Differences in syncytia formation by SARS-CoV-2 variants modify host chromatin accessibility and cellular senescence via TP53 (preprint)

COVID-19 remains a significant public health threat due to the ability of SARS-CoV-2 variants to evade the immune system and cause breakthrough infections. Although pathogenic coronaviruses such as SARS-CoV-2 and MERS-CoV lead to severe respiratory infections, how these viruses affect the chromatin proteomic composition upon infection remains largely uncharacterized. Here we used our recently developed integrative DNA And Protein Tagging (iDAPT) methodology to identify changes in host chromatin accessibility states and chromatin proteomic composition upon infection with pathogenic coronaviruses. SARS-CoV-2 infection induces TP53 stabilization on chromatin, which contributes to its host cytopathic effect. We mapped this TP53 stabilization to the SARS-CoV-2 spike and its propensity to form syncytia, a consequence of cell-cell fusion. Differences in SARS-CoV-2 spike variant-induced syncytia formation modify chromatin accessibility, cellular senescence, and inflammatory cytokine release via TP53. Our findings suggest that differences in syncytia formation alter senescence-associated inflammation, which varies among SARS-CoV-2 variants.

Building Back Better in Latin America: Examining the Sustainability of Covid-19 Recovery and Development Programs

NON-TECHNICAL SUMMARY The significant outlays by countries in the Global South to recover from the Covid-19 crisis could have been an opportunity to build back better, advancing both a green recovery and addressing pressing social problems, thus advancing sustainability. To examine if this was the case, in this paper we analyze the expected impacts of recovery initiatives in five Latin American countries. Our results show that these programs do not support the possibility of building back better, weakly impacting twelve dimensions related to sustainability. We also propose a methodology to improve how sustainability concerns can be included in future choice of projects. TECHNICAL SUMMARY It has been argued that the significant outlays by governments across the world required to recover from the Covid-19 crisis can be an opportunity to build back better, i.e. advance towards greener societies. In the Global South, which suffered acute social, economic and environmental problems prior to this health crisis, recovery initiatives would be best suited to focus on sustainable economic recovery which — along with the environmental concerns of a green recovery — could address pressing local problems. To this end, we analyzed the expected impacts of recovery initiatives in five Latin American countries on each of 71 sustainability criteria. These criteria are based on the UN sustainable development goals and other relevant literature related to sustainable development. This is an Open Access article, distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is unaltered and is properly cited. The written permission of Cambridge University Press must be obtained for commercial re-use or in order to create a derivative work. Using principal component analysis, criteria are grouped into twelve dimensions. Our results show that recovery programs examined do not take advantage of the possibility of building back better, and many relevant dimensions related to a sustainable recovery are only weakly considered. Our methodology provides a step forward towards supporting governments in their efforts to identify better policies and investment projects and consequently put together packages of initiatives that advance on sustainability, green recovery, or other long-term goals they may have. SOCIAL MEDIA SUMMARY Methodology to analyze covid-19 recovery packages shows small impact on sustainability in 5 Latin American countries. © 2023 Cambridge University Press. All rights reserved.

Residual antimicrobial coating efficacy against SARS-CoV-2.

AIMS: This study evaluated the residual efficacy of commercially available antimicrobial coatings or films against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on non-porous surfaces. METHODS AND RESULTS: Products were applied to stainless steel or ABS plastic coupons and dried overnight. Coupons were inoculated with SARS-CoV-2 in the presence of 5% soil load. Recovered infectious SARS-CoV-2 was quantified by TCID50 assay. Tested product efficacies ranged from <1.0 to >3.0 log10 reduction at a 2-h contact time. The log10 reduction in recovered infectious SARS-CoV-2 ranged from 0.44 to 3 log10 reduction on stainless steel and 0.25 to >1.67 log10 on ABS plastic. The most effective products tested contained varying concentrations (0.5%-1.3%) of the same active ingredient: 3-(trihydroxysilyl) propyldimethyloctadecyl ammonium chloride. Products formulated with other quaternary ammonium compounds were less effective against SARS-CoV-2 in this test. CONCLUSIONS: The residual antimicrobial products tested showed varied effectiveness against SARS-CoV-2 as a function of product tested. Several products were identified as efficacious against SARS-CoV-2 on both stainless steel and ABS plastic surfaces under the conditions evaluated. Differences in observed efficacy may be due to variation in active ingredient formulation; efficacy is, therefore, difficult to predict based upon listed active ingredient and its concentration. SIGNIFICANCE AND IMPACT: This study highlights the formulation-specific efficacy of several products against SARS-CoV-2 and may inform future development of residual antiviral products for use on non-porous surfaces. The identification of antimicrobial coatings or films showing promise to inactivate SARS-CoV-2 suggests that these products may be worth future testing and consideration.

