Aerosol delivery of SARS-CoV-2 human monoclonal antibodies in macaques limits viral replication and lung pathology.

Passively administered monoclonal antibodies (mAbs) given before or after viral infection can prevent or blunt disease. Here, we examine the efficacy of aerosol mAb delivery to prevent infection and disease in rhesus macaques inoculated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant via intranasal and intratracheal routes. SARS-CoV-2 human mAbs or a human mAb directed to respiratory syncytial virus (RSV) are nebulized and delivered using positive airflow via facemask to sedated macaques pre- and post-infection. Nebulized human mAbs are detectable in nasal, oropharyngeal, and bronchoalveolar lavage (BAL) samples. SARS-CoV-2 mAb treatment significantly reduces levels of SARS-CoV-2 viral RNA and infectious virus in the upper and lower respiratory tracts relative to controls. Reductions in lung and BAL virus levels correspond to reduced BAL inflammatory cytokines and lung pathology. Aerosolized antibody therapy for SARS-CoV-2 could be effective for reducing viral burden and limiting disease severity.

Multiple Hospital In-Situ Mass Casualty Incident Training Simulation for Emergency Medicine Residents: A Sarin Bomb Scenario.

INTRODUCTION: We simulated an on-site, multi-hospital mass casualty incident (MCI) to educate emergency medicine providers in the principles of trauma resuscitation and collaboration with administration and staff during an MCI. METHODS: We implemented high-fidelity manikins, inflatable manikins, and actors to simulate a sarin gas bombing. Learners triaged patients at a decontamination tent using the simple triage and rapid treatment (START) tool, or they participated in a simulation in a resuscitation bay. RESULTS: Forty participants anonymously rated the learning impact of the exercise, the clinical relevance to emergency medicine, and the effectiveness of the faculty facilitation and debriefing on a 1-5 Likert scale. The average responses to all questions were 4.45 or greater, and 98% of respondents recommended adding the scenario to the standard curriculum. DISCUSSION: We successfully executed a novel, multi- hospital, MCI drill that was rated to be a better alternative to sequential simulation in a simulation center.

Unfilled in emergency medicine: An analysis of the 2022 and 2023 Match by program accreditation, ownership, and geography.

Background: The two most recent National Resident Matching Program (NRMP) Match cycles saw a high number of initially unfilled emergency medicine (EM) residency positions. We sought to identify the risk of EM residency program characteristics including accreditation duration, primary clinical site ownership status, and geography pertaining to not initially filling all positions. Methods: We performed a repeated cross-sectional observational study of EM residency programs participating in the 2022 and 2023 NRMP Match cycles and used publicly available data from the NRMP, the Accreditation Council for Graduate Medical Education, the Centers for Medicare & Medicaid Services, and the U.S. Department of Housing and Urban Development. Our primary outcome was the proportion of EM residency programs that did not initially fill positions, with analyses stratified by accreditation duration (>5 or ≤5 years), primary clinical site ownership status, and geographic core-based statistical areas (CBSAs). Results: A total of 219 of 2921 (7.5%) positions in the 2022 Match and 554 of 3010 (18.4%) positions in the 2023 Match were initially unfilled. Over the 2-year period, EM residency programs accredited within the past 5 years had more than double the risk (relative risk [RR] 2.08, 95% confidence interval [CI] 1.69-2.57, chi-square p < 0.001) of not filling all positions compared to those accredited more than 5 years previously. EM residency programs with a primary clinical site under for-profit ownership had a 50% greater risk of not filling all positions when compared to those under nonprofit or governmental ownership (RR 1.50, 95% CI 1.14-1.98, chi-square p = 0.009). In 2023, several CBSAs had a high number of both offered and unfilled positions. Conclusions: EM residency programs accredited within the past 5 years or those with a primary clinical site under for-profit ownership had a greater risk of not filling all positions within the past two Match cycles.

Blood-brain barrier penetration of non-replicating SARS-CoV-2 and S1 variants of concern induce neuroinflammation which is accentuated in a mouse model of Alzheimer's disease.

COVID-19 and especially Long COVID are associated with severe CNS symptoms and may place persons at risk to develop long-term cognitive impairments. Here, we show that two non-infective models of SARS-CoV-2 can cross the blood-brain barrier (BBB) and induce neuroinflammation, a major mechanism underpinning CNS and cognitive impairments, even in the absence of productive infection. The viral models cross the BBB by the mechanism of adsorptive transcytosis with the sugar N-acetylglucosamine being key. The delta and omicron variants cross the BB B faster than the other variants of concern, with peripheral tissue uptake rates also differing for the variants. Neuroinflammation induced by icv injection of S1 protein was greatly enhanced in young and especially in aged SAMP8 mice, a model of Alzheimer's disease, whereas sex and obesity had little effect.

