T Lymphocyte Subset Counts and Interferon-Gamma Production in Adults and Children with COVID-19: A Narrative Review.

Adults and children exhibit a broad range of clinical outcomes from SARS-CoV-2 infection, with minimal to mild symptoms, especially in the pediatric age. However, some children present with a severe hyperinflammatory post-infectious complication named multisystem inflammatory syndrome in children (MIS-C), mainly affecting previously healthy subjects. Understanding these differences is still an ongoing challenge, that can lead to new therapeutic strategies and avoid unfavorable outcomes. In this review, we discuss the different roles of T lymphocyte subsets and interferon-γ (IFN-γ) in the immune responses of adults and children. Lymphopenia can influence these responses and represent a good predictor for the outcome, as reported by most authors. The increased IFN-γ response exhibited by children could be the starting point for the activation of a broad response that leads to MIS-C, with a significantly higher risk than in adults, although a single IFN signature has not been identified. Multicenter studies with large cohorts in both age groups are still needed to study SARS-CoV-2 pathogenesis with new tools and to understand how is possible to better modulate immune responses.

Lessons from SARS-CoV-2 Pandemics: How Restrictive Measures Impacted the Trend of Respiratory Infections in Neonates and Infants up to Three Months of Age.

(1) Background: Massive social efforts to prevent the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic have affected the epidemiological features of respiratory infections. (2) Methods: The study aims to describe the trend of hospitalizations for bronchiolitis among newborns and infants up to three months of life in Rome (Italy), in the pre-COVID-19 era and during the pandemic. (3) Results: We observed a marked decrease in the number of neonates and infants with bronchiolitis after national lockdowns in 2020 and the first months of 2021 and a similar trend in the number of bronchiolitis caused by respiratory syncytial virus (RSV). RSV was the leading pathogen responsible for bronchiolitis before the national lockdown in March 2020 (70.0% of cases), while Rhinovirus was the leading pathogen responsible for bronchiolitis (62.5%) during the pandemic while strict restrictions were ongoing. As Italy approached the COVID-19 vaccination target, the national government lifted some COVID-19-related restrictions. A surprising rebound of bronchiolitis (particularly cases caused by RSV) was observed in October 2021. (4) Conclusions: In this study, we describe for the first time the fluctuations over time of RSV bronchiolitis among newborns and young infants in Italy in relation to the restrictive measures containing the spread of the COVID-19 pandemic. Our results are in line with other countries' reports.

Multisystem Inflammatory Syndrome in Neonates Born to Mothers with SARS-CoV-2 Infection (MIS-N) and in Neonates and Infants Younger Than 6 Months with Acquired COVID-19 (MIS-C): A Systematic Review.

(1) Introduction: There is an increasing literature describing neonates born to mothers with SARS-CoV-2 infection (MIS-N) and infants infected with SARS-CoV-2 who presented with a severe disease (MIS-C). (2) Methods: To investigate clinical features of multisystem inflammatory syndrome in neonates and infants under six months of age, we used a systematic search to retrieve all relevant publications in the field. We screened in PubMed, EMBASE and Scopus for data published until 10 October 2021. (3) Results: Forty-eight articles were considered, including 29 case reports, six case series and 13 cohort studies. Regarding clinical features, only 18.2% of MIS-N neonates presented with fever; differently from older children with MIS-C, in which gastrointestinal symptoms were the most common manifestation, we displayed that cardiovascular dysfunction and respiratory distress are the prevalent findings both in neonates with MIS-N and in neonates/infants with MIS-C. (4) Conclusions: We suggest that all infants with suspected inflammatory disease should undergo echocardiography, due to the possibility of myocardial dysfunction and damage to the coronary arteries observed both in neonates with MIS-N and in neonates/infants with MIS-C. Moreover, we also summarize how they were treated and provide a therapeutic algorithm to suggest best management of these fragile infants.

SARS-CoV-2 Vaccines during Pregnancy and Breastfeeding: A Systematic Review of Maternal and Neonatal Outcomes.

(1) Objective: This systematic review summarizes current knowledges about maternal and neonatal outcomes following COVID-19 vaccination during pregnancy and breastfeeding. (2) Study design: PubMed, Cochrane Library, and the Education Resources Information Center (ERIC) were searched up to 27 October 2021. The primary outcome was to estimate how many pregnant and lactating women were reported to be vaccinated and had available maternal and neonatal outcomes. (3) Results: Forty-five studies sourcing data of 74,908 pregnant women and 5098 lactating women who received COVID-19 vaccination were considered as eligible. No major side-effects were reported, especially during the second and third trimester of pregnancy and during breastfeeding. Conversely, available studies revealed that infants received specific SARS-CoV-2 antibodies after maternal vaccination. (4) Conclusions: Vaccination against the SARS-CoV-2 virus should be recommended for pregnant women, after the pros and cons have been adequately explained. In particular, given the still limited evidence and considering that fever during the first months of gestation increases the possibility of congenital anomalies, they should be carefully counseled. The same considerations apply to breastfeeding women, also considering the immune responses that mRNA vaccines can generate in their human milk.

