Welcome to the ESPID 2022 Meeting Calendar
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LONGITUDINAL CYTOKINE ANALYSIS OF COVID-19 PREGNANT WOMEN AND THEIR INFANTS REVEALS PERSISTENTLY DYSREGULATED INFLAMMATORY RESPONSES
Abstract
Backgrounds:
COVID-19 is associated with adverse maternal outcomes and may affect infant immune development. There is a need to understand its impact on these unique populations. Our aim is to characterize the cytokine profiles in women with COVID-19 during pregnancy and their infants.
Methods
From August 2020–October 2021, pregnant women with (C19) and without COVID-19 (HC) and their infants were enrolled in a multicenter study. Blood samples were obtained at delivery, cord blood (CB), and at birth (<48 hours), 1 week, 1 month, and 2 months. Samples were analyzed using Olink inflammation panel and data with R software.
Results:
We included 36 C19 mother-infant dyads (2 infected in 1st trimester, 11 in 2nd, and 23 in 3rd) and 17 HC. Compared with HC, C19 showed increased proinflammatory cytokines (IL6, IL17A) and growth factors (CSF1); and decreased cytokines related to apoptosis, migration, and chemotaxis (CD244, CXCL5, DNER) at delivery. Longitudinal analysis of CB and infants born to C19 and age-matched HC identified 17 cytokines that were significantly different and with variable trajectories over time: IL17C, IL1a, FGF21, 4EBP1, CCL20, CXCL11, SIRT2, STAMBP, ADA were increased in C19 CB, at birth and 1 week; while IL4, VEGFA, IL18 were decreased. FGF21, VEGFA, CCL19, CCL23, LIF, ARTN, NT3 were decreased at 1 and 2 months (Figure).
Conclusions/Learning Points:
We identified significantly different cytokine profiles in C19 compared with HC. COVID-19 during pregnancy induced distinct cytokine signatures in infants that persist at least until 2 months. Infant cytokine profiles exhibited different patterns than their mothers. These observations suggest that COVID-19 during pregnancy alters immunologic profiles of women and their infants and highlights the need for longitudinal studies to determine the long-term immunologic impact in both women and their children.
LOW PARENTERAL GLUCOSE MODULATES IMMUNE-METABOLIC RESPONSES AND DECREASES SEPSIS SEVERITY IN INFECTED NEWBORN PRETERM PIGS
Abstract
Backgrounds:
Preterm infants have impaired immunity and high susceptibility to neonatal sepsis, and often rely on parenteral nutrition (PN) rich in glucose. Using preterm pigs as models, we have shown that high PN glucose caused hyperglycemia and severe sepsis following neonatal infection, whereas glucose restriction prevented sepsis but induced severe hypoglycemia. Now we aimed to examine possibilities of PN glucose levels to lower sepsis risks without inducing hypoglycemia.
Methods
In two experiments with similar setups, caesarian section-delivered preterm pigs (90% gestation) were infused with Staphylococcus epidermidis or saline and nourished with PN for 22 h. Systemic metabolic and immunological response to infection were evaluated over time. In experiment 1, animals were kept on either high (21%, 30 g/kg/d, n=25) or low (5%, 7.2 g/kg/d, n=25) glucose PN until sacrifice. In experiment 2 all animals (n=41) were started on high glucose PN and 1/3 of animals were switched to low glucose PN after 3 and 6 hours, respectively.
Results:
Experiment 1: Low parenteral glucose reduced mortality (25 vs 87%) and sepsis severity outcomes (higher blood pH, lower lactate and cytokines) while maintaining normoglycaemia. Proteomics and transcriptomics further revealed decreased inflammation and up-regulated anti-inflammatory apolipoproteins and complement proteins in blood, as well as decreased the hepatic Warburg effects (ratio of glycolysis/oxidative phosphorylation). Experiment 2: Switching from a high to a low glucose PN 3-6h post-infection did not change sepsis severity outcomes or mortality.
Conclusions/Learning Points:
Low parenteral glucose decreased systemic glycolytic activity and the severity of sepsis outcomes, but switching from high to low glucose levels 3-6h post-infection had minimal impact on the clinical or immunological responses. This suggests systemic glucose conditions at the time of infection are key in guiding the immune-metabolic responses leading to sepsis.
