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RATIONALE: In 2016, a new interferon-gamma release assay (IGRA) was introduced, QuantiFERON-TB Gold Plus (QFT-Plus), claimed to have improved sensitivity in active tuberculosis (TB). OBJECTIVES: This study aimed to determine the performance of QFT-Plus, compared with previous generation IGRAs and the tuberculin skin test (TST), in children with TB in Europe. METHODS: Multicentre, ambispective cohort study within the Paediatric Tuberculosis Network European Trials Group (ptbnet), a dedicated paediatric TB research network comprising >300 members, capturing TB cases <18 years-of-age diagnosed between January 2009 and December 2019. MEASUREMENTS AND MAIN RESULTS: 1001 TB cases from 16 countries were included (mean age (IQR) 5.6 (2.4-12.1) years). QFT-Plus was performed in 358, QFT Gold in-Tube (QFT-GIT) in 600, T-SPOT.TB in 58 and TST in 636 cases. The overall test sensitivities were: QFT-Plus 83.8% (95% CI 80.2% to 87.8%), QFT-GIT 85.5% (95% CI 82.7% to 88.3%), T-SPOT.TB 77.6% (95% CI 66.9% to 88.3%) and TST (cut-off ≥10 mm) 83.3% (95% CI 83.3% to 86.2%). There was a trend for tests to have lower sensitivity in patients with miliary and/or central nervous system (CNS) TB (73.1%, 70.9%, 63.6% and 43.5%, respectively), and in immunocompromised patients (75.0%, 59.6%, 45.5% and 59.1%, respectively). CONCLUSIONS: The results indicate that the latest generation IGRA assay, QFT-Plus, does not perform better than previous generation IGRAs or the TST in children with TB disease. Overall, tests performed worse in CNS and miliary TB, and in immunocompromised children. None of the tests evaluated had sufficiently high sensitivity to be used as a rule-out test in children with suspected TB.
Subject(s)
Latent Tuberculosis , Tuberculosis , Humans , Child , Child, Preschool , Cohort Studies , Tuberculosis/diagnosis , Interferon-gamma Release Tests/methods , Tuberculin Test/methods , Europe , Latent Tuberculosis/diagnosisABSTRACT
BACKGROUND: It is known that SARS-CoV-2 antibodies from pregnant women with SARS-CoV-2 infection during pregnancy cross the placenta but the duration and the protective effect of these antibodies in infants is scarce. METHODS: This prospective study included mothers with SARS-COV-2 infection during pregnancy and their infants from April 2020 to March 2021. IgG antibodies to SARS-CoV-2 spike protein were performed on women and infants at birth and at two and six months during follow-up. Anthropometrical measures and physical and neurological examinations and a clinical history of symptoms and COVID-19 diagnosis were collected. Simple linear regression was performed to compare categorical and continuous variables. To compare the mother's and infant's antibody titers evolution, a mixed linear regression model was used. A predictive model of newborn antibody titers at birth has been established by means of simple stepwise linear regression. RESULTS: 51 mother-infant couples were included. 45 (90%) of the mothers and 44 (86.3%) of the newborns had a positive serology al birth. These antibodies were progressively decreasing and were positive in 34 (66.7%) and 7 (13.7%) of infants at 2 and 6 months, respectively. IgG titers of newborns at birth were related to mothers' titers, with a positive moderate correlation (Pearson's correlation coefficient: 0.82, p < 0,001). Fetal/maternal antibodies placental transference rate was 1.3 (IQR: 0.7-2.2). The maternal IgG titers at delivery and the type of maternal infection (acute, recent, or past infection) was significantly related with infants' antibody titers at birth. No other epidemiological or clinical factors were related to antibodies titers. Neurodevelopment, psychomotor development, and growth were normal in 94.2% of infants in the third follow-up visit. No infants had a COVID-19 diagnosis during the follow-up period. CONCLUSIONS: Transplacental transfer of maternal antibodies is high in newborns from mothers with recent or past infection at delivery, but these antibodies decrease after the first months of life. Infant's IgG titers were related to maternal IgG titers at delivery. Further studies are needed to learn about the protective role of maternal antibodies in infants.
Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Infant, Newborn , Pregnancy , Female , Humans , Immunoglobulin G , Mothers , COVID-19 Testing , Follow-Up Studies , Prospective Studies , COVID-19/diagnosis , COVID-19/epidemiology , Placenta , SARS-CoV-2 , Pregnancy Complications, Infectious/diagnosisABSTRACT
AIM: Acute Epstein-Barr virus (aEBV) and cytomegalovirus (CMV) infections frequently have similar manifestations. We aim to evaluate the characteristics of aEBV infection, risk factors for hospitalisation and differences according to CMV IgM detection (EBV-CMV co-detection) in children. METHODS: Retrospective, single-centre study including patients <16 years diagnosed with aEBV infection (positive anti-EBV IgM/Paul-Bunnell test and acute symptomatology). EBV-CMV co-detection was defined as positive CMV IgM. Factors associated with age, hospitalisation and EBV-CMV co-detection were analysed in a multivariate analysis. RESULTS: A total of 149 patients were included (median age 4.6 years). Most frequent manifestations were fever (77%), cervical lymphadenopathy (64%) and elevated liver enzymes (54%). Younger children had lower rate of positive Paul-Bunnell test (35% vs. 87%; p < 0.01), but higher rate of EBV-CMV co-detection (54% vs. 29%; p = 0.03). These children tended to have less typical symptoms of infectious mononucleosis and higher hospitalisation rate. The overall antibiotic prescription was 49%. Hospitalisation (27 children; 18%) was independently associated with prior antibiotic therapy and anaemia. Sixty-two cases (42%) had EBV-CMV co-detection, which was independently associated with elevated liver enzymes and younger age. CONCLUSION: In this study, younger children with aEBV infection presented more frequently with atypical clinical symptoms, had higher EBV-CMV co-detection rates and were more often hospitalised. Hospitalisation was associated with prior antibiotic prescription.
Subject(s)
Cytomegalovirus Infections , Epstein-Barr Virus Infections , Liver Diseases , Humans , Child , Child, Preschool , Epstein-Barr Virus Infections/diagnosis , Epstein-Barr Virus Infections/epidemiology , Epstein-Barr Virus Infections/complications , Cytomegalovirus , Herpesvirus 4, Human , Retrospective Studies , Risk Factors , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/complications , Liver Diseases/complications , Hospitalization , Antibodies, Viral , Immunoglobulin MABSTRACT
BACKGROUND: Important prevention efforts have led to a reduction in mother-to-child transmission of HIV (MTCT) globally. However, new cases of paediatric HIV infections still occur. Early diagnosis of new HIV infections is essential to start an appropriate antiretroviral treatment to avoid childhood morbidity and mortality related to infection. The aim of this study was to describe the new cases of MTCT in Latin-American referral hospitals. METHODS: A retrospective, multicentre and descriptive study of the new cases of MTCT diagnosed during 2018 in 13 referral hospitals from 8 Latin-American countries (Costa Rica, Ecuador, El Salvador, Guatemala, Honduras, Mexico, Nicaragua, and Panama) belonging to PLANTAIDS (Paediatric Network for Prevention, Early Detection and Treatment of HIV in Children), was conducted. PLANTAIDS is included in CYTED (Ibero-American Programme of Science and Technology for Development). RESULTS: Eighty-one children (40.7% males) were included, median age at diagnosis of 2.33 years (IQR:0.7-4.7). Less than 3% of women knew their HIV diagnosis before pregnancy. More than 80% of them were diagnosed after delivery, 8.7% during pregnancy, and 2.9% at delivery. Only one patient underwent antiretroviral therapy (ART) prior to pregnancy. At diagnosis, 50.0% of the children presented with an advanced stage of disease (stage C following the current CDC classification for HIV infection), and 34.4% had less than 15% CD4+ cells/mm3. The time elapsed between delivery and the maternal diagnosis was correlated with the age of children at diagnosis, ρ = 0.760, p < 0.001. Younger age at diagnosis (p = 0.03), a smaller number of previous hospitalizations (p < 0.01), and better immunovirological status (p < 0.01) were found in children whose mothers knew their HIV status at delivery, compared to mothers who were not aware of it. CONCLUSIONS: Although MTCT in Latin America has declined in recent years, our series shows there are still cases that indicate some failures in prevention, being a critical point to improve an earlier diagnosis of pregnant women. Half of the children were diagnosed in an advanced stage of disease and the delay in maternal diagnosis entailed a worse clinical and immunological child' prognosis.