Curricular Change and Resiliency in the Era of Coronavirus (COVID-19): The Uniformed Services University of the Health Sciences (USU) Experience.

INTRODUCTION: The Coronavirus (COVID-19) pandemic has presented a myriad of organizational and institutional challenges. The Uniformed Services University of the Health Sciences, like many other front line hospitals and clinics, encountered a myriad of challenges in fostering and sustaining the education of students enrolled at the nation's only military medical school. Critical to the function of any academic medical institution, but particularly one devoted to the training of future physicians for the Military Health System, was the ability to rapidly adapt, modify, and create new means of keeping medical students engaged in their core curricula and progressing toward full and timely attainment of established educational goals and objectives. METHODS: This article highlights some of the particular challenges faced by faculty and students during the first 6 months of the COVID-19 pandemic and describes how they were managed and/or mitigated. RESULTS: Six key "lessons learned" were identified and summarized in this manuscript. These lessons may be applicable to other academic institutions both within and outside of the Military Health System. CONCLUSIONS: Recognizing and embracing these key tenets of academic change management can accelerate the generation of a cohesive, organizational response to the next pandemic or public health crisis.

Efficacy of chemical disinfectants against SARS-CoV-2 on high-touch surface materials.

AIMS: This study aimed to provide operationally relevant SARS-CoV-2 surface disinfection efficacy information. METHODS AND RESULTS: Three EPA-registered disinfectants (Vital Oxide, Peroxide, Clorox Total 360 (C360)) and one antimicrobial formulation (CDC Bleach) were evaluated against SARS-CoV-2 on material coupons and were tested using Spray (no-touch with contact time) and Spray & Wipe (wipe immediately post-application) methods immediately and 2 hours post-contamination. Efficacy was evaluated for infectious virus, with a subset tested for vRNA recovery. Efficacy varied by method, disinfectant and material. CDC Bleach solution showed low efficacy against SARS-CoV-2 (Log Reduction < 1.7), unless applied via Spray & Wipe. Additionally, mechanical wiping increased the efficacy of treatments against SARS-CoV-2. Recovery of vRNA post-disinfection suggested vRNA may overestimate infectious virus remaining. CONCLUSIONS: Efficacy depends on surface material, chemical, and disinfection procedure, and suggests that mechanical wiping alone has some efficacy at removing SARS-CoV-2 from surfaces. We observed that disinfectant treatment biased recovery of vRNA over infectious virus.

Food Insecurity and Health Behaviors Among a Sample of Undergraduate Students at an Urban University

Students at universities are experiencing food insecurity, which may be associated with health behaviors. In a pilot study to build a survey that assesses food insecurity and health behaviors among undergraduates, we distributed the survey before (Wave 1;fall 2019) and during (Wave 2;summer 2020) COVID-19. During Wave 1, 41% of students reported food insecurity and 61% met criteria for poor sleep. In Wave 2, 26% reported food insecurity and 49% met criteria for poor sleep. Students experiencing food insecurity were more likely to report poor sleep. This survey will inform recruitment and design of a scaled-up multi-campus study. (100/100 words). © 2022 Taylor & Francis Group, LLC.

Optimization of storage conditions for lipid nanoparticle-formulated self-replicating RNA vaccines.

