Comparison of Characteristics and Outcomes of Multisystem Inflammatory Syndrome, Kawasaki Disease and Toxic Shock Syndrome in Children.

Background and Objectives: Since the first cases of multisystem inflammatory syndrome in children (MIS-C) in April 2020, the diagnostic challenge has been to recognize this syndrome and to differentiate it from other clinically similar pathologies such as Kawasaki disease (KD) and toxic shock syndrome (TSS). Our objective is to compare clinical signs, laboratory data and instrumental investigations between patients with MIS-C, KD and TSS. Materials and Methods: This retrospective observational study was conducted at the Children's Clinical University Hospital, Latvia (CCUH). We collected data from all pediatric patients <18 years of age, who met the Centers for Disease Control and Prevention case definition for MIS-C, and who presented to CCUH between December 2020 and December 2021. We also retrospectively reviewed data from inpatient medical records of patients <18 years of age diagnosed as having KD and TSS at CCUH between December 2015 and December 2021. Results: In total, 81 patients were included in this study: 39 (48.1%) with KD, 29 (35.8%) with MIS-C and 13 (16.1%) with TSS. In comparison with TSS and KD, patients with MIS-C more often presented with gastrointestinal symptoms (abdominal pain (p < 0.001), diarrhea (p = 0.003)), shortness of breath (p < 0.02) and headache (p < 0.003). All MIS-C patients had cardiovascular involvement and 93.1% of MIS-C patients fulfilled KD criteria, showing higher prevalence than in other research. Patients with KD had higher prevalence of cervical lymphadenopathy (p < 0.006) and arthralgias (p < 0.001). In comparison with KD and TSS, MIS-C patients had higher levels of ferritin (p < 0.001), fibrinogen (p = 0.04) and cardiac biomarkers, but lower levels of platelets and lymphocytes (p < 0.001). KD patients tended to have lower peak C-reactive protein (CRP) (p < 0.001), but higher levels of platelets. Acute kidney injury was more often observed in TSS patients (p = 0.01). Pathological changes in electrocardiography (ECG) and echocardiography were significantly more often observed in MIS-C patients (p < 0.001). Conclusions: This research shows that MIS-C, KD and TSS have several clinical similarities and additional investigations are required for reaching final diagnosis. All the patients with suspected MIS-C diagnosis should be examined for possible cardiovascular involvement including cardiac biomarkers, ECG and echocardiography.

Impact of educational training and C-reactive protein point-of-care testing on antibiotic prescribing in rural and urban family physician practices in Latvia: a randomised controlled intervention study.

BACKGROUND: Although self-limiting viral infections are predominant, children with acute infections are often prescribed antibiotics by family physicians. The aim of the study is to evaluate the impact of two interventions, namely C-reactive protein point-of-care testing and educational training, on antibiotic prescribing by family physicians. METHODS: This randomised controlled intervention study included acutely ill children consulted by 80 family physicians from urban and rural practices in Latvia. The family physicians were divided into two groups of 40. The family physicians in the intervention group received both interventions, i.e. C-reactive protein point-of-care testing and educational training, whereas the family physicians in the control group continued to dispense their standard care. The primary outcome measure was the antibiotic prescribing at the index consultation (delayed or immediate prescription) in both study groups. The secondary outcome was CRP testing per study group. Patient- and family physician- related predictors of antibiotic prescribing were analysed as associated independent variables. Practice location effect on the outcomes was specially addressed, similar to other scientific literature. RESULTS: In total, 2039 children with acute infections were enrolled in the study. The most common infections observed were upper and lower respiratory tract infections. Overall, 29.8% (n = 607) of the study population received antibiotic prescription. Our binary logistic regression analysis did not find a statistically significant association between antibiotic prescriptions and the implemented interventions. In the control group of family physicians, a rural location was associated with more frequent antibiotic prescribing and minimal use of CRP testing of venous blood samples. However, in the intervention group of family physicians, a rural location was associated with a higher level of C-reactive protein point-of-care testing. Furthermore, in rural areas, a significant reduction in antibiotic prescribing was observed in the intervention group compared with the control group (29.0% (n = 118) and 37.8% (n = 128), respectively, p = 0.01). CONCLUSION: Our results show that the availabilty of C-reactive protein point-of-care testing and educational training for family physicians did not reduce antibiotic prescribing. Nevertheless, our data indicate that regional variations in antibiotic-prescribing habits exist and the implemented interventions had an effect on family physicians practices in rural areas.

