International Care programs for Pediatric Post-COVID Condition (Long COVID) and the way forward.

BACKGROUND: Pediatric Post-COVID-Condition (PPCC) clinics treat children despite limited scientific substantiation. By exploring real-life management of children diagnosed with PPCC, the International Post-COVID-Condition in Children Collaboration (IP4C) aimed to provide guidance for future PPCC care. METHODS: We performed a cross-sectional international, multicenter study on used PPCC definitions; the organization of PPCC care programs and patients characteristics. We compared aggregated data from PPCC cohorts and identified priorities to improve PPCC care. RESULTS: Ten PPCC care programs and six COVID-19 follow-up research cohorts participated. Aggregated data from 584 PPCC patients was analyzed. The most common symptoms included fatigue (71%), headache (55%), concentration difficulties (53%), and brain fog (48%). Severe limitations in daily life were reported in 31% of patients. Most PPCC care programs organized in-person visits with multidisciplinary teams. Diagnostic testing for respiratory and cardiac morbidity was most frequently performed and seldom abnormal. Treatment was often limited to physical therapy and psychological support. CONCLUSIONS: We found substantial heterogeneity in both the diagnostics and management of PPCC, possibly explained by scarce scientific evidence and lack of standardized care. We present a list of components which future guidelines should address, and outline priorities concerning PPCC care pathways, research and international collaboration. IMPACT: Pediatric Post-COVID Condition (PPCC) Care programs have been initiated in many countries. Children with PPCC in different countries are affected by similar symptoms, limiting many to participate in daily life. There is substantial heterogeneity in diagnostic testing. Access to specific diagnostic tests is required to identify some long-term COVID-19 sequelae. Treatments provided were limited to physical therapy and psychological support. This study emphasizes the need for evidence-based diagnostics and treatment of PPCC. The International Post-COVID Collaboration for Children (IP4C) provides guidance for guideline development and introduces a framework of priorities for PPCC care and research, to improve PPCC outcomes.

Pre-admission virus detection during the COVID-19 pandemic in children with and without symptoms of infection.

AIM: Pre-admission viral screening is used only in exceptional situations such as pandemics. We therefore evaluated pre-admission screening for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respiratory syncytial virus (RSV) and influenza during the COVID-19 pandemic, comparing epidemiology and clinical features of admitted children. METHODS: Children were screened at a paediatric emergency department from 1 March 2020 to 30 June 2022 by nasopharyngeal sampling and polymerase chain reaction kit. We retrospectively retrieved positive results from the laboratory and scrutinised charts of admitted children. RESULTS: Out of 15 927 screened children, 522, 127 and 572 were positive and admitted with RSV, influenza A or SARS-CoV-2, respectively. Of these, 29 (5.6%), 26 (24.1%) and 245 (44.8%) were incidental findings, lacking symptoms of infection. RSV and influenza A were initially absent but re-emerged in the autumn of 2021. The rate of COVID-19 rose when the Omicron variant emerged in December 2021. The median age of children with RSV was 0.3 years, of those with influenza A 6.7 years and of those with COVID-19 1.6 years. Major complications were rare. CONCLUSION: Frequent incidental detections of SARS-CoV-2 likely reflected widespread presence of a mild infection. Clinically, COVID-19 was like other viral respiratory infections in children.

Early-onset group B streptococcal infections in five Nordic countries with different prevention policies, 1995 to 2019.

BackgroundNeonatal early-onset disease caused by group B Streptococcus (GBS) is a leading cause of infant morbidity. Intrapartum antibiotic prophylaxis (IAP) is effective in preventing early-onset GBS disease, but there is no agreement on the optimal strategy for identifying the pregnant women requiring this treatment, and both risk-based prophylaxis (RBP) and GBS screening-based prophylaxis (SBP) are used.AimThe aim of this study was to evaluate the effect of SBP as a public health intervention on the epidemiology of early-onset GBS infections.MethodsIn 2012, Finland started the universal SBP, while Denmark, Iceland, Norway and Sweden continued with RBP. We conducted an interrupted time series analysis taking 2012 as the intervention point to evaluate the impact of this intervention. The incidences of early- and late-onset GBS infections during Period I (1995-2011) and Period II (2012-2019) were collected from each national register, covering 6,605,564 live births.ResultsIn Finland, a reduction of 58% in the incidence of early-onset GBS disease, corresponding to an incidence rate ratio (IRR) of 0.42 (95% CI: 0.34-0.52), was observed after 2012. At the same time, the pooled IRR of other Nordic countries was 0.89 (95% CI: 0.80-1.0), specifically 0.89 (95% CI: 0.70-1.5) in Denmark, 0.34 (95% CI: 0.15-0.81) in Iceland, 0.72 (95% CI: 0.59-0.88) in Norway and 0.97 (95% CI: 0.85-1.1) in Sweden.ConclusionsIn this ecological study of five Nordic countries, early-onset GBS infections were approximately halved following introduction of the SBP approach as compared with RBP.

