Effect of the COVID-19 Pandemic on Trauma Volume and Transport Time at a Level I Trauma Center

Introduction: Baystate Medical Center is the only Level I Trauma Center in Western, MA. The COVID-19 pandemic has had varying effects on Trauma Centers in regards to volume. Initial studies showed an increase in volume during the lockdown phase, but there has been no evidence of trends after lockdown. Method(s): Retrospective, review of trauma registry data pre- COVID (1/2016-2/2020) and during COVID-19 pandemic (3/2020-12/2021). Comparisons between time periods performed using T-Test. Result(s): Mean total traumas per month were significantly increased during the pandemic (191.3 v. 110.3 patients per month, p <0.001). Both blunt (174.2 v. 100.4, p <0.001) and penetrating (17.1 v 9.9, p <0.001) traumas increased during the COVID pandemic. There was a significant increase in both scene calls (105.0 v 73.8, p<0.001) and interfacility transfers (IFT) (42.7 v 36.0 P = 0.004) during the pandemic. There was no change in injury severity score (11.0 v 11.2, p = 0.498) during the pandemic. Ground interfacility transport times (34.13 min v 28.60 min, p = 0.036) increased significantly during COVID. Other transport times were not changed. Conclusion(s): During the COVID-19 pandemic, Baystate Medical Center saw a statistically significant increase in trauma volume across multiple dimensions that continued even after the end of the lockdown period. In addition, IFT ground transport times increased suggesting that patients were being transported from facilities farther away likely due to the strain on the regional health system from the pandemic.

Ongoing traumatic stress during a global pandemic.

OBJECTIVE: The COVID-19 pandemic has been conceptualized as a potentially traumatic event, although heterogeneity in experience (e.g., isolation) and in type and severity of traumatic stress response (e.g., hygiene hypervigilance) query the applicability of the posttraumatic stress disorder (PTSD) diagnostic construct. Parallels may be drawn to chronic illness and continuous traumatic situations (CTS) literature, which suggests unique symptom presentations that may occur during cumulative, ongoing traumas. METHOD: Eighty-four adults completed the PTSD Checklist with appended questions evaluating pandemic index events, temporality of intrusive symptoms, self-appraised abnormality, and context dependence of symptoms. Using exploratory latent profile analysis, we modeled the latent structure of traumatic stress response to COVID-19 in order to evaluate possible nuanced patterns of symptoms differentiating PTSD from a transient ongoing trauma response. RESULTS: Two profiles broadly delineated by severity across all variables emerged, suggesting the framework of PTSD is apt when applied to COVID-19. However, secondary analyses revealed subtle signals supporting chronic illness and CTS frameworks. Specifically, some participants who met criteria for PTSD did not endorse index events meeting Criterion A, most endorsed intrusive symptoms related to a present or future threat (versus a past trauma), and 30% reported their symptoms to be context dependent. CONCLUSION: Results highlight a need for improved assessment and opportunities for treatment modification. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Lipase Elevation in Patients With COVID-19.

INTRODUCTION: Although coronavirus disease (COVID-19) has been associated with gastrointestinal manifestations, its effect on the pancreas remains unclear. We aimed to assess the frequency and characteristics of hyperlipasemia in patients with COVID-19. METHODS: A retrospective cohort study of hospitalized patients across 6 US centers with COVID-19. RESULTS: Of 71 patients, 9 (12.1%) developed hyperlipasemia, with 2 (2.8%) greater than 3 times upper limit of normal. No patient developed acute pancreatitis. Hyperlipasemia was not associated with poor outcomes or symptoms. DISCUSSION: Although a mild elevation in serum lipase was observed in some patients with COVID-19, clinical acute pancreatitis was not seen.

Serodominant SARS-CoV-2 Nucleocapsid Peptides Map to Unstructured Protein Regions.