Biomarker combinations in predicting sepsis in hospitalized children with fever.

Sepsis is among the leading causes of critical illness worldwide. It includes physiologic, pathologic, and biochemical abnormalities, induced by infection. Novel methods for recognizing a dysregulated inflammatory response and predicting associated mortality must be developed. Our aim was to investigate biomarkers that characterize a pro-inflammatory and anti-inflammatory response in patients with fever by comparing predictive validity for sepsis. 165 patients with fever were enrolled in this study, 55 of them had sepsis according to pSOFA criteria. All patients had blood samples drawn at the time of inclusion and after 24 h. CRP, PCT and also IL-6, IL-8 and sFAS levels were significantly higher in patients with sepsis. The AUC of CRP to predict sepsis was 0.799, all the other biomarkers had AUC's lower than that. Cytokines, when used as a single marker, did not show a significant diagnostic performance We analyzed various models of biomarker combinations. CRP combined with sFAS showed increase in sensitivity in predicting sepsis (88% vs. 83%). The highest AUC was achieved, when CRP, IL-6, sFAS and sVCAM-1 markers were combined 0.830 (95% CI 0.762-0.884) with a sensitivity of 70% and specificity of 84%. vs. 0.799 for CRP alone.

Latvian Primary Care Management of Children with Acute Infections: Antibiotic-Prescribing Habits and Diagnostic Process Prior to Treatment.

Background and Objectives: Primary care physicians frequently prescribe antibiotics for acutely ill children, even though they usually have self-limiting diseases of viral etiology. The aim of this research was to evaluate the routine antibiotic-prescribing habits of primary care in Latvia, in response to children presenting with infections. Materials and Methods: This cross-sectional study included acutely ill children who consulted eighty family physicians (FP) in Latvia, between November 2019 and May 2020. The data regarding patient demographics, diagnoses treated with antibiotics, the choice of antibiotics and the use of diagnostic tests were collected. Results: The study population comprised 2383 patients aged between one month and 17 years, presenting an acute infection episode, who had a face-to-face consultation with an FP. Overall, 29.2% of these patients received an antibiotic prescription. The diagnoses most often treated with antibiotics were otitis (45.8% of all antibiotic prescriptions), acute bronchitis (25.0%) and the common cold (14.8%). The most commonly prescribed antibiotics were amoxicillin (55.9% of prescriptions), amoxicillin/clavulanate (18.1%) and clarithromycin (11.8%). Diagnostic tests were carried out for 59.6% of children presenting with acute infections and preceded 66.4% of antibiotic prescriptions. Conclusion: Our data revealed that a high level of antibiotic prescribing for self-limiting viral infections in children continues to occur. The underuse of narrow-spectrum antibiotics and suboptimal use of diagnostic tests before treatment decision-making were also identified. To achieve a more rational use of antibiotics in primary care for children with a fever, professionals and parents need to be better educated on this subject, and diagnostic tests should be used more extensively, including the implementation of daily point-of-care testing.

A Comparison of the Epidemiology, Clinical Features, and Treatment of Acute Osteomyelitis in Hospitalized Children in Latvia and Norway.

Background and objectives: Paediatric acute osteomyelitis (AO) may result in major life-threatening and limb-threatening complications if not recognized and treated early. The management of AO may depend on local microbial prevalence and virulence factors. This study compares the approach to paediatric AO in hospitals in two countries-Latvia and Norway. Materials and Methods: The study includes patients with AO hospitalized in the paediatric department in the Norwegian hospital Sørlandet Sykehus Kristiansand (SSK), in the period between the 1st of January 2012 and the 31st of December 2019. The results from SSK are compared to the results of a published study of AO in patients hospitalized at the Children's Clinical University Hospital (CCUH) in Riga, Latvia. Results: The most isolated pathogen from cultures in both hospitals was S. aureus (methicillin-sensitive). The lower extremity was the most affected body part (75% in CCUH, 95% in SSK), the main clinical symptom was pain (CCUH 92%, SSK 96.6%). Deep culture aspiration was most often taken intraoperatively in CCUH (76.6%) and percutaneously in SSK (44.8%). Oxacillin was the most applied antibiotic in CCUH (89.4%), and Cloxacillin in SSK (84.6%). Combined treatment with anti-Staphylococcal penicillins and Clindamycin was administered in 25.5% and 33.8% of CCUH and SSK patients, respectively. The median duration of the intravenous antibacterial treatment in CCUH and SSK was 15 and 10 days, respectively, and a switch to oral therapy was mainly made at discharge in both hospitals. The median total duration of antibiotic treatment was 25 days in CCUH and 35 days in SSK. 75% of CCUH and 10.3% of SSK patients were treated surgically. Complications were seen in 47% of patients in CCUH and in 38% in SSK. Conclusions: The transition to oral antibacterial treatment in both hospitals was delayed, which suggests a lack of criteria for discontinuation of intravenous therapy and could potentially contribute to longer hospitalization, higher cost of treatment and risk of complications. The use of more invasive techniques for deep culturing and significantly more common surgical interventions could possibly be linked to a higher complication rate in AO patients treated at the Latvian hospital.