Clinical phenotypes and outcomes of SARS-CoV-2, influenza, RSV and seven other respiratory viruses: a retrospective study using complete hospital data.

BACKGROUND: An understanding of differences in clinical phenotypes and outcomes COVID-19 compared with other respiratory viral infections is important to optimise the management of patients and plan healthcare. Herein we sought to investigate such differences in patients positive for SARS-CoV-2 compared with influenza, respiratory syncytial virus (RSV) and other respiratory viruses. METHODS: We performed a retrospective cohort study of hospitalised adults and children (≤15 years) who tested positive for SARS-CoV-2, influenza virus A/B, RSV, rhinovirus, enterovirus, parainfluenza viruses, metapneumovirus, seasonal coronaviruses, adenovirus or bocavirus in a respiratory sample at admission between 2011 and 2020. RESULTS: A total of 6321 adult (1721 SARS-CoV-2) and 6379 paediatric (101 SARS-CoV-2) healthcare episodes were included in the study. In adults, SARS-CoV-2 positivity was independently associated with younger age, male sex, overweight/obesity, diabetes and hypertension, tachypnoea as well as better haemodynamic measurements, white cell count, platelet count and creatinine values. Furthermore, SARS-CoV-2 was associated with higher 30-day mortality as compared with influenza (adjusted HR (aHR) 4.43, 95% CI 3.51 to 5.59), RSV (aHR 3.81, 95% CI 2.72 to 5.34) and other respiratory viruses (aHR 3.46, 95% CI 2.61 to 4.60), as well as higher 90-day mortality, ICU admission, ICU mortality and pulmonary embolism in adults. In children, patients with SARS-CoV-2 were older and had lower prevalence of chronic cardiac and respiratory diseases compared with other viruses. CONCLUSIONS: SARS-CoV-2 is associated with more severe outcomes compared with other respiratory viruses, and although associated with specific patient and clinical characteristics at admission, a substantial overlap precludes discrimination based on these characteristics.

SARS-CoV-2 testing in patients with low COVID-19 suspicion at admission to a tertiary care hospital, Stockholm, Sweden, March to September 2020.

BackgroundUniversal SARS-CoV-2 testing at hospital admission has been proposed to prevent nosocomial transmission.AimTo investigate SARS-CoV-2 positivity in patients tested with low clinical COVID-19 suspicion at hospital admission.MethodsWe characterised a retrospective cohort of patients admitted to Karolinska University Hospital tested for SARS-CoV-2 by PCR from March to September 2020, supplemented with an in-depth chart review (16 March-12 April). We compared positivity rates in patients with and without clinical COVID-19 suspicion with Spearman's rank correlation coefficient. We used multivariable logistic regression to identify factors associated with test positivity.ResultsFrom March to September 2020, 66.9% (24,245/36,249) admitted patient episodes were tested; of those, 61.2% (14,830/24,245) showed no clinical COVID-19 suspicion, and the positivity rate was 3.2% (469/14,830). There was a strong correlation of SARS-CoV-2 positivity in patients with low vs high COVID-19 suspicion (rho = 0.92; p < 0.001).From 16 March to 12 April, the positivity rate was 3.9% (58/1,482) in individuals with low COVID-19 suspicion, and 3.1% (35/1,114) in asymptomatic patients. Rates were higher in women (5.0%; 45/893) vs men (2.0%; 12/589; p = 0.003), but not significantly different if pregnant women were excluded (3.7% (21/566) vs 2.2% (12/589); p = 0.09). Factors associated with SARS-CoV-2 positivity were testing of pregnant women before delivery (odds ratio (OR): 2.6; 95% confidence interval (CI): 1.3-5.4) and isolated symptoms in adults (OR: 3.3; 95% CI: 1.8-6.3).ConclusionsThis study shows a relatively high SARS-CoV-2 positivity rate in patients with low COVID-19 suspicion upon hospital admission. Universal SARS-CoV-2 testing of pregnant women before delivery should be considered.

