Enteroviruses in Respiratory Samples from Paediatric Patients of a Tertiary Care Hospital in Germany

Enteroviruses are associated with various diseases accompanied by rare but severe complications. In recent years, outbreaks of enterovirus D68 and enterovirus A71 associated with severe respiratory infections and neurological complications have been reported worldwide. Since information on molecular epidemiology in respiratory samples is still limited, the genetic diversity of enteroviruses was retrospectively analysed over a 4-year period (2013–2016) in respiratory samples from paediatric patients. Partial viral major capsid protein gene (VP1) sequences were determined for genotyping. Enteroviruses were detected in 255 (6.1%) of 4187 specimens. Phylogenetic analyses of 233 (91.4%) strains revealed 25 different genotypes distributed to Enterovirus A (39.1%), Enterovirus B (34.3%), and Enterovirus D (26.6%). The most frequently detected genotypes were enterovirus D68 (26.6%), coxsackievirus A6 (15.9%), and enterovirus A71 (7.3%). Enterovirus D68 detections were associated with lower respiratory tract infections and increased oxygen demand. Meningitis/encephalitis and other neurological symptoms were related to enterovirus A71, while coxsackievirus A6 was associated with upper respiratory diseases. Prematurity turned out as a potential risk factor for increased oxygen demand during enterovirus infections. The detailed analysis of epidemiological and clinical data contributes to the non-polio enterovirus surveillance in Europe and showed high and rapidly changing genetic diversity of circulating enteroviruses, including different enterovirus D68 variants

Photodynamic inactivation of SARS-CoV-2 infectivity and antiviral treatment effects in vitro

Despite available vaccines, antibodies and antiviral agents, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic still continues to cause severe disease and death. Current treatment options are limited, and emerging new mutations are a challenge. Thus, novel treatments and measures for prevention of viral infections are urgently required. Photodynamic inactivation (PDI) is a potential treatment for infections by a broad variety of critical pathogens, including viruses. We explored the infectiousness of clinical SARS-CoV-2 isolates in Vero cell cultures after PDI-treatment, using the photosensitizer Tetrahydroporphyrin-tetratosylate (THPTS) and near-infrared light. Replication of viral RNA (qPCR), viral cytopathic effects (microscopy) and mitochondrial activity were assessed. PDI of virus suspension with 1 µM THPTS before infection resulted in a reduction of detectable viral RNA by 3 log levels at day 3 and 6 after infection to similar levels as in previously heat-inactivated virions (<99.9%; p < 0.05). Mitochondrial activity, which was significantly reduced by viral infection, was markedly increased by PDI to levels similar to uninfected cell cultures. When applying THPTS-based PDI after infection, a single treatment had a virus load-reducing effect only at a higher concentration (3 µM) and reduced cell viability in terms of PDI-induced toxicity. Repeated PDI with 0.3 µM THPTS every 4 h for 3 d after infection reduced the viral load by more than 99.9% (p < 0.05), while cell viability was maintained. Our data demonstrate that THPTS-based antiviral PDI might constitute a promising approach for inactivation of SARS-CoV-2. Further testing will demonstrate if THPTS is also suitable to reduce the viral load in vivo

Human Infection with G12 Rotaviruses, Germany

Rotavirus group A G12 genotypes were detected in 3 (1.5%) of 198 stool samples positive for human rotavirus. G12P[6] was present in 2 samples, and a mixed G3G12P[8] was found in 1 sample. Phylogenetic analysis of complete open reading frames of all 11 genomic RNA segments proved their Wa-like genogroup affiliation

A high-risk gut microbiota configuration associates with fatal hyperinflammatory immune and metabolic responses to SARS-CoV-2.

Protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and associated clinical sequelae requires well-coordinated metabolic and immune responses that limit viral spread and promote recovery of damaged systems. However, the role of the gut microbiota in regulating these responses has not been thoroughly investigated. In order to identify mechanisms underpinning microbiota interactions with host immune and metabolic systems that influence coronavirus disease 2019 (COVID-19) outcomes, we performed a multi-omics analysis on hospitalized COVID-19 patients and compared those with the most severe outcome (i.e. death, n = 41) to those with severe non-fatal disease (n = 89), or mild/moderate disease (n = 42), that recovered. A distinct subset of 8 cytokines (e.g. TSLP) and 140 metabolites (e.g. quinolinate) in sera identified those with a fatal outcome to infection. In addition, elevated levels of multiple pathobionts and lower levels of protective or anti-inflammatory microbes were observed in the fecal microbiome of those with the poorest clinical outcomes. Weighted gene correlation network analysis (WGCNA) identified modules that associated severity-associated cytokines with tryptophan metabolism, coagulation-linked fibrinopeptides, and bile acids with multiple pathobionts, such as Enterococcus. In contrast, less severe clinical outcomes are associated with clusters of anti-inflammatory microbes such as Bifidobacterium or Ruminococcus, short chain fatty acids (SCFAs) and IL-17A. Our study uncovered distinct mechanistic modules that link host and microbiome processes with fatal outcomes to SARS-CoV-2 infection. These features may be useful to identify at risk individuals, but also highlight a role for the microbiome in modifying hyperinflammatory responses to SARS-CoV-2 and other infectious agents

Re-emergence of enterovirus D68 in Europe after easing the COVID-19 lockdown, September 2021

We report a rapid increase in enterovirus D68 (EV-D68) infections, with 139 cases reported from eight European countries between 31 July and 14 October 2021. This upsurge is in line with the seasonality of EV-D68 and was presumably stimulated by the widespread reopening after COVID-19 lockdown. Most cases were identified in September, but more are to be expected in the coming months. Reinforcement of clinical awareness, diagnostic capacities and surveillance of EV-D68 is urgently needed in Europe

Genetic Diversity of Sapoviruses among Inpatients in Germany, 2008−2018

Sapovirus enteric disease affects people of all ages across the globe, in both sporadic cases and outbreak settings. Sapovirus is seldom assessed in Germany and its epidemiology in the country is essentially unknown. Thus, sapovirus occurrence and genetic diversity were studied by real-time reverse transcription polymerase chain reaction (RT-PCR) and partial sequencing of major viral structural protein (VP1) gene in two different sets of stool samples: (1) a selection of 342 diarrheal stools collected from inpatient children during 2008&minus;2009, and (2) 5555 stool samples collected during 2010&ndash;2018 from inpatients of all age groups with gastrointestinal complaints. Results showed year-round circulation of sapoviruses, with peaks during cooler months. In total, 30 samples (8.8%) of the first and 112 samples of the second set of samples (2.0%) were sapovirus positive. Capsid gene sequencing was successful in 134/142 samples (94.4%) and showed circulation of all known human pathogenic genogroups. Genotype GI.1 predominated (31.8%), followed by GII.1 (16.7%), GII.3 (14.5%), GI.2 (13.8%) and GV.1 (12.3%). Additionally, minor circulation of GI.3, GI.6, GII.2, GII.4, GII.6 and GIV.1 was shown. Consequently, sapovirus diagnostics need broadly reactive RT-PCR protocols and should particularly be considered in infants and young children. Further studies from other sampling sites are essential to extend our knowledge on sapovirus epidemiology in Germany

Norovirus Epidemiology and Genetic Diversity in Leipzig, Germany during 2013–2017

