e.g. Erythromycin-estolate) are valuable alternatives.

ß-Hemolytic streptococcal throat carriage and tonsillopharyngitis: a cross-sectional prevalence study in Gabon, Central Africa.

BACKGROUND: Group A streptococcus (GAS) and possibly other ß-hemolytic streptococci (BHS) account for a considerable morbidity and mortality burden in African populations; however, disproportionately little is known about the epidemiology of BHS in sub-Saharan Africa. This study assessed the prevalence of GAS, group G streptococcus (GGS) and group C streptococcus (GCS) carriage and tonsillopharyngitis in a Central African population. METHODS: A prospective cross-sectional study was performed to assess the prevalence of and risk factors for BHS carrier status and tonsillopharyngitis in children and adults in Gabon. RESULTS: The overall BHS carrier prevalence was 135/1,005 (13.4%); carrier prevalence of GAS, GGS, and GCS was 58/1,005 (5.8%), 50/1,005 (5.0%), and 32/1,005 (3.2%), respectively. Streptococcal carriage was associated with school and pre-school age (adjusted OR 2.65, 95% CI 1.62-4.36, p = 0.0001 and 1.90, 95% CI 1.14-3.17, p = 0.0141, respectively). Participants residing in urban areas were less likely carriers (OR 0.52, p = 0.0001). The point-prevalence of BHS-positive tonsillopharyngitis was 1.0% (9/1,014) and 15.0% (6/40) in school children with sore throat. CONCLUSIONS: Non-GAS exceeded GAS throat carriage and tonsillopharyngitis suggesting a yet underestimated role of non-GAS streptococci in BHS diseases.

Are Invasive Group A Streptococcal Infections Preventable by Antibiotic Therapy?: A Collaborative Retrospective Study.

BACKGROUND: In winter 2022/2023, a resurgence of invasive group A streptococcal (iGAS) infections in children was observed in Europe, including Germany and Switzerland. While a simultaneous increase in consultations for scarlet fever and pharyngitis was reported in England, leading to the recommendation to treat any suspected GAS disease with antibiotics, guidelines in Germany and Switzerland remained unchanged. We aimed to investigate whether this policy was appropriate. METHODS: We conducted a retrospective multicenter study of children hospitalized for invasive GAS disease between September 2022 and March 2023 in pediatric departments in Dresden and Berlin (Germany) and Basel (Switzerland). We reviewed medical records and conducted structured telephone interviews to analyze whether suspected GAS infections with or without antibiotic treatment were reported prehospitalization. RESULTS: In total, 63 patients met the inclusion criteria (median age 4.2 years, 57% males); however, clinical information was not complete for all analyzed characteristics; 32/54 (59%) had ≥1 physician visit ≤4 weeks prehospitalization. In 4/32 (13%) patients, GAS disease, that is, tonsillitis or scarlet fever, was suspected; 2/4 of them received antibiotics, and a positive rapid antigen test for GAS was documented in 1 of them. CONCLUSIONS: A small minority of patients had suspected GAS infection within 4 weeks before iGAS disease. These data suggest that there is little opportunity to prevent iGAS disease by antibiotic therapy, because in most patients-even if seen by a physician-there was either no evidence of GAS disease or when GAS disease was suspected and treated with antibiotics, consecutive invasive GAS disease was not prevented.