Atypical presentation of Neisseria meningitidis serogroup W disease is associated with the introduction of the 2013 strain.

Since 2015, the incidence of invasive meningococcal disease (IMD) caused by serogroup W (MenW) has increased in Sweden, due to the introduction of the 2013 strain belonging to clonal complex 11. The aim of this study was to describe the clinical presentation of MenW infections, in particular the 2013 strain, including genetic associations. Medical records of confirmed MenW IMD cases in Sweden during the years 1995-2019 (n = 113) were retrospectively reviewed and the clinical data analysed according to strain. Of all MenW patients, bacteraemia without the focus of infection was seen in 44%, bacteraemic pneumonia in 26%, meningitis in 13% and epiglottitis in 8%, gastrointestinal symptoms in 48% and 4% presented with petechiae. Phylogenetic analysis was used for possible links between genetic relationship and clinical picture. The 2013 strain infections, particularly in one cluster, were associated with more severe disease compared with other MenW infections. The patients with 2013 strain infections (n = 68) were older (52 years vs. 25 years for other strains), presented more often with diarrhoea as an atypical presentation (P = 0.045) and were more frequently admitted for intensive care (P = 0.032). There is a risk that the atypical clinical presentation of MenW infections, with predominantly gastrointestinal or respiratory symptoms rather than neck stiffness or petechiae, may lead to delay in life-saving treatment.

Acute infection as cause of hospitalization of asylum-seeking children and adolescents in Stockholm, Sweden 2015-2016.

We aimed to identify hospitalizations due to infectious diseases among asylum seekers and compare them to those of the resident population 1.6.2015-31.10.2016. Administrative numbers assigned to hospitalized non-resident children made them identifiable in the discharge register. The examined populations, expressed as person-years, were 334,573 residents and 7565 asylum seekers. There were 2500 episodes of infectious disease in 2240 resident children and 139 episodes in 121 asylum seekers. Among prevalent infections contracted before or during migration, there were 33 cases of tuberculosis, four of malaria, and one of louse-borne relapsing fever, all of which occurred in 13-17-year-old unaccompanied minors. Among younger asylum seekers, there were no significant differences in the spectrum of infectious discharge diagnoses compared to residents, but across all incident infections, 0-6-year-old asylum seekers had 3.2-fold and 7-12-year-old a 4.7-fold greater risk of being admitted. Screening for multidrug-resistant bacteria showed that 45/160 (28%) of the asylum seekers were colonized, but clinical infections caused by these species were rare.Conclusion: There was a high rate of hospitalizations for acute infectious diseases in asylum-seeking children, but the spectrum and severity of infections were similar to that in resident children. What is known: • Mental and physical health problems are common in immigrant children and adolescents. What is new: • Hospitalizations due to acute infections in asylum-seeking children and adolescents are common. In the context of this study, the severity and spectrum of infectious diseases seemed to be the same in the two groups; the increased hospitalization rate in asylum seekers may be due to social factors and perceived need for more support.

Vitamin D strengthens the bladder epithelial barrier by inducing tight junction proteins during E. coli urinary tract infection.

Tight junction proteins are pivotal to prevent bacterial invasion of the epithelial barrier. We here report that supplementation with vitamin D can strengthen the urinary bladder lining. Vitamin D deficient and sufficient mice were infected with Escherichia coli (E. coli) transurethrally to cause urinary tract infection. In addition, bladder biopsies were obtained from postmenopausal women before and after a 3-month period of supplementation with 25-hydroxyvitamin D3 (25D3) and ex vivo infected with E. coli. In biopsies, obtained before E. coli infection, vitamin D had no impact on tight junction proteins. However, during E. coli infection, vitamin D induced occludin and claudin-14 in mature superficial umbrella cells of the urinary bladder, as demonstrated by immunohistochemistry. Increased cell-cell adhesion consolidating the epithelial integrity is thereby promoted. We here describe a novel role of vitamin D in the urinary tract supporting vitamin D supplementation to restore the bladder epithelial integrity.

A 10-year retrospective survey of acute childhood osteomyelitis in Stockholm, Sweden.

