Changes in Prenatal Care Utilization:United States, 2019-2021.

Objectives-This report describes changes in prenatal care use (utilization) in the United States before and during the COVID-19 pandemic by month of birth and the mother's race and Hispanic origin.

An Audit of Demographics, Symptoms & Investigations: Part of the Survey of Gca in the Sehsct during the Covid-19 Pandemic

Background/Aims Giant cell arteritis (GCA) is the most common vasculitis in adults aged over 50 years old with the highest incidence among persons aged 70- 79. It is more commonly seen in female patients. Most cases have been reported in whites of Northern European descent. A broad range of symptoms can be reported including headache, jaw or tongue claudication, visual disturbances, PMR and other systemic features including weight loss, fever and sweats. In recent years new evidence has emerged regarding the investigation and treatment of GCA. This audit is to review the demographics, symptoms and investigations of patients who presented to the Rheumatology Department in SEHSCT with features concerning for possible GCA. Methods Retrospective collection of data from January 2020 to July 2021 using the regional Electronic Care Record NI with reference to presentations, investigation results, clinic records and follow-up letters. Results 70 patients were included (24 males and 46 females). Mean age was 72 years old. Table 1 shows the percentages of clinical symptoms reported. All patients investigated had an ESR (mean 57.8) and CRP (mean 54.1) checked. 43 patients had ANCA checked with 3 positive results. 40 patients underwent CT brain with 2 abnormalities reported unrelated to GCA. TA ultrasound was performed on one occasion with a positive result demonstrating ''halo'' sign recorded. 6 patients underwent CTPET with 3 diagnoses of LVV and 1 of PMR. 70 TAB performed with 12 positive results and 4 'suggestive' of GCA. Conclusion Our cohort of patients demonstrated demographics similar to the current global geographic trends in GCA. There are a broad range of clinical symptoms that can present in GCA, none of which are entirely specific or pathognomonic. Clinical diagnosis is based on clinical symptoms, signs and laboratory tests, each of which are imperfect markers for GCA. Our audit demonstrated that the use of additional confirmatory diagnostic tests including temporal artery ultrasound and CTPET was being under-utilized in the SEHSCT. Use of these tests may improve the diagnostic yield in this challenging condition. As a result of this audit, a quality improvement project to provide a rapid access GCA pathway is being designed. (Table Presented).

1-O-Octadecyl-2-O-benzyl-sn-glyceryl-3-phospho-GS-441524 (V2043). Evaluation of Oral V2043 in a Mouse Model of SARS-CoV-2 Infection and Synthesis and Antiviral Evaluation of Additional Phospholipid Esters with Enhanced Anti-SARS-CoV-2 Activity.

Early antiviral treatments, including intravenous remdesivir (RDV), reduce hospitalization and severe disease caused by COVID-19. An orally bioavailable RDV analog may facilitate earlier treatment of non-hospitalized COVID-19 patients. Here we describe the synthesis and evaluation of alkyl glyceryl ether phosphodiesters of GS-441524 (RVn), lysophospholipid analogs which allow for oral bioavailability and stability in plasma. Oral treatment of SARS-CoV-2-infected BALB/c mice with 1-O-octadecyl-2-O-benzyl-sn-glyceryl-3-phospho-RVn (60 mg/kg orally, once daily for 5 days starting 12h after infection) reduced lung viral load by 1.5 log10 units versus vehicle at day 2 and to below the limit of detection at day 5. Structure/activity evaluation of additional analogs that have hydrophobic ethers at the sn-2 of glycerol revealed improved in vitro antiviral activity by introduction of a 3-fluoro-4-methoxy-substituted benzyl or a 3- or 4-cyano-substituted benzyl. Collectively, our data support the development of RVn phospholipid prodrugs as oral antiviral agents for prevention and treatment of SARS-CoV-2 infections.

Quality of nursing care and its relationship to work environment from the perspective of bedside nurses

Quality of nursing care has become an important when looking at patient outcomes and the impact it has on long-term care of the patient. Quality can be defined in many ways. Defining quality of nursing care can be a diverse approach based on the perspective of many individuals, including the perspective of nurses. Quality of nursing care from the nursing perspective is complex and has many variables that influence that perspective. Variables include nursing work load, patient acuity, supportive administration, teamwork within the facility/unit, patient/family conflict, and overtime shifts. Patients are the individuals that nurses commit to caring for and throughout research;the patient identifies the quality nursing care provided. Facilities often utilize patient satisfaction and patient outcomes when evaluating nursing care. The purpose of this research is to explore how quality of nursing care is defined historically and how the nurse perceives quality of nursing care and its relationship to work environment. Additionally, how their perception may change based on the COVID-19 pandemic. Existing evidence indicates that if nurses have a supportive or positive work environment, then a nurse is motivated to provide quality of nursing care. Healthcare presents its own unique stressor to nurses in their attempt to provide quality care. Healthcare is constantly changing, and it impacts the work environment of the nurse. There is a significant shortage of the nursing workforce. More nursing jobs will be needed in the United States than any other profession through 2022. 11 million more nurses are needed to prevent a further shortage. The aging population, aging workforce, workforce burnout, violence in the health care setting, and growth in certain regions make it difficult to provide the support nurses need in health care facilities. Measuring quality from the nursing perspective is complex. Ways to measure quality address the connection of quality of nursing care and nurse work environment. The hypothesis is supportive that quality of nursing care is given if there is a supportive work environment. The challenge is what a nurse identifies as a barrier, in giving quality of nursing care and what their facilities identify as quality of nursing care. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Identification of Human Host Substrates of the SARS-CoV-2 Mpro and PLpro Using Subtiligase N-Terminomics.