A SINGLE HOST BIOMARKER COULD HELP IN REDUCING UNJUSTIFIED ANTIBIOTIC TREATMENTS IN HOSPITALIZED NEONATES
Abstract
Backgrounds:
Late-onset neonatal sepsis (LOS) is frequently observed in Neonatal Intensive Care Units (NICUs) and potentially severe. Despite its high prevalence, diagnostic remains difficult. Biological markers (CRP and PCT) had low performance at LOS onset. Blood culture results are too late and lack sensitivity. These difficulties lead to antibiotic overuse in hospitalized newborns, resulting in an increased antibiotic resistance, microbiota modification, neonatal complications. Our aim was to identify a biomarker combination to early exclude the diagnosis of LOS in newborn with suggestive clinical signs.
Methods
We conducted a prospective, multicenter cohort study (EMERAUDE) (NCT03299751). Hospitalized preterm neonates of at least 7 days with signs of suspected LOS were enrolled. Serum samples were collected at the time of the venipuncture prescribed for standard care. We assessed the performance of 11 protein markers using Simple PlexTM technology (Protein simple©, CA, USA). An adjudication committee, assigned each patient to one category among “confirmed infection”, “infirmed infection” or “undetermined infection”.
Results:
234 patients were enrolled and 230 had analyzable samples. The patients were mainly preterm (80%) with a median gestational age of 27 weeks, a median birth weight of 940 grams. 22% had a confirmed infection and all of them received antibiotics. Among the infirmed infection group, 27% received antibiotics. Among all analysed biomarkers IL10 had the best performance, with an area under the curve [IC95%] of 0.845[0.777-0.914]. Using optimal threshold value, we highlighted that more than a half of unjustified antibiotics in non-infected neonates could be avoided.
Conclusions/Learning Points:
At the onset of clinical suspicion of LOS, additional biomarkers could help the clinician in its choice of prescribing or not antibiotics. Validation studies will be performed to assess the interest of IL10 biomarker in a clinical decision rule.
A REVIEW OF LUMBAR PUNCTURES PERFORMED FOR EARLY ONSET NEONATAL SEPSIS IN NEONATES OF 35 WEEKS GESTATION OR GREATER IN A TERTIARY NEONATAL UNIT BETWEEN 2016 AND 2020
Abstract
Backgrounds:
Early onset sepsis (EOS) is a diagnostically challenging clinical concern in neonatology. We sought to ascertain the incidence of EOS in our unit, and to examine the role of lumbar puncture (LP) in EOS evaluation, including the use of CRP as an indication.
Methods
A retrospective electronic chart review of neonates who were born in CUMH at greater than 35 weeks gestational age from 01/01/2016-31/12/2020 who underwent a LP due to concern for EOS. Neonates were identified based on electronic chart pharmacy records of receiving 3+ days of IV benzylpenicilin or cefotaxime, correlated with laboratory reports for LP.
Results:
676 neonates were treated for greater than 3 days with intravenous antibiotics due to concern for EOS (23/1000). 205 LPs were undertaken (7/1000). In 41 cases (20%) CSF was either not obtained, or was too bloodstained for microscopy. 18 neonates had proven bacteraemia (0.62/1000). There were 6 cases of culture/PCR negative CSF with a high cell count concerning for ventriculitis and 1 case of culture positive group B streptococcus meningitis in the setting of bacteraemia with the same organism. The incidence of confirmed or suspected bacterial meningitis was 0.24/1000.
Conclusions/Learning Points:
In neonates without bacteraemia or signs of meningism, none had suspected or confirmed bacterial meningitis with a pre-LP CRP less than 45 or a maximum CRP less than 50. The relative rarity of neonatal meningitis precludes definitive threshold definition by this study. However using higher CRP thresholds of 40 versus 20 in neonates without other indications for LP in this cohort would have prevented 34 LPs without missing a case of ventriculitis/meningitis. A sizable cohort (20%) in whom LP was felt indicated had failed or entirely bloodstained CSF collection, challenging diagnosis.