AIM: Children with osteomyelitis present with a range of signs and symptoms and with varying degree of severity. The purpose of this study was to provide data on a population-based 10-year material of children with acute osteomyelitis. METHODS: All children, 0-14 years in Stockholm Region with acute osteomyelitis hospitalised in July 2005-June 2015, were retrospectively studied. Time to hospital presentation, disease localization, inflammation markers, imaging procedures, microbiology, severity classified by the presence of complications, surgical procedures, hospital length of stay and seasonal variation were recorded. RESULTS: There were 430 children with acute osteomyelitis; 61% were boys. The incidence per 100 000 person-years was 11.6; 9.3 in girls and 13.1 in boys. Median age at admission was 2.9 years with no peak later in childhood. Median time from first symptom to diagnosis was 4 days (range 1-21) and 48% of the cases were localised to femur or tibia. Mean C-reactive protein was 59 mg/L (range 1-376). Blood (n = 82) or tissue cultures (n = 54) were positive in 118 (28%) children. The most common pathogen was Staphylococcus aureus (n = 88) followed by Streptococcus pyogenes (n = 12). Surgery was performed in 71 children (17%). There was no mortality. Severe complications were seen in 14 (3.3%) children, five of whom were admitted to intensive care. Median hospital length of stay was 4 days (range 1-60). CONCLUSIONS: Osteomyelitis in children is a diagnostic challenge with a low yield of positive bacterial cultures. Few children with uncomplicated disease need surgery, but the risk of severe complications is not negligible.

An overview of how on-call consultant paediatricians can recognise and manage severe primary immunodeficiencies.

Severe primary paediatric immunodeficiency syndromes are rare and potentially fatal unless suspected, diagnosed and treated early. We provide clinical guidance and support for on-call consultant paediatricians working in secondary level hospitals on how to recognise and manage children with these conditions. Our paper addresses four conditions that risk the most severe outcomes if they are not adequately cared for during on-call periods, such as weekends: severe combined immunodeficiency, haemophagocytic lymphohistiocytosis, severe congenital neutropaenia and chronic granulomatous disease. CONCLUSION: On-call paediatricians are provided with advice on handling the most severe primary immunodeficiencies.

Fifteen-minute consultation: Recognising primary immune deficiencies in children.

Children with primary immunodeficiency syndromes present with broad variation of clinical features and the consequences are often severe if not promptly recognised. Here, support is provided for the general paediatrician to recognise primary immunodeficiencies among the many children they meet in their clinical practice.

Seizures in hospitalised paediatric patients with SARS-CoV-2 and comparison of severity with seizures in hospitalised paediatric patients with other respiratory viruses during the COVID-19 pandemic: a population-based cohort study.

OBJECTIVE: To study seizures in patients hospitalised due to SARS-CoV-2 infection, and compare their severity with seizures in patients hospitalised due to other viral respiratory tract infections (RTIs). DESIGN: Observational population-based cohort study. SETTING: Northern Stockholm. PATIENTS: Patients aged 1 month-18 years hospitalised due to SARS-CoV-2 with and without seizures, and patients of the same age hospitalised due to other viral RTIs with seizures, between 1 March 2020 and 30 June 2022. MAIN OUTCOME MEASURES: The prevalence of seizures in hospitalised patients due to SARS-CoV-2, the evaluation of assumed predictors of seizures and the comparison of severity markers in patients with SARS-CoV-2 versus other RTIs. RESULTS: 32 of 239 included patients (13.4%) admitted due to SARS-CoV-2 infection had seizures. Central nervous system (CNS) disease and the omicron period had significantly increased OR for seizures (OR: 5.12; CI: 2.06 to 12.72 and OR: 3.01; CI: 1.15 to 7.88, respectively). Seizures in patients with SARS-CoV-2 were more common in children older than 5 years (p=0.001), even in the absence of fever (p=0.007), as compared with other viral RTIs. The duration of hospitalisation was longer in patients with seizures due to other viral RTIs (p=0.023). There was no significant difference regarding severity markers of seizures between the two groups. CONCLUSIONS: CNS disease and the omicron period were risk factors for seizures in patients with SARS-CoV-2, who were older than patients with other RTIs. The severity of seizures was comparable between the two groups; hospitalisation was however longer in patients with other RTIs.

Malaria parasite prevalence in Sub-Saharan African migrants screened in Sweden: a cross-sectional study.

