Sustained chronic inflammation and altered childhood vaccine responses in children exposed to Zika virus.

BACKGROUND: Congenital Zika virus (ZIKV) infection leads to severe newborn abnormalities, but its long-term impact on childhood immunity is not well understood. This study aims to investigate the serum proteomics in children exposed to ZIKV during pregnancy to understand potential immunological consequences during early childhood. METHODS: The study included ZIKV-exposed infants (ZEI) at birth (n = 42) and children exposed to ZIKV (ZEC) at two years of age (n = 20) exposed to ZIKV during pregnancy, as well as healthy controls. Serum proteomic analysis was performed on these groups to assess inflammation and immune profiles. Additionally, antibody titres against two common childhood vaccines, DTaP and MMR, were measured in healthy controls (n = 50) and ZEC (n = 92) to evaluate vaccine-induced immunity. FINDINGS: Results showed elevated inflammation in ZEI with birth abnormalities. Among ZEC, despite most having normal clinical outcomes at two years, their serum proteomics indicated a bias towards Th1-mediated immune responses. Notably, ZEC displayed reduced anti-Diphtheria toxin and anti-Clostridium tetani IgG levels against DTaP and MMR vaccines. They also exhibited lower antibody titres particularly against Th2-biased DTaP vaccines, but not Th1-biased MMR vaccines. INTERPRETATION: In conclusion, the study highlights the long-term immunological consequences of congenital ZIKV exposure. Heightened inflammation was observed in ZEI with abnormalities at birth, while ZEC maintained a chronic Th1-biased immune profile. The impaired response to Th2-biased vaccines raises concerns about lasting effects of ZIKV exposure on immune responses. Consequently, there is a need for continued longitudinal clinical monitoring to identify potential immune-related complications arising from prenatal exposure to ZIKV. FUNDING: This work was partially funded by the National Institute of Allergy and Infectious Diseases (NIAID) and National Institute of Dental and Craniofacial Research (NIDCR).

Contribution of syphilis to adverse pregnancy outcomes in people living with and without HIV in south Brazil: 2008-2018.

BACKGROUND: Syphilis co-infection among pregnant people living with HIV (PLH) may worsen pregnancy outcomes. We evaluated the impact of syphilis co-infection on pregnancies in south Brazil. METHODS: Data was extracted from hospital records between 1/1/2008 -12/31/2018. Preterm birth (PTB), low birth weight (LBW < 2500 g), and a composite adverse infant outcome [AIO: HIV vertical transmission, loss to follow-up before HIV diagnosis (LTFU), stillbirth, congenital syphilis] were evaluated among pregnancies without HIV and syphilis (PWOH+S), PLH mono-infection, syphilis mono-infection (PLS), and PLH with syphilis (PLH + S). RESULTS: Among 48,685 deliveries where patients were tested for HIV and syphilis, 1,353 (2.8%) occurred in PLH; of these, 181 (13.4%) were HIV/syphilis co-infected (PLH + S). Among PLH, 2.4% of infants acquired HIV and 13.1% were LTFU. Among all PLS, 70.5% of infants acquired congenital syphilis. Across the cohort, 1.2% stillbirths/neonatal deaths occurred. 37.0% of PLH + S did not initiate ART versus 15.4% of PLH mono-infection (p < 0.001). 37.6% of PLH + S had VDRL titers > 1:16 compared to 21.7% of PLS only (p < 0.001). Among PLH, syphilis co-infection and unknown/high VDRL titers ( > 1:16) increased AIO risk more (aRR:3.96, 95%CI:3.33-4.70) compared to low VDRL titers ( < 1:8) (aRR:3.51, 95%CI:2.90-4.25). Unsuppressed viremia ( > 50 copies/mL) was associated with risk of PTB (aRR:1.43, 95%CI:1.07-1.92) and AIO (aRR:1.38, 95%CI:1.11-1.70) but not LBW. Lack of prenatal care was significant in predicting PTB and LBW in all PLH and PLS mono-infection. CONCLUSION: Syphilis co-infection worsens adverse infant outcomes in all women and compounds negative effects of HIV infection during pregnancy. Effective syphilis treatment and HIV VL suppression are paramount for optimal obstetric care.

Neurodevelopmental delay in children exposed to maternal SARS-CoV-2 in-utero.

