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.

Demographics of Youth With Newly Diagnosed Acute/Recent HIV Infection in Adolescent Trials Network 147: Early Treatment of Acute HIV Infection.

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-naïve, recently identified HIV + 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 = 1,727, 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.

Contraception and Abortion Care for People Living With HIV: A Clinical Guide for Reproductive Health Practitioners.

People capable of pregnancy are disproportionately affected by HIV. Family planning needs and services are often unmet in this population, and clinical care guidelines regarding contraceptive options and abortion care are not well elucidated. Individuals living with HIV often face unique barriers in accessing contraception and abortion services due to internalized stigma, medically complex care (eg, drug-drug interactions, adverse effects of antiretroviral therapy), and distrust of health care providers. There is also a lack of clarity among reproductive health, primary, and infectious disease care providers on best-practice contraceptive counseling and contraceptive care for individuals living with HIV, given limited opportunities to enhance expertise in reproductive infectious disease. In this review, we summarize existing and updated evidence and clinical considerations regarding contraceptive counseling and abortion care in this population.

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.

Using Machine Learning to Identify Predictors of Sexually Transmitted Infections Over Time Among Young People Living With or at Risk for HIV Who Participated in ATN Protocols 147, 148, and 149.

BACKGROUND: Sexually transmitted infections (STIs) among youth aged 12 to 24 years have doubled in the last 13 years, accounting for 50% of STIs nationally. We need to identify predictors of STI among youth in urban HIV epicenters. METHODS: Sexual and gender minority (gay, bisexual, transgender, gender-diverse) and other youth with multiple life stressors (homelessness, incarceration, substance use, mental health disorders) were recruited from 13 sites in Los Angeles and New Orleans (N = 1482). Self-reports and rapid diagnostic tests for STI, HIV, and drug use were conducted at 4-month intervals for up to 24 months. Machine learning was used to identify predictors of time until new STI (including a new HIV diagnosis). RESULTS: At recruitment, 23.9% of youth had a current or past STI. Over 24 months, 19.3% tested positive for a new STI. Heterosexual males had the lowest STI rate (12%); African American youth were 23% more likely to acquire an STI compared with peers of other ethnicities. Time to STI was best predicted by attending group sex venues or parties, moderate but not high dating app use, and past STI and HIV seropositive status. CONCLUSIONS: Sexually transmitted infections are concentrated among a subset of young people at highest risk. The best predictors of youth's risk are their sexual environments and networks. Machine learning will allow the next generation of research on predictive patterns of risk to be more robust.

Infant movement classification through pressure distribution analysis.

BACKGROUND: Aiming at objective early detection of neuromotor disorders such as cerebral palsy, we propose an innovative non-intrusive approach using a pressure sensing device to classify infant general movements. Here we differentiate typical general movement patterns of the "fidgety period" (fidgety movements) vs. the "pre-fidgety period" (writhing movements). METHODS: Participants (N = 45) were sampled from a typically-developing infant cohort. Multi-modal sensor data, including pressure data from a pressure sensing mat with 1024 sensors, were prospectively recorded for each infant in seven succeeding laboratory sessions in biweekly intervals from 4 to 16 weeks of post-term age. 1776 pressure data snippets, each 5 s long, from the two targeted age periods were taken for movement classification. Each snippet was pre-annotated based on corresponding synchronised video data by human assessors as either fidgety present or absent. Multiple neural network architectures were tested to distinguish the fidgety present vs. fidgety absent classes, including support vector machines, feed-forward networks, convolutional neural networks, and long short-term memory networks. RESULTS: Here we show that the convolution neural network achieved the highest average classification accuracy (81.4%). By comparing the pros and cons of other methods aiming at automated general movement assessment to the pressure sensing approach, we infer that the proposed approach has a high potential for clinical applications. CONCLUSIONS: We conclude that the pressure sensing approach has great potential for efficient large-scale motion data acquisition and sharing. This will in return enable improvement of the approach that may prove scalable for daily clinical application for evaluating infant neuromotor functions.