Titration and neutralizing antibody quantification by focus forming assay for Powassan virus.

The development of high-throughput assays measuring Powassan virus (POWV) lineage I and II represents an important step in virological and immunological studies. By adapting focus-forming assays previously optimized for West Nile virus and Zika virus, this protocol is able to determine viral load, evaluate antivirals, and measure neutralizing antibodies. Although limited by its requirement of a detection antibody, this protocol includes a rapid and high-throughput assay for measuring viral titer. By utilizing a baby hamster kidney cell line and a 96-well plate format, this protocol allows for more sensitivity in the detection of POWV lineage I. For complete details on the use and execution of this protocol, please refer to Stone et al. (2022).

A lyophilized colorimetric RT-LAMP test kit for rapid, low-cost, at-home molecular testing of SARS-CoV-2 and other pathogens.

Access to fast and reliable nucleic acid testing continues to play a key role in controlling the COVID-19 pandemic, especially in the context of increased vaccine break-through risks due to new variants. We report a rapid, low-cost (~ 2 USD), simple-to-use nucleic acid test kit for self-administered at-home testing without lab instrumentation. The entire sample-to-answer workflow takes < 60 min, including noninvasive sample collection, one-step RNA preparation, reverse-transcription loop-mediated isothermal amplification (RT-LAMP) in a thermos, and direct visual inspection of a colorimetric test result. To facilitate long-term storage without cold-chain, a fast one-pot lyophilization protocol was developed to preserve all required biochemical reagents of the colorimetric RT-LAMP test in a single microtube. Notably, the lyophilized RT-LAMP assay demonstrated reduced false positives as well as enhanced tolerance to a wider range of incubation temperatures compared to solution-based RT-LAMP reactions. We validated our RT-LAMP assay using simulated infected samples, and detected a panel of SARS-CoV-2 variants with successful detection of all variants that were available to us at the time. With a simple change of the primer set, our lyophilized RT-LAMP home test can be easily adapted as a low-cost surveillance platform for other pathogens and infectious diseases of global public health importance.

Balanced T and B cell responses are required for immune protection against Powassan virus in virus-like particle vaccination.

Powassan virus (POWV) is a tick-borne pathogen for which humans are an incidental host. POWV infection can be fatal or result in long-term neurological sequelae; however, there are no approved vaccinations for POWV. Integral to efficacious vaccine development is the identification of correlates of protection, which we accomplished in this study by utilizing a murine model of POWV infection. Using POWV lethal and sub-lethal challenge models, we show that (1) robust B and T cell responses are necessary for immune protection, (2) POWV lethality can be attributed to both viral- and host-mediated drivers of disease, and (3) knowledge of the immune correlates of protection against POWV can be applied in a virus-like particle (VLP)-based vaccination approach that provides protection from lethal POWV challenge. Identification of these immune protection factors is significant as it will aid in the rational design of POWV vaccines.

Clinical Models to Define Response and Survival With Anti-PD-1 Antibodies Alone or Combined With Ipilimumab in Metastatic Melanoma.

PURPOSE: Currently, there are no robust biomarkers that predict immunotherapy outcomes in metastatic melanoma. We sought to build multivariable predictive models for response and survival to anti-programmed cell death protein 1 (anti-PD-1) monotherapy or in combination with anticytotoxic T-cell lymphocyte-4 (ipilimumab [IPI]; anti-PD-1 ± IPI) by including routine clinical data available at the point of treatment initiation. METHODS: One thousand six hundred forty-four patients with metastatic melanoma treated with anti-PD-1 ± IPI at 16 centers from Australia, the United States, and Europe were included. Demographics, disease characteristics, and baseline blood parameters were analyzed. The end points of this study were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The final predictive models for ORR, PFS, and OS were determined through penalized regression methodology (least absolute shrinkage and selection operator method) to select the most significant predictors for all three outcomes (discovery cohort, N = 633). Each model was validated internally and externally in two independent cohorts (validation-1 [N = 419] and validation-2 [N = 592]) and nomograms were created. RESULTS: The final model for predicting ORR (area under the curve [AUC] = 0.71) in immunotherapy-treated patients included the following clinical parameters: Eastern Cooperative Oncology Group Performance Status, presence/absence of liver and lung metastases, serum lactate dehydrogenase, blood neutrophil-lymphocyte ratio, therapy (monotherapy/combination), and line of treatment. The final predictive models for PFS (AUC = 0.68) and OS (AUC = 0.77) included the same variables as those in the ORR model (except for presence/absence of lung metastases), and included presence/absence of brain metastases and blood hemoglobin. Nomogram calculators were developed from the clinical models to predict outcomes for patients with metastatic melanoma treated with anti-PD-1 ± IPI. CONCLUSION: Newly developed combinations of routinely collected baseline clinical factors predict the response and survival outcomes of patients with metastatic melanoma treated with immunotherapy and may serve as valuable tools for clinical decision making.