Pediatric Readiness in the Emergency Department and Its Association With Patient Outcomes in Critical Care: A Prospective Cohort Study.

OBJECTIVES: Pediatric mortality in Latvia remains one of the highest among Europe. The purpose of this study was to assess the quality of pediatric acute care and pediatric readiness and determine their association with patient outcomes using a patient registry. DESIGN: This was a prospective cohort study. Pediatric readiness was measured using the weighted pediatric readiness score based on a 100-point scale. The processes of care were measured using in situ simulations to generate a composite quality score. Clinical outcome data-including PICU and hospital length of stay as well as 6-month mortality-were collected from the Pediatric Intensive Care Audit Network registry. The associations between composite quality score and weighted pediatric readiness score on patient outcomes were explored with mixed-effects regressions. SETTING: This study was conducted in all Latvian Emergency Departments and in the national PICU. PATIENTS: All patients who were transferred into the national PICU were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All (16/16) Latvian Emergency Departments participated with a mean composite quality score of 35.3 of 100 and a median weighted pediatric readiness score of 31 of 100. A total of 254 patients were included in the study and followed up for a mean of 436 days, of which nine died (3.5%). Higher weighted pediatric readiness score was associated significantly with lower length of stay in both the PICU and hospital (adjusted ß, -0.06; p = 0.021 and -0.36; p = 0.011, respectively) and lower 6-month mortality (adjusted odds ratio, 0.93; 95% CI, 0.88-0.98). CONCLUSIONS: These data provide a national assessment of pediatric emergency care in a European country. Pediatric readiness in the emergency department was associated with patient outcomes in this population of pediatric patients transferred to the national PICU.

Value of parental concern and clinician's gut feeling in recognition of serious bacterial infections: a prospective observational study.

BACKGROUND: Serious bacterial infections (SBI) are a significant cause of mortality worldwide. Parental concern and clinician's gut feeling that there is something wrong has been associated with increased likelihood of developing SBI in primary care studies. The aim of this study is to assess the diagnostic value of parental concern and gut feeling at the emergency department of a tertiary hospital. METHODS: This prospective observational study included children with fever attending the emergency department of Children's Clinical University hospital in Riga between October 2017 and July 2018. Data were collected via parental and clinician questionnaires. "Gut feeling" was defined as intuitive feeling that the child may have a serious illness, and "Sense of reassurance" as a feeling that the child has a self-limiting illness. "Parental concern" was defined as impression that this illness is different from previous illnesses. SBI included bacterial meningitis, sepsis, bacteraemia, pneumonia, urinary tract infection, appendicitis, bacterial gastroenteritis, and osteomyelitis. Pearson's Chi-Squared test or Fisher's exact test were used to compare the variables between children with and without SBI. Positive likelihood ratio was calculated for "gut feeling", "sense of reassurance", and parental concern. RESULTS: The study included 162 patients aged 2 months to 17.8 years. Forty-six patients were diagnosed with SBI. "Sense of reassurance" expressed by all clinicians was associated with lower likelihood of SBI (positive likelihood ratio 8.8, 95% confidence interval 2.2-34.8). "Gut feeling" was not significantly predictive of the patient being diagnosed with SBI (positive likelihood ratio 3.1, 95% confidence interval 1.9-5.1), The prognostic rule-in value of parental concern was insignificant (positive likelihood ratio 1.4, 95% confidence interval 1.1-1.7). CONCLUSION: Sense of reassurance was useful in ruling out SBI. Parental concern was not significantly predictive of SBI.

