Integrated plasma proteomic and single-cell immune signaling network signatures demarcate mild, moderate, and severe COVID-19

The biological determinants of the wide spectrum of COVID-19 clinical manifestations are not fully understood. Here, over 1400 plasma proteins and 2600 single-cell immune features comprising cell phenotype, basal signaling activity, and signaling responses to inflammatory ligands were assessed in peripheral blood from patients with mild, moderate, and severe COVID-19, at the time of diagnosis. Using an integrated computational approach to analyze the combined plasma and single-cell proteomic data, we identified and independently validated a multivariate model classifying COVID-19 severity (multi-class AUCtraining = 0.799, p-value = 4.2e-6; multi-class AUCvalidation = 0.773, p-value = 7.7e-6). Features of this high-dimensional model recapitulated recent COVID-19 related observations of immune perturbations, and revealed novel biological signatures of severity, including the mobilization of elements of the renin-angiotensin system and primary hemostasis, as well as dysregulation of JAK/STAT, MAPK/mTOR, and NF-{kappa}B immune signaling networks. These results provide a set of early determinants of COVID-19 severity that may point to therapeutic targets for the prevention of COVID-19 progression. SummaryFeyaerts et al. demonstrate that an integrated analysis of plasma and single-cell proteomics differentiates COVID-19 severity and reveals severity-specific biological signatures associated with the dysregulation of the JAK/STAT, MAPK/mTOR, and NF-{kappa}B immune signaling networks and the mobilization of the renin-angiotensin and hemostasis systems.

Recommendation for hygiene and topical in neonatology from the French Neonatal Society.

We sought to establish guidelines for hygiene care in newborns based on a systematic review of the literature and grading of evidence using the Groupe de Réflexion et d'Evaluation de l'Environement des Nouveau-nés (GREEN) methodology. We examined 45 articles and 4 reports from safety agencies. These studies recommend a tub bath (rather than a sponge bath) for full-term infants and a swaddle bath for preterm newborns. They also recommend against daily cleansing of preterm infants. The literature emphasized that hygiene care must consider the clinical state of the newborn, including the level of awareness and behavioral responses. Hospitalized newborns treated with topical agents may also experience high exposure to potentially harmful excipients of interest. Caregivers should therefore be aware of the excipients present in the different products they use. In high-resource countries, the available data do not support the use of protective topical agents for preterm infants.Conclusions: We recommend individualization of hygiene care for newborns. There is increasing concern regarding the safety of excipients in topical agents that are used in neonatology. A multidisciplinary approach should be used to identify an approach that requires lower levels of excipients and alternative excipients. What is known: • Hygiene care is one of the most basic and widespread types of care received by healthy and sick newborns worldwide. • There is no current guideline on hygiene for preterm or hospitalized term newborn. What is new: • The French Group of Reflection and Evaluation of the environment of Newborns (GREEN) provided here guidelines based on the current body of evidence. • Caregivers should be aware of the many issues related to hygiene care of newborns including newborns' behavioral responses to hygiene care, exposition to excipients of interest, and the potential risk of protective topical agents in a preterm infant. provided here guidelines based on the current body of evidence. • Caregivers should be aware of the many issues related to hygiene care of newborns including newborns' possible behavioral responses to hygiene care, exposition to excipients of interest and the potential risk of protective topical agents in a preterm infant.

Father's role in supporting breastfeeding of preterm infants in the neonatal intensive care unit: a qualitative study.

OBJECTIVE: To analyse the social beliefs, representations and experiences of fathers of preterm newborns (NBs) regarding breastfeeding. DESIGN: A qualitative interview study with analysis of transcripts using the Alceste software. SETTING: A tertiary university hospital neonatal intensive care unit (NICU) in France. PARTICIPANTS: 20 fathers of preterm NBs hospitalised in an NICU. RESULTS: The software classified 72% of the corpus into six lexical classes. Two main networks of classes emerged from the analysis: one for lactation, consisted of 'breastfeeding' and 'expression of milk' classes, and one for 'care'. The analysis demonstrated that fathers were sensitive to arguments related to the health benefits of human milk. Fathers mentioned that breastfeeding preterm NBs was constraining and tiring for their partners (multiple daily sessions of milk expression with breast pumps, time constraints and need for supplements to tube-feeding…). They also mentioned how they could genuinely help their partners during breastfeeding. CONCLUSIONS: The results of this qualitative study provide insight into how fathers can be supportive of breastfeeding when experiencing a preterm birth. Targeted information and practical advice provided by caregivers on the first days of life can help fathers to get involved in the breastfeeding process.

