Outcome of SARS-CoV-2 Infection in 121 Patients with Inborn Errors of Immunity: A Cross-Sectional Study.

PURPOSE: There is still scarce data on SARS-CoV-2 infection in patients with Inborn Errors of Immunity (IEI) and many unresolved questions. We aimed to describe the clinical outcome of SARS-CoV-2 infection in Brazilian IEI patients and identify factors influencing the infection. METHODS: We did a cross-sectional, multicenter study that included patients of any age affected by IEI and SARS-CoV-2 infection. The variables studied were sex, age, type of IEI, comorbidities (number and type), treatment in use for IEI, clinical manifestations and severity of SARS-CoV-2 infection. RESULTS: 121 patients were included: 55.4% female, ages from six months to 74 yo (median age = 25.1 yo). Most patients had predominantly antibody deficiency (n = 53). The infection was mostly asymptomatic (n = 21) and mild (n = 66), and one child had multisystem inflammatory syndrome (MIS-C). We could not observe sex-related susceptibility, and there was a weak correlation between age and severity of infection. The number of comorbidities was higher in severe cases, particularly bronchiectasis and cardiopathy. There were no severe cases in hereditary angioedema patients. Six patients aged 2 to 74 years died, three of them with antibody deficiency. CONCLUSION: The outcome was mild in most patients, but the Case Fatality Ratio was higher than in the general population. However, the type of IEI was not a determining factor for severity, except for complement deficiencies linked to milder COVID-19. The severity of SARS-CoV-2 infection seems to be more related to older age, a higher number of comorbidities and type of comorbidities (bronchiectasis and cardiopathy).

Acquisition of specific antibodies and their influence on cell-mediated immune response in neonatal cord blood after maternal pertussis vaccination during pregnancy.

Maternal immunization with pertussis acellular vaccine (Tdap) is an intervention that provides protection to newborns. However, it has been reported that high maternal antibody levels may adversely affect the immune response of infants after active immunization. In this study, we evaluated neonatal passive acquisition of pertussis-specific antibodies and their influence on the neonatal cell-mediated immune response. Pregnant women were either vaccinated with Tdap vaccine (case group, n = 66) or received no vaccine (control group, n = 101). Whole-cell Bordetella pertussis (Bp), pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN)-specific serum IgG were quantified in paired maternal-cord sera, and Bp- and PT-specific IgA were evaluated in colostrum by ELISA. Ex vivo neonatal blood lymphocyte responsiveness after Bp stimulation was assessed in case (n = 17) and control (n = 15) groups using flow cytometry to detect proliferation, cytokine production and activation phenotype of lymphocytes in the context of high specific IgG acquired after maternal vaccination. Anti-Bp, PT, FHA and PRN IgG concentrations in maternal and cord sera from case group were higher than those in control group with positive correlation indexes in both groups for all pertussis antigens. The control group presented higher placental transfer ratios of specific antibodies and, in the case group, vaccination between 26 and 31 gestation weeks was associated with the best placental transfer ratios. Specific IgA concentrations in colostrum were not affected by vaccine status. Whole blood assays revealed that newborns responded to Bp stimulation with higher expression of CD40L, CD69 and CD4+ T cell proliferation compared to unstimulated cells, and a lower Th1 response, while a preserved Th2 response compared to adults, but there were no differences between the neonatal groups for any of the studied parameters. Our results indicate that higher pertussis-specific IgG levels in newborn sera after maternal vaccination do not affect the neonatal ex vivo cell-mediated immune response.

Assessment and comparison of bacterial load levels determined by quantitative amplifications in blood culture-positive and negative neonatal sepsis.

Bacterial sepsis remains a major cause of mortality and blood cultures are the gold standard of laboratory diagnosis even though they lack sensitivity in neonates. Culturenegative sepsis, also known as clinical sepsis, has long been considered a diagnosis in neonatal intensive care units because, as well as culture-positive infants, culture-negative neonates have worse prognosis in comparison with non-infected ones. Quantitative amplifications are used to detect bacterial infections in neonates but results are considered only in a qualitative way (positive or negative). The aim of the present study was to determine and compare bacterial load levels in blood culture-positive and culture-negative neonatal sepsis. Seventy neonates with clinical and laboratory evidence of infection admitted at three neonatal intensive care units were classified as blood culture-positive or culture-negative. Blood samples obtained at the same time of blood cultures had bacterial load levels assessed through a 16S rDNA qPCR. Blood cultures were positive in 29 cases (41.4%) and qPCR in 64 (91.4%). In the 29 culture-positive cases, 100% were also positive by qPCR, while in the 41 culture-negative cases, 35 (85.4%) were positive by qPCR. Bacterial load levels were in general < 50 CFU/mL, but were significantly higher in culture-positive cases (Mann-Whitney, p = 0.013), although clinical and laboratory findings were similar, excepting for deaths. In conclusion, the present study has shown that blood culture-negative neonates have lower bacteria load levels in their bloodstream when compared to blood culture-positive infants.