The recent emergence of SARS-CoV-2 in the human population has caused a global pandemic. The virus encodes two proteases, Mpro and PLpro, that are thought to play key roles in the suppression of host protein synthesis and immune response evasion during infection. To identify the specific host cell substrates of these proteases, active recombinant SARS-CoV-2 Mpro and PLpro were added to A549 and Jurkat human cell lysates, and subtiligase-mediated N-terminomics was used to capture and enrich protease substrate fragments. The precise location of each cleavage site was identified using mass spectrometry. Here, we report the identification of over 200 human host proteins that are potential substrates for SARS-CoV-2 Mpro and PLpro and provide a global mapping of proteolysis for these two viral proteases in vitro. Modulating proteolysis of these substrates will increase our understanding of SARS-CoV-2 pathobiology and COVID-19.

Generation of a SARS-CoV-2 reverse genetics system and novel human lung cell lines that exhibit high virus-induced cytopathology (preprint)

The global COVID-19 pandemic continues with an increasing number of cases worldwide and the emergence of new SARS-CoV-2 variants. In our study, we have developed novel tools with applications for screening antivirals, identifying virus-host dependencies, and characterizing viral variants. Using reverse genetics, we rescued SARS-CoV-2 Wuhan1 (D614G variant) wild type (WTFL) and reporter virus (NLucFL) using molecular BAC clones. The replication kinetics, plaque morphology and titers were comparable between rescued molecular clones and a clinical isolate (VIDO strain), thus providing confidence that the rescued viruses can be used as effective replication tools. Furthermore, the reporter SARS-CoV-2 NLucFL virus exhibited robust luciferase values over the time course of infection and was used to develop a rapid antiviral assay using remdesivir as proof-of-principle. In addition, as a tool to study lung-relevant virus-host interactions, we established novel human lung cell lines that support SARS-CoV-2 infection with high virus-induced cytopathology. Six lung cell lines (NCI-H23, A549, NCI-H1703, NCI-H520, NCI-H226, and HCC827) and HEK293T cells, were transduced to stably express ACE2 and tested for their ability to support virus infection. A549ACE2 B1 and HEK293TACE2 A2 cell lines exhibited more than 70% virus-induced cell death and a novel lung cell line NCI-H23ACE2 A3 showed about ~99% cell death post-infection. These cell lines are ideal for assays relying on live-dead selection and are currently being used in CRISPR knockout and activation screens in our lab.

Comparison of National and Global Asthma Management Guiding Documents.

Asthma is a common chronic disease that affects both adults and children, and that continues to have a high economic burden. Asthma management guidelines were first developed nearly 30 years ago to standardize care, maintain asthma control, improve quality of life, maintain normal lung function, prevent exacerbations, and prevent asthma mortality. The two most common asthma guidelines used today were developed by the National Asthma Education and Prevention Program (NAEPP) Expert Panel Working Group and the Global Initiative for Asthma Science Committee. Both guiding documents use scientific methodology to standardize their approach for formulating recommendations based on pertinent literature. Before the 2020 National Asthma Education and Prevention Program (Expert Panel Report 4), nothing had been released since the 2007 guidelines, whereas the Global Initiative for Asthma publishes updates annually. Although each of these asthma strategies is similar, there are some noted differences. Over the years, the focus of asthma treatment has shifted from acute to chronic management. Frontline respiratory therapists and other health-care providers should have a good understanding of these 2 guiding references and how they can impact acute and chronic asthma management. The primary focus of this narrative is to look at the similarities and differences of these 2 guiding documents as they pertain to the 6 key questions identified by the Expert Panel of the National Asthma Education and Prevention Program.