The movement of a baby is used by health care professionals to determine whether they are developing as expected. The aim of this study was to investigate whether a pad containing sensors that measured pressure occurring as the babies moved could enable identification of different movements of the babies. The results we obtained were similar to those obtained from use of a computer to process videos of the moving babies or other methods using movement sensors. This method could be more readily used to check the movement development of babies than other methods that are currently used.

SARS-CoV-2 Reinfection Cases in a Household-Based Prospective Cohort in Rio de Janeiro.

This was a household-based prospective cohort study conducted in Rio de Janeiro, in which people with laboratory-confirmed coronavirus disease 2019 (COVID-19) and their household contacts were followed from April 2020 through June 2022. Ninety-eight reinfections were identified, with 71 (72.5%) confirmed by genomic analyses and lineage definition in both infections. During the pre-Omicron period, 1 dose of any COVID-19 vaccine was associated with a reduced risk of reinfection, but during the Omicron period not even booster vaccines had this effect. Most reinfections were asymptomatic or milder in comparison with primary infections, a justification for continuing active surveillance to detect infections in vaccinated individuals. Our findings demonstrated that vaccination may not prevent infection or reinfection with severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). Therefore we highlight the need to continuously update the antigenic target of SARS CoV-2 vaccines and administer booster doses to the population regularly, a strategy well established in the development of vaccines for influenza immunization programs.

Epidemiology and SARS-CoV-2 Infection Patterns among Youth Followed at a Large Los Angeles Health Network during 2020-2022: Clinical Presentation, Prevalent Strains, and Correlates of Disease Severity.

BACKGROUND: Outcomes of SARS CoV-2 infection in infants, children and young adults are reported less frequently than in older populations. The evolution of SARS-CoV-2 cases in LA County youths followed at a large health network in southern California over two years was evaluated. METHODS: A prospective cohort study of patients aged 0-24 years diagnosed with COVID-19 was conducted. Demographics, age distribution, disease severity, circulating variants of concern (VOCs), and immunization rates were compared between first and second pandemic years. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) of factors associated with severe/critical COVID-19. RESULTS: In total, 61,208 patients 0-24 years of age were tested for SARS-CoV-2 by polymerase chain reaction (PCR); 5263 positive patients (8.6%) with available data were identified between March 2020 and March 2022. In Year 1, 5.8% (1622/28,088) of youths tested positive, compared to 11% (3641/33,120) in Year 2 (p < 0.001). Most youths had mild/asymptomatic illness over two years. SARS-CoV-2 positivity was >12% across all age groups in the second half of Year 2, when Omicron prevailed. Pulmonary disease was associated with higher risk of severe COVID-19 in both years (OR: 2.4, 95% CI: 1.4-4.3, p = 0.002, Year 1; OR: 11.3, 95% CI: 4.3-29.6, Year 2, p < 0.001). Receipt of at least one COVID-19 vaccine dose was protective against severe COVID-19 (OR: 0.3, 95% CI: 0.11-0.80, p < 0.05). CONCLUSIONS: Despite different VOCs and higher rates of test positivity in Year 2 compared to Year 1, most youths with COVID-19 had asymptomatic/mild disease. Underlying pulmonary conditions increased the risk of severe COVID-19, while vaccination was highly protective against severe disease in youths.

The Role of Children in Household Transmission of SARS-CoV-2 Across Four Waves of the Pandemic.

BACKGROUND: It is important to understand the dynamics of SARS-CoV-2 transmission in close-contact settings such as households. We hypothesized that children would most often acquire SARS-CoV-2 from a symptomatic adult caregiver. METHODS: This prospective cohort study was conducted from April 2020 to July 2022 in a low-resource, urban settlement in Brazil. We recruited families who brought their children to a public clinic. We collected nasopharyngeal and oral swabs from household members and tracked symptoms and vaccination. RESULTS: In total, 1256 participants in 298 households were tested for SARS-CoV-2. A total of 4073 RT-PCR tests were run with 893 SARS-CoV-2 positive results (21.9%). SARS-CoV-2 cases were defined as isolated cases (N = 158) or well-defined transmission events (N = 175). The risk of household transmission was lower if the index case was a child (OR: 0.3 [95% CI: 0.16-0.55], P < .001) or was vaccinated (OR: 0.29 [95% CI: 0.1-0.85], P = .024), and higher if the index was symptomatic (OR: 2.53 [95% CI: 1.51-4.26], P < .001). The secondary attack rate for child index cases to child contacts was 0.29, whereas the secondary attack rate for adult index cases to child contacts was 0.47 (P = .08). CONCLUSIONS: In this community, children were significantly less infectious to their household contacts than adolescents or adults. Most children were infected by a symptomatic adult, usually their mother. There was a double benefit of vaccination as it protected the vaccine from severe illness and prevented onward transmission to household contacts. Our findings may also be valid for similar populations throughout Latin America.