Subject(s)
HIV Infections , Pregnancy Complications, Infectious , Anti-Retroviral Agents/therapeutic use , Child , Female , HIV Infections/diagnosis , HIV Infections/drug therapy , HIV Infections/prevention & control , Humans , Infectious Disease Transmission, Vertical/prevention & control , Male , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/drug therapy , Retrospective StudiesABSTRACT
BACKGROUND: The main objective was to determine the clinical or analytical factors that independently predict risk of serious bacterial infection (RSBI) in immunocompetent patients older than 90 days given a diagnosis of fever and for whom neutropenia was an incidental finding. The secondary objective was to describe the prevalence of serious bacterial infections (SBIs). METHODS: This is a 3-year-long, multicenter, prospective analytical and observational study carried out at 6 pediatric emergency departments. Data for epidemiological, clinical, and analytical variables were collected. RESULTS: One hundred forty patients with febrile neutropenia (60.7% mild, 39.3% moderate to severe) were recruited. Serious bacterial infection incidence was 15.0% (95% confidence interval [CI], 9-21): 1 Invasive Bacterial Infection (Staphylococcus epidermidis bacteremia), 10 urinary tract infections, 8 pneumonias, and 2 cellulitis. Median total neutrophil counts per microliter showed no statistically significant differences (P = 0.512; 1000 [750-1200] in SBI patients vs 1100 [800-1300] in non-SBI patients). Higher RSBI was observed in patients with neutrophils less than 20% relative to total leukocytes (SBI, 15, 26.3%) than in those with neutrophils of 20% or greater (SBI, 6, 7.2%) (odds ratio, 4.6; 95% CI, 1.7-12.7). In patients with greater than 5000 leukocytes/µL, a percentage of neutrophils less than 20% was related to a greater RSBI with a trend toward statistical significance (odds ratio, 6.1; 95% CI, 0.7-51.1; P = 0.066). The clinical variables did not show a significant association with RSBI. CONCLUSIONS: None of the clinical or analytical variables assessed were associated with the RSBI. However, according to a post hoc analysis, in patients with greater than 5000 leukocytes/µL, a neutrophil percentage less than 20% could be an independent risk factor for SBI. A thorough physical examination and basic diagnostic tests (urinalysis and chest x-ray) may help to establish a diagnosis of SBI in the vast majority of cases.
Subject(s)
Bacterial Infections , Neutropenia , Bacterial Infections/diagnosis , Child , Fever/etiology , Humans , Infant , Neutropenia/epidemiology , Prospective Studies , Risk FactorsABSTRACT
BACKGROUND: Knowledge about SARS-CoV-2 infection in pregnancy and newborns is scarce. The objective of this study is to analyse clinical and epidemiological characteristics of a cohort of women infected with SARS-CoV-2 during pregnancy and their newborns exposed to SARS-CoV-2 during gestation. METHODS: Multicentric observational study of Spanish hospitals from the GESNEO-COVD cohort, participants in RECLIP (Spanish Network of Paediatric Clinical Assays). Women with confirmed SARS-CoV-2 infection by PCR and/or serology during pregnancy, diagnosed and delivering during the period 15/03/2020-31/07/2020 were included. Epidemiological, clinical, and analytical data was collected. RESULTS: A total of 105 pregnant women with a median of 34.1 years old (IQR: 28.8-37.1) and 107 newborns were included. Globally, almost 65% of pregnant women had some COVID-19 symptoms and more than 43% were treated for SARS-COV-2. Overall, 30.8% of pregnant women had pneumonia and 5 (4.8%) women were admitted to the intensive care unit needing invasive mechanical ventilation. There was a rate of 36.2% of caesarean sections, which was associated with pneumonia during pregnancy (OR: 4.203, CI 95%: 1.473-11.995) and lower gestational age at delivery (OR: 0.724, CI 95%: 0.578-0.906). The prevalence of preterm birth was 20.6% and prematurity was associated with pneumonia during gestation (OR: 6.970, CI95%: 2.340-22.750) and having a positive SARS-CoV-2 PCR at delivery (OR: 6.520, CI95%: 1.840-31.790). All nasopharyngeal PCR in newborns were negative at birth and one positivized at 15 days of life. Two newborns died, one due to causes related to prematurity and another of unexpected sudden death during early skin-to-skin contact after delivery. CONCLUSIONS: Although vertical transmission has not been reported in this cohort, the prognosis of newborns could be worsened by SARS-CoV-2 infection during pregnancy as COVID-19 pneumonia increased the risk of caesarean section deliveries and preterm births.