The SARS-CoV-2 nucleocapsid (N) protein is highly immunogenic, and anti-N antibodies are commonly used as markers for prior infection. While several studies have examined or predicted the antigenic regions of N, these have lacked consensus and structural context. Using COVID-19 patient sera to probe an overlapping peptide array, we identified six public and four private epitope regions across N, some of which are unique to this study. We further report the first deposited X-ray structure of the stable dimerization domain at 2.05 Å as similar to all other reported structures. Structural mapping revealed that most epitopes are derived from surface-exposed loops on the stable domains or from the unstructured linker regions. An antibody response to an epitope in the stable RNA binding domain was found more frequently in sera from patients requiring intensive care. Since emerging amino acid variations in N map to immunogenic peptides, N protein variation could impact detection of seroconversion for variants of concern. IMPORTANCE As SARS-CoV-2 continues to evolve, a structural and genetic understanding of key viral epitopes will be essential to the development of next-generation diagnostics and vaccines. This study uses structural biology and epitope mapping to define the antigenic regions of the viral nucleocapsid protein in sera from a cohort of COVID-19 patients with diverse clinical outcomes. These results are interpreted in the context of prior structural and epitope mapping studies as well as in the context of emergent viral variants. This report serves as a resource for synthesizing the current state of the field toward improving strategies for future diagnostic and therapeutic design.

The Role of Social Work Education in Relation to Empathy and Self-Reported Resilience: Results from Entry to Exit of Social Work Education on the Island of Ireland during the COVID-19 Pandemic

The COVID-19 pandemic has affected all aspects of people's lives worldwide, including the work of social workers and the education of social work students. Field placements are a significant part of social work education, but during the pandemic they were cut short and most teachings moved online. The current mixed methods study examined the effects of social work education on social work students' empathy and resilience during the COVID-19 pandemic on the island of Ireland. A matched sample of forty-nine students completed an online survey at the start (T1) of their degree and at the end (T2). A further 229 students who only completed the T1 survey were compared to 70 others who only completed the T2 survey. The results showed improved resilience in the cohort comparison. There were no differences in empathy in the matched sample nor between the cohorts. Thematic analysis of students' narratives showed that they found the switch to online learning difficult, with some reporting negative impacts on their mental health and the abrupt ending of placements impacting their feelings of preparedness for practice. Implications of this study and future research areas are discussed. In this article, we examined the possible effects of the COVID-19 pandemic on the education of social work students. The data come from a wider study, in which social work students at six universities in Northern Ireland and the Republic of Ireland completed an online survey. Relevant to the current article were questions about resilience, empathy and how the students' education was impacted by the pandemic. Forty-nine students completed the survey twice: at the start of their education and at the end. This was our matched sample. A further 229 students only completed the survey at the start of their degree and 70 students only completed it at the end of their degree. We compared these two cohorts of students separately from the matched sample. We found that (i) the cohort of final year students was more resilient than the cohort of the first year students;(ii) there were no differences in empathy either in the matched sample or between the cohorts from the beginning to the end of their training;and (iii) students reported that the move towards online learning negatively impacted their education.

Regulation of provider networks in response to COVID-19.

In public health insurance programs, federal and state regulators use network adequacy standards to ensure that health plans provide enrollees with adequate access to care. These standards are based on provider availability, anticipated enrollment, and patterns of care delivery. We anticipate that the coronavirus disease 2019 pandemic will have 3 main effects on provider networks and their regulation: enrollment changes, changes to the provider landscape, and changes to care delivery. Regulators will need to ensure that plans adjust their network size should there be increased enrollment or increased utilization caused by forgone care. Regulators will also require updated monitoring data and plan network data that reflect postpandemic provider availability. Telehealth will have a larger role in care delivery than in the prepandemic period, and regulators will need to adapt network standards to accommodate in-person and virtual care delivery.