Can prenatal ultrasound predict adverse neonatal outcomes in SARS-CoV-2-affected pregnancies?

BACKGROUND: On the basis of available data, at least 1 ultrasound assessment of pregnancies recovering from SARS-CoV-2 infection is recommended. However, reports on prenatal imaging findings and potential associations with neonatal outcomes following SARS-CoV-2 infection in pregnancy have been inconclusive. OBJECTIVE: This study aimed to describe the sonographic characteristics of pregnancies after confirmed SARS-CoV-2 infection and assess the association of prenatal ultrasound findings with adverse neonatal outcomes. STUDY DESIGN: This was an observational prospective cohort study of pregnancies diagnosed with SARS-CoV-2 by reverse transcription polymerase chain reaction between March 2020 and May 2021. Prenatal ultrasound evaluation was performed at least once after diagnosis of infection, with the following parameters measured: standard fetal biometric measurements, umbilical and middle cerebral artery Dopplers, placental thickness, amniotic fluid volume, and anatomic survey for infection-associated findings. The primary outcome was the composite adverse neonatal outcome, defined as ≥1 of the following: preterm birth, neonatal intensive care unit admission, small for gestational age, respiratory distress, intrauterine fetal demise, neonatal demise, or other neonatal complications. Secondary outcomes were sonographic findings stratified by trimester of infection and severity of SARS-CoV-2 infection. Prenatal ultrasound findings were compared with neonatal outcomes, severity of infection, and trimester of infection. RESULTS: A total of 103 SARS-CoV-2-affected mother-infant pairs with prenatal ultrasound evaluation were identified; 3 cases were excluded because of known major fetal anomalies. Of the 100 included cases, neonatal outcomes were available in 92 pregnancies (97 infants); of these, 28 (29%) had the composite adverse neonatal outcome, and 23 (23%) had at least 1 abnormal prenatal ultrasound finding. The most common abnormalities seen on ultrasound were placentomegaly (11/23; 47.8%) and fetal growth restriction (8/23; 34.8%). The latter was associated with a higher rate of the composite adverse neonatal outcome (25% vs 1.5%; adjusted odds ratio, 22.67; 95% confidence interval, 2.63-194.91; P<.001), even when small for gestational age was removed from this composite outcome. The Cochran Mantel-Haenszel test controlling for possible fetal growth restriction confounders continued to show this association (relative risk, 3.7; 95% confidence interval, 2.6-5.9; P<.001). Median estimated fetal weight and birthweight were lower in patients with the composite adverse neonatal outcome (P<.001). Infection in the third trimester was associated with lower median percentile of estimated fetal weight (P=.019). An association between placentomegaly and third-trimester SARS-CoV-2 infection was noted (P=.045). CONCLUSION: In our study of SARS-CoV-2-affected maternal-infant pairs, rates of fetal growth restriction were comparable to those found in the general population. However, composite adverse neonatal outcome rates were high. Pregnancies with fetal growth restriction after SARS-CoV-2 infection were associated with an increased risk for the adverse neonatal outcome and may require close surveillance.

Mobile Solutions for Clinical Surveillance and Evaluation in Infancy-General Movement Apps.