The recent clinical success of multiple mRNA-based SARS-CoV-2 vaccines has proven the potential of RNA formulated in lipid nanoparticles (LNPs) in humans, and products based on base-modified RNA, sequence-optimized RNA, and self-replicating RNAs formulated in LNPs are all in various stages of clinical development. However, much remains to be learned about critical parameters governing the manufacturing and use of LNP-RNA formulations. One important issue that has received limited attention in the literature to date is the identification of optimal storage conditions for LNP-RNA that preserve long-term activity of the formulations. Here, we analyzed the physical structure, in vivo expression characteristics, and functional activity of alphavirus-derived self-replicating RNA (repRNA)-loaded LNPs encoding HIV vaccine antigens following storage in varying temperatures, buffers, and in the presence or absence of cryoprotectants. We found that for lipid nanoparticles with compositions similar to clinically-used LNPs, storage in RNAse-free PBS containing 10% (w/v) sucrose at -20 °C was able to maintain vaccine stability and in vivo potency at a level equivalent to freshly prepared vaccines following 30 days of storage. LNPs loaded with repRNA could also be lyophilized with retention of bioactivity.

The clinical impact of COVID-19 on patients with cancer in British Columbia: An observational study.

Objective: We evaluated survival outcomes for patients with cancer and COVID-19 in this population-based study. Methods: A total of 631 patients who tested positive for severe acute respiratory syndrome coronavirus 2 and were seen at BC Cancer between 03/03/2020 and 01/21/2021 were included, of whom 506 had a diagnosis of cancer and PCR-confirmed positive test for coronavirus disease 2019. Patient clinical characteristics were retrospectively reviewed and the influence of demographic data, cancer diagnosis, comorbidities, and anticancer treatment(s) on survival following severe acute respiratory syndrome coronavirus 2 infection were analyzed. Results: Age ≥65 years (Hazard Ratio [HR] 4.77, 95% Confidence Interval [CI] 2.72-8.35, P < 0.0001), those with Eastern Cooperative Oncology Group Performance Status ≥2 (HR 8.36, 95% CI 2.89-24.16, P < 0.0001), hypertension (HR 3.17, 95% CI 1.77-5.66, P < 0.0001), and metastatic/advanced stage (HR 3.70, 95% CI 1.77-7.73, P < 0.0001) were associated with worse coronavirus disease 2019 specific survival outcomes following severe acute respiratory syndrome coronavirus 2 infection. Patients with lung cancer had the highest 30-day COVID-19 specific mortality (25.0%), followed by genitourinary (18.1%), gastrointestinal (16.0%), and other cancer types (<10.0%). Patients with the highest 30-day coronavirus disease 2019 specific mortality according to treatment type were those on chemotherapy (23.0%), rituximab (22.2%), and immunotherapy (16.7%) while patients on hormonal treatments (2.2%) had better survival outcomes (P = 0.041) compared to those on other anticancer treatments. Conclusion: This study provides further evidence that patients with cancer are at increased risk of mortality from coronavirus disease 2019 and emphasizes the need for vaccination.

Substance use disorder treatment and technology access among people who use drugs in rural areas of the United States: A cross-sectional survey.

PURPOSE: To evaluate how technology access affected substance use disorder (SUD) treatment prior to COVID-19 for people who use drugs in rural areas. METHODS: The Rural Opioid Initiative (January 2018-March 2020) was a cross-sectional study of people with prior 30-day injection drug or nonprescribed opioid use from rural areas of 10 states. Using multivariable mixed-effect regression models, we examined associations between participant technology access and SUD treatment. FINDINGS: Of 3,026 participants, 71% used heroin and 76% used methamphetamine. Thirty-five percent had no cell phone and 10% had no prior 30-day internet use. Having both a cell phone and the internet was associated with increased days of medication for opioid use disorder (MOUD) use (aIRR 1.29 [95% CI 1.11-1.52]) and a higher likelihood of SUD counseling in the prior 30 days (aOR 1.28 [95% CI 1.05-1.57]). Lack of cell phone was associated with decreased days of MOUD (aIRR 0.77 [95% CI 0.66-0.91]) and a lower likelihood of prior 30-day SUD counseling (aOR 0.77 [95% CI 0.62-0.94]). CONCLUSIONS: Expanding US rural SUD treatment engagement via telemedicine may require increased cell phone and mobile network access.