COMPARISON OF HUMAN CYTOMEGALOVIRUS (HCMV)-ENZYME-LINKED IMMUNE ABSORBENT SPOT (ELISPOT) AND CMV-QUANTIFERON CELL-MEDIATED IMMUNE ASSAY SERIAL MEASUREMENTS, IN HCMV-SEROPOSITIVE PREGNANT WOMEN IN SOUTH LONDON, ENGLAND
Abstract
Backgrounds:
HCMV-specific cell-mediated immunity (CMI) is essential in the control of viral replication to prevent end-organ HCMV disease. HCMV-specific interferon gamma release assays, such as HCMV-ELISPOT and HCMV-QuantiFERON, have been used to measure HCMV-specific CMI. In pregnant women, the role of HCMV-specific CMI in controlling viral replication and transmission to the foetus have not been fully investigated. We aimed to perform serial HCMV-ELISPOT and HCMV-QuantiFERON measurements in HCMV-seropositive women during pregnancy.
Methods
HCMV-seropositive pregnant women receiving antenatal care at a tertiary hospital in London (UK) were enrolled. Blood samples were collected at three time-points in pregnancy and a fourth time-point after delivery, and HCMV-ELISPOT and HCMV-QuantiFERON assays were performed on these samples. HCMV-ELISPOT was recorded as responsive or non-responsive, as a spot count, and as specific spot counts to IE-1 and pp65 antigens. HCMV-QuantiFERON was recorded as positive or negative.
Results:
From 67 HCMV-seropositive pregnant women, 105 blood samples were tested with both assays. All women had a responsive HCMV-ELISPOT result on at least one time-point, and 70% (47/67) of women had a positive HCMV-QuantiFERON result on at least one time-point. The two assays showed no overall agreement (Cohen’s Kappa 0.032), although the overall mean HCMV-ELISPOT spot counts to IE-1 and pp65 antigens were higher when HCMV-QuantiFERON was positive than when it was negative (Figure 1).
Conclusions/Learning Points:
In this cohort, the HCMV-ELISPOT assay was more likely than the HCMV-QuantiFERON assay to detect HCMV-specific CMI in HCMV-seropositive pregnant women. This may have implications for optimal CMI monitoring in this important population.
HERPES SIMPLEX VIRUS IN INFANTS UNDER 90 DAYS OF AGE: INTERIM RESULTS OF THE 2019-2021 BRITISH PAEDIATRIC SURVEILLANCE UNIT (BPSU) STUDY
Abstract
Backgrounds:
Neonatal herpes simplex virus (HSV) infection is a rare but dangerous condition. A recent study suggests that the UK incidence may have increased since the last national surveillance study in 2007. Rising numbers of cases may support the wider use of empirical treatment. Postnatal transmission is thought to account for ~10% of cases. More information about this disease is required to inform future prevention and treatment strategies.
Methods
Analysis of questionnaires completed for the current British Paediatric Surveillance Unit neonatal HSV study was conducted. Semi-anonymised patient identifiers allow removal of duplicate cases. The study was extended from 25 months to 30 months to capture additional data on changing trends during the COVID-19 pandemic. Interim results are reported here.
Results:
228 cases were notified July 19 - Dec 2021. 159 questionnaires were completed and basic data on 111 cases was available after duplications and incomplete records were removed. 29.7% were premature, 26.1% died. Full data analysed on the first 80 cases (July 19-April 21) show: 27.0% were premature, 26.9% had disseminated disease and mortality was 71.0% in disseminated disease. 23.8% of babies with disseminated disease had no fever at presentation. Treatment was delayed by more than one day in 60%. Case notifications reduced during UK lockdown periods.
Conclusions/Learning Points:
UK incidence of neonatal HSV disease has increased since the last BPSU study. Mortality remains high and presenting features are non-specific. Absence of fever at presentation demonstrates that HSV should not only be considered in febrile infants. Falling numbers of reported cases during periods of social distancing and strict public hygiene measures may highlight the importance of postnatal transmission. Follow-up focusing on disease recurrence and long-term complications at 12 and 24 months is ongoing.