Clinical characteristics and comorbidities associated with SARS-CoV-2 breakthrough infection in the University of California Healthcare Systems.

BACKGROUND: To evaluate the degree to which clinical comorbidities or combinations of comorbidities are associated with SARS-CoV-2 breakthrough infection. MATERIALS AND METHODS: A breakthrough infection was defined as a positive test at least 14 days after a full vaccination regimen. Logistic regression was used to calculate aORs, which were adjusted for age, sex, and race information. RESULTS: A total of 110,380 patients from the UC CORDS database were included. After adjustment, stage 5 CKD due to hypertension (aOR: 7.33; 95% CI: 4.86-10.69; p<.001; power=1) displayed higher odds of infection than any other comorbidity. Lung transplantation history (aOR: 4.79; 95% CI: 3.25-6.82; p<.001; power= 1), coronary atherosclerosis (aOR: 2.12; 95% CI: 1.77-2.52; p<.001; power=1), and vitamin D deficiency (aOR: 1.87; 95% CI: 1.69-2.06; p<.001; power=1) were significantly correlated to breakthrough infection. Patients with obesity in addition to essential hypertension (aOR: 1.74; 95% CI: 1.51-2.01; p<.001; power=1) and anemia (aOR: 1.80; 95% CI: 1.47-2.19; p<.001; power=1) were at additional risk of breakthrough infection compared to those with essential hypertension and anemia alone. CONCLUSIONS: Further measures should be taken to prevent breakthrough infection for individuals with these conditions, such as acquiring additional doses of the SARS-CoV-2 vaccine to boost immunity.

The TeleKidSeq pilot study: incorporating telehealth into clinical care of children from diverse backgrounds undergoing whole genome sequencing.

BACKGROUND: The COVID-19 pandemic forced healthcare institutions and many clinical research programs to adopt telehealth modalities in order to mitigate viral spread. With the expanded use of telehealth, there is the potential to increase access to genomic medicine to medically underserved populations, yet little is known about how best to communicate genomic results via telehealth while also ensuring equitable access. NYCKidSeq, a multi-institutional clinical genomics research program in New York City, launched the TeleKidSeq pilot study to assess alternative forms of genomic communication and telehealth service delivery models with families from medically underserved populations. METHODS: We aim to enroll 496 participants between 0 and 21 years old to receive clinical genome sequencing. These individuals have a neurologic, cardiovascular, and/or immunologic disease. Participants will be English- or Spanish-speaking and predominantly from underrepresented groups who receive care in the New York metropolitan area. Prior to enrollment, participants will be randomized to either genetic counseling via videoconferencing with screen-sharing or genetic counseling via videoconferencing without screen-sharing. Using surveys administered at baseline, results disclosure, and 6-months post-results disclosure, we will evaluate the impact of the use of screen-sharing on participant understanding, satisfaction, and uptake of medical recommendations, as well as the psychological and socioeconomic implications of obtaining genome sequencing. Clinical utility, cost, and diagnostic yield of genome sequencing will also be assessed. DISCUSSION: The TeleKidSeq pilot study will contribute to innovations in communicating genomic test results to diverse populations through telehealth technology. In conjunction with NYCKidSeq, this work will inform best practices for the implementation of genomic medicine in diverse, English- and Spanish-speaking populations.

Epitope-focused immunogen design based on the ebolavirus glycoprotein HR2-MPER region.

The three human pathogenic ebolaviruses: Zaire (EBOV), Bundibugyo (BDBV), and Sudan (SUDV) virus, cause severe disease with high fatality rates. Epitopes of ebolavirus glycoprotein (GP) recognized by antibodies with binding breadth for all three ebolaviruses are of major interest for rational vaccine design. In particular, the heptad repeat 2 -membrane-proximal external region (HR2-MPER) epitope is relatively conserved between EBOV, BDBV, and SUDV GP and targeted by human broadly-neutralizing antibodies. To study whether this epitope can serve as an immunogen for the elicitation of broadly-reactive antibody responses, protein design in Rosetta was employed to transplant the HR2-MPER epitope identified from a co-crystal structure with the known broadly-reactive monoclonal antibody (mAb) BDBV223 onto smaller scaffold proteins. From computational analysis, selected immunogen designs were produced as recombinant proteins and functionally validated, leading to the identification of a sterile alpha motif (SAM) domain displaying the BDBV-HR2-MPER epitope near its C terminus as a promising candidate. The immunogen was fused to one component of a self-assembling, two-component nanoparticle and tested for immunogenicity in rabbits. Robust titers of cross-reactive serum antibodies to BDBV and EBOV GPs and moderate titers to SUDV GP were induced following immunization. To confirm the structural composition of the immunogens, solution NMR studies were conducted and revealed structural flexibility in the C-terminal residues of the epitope. Overall, our study represents the first report on an epitope-focused immunogen design based on the structurally challenging BDBV-HR2-MPER epitope.

