Objective To evaluate neuromotor repertoires and developmental milestones in infants exposed to antenatal COVID-19. Design Longitudinal cohort study. Setting Hospital-based study in Los Angeles, USA and Rio de Janeiro, Brazil between March 2020 and December 2021. Participants Infants born to mothers with COVID-19 during pregnancy and prepandemic control infants from the Graz University Database. Interventions General movement assessment (GMA) videos between 3 and 5 months post-term age were collected and clinical assessments/developmental milestones evaluated at 6–8 months of age. Cases were matched by gestational age, gender and post-term age to prepandemic neurotypical unexposed controls from the database. Main outcome measures Motor Optimality Scores Revised (MOS-R) at 3–5 months. Presence of developmental delay (DD) at 6–8 months. Results 239 infants were enrolled; 124 cases (83 in the USA/41 in Brazil) and 115 controls. GMA was assessed in 115 cases and 115 controls; 25% were preterm. Median MOS-R in cases was 23 (IQR 21–24, range 9–28) vs 25 (IQR 24–26, range 20–28) in controls, p<0.001. Sixteen infants (14%) had MOS-R scores <20 vs zero controls, p<0.001. At 6–8 months, 13 of 109 case infants (12%) failed to attain developmental milestones; all 115 control infants had normal development. The timing of maternal infection in pregnancy (first, second or third trimester) or COVID-19 disease severity (NIH categories asymptomatic, mild/moderate or severe/critical) was not associated with suboptimal MOS-R or DD. Maternal fever in pregnancy was associated with DD (OR 3.7; 95% CI 1.12 to 12.60) but not suboptimal MOS-R (OR 0.25; 95% CI 0.04 to 0.96). Conclusions Compared with prepandemic controls, infants exposed to antenatal COVID-19 more frequently had suboptimal neuromotor development.

Background. Because >60 rotavirus strains have been reported worldwide, concerns exist about strain replacement after the introduction of rotavirus vaccines, particularly in developing countries with diverse strains and lower efficacy. Methods. We used the case-control design in 4 hospitals in Nicaragua to assess strain-specific vaccine effectiveness (VE) of a pentavalent rotavirus vaccine (RotaTeq) against rotavirus diarrhea. Cases were identified through prospective strain surveillance with reverse transcription–polymerase chain reaction for 3 years among children hospitalized for diarrhea, and controls were children negative for rotavirus. Results. We enrolled 1178 case-patients, 1082 (92%) with G and P typing, and 4927 controls. A different strain predominated each year with increasing age of the vaccine-eligible cohort during the study period: G2P[4] in 2008 (97%; mean age, 11.9 months), G1P[8] in 2009 (55%; mean age, 17.0 months), and G3P[8] in 2010 (78%; mean age, 17.3 months). Overall VE was 45% (95% confidence interval, 25%–59%). Regardless of the strain, VE estimates were 12%–79% lower among children aged ≥12 months relative to those 6–11 months of age. The lower VE for G3P[8] was related to the higher mean age of cases (17.3 months) compared with the G2P[4] strains (11.9 months), with a significant trend (R² = 0.819; P < .001) of declining effectiveness with increasing mean age of the cases. Conclusions. Introduction of RotaTeq did not result in sustained emergence of any particular strain in Nicaragua. Variation in strain-specific effectiveness was due to an age-related decline in effectiveness rather than differences in protection against the observed strains.

Background: Identify early predictors of poor neurodevelopment in infants with antenatal Zika virus (ZIKV) exposure. Methods: Analysis of a prospective cohort of infants with antenatal ZIKV exposure confirmed by maternal or infant RT-PCR or IgM during the epidemic in Rio de Janeiro, Brazil. Clinical findings before 3 months of age were associated with Bayley-III Scales of Infant and Toddler Development conducted after 6 months of age. Results: ZIKV exposure was confirmed in 219 cases; 162 infants were normocephalic, 53 were microcephalic, 4 had no head circumference recorded because of perinatal death/LTFU. Seven of the 112 normocephalic infants developed secondary microcephaly between 3 weeks and 8 months of age. Among the normocephalic at birth cohort, the mean HCZ among normal, at risk, and developmentally delayed children was significantly different (ANOVA, P = 0.02). In particular, the mean HCZ of the developmentally delayed group was significantly lower than that of the normal group (Tukey’s test, P = 0.014). HCZ was more strongly associated with lower expressive language scores (P = 0.04) than receptive language scores (P = 0.06). The rate of auditory abnormalities differed among the normal, at risk, and developmentally delayed groups (Chi-squared test, P = 0.016), which was driven by the significant difference between the normal and at risk groups (post hoc test, P = 0.011, risk ratio 3.94). Auditory abnormalities were associated with both expressive and receptive language delays (P = 0.02 and P = 0.02, respectively). Conclusions: Clear predictors of neurodevelopment in normocephalic ZIKV-exposed children have not been previously identified. Our findings demonstrate that smaller HCZ and auditory abnormalities in these infants correlate with poor neurodevelopment as toddlers. Language delay is the most prominent developmental concern among these children, who will require frequent auditory and speech evaluations throughout childhood.