It is unclear if SARS CoV-2 infection during pregnancy is associated with adverse neurodevelopmental repercussions to infants. We assessed pediatric neurodevelopmental outcomes in children born to mothers with laboratory-confirmed SARS CoV-2 infection during pregnancy. Neurodevelopmental outcomes of in-utero exposed children were compared to that of pre-pandemic control children in Los Angeles (LA), CA, USA and Rio de Janeiro, Brazil. Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III), the gold standard tool for evaluating neurodevelopment until 36 months of age and Ages and Stages Questionnaires (ASQ-3), a frequently used screening instrument for evaluating neurodevelopment in this same age group were the assessment tools used. Developmental delay (DD) was defined as having a score < - 2 SD below the norm (< 70) in at least one of three Bayley-III domains, (cognitive, motor or language) or a score below the cut-off (dark zone) in at least one of five ASQ-3 domains (communication, gross motor, fine motor, problem solving, personal-social). Exposed children were born between April 2020 and December 2022 while control children were born between January 2016 to December 2019. Neurodevelopmental testing was performed in 300 children total: 172 COVID-19 exposed children between 5-30 months of age and 128 control children between 6-38 months of age. Bayley-III results demonstrated that 12 of 128 exposed children (9.4%) had DD versus 2 of 128 controls (1.6%), p = 0.0007. Eight of 44 additional exposed children had DD on ASQ-3 testing. Fully, 20 of 172 exposed children (11.6%) and 2 of 128 control children (1.6%), p = 0.0006 had DD. In Rio, 12% of exposed children versus 2.6% of controls, p = 0.02 had DD. In LA, 5.7% of exposed children versus 0 controls, p = 0.12 had DD. Severe/critical maternal COVID-19 predicted below average neurodevelopment in the exposed cohort (OR 2.6, 95% CI 1.1-6.4). Children exposed to antenatal COVID-19 have a tenfold higher frequency of DD as compared to controls and should be offered neurodevelopmental follow-up.

Respiratory distress in SARS-CoV-2 exposed uninfected neonates followed in the COVID Outcomes in Mother-Infant Pairs (COMP) Study.

Respiratory distress (RD) has been reported in SARS-CoV-2 exposed uninfected (SEU) term neonates. Prior studies suggest that prenatal exposure to Coronavirus Disease 19 (COVID-19) may activate an inflammatory cascade in the newborn airway. In this study, we examine the relationship between maternal COVID-19 vaccination and neonatal RD using a longitudinal cohort of mother-infant pairs in Los Angeles, CA. Two-hundred and twenty-one mothers with laboratory confirmed SARS-CoV-2 during pregnancy and 227 exposed fetuses are enrolled in our study. Maternal disease severity and neonatal RD variables were defined based on current accepted clinical criteria. To explore the multifactorial associations between maternal COVID-19 parameters and infant RD, we utilize a multivariable logistic regression model and a proteomic sub-analysis to propose a pathway for the development of RD following in utero exposure to SARS-CoV-2. Unusually high rates of RD are observed in SEU infants (17%). The odds ratio of RD is 3.06 (95% CI:1.08-10.21) in term neonates born to unvaccinated individuals versus those born to individuals vaccinated prior to maternal infection. Proteomic analysis reveals a robust inflammatory response associated with ciliary dysregulation and enhanced IgE production among SEU neonates with RD. Maternal vaccination against COVID-19 reduces the frequency of neonatal RD.

Long COVID-19 syndrome associated with Omicron XBB.1.5 infection: a case report

BACKGROUND There is interest in lingering non-specific symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, referred to as Long coronavirus disease 2019 (Long COVID-19). It remains unknown whether the risk of Long COVID-19 is associated with pre-existing comorbidities or initial COVID-19 severity, including infections due to new Omicron lineages which predominated in 2023. OBJECTIVES The aim of this case report was to characterize the clinical features of acute XBB.1.5 infection followed by Long COVID-19. METHODS We followed a 73-year old female resident of Rio de Janeiro with laboratory-confirmed SARS-CoV-2 during acute infection and subsequent months. The SARS-CoV-2 lineage was determined by genome sequencing. FINDINGS The participant denied comorbidities and had completed a two-dose vaccination schedule followed by two booster doses eight months prior to SARS-CoV-2 infection. Primary infection by viral lineage XBB.1.5. was clinically mild, but the participant subsequently reported persistent fatigue. MAIN CONCLUSIONS This case demonstrates that Long COVID-19 may develop even after mild disease due to SARS-CoV-2 in fully vaccinated and boosted individuals without comorbidities. Continued monitoring of new SARS-CoV-2 lineages and associated clinical outcomes is warranted. Measures to prevent infection should continue to be implemented including development of new vaccines and antivirals effective against novel variants.