Nirsevimab binding-site conservation in respiratory syncytial virus fusion glycoprotein worldwide between 1956 and 2021: an analysis of observational study sequencing data

BACKGROUND: Nirsevimab is an extended half-life monoclonal antibody to the respiratory syncytial virus (RSV) fusion protein that has been developed to protect infants for an entire RSV season. Previous studies have shown that the nirsevimab binding site is highly conserved. However, investigations of the geotemporal evolution of potential escape variants in recent (ie, 2015-2021) RSV seasons have been minimal. Here, we examine prospective RSV surveillance data to assess the geotemporal prevalence of RSV A and B, and functionally characterise the effect of the nirsevimab binding-site substitutions identified between 2015 and 2021. METHOD(S): We assessed the geotemporal prevalence of RSV A and B and nirsevimab binding-site conservation between 2015 and 2021 from three prospective RSV molecular surveillance studies (the US-based OUTSMART-RSV, the global INFORM-RSV, and a pilot study in South Africa). Nirsevimab binding-site substitutions were assessed in an RSV microneutralisation susceptibility assay. We contextualised our findings by assessing fusion-protein sequence diversity from 1956 to 2021 relative to other respiratory-virus envelope glycoproteins using RSV fusion protein sequences published in NCBI GenBank. FINDINGS: We identified 5675 RSV A and RSV B fusion protein sequences (2875 RSV A and 2800 RSV B) from the three surveillance studies (2015-2021). Nearly all (25 [100%] of 25 positions of RSV A fusion proteins and 22 [88%] of 25 positions of RSV B fusion proteins) amino acids within the nirsevimab binding site remained highly conserved between 2015 and 2021. A highly prevalent (ie, >40.0% of all sequences) nirsevimab binding-site Ile206Met:Gln209Arg RSV B polymorphism arose between 2016 and 2021. Nirsevimab neutralised a diverse set of recombinant RSV viruses, including new variants containing binding-site substitutions. RSV B variants with reduced susceptibility to nirsevimab neutralisation were detected at low frequencies (ie, prevalence <1.0%) between 2015 and 2021. We used 3626 RSV fusion-protein sequences published in NCBI GenBank between 1956 and 2021 (2024 RSV and 1602 RSV B) to show that the RSV fusion protein had lower genetic diversity than influenza haemagglutinin and SARS-CoV-2 spike proteins. INTERPRETATION: The nirsevimab binding site was highly conserved between 1956 and 2021. Nirsevimab escape variants were rare and have not increased over time. FUNDING: AstraZeneca and Sanofi.Copyright © 2023 Elsevier Ltd. All rights reserved.

Antibiotic Use and Associated Risk Factors for Antibiotic Prescribing in COVID-19 Hospitalized Patients.

BACKGROUND: Literature suggests that antibiotic prescribing in COVID-19 patients is high. Currently, there are insufficient data on what drives antibiotic prescribing practices throughout the COVID-19 pandemic. OBJECTIVE: This study sought to determine antibiotic use rates and identify risk factors for antibiotic prescribing in hospitalized patients. It was the first study to assess risk factors for receiving more than 1 course of antibiotics. METHODS: This was a retrospective, multi-center, observational study. Patients admitted from March 1, 2020, to May 31, 2020, and treated for COVID-19 were included. The primary endpoint was the rate of antibiotic use during hospitalization. Secondary endpoints included risk factors associated with antibiotic use, risk factors associated with receiving more than 1 antibiotic course, and rate of microbiologically confirmed infections. RESULTS: A total of 208 encounters (198 patients) were included in the final analysis. Eighty-three percent of patients received at least 1 course of antibiotics, despite low rates of microbiologically confirmed infection (12%). Almost one-third of patients (30%) received more than 1 course of antibiotics. Risk factors identified for both antibiotic prescribing and receiving more than 1 course of antibiotics included increased hospital length of stay (median 12 days), intensive care unit admission, and the necessity for mechanical ventilation. CONCLUSION AND RELEVANCE: There were high rates of antibiotic prescribing with low rates of microbiologically confirmed bacterial co-infection. Many patients received more than 1 course of antibiotics during hospitalization. This study highlights the importance and demand for appropriate antibiotic stewardship practices in COVID-19 patients.