Subject(s)
COVID-19/epidemiology , Carrier State/epidemiology , Pregnancy Complications, Infectious/epidemiology , Premature Birth/epidemiology , Adult , Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/physiopathology , COVID-19/therapy , COVID-19 Nucleic Acid Testing , Cesarean Section/statistics & numerical data , Cohort Studies , Comorbidity , Cough/physiopathology , Diabetes, Gestational/epidemiology , Dyspnea/physiopathology , Female , Fever/physiopathology , Gestational Age , Humans , Hypertension/epidemiology , Hypothyroidism/epidemiology , Immunologic Factors/therapeutic use , Infant, Newborn , Infectious Disease Transmission, Vertical , Intensive Care Units/statistics & numerical data , Lung/diagnostic imaging , Male , Obesity, Maternal/epidemiology , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Pregnancy , Pregnancy Complications/epidemiology , Pregnancy Complications, Infectious/physiopathology , Pregnancy Complications, Infectious/therapy , Pregnancy Trimester, Second , Pregnancy Trimester, Third , Radiography, Thoracic , Respiration, Artificial , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Spain/epidemiology , COVID-19 Drug TreatmentABSTRACT
INTRODUCTION: Tuberculosis remains one of the top ten causes of mortality globally. Children accounted for 12% of all TB cases and 18% of all TB deaths in 2022. Paediatric TB is difficult to diagnose with conventional laboratory tests, and chest radiographs remain crucial. However, in low-and middle-income countries with high TB burden, the capacity for radiological diagnosis of paediatric TB is rarely documented and data on the associated radiation exposure limited. METHODS: A multicentre, mixed-methods study is proposed in three countries, Mozambique, South Africa and Spain. At the national level, official registry databases will be utilised to retrospectively compile an inventory of licensed imaging resources (mainly X-ray and Computed Tomography (CT) scan equipment) for the year 2021. At the selected health facility level, three descriptive cross-sectional standardised surveys will be conducted to assess radiology capacity, radiological imaging diagnostic use for paediatric TB diagnosis, and radiation protection optimization: a site survey, a clinician-targeted survey, and a radiology staff-targeted survey, respectively. At the patient level, potential dose optimisation will be assessed for children under 16 years of age who were diagnosed and treated for TB in selected sites in each country. For this component, a retrospective analysis of dosimetry will be performed on TB and radiology data routinely collected at the respective sites. National inventory data will be presented as the number of units per million people by modality, region and country. Descriptive analyses will be conducted on survey data, including the demographic, clinical and programmatic characteristics of children treated for TB who had imaging examinations (chest X-ray (CXR) and/or CT scan). Dose exposure analysis will be performed by children's age, gender and disease spectrum. DISCUSSION: As far as we know, this is the first multicentre and multi-national study to compare radiological capacity, radiation protection optimization and practices between high and low TB burden settings in the context of childhood TB management. The planned comparative analyses will inform policy-makers of existing radiological capacity and deficiencies, allowing better resource prioritisation. It will inform clinicians and radiologists on best practices and means to optimise the use of radiological technology in paediatric TB management.