The Prechtl General Movements Assessment (GMA) has become a clinician and researcher toolbox for evaluating neurodevelopment in early infancy. Given that it involves the observation of infant movements from video recordings, utilising smartphone applications to obtain these recordings seems like the natural progression for the field. In this review, we look back on the development of apps for acquiring general movement videos, describe the application and research studies of available apps, and discuss future directions of mobile solutions and their usability in research and clinical practice. We emphasise the importance of understanding the background that has led to these developments while introducing new technologies, including the barriers and facilitators along the pathway. The GMApp and Baby Moves apps were the first ones developed to increase accessibility of the GMA, with two further apps, NeuroMotion and InMotion, designed since. The Baby Moves app has been applied most frequently. For the mobile future of GMA, we advocate collaboration to boost the field's progression and to reduce research waste. We propose future collaborative solutions, including standardisation of cross-site data collection, adaptation to local context and privacy laws, employment of user feedback, and sustainable IT structures enabling continuous software updating.

Cesarean delivery and risk of HIV vertical transmission in Southern Brazil, 2008-2018.

BACKGROUND: Childbirth via cesarean delivery can prevent intrapartum vertical transmission for women who are not virally suppressed at the time of delivery. Few studies have compared cesarean delivery trends between women living with HIV and women without HIV and have examined the role of cesarean delivery in the prevention of vertical transmission in the era of potent combination antiretroviral therapy. OBJECTIVE: We hypothesized that the cesarean delivery rate is high in women living with HIV compared with women without HIV and that cesarean delivery usage decreases over time among women living with HIV with advances in combined antiretroviral therapy in a country with a high national cesarean delivery rate. This study aimed (1) to evaluate cesarean delivery trends in women with and without HIV and (2) to examine its role in preventing vertical transmission among women living with HIV in a setting of free, universal combined antiretroviral therapy coverage in a retrospective cohort of nearly 56,000 deliveries at a major referral institution in a city with the highest prevalence of maternal HIV in Brazil. STUDY DESIGN: Data from maternal-infant pairs from January 1, 2008, to December 31, 2018, were extracted. Cesarean delivery rates were compared using the Pearson chi-square test. Cesarean delivery predictors were evaluated by multivariate log-linear Poisson regression using a generalized estimating equations approach. HIV viral suppression was defined as a viral load of <1000 copies/ml at delivery. HIV vertical transmission was determined following national guidelines. RESULTS: Over 11 years, 48,688 pregnancies occurred in 40,375 women; HIV seroprevalence was 2.7%; 18,886 cesarean deliveries (38.8%) were performed; 47.7% of women living with HIV and 38.6% of women without HIV underwent cesarean delivery (P<.001). Although HIV was associated with cesarean delivery (adjusted relative risk, 1.17 [95% confidence interval, 1.05-1.29]), women living with HIV with vertical transmission achieved similar cesarean delivery rates (36.7%) as women without HIV (39.8%) in 2018. Cesarean delivery in women living with HIV with an unknown viral load at delivery (42.6%) did not increase over time. HIV vertical transmission rate was 2.2%, the highest in women living with HIV with an unknown viral load (8.4%) vs women living with HIV without vertical transmission (4.1%) and women living with HIV with vertical transmission (0.5%) (P<.001). CONCLUSION: In the HIV epicenter of Brazil, women living with HIV with vertical transmission had fewer surgical deliveries, likely because of the use of potent combination antiretroviral therapy. Nearly half of the women living with HIV with an unknown viral load did not undergo cesarean delivery, a potential missed opportunity for the prevention of HIV vertical transmission.

Open video data sharing in developmental science and clinical practice.

In behavioral research and clinical practice video data has rarely been shared or pooled across sites due to ethical concerns of confidentiality, although the need of shared large-scaled datasets remains increasing. This demand is even more imperative when data-heavy computer-based approaches are involved. To share data while abiding by privacy protection rules, a critical question arises whether efforts at data de-identification reduce data utility? We addressed this question by showcasing an established and video-based diagnostic tool for detecting neurological deficits. We demonstrated for the first time that, for analyzing infant neuromotor functions, pseudonymization by face-blurring video recordings is a viable approach. The redaction did not affect classification accuracy for either human assessors or artificial intelligence methods, suggesting an adequate and easy-to-apply solution for sharing behavioral video data. Our work shall encourage more innovative solutions to share and merge stand-alone video datasets into large data pools to advance science and public health.

The End Is in Sight: Current Strategies for the Elimination of HIV Vertical Transmission.