COVID-19 Outbreaks Linked to Workplaces, 23 US Jurisdictions, August-October 2021.

OBJECTIVES: Early in the COVID-19 pandemic, several outbreaks were linked with facilities employing essential workers, such as long-term care facilities and meat and poultry processing facilities. However, timely national data on which workplace settings were experiencing COVID-19 outbreaks were unavailable through routine surveillance systems. We estimated the number of US workplace outbreaks of COVID-19 and identified the types of workplace settings in which they occurred during August-October 2021. METHODS: The Centers for Disease Control and Prevention collected data from health departments on workplace COVID-19 outbreaks from August through October 2021: the number of workplace outbreaks, by workplace setting, and the total number of cases among workers linked to these outbreaks. Health departments also reported the number of workplaces they assisted for outbreak response, COVID-19 testing, vaccine distribution, or consultation on mitigation strategies. RESULTS: Twenty-three health departments reported a total of 12 660 workplace COVID-19 outbreaks. Among the 12 470 workplace types that were documented, 35.9% (n = 4474) of outbreaks occurred in health care settings, 33.4% (n = 4170) in educational settings, and 30.7% (n = 3826) in other work settings, including non-food manufacturing, correctional facilities, social services, retail trade, and food and beverage stores. Eleven health departments that reported 3859 workplace outbreaks provided information about workplace assistance: 3090 (80.1%) instances of assistance involved consultation on COVID-19 mitigation strategies, 1912 (49.5%) involved outbreak response, 436 (11.3%) involved COVID-19 testing, and 185 (4.8%) involved COVID-19 vaccine distribution. CONCLUSIONS: These findings underscore the continued impact of COVID-19 among workers, the potential for work-related transmission, and the need to apply layered prevention strategies recommended by public health officials.

Impaired SARS-CoV-2 Variant Neutralization and CD8+ T-cell Responses Following 3 Doses of mRNA Vaccines in Myeloma: Correlation with Breakthrough Infections.

Patients with multiple myeloma (MM) mount suboptimal neutralizing antibodies (nAb) following 2 doses of SARS-CoV-2 mRNA vaccines. Currently, circulating SARS-CoV-2 variants of concern (VOC) carry the risk of breakthrough infections. We evaluated immune recognition of current VOC including BA.1, BA.2, and BA.5 in 331 racially representative patients with MM following 2 or 3 doses of mRNA vaccines. The third dose increased nAbs against WA1 in 82%, but against BA variants in only 33% to 44% of patients. Vaccine-induced nAbs correlated with receptor-binding domain (RBD)-specific class-switched memory B cells. Vaccine-induced spike-specific T cells were detected in patients without seroconversion and cross-recognized variant-specific peptides but were predominantly CD4+ T cells. Detailed clinical/immunophenotypic analysis identified features correlating with nAb/B/T-cell responses. Patients who developed breakthrough infections following 3 vaccine doses had lower live-virus nAbs, including against VOC. Patients with MM remain susceptible to SARS-CoV-2 variants following 3 vaccine doses and should be prioritized for emerging approaches to elicit variant-nAb and CD8+ T cells. SIGNIFICANCE: Three doses of SARS-CoV-2 mRNA vaccines fail to yield detectable VOC nAbs in nearly 60% and spike-specific CD8+ T cells in >80% of myeloma patients. Patients who develop breakthrough infections following vaccination have low levels of live-virus nAb. This article is highlighted in the In This Issue feature, p. 101.

Thromboprophylaxis for children hospitalized with COVID-19 and MIS-C.

