Clinical manifestations and risk factors of shock in children with multisystem inflammatory syndrome.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a novel disease associated with COVID-19. The COVID-19 epidemic peaked in May 2022 in Taiwan, and we encountered our first case of MIS-C in late May 2022. We aimed to present patients' clinical manifestations and identify risk factors for shock. METHODS: We included patients diagnosed with MIS-C at two medical centers from May 2022 to August 2022. We separated those patients into two groups according to whether they experienced shock. We collected demographic, clinical manifestation, and laboratory data of the patients and performed statistical analysis between the two groups. RESULTS: We enrolled 28 patients, including 13 (46 %) with shock and 15 (54 %) without shock. The median age was 6.4 years (IQR: 1.9-7.5). In single variable analysis, patients with shock tended to be older, had more neurological symptoms, more conjunctivitis and strawberry tongue, lower lymphocyte count, lower platelet counts, and higher C-reactive protein, higher procalcitonin, higher ferritin, and higher D-dimer levels than those without shock. The area under the ROC curve that used procalcitonin to be the risk factor of shock with MIS-C was 0.815 (95 % CI 0.644 to 0.987). The cutoff value obtained by ROC analysis of procalcitonin was 1.68 ng/mL. With this cutoff, the test characteristics of procalcitonin were as follows: sensitivity 77 %, specificity 93 %, positive predictive value 91 %, negative predictive value 82 %. Multivariable analysis revealed that procalcitonin was the only independent risk factor of shock with MIS-C on admission (OR, 26.00, 95 % CI, 1.01-668.89). CONCLUSIONS: MIS-C patients with high initial procalcitonin levels have higher risks of experiencing shock and may need ICU admission.

Clinical characteristics of hospitalized children with community-acquired pneumonia and respiratory infections: Using machine learning approaches to support pathogen prediction at admission.

BACKGROUND: Acute respiratory infections (ARIs) are common in children. We developed machine learning models to predict pediatric ARI pathogens at admission. METHODS: We included hospitalized children with respiratory infections between 2010 and 2018. Clinical features were collected within 24 h of admission to construct models. The outcome of interest was the prediction of 6 common respiratory pathogens, including adenovirus, influenza virus types A and B, parainfluenza virus (PIV), respiratory syncytial virus (RSV), and Mycoplasma pneumoniae (MP). Model performance was estimated using area under the receiver operating characteristic curve (AUROC). Feature importance was measured using Shapley Additive exPlanation (SHAP) values. RESULTS: A total of 12,694 admissions were included. Models trained with 9 features (age, event pattern, fever, C-reactive protein, white blood cell count, platelet count, lymphocyte ratio, peak temperature, peak heart rate) achieved the best performance (AUROC: MP 0.87, 95% CI 0.83-0.90; RSV 0.84, 95% CI 0.82-0.86; adenovirus 0.81, 95% CI 0.77-0.84; influenza A 0.77, 95% CI 0.73-0.80; influenza B 0.70, 95% CI 0.65-0.75; PIV 0.73, 95% CI 0.69-0.77). Age was the most important feature to predict MP, RSV and PIV infections. Event patterns were useful for influenza virus prediction, and C-reactive protein had the highest SHAP value for adenovirus infections. CONCLUSION: We demonstrate how artificial intelligence can assist clinicians identify potential pathogens associated with pediatric ARIs upon admission. Our models provide explainable results that could help optimize the use of diagnostic testing. Integrating our models into clinical workflows may lead to improved patient outcomes and reduce unnecessary medical costs.

Circulating pediatric respiratory pathogens in Taiwan during 2020: Dynamic change under low COVID-19 incidence.

