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1.
Diagnostics (Basel) ; 12(5)2022 May 07.
Article in English | MEDLINE | ID: covidwho-1862746

ABSTRACT

COVID-19 (COronaVIrus Disease 19) is an infectious disease also known as an acute respiratory syndrome caused by the SARS-CoV-2. Although in children and adolescents SARS-CoV-2 infection produces mostly mild or moderate symptoms, in a certain percentage of recovered young people a condition of malaise, defined as long-COVID-19, remains. To date, the risk factors for the development of long-COVID-19 are not completely elucidated. Neurotrophins such as NGF (Nerve Growth Factor) and BDNF (Brain-Derived Neurotrophic Factor) are known to regulate not only neuronal growth, survival and plasticity, but also to influence cardiovascular, immune, and endocrine systems in physiological and/or pathological conditions; to date only a few papers have discussed their potential role in COVID-19. In the present pilot study, we aimed to identify NGF and BDNF changes in the serum of a small cohort of male and female adolescents that contracted the infection during the second wave of the pandemic (between September and October 2020), notably in the absence of available vaccines. Blood withdrawal was carried out when the recruited adolescents tested negative for the SARS-CoV-2 ("post-infected COVID-19"), 30 to 35 days after the last molecular test. According to their COVID-19 related outcomes, the recruited individuals were divided into three groups: asymptomatics, acute symptomatics and symptomatics that over time developed long-COVID-19 symptoms ("future long-COVID-19"). As a control group, we analyzed the serum of age-matched healthy controls that did not contract the infection. Inflammatory biomarkers (TNF-α, TGF-ß), MCP-1, IL-1α, IL-2, IL-6, IL-10, IL-12) were also analyzed with the free oxygen radicals' presence as an oxidative stress index. We showed that NGF serum content was lower in post-infected-COVID-19 individuals when compared to healthy controls; BDNF levels were found to be higher compared to healthy individuals only in post-infected-COVID-19 symptomatic and future long-COVID-19 girls, leaving the BDNF levels unchanged in asymptomatic individuals if compared to controls. Oxidative stress and inflammatory biomarkers were unchanged in male and female adolescents, except for TGF-ß that, similarly to BDNF, was higher in post-infected-COVID-19 symptomatic and future long-COVID-19 girls. We predicted that NGF and/or BDNF could be used as early biomarkers of COVID-19 morbidity in adolescents.

2.
Clin Infect Dis ; 2022 May 10.
Article in English | MEDLINE | ID: covidwho-1831061

ABSTRACT

BACKGROUND: SARS-CoV-2 infection has been associated with adverse maternal and neonatal outcomes, yet uptake of SARS-CoV-2 vaccines during pregnancy and lactation has been slow. As a result, millions of pregnant and lactating women and their infants remain susceptible to the virus. METHODS: We measured Spike-specific immunoglobulin G (anti-S IgG) and A (anti-S IgA) in serum and breastmilk (BM) samples from 3 prospective mother-infant cohorts recruited in two academic medical centers. The primary aim was to determine the impact of maternal SARS-CoV-2 immunization vs infection and their timing on systemic and mucosal immunity. RESULTS: The study included 28 mothers infected with SARS-CoV-2 in late pregnancy (INF), 11 uninfected mothers who received 2 doses of the BNT162b2 vaccine in the latter half of pregnancy (VAX-P) and 12 uninfected mothers who received 2 doses of BNT162b2 during lactation (VAX-L). VAX dyads had significantly higher serum anti-S IgG compared to INF dyads (p < .0001), while INF mothers had higher BM: serum anti-S IgA ratios compared to VAX mothers (p = .0001). Median IgG placental transfer ratios were significantly higher in VAX-P compared to INF mothers (p < 0.0001). There was a significant positive correlation between maternal and neonatal serum anti-S IgG after vaccination (r = 0.68, p = 0.013), but not infection. CONCLUSIONS: BNT161b2 vaccination in late pregnancy or lactation enhances systemic immunity through serum anti-S Ig, while SARS-CoV-2 infection induces mucosal over systemic immunity more efficiently through BM Ig production. Next generation vaccines boosting mucosal immunity could provide additional protection to the mother-infant dyad. Future studies should focus on identifying the optimal timing of primary and/or booster maternal vaccination for maximal benefit.