Surviving Fiscal Odysseys in the Caribbean

In the aftermath of the globalfinancial crisis and in the wake of the COVID-19 pandemic, and the subsequent diminishing fiscal spaces of small islands, fiscalpolicy and the search forfiscal sustainability have regainedprominence on both policy and research agendas. Strengtheningfiscal rules andfiscal institutions have indeed emerged as a key response to the fiscal legacy of the crisis. This is more evident across small island economies in the Caribbean, especially the tourism-dependent island economies. While the recent surge in policy debates and discussion is certainly a sign of the mountingfiscalpressures, these are by no means new to the Caribbean. Over half-a-century ago fiscal matters were prominently on the Caribbean federation agenda. Nevertheless, fiscal sustainability remains ephemeral and illusionary;indeed, an odyssey in the Caribbean.

Sentinel Surveillance System Implementation and Evaluation for SARS-CoV-2 Genomic Data, Washington, USA, 2020-2021.

Genomic data provides useful information for public health practice, particularly when combined with epidemiologic data. However, sampling bias is a concern because inferences from nonrandom data can be misleading. In March 2021, the Washington State Department of Health, USA, partnered with submitting and sequencing laboratories to establish sentinel surveillance for SARS-CoV-2 genomic data. We analyzed available genomic and epidemiologic data during presentinel and sentinel periods to assess representativeness and timeliness of availability. Genomic data during the presentinel period was largely unrepresentative of all COVID-19 cases. Data available during the sentinel period improved representativeness for age, death from COVID-19, outbreak association, long-term care facility-affiliated status, and geographic coverage; timeliness of data availability and captured viral diversity also improved. Hospitalized cases were underrepresented, indicating a need to increase inpatient sampling. Our analysis emphasizes the need to understand and quantify sampling bias in phylogenetic studies and continue evaluation and improvement of public health surveillance systems.

The clinical impact of COVID-19 on patients with cancer in British Columbia: An observational study

Objective We evaluated survival outcomes for patients with cancer and COVID-19 in this population-based study. Methods A total of 631 patients who tested positive for severe acute respiratory syndrome coronavirus 2 and were seen at BC Cancer between 03/03/2020 and 01/21/2021 were included, of whom 506 had a diagnosis of cancer and PCR-confirmed positive test for coronavirus disease 2019. Patient clinical characteristics were retrospectively reviewed and the influence of demographic data, cancer diagnosis, comorbidities, and anticancer treatment(s) on survival following severe acute respiratory syndrome coronavirus 2 infection were analyzed. Results Age ≥65 years (Hazard Ratio [HR] 4.77, 95% Confidence Interval [CI] 2.72–8.35, P < 0.0001), those with Eastern Cooperative Oncology Group Performance Status ≥2 (HR 8.36, 95% CI 2.89–24.16, P < 0.0001), hypertension (HR 3.17, 95% CI 1.77–5.66, P < 0.0001), and metastatic/advanced stage (HR 3.70, 95% CI 1.77–7.73, P < 0.0001) were associated with worse coronavirus disease 2019 specific survival outcomes following severe acute respiratory syndrome coronavirus 2 infection. Patients with lung cancer had the highest 30-day COVID-19 specific mortality (25.0%), followed by genitourinary (18.1%), gastrointestinal (16.0%), and other cancer types (<10.0%). Patients with the highest 30-day coronavirus disease 2019 specific mortality according to treatment type were those on chemotherapy (23.0%), rituximab (22.2%), and immunotherapy (16.7%) while patients on hormonal treatments (2.2%) had better survival outcomes (P = 0.041) compared to those on other anticancer treatments. Conclusion This study provides further evidence that patients with cancer are at increased risk of mortality from coronavirus disease 2019 and emphasizes the need for vaccination. Cancer;COVID-19;SARS-CoV-2;Comorbidities;Chemotherapy;Treatment.