[Results of a survey aimed at dietitians-nutritionists on the management of clinical nutrition teams during the COVID-19 pandemic in hospitals in Catalonia]. / Resultados de una encuesta dirigida a dietistas-nutricionistas sobre la gestión de los equipos de nutrición clínica durante la pandemia de COVID-19 en centros hospitalarios de Cataluña.

INTRODUCTION: Introduction: the COVID-19 pandemic has had direct implications for clinical nutrition teams (NT), both at an organizational and healthcare level. Since March 2020, expert recommendations on nutritional intervention for patients with COVID-19 have been available. Objectives: to describe the nutritional intervention that has been carried out in patients with COVID-19, to estimate the presence of clinical dietitians-nutritionists (DN) in hospitals in Catalonia, and to know the organization of NTs. Methods: a cross-sectional study through an online survey directed to clinical DNs at hospitals in Catalonia (March 2021) was made. Results: the surveys of 36 NTs, made up of 104 DNs, have been analysed. A total of 44.44 % of NTs had to interrupt or reduce some of their usual activities during the pandemic. When nutritional screening was used, it was carried out early (24-48 h) in 56.25 % of cases, and the most common tool was the NRS-2002 (66.67 %). In 41.67 % of NTs a specific hospital diet was established, this being generally hyperproteic (89.66 %). Oral nutritional supplementation was systematically prescribed by 41.67 % of NTs, prioritizing hyperproteic (97.14 %) and hypercaloric (74.29 %) formulas. It is estimated that clinical DNs are present in approximately 61.54 % of public acute hospitals in Catalonia. Conclusions: the results reflect the adaptive capacity of NTs, reorganizing and redistributing their usual tasks and establishing infrequent measures to ensure nutritional support.

INTRODUCCIÓN: Introducción: la pandemia por COVID-19 ha tenido implicaciones directas en los equipos de nutrición (EN) clínica a nivel tanto organizativo como asistencial. Desde marzo de 2020 se dispone de recomendaciones de expertos sobre la intervención nutricional en pacientes con COVID-19. Objetivos: describir la intervención nutricional que se ha llevado a cabo en los pacientes con COVID-19, estimar la presencia de dietistas-nutricionistas (DN) clínicos en los hospitales de Cataluña y conocer la organización de los EN. Métodos: estudio transversal realizado a través de una encuesta online dirigida a los DN clínicos de los hospitales de Cataluña (marzo 2021). Resultados: se han analizado las encuestas de 36 EN, formados por 104 DN. El 44,44 % de los EN han tenido que dejar de hacer o reducir alguna de sus actividades habituales durante la pandemia. Cuando se ha empleado el cribado nutricional, este se ha realizado de forma precoz (24-48 h) en el 56,25 % de los casos y la herramienta más común ha sido el NRS-2002 (66,67 %). El 41,67 % de los EN han instaurado una dieta hospitalaria específica, siendo esta generalmente hiperproteica (89,66 %). El 41,67 % de los EN han pautado la suplementación nutricional oral de forma sistemática, priorizando las fórmulas hiperproteicas (97,14 %) e hipercalóricas (74,29 %). Se estima que la figura del DN clínico está presente en aproximadamente el 61,54 % de los hospitales de agudos públicos de Cataluña. Conclusiones: los resultados reflejan la capacidad de adaptación de los EN, reorganizando y redistribuyendo sus tareas habituales e instaurando medidas poco habituales para asegurar el soporte nutricional.

Risk Factors for COVID-19 Morbidity and Mortality in Institutionalised Elderly People.