PURPOSE OF REVIEW: The goal of this review is to highlight and interpret recent trends and developments in the diagnosis, treatment, and prevention of HIV vertical transmission from a clinical perspective. RECENT FINDINGS: Universal third-trimester retesting and partner testing may better identify incident HIV among pregnant patients and result in early initiation of antiretroviral therapy to prevent vertical transmission. The proven safety and efficacy of integrase inhibitors such as dolutegravir may be particularly useful in suppressing viremia in pregnant persons who present late for ART treatment. Pre-exposure prophylaxis (PrEP) during pregnancy may play a role in preventing HIV acquisition; however, its role in preventing vertical transmission is difficult to elucidate. Substantial progress has been made in recent years to eliminate HIV perinatal transmission. Future research hinges upon a multipronged approach to improving HIV detection, risk-stratified treatment strategies, and prevention of primary HIV infection among pregnant persons.

Reliability of the Motor Optimality Score-Revised: A study of infants at elevated likelihood for adverse neurological outcomes.

AIM: To assess the inter-assessor reliability of the Motor Optimality Score-Revised (MOS-R) when used in infants at elevated likelihood for adverse neurological outcome. METHODS: MOS-R were assessed in three groups of infants by two assessors/cohort. Infants were recruited from longitudinal projects in Sweden (infants born extremely preterm), India (infants born in low-resource communities) and the USA (infants prenatally exposed to SARS-CoV-2). Intraclass correlation coefficients (ICC) and kappa (κw) were applied. ICC of MOS-R subcategories and total scores were presented for cohorts together and separately and for age-spans: 9-12, 13-16 and 17-25-weeks post-term age. RESULTS: 252 infants were included (born extremely preterm n = 97, born in low-resource communities n = 97, prenatally SARS-CoV-2 exposed n = 58). Reliability of the total MOS-R was almost perfect (ICC: 0.98-0.99) for all cohorts, together and separately. Similar result was found for age-spans (ICC: 0.98-0.99). Substantial to perfect reliability was shown for the MOS-R subcategories (κw: 0.67-1.00), with postural patterns showing the lowest value 0.67. CONCLUSION: The MOS-R can be used in high-risk populations with substantial to perfect reliability, both in regards of total/subcategory scores as well as in different age groups. However, the subcategory postural patterns as well as the clinical applicability of the MOS-R needs further study.

Adolescents Living With or at Risk for HIV: A Pooled Descriptive Analysis of Studies From the Adolescent Medicine Trials Network for HIV/AIDS Interventions.

PURPOSE: This study aims to describe the cohort of Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) research program participants and evaluate whether the ATN's recently completed 5-year cycle recruited study participants who parallel the populations most impacted by HIV in the United States. METHODS: Harmonized measures across ATN studies collected at baseline were aggregated for participants aged 13-24 years. Pooled means and proportions stratified by HIV status (at risk for or living with HIV) were calculated using unweighted averages of study-specific aggregate data. Medians were estimated using a weighted median of medians method. Public use 2019 Centers for Disease Control and Prevention surveillance data for state-level new HIV diagnoses and HIV prevalence among US youth aged 13-24 years were obtained for use as reference populations for ATN at-risk youth and youth living with HIV (YLWH), respectively. RESULTS: Data from 3,185 youth at-risk for HIV and 542 YLWH were pooled from 21 ATN study phases conducted across the United States. Among ATN studies tailored to at-risk youth, a higher proportion of participants were White and a lower proportion were Black/African American and Hispanic/Latinx compared to youth newly diagnosed with HIV in the United States in 2019. Participants in ATN studies tailored to YLWH were demographically similar to YLWH in the United States. DISCUSSION: The development of data harmonization guidelines for ATN research activities facilitated this cross-network pooled analysis. These findings suggest the ATN's YLWH are representative, but that future studies of at-risk youth should prioritize recruitment strategies to enroll more participants from African American and Hispanic/Latinx populations.

Differential Susceptibility of Fetal Retinal Pigment Epithelial Cells, hiPSC- Retinal Stem Cells, and Retinal Organoids to Zika Virus Infection.