[Family-centered rounds in hospital settings]. / Visite médicale centrée sur la famille en pédiatrie hospitalière.

Family-centered care is an approach to the planning, delivery, and evaluation of healthcare based on partnership between parents and professionals. Family-centered rounds (FCRs) are a practical application in hospital settings. They are multidisciplinary rounds with active participation of the parents in the decision-making process. FCRs appear to have a positive impact on parents' satisfaction, information provision, and comprehension of care plans. Three concerns have been underlined: time management, confidentiality, and teaching students. FCR implementation is a process that requires in-depth thinking on the philosophy of care, staff information and training, and a specific organizational change.

Accidental out-of-hospital deliveries: a case-control study.

AIM: To determine risk factors for accidental out-of-hospital deliveries (OHDs), which represent 0.5% of live births in France and are associated with poor neonatal outcomes. METHODS: This retrospective case-control study assessed accidental OHDs that occurred in the Finistère District (Brittany, France) between January 2007 and December 2009. For each OHD case, two controls were randomly selected. Outcome measures included maternal demographics, obstetric characteristics and neonatal outcomes. RESULTS: During the study period, accidental OHDs accounted for 0.42% of all births; 76 accidental OHDs were included in the analysis. Multivariate analysis found four independent risk factors for accidental OHD: multiparity [OR: 8.84 (3.22-24.29)], unemployment [OR: 4.99 (1.85-13.47)], lack of or poor antenatal care [OR: 9.00 (2.41-33.72)] and a travel time >45 min from home to the delivery unit [OR: 6.18 (1.33-28.65) versus < 15 min]. Significantly more newborns from the OHD group required admission to the neonatal unit (p = 0.04), but accidental OHD was not significantly associated with prematurity or low birth weight. CONCLUSION: Four risk factors for accidental OHD were identified. Setting up an anonymous registry of OHD cases could improve our knowledge and screening of women at risk.

[Breastfeeding in a population of preterm infants: a prospective study in a university-affiliated hospital]. / Allaitement maternel du nouveau-né prématuré : évaluation prospective dans une maternité universitaire.

AIMS: To evaluate mothers' breastfeeding intention at birth and the breastfeeding rate at hospital discharge and at 3 months of life in a population of preterm infants. To study the relation between gestational age and the breastfeeding rate at birth. To analyze sociodemographic and neonatal factors that could influence breastfeeding rate. METHODS: We present a prospective study concerning preterm infants born between November 1st 2006 and April 20th 2007 at Brest University Hospital. Exclusion criteria were: death during hospitalization and neurological or digestive diseases not allowing enteral feeding. The following data were extracted from medical charts: birth weight, gestational age, medical care in the neonatal period, delivery circumstances, and feeding mode at hospital discharge. Mothers were asked their sociodemographic status and their intention to breastfeed. Parents were contacted 3 months later to determine the feeding mode at that time. Risk factors were studied for single births through univariate and multivariate analysis. RESULTS: We recruited 149 mother-infant dyads. There were 9 lost to follow-up at 3 months. Breastfeeding rates were: 69.13% (range: 61.7-76.5) at birth, 57.82% (range: 49.8-65.8) at hospital discharge, and 33.57% (range: 25.9-41.7) at 3 months. There was an inverse relation between breastfeeding rate and gestational age: OR=0.07 (0; 0.50). Other factors significantly associated with a high breastfeeding rate were: mother's high level of education: OR=3.19 (1.39; 7.33) and low birth weight: OR=0.20 (0.08; 0.53). CONCLUSION: Our breastfeeding rates are lower than recommended by WHO. Mothers of late preterm infants or with a low socioeconomic status should benefit from supportive care.

