ABSTRACT
Background: We aimed to analyse the effects of steroids, intravenous immunoglobulin (IVIG), and their combination on the probability of discharge over time, probability of switching to second-line treatment over time, and persistent fever after 2 days of treatment. Methods: We did a retrospective study to investigate the effect of treatments (IVIG plus steroids, steroids alone or IVIG alone) of children with MIS-C in a nationwide study, from 1 March to 1 June 2021. We used a Markovian multi-state model with the clock-forward approach and unidirectional arrows to build a multi-state model. Three transitions were defined: initiation of treatment to hospital discharge (t1), initiation of treatment to second-line therapy (t2), and second-line therapy to hospital discharge (t3). A treatment was considered as second-line if initiated >2 days after the first therapy. We estimated the time-to-event probability using a Cox model weighted by the propensity score to balance the baseline characteristics. Results: 30/132 (22.7%) patients were initially treated with steroids alone, 29/132 (21.9%) with IVIG alone, and 73/132 (55%) with IVIG plus steroids. The probability of early discharge was higher with IVIG than with IVIG plus steroids (hazard ratio [HR] 1.65, 95% CI 1.11-2.45, p=0.013), but with a higher probability of needing second-line therapy versus IVIG plus steroids (HR 3.05, 95% CI 1.12-8.25, p=0.028). Patients on steroids had a lower probability of persistent fever after 2 days of treatment (odds ratio [OR] 0.55, 95% CI, 0.28-1.05, p=0.081) versus patients on IVIG plus steroids, and those on the combination had with a lower probability versus IVIG alone (OR 0.21, 95% CI, 0.09-0.46, p=0.0001). We also directly compared the IVig-and steroid-alone treatments. The probability of early discharge of the patients on steroids and on IVig were not different (HR 0·58, 95% CI 0·27-1·24, p=0·166). The probability of transition second-line therapy was also similar (HR 0·71, 95% CI 0·29-1·74, p=0·456). IVIG had a 4-fold higher probability of persistent fever after treatment initiation than steroids (OR 4·23 95% CI 1·43-13·5, p=0·011). Conclusion: IVIG seemed to increase the probability of discharge over time but increased the probability of needing second-line treatment over time. Steroids seemed to reduce persistent fever after 2 days of treatment, and combination therapy reduced the need for escalating treatment.
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Background: Testing using nasopharyngeal swabs (NPS) samples is the cornerstone for the control of the COVID-19 pandemic, but the procedure is uncomfortable and generates anxiety, especially in children. We aimed to evaluate the adequacy of oral saliva swab analysis using RT-PCR comparing to NPS by RT-PCR and Antigen Rapid Test (AgRT) on NPS in children. Methods: Cross-sectional multicenter diagnostic study nested in a prospective, observational cohort (EPICO-AEP) carried out between February and March 2021 at 10 hospitals in Spain. Participants were children 0 to 18 years old with symptoms compatible with SARS-CoV-2 infection of ≤5 days of duration attending at emergency departments. Three samples were collected, two NPS (for AgRT and for RT-PCR) and one oral saliva swab for RT-PCR. In patients with discordant results, new NPS was collected for viral culture and original samples were tested for viral RNA subgenomic (sgRNA) study. Results: 1174 children were included in the analysis, aged 3.8 years (IQR, 1.7-9.0), 647/1174 (55.1%) were male and 760/1174 (64.7%) presented fever 1 day before