Subject(s)
Radiology , Humans , Child , Retrospective Studies , South Africa/epidemiology , Mozambique/epidemiology , Cross-Sectional Studies , Spain/epidemiologyABSTRACT
BACKGROUND: Tuberculosis (TB) remains a major cause of morbidity and death worldwide, with a significant impact on children, especially those under the age of 5 years. The complex diagnosis of pediatric TB, compounded by limited access to more accurate diagnostic tests, underscores the need for improved tools to enhance diagnosis and care in resource-limited settings. OBJECTIVE: This study aims to present a telemedicine web platform, BITScreen PTB (Biomedical Image Technologies Screen for Pediatric Tuberculosis), aimed at improving the evaluation of pulmonary TB in children based on digital chest x-ray (CXR) imaging and clinical information in resource-limited settings. METHODS: The platform was evaluated by 3 independent expert readers through a retrospective assessment of a data set with 218 imaging examinations of children under 3 years of age, selected from a previous study performed in Mozambique. The key aspects assessed were the usability through a standardized questionnaire, the time needed to complete the assessment through the platform, the performance of the readers to identify TB cases based on the CXR, the association between the TB features identified in the CXRs and the initial diagnostic classification, and the interreader agreement of the global assessment and the radiological findings. RESULTS: The platform's usability and user satisfaction were evaluated using a questionnaire, which received an average rating of 4.4 (SD 0.59) out of 5. The average examination completion time ranged from 35 to 110 seconds. In addition, the study on CXR showed low sensitivity (16.3%-28.2%) but high specificity (91.1%-98.2%) in the assessment of the consensus case definition of pediatric TB using the platform. The CXR finding having a stronger association with the initial diagnostic classification was air space opacification (χ21>20.38, P<.001). The study found varying levels of interreader agreement, with moderate/substantial agreement for air space opacification (κ=0.54-0.67) and pleural effusion (κ=0.43-0.72). CONCLUSIONS: Our findings support the promising role of telemedicine platforms such as BITScreen PTB in enhancing pediatric TB diagnosis access, particularly in resource-limited settings. Additionally, these platforms could facilitate the multireader and systematic assessment of CXR in pediatric TB clinical studies.
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International adoption has declined in recent years, although the adoption of children with special needs has arisen. We aim to describe our experience in the international adoption of children with special needs and to analyze the concordance between the pathologies included in pre-adoption reports and the diagnosis made upon arrival. We conducted a retrospective descriptive study including internationally adopted children with special needs evaluated at a reference Spanish unit between 2016 and 2019. Epidemiological and clinical variables were collected from medical records, and pre-adoption reports were compared to established diagnoses following their evaluation and complementary tests. Fifty-seven children were included: 36.8% females, a median age of 27 months [IQR:17-39], mostly coming from China (63.2%) and Vietnam (31.6%). The main pathologies described in the pre-adoption reports were congenital surgical malformations (40.3%), hematological (22.6%), and neurological (24.6%). The initial diagnosis that motivated the international adoption via special needs was confirmed in 79% of the children. After evaluation, 14% were diagnosed with weight and growth delay, and 17.5% with microcephaly, not previously reported. Infectious diseases were also prevalent (29.8%). According to our series, the pre-adoption reports of children with special needs appear accurate, with a low rate of new diagnoses. Pre-existing conditions were confirmed in almost 80% of cases.
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BACKGROUND: To assess the prevalence and characteristics of nonsevere TB among children in Spain. It has been recently demonstrated that these children can be treated with a 4-month regimen instead of the classical 6-month treatment regimen, with the same effectivity and outcomes, decreasing toxicity and improving adherence. METHODS: We conducted a retrospective cohort study in a cohort of children ≤16 years of age with TB. Nonsevere TB cases included smear-negative children with respiratory TB confined to 1 lobe, with no significant airway obstruction, no complex pleural effusion, no cavities and no signs of miliary disease, or with peripheral lymph-node disease. The remaining children were considered to have severe TB. We estimated the prevalence of nonsevere TB and compared the clinical characteristics and outcomes between children with nonsevere and severe TB. RESULTS: A total of 780 patients were included [46.9% males, median age 5.5 years (IQR: 2.6-11.1)], 477 (61.1%) of whom had nonsevere TB. Nonsevere TB was less frequent in children <1 year (33% vs 67%; P < 0.001), and >14 years of age (35% vs 65%; P = 0.002), mostly diagnosed in contact tracing studies (60.4% vs 29.2%; P < 0.001) and more frequently asymptomatic (38.3% vs 17.7%; P < 0.001). TB confirmation in nonsevere disease was less frequent by culture (27.0% vs 57.1%; P < 0.001) and by molecular tests (18.2% vs 48.8%; P < 0.001). Sequelae were less frequent in children with nonsevere disease (1.7 vs 5.4%; P < 0.001). No child with nonsevere disease died. CONCLUSIONS: Two-thirds of children had nonsevere TB, mostly with benign clinical presentation and negative microbiologic results. In low-burden countries, most children with TB might benefit from short-course regimens.