Neurodevelopment in the third year of life in children with antenatal ZIKV-exposure

ABSTRACT We report cognitive, language and motor neurodevelopment, assessed by the Bayley-III test, in 31 non-microcephalic children at age 3 with PCR-confirmed maternal Zika virus exposure (Rio de Janeiro, 2015-2016). Most children had average neurodevelopmental scores, however, 8 children (26%) presented delay in some domain. Language was the most affected: 7 children (22.6%) had a delay in this domain (2 presenting severe delay). Moderate delay was detected in the cognitive (3.2%) and motor (10%) domains. Maternal illness in the third trimester of pregnancy and later gestational age at birth were associated with higher Bayley-III scores. Zika-exposed children require long-term follow-up until school age.

Trends in a Cohort of HIV-infected pregnant women in Rio de Janeiro, 1996-2004

OBJECTIVE: To describe trends in sociodemographic, immunological and virological profiles and interventions to decrease the risk of mother-to-child HIV transmission. METHODS: Retrospective cohort study conducted at a tertiary institution in Rio de Janeiro, Brazil from January 1996 to December 2004. Analysis was performed by stratification in three time periods: 1996-1998 (P1), 1999-2001 (P2) and 2002-2004 (P3). RESULTS: In 9 years, 622 pregnancies occurred. Complications included: maternal mortality 0.3 percent, stillbirths 2.5 percent, miscarriages 0.6 percent, neonatal mortality 1.1 percent, prematurity 9.9 percent, low birth weight (LBW) 16.5 percent, congenital malformations 2.2 percent. The number of HIV-infected pregnant patients grew threefold over time reflecting increased prevalence of disease and patient identification. HIV diagnosis before pregnancy increased from 30 percent in P1 to 45 percent in P3. The proportion of pregnant women receiving highly active antiretroviral therapy increased from none (P1) to 88 percent (P3) with a significant trend towards women delivering at undetectable viral loads in later years despite a higher frequency of advanced disease. Scheduled cesarean deliveries increased from 35 percent in P1 to 48 percent in P3. Perinatal transmission rates were 2.4 percent with a decline from 3.5 percent in P1 to 1.6 percent in P3. Neonatal outcomes tended to remain constant or improve with time. A slight rise in LBW and congenital malformations were observed. CONCLUSIONS: During the observational period, HIV+ pregnant women presented with more advanced disease and lower socio-economic status. However, improved management of HIV-infected patients (associated with increased identification and increased availability of treatment) resulted into very low transmission rates similar to those of developed countries with overall improvement of patient outcomes.

OBJETIVOS: Descrever as tendências temporais nas características sociodemográficas, imunológicas e virológicas e as das condutas utilizadas para reduzir o risco da transmissão mãe-filho do HIV. MÉTODOS: Estudo de coorte retrospectivo em uma instituição de saúde terciária no Rio de Janeiro de janeiro de 1996 a dezembro de 2004. A análise utilizou a estratificação em três períodos de tempo: 1996-1998 (P1), 1999-2001 (P2) e 2002-2004 (P3). RESULTADOS: Em 9 anos, 622 gestações foram acompanhadas. As complicações foram: mortalidade materna 0,3 por cento, natimortos 2,5 por cento, abortos 0,6 por cento, mortalidade neonatal 1,1 por cento, prematuridade 9,9 por cento, baixo peso ao nascer (BPN) 16,5 por cento, malformações congênitas 2,2 por cento. O número de gestantes HIV positivo triplicou ao longo do tempo, refletindo o aumento da prevalência da doença e a melhor identificação das pacientes. O diagnóstico da infecção pelo HIV antes da gestação aumentou de 30 por cento em P1 para 45 por cento em P3. A proporção de gestantes recebendo o tratamento combinado potente aumentou de zero em P1 para 88 por cento em P3 com uma tendência significativa a ter uma carga viral abaixo do limite de detecção no parto nos últimos anos apesar de uma maior proporção de pacientes com doença mais avançada. O índice de cesarianas eletivas aumentou de 35 por cento em P1 para 48 por cento em P3. A taxa de transmissão perinatal global foi de 2,4 por cento caindo de 3,5 por cento em P1 para 1,6 por cento em P3. Os desfechos neonatais tenderam a permanecer constantes ou a melhorar ao longo do tempo. Um discreto aumento dos índices de BPN e de malformações congênitas foi observado. CONCLUSÕES: Ao longo do período de estudo aumentou a proporção de gestantes HIV positivo com doença mais avançada e com padrão socioeconômico mais baixo. Por outro lado, a melhora da abordagem terapêutica dos pacientes infectados pelo HIV, associada a uma maior detecção de casos e maior acesso...