3.
Front Pediatr ; 9: 701722, 2021.
Article in English | MEDLINE | ID: covidwho-1551524

ABSTRACT

Neonatal SARS-CoV-2 infection can occur antenatally, peripartum, or postnatally. In the newborn, clinical manifestations may vary including fever and respiratory, gastrointestinal and neurological symptoms. Most commonly, they are subclinical. We herein present a case of vertical transmission of SARS-CoV-2 presenting with liver injury, characterized by an increase in serum transaminases.

4.
JAMA Netw Open ; 4(11): e2132563, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1499193

ABSTRACT

Importance: Although several studies have provided information on short-term clinical outcomes in children with perinatal exposure to SARS-CoV-2, data on the immune response in the first months of life among newborns exposed to the virus in utero are lacking. Objective: To characterize systemic and mucosal antibody production during the first 2 months of life among infants who were born to mothers infected with SARS-CoV-2. Design, Setting, and Participants: This prospective cohort study enrolled 28 pregnant women who tested positive for SARS-CoV-2 infection and who gave birth at Policlinico Umberto I in Rome, Italy, from November 2020 to May 2021, and their newborns. Maternal and neonatal systemic immune responses were investigated by detecting spike-specific antibodies in serum, and the mucosal immune response was assessed by measuring specific antibodies in maternal breastmilk and infant saliva 48 hours after delivery and 2 months later. Exposures: Maternal infection with SARS-CoV-2 in late pregnancy. Main Outcomes and Measures: The systemic immune response was evaluated by the detection of SARS-CoV-2 IgG and IgA antibodies and receptor binding domain-specific IgM antibodies in maternal and neonatal serum. The mucosal immune response was assessed by measuring spike-specific antibodies in breastmilk and in infant saliva, and the presence of antigen-antibody spike IgA immune complexes was investigated in breastmilk samples. All antibodies were detected using an enzyme-linked immunosorbent assay. Results: In total, 28 mother-infant dyads (mean [SD] maternal age, 31.8 [6.4] years; mean [SD] gestational age, 38.1 [2.3] weeks; 18 [60%] male infants) were enrolled at delivery, and 21 dyads completed the study at 2 months' follow-up. Because maternal infection was recent in all cases, transplacental transfer of virus spike-specific IgG antibodies occurred in only 1 infant. One case of potential vertical transmission and 1 case of horizontal infection were observed. Virus spike protein-specific salivary IgA antibodies were significantly increased (P = .01) in infants fed breastmilk (0.99 arbitrary units [AU]; IQR, 0.39-1.68 AU) vs infants fed an exclusive formula diet (0.16 AU; IQR, 0.02-0.83 AU). Maternal milk contained IgA spike immune complexes at 48 hours (0.53 AU; IQR, 0.25-0.39 AU) and at 2 months (0.09 AU; IQR, 0.03-0.17 AU) and may have functioned as specific stimuli for the infant mucosal immune response. Conclusions and Relevance: In this cohort study, SARS-CoV-2 spike-specific IgA antibodies were detected in infant saliva, which may partly explain why newborns are resistant to SARS-CoV-2 infection. Mothers infected in the peripartum period appear to not only passively protect the newborn via breastmilk secretory IgA but also actively stimulate and train the neonatal immune system via breastmilk immune complexes.


Subject(s)
COVID-19/immunology , Immunoglobulin A/immunology , Milk, Human/immunology , Pregnancy Complications, Infectious/immunology , Adult , COVID-19/blood , COVID-19/transmission , COVID-19 Serological Testing , Female , Humans , Immunoglobulin A/isolation & purification , Immunoglobulin G/immunology , Immunoglobulin G/isolation & purification , Infant , Infant, Newborn , Infectious Disease Transmission, Vertical/prevention & control , Male , Pregnancy , Pregnancy Complications, Infectious/blood , Prospective Studies , SARS-CoV-2 , Saliva/immunology , Spike Glycoprotein, Coronavirus/immunology
5.
Front Pediatr ; 9: 638871, 2021.
Article in English | MEDLINE | ID: covidwho-1457675