Background: Asymptomatic infections with malaria parasites are common in populations in endemic areas. These infections may persist in migrants after arrival in a non-endemic area. Screening to find and clear these infections is generally not implemented in non-endemic countries, despite a potential negative health impact. We performed a study to evaluate the Plasmodium parasite prevalence in migrants living in Sweden. Methods: Adults and children born in Sub-Saharan Africa (SSA) were invited in the study between April 2019 and June 2022 at 10 different sites, mainly as part of the national Migrant Health Assessment Program in Stockholm and Västerås, Sweden. Rapid diagnostic tests (RDT) and real-time PCR were used to detect malaria parasites. Prevalence and test sensitivity were calculated with 95% confidence intervals (CI). Univariate and multivariable logistic regression were used to evaluate associations with PCR positivity. Findings: In total, 789 individuals were screened for Plasmodium spp. of which 71 (9.0%) were positive by PCR and 18 (2.3%) also by RDT. When performed during the national screening program, 10.4% was PCR positive. A high prevalence was detected in migrants with Uganda as the country of last residence, 53/187 (28.3%), and in this group the prevalence was highest in children, 29/81 (35.8%). Among the PCR positive, 47/71 (66.2%) belonged to families with at least one other member testing positive (odds ratio [OR] 43.4 (95% CI 19.0-98.9), and the time lived in Sweden ranged between 6 and 386 days. Interpretation: A high malaria parasite prevalence was found in migrants from SSA, particularly in children offered screening in Stockholm, Sweden during the study period. Awareness of asymptomatic malaria infection is needed and screening for malaria in migrants arriving from high endemic countries should be considered. Funding: The Swedish Research Council, Stockholm County Council and Centre for Clinical Research, Västmanland, Sweden.

A Swedish population-based study of complications due to acute rhinosinusitis in children 5-18 years old.

BACKGROUND: There are few population-based studies of complications due to acute rhinosinusitis in children. The aim was to clarify the admission and complication rate and analyze bacterial cultures in children five to 18 years old in Stockholm, Sweden. METHODS: This was a population-based observational cohort study with retrospectively collected data from individual medical records, from 1 July 2003 to 30 June 2016 in Stockholm, Sweden. Hospital admissions of children with a discharge diagnosis of rhinosinusitis and related complications were reviewed. RESULTS: Incidence of admission due to acute rhinosinusitis was 7.8 per 100 000 children per year (boys 9.2, girls 6.2) and 61% of the admitted children were boys. A severe - postseptal orbital, intracranial or osseous - complication, was present in 34% of admissions (postseptal orbital 28%, intracranial 6%, osseous 4%), resulting in an incidence of 2.6 severe complications per 100 000 children per year (boys 3.6, girls 1.6). Orbital preseptal cellulitis was present in 88% of admissions. Incidence of surgery was 1.3 per 100 000 per year (boys 1.8, girls 0.8) and the percentage of admitted children that had surgery increased with age. S. pyogenes was the most common pathogen found in the whole cohort (29 admissions), while S. milleri was the most common pathogen found among the children with severe complication and surgery. CONCLUSIONS: There is a relative high risk of severe complications in children between five to 18 years that are admitted due to acute rhinosinusitis. There is a need for prospective studies to further analyze the pathogens involved in complications due to acute rhinosinusitis.

[Leishmaniasis a neglected but serious tropical disease]. / Leishmaniasis ­ en bortglömd men allvarlig parasitsjukdom.

Visceral leishmaniasis is an uncommon, imported infectious disease in Sweden. Only two cases have been reported 1996-2016. During the last year, however, three cases of visceral leishmaniasis in children less than 3 years old have been treated at the Astrid Lindgren Children's Hospital in Stockholm. They have all been infected during vacation in Southern Europe within their first year of life. We want to raise the awareness regarding this serious neglected tropical disease in the Swedish health care by describing these three cases.

Cytotoxic necrotizing factor 1 (CNF1) induces an inflammatory response in the urinary tract in vitro but not in vivo.

Cytotoxic necrotizing factor 1 (CNF1) is a well-defined virulence factor of uropathogenic Escherichia coli. We studied the role of CNF1 in uroepithelial cells as well as in children and adults with sporadic and recurrent UTI. Our study suggests that CNF1 may promote bacterial attachment and invasion and can induce an inflammatory response in the urinary tract in vitro but that its role in vivo is possibly minor in comparison with other virulence factors of the uropathogenic E. coli.