Beliefs, Practices and Health Care Seeking Behavior of Parents Regarding Fever in Children.

Background and objectives: Fever in children is one of the most common reasons for seeking medical attention. Parents often have misconceptions about the effects to fever, which leads to inappropriate use of medication and nonurgent visits to emergency departments (ED). The aim of this study was to clarify the beliefs on the effects and management of fever and to identify healthcare seeking patterns among parents of febrile children in Latvia. Materials and Methods: Parents and legal guardians of children attending ED with febrile illness were included in the study. Participants were recruited in Children's Clinical University Hospital (CCUH) in Riga, and in six regional hospitals in Latvia. Data on beliefs about fever, administration of antipyretics, healthcare-seeking behavior, and experience in communication with health care workers were collected via questionnaire. Results: In total, 355 participants were enrolled: 199 in CCUH and 156 in regional hospitals; 59.2% of participants considered fever itself as indicative of serious illness and 92.8% believed it could raise the child's body temperature up to a dangerous level. Antipyretics were usually administered at median temperature of 38.0 °C, and the median temperature believed to be dangerous was 39.7 °C; 56.7% of parents usually contacted a doctor within the first 24 h of the illness. Parents who believed that lower temperatures are dangerous to a child were more likely to contact a doctor earlier and out-of-hours; 60.1% of participants had contacted their family doctor prior their visit to ED. Parental evaluation of satisfaction with the information and reassurance provided by the doctors at the hospital was higher than of that provided by their family doctor; 68.2% of participants felt safer when their febrile children were treated at the hospital. Conclusions: Fever itself was regarded as indicative of serious illness and potentially dangerous to the child's life. These misconceptions lead to inappropriate administration of antipyretics and early-seeking of medical attention, even out-of-hours. Hospital environment was viewed as safer and more reassuring when dealing with febrile illness in children. More emphasis must be placed on parental education on proper management of fever, especially in primary care.

Inflammatory Cytokine and Chemokine Patterns in Paediatric Patients with Suspected Serious Bacterial Infection.

Background and objectives: In children, acute infection is the most common cause of visits to the emergency department. Although most of them are self-limiting, mortality due to severe bacterial infections (SBI) in developed countries is still high. When the risk of serious bacterial infection is too high to ignore, yet too low to justify admission and hospital observation, clinicians try to improve diagnostic accuracy by performing various laboratory tests. The aim of the study was to investigate whether an early inflammatory cytokine and chemokine panel can add information in diagnostics of SBI and assessment of efficacy of early therapies in hospitalized children with fever. Methods: This study included 51 children with febrile infections that were admitted to the emergency department (ED). Clinical examination and microbiological and radiological tests were used as reference standards for the definition of SBI. Study population was categorized into two groups: (1) patients with SBI (n = 21); (2) patients without SBI (n = 30). Inflammatory cytokine and chemokine panels were analyzed from the first routine blood samples at hospital admission and after 24 h. Results: Out of 12 cytokines and chemokines, only Eotaxin and granulocyte colony-stimulating factor (G-CSF) had statistically significant differences between groups at the time of inclusion. Receiver operator characteristic analysis to predict SBI showed an area under the curve (AUC) of 0.679 for G-CSF. Conclusions: Analysis of inflammatory cytokine profiles may provide additional information in early diagnostics of SBI.

Assessment of ADAMTS-13 Level in Hospitalized Children with Serious Bacterial Infections as a Possible Prognostic Marker.