emergency department admission (IQR 1.0-2.0). Overall, 73/1174 (6.2%) patients tested positive in at least one of the techniques. Sensitivity for RT-PCR in oral saliva swab was 72.1% (95%CI, 59.7-81.9) and specificity 99.6% (95%CI, 99.0-99.9);AgRT in NPS was 61.8% (95%CI, 49.1-73.0) and 99.9% (95%CI, 99.4-100). Kappa index for RT-PCR oral saliva swab was 0.80 (95%CI, 0.72-0.88), and for AgRT was 0.74 (95%CI, 0.65-0.84) vs RT-PCR in NPS. A Bayesian model was used to estimate the accuracy assuming that RT-PCR in NPS is not a perfect gold standard. In this model, sensitivity for RT-PCR oral saliva swab was 84.8% (95%Cr 71.5-93.6), and for AgRT, it was 72.5% (95%Cr, 58.8-83.6). Specificity for RT-PCR oral saliva swab was 99.7% (95%Cr, 99.2-99.9), and for AgRT it was 99.9% (95% Cr, 99.6-100). The Cts were higher in oral saliva swabs compared with NPS;being Ct (NPS)=0.5 x (Ct saliva) + 4.5 (p=0.027). Overall, 4 (10.8%) patients with discordant results had a positive culture. In 3 of the 4 patients, the discordance consisted of positive result on oral saliva swab and nasopharyngeal swabs RT-PCR but negative by antigen rapid diagnostic test. No patient had (+) culture, (+)NP, (-)oral swab. Conclusion: RT-PCR on oral saliva swab is an accurate option for SARS-CoV-2 testing in children. A friendlier technique for younger patients, who must be tested very frequently, may help to increase the number of patients tested.
ABSTRACT
Background: The accuracy of rapid antigen tests (RAT) SARS-CoV-2 for in children is unknown. Our aim was to determine the diagnostic accuracy and concordance of the RAT PanBioTM (Abbott) compared to RT-PCR in nasopharyngeal smear (NPS) samples, in symptomatic pediatric population. Methods: This is a descriptive, retrospective, multicentre clinical study nested in a prospective, observational, multicenter cohort study. We included pediatric patients aged 0 to 16 years with symptoms consistent with COVID-19 of ≤5 days of evolution, attended in the Emergency Departments of the seven centers involved. A total of two consecutive NPS were obtained from each patient: one was employed to perform the RAT and the other to perform RT-PCR. Sample size for a non-inferiority study was calculated considering 80% power, for a 5% prevalence and a 90% sensitivity, using RT-PCR as the gold standard reference. A confusion matrix was displayed. Non-inferiority of sensitivity and specificity between diagnostic tests was assessed using the McNemar's test. The agreement between the two methods was calculated using Cohen's kappa index. Results: A total of 1620 patients were tested in 7 hospitals. The overall sensitivity for RAT PanBioTM was 45.4% (95%CI, 34.1-57.2), and specificity was 99.8% (95%CI, 99.4-99.9) (Figure 1). The positive predictive value (PPV) for this 4.8% prevalence was 92.5% (95%CI, 78.6-97.4). The negative predictive value was 97.3 % (95%CI, 96.8-97.8). Positive likelihood ratio (PLR) was high - 233.8 (IC 95%, 73.5-743.3), and negative likelihood ratio (NLR) was low - 0.54 (95%CI, 0.44-0.67). Conclusion: Compared to RT-PCR, the sensitivity of the RAT PanBioTM was low in children with <5 days of symptoms of COVID-19. The specificity and PLR were good, and the NLR and concordance with RT-PCR were only moderate. These results suggest that the test is very good when the result is positive, and that the test has only a limited value when the result is negative. In relation with screening and public health policy, these results should be interpreted considering also rapidness, availability and false positives ratio compared to RT-PCR or other tests.