Faculty support bundle for simulation education.

BACKGROUND: Postgraduate training programmes rely on faculty to meet core educational needs, including simulation. Time is arguably the most valuable resource for academic physicians, which presents a challenge for recruiting faculty to provide extra-clinical teaching. To increase faculty engagement in simulation-based education (SBE), we first identified barriers to participation. Next, we sought to overcome barriers using a self-determination theory (SDT) framework to increase motivation using strategies that addressed faculty autonomy, competence and relatedness. METHODS: Faculty from a single department of emergency medicine were surveyed about factors influencing participation in SBE. Responses were grouped into themes and used to develop the intervention-a faculty support bundle-to overcome common barriers and promote participation. Supports focused on course materials, organisational consistency and peer recognition. Faculty participation in SBE pre- and post-implementation of the support bundle was analysed via chi-squared analysis. Faculty who delivered SBE were resurveyed after the implementation phase to explore how the support bundle affected their experience. RESULTS: Initial survey response was 41%. Reported barriers to participation in SBE included scheduling issues, preparation time, competing responsibilities, lack of confidence with simulation and lack of interest. Twenty-four faculty participated in SBE during the pre-implementation phase, compared to 39 post implementation (p = 0.03). DISCUSSION: The faculty support bundle increases faculty participation in SBE. Strategies focused on internal motivators identified using an SDT framework. In contrast to traditional external motivators, these were no cost interventions. Those seeking to increase faculty participation in SBE should consider implementing similar strategies.

Chemotherapy after immune checkpoint inhibitor failure in metastatic melanoma: a retrospective multicentre analysis.

INTRODUCTION: Despite remarkably improved outcomes with immune checkpoint inhibition, many patients with metastatic melanoma will eventually require further therapy. Chemotherapy has limited activity when used first-line but can alter the tumour microenvironment and does improve efficacy when used in combination with immunotherapy in lung cancer. Whether chemotherapy after checkpoint inhibitor failure has relevant activity in patients with metastatic melanoma is unknown. METHODS: Patients with metastatic melanoma treated with chemotherapy after progression on immunotherapy with checkpoint inhibitors were identified retrospectively from 24 melanoma centres. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and safety were examined. RESULTS: In total, 463 patients were treated between 2007 and 2017. Fifty-six per cent had received PD-1-based therapy before chemotherapy. Chemotherapy regimens included carboplatin + paclitaxel (32%), dacarbazine (25%), temozolomide (15%), taxanes (9%, nab-paclitaxel 4%), fotemustine (6%) and others (13%). Median duration of therapy was 7.9 weeks (0-108). Responses included 0.4% complete response (CR), 12% partial response (PR), 21% stable disease (SD) and 67% progressive disease (PD). Median PFS was 2.6 months (2.2, 3.0), and median PFS in responders was 8.7 months (6.3, 16.3), respectively. Twelve-month PFS was 12% (95% CI 2-15%). In patients who had received anti-PD-1 before chemotherapy, the ORR was 11%, and median PFS was 2.5 months (2.1, 2.8). The highest activity was achieved with single-agent taxanes (N = 40), with ORR 25% and median PFS 3.9 months (2.1, 6.2). Median OS from chemotherapy start was 7.1 months (6.5, 8.0). Subsequent treatment with checkpoint inhibitors achieved a response rate of 16% with a median PFS of 19.1 months (2.0-43.1 months). No unexpected toxicities were observed. CONCLUSION: Chemotherapy has a low response rate and short PFS in patients with metastatic melanoma who have failed checkpoint inhibitor therapy, although activity varied between regimens. Chemotherapy has a limited role in the management of metastatic melanoma.