Background: Limited data exist about effective regimens for pharmacological thromboprophylaxis in children with acute coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C). Objectives: Study the outcomes of institutional thromboprophylaxis protocol for primary venous thromboembolism (VTE) prevention in children hospitalized with acute COVID-19/MIS-C. Methods: This single-center retrospective cohort study included consecutive children (aged less than 21 years) with COVID-19/MIS-C who received tailored intensity thromboprophylaxis, primarily with low-molecular-weight heparin, from April 2020 through October 2021. Thromboprophylaxis was given to those with moderate to severe disease based on the World Health Organization scale and exposure to two or more VTE risk factors. Therapeutic intensity was considered for severe illness. Clinical recovery along with D-dimer improvement determined thromboprophylaxis duration. Outcomes were incident VTEs, bleeding, and mortality. Results: Among 211 hospitalizations, 45 (21.3%) received thromboprophylaxis (COVID-19, 16; MIS-C, 29). Median age was 14.8 years (interquartile range [IQR], 8.9-16.1). Among 35 (77.8%) with severe illness, 27 (60.0%) required respiratory support, and 19 (42.2%) required an intensive care unit stay. Median hospitalization was 6 days (IQR, 5.0-10.5). Median thromboprophylaxis duration was 19 days (IQR, 6.0-31.0) with therapeutic intensity in 24 (53.3%) and prophylactic in 21 (46.7%). Outcomes were as follows: VTE, 1 (2.2%); death, 1 (2.2%, unrelated to bleeding/thrombosis); major/clinically relevant nonmajor bleeding, 0; and minor bleeding, 7 (15.5%). D-dimer was elevated in a majority at diagnosis (median, 2.3; IQR, 1.2-3.3 mg/ml fibrinogen-equivalent units) and was noninformative in assessing disease severity. D-dimer normalized at thromboprophylaxis discontinuation. Conclusions: Our experience of using clinically directed thromboprophylaxis with tailored intensity approach for children hospitalized with COVID-19 and MIS-C favors its inclusion in current standard of care. The role of D-dimer in directing thromboprophylaxis management deserves further evaluation.

Working from Home and Worker Well-being: New Evidence from Germany

The COVID-19 pandemic piqued interest in remote work, but research yields mixed findings on the impact of working from home on workers' well-being and job attitudes. The authors develop a conceptual distinction between working from home that occurs during regular work hours (replacement work-from-home) and working from home that occurs outside of those hours (extension work-from-home). Using linked establishment-employee survey data from Germany, the authors find that extension work-from-home is associated with lower psychological well-being, higher turnover intentions, and higher work-to-family and family-to-work conflicts. By contrast, replacement work-from-home is associated with better well-being and higher job satisfaction, but higher work-to-family conflict. Extension work-from-home has more negative effects for women's well-being and work-to-family conflict. This distinction clarifies the conditions under which remote work can have positive consequences for workers and for organizations. © The Author(s) 2023.

Transplant of organs from donors with positive SARS-CoV-2 nucleic acid testing: A report from the organ procurement and transplantation network ad hoc disease transmission advisory committee.

BACKGROUND: Decisions to transplant organs from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid test-positive (NAT+) donors must balance risk of donor-derived transmission events (DDTE) with the scarcity of available organs. METHODS: Organ Procurement and Transplantation Network (OPTN) data were used to compare organ utilization and recipient outcomes between SARS-CoV-2 NAT+ and NAT- donors. NAT+ was defined by either a positive upper or lower respiratory tract (LRT) sample within 21 days of procurement. Potential DDTE were adjudicated by OPTN Disease Transmission Advisory Committee. RESULTS: From May 27, 2021 (date of OTPN policy for required LRT testing of lung donors) to January 31, 2022, organs were recovered from 617 NAT+ donors from all OPTN regions and 53 of 57 (93%) organ procurement organizations. NAT+ donors were younger and had higher organ quality scores for kidney and liver. Organ utilization was lower for NAT+ donors compared to NAT- donors. A total of 1241 organs (776 kidneys, 316 livers, 106 hearts, 22 lungs, and 21 other) were transplanted from 514 NAT+ donors compared to 21 946 organs from 8853 NAT- donors. Medical urgency was lower for recipients of NAT+ liver and heart transplants. The median waitlist time was longer for liver recipients of NAT+ donors. The match run sequence number for final acceptor was higher for NAT+ donors for all organ types. Outcomes for hospital length of stay, 30-day mortality, and 30-day graft loss were similar for all organ types. No SARS-CoV-2 DDTE occurred in this interval. CONCLUSIONS: Transplantation of SARS-CoV-2 NAT+ donor organs appears safe for short-term outcomes of death and graft loss and ameliorates the organ shortage. Further study is required to assure comparable longer term outcomes.