State of the art and recommendations. Kangaroo mother care: application in a high-tech environment.

UNLABELLED: Since Kangaroo Mother Care (KMC) was developed in Colombia in the 1970s, two trends in clinical application emerged. In low income settings, the original KMC model is implemented. This consists of continuous (24 h/day, 7 days/week) and prolonged mother/parent-infant skin-to-skin contact; early discharge with the infant in the kangaroo position; (ideally) exclusive breastfeeding; and, adequate follow-up. In affluent settings, intermittent KMC with sessions of one or a few hours skin-to-skin contact for a limited period is common. As a result of the increasing evidence of the benefits of KMC for both infants and families in all intensive care settings, KMC in a high-tech environment was chosen as the topic for the first European Conference on KMC, and the clinical implementation of the KMC model in all types of settings was discussed at the 7th International Workshop on KMC. Kangaroo Mother Care protocols in high-tech Neonatal Intensive Care Units (NICU) should specify criteria for initiation, kangaroo position, transfer to/from KMC, transport in kangaroo position, kangaroo nutrition, parents' role, modification of the NICU environment, performance of care in KMC, and KMC in case of infant instability. CONCLUSION: Implementation of the original KMC method, with continuous skin-to-skin contact whenever possible, is recommended for application in high-tech environments, although scientific evaluation should continue.

Towards universal Kangaroo Mother Care: recommendations and report from the First European conference and Seventh International Workshop on Kangaroo Mother Care.

UNLABELLED: The hallmark of Kangaroo Mother Care (KMC) is the kangaroo position: the infant is cared for skin-to-skin vertically between the mother's breasts and below her clothes, 24 h/day, with father/substitute(s) participating as KMC providers. Intermittent KMC (for short periods once or a few times per day, for a variable number of days) is commonly employed in high-tech neonatal intensive care units. These two modalities should be regarded as a progressive adaptation of the mother-infant dyad, ideally towards continuous KMC, starting gradually and progressively with intermittent KMC. The other components in KMC are exclusive breastfeeding (ideally) and early discharge in kangaroo position with strict follow-up. Current evidence allows the following general statements about KMC in affluent and low-income settings: KMC enhances bonding and attachment; reduces maternal postpartum depression symptoms; enhances infant physiologic stability and reduces pain, increases parental sensitivity to infant cues; contributes to the establishment and longer duration of breastfeeding and has positive effects on infant development and infant/parent interaction. Therefore, intrapartum and postnatal care in all types of settings should adhere to a paradigm of nonseparation of infants and their mothers/families. Preterm/low-birth-weight infants should be regarded as extero-gestational foetuses needing skin-to-skin contact to promote maturation. CONCLUSION: Kangaroo Mother Care should begin as soon as possible after birth, be applied as continuous skin-to-skin contact to the extent that this is possible and appropriate and continue for as long as appropriate.

State of the art and recommendations. Kangaroo mother care: application in a high-tech environment.

UNLABELLED: Since Kangaroo Mother Care (KMC) was developed in Colombia in the 1970s, two trends in clinical application emerged. In low-income settings, the original KMC modelis implemented. This consists of continuous (24 h/day; 7 days/week) and prolonged mother/parent-infant skin-to-skin contact; early discharge with the infant in the kangaroo position; (ideally) exclusive breastfeeding and, adequate follow up. In affluent settings, intermittent KMC with sessions of one or a few hours skin-to-skin contact for a limited period is common. As a result of the increasing evidence of the benefits of KMC for both infants and families in all intensive care settings, KMC in a high-tech environment was chosen as the topic for the first European Conference on KMC, and the clinical implementation of the KMC modelin all types of settings was discussed at the 7th International Workshop on KMC Kangaroo Mother Care protocols in high-tech Neonatal Intensive Care Units (NICU) should specify criteria for initiation, kangaroo position, transfer to/from KMC, transport in kangaroo position, kangaroo nutrition, parents'role, modification of the NICU environment, performance of care in KMC, and KMCin case of infant instability. CONCLUSION: Implementation of the original KMC method, with continuous skin-to-skin contact whenever possible, is recommended for application in high-tech environments, although scientific evaluation should continue.