Sequencing of an Undifferentiated Carcinoma with Osteoclast-Like Giant Cells of the Pancreas: A Case Report.

Background: Undifferentiated carcinoma with osteoclast-like giant cells/osteoclast-like giant cell reaction (UC-OGC) is a rare form of pancreatic cancer historically associated with a poor prognosis. Molecular tumor profiling provides new information about tumor origins and a more nuanced understanding of the potential efficacy of different chemotherapeutic agents. Presentation: A 69-year-old man presented with a 13-cm periampullary pancreatic mass. Biopsy of a neighboring lymph node was consistent with adenocarcinoma. After neoadjuvant chemoradiation, the patient underwent resection and the tumor was consistent with UC-OGC. Next-generation sequencing was performed with genomic and proteomic analyses analyzed by a molecular tumor board review. These analyses revealed genetic alterations similar to those seen in pancreatic ductal adenocarcinoma, as well as potential therapeutic targets for the patient's subsequent therapy. Conclusions: Understanding a tumor's genetic changes allows for better understanding of its biology and may improve treatment efficacy. We believe that future study in tumor profiling will improve our understanding of rare cancers such as UC-OGC and also pave the way for the use of novel therapies to specifically target mutations in a broad range of more common tumors.

Maintaining procedural skills for academic emergency medicine faculty: A needs assessment.

BACKGROUND: Emergency physicians require competence performing critical and routine procedures. The clinical practice of emergency medicine (EM) alone may be insufficient for the acquisition and maintenance of skills. Prior studies suggest the presence of trainees in academic settings and/or the low frequency of procedures increase the risk of skills attrition among faculty. We sought to develop a valid needs assessment survey to inform a faculty procedural skills (FPS) maintenance curriculum. METHODS: A Web-based FPS survey was designed to assess experiences performing procedures, self-reported confidence with procedures, and learning preferences for skills maintenance. The survey was administered at a large academic department of EM. Responses were analyzed to determine survey construct validity, faculty attitudes about procedural attrition, and preferred learning methods. RESULTS: Among EM faculty, confidence was significantly higher for common versus uncommon procedures (p < 0.001). EM faculty respondents reported significantly greater confidence than pediatric EM (PEM) faculty for both common adult procedures (EM mean = 3.7 [±0.3], PEM = 3.0 [±0.4], p < 0.001), and uncommon adult procedures (EM = 2.7 [±0.4], PEM = 2.1 [±0.5], p < 0.001). PEM faculty reported significantly greater confidence with pediatric procedures than EM faculty (PEM mean [±SD] = 3.5 [±0.8], EM = 2.2 [±0.8], p < 0.001). Nearly all faculty (93% [52/56]) agreed that procedural attrition is a concerning problem, and 80% (44/56) had personally experienced it. The most preferred learning methods were task trainers and simulation. Faculty preferred learning environments with faculty peers (91%) over mixed groups with trainees (50%). CONCLUSIONS: Significant differences in procedural skills confidence between common and uncommon procedures, and between EM and PEM faculty, indicate that the FPS survey displayed appropriate construct validity. The finding that skills attrition is prevalent among EM and PEM faculty highlights the need for skill maintenance programming, preferably in peer groups employing task trainers and simulation.

DICOM Image ANalysis and Archive (DIANA): an Open-Source System for Clinical AI Applications.

In the era of data-driven medicine, rapid access and accurate interpretation of medical images are becoming increasingly important. The DICOM Image ANalysis and Archive (DIANA) system is an open-source, lightweight, and scalable Python interface that enables users to interact with hospital Picture Archiving and Communications Systems (PACS) to access such data. In this work, DIANA functionality was detailed and evaluated in the context of retrospective PACS data retrieval and two prospective clinical artificial intelligence (AI) pipelines: bone age (BA) estimation and intra-cranial hemorrhage (ICH) detection. DIANA orchestrates activity beginning with post-acquisition study discovery and ending with online notifications of findings. For AI applications, system latency (exam completion to system report time) was quantified and compared to that of clinicians (exam completion to initial report creation time). Mean DIANA latency was 9.04 ± 3.83 and 20.17 ± 10.16 min compared to clinician latency of 51.52 ± 58.9 and 65.62 ± 110.39 min for BA and ICH, respectively, with DIANA latencies being significantly lower (p < 0.001). DIANA's capabilities were also explored and found effective in retrieving and anonymizing protected health information for "big-data" medical imaging research and analysis. Mean per-image retrieval times were 1.12 ± 0.50 and 0.08 ± 0.01 s across x-ray and computed tomography studies, respectively. The data herein demonstrate that DIANA can flexibly integrate into existing hospital infrastructure and improve the process by which researchers/clinicians access imaging repository data. This results in a simplified workflow for large data retrieval and clinical integration of AI models.