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Background: This study aimed to identify the different syndromes presented in hospitalized children with SARS-CoV-2, to analyze if the clinical features and biomarkers confer different risk depending on the syndromes, and to create a predictive model to anticipate the probability of the need for critical care Methods: We conducted a multicenter, prospective study of children aged 0 to 18 years old with SARS-CoV-2 infection in 52 Spanish hospitals. The primary outcome was the need for critical care: defined as the combined outcome of admission into a PICU, and/or need for respiratory support beyond nasal prongs. To understand the probability of needing critical care according to the diagnostic group and for each risk factor, a Bayesian multivariable model was applied. To build a predictive model of critical care, a naïve Bayes algorithm was implemented in a web app. Results: 292 children were hospitalized from March 12th, 2020 to July 1st, 2020;Of them, 214 (73.3%) were considered to have relevant COVID-19 (r-COVID-19). Among patients with r-COVID-19, 24.2% needed critical care. Out of 214 patients, 22.4% were admitted into a pediatric intensive care unit, 41.6% required respiratory support, and 38.8% presented complications (mostly cardiological). Four patients (1.8%) died, all of them had severe comorbidities. We identified 11 primaries diagnoses and grouped them into 4 large syndromes of decreasing severity: MIS-C (17.3%), bronchopulmonary (51.4%), gastrointestinal (11.6%), and mild syndrome with complications (19.6%). In the predictive model, the predictors with higher relative importance were high C-reactive protein, anemia, lymphopenia, platelets <220 000/mm3, type of syndrome, high creatinine, and days of fever. The different risk factors increase the risk differently depending on the patient's syndrome: the more severe the syndrome, the more risk the factor confers. We developed an online risk prediction tool to quantify the risk of critical disease (https://rserver.h12o. es/pediatria/EPICOAPP/, username: user, password:0000) Conclusion: We described the spectrum of r-COVID-19 in hospitalized children, consisting of 4 large syndromes of decreasing severity: MIS-C, bronchopulmonary syndrome, gastrointestinal syndrome, and a mild syndrome with complications. The risk factors increase the risk differently depending on the syndrome. A Bayesian model was implemented in an online app to anticipate the individual risk of critical care.
ABSTRACT
Background: SARS-CoV2 infection severity during pregnancy and posible consequences for exposed newborns information is still unknown. The objective of this study is to analyse clinical and epidemiological characteristics of a SARS-CoV2 infected women during pregnancy and their newborns cohort. Methods: Multicentric observational study from the Spanish GENEO-COVID cohort (participating in RECLIP). Infected pregnant women and their newborns born from 15 March to 31 July with a 15 days follow up were included. Data regarding epidemiological, clinical, virological and immunological characteristics of the patients was collected. Results: Globally, 105 pregnant women with a median age of 34 (IQR: 29-37) years old and 107 newborns were included in the study. Median gestational age at diagnosis was 36.9 (IQR-33.4-39.2) weeks, and 6.7% os women were diagnosed in the second trimester. More than 34% of the women presented at least one comorbidity and almost 65% of women had COVID19 symptoms and 43% of them were treated for the infection. Overall, 30.8% had COVID-19 pneumonia and 4.8% were admitted to the intensive care unit (ICU) needing invasive mechanical ventilation. The rate of positive RT-PCR at delivery was 61.9%. There was a 36.2% rate of caesarean sections, associated with pneumonia during pregnancy OR:4.2 (95% CI 1.5,12.0) and lower gestational age at delivery OR:0.7 (95% CI: 0.6,0.9). Regarding newborns, 46.7% were male, 66.4% breastfed, with median Apgar 1' of 9 and Apgar 5' of 10. Almost 6% were small for gestational age and 16.8% needed admission to the neonatal ICU. Oxygen was needed by 12.1% and surfactant by 5.6% newborns. Prematurity rate was 20.6%, associated with pneumonia during gestation OR:7.0 (95% CI: 2.3,22.8) and with a positive RT-PCR at delivery OR:6.5 (95% CI: 1.8,31.8). No associations were found with age, comorbidities or blood group. No vertical transmission was reported but one newborn was horizontally infected. Two newborns died, one due to prematurity causes and another of unexpected sudden death during early skin-to-skin contact after delivery. Conclusion: Even there is no vertical transmission reported in this cohort, we found a case of horizontal transmission. SARS-CoV2 infection could produce COVID19 pneumonia during pregnancy, that increases caesarean sections and prematurity rates worsening exposed newborns prognosis. (Figure Presented).