Zika virus (ZIKV) causes microcephaly and congenital eye disease. The cellular and molecular basis of congenital ZIKV infection are not well understood. Here, we utilized a biologically relevant cell-based system of human fetal retinal pigment epithelial cells (FRPEs), hiPSC-derived retinal stem cells (iRSCs), and retinal organoids to investigate ZIKV-mediated ocular cell injury processes. Our data show that FRPEs were highly susceptible to ZIKV infection exhibiting increased apoptosis, whereas iRSCs showed reduced susceptibility. Detailed transcriptomics and proteomics analyses of infected FRPEs were performed. Nucleoside analogue drug treatment inhibited ZIKV replication. Retinal organoids were susceptible to ZIKV infection. The Asian genotype ZIKV exhibited higher infectivity, induced profound inflammatory response, and dysregulated transcription factors involved in retinal organoid differentiation. Collectively, our study shows that ZIKV affects ocular cells at different developmental stages resulting in cellular injury and death, further providing molecular insight into the pathogenesis of congenital eye disease.

Neuromotor repertoires in infants exposed to maternal COVID-19 during pregnancy: a cohort study.

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.

SERTAD3 induces proteasomal degradation of ZIKV capsid protein and represents a therapeutic target.

Zika virus (ZIKV) is a mosquito-borne RNA virus that belongs to the Flaviviridae family. While flavivirus replication is known to occur in the cytoplasm, a significant portion of the viral capsid protein localizes to the nucleus during infection. However, the role of the nuclear capsid is less clear. Herein, we demonstrated SERTA domain containing 3 (SERTAD3) as an antiviral interferon stimulatory gene product had an antiviral ability to ZIKV but not JEV. Mechanistically, we found that SERTAD3 interacted with the capsid protein of ZIKV in the nucleolus and reduced capsid protein abundance through proteasomal degradation. Furthermore, an eight amino acid peptide of SERTAD3 was identified as the minimum motif that binds with ZIKV capsid protein. Remarkably, the eight amino acids synthetic peptide from SERTAD3 significantly prevented ZIKV infection in culture and pregnant mouse models. Taken together, these findings not only reveal the function of SERTAD3 in promoting proteasomal degradation of a specific viral protein but also provide a promising host-targeted therapeutic strategy against ZIKV infection.

Risk of adverse outcomes in offspring with RT-PCR confirmed prenatal Zika virus exposure: An individual participant data meta-analysis of 13 cohorts in the Zika Brazilian Cohorts Consortium.

Background: Knowledge regarding the risks associated with Zika virus (ZIKV) infections in pregnancy has relied on individual studies with relatively small sample sizes and variable risk estimates of adverse outcomes, or on surveillance or routinely collected data. Using data from the Zika Brazilian Cohorts Consortium, this study aims, to estimate the risk of adverse outcomes among offspring of women with RT-PCR-confirmed ZIKV infection during pregnancy and to explore heterogeneity between studies. Methods: We performed an individual participant data meta-analysis of the offspring of 1548 pregnant women from 13 studies, using one and two-stage meta-analyses to estimate the absolute risks. Findings: Of the 1548 ZIKV-exposed pregnancies, the risk of miscarriage was 0.9%, while the risk of stillbirth was 0.3%. Among the pregnancies with liveborn children, the risk of prematurity was 10,5%, the risk of low birth weight was 7.7, and the risk of small for gestational age (SGA) was 16.2%. For other abnormalities, the absolute risks were: 2.6% for microcephaly at birth or first evaluation, 4.0% for microcephaly at any time during follow-up, 7.9% for neuroimaging abnormalities, 18.7% for functional neurological abnormalities, 4.0% for ophthalmic abnormalities, 6.4% for auditory abnormalities, 0.6% for arthrogryposis, and 1.5% for dysphagia. This risk was similar in all sites studied and in different socioeconomic conditions, indicating that there are not likely to be other factors modifying this association. Interpretation: This study based on prospectively collected data generates the most robust evidence to date on the risks of congenital ZIKV infections over the early life course. Overall, approximately one-third of liveborn children with prenatal ZIKV exposure presented with at least one abnormality compatible with congenital infection, while the risk to present with at least two abnormalities in combination was less than 1.0%.