Supporting best practice telehealth in cancer care: Findings from a national study of telehealth use by cancer services and consumers during the COVID-19 pandemic

Aims: To understand consumer and clinician experiences in utilizing telehealth in cancer care since the introduction of newMedicare Benefits Schedule (MBS) item numbers for telehealth in response to the COVID-19 pandemic. Method(s): A mixed-methods approach was used to collect qualitative and quantitative data on telehealth use during the pandemic: MBS services for cancer-related professional attendances were examined by delivery type, provider type and population group. Health service staff (n = 59) and consumers (n = 1162) from cancer services acrossAustralia were invited to complete online surveys and semi-structured interviews about the use of video and telephone telehealth, perceived effectiveness of video and telephone compared to in-person consultations, and the key barriers and enablers. A virtual roundtable was held with more than 40 key cancer control stakeholders regarding strategies to support the cancer community to offer and utilize best practice approaches to telehealth. Result(s): Telehealth was used across all stages of the cancer care pathway, and was most frequently used during the 'treatment' and 'care after initial treatment and recovery' stages. Although video consults were perceived to be more effective than telephone consults, telephone use was more frequent. Patients and their carers often felt less engagedwith their clinician during telephone consults and perceived that they were rarely given a choice between the consultation modes. Key enablers included medical leadership and administrative support, remuneration (MBS telehealth items), reduced risk of infection, reduction in travel time and costs and existing relationship between patient and clinician. Key barriers included inadequate infrastructure, lack of training, access issues (e.g., internet connectivity) and not being offered the choice of a video consultation. Conclusion(s): Telehealth is appropriate for the delivery of cancer care. A hybrid model of care (telehealth and in-person options) and the ability to give consumers choice is integral to supporting best practice telehealth in cancer care.

Anti-membrane Antibodies Persist at Least One Year and Discriminate Between Past Coronavirus Disease 2019 Infection and Vaccination.

BACKGROUND: The consequences of past coronavirus disease 2019 (COVID-19) infection for personal and population health are emerging, but accurately identifying distant infection is a challenge. Anti-spike antibodies rise after both vaccination and infection and anti-nucleocapsid antibodies rapidly decline. METHODS: We evaluated anti-membrane antibodies in COVID-19 naive, vaccinated, and convalescent subjects to determine if they persist and accurately detect distant infection. RESULTS: We found that anti-membrane antibodies persist for at least 1 year and are a sensitive and specific marker of past COVID-19 infection. CONCLUSIONS: Thus, anti-membrane and anti-spike antibodies together can differentiate between COVID-19 convalescent, vaccinated, and naive states to advance public health and research.

Common and rare variant associations with clonal haematopoiesis phenotypes.

Clonal haematopoiesis involves the expansion of certain blood cell lineages and has been associated with ageing and adverse health outcomes1-5. Here we use exome sequence data on 628,388 individuals to identify 40,208 carriers of clonal haematopoiesis of indeterminate potential (CHIP). Using genome-wide and exome-wide association analyses, we identify 24 loci (21 of which are novel) where germline genetic variation influences predisposition to CHIP, including missense variants in the lymphocytic antigen coding gene LY75, which are associated with reduced incidence of CHIP. We also identify novel rare variant associations with clonal haematopoiesis and telomere length. Analysis of 5,041 health traits from the UK Biobank (UKB) found relationships between CHIP and severe COVID-19 outcomes, cardiovascular disease, haematologic traits, malignancy, smoking, obesity, infection and all-cause mortality. Longitudinal and Mendelian randomization analyses revealed that CHIP is associated with solid cancers, including non-melanoma skin cancer and lung cancer, and that CHIP linked to DNMT3A is associated with the subsequent development of myeloid but not lymphoid leukaemias. Additionally, contrary to previous findings from the initial 50,000 UKB exomes6, our results in the full sample do not support a role for IL-6 inhibition in reducing the risk of cardiovascular disease among CHIP carriers. Our findings demonstrate that CHIP represents a complex set of heterogeneous phenotypes with shared and unique germline genetic causes and varied clinical implications.

Host protein kinases required for SARS-CoV-2 nucleocapsid phosphorylation and viral replication.

