Recombinant Bacillus Calmette-Guérin Expressing SARS-CoV-2 Chimeric Protein Protects K18-hACE2 Mice against Viral Challenge.

COVID-19 has accounted for more than 6 million deaths worldwide. Bacillus Calmette-Guérin (BCG), the existing tuberculosis vaccine, is known to induce heterologous effects over other infections due to trained immunity and has been proposed to be a potential strategy against SARS-CoV-2 infection. In this report, we constructed a recombinant BCG (rBCG) expressing domains of the SARS-CoV-2 nucleocapsid and spike proteins (termed rBCG-ChD6), recognized as major candidates for vaccine development. We investigated whether rBCG-ChD6 immunization followed by a boost with the recombinant nucleocapsid and spike chimera (rChimera), together with alum, provided protection against SARS-CoV-2 infection in K18-hACE2 mice. A single dose of rBCG-ChD6 boosted with rChimera associated with alum elicited the highest anti-Chimera total IgG and IgG2c Ab titers with neutralizing activity against SARS-CoV-2 Wuhan strain when compared with control groups. Importantly, following SARS-CoV-2 challenge, this vaccination regimen induced IFN-γ and IL-6 production in spleen cells and reduced viral load in the lungs. In addition, no viable virus was detected in mice immunized with rBCG-ChD6 boosted with rChimera, which was associated with decreased lung pathology when compared with BCG WT-rChimera/alum or rChimera/alum control groups. Overall, our study demonstrates the potential of a prime-boost immunization system based on an rBCG expressing a chimeric protein derived from SARS-CoV-2 to protect mice against viral challenge.

Simon Wile Symposium: Pivoting in the Pandemic for Pediatric Consultation-Liaison Psychiatry Services

Objectives: The goal of this year's Simon Wile Symposium is to explore innovative strategies to adjust systems and services addressing pediatric mental health challenges in hospital settings during the COVID-19 pandemic. Pediatric mental health needs climbed significantly during the pandemic, and pediatric consultation-liaison psychiatry services (PCLPS) have been at the forefront of addressing these needs in our community health systems. They have also been critical in supporting emotional health and well-being of fellow healthcare workers. National experts will share their innovative approaches to pivoting their PCLPS in their respective institutions and communities during the pandemic. Method(s): Center for Inclusive Child Care (CICC) members were polled on preferred topics in collaborative care and pediatric consultation-liaison to be presented at the upcoming annual meeting. We sought those pursuing innovative strategies that also might be able to provide to a variety of regions and programs. The literature around the PCLPS provision during the pandemic was reviewed, resulting in the current Symposium submission. Result(s): We will share data and strategies to support emotional health and well-being of healthcare workers in a large hospital system in an urban area that was hit hard by the COVID-19 pandemic. We will share data and lessons learned from one PCLPS in utilizing telehealth to support and augment pediatric mental health services in a large children's hospital. We will also review from a multisite survey of pediatric consultation-liaison and other data in comparison to one academic site, reviewing adaptations in services and utilization in children's hospitals across the country. We will present the recipient of the 2022 Simon Wile Award, who will present on a consultation-liaison or collaborative care topic. Conclusion(s): As child and adolescent psychiatrists continue to work to address the significantly increased child mental health needs in communities across the country during the COVID-19 pandemic, programs that have found innovative strategies to address these needs in children's hospitals and large health systems can help us learn how to respond to similar public health challenges in the future. Our speakers will share how child and adolescent psychiatrists can be at the forefront of meeting public health challenges now and in the future. CON, DS, PYI Copyright © 2022

ECHOCARDIOGRAPHIC ABNORMALITIES ARE COMMON AMONG PATIENTS WITH COVID-19 INFECTION AND INDEPENDENTLY CONFER INCREASED RISK OF IN-HOSPITAL MORTALITY

Background Biomarker-evidenced myocardial injury is common among patients with COVID-19 infection and confers an increased risk of mortality. Prevalence and incremental prognostic impact of myocardial dysfunction is unknown. Methods Consecutive COVID-19 patients undergoing clinical echocardiography during their index hospitalization at three New York City hospitals were studied. Images were analyzed by a central core lab blinded to all clinical data. LV dysfunction was defined as LVEF < 55% and RV dysfunction as TAPSE <1.6 cm or S’<10 mm/s. Results 733 patients (64 ± 15 years, 61% men) were studied. Myocardial injury (elevated troponin) occurred in 21% of patients, among whom either LV or RV myocardial dysfunction occurred in 72% (LV: 54%, RV:24%). Myocardial dysfunction was more common among patients with myocardial injury vs. without (LV: 54 vs. 32% p<0.001;RV: 24 vs. 10% p=0.001). During inpatient follow-up (median 15 [IQR 6-35] days), in-hospital mortality occurred in 34% with myocardial injury and 44% with LV or RV dysfunction vs. 23% without myocardial injury (p<0.001). Risk for death was greatest among patients with combined myocardial dysfunction and myocardial injury, and less with myocardial injury alone [Figure]. Conclusion Echo-evidenced myocardial dysfunction occurs in nearly three quarters of patients with myocardial injury and is a powerful predictor of in-hospital mortality. [Formula presented]

Immunoinformatic Analysis of SARS-CoV-2 Nucleocapsid Protein and Identification of COVID-19 Vaccine Targets.

COVID-19 is a worldwide emergency; therefore, there is a critical need for foundational knowledge about B and T cell responses to SARS-CoV-2 essential for vaccine development. However, little information is available defining which determinants of SARS-CoV-2 other than the spike glycoprotein are recognized by the host immune system. In this study, we focus on the SARS-CoV-2 nucleocapsid protein as a suitable candidate target for vaccine formulations. Major B and T cell epitopes of the SARS-CoV-2 N protein are predicted and resulting sequences compared with the homolog immunological domains of other coronaviruses that infect human beings. The most dominant of B cell epitope is located between 176-206 amino acids in the SRGGSQASSRSSSRSRNSSRNSTPGSSRGTS sequence. Further, we identify sequences which are predicted to bind multiple common MHC I and MHC II alleles. Most notably there is a region of potential T cell cross-reactivity within the SARS-CoV-2 N protein position 102-110 amino acids that traverses multiple human alpha and betacoronaviruses. Vaccination strategies designed to target these conserved epitope regions could generate immune responses that are cross-reactive across human coronaviruses, with potential to protect or modulate disease. Finally, these predictions can facilitate effective vaccine design against this high priority virus.

Vaccines for COVID-19: perspectives from nucleic acid vaccines to BCG as delivery vector system.

This article discusses standard and new disruptive strategies in the race to develop an anti-COVID-19 vaccine. We also included new bioinformatic data from our group mapping immunodominant epitopes and structural analysis of the spike protein. Another innovative approach reviewed here is the use of BCG vaccine as priming strategy and/or delivery system expressing SARS-CoV-2 antigens.