Quality of nursing care and its relationship to work environment from the perspective of bedside nurses

Quality of nursing care has become an important when looking at patient outcomes and the impact it has on long-term care of the patient. Quality can be defined in many ways. Defining quality of nursing care can be a diverse approach based on the perspective of many individuals, including the perspective of nurses. Quality of nursing care from the nursing perspective is complex and has many variables that influence that perspective. Variables include nursing work load, patient acuity, supportive administration, teamwork within the facility/unit, patient/family conflict, and overtime shifts. Patients are the individuals that nurses commit to caring for and throughout research;the patient identifies the quality nursing care provided. Facilities often utilize patient satisfaction and patient outcomes when evaluating nursing care. The purpose of this research is to explore how quality of nursing care is defined historically and how the nurse perceives quality of nursing care and its relationship to work environment. Additionally, how their perception may change based on the COVID-19 pandemic. Existing evidence indicates that if nurses have a supportive or positive work environment, then a nurse is motivated to provide quality of nursing care. Healthcare presents its own unique stressor to nurses in their attempt to provide quality care. Healthcare is constantly changing, and it impacts the work environment of the nurse. There is a significant shortage of the nursing workforce. More nursing jobs will be needed in the United States than any other profession through 2022. 11 million more nurses are needed to prevent a further shortage. The aging population, aging workforce, workforce burnout, violence in the health care setting, and growth in certain regions make it difficult to provide the support nurses need in health care facilities. Measuring quality from the nursing perspective is complex. Ways to measure quality address the connection of quality of nursing care and nurse work environment. The hypothesis is supportive that quality of nursing care is given if there is a supportive work environment. The challenge is what a nurse identifies as a barrier, in giving quality of nursing care and what their facilities identify as quality of nursing care. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Births in the United States, 2021.

This report presents selected highlights from 2021 final birth data on key demographic, healthcare use, and infant health indicators. The number of births, general fertility rates (GFRs) (births per 1,000 females aged 15-44), age-specific birth rates (births per 1,000 females in specified age group), vaginal birth after cesarean (VBAC) delivery rates, and preterm (less than 37 weeks of gestation) birth rates are presented. Results for 2019, 2020, and 2021 are shown for all births to provide context for changes in birth patterns noted during 2020, the first year of the COVID-19 pandemic (1,2). VBAC and preterm birth rates are shown for the three largest race and Hispanic-origin groups: non-Hispanic White, non-Hispanic Black, and Hispanic.

Immunogenicity and Reactogenicity of COVID-19 mRNA Vaccines in Allogeneic Stem Cell Transplant Recipients

Background. Allogeneic stem cell transplant (SCT) recipients are at an increased risk of poor outcomes from COVID-19. While the mRNA-1273 (Moderna) and BNT162b2 (Pfizer) COVID-19 mRNA vaccines are highly immunogenic in the general population, the immune response in SCT recipients is poorly understood. We characterized the immunogenicity and reactogenicity of COVID-19 mRNA vaccines in a cohort of SCT patients. Methods. We performed a prospective cohort study of 16 allogeneic SCT patients and 23 healthy controls. Blood samples for both cohorts were collected prior to first vaccination (baseline), at the time of second vaccination, and approximately 28 days post-second vaccination. Anti-Spike (S), anti-S1, anti-receptor binding domain (RBD), and anti-Nucleocapsid (N) IgG levels were measured quantitatively from plasma using a multiplexed single molecule array (Simoa) immunoassay. Reactogenicity was captured for the SCT cohort via a self-reported post-vaccination diary for 7 days after each dose. Results. Demographics and SCT recipients' characteristics are shown in Table 1. In the SCT cohort, we observed a significantly lower anti-S (p< 0.0001), S1 (p< 0.0001), and RBD (p< 0.0001) IgG responses as compared to healthy controls, both at the time of dose 2 and 28 days post-vaccine series (Fig 1). Overall, 62.5% of SCT recipients were responders after vaccine series completion, as compared to 100% of healthy controls (Fig 2). While no patients had a reported history of COVID-19 diagnosis, 2 patients in the SCT cohort had elevated anti-S IgG levels and 1 showed elevated anti-N at baseline. 10/16 participants in the SCT cohort completed at least one post-vaccination diary. Local and systemic reactions were reported by 67% and 22% of participants, respectively, after dose 1, and 63% and 50% after dose 2 (Figure 3). All reported events were mild. Anti-Spike (A), anti-S1 (B), anti-RBD (C), and anti-nucleocapsid (D) IgG titers were measured at baseline, time of second dose, and approximately 28 days after second vaccination. IgG levels were measured quantitatively using multiplexed single molecule array (Simoa) immunoassays, and are reported as Normalized Average Enzymes per Bead (AEB). Allogeneic stem cell transplant recipients (mauve) showed significantly lower anti-S, S1, and RBD IgG responses as compared to healthy controls (mint). Low titers of anti-N IgG demonstrates no history of COVID-19 natural infection during the course of the study. 10 allogeneic stem cell transplant recipients completed at least one diary for 7 days after vaccination. Reactions after dose 1 are shown in light blue, and reactions after dose 2 are shown in dark blue. Local reactions (A) were reported by 67% (6/9) of participants after dose 1, and 63% (5/8) after dose 2. Systemic reactions (B) were reported by 22% (2/9) of participants after dose 1, and 50% (4/8) after dose 2. All reported events were mild (Grade 1). Conclusion. Among SCT recipients, mRNA COVID-19 vaccines were well-tolerated but less immunogenic than in healthy controls. Further study is warranted to better understand heterogeneous characteristics that may affect the immune response in order to optimize COVID-19 vaccination strategies for SCT recipients. Figure 2: Response Rate to COVID-19 Vaccination An internally validated threshold for responders was established using pre-pandemic sera from healthy adults. A positive antibody response was was defined as individuals with anti-Spike IgG levels above the 1.07 Normalized AEB threshold.