Multiple coronaviruses have emerged independently in the past 20 years that cause lethal human diseases. Although vaccine development targeting these viruses has been accelerated substantially, there remain patients requiring treatment who cannot be vaccinated or who experience breakthrough infections. Understanding the common host factors necessary for the life cycles of coronaviruses may reveal conserved therapeutic targets. Here, we used the known substrate specificities of mammalian protein kinases to deconvolute the sequence of phosphorylation events mediated by three host protein kinase families (SRPK, GSK-3, and CK1) that coordinately phosphorylate a cluster of serine and threonine residues in the viral N protein, which is required for viral replication. We also showed that loss or inhibition of SRPK1/2, which we propose initiates the N protein phosphorylation cascade, compromised the viral replication cycle. Because these phosphorylation sites are highly conserved across coronaviruses, inhibitors of these protein kinases not only may have therapeutic potential against COVID-19 but also may be broadly useful against coronavirus-mediated diseases.

Detection of SARS-CoV-2 and HHV-8 from a large pericardial effusion in an HIV-positive patient with COVID-19 and clinically diagnosed Kaposi sarcoma: a case report.

BACKGROUND: Pericardial effusion is a late manifestation of HIV more commonly observed in individuals with depressed CD4 counts. Although Mycobacterium tuberculosis remains to be one of the most frequently identified pathogens in the pericardial fluid among people living with HIV, less commonly described etiologies include SARS-CoV-2 that causes coronavirus disease and human herpesvirus-8 which is associated with Kaposi sarcoma. Isolation of more than one pathogen in normally sterile sites remains challenging and rare. We report the first documentation of both SARS-CoV-2 and HHV-8 in the pericardial fluid. CASE PRESENTATION: We present the case of a young man in his 20s with a recent history of clinically diagnosed pulmonary tuberculosis who was admitted for progressive dyspnea and cough. He had multiple violaceous cutaneous lesions on the face, neck, and trunk and diffused lymphadenopathies. He tested positive for SARS-CoV-2 on admission. The patient was clinically diagnosed with pneumonia, Kaposi sarcoma, and HIV/AIDS. Empiric broad spectrum antimicrobial regimen was subsequently initiated. HIV with low CD4 count was confirmed during hospitalization. Echocardiography revealed a large pericardial effusion, in impending cardiac tamponade. Frond-like fibrin strands, extending to the parietal pericardium, were also observed. Pericardiostomy yielded hemorrhagic, exudative effusion with lymphocytic predominance. SARS-CoV-2 and HHV-8 were detected in the pericardial fluid, and bacterial, fungal, and tuberculous studies were negative. The patient had clinical improvement after pericardial drainage. However, despite our best clinical care, he developed a nosocomial infection leading to clinical deterioration and death. CONCLUSION: Detection of SARS-CoV-2 and HHV-8 in the pericardial fluid is rare, and interpretation of their significance in clinical care is challenging. However, coronavirus disease and Kaposi sarcoma must be considered and adequately addressed in immunocompromised adults presenting with large pericardial effusion.

Predicting the cost of COVID-19 treatment and its drivers in Indonesia: analysis of claims data of COVID-19 in 2020-2021.