Immune responses, viral shedding, and COVID-19 symptom burden from breakthrough SARS-CoV-2 infection in a 2:1 randomized, double-blind, placebo-controlled Phase 3 study of AZD1222 (ChAdOx1 nCoV-19) vaccination

Background. Breakthrough infections post-COVID-19 vaccination increase with waning immunity and typically produce milder disease than infections in unvaccinated individuals. We investigated immuno-virologic responses and COVID-19 symptom burden upon breakthrough infection in participants from a Phase 3 study of 2-dose primary series AZD1222 vaccination (NCT04516746) to explore disease attenuation. Methods. Study participants who experienced protocol-defined COVID-19 symptoms initiated a series of illness visits over 28 days with collection of sera, nasopharyngeal (NP) swabs and saliva samples (SS), and documentation of symptoms (data-cut off: July 30, 2021). For baseline-seronegative participants with PCR-confirmed SARS-CoV-2 infection >=15 days after dose 2 of AZD1222 or placebo we assessed: anti-SARS-CoV-2 spike (S), nucleocapsid (N) and neutralizing antibody (Ab) titers by multiplex immunoassay and SARS-CoV-2 pseudovirus assay in sera;viral load by quantitative RT-PCR in NP swabs;and viral shedding by qualitative and quantitative RT-PCR in SS. Data were stratified by age and SARS-CoV-2 variant, and time since primary series dose 2. Results. Illness Day 1 (ILL-D1) S Ab GMTs in AZD1222 vaccinees were similar to peak GMTs seen 14 days after dose 2 of AZD1222 and were higher vs placebo at all timepoints. The magnitude of S Ab response differed by age: median GMTs were lower at ILL-D1 and higher at ILL-D14 in vaccinees aged >=65 vs 18-64 years (Fig.1). ILL-D1 overall, SARS-CoV-2 ancestral, alpha, and epsilon variant viral load titers in NP swabs were lower in vaccinees vs placebo (Fig 2). Mean viral load in NP swabs and viral shedding titers in SS were lower in vaccinees vs placebo at all timepoints. Vaccinees reported fewer COVID-19 symptoms than placebo participants, and experienced shorter symptom duration, particularly for fatigue and difficulty breathing. Figure 1. SARS-CoV-2 spike IgG antibody titers upon SARS-CoV-2 infection by participant age in AZD1222 vaccinees and placebo recipients during illness visits Figure 2. Quantification of viral load (nasopharyngeal swabs quantitative viral titer) by SARS- CoV-2 variant at Illness Visit Day 1 Conclusion. Improved S Ab responses, lower viral loads, and reduced symptom burden upon breakthrough infection in vaccinees vs placebo recipients, suggest that robust recall responses to AZD1222 vaccination may attenuate COVID-19 disease severity and duration. These findings alongside data on cellular immune responses to breakthrough infection will inform understanding of protective immunity to SARS-CoV-2 infection.