Background and objectives: In children, acute infection is the most common cause of visits in the primary care or emergency department. In 2002, criteria for diagnostics of pediatric sepsis were published, and then revised in 2016 as "life-threatening organ dysfunction due to a dysregulated host response to infection". In the pathophysiology of sepsis endothelial dysfunction plays a very important role. Deficient proteolysis of von Willebrand factor, due to reduced ADAMTS-13 activity, results in disseminated platelet-rich thrombi in the microcirculation. ADAMTS-13 deficiency has been detected in systemic inflammation. The clinical relevance of ADAMTS-13 during sepsis is still unclear. We aimed to investigate the possible use of ADAMTS-13 as a prognostic marker in children with serious bacterial infection (SBI). Materials and Methods: Inclusion criteria were hospitalized children with SBI, aged from 1 month to 17 years. SBI was defined based on available clinical, imaging, and later also on microbiological data. Sepsis was diagnosed using criteria by The International Consensus Conference. In all the patients, the levels of ADAMTS-13 were measured at the time of inclusion. Results: Data from 71 patients were analyzed. A total of 47.9% (34) had sepsis, 21.1% (15) were admitted to the ICU, 8.5% (6) had mechanical ventilator support, and 4.2% (3) patients had a positive blood culture. The median level of ADAMTS-13 in this study population was 689.43 ng/mL. Patients with sepsis, patients admitted to the Intensive Care Unit, and patients in need of mechanical ventilator support had significantly lower levels of ADAMTS-13. None of the patients had ADAMTS-13 deficiency. In patients with SBI, the area under the curve (AUC) to predict sepsis was 0.67. A cut-off ADAMTS-13 level of ≤730.49 had 82% sensitivity and 60% specificity for sepsis in patients with SBI. Conclusions: ADATMS-13 levels were lower in patients with SBI and sepsis, but AUC and sensitivity were too low to accept it as a prognostic marker.

Assessment of Immature Granulocytes Percentage to Predict Severe Bacterial Infection in Latvian Children: An Analysis of Secondary Data.

Background: Detection of small proportion of serious bacterial infections (SBI) with a potentially life threating course in a large group of children with fever admitted to emergency department (ED) is still complicated. Measurement of immature granulocytes (IG) percentage may be used as a marker of bacterial infections. The aim of the study was to evaluate whether the IG percentage is a useful additional predictive marker of SBI. Methods: This study included 258 children with febrile infections that were admitted to the ED. Clinical follow-up, microbiological and radiological tests were used as reference standards for the definition of SBI. Study population was categorized into two groups: (1) infected patients with no suspicion of SBI (n = 75); (2) patients with suspicion of SBI (n = 183). IG percentage, white blood cell count (WBC), and C-reactive protein (CRP) levels were analyzed from the first routine blood samples at hospital admission. Results: A statistically significant difference in IG percentage levels was observed in children with SBI and those without-the mean IG percentage was 1.2% for the SBI group, 0.3% for those without SBI. The cutoff level of IG percentage to predict SBI was 0.45 (84% specificity, 66% sensitivity, 90% positive predictive value). We combine variables and evaluate their additive values. The sensitivity of WBC to detected SBI improved from 74% to 85% when IG percentage was added to the prediction models. When CRP, WBC, and IG percentage were combined, the sensitivity to predict SBI increased to 93%, the specificity to 86% (95% CI 77%⁻93%). Receiver operator characteristic analysis to predict SBI showed an area under the curve (AUC) of 0.80 for IG percentage. Conclusion: Addition of IG percentage to traditionally used markers of SBI as WBC and CRP may help to identify children with serious bacterial infections. Furthermore, IG percentage can be rapidly obtained from the traditional full blood count without any extra sampling and costs.

Factors related to poor asthma control in Latvian asthma patients between 2013 and 2015.

OBJECTIVES: To investigate whether beliefs about asthma medication, cognitive and emotional factors are related to poor asthma control in a sample of Latvian asthma patients in 2015. DESIGN: Cross-sectional, self-administered survey. SUBJECTS: Three hundred and fifty two asthma patients (mean age 57.5 years) attending outpatient pulmonologist consultations in Riga, Latvia during September 2013 to December 2015. The sample size was calculated to detect a prevalence of poor asthma control of 50% with a margin of error of 5% and a power of 95%. MAIN OUTCOME MEASURES: The validated Beliefs about Medication Questionnaire (BMQ) and the Brief Illness Perception Questionnaire (brief IPQ) were used. Good asthma control was assessed using the asthma control test (ACT), a validated five-item scale that reliably assesses asthma control over a recall period of four weeks. Logistic regression models were used to predict poor asthma control. RESULTS: Patients who had a good control of asthma medication (OR 0.70; 95% CI 0.61-0.79) or were confident that their asthma medication improves illness (OR 0.84; 95% CI 0.74-0.95) had a reduced risk of poor asthma control. The more symptoms (OR 1.63; 95% CI 1.44-1.84) the asthma patients perceived or the more their illness affects their life, the higher the probability of poor asthma control (OR 1.47; 95% CI 1.31-1.65). Some beliefs of necessity and concerns of asthma medication were also statistically significantly related to poor asthma control. CONCLUSIONS: Beliefs of necessity of asthma medication, cognitive and emotional illness perception factors correlate well with poor asthma control in Latvian patients.