Materno-fetal transmission of human coronaviruses: a prospective pilot study.

This prospective pilot study investigates the possibility of materno-fetal transmission of human coronaviruses (HCoV) responsible for cases of neonatal infection. This vertical transmission was studied with 159 samples from mother-child couples: maternal vaginal (MV) and respiratory (MR) samples during labor; and newborn gastric sample (NG) with detection of HCoV (229E, OC-43, NL-63, HKU1) via real time RT PCR. HCoV was detected in 12 samples (229E: 11; HKU1: 1) from seven mother-child couples. For three couples, only MR tested positive (cases 1-3). For two other couples all three samples (MV, MR and NG) tested positive (cases 4 and 5). For case 6, only MV and NG tested positive. In case 7, only MV was positive. Possible vertical transmission of HCoV was hypothesized in this pilot study and requires further investigation on a larger scale.

[Research, developmental care and NIDCAP: specific methodological issues]. / Recherche clinique, soins de développement et NIDCAP: aspects méthodologiques spécifiques.

Developmental care is the use of a range of medical and nursing interventions to decrease the stress of preterm neonates in neonatal intensive care units. Interventions may be integrated into an individualized approach known as the Neonatal Individualized Developmental Care and Assessment Programme (NIDCAP). In comparison with drug trials, it is more difficult to achieve a standard experimental design in this kind of study as the experiments may include several individual approaches. Randomized control trials must remain a predominant practice but use of other methodologies can help to evaluate the benefits of developmental care and offer a better understanding of the impact of this kind of care : qualitative research, benchmarking or animal studies.

[Vertical transmission of human coronavirus. Prospective pilot study]. / Transmission maternofoetale des coronavirus humains. Etude prospective pilote.

UNLABELLED: Human coronaviruses (HCoV) have been implicated in neonatal nosocomial respiratory infection. Prior to our study, several cases of neonatal infection were observed in infants born at our hospital. This prospective pilot monocentric pilot study investigates the possibility of maternofetal transmission of HCoV responsible for cases of neonatal infection observed within the first 24 hours of life. MATERIALS AND METHODS: Three samples from mother-child couples, maternal vaginal (VM) and respiratory (RM) samples during labor; newborn gastric sample (GNN), were assessed for viral analysis using real time RT-PCR for the detection of HCoV 229-E and OC43. Clinical follow-up of infants and mothers was up to Day 3 after birth. RESULTS: One hundred (and) fifty-nine mother-child couples were included between July 2003 and August 2005. HCoV 229-E only was detected in 11 samples from 6 mother-child couples. For 2 couples, all 3 samples (VM, RM and GNN) were tested positive (cases 1 and 2). For case 3, both VM and GNN were positive. For 2 couples, only RM was positive (cases 4 and 5). In case 6, only VM was positive. Of the 3 positive GNN, no infant was symptomatic. CONCLUSION: Possible vertical transmission of HCoV was evidenced in this pilot study and requires further investigation on a larger scale. Equally indicated is the inclusion of tests to detect recently identified human coronaviruses HCoV NL63 and HKU1, as well as genomic profile analysis of HCoV 229-E detected in the 3 positive mother-child couples.

Sleep in the neonatal intensive care unit.

Recent experimental data suggest a strong role for sleep in brain development. As sleep is the predominant behavioral state in the term and especially the preterm newborn, these data underline the importance of respecting sleep duration and organization within the different sleep states. Polysomnography is the preferred technique used for identification of sleep state; however, behavioral observations-under the condition that the observer is well trained-may prove as efficient. Newborns hospitalized in the neonatal intensive care unit are exposed to many stimuli and care activities that disrupt their sleep organization and may have irreversible effects on their brain development. In order to improve the long-term neurobehavioral outcome of these high-risk subjects, a consistent care approach is proposed. Application of the Neonatal Individualized Developmental Care and Assessment Program decreases environmental stressful events and promotes harmonious well-being behaviors, based on an individual approach. This strategy has encouraging results, showing an increase in sleep duration under Neonatal Individualized Developmental Care and Assessment Program conditions, but further studies are needed to assess its long-term neurobehavioral impact.