Neonatal Cerebral Venous Thrombosis following Maternal SARS-CoV-2 Infection in Pregnancy.

A possible consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the development of an exacerbated thrombophilic status, and cerebral venous thrombosis (CVT) is a rare but possible complication of SARS-CoV-2 infection reported both in adults and in children. The present case report describes the clinical course of a term neonate showing extended CVT of unclear origin, whose mother had developed SARS-CoV-2 infection during the third trimester of pregnancy. We speculate that the prothrombotic status induced by maternal SARS-CoV-2 infection may have played a pathophysiological role in the development of such severe neonatal complication. Further investigations are required to confirm such hypothesis.

The NICU during COVID-19 Pandemic: Impact on Maternal Pediatric Medical Traumatic Stress (PMTS).

OBJECTIVE: The objective of this paper was to assess how hospital and outpatient clinic policies changes due to the coronavirus disease 2019 (COVID-19) pandemic impact pediatric medical traumatic stress (PMTS) symptoms in mothers of newborns admitted in a neonatal intensive care unit (NICU). STUDY DESIGN: Observational case-control study included the comparison between mothers of infants admitted in the NICU at birth during the COVID-19 pandemic and mothers of infants admitted in the NICU before the COVID-19 pandemic. The control group was selected matching 1:1 with the study group for the following infants' clinical variables: gender, type of pathology, gestational age, weight at birth, day of recovery, ventilator time days, and associated malformations. The Italian version of the Impact of Event Scale-Revised (IES-R) was used as a measure of PMTS. RESULT: Mothers of the study group (50) scored significantly higher than mothers of the control group on three of four scales of IES-R ("IES-R total": F = 6.70; p = 0.011; IES-R subscale "intrusion": F = 7.45; p = 0.008; IES-R subscale "avoidance": F = 8.15; p = 0.005). A significantly higher number of mothers in the study group scored above the IES-R total clinical cut-off compared with mothers of control group (72 vs. 48%; Chi2 = 6.00; p = 0.012). CONCLUSION: The COVID-19 pandemic acted as superimposed stress in mothers of newborns admitted in the NICU at birth determining high levels of PMTS. Clinicians and researchers should identify and implement novel strategies to provide family-centered care during the COVID-19 pandemic and beyond. KEY POINTS: · COVID-19 acted as superimposed stress on NICU population.. · PMTS in mothers got significantly worse during the COVID-19 pandemic.. · Alert on long-term consequences on child development..

A neonatal cluster of novel coronavirus disease 2019: clinical management and considerations.

BACKGROUND: Lately, one of the major clinical and public health issues has been represented by Coronavirus disease of 2019 (COVID-19) during pregnancy and the risk of transmission of the infection from mother to child. Debate on perinatal management and postnatal care is still ongoing, principally questioning the option of the joint management of mother and child after birth and the safety of breastfeeding. According to the available reports, neonatal COVID-19 appears to have a horizontal transmission and seems to be paucisymptomatic or asymptomatic, compared to older age groups. The aim of this work is to describe a cluster of neonatal COVID-19 and discuss our experience, with reference to current evidence on postnatal care and perinatal management. METHODS: This is a retrospective observational case series of five mother-child dyads, who attended the Labor and Delivery Unit of a first-level hospital in Italy, in March 2020. Descriptive statistics for continuous variables consisted of number of observations, mean and the range of the minimum and maximum values. RESULTS: Five women and four neonates tested positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). In one case, the mother-child dyad was separated and the neonate remained negative on two consecutive tests. Two positive neonates developed symptoms, with a predominant involvement of the gastrointestinal tract. Blood tests were unremarkable, except for a single patient who developed mild neutropenia. No complications occurred. CONCLUSIONS: We agree that the decision on whether or not to separate a positive/suspected mother from her child should be made on an individual basis, taking into account the parent's will, clinical condition, hospital logistics and the local epidemiological situation. In conformity with literature, in our study, affected neonates were asymptomatic or paucisymptomatic. Despite these reassuring findings, a few cases of severe presentation in the neonatal population have been reported. Therefore, we agree on encouraging clinicians to monitor the neonates with a suspected or confirmed infection.

Novel Coronavirus disease (COVID-19) in newborns and infants: what we know so far.

Recently, an outbreak of viral pneumonitis in Wuhan, Hubei, China successively spread as a global pandemia, led to the identification of a novel betacoronavirus species, the 2019 novel coronavirus, successively designated 2019-nCoV then SARS-CoV-2). The SARS-CoV-2 causes a clinical syndrome designated coronavirus disease 2019 (COVID19) with a spectrum of manifestations ranging from mild upper respiratory tract infection to severe pneumonitis, acute respiratory distress syndrome (ARDS) and death. Few cases have been observed in children and adolescents who seem to have a more favorable clinical course than other age groups, and even fewer in newborn babies. This review provides an overview of the knowledge on SARS-CoV-2 epidemiology, transmission, the associated clinical presentation and outcomes in newborns and infants up to 6 months of life.