BACKGROUND: SARS-CoV-2 has caused a high mortality in institutionalised individuals. There are very few studies on the involvement and the real impact of COVID-19 in nursing homes. This study analysed factors related to morbidity and mortality of COVID-19 in institutionalised elderly people. METHODS: This cohort study included 842 individuals from 12 nursing homes in Sant Cugat del Vallès (Spain) from 15 March to 15 May 2020. We evaluated individual factors (demographic, dependence, clinical, and therapeutic) and those related to the nursing homes (size and staff) associated with infection and mortality by SARS-CoV-2. Infection was diagnosed by molecular biology test. RESULTS: Of the 842 residents included in the analysis, 784 underwent a Polymerase Chain Reaction (PCR) test; 74.2% were women, the mean age was 87.1 years, and 11.1% died. The PCR test was positive in 44%. A total of 33.4% of the residents presented symptoms compatible with COVID-19 and of these, 80.9% were PCR-positive for SARS-CoV-2. Infection by SARS-CoV-2 among residents was associated with the rate of staff infected in the homes. Mortality by SARS-CoV-2 was related to male sex and a greater grade of dependence measured with the Barthel index. CONCLUSIONS: SARS-Cov-2 infection in institutionalised people is associated with the infection rate in nursing home workers and mortality by SARS-Cov-2 with sex and greater dependency according to the Barthel index. Adequate management of nursing home staff and special attention to measures of infection control, especially of individuals with greater dependence, are keys for successful management of future pandemic situations.

Genetic and structural basis for SARS-CoV-2 variant neutralization by a two-antibody cocktail.

Understanding the molecular basis for immune recognition of SARS-CoV-2 spike glycoprotein antigenic sites will inform the development of improved therapeutics. We determined the structures of two human monoclonal antibodies-AZD8895 and AZD1061-which form the basis of the investigational antibody cocktail AZD7442, in complex with the receptor-binding domain (RBD) of SARS-CoV-2 to define the genetic and structural basis of neutralization. AZD8895 forms an 'aromatic cage' at the heavy/light chain interface using germ line-encoded residues in complementarity-determining regions (CDRs) 2 and 3 of the heavy chain and CDRs 1 and 3 of the light chain. These structural features explain why highly similar antibodies (public clonotypes) have been isolated from multiple individuals. AZD1061 has an unusually long LCDR1; the HCDR3 makes interactions with the opposite face of the RBD from that of AZD8895. Using deep mutational scanning and neutralization escape selection experiments, we comprehensively mapped the crucial binding residues of both antibodies and identified positions of concern with regards to virus escape from antibody-mediated neutralization. Both AZD8895 and AZD1061 have strong neutralizing activity against SARS-CoV-2 and variants of concern with antigenic substitutions in the RBD. We conclude that germ line-encoded antibody features enable recognition of the SARS-CoV-2 spike RBD and demonstrate the utility of the cocktail AZD7442 in neutralizing emerging variant viruses.

Convergent antibody responses to the SARS-CoV-2 spike protein in convalescent and vaccinated individuals.

Unrelated individuals can produce genetically similar clones of antibodies, known as public clonotypes, which have been seen in responses to different infectious diseases, as well as healthy individuals. Here we identify 37 public clonotypes in memory B cells from convalescent survivors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or in plasmablasts from an individual after vaccination with mRNA-encoded spike protein. We identify 29 public clonotypes, including clones recognizing the receptor-binding domain (RBD) in the spike protein S1 subunit (including a neutralizing, angiotensin-converting enzyme 2 [ACE2]-blocking clone that protects in vivo) and others recognizing non-RBD epitopes that bind the S2 domain. Germline-revertant forms of some public clonotypes bind efficiently to spike protein, suggesting these common germline-encoded antibodies are preconfigured for avid recognition. Identification of large numbers of public clonotypes provides insight into the molecular basis of efficacy of SARS-CoV-2 vaccines and sheds light on the immune pressures driving the selection of common viral escape mutants.

[Comparison of expert recommendations on clinical nutrition for hospitalized patients with COVID-19]. / Comparación de las recomendaciones de expertos sobre nutrición clínica en pacientes hospitalizados con COVID-19.

INTRODUCTION: Introduction: in SARS-CoV-2-infected patients nutritional requirements are increased. These patients present symptoms that make food intake and nutrient absorption difficult, therefore involving nutritional risk. On the other hand, acute respiratory complications require prolonged ICU stays, and this predisposes to increased malnutrition and loss of skeletal muscle mass and function, which can lead to poor quality of life, disability and morbidity long after discharge. For this reason, the world's leading nutrition societies and associations believe that nutritional therapy should be considered a part of the basic treatment of patients with COVID-19. Methods: we have reviewed and compared 9 expert recommendations (ER) published by nutrition societies and associations from China, Spain, Brazil, Europe, Colombia, Australia, America, and the United Kingdom, in relation to critical and non-critical hospitalized patients due to the COVID-19 pandemic. Conclusions: the 9 ERs reviewed agree on the importance of nutritional management in critical and non-critical hospitalized patients with COVID-19, as well as on the early detection of nutritional risk, the intervention, and subsequent follow-up. Even so, each published document has its own particularities and puts a special stress on some specific aspect.