Globally and in all age groups, noroviruses are a main cause of gastroenteritis. To assess their local epidemiology and genetic diversity, stool samples of 7509 inpatients with gastrointestinal complaints from all age groups were analyzed. After detection of norovirus genogroup I and II RNA by real-time RT-PCR, viral capsids were genotyped by partial nucleic acid sequencing. In the case of GII.2 strains, polymerase genotypes were also assessed. Between October 2013 and September 2017, presence of norovirus RNA was shown in 611 samples (8.1%), of which 610 (99.8%) were typed successfully. Norovirus positivity rate was higher in patients aged below five years (14.8%) than in older patients (5.7%). Among the 611 norovirus positive samples, GII.4 (56.6%) strains prevailed, followed by GII.6 (11.3%), GII.3 (11.0%) and GII.2 (9.5%). The most common genogroup I (GGI) genotype was GI.3 (3.6%). In addition, rare genotypes such as GII.13, GII.14 and GII.26 were detected. Interestingly, GII.3 infections were most common in children under the age of five years. Assessment of polymerase genotypes in GII.2 viruses showed a shift from P2 to P16, with higher diversity in P2 sequences. The varying distribution of norovirus genotypes depending on season, age and setting of infection highlights the importance of frequent genotyping as a basis for vaccine development and needful adjustments

SARS-CoV-2-Screening von Bewohner*innen und Personal in Alten- und Pflegeheimen der Stadt Leipzig

Die Stadt Leipzig führte im Rahmen eines ersten Pilotprojekts eine Erhebung zu SARS-CoV-2-Infektionen bei Personal und Bewohner*innen in Heimen durch. Ziel des Pilotprojekts war es, die Punktprävalenz asymptomatischer und präsymptomatischer SARS-CoV-2 Träger in diesen Einrichtungen zu ermitteln. Die Ergebnisse dieser Erhebung werden im Epidemiologischen Bulletin 22/2020 vorgestellt

Disorders of the Calcium Sensing Signaling Pathway: From Familial Hypocalciuric Hypercalcemia (FHH) to Life Threatening Conditions in Infancy

Familial hypocalciuric hypercalcemia (FHH) is a mostly benign condition of elevated calcium and PTH levels based on a hyposensitive calcium sensing receptor (CaSR) in FHH 1 or its downstream regulatory pathway in FHH2 and FHH3. In children, adolescents and young adults with FHH the main challenge is to distinguish the condition from primary hyperparathyroidism and thereby to avoid unnecessary treatments including parathyroidectomy. However, inheritance of FHH may result in neonatal hyperparathyroidism (NHPT) or neonatal severe hyperparathyroidism (NSHPT), conditions with high morbidity, and in the latter even high mortality. This review focuses on the genetic and pathophysiological framework that leads to the severe neonatal form, gives recommendations for counselling and summarizes treatment options

Enteroviruses in Respiratory Samples from Paediatric Patients of a Tertiary Care Hospital in Germany

Enteroviruses are associated with various diseases accompanied by rare but severe complications. In recent years, outbreaks of enterovirus D68 and enterovirus A71 associated with severe respiratory infections and neurological complications have been reported worldwide. Since information on molecular epidemiology in respiratory samples is still limited, the genetic diversity of enteroviruses was retrospectively analysed over a 4-year period (2013–2016) in respiratory samples from paediatric patients. Partial viral major capsid protein gene (VP1) sequences were determined for genotyping. Enteroviruses were detected in 255 (6.1%) of 4187 specimens. Phylogenetic analyses of 233 (91.4%) strains revealed 25 different genotypes distributed to Enterovirus A (39.1%), Enterovirus B (34.3%), and Enterovirus D (26.6%). The most frequently detected genotypes were enterovirus D68 (26.6%), coxsackievirus A6 (15.9%), and enterovirus A71 (7.3%). Enterovirus D68 detections were associated with lower respiratory tract infections and increased oxygen demand. Meningitis/encephalitis and other neurological symptoms were related to enterovirus A71, while coxsackievirus A6 was associated with upper respiratory diseases. Prematurity turned out as a potential risk factor for increased oxygen demand during enterovirus infections. The detailed analysis of epidemiological and clinical data contributes to the non-polio enterovirus surveillance in Europe and showed high and rapidly changing genetic diversity of circulating enteroviruses, including different enterovirus D68 variants