Short- and mid-term outcomes of multisystem inflammatory syndrome in children: a longitudinal prospective single-center cohort study.

Background: Multisystem inflammatory syndrome in children (MIS-c) emerged during the coronavirus disease 2019 pandemic and is associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite the extensively studied clinical manifestation of acute condition, the short- and long-term effects of MIS-c on children's health are unknown. Methods: This was a prospective longitudinal cohort study. Children aged <18 years who met the Centers for Disease Prevention and Control (CDC) diagnostic criteria and who were admitted to the Children's Clinical University Hospital of Latvia (CCUH) between July 1, 2020, and April 15, 2022, were enrolled in the study. An outpatient follow-up program was initiated in July 2020. All children were evaluated at 2 weeks, 2 months (1-3 months), and 6 months (5-7 months) after discharge. The face-to-face interviews comprised four domains as follows: symptom assessment, physical examination, laboratory testing, and cardiological investigation [including electrocardiogram (ECG) and echocardiography (echo)]. Results: Overall, 21 patients with MIS-c were enrolled. The median age of the study group was 6 years. At the 2-week follow-up, almost half of the patients (N = 10, 47.6%) reported exercise intolerance with provoked tiredness. Laboratory tests showed a considerable increase in blood cell count, with a near doubling of leukocyte and neutrophil counts and a tripling of thrombocyte levels. However, a decline in the levels of inflammatory and organ-specific markers was observed. Cardiological investigation showed significant improvement with gradual resolution of the acute-phase pathological findings. Within 2 months, improvement in exercise capacity was observed with 5-fold and 2-fold reductions in physical intolerance (N = 2, 9.5%) and physical activity-induced fatigue (N = 5, 23.8%), respectively. Normalization of all blood cell lines was observed, and cardiological investigation showed no persistent changes. At the 6-month visit, further improvement in the children's exercise capacity was observed, and both laboratory and cardiological investigation showed no pathological changes. Conclusions: Most persistent symptoms were reported within the first 2 weeks after the acute phase, with decreased physical activity tolerance and activity-induced fatigue as the main features. A positive trend was observed at each follow-up visit as the spectrum of the children's complaints decreased. Furthermore, rapid normalization of laboratory markers and cardiac abnormalities was observed.

SARS-CoV-2 seroprevalence among children in Latvia: A cross-sectional study.

Coronavirus disease 2019 (COVID-19) is a major global health concern. In contrast to adults, the course of the disease has been observed to be mild or even asymptomatic in children. It is therefore both clinically and epidemiologically important to measure the seroprevalence in children and adolescents to discern the overall morbidity of the disease and to compare these findings with similar data collected globally. We conducted a cross-sectional study between March and July of 2022 at the Children Clinical University Hospital in Riga, Latvia, to evaluate the seroprevalence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Participants aged 0 to 18 years were enrolled during hospitalization for reasons other than COVID-19. The levels of SARS-CoV-2 spike protein and nucleocapsid antibodies were measured in blood samples. The possibility of transplacental antibody transport was evaluated by directly interviewing the mothers of participants aged 18 months and younger. Various demographic and epidemiological risk factors and their association with seroprevalence were analyzed. Positive SARS-CoV-2 nucleocapsid antibodies were designated the main criterion for seropositivity. Of 200 enrolled children, 173 were found to be seropositive, resulting in an overall seroprevalence of 86.5%. The highest seroprevalence was detected in children and adolescents aged 12 to 18 years. With the progression of the COVID-19 pandemic, the seroprevalence in children has increased significantly. We found that almost 1-third of seropositive children in our study population were unaware of being previously infected with SARS-CoV-2 due to an asymptomatic course of the disease. Our study findings pertaining to high seropositivity among children and adolescents might be beneficial for public authorities to adapt epidemiological strategies and prevention measures. The high seroprevalence rate reported here and in many other populations around the world suggests that COVID-19 will likely become one of the many seasonal viral infections.

Integrating Clinical Signs at Presentation and Clinician's Non-analytical Reasoning in Prediction Models for Serious Bacterial Infection in Febrile Children Presenting to Emergency Department.