Subject(s)
Tuberculosis, Pulmonary , Tuberculosis , Male , Humans , Child , Child, Preschool , Female , Tuberculosis, Pulmonary/diagnosis , Retrospective Studies , Prevalence , Spain/epidemiology , Tuberculosis/diagnosis , Tuberculosis/drug therapy , Tuberculosis/epidemiologyABSTRACT
According to World Health Organization estimates, more than 1 million patients aged less than 15 years develop tuberculosis (TB) each year worldwide. In some regions, up to 25% of new TB cases are caused by drug-resistant strains. Although Spain is considered a low-incidence country, several hundred children and adolescents develop TB each year. The importance of paediatric TB has been minimized for years due to the lack of microbiological confirmation in many patients and because these patients are not usually contagious. Nevertheless, in the past 15 years there have been major improvements in the epidemiological reporting of TB in children and adolescents, new immunodiagnostic tests have been developed, molecular methods that allow rapid microbiological diagnosis and detection of variants associated with drug resistance have become available, novel second-line antituberculosis drugs have been discovered, including for paediatric use, and the results of clinical trials have validated shorter courses of treatment for some patients. This document, developed by a group of experts from the Sociedad Española de Infectología Pediátrica and the Sociedad Española de Neumología Pediátrica, updates and complements the previous guidelines for the diagnostic and therapeutic management of children with TB in Spain based on the newly available scientific evidence.
Subject(s)
Tuberculosis , Adolescent , Humans , Child , Tuberculosis/diagnosis , Tuberculosis/drug therapy , Antitubercular Agents/therapeutic use , SpainABSTRACT
This study aimed to analyse the long-term effect of direct-acting antivirals (DAAs) in vertically acquired HIV/HCV-coinfected youths. We performed a multicentre, longitudinal and observational study within the Spanish Cohort of HIV-infected children and adolescents and vertically HIV-infected patients transferred to Adult Units (CoRISpe-FARO). We included HIV/HCV-coinfected youths (n = 24) that received DAAs between 2015 and 2017 with successful sustained viral response (SVR) with a subsequent follow-up of at least three years. Long-term evolution in liver disease severity and haematologic markers, lipid and immune profiles after SVR were assessed. Study times were the start date of DAAs treatment (baseline, T0) and 1, 2, 3, 4 and 5 years after SVR (T1, T2, T3, T4 and T5, respectively). We observed global improvements in liver function data that persist over time and a favourable haematologic and immune outcome at the long-term including a constant augment in leucocytes, neutrophils, neutrophils to lymphocytes ratio (NLR) and CD4/CD8 ratio over-time. Regarding the lipid profile, we found a significant increase in total cholesterol T2, total cholesterol/high-density lipoprotein (HDL) ratio at T4, triglycerides at T5, low-density lipoprotein (LDL) over time, and a decrease in HDL in all patients but with marked higher levels in the subgroup receiving anti-HIV Protease Inhibitor (PI)-based regimens. Comparisons of vertically HIV/HCV-coinfected youths after SVR at 3-year follow-up and a control group of vertically HIV-monoinfected youths never infected by HCV showed no significant differences in most variables analysed, suggesting a possible normalization in all parameters.
