Clinical outcomes and antibody transfer in a cohort of infants born to mothers with SARS-COV-2 infection during pregnancy (Coronascope Study) (preprint)

Purpose: We aimed to describe the outcomes, focusing on the hearing and neurological development, of children born to mothers with SARS-CoV-2 infection during pregnancy, and to evaluate the persistence of maternal antibodies in the first months of life. Methods:An observational, prospective study at a tertiary hospital in Madrid (Spain) on infants born to mothers infected with SARS CoV-2 during pregnancy between March and September 2020. A follow-up visit at 1-3 months of age with a physical and neurological examination, cranial ultrasound (cUS), SARS-CoV-2 RT-PCR on NPS and SARS-CoV-2 serology were performed. Hearing was evaluated at birth through the automated auditory brainstem response and at six months of age through the auditory steady-state response. A neurodevelopmental examination using the Bayley-III scale was performed at 12 months of age. Results:Of 95 infants studied, neurological examination was normal in all of them at the follow-up visit, as was the cUS in 81/85 (95%) infants, with only mild abnormalities in four of them. Serology was positive in 47/95 (50%) infants, which was not associated with symptoms or severity of maternal infection. No hearing loss was detected and neurodevelopment was normal in 96% of the children (median Z score: 0). Conclusions: In this cohort, the majority of infants born to mothers with SARS-CoV-2 infection during pregnancy were healthy children with a normal cUS, no hearing loss and normal neurodevelopment in the first year of life. Only half of the infants had a positive serological result during the follow-up.

Comparison of pneumonia features in children caused by SARS-CoV-2 and other viral respiratory pathogens. (preprint)

Pneumonia is a frequent manifestation of COVID-19 in hospitalized children. Methods The study involved 80 hospitals in the SARS-CoV-2 Spanish Pediatric National Cohort. Participants were children <18 years, hospitalized with SARS-CoV-2 community-acquired pneumonia (CAP). We compared the clinical characteristics of SARS-CoV-2-associated CAP with CAP due to other viral etiologies from 2012 to 2019. Results In total, 151 children with SARS-CoV-2-associated CAP and 138 with other viral CAP included. Main clinical features of SARS-CoV-2-associated CAP were cough 117/151(77%), fever 115/151(76%) and dyspnea 63/151(46%); 22/151(15%) patients were admitted to a pediatric intensive care unit (PICU), and 5/151(3%) patients died. Lymphopenia was found in 63/147(43%) patients. Chest X-ray revealed condensation (64/151[42%]) and other infiltrates (87/151[58%]). Compared with CAP from other viral pathogens, COVID-19 patients were older (8 vs.1 year; odds ratio [OR] 1.42 [95% confidence interval, CI 1.23;1.42]), with lower CRP levels (23 vs.48 mg/L; OR 1 [95%CI 0.99;1]), less wheezing (17 vs.53%; OR 0.18 [95%CI 0.11;0.31]) and greater need of mechanical ventilation, MV (7 vs.0.7%, OR 10.8 [95%CI 1.3;85). Patients with non-SARS-CoV-2-associated CAP had a greater need for oxygen therapy (77 vs.44%, OR 0.24 [95%CI 0.14;0.40]). There were no differences in the use of CPAP or HVF or PICU admission between groups. Conclusion SARS-CoV-2-associated CAP in children presents differently to other virus-associated CAP: children are older and rarely have wheezing or high CRP levels; they need less oxygen but more CPAP or MV. However, several features overlap, and differentiating the etiology may be difficult. The overall prognosis is good.

The Spectrum of COVID-19 in Children in Spain (preprint)

Background: We aimed to identify the spectrum of disease in children with COVID-19, and the risk factors for admission in paediatric intensive care units (PICUs). Methods: : We conducted a multicentre, prospective study of children with SARS-CoV-2 infection in 76 Spanish hospitals. We included children with COVID-19 or multi-inflammatory syndrome (MIS-C) younger than 18 years old, attended during the first year of the pandemic. Results: We enrolled 1 200 children. A total of 666 (55.5%) were hospitalized, and 123 (18.4%) required admission to PICU. Most frequent major clinical syndromes in the cohort were: mild syndrome (including upper respiratory tract infection and flu-like syndrome, skin or mucosae problems and asymptomatic), 44.8%; bronchopulmonary syndrome (including pneumonia, bronchitis and asthma flare), 18.5%; fever without a source, 16.2%; MIS-C, 10.6%; and gastrointestinal syndrome, 10%. In hospitalized children, the proportions were: 28.5%, 25.7%, 16.5%, 19.1% and 10.2%, respectively. Risk factors associated with PICU admission were MIS-C (odds ratio [OR]: 37.5,95% CI 22.7 to 57.8), moderate or severe liver disease (OR: 9,95% CI 1.6 to 47.6), chronic cardiac disease (OR: 4.8,95% CI 1.8 to 13) and asthma or recurrent wheezing (OR: 2.8,95% CI 1.3 to 5.8). However, asthmatic children were admitted into the PICU due to MIS-C or pneumonia, not due to asthma flare. Conclusion: Hospitalized children with COVID-19 usually present as one of five major clinical phenotypes of decreasing severity. Risk factors for PICU include MIS-C, elevation of inflammation biomarkers, asthma, moderate or severe liver disease and cardiac disease.

Fever without source as the first manifestation of SARS-CoV-2 infection in infants less than 90 days old. (preprint)

Fever without source (FWS) in infants is a frequent cause of consultation at the emergency department and the emergence of SARS-CoV-2 could affect the approach to those infants. The aim of this study is to define the clinical characteristics and rates of bacterial coinfections of infants < 90 days with FWS as the first manifestation of SARS-CoV-2 infection. This is a cross-sectional study of infants under 90 days of age with FWS and positive SARS-CoV2 PCR in nasopharyngeal swab/aspirate, attended at the emergency departments of 49 Spanish hospitals (EPICO-AEP cohort) from March 1st to June 26th, 2020. Three hundred and thirty-three  children with COVID-19 were included in EPICO-AEP. A total of 67/336 (20%) were infants less than 90 days old, and 27/67(40%) presented with FWS. Blood cultures were performed in 24/27(89%) and were negative in all but one (4%) who presented a Streptococcus mitis bacteremia. Urine culture was performed in 26/27(97%) children and was negative in all, except in two (7%) patients. Lumbar puncture was performed in 6/27(22%) cases, with no growth of bacteria. Two children had bacterial coinfections: 1 had UTI and bacteremia, and 1 had UTI. C-reactive was protein over 20 mg/L in two children (one with bacterial coinfection), and procalcitonin was normal in all. One child was admitted to the Pediatric Intensive Care Unit because of apnea episodes. No patients died. Conclusion: FWS was frequent in infants under 90 days of age with SARS-CoV-2 infection. Standardized markers to rule out bacterial infections remain useful in this population, and the outcome is generally good.