Highly Specific Sigma Receptor Ligands Exhibit Anti-Viral Properties in SARS-CoV-2 Infected Cells.

(1) Background: There is a strong need for prevention and treatment strategies for COVID-19 that are not impacted by SARS-CoV-2 mutations emerging in variants of concern. After virus infection, host ER resident sigma receptors form direct interactions with non-structural SARS-CoV-2 proteins present in the replication complex. (2) Methods: In this work, highly specific sigma receptor ligands were investigated for their ability to inhibit both SARS-CoV-2 genome replication and virus induced cellular toxicity. This study found antiviral activity associated with agonism of the sigma-1 receptor (e.g., SA4503), ligation of the sigma-2 receptor (e.g., CM398), and a combination of the two pathways (e.g., AZ66). (3) Results: Intermolecular contacts between these ligands and sigma receptors were identified by structural modeling. (4) Conclusions: Sigma receptor ligands and drugs with off-target sigma receptor binding characteristics were effective at inhibiting SARS-CoV-2 infection in primate and human cells, representing a potential therapeutic avenue for COVID-19 prevention and treatment.

Favorable postoperative outcomes for children with COVID-19 infection undergoing surgical intervention: Experience at a free-standing children's hospital.

BACKGROUND: Current literature has shown that adult patients with perioperative Coronavirus Disease-2019 (COVID-19) have increased rates of postoperative morbidity and mortality. We hypothesized that children with COVID-19 have favorable postoperative outcomes compared to the reported adult experience. METHODS: We performed a retrospective cohort study for children with a confirmed preoperative COVID-19 diagnosis from April 1st, 2020 to August 15th, 2020 at a free-standing children's hospital. Primary outcomes evaluated were postoperative complications, readmissions, reoperations, and mortality within 30 days of operation. Secondary outcomes included hospital resource utilization, hospital length of stay, and postoperative oxygen support. RESULTS: A total of 66 children with preoperative confirmed COVID-19 were evaluated with median age of 9.5 years (interquartile range (IQR) 5-14) with 65% male and 70% Hispanic White. Sixty-five percent of patients had no comorbidities, with abdominal pain identified as the most common preoperative symptom (65%). Twenty-three percent of patients presented with no COVID-19 related symptoms. Eighty-two percent of patients had no preoperative chest imaging and 98% of patients did not receive preoperative oxygen support. General pediatric surgeons performed the majority of procedures (68%) with the most common diagnosis appendicitis (47%). Forty-one percent of patients were discharged the same day as surgery with 9% of patients utilizing postoperative intensive care unit resources and only 5% receiving postoperative invasive mechanical ventilation. Postoperative complications (7%), readmission (6%), and reoperation (6%) were infrequent, with no mortality. CONCLUSION: COVID-19+ children requiring surgery have a favorable postoperative course and short-term outcomes compared to the reported adult experience. TYPE OF STUDY: Prognosis Study. LEVEL OF EVIDENCE: Level IV.

Rethinking Remdesivir: Synthesis of Lipid Prodrugs that Substantially Enhance Anti-Coronavirus Activity (preprint)

The FDA has granted Remdesivir (RDV, GS-5734) an emergency use authorization on the basis of an acceleration of clinical recovery in hospitalized patients with COVID-19. Unfortunately, the drug must be administered intravenously, restricting its use to those with relatively advanced disease. RDV is also unstable in plasma and has a complex activation pathway which may contribute to its highly variable antiviral efficacy in SARS-CoV-2 infected cells. A potent orally bioavailable antiviral for early treatment of SARS-CoV-2 infection is needed. We focused on making simple orally bioavailable lipid analogs of Remdesivir nucleoside (RVn, GS-441524) that are processed to RVn-monophosphate, the precursor of the active RVn-triphosphate, by a single step intracellular cleavage. In addition to likely improved oral bioavailability and simpler metabolic activation, two of the three new lipid prodrugs of RVn had anti-SARS-CoV-2 activity 9 to 24 times greater than that of RDV in Vero E6 cells