Subject(s)
Coinfection , HIV Infections , HIV Protease Inhibitors , Hepatitis C, Chronic , Adult , Child , Humans , Adolescent , Antiviral Agents/pharmacology , HIV Infections/drug therapy , Hepatitis C, Chronic/drug therapy , Hepacivirus , Lipoproteins, LDL/pharmacology , Cholesterol/pharmacology , Treatment OutcomeABSTRACT
SARS-CoV2 infection in pregnancy and exposed newborns is poorly known. We performed a longitudinal analysis of immune system and determined soluble cytokine levels in pregnant women infected with SARS-CoV2 and in their newborns. Women with confirmed SARS-CoV2 infection and their exposed uninfected newborns were recruited from Hospital General Universitario Gregorio Marañón. Peripheral blood mononuclear cells (PBMCs), cord cells and plasma were collected at birth and 6 months later. Immunophenotyping of natural killer (NK), monocytes and CD4/CD8 T-cells were studied in cryopreserved PBMCs and cord cells by multiparametric flow cytometry. Up to 4 soluble pro/anti-inflammatory cytokines were assessed in plasma/cord plasma by ELISA assay. SARS-CoV2-infected mothers and their newborns were compared to matched healthy non-SARS-CoV2-infected mothers and their newborns. The TNFα and IL-10 levels of infected mothers were higher at baseline than those of healthy controls. Infected mothers showed increased NK cells activation and reduced expression of maturation markers that reverted after 6 months. They also had high levels of Central Memory and low Effector Memory CD4-T cell subsets. Additionally, the increased CD4- and CD8-T cell activation (CD154 and CD38) and exhaustion (TIM3/TIGIT) levels at baseline compared to controls remained elevated after 6 months. Regarding Treg cells, the levels were lower at infected mothers at baseline but reverted after 6 months. No newborn was infected at birth. The lower levels of monocytes, NK and CD4-T cells observed at SARS-CoV2-exposed newborns compared to unexposed controls significantly increased 6 months later. In conclusion, SARS-CoV2 infection during pregnancy shows differences in immunological components that could lead newborns to future clinical implications after birth. However, SARS-CoV2 exposed 6-months-old newborns showed no immune misbalance, whereas the infected mothers maintain increased activation and exhaustion levels in T-cells after 6 months.
Subject(s)
COVID-19 , Immune System Diseases , Pregnancy Complications , COVID-19/complications , Cytokines , Female , Humans , Immune System Diseases/etiology , Infant , Infant, Newborn , Leukocytes, Mononuclear , Lymphocyte Activation , Pregnancy , Pregnancy Complications/virology , SARS-CoV-2ABSTRACT
BACKGROUND: The vertical transmission of severe acute respiratory coronavirus-2 (SARS-CoV-2) remains highly debated. Here, we evaluated SARS-CoV-2-transmission in newborns with intrauterine conditions. METHODS: This was a prospective, observational and multicentric study involving 13 Spanish hospitals included in the GEStational and NEOnatal-COVID cohort. Pregnant women with microbiologically confirmed SARS-CoV-2 infection during any trimester of pregnancy or delivery and their newborns were included from March to November 2020. Demographic, clinical and microbiological data were also obtained. Viral loads were analyzed in different maternal and newborn biological samples (placenta, breast milk and maternal blood; urine, meconium and newborn blood). RESULTS: A total of 177 newborns exposed to SARS-CoV-2 were included. Newborns were tested by reverse transcriptase-polymerase chain reaction using nasopharyngeal swabs within the first 24-48 hours of life and at 14 days of life. In total 5.1% were considered to have SARS-CoV-2 infection in the neonatal period, with 1.7% considered intrauterine and 3.4% intrapartum or early postnatal transmission cases. There were no differences in the demographic and clinical characteristics of the pregnant women and their newborns' susceptibility to infections in their perinatal history or background. CONCLUSIONS: Intrauterine transmission of SARS-CoV-2 is possible, although rare, with early postnatal transmission occurring more frequently. Most infected newborns remained asymptomatic or had mild symptoms that evolved well during follow-up. We did not find any maternal characteristics predisposing infants to neonatal infection. All infected newborn mothers had acute infection at delivery.Although there was no presence of SARS-CoV2 in cord blood or breast milk samples, SARS-CoV-2 viral load was detected in urine and meconium samples from infected newborns.