Treatment-Emergent Viral Variants in the Phase 3 TACKLE Trial Investigating Efficacy and Safety of AZD7442 (Tixagevimab/Cilgavimab) for the Treatment of Mild to Moderate COVID-19 in Adults

Background. AZD7442 (tixagevimab/cilgavimab) is a combination of neutralizing monoclonal antibodies (mAbs) that bind to distinct epitopes on the SARS-CoV-2 spike protein, with neutralization activity against variants including Omicron. In the Phase 3 TACKLE study, AZD7442 significantly reduced severe disease progression or death and was well-tolerated through Day 29. Viral evolution during treatment has the potential for resistance selection, such as variants exhibiting reduced mAb binding. We report genotypic analysis and phenotypic characterization of variants identified over 15 days after AZD7442 treatment in TACKLE. Methods. In TACKLE (NCT04723394), non-hospitalized adults with mild to moderate COVID19 were randomized and dosed <=7 days from symptom onset with a single 600-mg AZD7442 dose (2 consecutive intramuscular injections, 300 mg of each antibody;n=452) or placebo (n=451). Next-generation sequencing of the spike gene was performed on SARS-CoV-2 reverse-transcription polymerase chain reaction-positive nasal swabs (at baseline and Days 3, 6, and 15). SARS-CoV-2 lineages were assigned using spike nucleotide sequences. Amino acid substitutions, insertions, and deletions were analyzed at allele fractions (AF, % of sequence reads represented by mutation) >=25% and 3-25%. Results. Baseline spike sequences were available from 744 participants (82.4%) (AZD7442, n=380;placebo, n=364);87% of sequences corresponded to variants of concern/interest;these were balanced between AZD7442 and placebo groups (Table 1). Treatment-emergent (post-dosing) viral variants were rare, with 11 (4.5%) AZD7442 and 3 (1.3%) placebo participants showing the emergence of >=1 mutation at tixagevimab/cilgavimab binding sites, with an AF >=25% (Table 2). At AF 3- 25%, treatment-emergent viral variants in the AZD7442 binding site were observed in 16 (6.6%) AZD7442 and 15 (6.5%) placebo participants. Conclusion. Following AZD7442 treatment, low levels of SARS-CoV-2 variants bearing mutations at tixagevimab/cilgavimab binding sites were identified. These data indicate that combination of two antibodies creates a high genetic barrier for resistance, supporting the use of mAb combinations that bind to distinct epitopes for the treatment of COVID-19.

AZD7442 (Tixagevimab/Cilgavimab) Demonstrates Potent In Vitro Activity Against SARS-CoV-2 Spike Variants Identified in Circulation and in Prophylaxis Clinical Studies

Background. AZD7442 is a combination of extended-half-life SARS-CoV-2- neutralizing monoclonal antibodies (tixagevimab/cilgavimab) that bind to distinct epitopes on the SARS-CoV-2 spike protein. In the PROVENT study, a single 300 mg intramuscular dose of AZD7442 demonstrated 77% efficacy for prevention of COVID-19 vs placebo at primary analysis, with 83% efficacy through 6-months follow-up, and was well-tolerated. We report conservation of AZD7442 binding sites and neutralizing activity against pseudotyped virus-like particles (VLPs) harboring spike substitutions identified in surveillance, and clinical SARS-CoV-2 isolates from the PROVENT study. Methods. Consensus SARS-CoV-2 whole genome sequences were analyzed from open source databases to identify prevalent spike substitutions within the AZD7442 binding site. Phenotypic analyses determined neutralization susceptibility of pseudotyped VLPs with identified spike substitutions. Genotypic analyses were also performed on SARS-CoV-2 spike sequences from PROVENT study (NCT04625725) participants with RT-PCR-positive symptomatic illness. Results. Most residues in tixagevimab (13/17) and cilgavimab (13/19) binding sites were >99% conserved among global SARS-CoV-2 isolates (N=8,373,740 through Apr 19, 2022). In 2021, AZD7442 binding site polymorphisms emerged among circulating strains (prevalence: R346K, 11%;N440K, 22%;G446S, 15%;S477N, 28%;L452R, 43%;T478K, 70%;E484A, 27%;E484K, 3%;Q493R, 27%), but these did not affect AZD7442 in vitro neutralization potency. AZD7442 retained neutralization activity against variants of concern or interest tested, including Omicron BA.2, with moderate reduction observed for Omicron BA.1. By median 6-months follow-up (Aug 29, 2021, data cut-off) in the PROVENT study, there were no AZD7442-resistant substitutions observed in breakthrough SARS-CoV-2 illness visits. Conclusion. AZD7442 retained neutralization activity against all SARS-CoV-2 variants of concern or interest evaluated. Binding site substitutions identified in circulation, and in breakthrough SARS-CoV-2 infections following a single 300 mg dose of AZD7442 in the PROVENT study, were not associated with AZD7442 escape.