Objective: Development and validation of clinical prediction model (CPM) for serious bacterial infections (SBIs) in children presenting to the emergency department (ED) with febrile illness, based on clinical variables, clinician's "gut feeling," and "sense of reassurance. Materials and Methods: Febrile children presenting to the ED of Children's Clinical University Hospital (CCUH) between April 1, 2017 and December 31, 2018 were enrolled in a prospective observational study. Data on clinical signs and symptoms at presentation, together with clinician's "gut feeling" of something wrong and "sense of reassurance" were collected as candidate variables for CPM. Variable selection for the CPM was performed using stepwise logistic regression (forward, backward, and bidirectional); Akaike information criterion was used to limit the number of parameters and simplify the model. Bootstrapping was applied for internal validation. For external validation, the model was tested in a separate dataset of patients presenting to six regional hospitals between January 1 and March 31, 2019. Results: The derivation cohort consisted of 517; 54% (n = 279) were boys, and the median age was 58 months. SBI was diagnosed in 26.7% (n = 138). Validation cohort included 188 patients; the median age was 28 months, and 26.6% (n = 50) developed SBI. Two CPMs were created, namely, CPM1 consisting of six clinical variables and CPM2 with four clinical variables plus "gut feeling" and "sense of reassurance." The area under the curve (AUC) for receiver operating characteristics (ROC) curve of CPM1 was 0.744 (95% CI, 0.683-0.805) in the derivation cohort and 0.692 (95% CI, 0.604-0.780) in the validation cohort. AUC for CPM2 was 0.783 (0.727-0.839) and 0.752 (0.674-0.830) in derivation and validation cohorts, respectively. AUC of CPM2 in validation population was significantly higher than that of CPM1 [p = 0.037, 95% CI (-0.129; -0.004)]. A clinical evaluation score was derived from CPM2 to stratify patients in "low risk," "gray area," and "high risk" for SBI. Conclusion: Both CPMs had moderate ability to predict SBI and acceptable performance in the validation cohort. Adding variables "gut feeling" and "sense of reassurance" in CPM2 improved its ability to predict SBI. More validation studies are needed for the assessment of applicability to all febrile patients presenting to ED.

Clinical features of pediatric post-acute COVID-19: a descriptive retrospective follow-up study.

To date, information on COVID-19 long-term post-recovery sequelae in children and adolescents remains scarce. A retrospective descriptive cohort study was performed by collecting data on 92 patients (age ≤ 18 years). All were evaluated during a face-to-face visit following a specially designed post-COVID-19 symptom assessment protocol at the following stage: 1-3 months after COVID-19 onset. Among the 92 children, 45 (49%) were completely free of any COVID-19-related symptoms, while 47 (51%) reported persistence of at least one symptom, in particular tiredness, loss of taste and/or smell and headaches. The most common post-acute COVID-19 clinical features were noted in children aged between 10 and 18 years. A detailed multidisciplinary follow-up of patients with COVID-19 seems relevant, whatever the severity of the symptoms.

Impact of Pediatric COVID-19 on Family Health-Related Quality of Life: A Qualitative Study from Latvia.

Information on family health-related quality of life (FHRQoL) among families of children with the coronavirus disease 2019 (COVID-19) is limited. This qualitative study explores the impact of pediatric COVID-19 on FHRQoL from the parents' perspective. Semi-structured interviews were conducted with parents (n = 20) whose children had tested positive for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Inductive thematic analysis revealed the following 10 themes that represented parents' perception of FHRQoL while taking care of a child with COVID-19: pediatric COVID-19 as a disease with many unknowns; emotional saturation; internal family relationships in the context of "a new experience"; routine household activities and daily regimen while family is in lockdown; plenty of free time; a wide social support network; social stigma associated with COVID-19; different options for work; savings and debts; challenges with family housing and transport availability. Our results show that parents experience multiple effects of pediatric COVID-19 with regard to FHRQoL.

Case Series of Multisystem Inflammatory Syndrome (MIS-C) in Children during the SARS-CoV-2 Pandemic in Latvia.