Background: Early treatment studies have shown that prompt treatment of HIV with combination antiretroviral therapy (cART) can limit the size of latent viral reservoirs, thereby providing clinical and public health benefits. Studies have demonstrated that adolescents have a greater capacity for immune reconstitution than adults. Nevertheless, adolescents who acquired HIV through sexual transmission have not been included in early treatment studies because of challenges in identification and adherence to cART. Objective: This study aimed to identify and promptly treat with cART youth aged 12 to 24 years in Los Angeles and New Orleans who have acute, recent, or established HIV infection, as determined by Fiebig stages 1 to 6 determined by viral RNA polymerase chain reaction, p24 antigen presence, and HIV-1 antigen Western blot. The protocol recommends treatment on the day of diagnosis when feasible. Surveillance and dedicated behavioral strategies are used to retain them in care and optimize adherence. Through serial follow-up, HIV biomarkers and response to antiretroviral therapy (ART) are assessed. The study aims to assess viral dynamics, decay and persistence of viral reservoirs over time, and correlate these data with the duration of viral suppression. Methods: A total of 72 youth (36 acutely infected and 36 treatment naïve controls) are enrolled across clinical sites using a current community-based strategy and direct referrals. Youth are prescribed ART according to the standard of care HIV-1 management guidelines and followed for a period of 2 years. Assessments are conducted at specific time points throughout these 2 years of follow-up for monitoring of adherence to ART, viral load, magnitude of HIV reservoirs, and presence of coinfections. Results: The study began enrolling youth in July 2017 across study sites in Los Angeles and New Orleans. As of September 30, 2018, a total of 37 youth were enrolled, 12 with recently acquired, 16 with established HIV infection as determined by Fiebig staging, and 9 pending determination of Fiebig status. Recruitment and enrollment are ongoing. Conclusions: We hypothesize that the size of the HIV reservoir and immune activation markers will be different across groups treated with cART, that is, those with acute or recent HIV infection and those with established infection. Adolescents treated early who are virally suppressed will have diminished HIV reservoirs than those with established infection. These youth may be potential candidates for a possible HIV vaccine and additional HIV remission intervention trials. Our study will inform future studies of viral remission strategies. International Registered Report Identifier (IRRID): DERR1-10.2196/10807

Background: We investigated the association between maternal neutralizing antibodies (nAb) to Zika virus (ZIKV) in pregnancy and neonatal outcomes. Methods: In pregnant participants with confirmed ZIKV infection, we determined trimester of infection, collected sera longitudinally, and measured nAbs via plaque reduction. In neonates, adverse outcomes included microcephaly (MC), structural brain abnormalities (SBA), hearing, and eye abnormalities. Associations between trimester of infection, nAbs, and neonatal outcomes were analyzed with Cox regression. Results: In total, 137 ZIKV-positive pregnant participants had neutralization assays performed during pregnancy and postdelivery. Infection rates were 29% in the first, 50% in the second, and 21% in the third trimester. Mean ZIKV nAb titer >2 weeks postinfection was 64 258 (SD 213 288). Ten percent of 90% plaque reduction neutralization assays (PRNT90) titers were 1000, and 7% did not have serologic follow-up; 15%. of infants had adverse findings. Protective factors against MC in 88 mothers with nAb titers available during pregnancy included infection later in gestation (adjusted hazard ratio [aHR], 0.06; P = .036) and adequate nAb titers (aHR, 0.17; P = .014). No SBA was associated with later infection in pregnancy (aHR, 0.16; P = .017) and adequate nAb titers (aHR, 0.34; P = .012). Adjusting for trimester, higher maternal nAb titers were associated with lower risk of MC and SBA. Seven of 137 participants (5.1%) had positive serum ZIKV polymerase chain reaction (PCR) results beyond 14 days (range, 35–269 days). Participants with ZIKV PCR positivity >60 days (n = 2) had infants with MC/SBA. Conclusions: MC and SBA were less frequent in infants of mothers with higher ZIKV nAb titers during pregnancy.

Purpose: Gay, bisexual, and other cisgender men who have sex with men, and racial minority youth are at elevated risk of acquiring HIV infection. The Adolescent Trials Network 147 recruited youth with acute/recent HIV -infection for early antiretroviral treatment. The cohort make-up is described here. Methods: Treatment -naive, recently identified HIV thorn youth, aged 12-24 years, from Los Angeles and New Orleans were recruited from community centers, clinics, social media, and a high-risk seronegative cohort (n 1/4 1,727, the Adolescent Trials Network 149) using point -of -care assays. Acute HIV infection was determined by Fiebig staging. HIV RNA viral load (VL) and CD4 cell counts, along with demographic and behavioral data were assessed at enrollment. Results: Between July 2017 and July 2021, 103 newly diagnosed youth were enrolled, initiating antiretroviral treatment within a week. Mean age was 20.8 years (standard deviation: 2.4); 90.3% identified as cis male, 83.5% were single or in casual relationships, 71.8% were gay, bisexual, and other cisgender men who have sex with men; 60.2% were Black. One-fourth (24.3%) reported homelessness ever; 10.7% within last 4 months. At enrollment, median plasma VL was 37,313 HIV RNA copies/ml (interquartile range: 5,849-126,162) and median CD4 count 445.5 cells/mm3 (interquartile range: 357-613). 40% of youth reported acute retroviral symptoms before or at enrollment. Acutely infected, seroconverting youth had the highest VL. Sexually transmitted coinfections were present at enrollment in 56% of the cohort, with syphilis being most frequent (39%). Discussion: Early identification and treatment of HIV can increase positive HIV outcomes. A high sexually transmitted infection burden was present in recently HIV-infected youth. Acute retroviral symptoms were not reported by most participants, demonstrating that broad universal HIV screening is needed for identification of recent infection in youth. (c) 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).