Hyperacute toxicity with combination ipilimumab and anti-PD1 immunotherapy.

BACKGROUND: Combination ipilimumab and nivolumab is approved for several malignancies. Toxicity most often occurs 6-10 weeks into treatment. Whether very early toxicity is harder to manage or influences efficacy is unknown. METHODS: Consecutive metastatic melanoma patients who developed hyperacute toxicity, defined as Grade 2+ irAE within 21 days of receiving ipilimumab + anti-PD-1 were retrospectively identified from nine centres. RESULTS: A total of 82 patients developed hyperacute toxicity (estimated incidence 9%), at a median 10 days (range 1-21). Toxicities included colitis (N = 23), rash (17), hepatitis (9), endocrine (9), pneumonitis (6) and neurotoxicity (4) and were G2 (38%), G3 (52%), G4 (6%) and G5 (2% myocarditis). Fifty-nine percent required treatment beyond oral steroids, including IV steroids (28%), infliximab and other immunosuppression (30%). A total of 29% patients developed an additional hyperacute toxicity and 26% another toxicity >21 days after treatment commencement but before further immunotherapy. The objective response rate (ORR) was 54%, and after a median 11.6 mo follow-up, median PFS was 7.4 mo. Increasing levels of immunosuppression was associated with a reduced PFS (12-month PFS 62% no immunosuppression versus 49% oral steroids versus 33% IV steroids versus 20% further immunosuppressants, p = 0.006). There was no significant difference in ORR or PFS by duration of immunosuppression. CONCLUSIONS: Hyperacute toxicities from combination immunotherapy have a wide spectrum and can be severe. Many patients require significant immunosuppression for prolonged durations and remain at risk of further severe toxicity. Melanoma outcomes in such patients appear similar to those of trial populations, although greater immunosuppression requirements may be associated with inferior outcomes.

Targeting Chikungunya Virus Replication by Benzoannulene Inhibitors.

A benzo[6]annulene, 4-(tert-butyl)-N-(3-methoxy-5,6,7,8-tetrahydronaphthalen-2-yl) benzamide (1a), was identified as an inhibitor against Chikungunya virus (CHIKV) with antiviral activity EC90 = 1.45 µM and viral titer reduction (VTR) of 2.5 log at 10 µM with no observed cytotoxicity (CC50 = 169 µM) in normal human dermal fibroblast cells. Chemistry efforts to improve potency, efficacy, and drug-like properties of 1a resulted in a novel lead compound 8q, which possessed excellent cellular antiviral activity (EC90 = 270 nM and VTR of 4.5 log at 10 µM) and improved liver microsomal stability. CHIKV resistance to an analog of 1a, compound 1c, tracked to a mutation in the nsP3 macrodomain. Further mechanism of action studies showed compounds working through inhibition of human dihydroorotate dehydrogenase in addition to CHIKV nsP3 macrodomain. Moderate efficacy was observed in an in vivo CHIKV challenge mouse model for compound 8q as viral replication was rescued from the pyrimidine salvage pathway.

Novel Two-Stage Open Spine and Robotic Thoracic Approach to Resection of a Mediastinal Tumor.

Posterior mediastinal dumbbell tumors are rare, and dumbbell tumors of nonneurogenic origin are even more infrequent. Here we discuss a novel surgical approach to resection. A 60-year-old man presented with several years of bilateral lower extremity weakness. Axial imaging demonstrated a large T3 paraspinal tumor with invasion into the spinal canal and left thorax. Resection was completed in a multidisciplinary staged approach: a partial mass resection and posterior spine decompression and fusion, followed by robotic-assisted left thoracoscopic extraspinal tumor excision. Staged robotic-assisted resection with this type of tumor has never been attempted.

The Emergency Medicine Group Standardized Letter of Evaluation as a Workplace-based Assessment: The Validity Is in the Detail.