The total number of COVID-19 positive cases in Latvia has escalated rapidly since October 2020, peaking in late December 2020 and early January 2021. Children generally develop COVID-19 more mildly than adults; however, it can be complicated by multisystem inflammatory syndrome in children (MIS-C). This case study aims were to assess demographic characteristics and the underlying medical conditions, and clinical, investigative and treatment data among 13 MIS-C patients using electronic medical records. All 13 had acute illness or contact with someone who was COVID-19 positive two to six weeks before MIS-C onset. Only five of the 13 were symptomatic during the acute COVID-19 phase. The median age was 8.8 years; 11/13 patients were male, 10/13 had been previously healthy, and all 13 patients tested positive for SARS-CoV-2 by RT-PCR or antibody testing. The most commonly involved organ systems were the gastrointestinal (13/13), hematologic (13/13), cardiovascular (13/13), skin and mucosa (13/13), and respiratory (12/13) ones. The median hospital stay was 13 (interquartile range, 11 to 18) days; 7/13 patients received intensive care, 6/13 oxygen support, and 5/13 received inotropic support. No deaths occurred. During the current pandemic, every child with a fever should have a clearly defined epidemiological history of COVID-19, a careful clinical assessment of possible multiple organ-system involvement, with a special focus on children with severe abdominal pain and/or skin and mucocutaneous lesions.

Comparison of Persistent Symptoms After COVID-19 and Other Non-SARS-CoV-2 Infections in Children.

Introduction: The data on long COVID in children is scarce since children and adolescents are typically less severely affected by acute COVID-19. This study aimed to identify the long-term consequences of SARS-CoV-2 infection in children, and to compare the persistent symptom spectrum between COVID-19 and community-acquired infections of other etiologies. Methods: This was an ambidirectional cohort study conducted at the Children's Clinical University Hospital in Latvia. The study population of pediatric COVID-19 patients and children with other non-SARS-CoV-2-community-acquired infections were invited to participate between July 1, 2020, and April 30, 2021. Results: In total, 236 pediatric COVID-19 patients were enrolled in the study. Additionally, 142 comparison group patients were also enrolled. Median follow-up time from acute symptom onset was 73.5 days (IQR; 43-110 days) in the COVID-19 patient group and 69 days (IQR, 58-84 days) in the comparison group. Most pediatric COVID-19 survivors (70%, N = 152) reported at least one persistent symptom, but more than half of the patients (53%, N = 117) noted two or more long-lasting symptoms. The most commonly reported complaints among COVID-19 patients included persistent fatigue (25.2%), cognitive sequelae, such as irritability (24.3%), and mood changes (23.3%), as well as headaches (16.9%), rhinorrhea (16.1%), coughing (14.4%), and anosmia/dysgeusia (12.3%). In addition, 105 (44.5%) COVID patients had persistent symptoms after the 12-week cut-off point, with irritability (27.6%, N = 29), mood changes (26.7%, N = 28), and fatigue (19.2%, N = 20) being the most commonly reported ones. Differences in symptom spectrum among the various age groups were seen. Logistic regression analysis showed that long-term persistent symptoms as fever, fatigue, rhinorrhea, loss of taste and/or smell, headaches, cognitive sequelae, and nocturnal sweating were significantly associated with the COVID-19 experience when compared with the controls. Conclusions: We found that at the time of interview almost three-quarters of children reported at least one persistent symptom, but the majority of patients (53%) had two or more concurrent symptoms. The comparison group's inclusion in the study allowed us to identify that symptom persistence is more apparent with COVID-19 than any other non-SARS-CoV-2 infection. More research is needed to distinguish the symptoms of long COVID from pandemic-associated complaints. Each persistent symptom is important in terms of child well-being during COVID-19 recovery.

Case Series of Variable Acute Appendicitis in Children with SARS-CoV-2 Infection.

This case series study consists of six children, aged 5-16 years, admitted to a centralized tertiary paediatric hospital serving a population of 1.9 million with acute appendicitis in the setting of SARS-CoV-2 infection. From the beginning of the pandemic in March 2020 until August 2021, 121 COVID-19-positive children were admitted to the hospital. A total of 49 (40.5%) of these patients presented with gastrointestinal symptoms, of which six were diagnosed with acute appendicitis. Five underwent an appendectomy, while one was treated conservatively. To date, it has been reported that appendicitis may have a plausible association with SARS-CoV-2 infection in children. With COVID-19 cases rising, every medical specialist, including all paediatric surgeons, must be ready to treat common acute diseases with SARS-CoV-2 infection as a comorbidity. Providers should consider testing for this infection in paediatric patients with severe gastrointestinal symptoms. Non-surgical treatment of acute appendicitis in children may gain new importance during and after the COVID-19 pandemic. Further studies are needed to prove the link of causality between COVID-19 and acute appendicitis in children.