ABSTRACT

With birth, the newborn is transferred from a quasi-sterile environment to the outside world. At this time, the neonatal immune system is inexperienced and continuously subject to a process of development as it encounters different antigenic stimuli after birth. It is initially characterized by a bias toward T helper 2 phenotype, reduced T helper 1, and cytotoxic responses to microbial stimuli, low levels of memory, and effector T and B cells and a high production of suppressive T regulatory cells. The aim of this setting, during fetal life, is to maintain an anti-inflammatory state and immune-tolerance. Maternal antibodies are transferred during pregnancy through the placenta and, in the first weeks of life of the newborn, they represent a powerful tool for protection. Thus, optimization of vaccination in pregnancy represents an important strategy to reduce the burden of neonatal infections and sepsis. Beneficial effects of maternal immunization are universally recognized, although the optimal timing of vaccination in pregnancy remains to be defined. Interestingly, the dynamic exchange that takes place at the fetal-maternal interface allows the transfer not only of antibodies, but also of maternal antigen presenting cells, probably in order to stimulate the developing fetal immune system in a harmless way. There are still controversial effects related to maternal immunization including the so called "immunology blunting," i.e., a dampened antibody production following infant's vaccination in those infants who received placentally transferred maternal immunity. However, clinical relevance of this phenomenon is still not clear. This review will provide an overview of the evolution of the immune system in early life and discuss the benefits of maternal vaccination. Current maternal vaccination policies and their rationale will be summarized on the road to promising approaches to enhance immunity in the neonate.

6.
Front Immunol ; 12: 690534, 2021.
Article in English | MEDLINE | ID: covidwho-1348488

ABSTRACT

High quality medical assistance and preventive strategies, including pursuing a healthy lifestyle, result in a progressively growing percentage of older people. The population and workforce is aging in all countries of the world. It is widely recognized that older individuals show an increased susceptibility to infections and a reduced response to vaccination suggesting that the aged immune system is less able to react and consequently protect the organism. The SARS-CoV-2 pandemic is dramatically showing us that the organism reacts to novel pathogens in an age-dependent manner. The decline of the immune system observed in aging remains unclear. We aimed to understand the role of B cells. We analyzed peripheral blood from children (4-18 years); young people (23-60 years) and elderly people (65-91 years) by flow cytometry. We also measured antibody secretion by ELISA following a T-independent stimulation. Here we show that the elderly have a significant reduction of CD27dull memory B cells, a population that bridges innate and adaptive immune functions. In older people, memory B cells are mostly high specialized antigen-selected CD27bright. Moreover, after in vitro stimulation with CpG, B cells from older individuals produced significantly fewer IgM and IgA antibodies compared to younger individuals. Aging is a complex process characterized by a functional decline in multiple physiological systems. The immune system of older people is well equipped to react to often encountered antigens but has a low ability to respond to new pathogens.


Subject(s)
Aging/immunology , B-Lymphocytes/immunology , COVID-19 , Immunologic Memory , Pandemics , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , COVID-19/immunology , Child , Child, Preschool , Cytokines/immunology , Female , Humans , Immunoglobulin A/immunology , Immunoglobulin M/immunology , Male , Middle Aged
7.
Int J Environ Res Public Health ; 18(11)2021 May 31.
Article in English | MEDLINE | ID: covidwho-1256538

ABSTRACT

As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues its spread all over the world, data on perinatal management of the maternal-infant dyad are urgent. We performed an observational study to describe the effects of the early separation of the maternal-infant dyad, in case of maternal SARS-CoV-2 infection. We reported the medical records for 37 neonates born to 37 SARS-CoV-2 positive mothers in a setting of separation of the dyad after birth. Data on neonatal infection, clinical condition, and breastfeeding rate were recorded until the first month of life. No maternal deaths were recorded; 37.8% of women had at least one pregnancy-related complication. We reported a high adherence to recommended safety measures after discharged with 84.8% of the mothers using at least one personal protective device and 51.5% using all the protective devices. We reported one case of vertical transmission and no cases of horizontal transmission. However, the separation of the dyad had a negative impact on breastfeeding because only 23.5% of the newborns received exclusively human milk during the first month of life. Despite early separation of the dyad protecting the newborns from possible horizontal transmission of SARS-CoV-2, it negatively affects breastfeeding during the first months of life.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Female , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Mothers , Pregnancy , SARS-CoV-2
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