Passive acquisition of anti-Staphylococcus aureus antibodies by newborns via transplacental transfer and breastfeeding, regardless of maternal colonization

OBJECTIVE: To investigate the transmission of anti-Staphylococcus aureus (Sa) IgG, IgG1 and IgG2 via placental transfer and the transfer of IgA via the colostrum according to maternal Sa carrier status at delivery. METHODS: We evaluated anti-Sa IgG, IgG1 and IgG2 in maternal and cord sera and IgA in colostrum from a case (n=49, Sa+) and a control group (n=98, Sa-). RESULTS: Of the 250 parturients analyzed for this study, 49 were nasally colonized with S. aureus (prevalence of 19.6%). Ninety-eight non-colonized subjects were selected for the control group. The anti-Sa IgG, IgG1 and IgG2 levels and the IgG avidity indexes in the maternal and cord sera did not differ between the groups, with a low transfer ratio of anti-Sa IgG to the newborns in both groups. The anti-Sa IgG2 titers were significantly higher than the IgG1 titers in the maternal and cord sera. Inversely, the transfer ratios were higher for anti-Sa IgG1 compared with IgG2; however, no differences between the groups were detected. The Sa-specific IgA levels and avidity indexes in the colostrum were equivalent between groups. CONCLUSIONS: Maternal Sa nasal colonization at delivery is not associated with higher antibody levels in the mother or newborns. The high titers of anti-Sa IgG2 found in the cord serum indicate a greater reactivity with non-protein antigens, which may further contribute to the susceptibility to staphylococcal infections at birth. The presence of IgA in the colostrum with avidity to S. aureus reinforces the importance of breastfeeding shortly after birth.

Passive acquisition of anti-Staphylococcus aureus antibodies by newborns via transplacental transfer and breastfeeding, regardless of maternal colonization.

OBJECTIVE:: To investigate the transmission of anti-Staphylococcus aureus (Sa) IgG, IgG1 and IgG2 via placental transfer and the transfer of IgA via the colostrum according to maternal Sa carrier status at delivery. METHODS:: We evaluated anti-Sa IgG, IgG1 and IgG2 in maternal and cord sera and IgA in colostrum from a case (n=49, Sa+) and a control group (n=98, Sa-). RESULTS:: Of the 250 parturients analyzed for this study, 49 were nasally colonized with S. aureus (prevalence of 19.6%). Ninety-eight non-colonized subjects were selected for the control group. The anti-Sa IgG, IgG1 and IgG2 levels and the IgG avidity indexes in the maternal and cord sera did not differ between the groups, with a low transfer ratio of anti-Sa IgG to the newborns in both groups. The anti-Sa IgG2 titers were significantly higher than the IgG1 titers in the maternal and cord sera. Inversely, the transfer ratios were higher for anti-Sa IgG1 compared with IgG2; however, no differences between the groups were detected. The Sa-specific IgA levels and avidity indexes in the colostrum were equivalent between groups. CONCLUSIONS:: Maternal Sa nasal colonization at delivery is not associated with higher antibody levels in the mother or newborns. The high titers of anti-Sa IgG2 found in the cord serum indicate a greater reactivity with non-protein antigens, which may further contribute to the susceptibility to staphylococcal infections at birth. The presence of IgA in the colostrum with avidity to S. aureus reinforces the importance of breastfeeding shortly after birth.

Usefulness of a 16S rDNA real-time PCR to monitor neonatal sepsis and to assist in medical decision to discontinue antibiotics.