BACKGROUND: Recent Coronavirus Disease-19 (COVID-19) pandemic shows that health system, particularly hospital care, takes the highest toll on COVID-19. As hospital gets to manage the surge of COVID-19 cases, it is important to standardize treatment standard and package for COVID-19. Until recently, in Indonesia, COVID-19 curative package in hospital is paid using a retrospective payment system (claims system) using a per-diem rate. Quantifying standard cost using an established retrospective claims dataset is important as a basis for standard formulation for COVID-19 package treatment, should COVID-19 be accommodated into the benefit package for Universal Health Coverage (UHC) under the National Health Insurance. METHODS: We estimated a standard cost for COVID-19 treatment using provider's perspective. The analysis was conducted retrospectively using established national COVID-19 claims dataset during January 2020 until 2021. Utilizing individual-or-patient level analysis, claims profile were broken down per-patient, yielding descriptive clinical and care-related profile. Estimate of price and charge were measured in average. Moreover, indicators were regressed to the total charged price (in logarithmic scale) so as to find the predictors of cost. RESULTS: Based on the analysis of 102,065 total claims data received by MOH in 2020-2021, there is an average claim payment for COVID-19 in the amount of IDR 74,52 million (USD$ 5175). Significant difference exists in hospital tariffs or price to the existing claims data, indicating profit for hospital within its role in managing COVID-19 cases. Claim amount predictors were found to be associated with change of claim amount, including high level of severity, hospital class, intensive care room occupancy and ventilator usage, as well as mortality. CONCLUSION: As COVID-19 pandemic shifts towards an endemic, countries including Indonesia need to reflect on the existing payment system and move towards a more sustainable payment mechanism for COVID-19. The COVID-19 payment system needs to be integrated into the existing national health insurance allowing bundled payment to become more sustainable, which can be achieved by comprehensively formulating the bundled payment package for COVID-19.

A Virion-Based Combination Vaccine Protects against Influenza and SARS-CoV-2 Disease in Mice.

Vaccines targeting SARS-CoV-2 have been shown to be highly effective; however, the breadth against emerging variants and the longevity of protection remains unclear. Postimmunization boosting has been shown to be beneficial for disease protection, and as new variants continue to emerge, periodic (and perhaps annual) vaccination will likely be recommended. New seasonal influenza virus vaccines currently need to be developed every year due to continual antigenic drift, an undertaking made possible by a robust global vaccine production and distribution infrastructure. To create a seasonal combination vaccine targeting both influenza viruses and SARS-CoV-2 that is also amenable to frequent reformulation, we have developed an influenza A virus (IAV) genetic platform that allows the incorporation of an immunogenic domain of the SARS-CoV-2 spike (S) protein onto IAV particles. Vaccination with this combination vaccine elicited neutralizing antibodies and provided protection from lethal challenge with both pathogens in mice. This approach may allow the leveraging of established influenza vaccine infrastructure to generate a cost-effective and scalable seasonal vaccine solution for both influenza and coronaviruses. IMPORTANCE The rapid emergence of SARS-CoV-2 variants since the onset of the pandemic has highlighted the need for both periodic vaccination "boosts" and a platform that can be rapidly reformulated to manufacture new vaccines. In this work, we report an approach that can utilize current influenza vaccine manufacturing infrastructure to generate combination vaccines capable of protecting from both influenza virus- and SARS-CoV-2-induced disease. The production of a combined influenza/SARS-CoV-2 vaccine may represent a practical solution to boost immunity to these important respiratory viruses without the increased cost and administration burden of multiple independent vaccines.

REDUCTIONS IN CANCER SERVICES IN AUSTRALIA DUE TO THE PANDEMIC: IMPLICATIONS FOR THE CANCER CARE WORKFORCE

Introduction To investigate immediate and longer-term impacts of the COVID-19 pandemic on cancer care in Australia and to provide context for consideration of system-level and oncology workforce challenges, we examined provision of a range of cancer services during 2020. Methods As a marker of cancer control activity, we examined sentinel diagnostic and therapeutic procedures relating to 14 cancer types using claims data for the Medicare Benefits Schedule, a listing of medical services subsidised by the Australian Government. Results Impacts of COVID-19 on cancer-related services were observed early in the pandemic with observed number of quarterly services notably lower than expected for most cancer types nationally. Some recovery of services through to March 2021 followed with modest increases in quarterly services above that expected for some cancer types. However, sustained impacts overall for 2020 were observed for many services with 8% (163,595) fewer diagnostic and 9% (14,600) fewer therapeutic procedures observed nationally in 2020 than were expected from historical data.1 Conclusions Recovery of service numbers may indicate workload increases for an already over-burdened oncology workforce and may contribute to physical and psychological fatigue in service providers.2 Potential implications of sustained impact on services include later stage at diagnosis, increased treatment complexity and poorer outcomes. Understanding of ongoing impacts on care delivery can inform cancer control planning beyond the pandemic.