INTRODUCCIÓN: Introducción: la infección por SARS-CoV-2 implica riesgo nutricional debido a la dificultad de cubrir los requerimientos nutricionales aumentados en presencia de una sintomatología que dificulta la ingesta y la absorción de nutrientes. Por otro lado, las complicaciones respiratorias agudas requieren estancias prolongadas en unidades de cuidados intensivos (UCI) y esto predispone a una mayor desnutrición y a pérdida de masa y función del músculo esquelético, que a su vez puede conducir a una mala calidad de vida, discapacidad y morbilidad mucho después del alta. Por este motivo, las principales sociedades y asociaciones de nutrición clínica del mundo consideran que la terapia nutricional debe considerarse parte del tratamiento básico de los pacientes con COVID-19. Métodos: se han revisado y comparado 9 recomendaciones de expertos (RE) publicadas por sociedades y asociaciones de nutrición clínica de China, España, Brasil, Europa, Colombia, Australia, América y Reino Unido, a raíz de la pandemia por COVID-19, en relación a los pacientes hospitalizados críticos y no críticos. Conclusiones: las 9 RE revisadas coinciden en la importancia del tratamiento nutricional en los pacientes hospitalizados críticos y no críticos con COVID-19, así como en la detección precoz del riesgo nutricional, la intervención y el seguimiento. Aun así, cada documento publicado tiene sus propias particularidades e incide especialmente en algún aspecto.

Tobacco, but Not Nicotine and Flavor-Less Electronic Cigarettes, Induces ACE2 and Immune Dysregulation.

The COVID-19 pandemic caused by the SARS-CoV-2 virus, overlaps with the ongoing epidemics of cigarette smoking and electronic cigarette (e-cig) vaping. However, there is scarce data relating COVID-19 risks and outcome with cigarette or e-cig use. In this study, we mined three independent RNA expression datasets from smokers and vapers to understand the potential relationship between vaping/smoking and the dysregulation of key genes and pathways related to COVID-19. We found that smoking, but not vaping, upregulates ACE2, the cellular receptor that SARS-CoV-2 requires for infection. Both smoking and use of nicotine and flavor-containing e-cigs led to upregulation of pro-inflammatory cytokines and inflammasome-related genes. Specifically, chemokines including CCL20 and CXCL8 are upregulated in smokers, and CCL5 and CCR1 are upregulated in flavor/nicotine-containing e-cig users. We also found genes implicated in inflammasomes, such as CXCL1, CXCL2, NOD2, and ASC, to be upregulated in smokers and these e-cig users. Vaping flavor and nicotine-less e-cigs, however, did not lead to significant cytokine dysregulation and inflammasome activation. Release of inflammasome products, such as IL-1B, and cytokine storms are hallmarks of COVID-19 infection, especially in severe cases. Therefore, our findings demonstrated that smoking or vaping may critically exacerbate COVID-19-related inflammation or increase susceptibility to COVID-19.

Head and neck surgical oncology in the time of a pandemic: Subsite-specific triage guidelines during the COVID-19 pandemic.

BACKGROUND: COVID-19 pandemic has strained human and material resources around the world. Practices in surgical oncology had to change in response to these resource limitations, triaging based on acuity, expected oncologic outcomes, availability of supportive resources, and safety of health care personnel. METHODS: The MD Anderson Head and Neck Surgery Treatment Guidelines Consortium devised the following to provide guidance on triaging head and neck cancer (HNC) surgeries based on multidisciplinary consensus. HNC subsites considered included aerodigestive tract mucosa, sinonasal, salivary, endocrine, cutaneous, and ocular. RECOMMENDATIONS: Each subsite is presented separately with disease-specific recommendations. Options for alternative treatment modalities are provided if surgical treatment needs to be deferred. CONCLUSION: These guidelines are intended to help clinicians caring for patients with HNC appropriately allocate resources during a health care crisis, such as the COVID-19 pandemic. We continue to advocate for individual consideration of cases in a multidisciplinary fashion based on individual patient circumstances and resource availability.