OBJECTIVE: To monitor the bacterial load in newborns with proven infections on the day of admission, 48 h and 7 days after treatment. METHODS: Real-time PCR (qPCR) targeting the 16S rDNA. RESULTS: The study recruited 17 newborns and the bacterial load was in general low (<50 CFU/mL). In three of four deaths, the bacterial load values increased, and in 11 of the 13 survivors the values decreased until the third evaluation. CONCLUSION: Considering the extreme sensitivity and high negative predictive value of qPCR, this test could help to monitor the treatment of neonatal sepsis and to assist in medical decision to discontinue antibiotics.

Avaliação da transferência placentária e pelo colostro de anticorpos IgG e IgA anti-Staphylococcus aureus em mães com e sem colonização nasal / Evaluation of placental and colostral transfer of anti-Staphylococcus aureus IgG and IgA antibodies in mothers with and without nasal colonization

A transferência passiva de anticorpos da mãe para o filho auxilia na adaptação ao meio externo. No recém-nascido (RN), a colonização pelo Staphylococcus aureus (S. aureus) é precoce, sendo este um importante agente etiológico em infecções neonatais e no lactente jovem, para o qual ainda não se dispõem de vacina. OBJETIVOS: Avaliar as concentrações, títulos e avidez de anticorpos maternos anti-S. aureus do tipo IgG e IgA e a passagem desses anticorpos para os RN por transferência placentária e pelo colostro. MÉTODOS: Estudo caso-controle de 147 parturientes saudáveis. Foram coletadas amostras de soros maternos, de cordão umbilical e colostro. O grupo caso foi definido pela colonização nasal natural pelo S. aureus, sendo que para cada caso (n=49) foram selecionados 2 controles (n=98). Foram utilizadas as metodologias de imunoturbidimetria para dosagem de IgG total, ensaio imunoenzimático para dosagem IgA total e para a aferição das concentrações e títulos de anticorpos específicos anti-S. aureus (IgG sérica, subclasses séricas IgG1 e IgG2, IgA de colostro e os índices de avidez). Foram aplicados testes não paramétricos de Wilcoxon para amostras pareadas e de Mann-Whitney para amostras não pareadas, com intervalo de confiança de 95%, nível de significância p < 0,05. RESULTADOS: No grupo caso, as concentrações séricas de IgG total materna foram maiores mas com menor taxa de transferência placentária de IgG total, ocorrendo o inverso para o grupo controle. Não foram observadas diferenças nas concentrações séricas de IgG materna anti-S. aureus entre os grupos, mas com taxa de transferência placentária significantemente menor no grupo caso. Observou-se que os títulos específicos de IgG1 anti-S. aureus foram mais baixos no soro materno e no cordão do grupo caso, com taxas de transferência similar para os grupos caso e controle. Para os títulos específicos de IgG2 anti-S. aureus, não foram observadas diferenças entre os grupos caso e controle, com taxas de...

The passive transfer of antibodies from mother to child assists in adjustment to the external environment. In the newborn (NB), colonization by Staphylococcus aureus (S. aureus) occurs early, which is an important etiologic agent in neonatal and young infant infections, for which no vaccine is available. AIMS: To evaluate concentrations, titers and avidity of anti-S. aureus maternal IgG and IgA antibodies and transmission of these antibodies to the newborns via placental transfer and colostrum. METHODS: Case-control study of 147 healthy pregnant women. Samples of maternal serum, cord blood and colostrum were collected. The case group was defined by natural nasal colonization with S. aureus, and for each case (n = 49) were selected 2 controls (n = 98). Immunoturbidimetric assay was used to measure total IgG, and immunoenzymatic assay to measure total IgA in colostrum and anti-S. aureus concentrations and titers (serum IgG, serum IgG1 and IgG2, colostrum IgA and IgG and IgA avidity indexes). Nonparametric Wilcoxon test for paired samples and the Mann-Whitney test for unpaired samples were applied, with a confidence interval of 95%, significance level of p < 0.05. RESULTS: In the study group, maternal total IgG serum concentrations were higher but with lower total IgG placental transfer ratio, while the opposite occurred for the control group. No differences were observed in anti-staphylococcal maternal IgG serum concentrations between groups, but placental transfer ratio was significantly lower in the case group. It was observed that anti-S. aureus IgG1 titers were lower in maternal and cord serum from the case group, with with similar transfer ratios for case and control groups. Regarding antistaphylococcal IgG2 titers, no differences were observed between case and control groups, with similar transfer ratios between groups. It was observed that specific IgG2 titers were higher than those of IgG1 in both maternal and cord serum from both groups. In...