ELECTIVE TELEMEDICINE: ARE OLDER WOMEN IN THE POSTPRIMARY TREATMENT PHASE OF EARLY BREAST CANCER INTERESTED?

Explosive growth in the use of telemedicine occurred during the COVID-19 pandemic. Telemedicine has the potential to lessen healthcare burden for older adults with frequent appointments, physical and cognitive disabilities, and reliance on caretakers. To benefit from telemedicine, patients must have the capacity to engage with technology, for which inexperience and access may pose barriers. This study aimed to better understand the perspectives of older women with non-metastatic breast cancer on telemedicine, in regards to visit convenience, completeness, and interpersonal satisfaction. In this qualitative study, semi-structured interviews were conducted in a convenience sample of women age 65+, post-primary treatment for Stage I-III breast cancer, who received in-person outpatient care at NC Cancer Hospital before transitioning to telemedicine after March 2020. Patients were interviewed about their perceptions of telemedicine (telephone, video) as compared to in-person visits. Audio files of interviews were transcribed and reviewed to identify themes established a priori in the interview protocol. 15 patients (telephone=5, video=10) were consented and interviewed (July-October 2021), mean age=74. 13/15 participants reported that they preferred a hybrid care model that included telemedicine care over in-person care alone. COVID-19, physical disability, and transportation burden were associated with telemedicine preference. Comfort with familiar patient-provider interaction and lack of physical exam were associated with in-person appointment preference. Patient-clinician conversations and clinic protocols guiding use of telemedicine should take into account newness of diagnosis, patient comfort and familiarity with the care team, travel burden, disability, and whether the physical exam is or is not essential.

Social Determinants of Health Associated with Intimate Partner Violence in an Urban Obstetric Population

Objective: Intimate partner violence (IPV) is pervasive and can lead to severe health consequences. In the US, 25% of women have experienced sexual violence, physical violence, and/or stalking by an intimate partner. However, less is known about the frequency and risk factors for IPV in the obstetric population. Study Design: Nested case-control study from a prospective cohort survey study of 606 parturients at a single academic medical center from 2011-2022. Structured surveys were administered to consented patients during their postpartum hospital stay to gather information on social determinants of health (SDoH) and birth outcomes. The case group included participants who reported forced sex causing pregnancy, verbal abuse before or during pregnancy, or physical abuse during pregnancy. The control group reported none of these. Odds ratios were used to quantify the relationship between IPV and maternal sociodemographic characteristics, pregnancy factors, and levels of perceived support and discrimination. Result(s): Of 606 study participants, 568 (94%) had data on IPV. Of those, 20.4% reported IPV (case) and 80.6% reported no IPV (control). 74.6% of the study population was enrolled pre-pandemic. Unmarried status, low income, food insecurity, housing insecurity, substance use during pregnancy, higher gravidity, unintended pregnancy, low social support, and racial and gender discrimination were all significantly associated with IPV;maternal race and pregnancy during the COVID-19 pandemic were not. Conclusion(s): IPV is common, reported by 1 in 5 parturients in our population. Although maternal race was not associated with IPV in this perinatal cohort, experiencing racism was. Initiatives aimed to address SDoH such as substance use, family planning, and access to food and housing remain key opportunities to support pregnant patients experiencing IPV. The connection between perceived discrimination and IPV found here highlight the importance of addressing the influence of racism and gender-based violence on adverse birth outcomes in the US. [Formula presented] [Formula presented] Copyright © 2022