BACKGROUND: In Taiwan, there were only 799 confirmed COVID-19 cases in 2020. The unique backdrop amidst a pandemic and promotion of nonpharmaceutical interventions generated some distinct changes in the epidemiology of common respiratory pathogens. In this study, we aimed to investigate the dynamic changes in respiratory pathogens in children during 2020. METHODS: We performed a retrospective cohort study at a tertiary hospital in southern Taiwan during 2020. Patients aged 0-18 years who visited the pediatric emergency department were enrolled. Children who presented with clinical symptoms (fever or respiratory illness) and received nasopharyngeal swabs for multiplex polymerase chain reaction (PCR) were included in our analysis. We also compared respiratory syncytial virus (RSV) trends from previous years by PCR and lateral flow immunochromatographic assays from 2017 to 2020. RESULTS: A total of 120 children were tested. The overall detection rate was 55%. With strengthened restrictions, the detection rate dropped from 70% to 30%. However, non-enveloped viruses (rhinovirus/enterovirus and adenovirus) were in constant circulation. Upon easing prevention measures, the detection rate remained above 60%, and an outbreak of an enveloped virus (RSV and parainfluenza virus) was noted. Compared with 2017-2019, the cyclical RSV epidemic was delayed, with a large surge in late 2020. CONCLUSIONS: We observed a constant circulation of non-enveloped viruses when strict nonpharmaceutical interventions were employed and a delayed surge of enveloped viruses during the easing of restrictions. Continuous surveillance and monitoring of the evolutionary dynamics of respiratory viruses is important, while easing restrictions requires balanced judgment.

Adenovirus replication and host innate response in primary human airway epithelial cells.

BACKGROUND: Adenovirus infections are very common in children and sometimes fatal. Immune responses and hypercytokinemia are related to disease severity in patients with adenovirus infection. Understanding of viral replication and immune responses could help elucidate the immunopathogenesis of severe adenovirus infections. METHODS: Polarized human airway epithelial cells (hAECs) were set up to mimic human airway, and we conducted high (1 the multiplicity of infection, MOI) and low dosage (0.5 MOI) of wild-type adenovirus serotype 3 infection in hAECs from both apical (AP) and basolateral (BL) compartments, compared the viral replication kinetics and measured 25 cytokine and 9 chemokine levels by multiplex immunoassay to evaluate the host immune response. RESULTS: Virus titer was the highest in the apical compartment in low dose apical infection. BL infection showed a relative steady viral titer in different doses and infection sites. Responses of several cytokines such as IL-1RA, IL-21 and all of the chemokines were found after adenovirus infection. Besides, the responses detected in the BL compartment were generally higher than those in the apical compartment, especially IL-1RA, IL-21, GM-CSF, GRO-α, SDF-1α and IL-8. CONCLUSION: During the infections of hAECs by adenovirus, higher viral replication was found in the apical compartment but cytokine and chemokine responses were higher in the basolateral compartment. This indicated viral entrance and replication occurred more in the apical part and major innate response took place in the basolateral part, which may make adenovirus infect human airway efficiently and cause different degree of severity.

Pathogens and outcomes in pediatric septic shock patients supported by extracorporeal membrane oxygenation.

BACKGROUND: Refractory septic shock is the leading cause of mortality in children. There is limited evidence to support extracorporeal membrane oxygenation (ECMO) use in pediatric septic shock. We described the etiology and outcomes of septic patients in our institution and attempted to find predictive factors. METHODS: We retrospectively reviewed 55 pediatric patients with septic shock who required ECMO support in a tertiary medical center from 2008 to 2015. Septic shock was defined as culture proved or clinical suspected sepsis with hypotension or end-organ hypoperfusion. ECMO would be applied when pediatric advanced life support steps were performed thoroughly without clinical response. Patient's demographics, laboratory parameters before and after ECMO, and outcomes were analyzed. RESULTS: Among 55 children with ECMO support, 31% of them survived on discharge. For 25 immunocompromised patients, causal pathogens were found in 17 patients: 7 due to bacteremia, 9 with preexisting virus infections and one with invasive fungal infection. Among 30 previously healthy patients, causal pathogens were found in 18 patients: 10 due to bacteremia (the most common was pneumococcus), 7 with preexisting virus infections including influenza (n = 4), adenovirus (n = 2), RSV, and 1 patient had mixed virus and bacterial infections. Predictive factors associated with death were arterial blood gas pH, CO2 and Glasgow Coma Scale (p < 0.05). SOFA score was a valuable predictive scoring system for outcome prediction (p < 0.05). CONCLUSIONS: Pediatric patients with refractory septic shock had high mortality rate and ECMO could be used as a rescue modality, and SOFA score could be applied to predict outcomes.