INTRODUCTION: Interest is growing in specialty-specific assessments of student candidates based on clinical clerkship performance to assist in the selection process for postgraduate training. The most established and extensively used is the emergency medicine (EM) Standardized Letter of Evaluation (SLOE), serving as a substitute for the letter of recommendation. Typically developed by a program's leadership, the group SLOE strives to provide a unified institutional perspective on performance. The group SLOE lacks guidelines to direct its development raising questions regarding the assessments, processes, and standardization programs employ. This study surveys EM programs to gather validity evidence regarding the inputs and processes involved in developing group SLOEs. METHODS: A structured telephone interview was administered to assess the input data and processes employed by United States EM programs when generating group SLOEs. RESULTS: With 156/178 (87.6%) of Accreditation Council of Graduate Medical Education-approved programs responding, 146 (93.6%) reported developing group SLOEs. Issues identified in development include the following: (1) 84.9% (124/146) of programs limit the consensus process by not employing rigorous methodology; (2) several stakeholder groups (nurses, patients) do not participate in candidate assessment placing final decisions at risk for construct under-representation; and (3) clinical shift assessments don't reflect the task-specific expertise of each stakeholder group nor has the validity of each been assessed. CONCLUSION: Success of the group SLOE in its role as a summative workplace-based assessment is dependent upon valid input data and appropriate processes. This study of current program practices provides specific recommendations that would strengthen the validity arguments for the group SLOE.

Analysis of Serum Anti-Zika Virus Antibodies by Focus Reduction Neutralization Test.

Zika virus (ZIKV) is a newly emerged mosquito-borne flavivirus that has been associated with birth defects of babies born to ZIKV-infected mothers. Neutralization activity of serum derived from ZIKV infected and vaccinated individuals is a critical component for characterizing immune response to infection and vaccine efficacy. This protocol describes a modified plaque reduction neutralization 50 (PRNT50) assay that includes an immunostaining step to improve reproducibility and throughput of the assay.

The E3 Ubiquitin Ligase SIAH1 Targets MyD88 for Proteasomal Degradation During Dengue Virus Infection.

The dengue virus presents a serious threat to human health globally and can cause severe, even life-threatening, illness. Dengue virus (DENV) is endemic on all continents except Antarctica, and it is estimated that more than 100 million people are infected each year. Herein, we further mine the data from a previously described screen for microRNAs (miRNAs) that block flavivirus replication. We use miR-424, a member of the miR-15/16 family, as a tool to further dissect the role of host cell proteins during DENV infection. We observed that miR-424 suppresses expression of the E3 ubiquitin ligase SIAH1, which is normally induced during dengue virus 2 (DENV2) infection through activation of the unfolded protein response (UPR). Specific siRNA-mediated knockdown of SIAH1 also results in inhibition of DENV replication, demonstrating that this target is at least partly responsible for the antiviral activity of miR-424. We further show that SIAH1 binds to and ubiquitinates the innate immune adaptor protein MyD88 and that the antiviral effect of SIAH1 knockdown is reduced in cells in which MyD88 has been deleted by CRISPR/Cas9 gene editing. Additionally, MyD88-dependent signaling, triggered either by DENV2 infection or the Toll-like receptor 7 (TLR7) ligand imiquimod, is increased in cells in which SIAH1 has been knocked down by miR-424 or a SIAH1-specific siRNA. These observations suggest an additional pathway by which DENV2 harnesses aspects of the UPR to dampen the host innate immune response and promote viral replication.

A neonatal nonhuman primate model of gestational Zika virus infection with evidence of microencephaly, seizures and cardiomyopathy.

Zika virus infection during pregnancy is associated with miscarriage and with a broad spectrum of fetal and neonatal developmental abnormalities collectively known as congenital Zika syndrome (CZS). Symptomology of CZS includes malformations of the brain and skull, neurodevelopmental delay, seizures, joint contractures, hearing loss and visual impairment. Previous studies of Zika virus in pregnant rhesus macaques (Macaca mulatta) have described injury to the developing fetus and pregnancy loss, but neonatal outcomes following fetal Zika virus exposure have yet to be characterized in nonhuman primates. Herein we describe the presentation of rhesus macaque neonates with a spectrum of clinical outcomes, including one infant with CZS-like symptoms including cardiomyopathy, motor delay and seizure activity following maternal infection with Zika virus during the first trimester of pregnancy. Further characterization of this neonatal nonhuman primate model of gestational Zika virus infection will provide opportunities to evaluate the efficacy of pre- and postnatal therapeutics for gestational Zika virus infection and CZS.