Challenges and lessons in establishing human immune profiling cohort studies for pandemic response.

Pandemics have devastating effects that can be mitigated with the existence of global infrastructure for pandemic preparedness along with the adaptation of existing research studies and establishment of biorepositories early in an outbreak. Observational cohort studies in place prior to a pandemic, that are rapidly scalable in response to emerging infectious diseases, are essential for both the early pandemic response and evaluation of its long-term effects. The ability to quickly collect and share samples from convalescent individuals is also critical for the development of vaccines and therapeutics. We provide a reflection on key lessons learned from establishing a longitudinal observational cohort study during the SARS-CoV-2 pandemic in order to provide guidance for future pandemic preparedness.

Accelerated and intensified manufacturing of an adenovirus-vectored vaccine to enable rapid outbreak response.

The Coalition for Epidemic Preparedness Innovations' "100-day moonshot" aspires to launch a new vaccine within 100 days of pathogen identification, followed by large-scale vaccine availability within the "second hundred days." Here, we describe work to optimize adenoviral vector manufacturing for rapid response, by minimizing time to clinical trial and first large-scale supply, and maximizing output from the available manufacturing footprint. We describe a rapid virus seed expansion workflow that allows vaccine release to clinical trials within 60 days of antigen sequence identification, followed by vaccine release from globally distributed sites within a further 40 days. We also describe a perfusion-based upstream production process, designed to maximize output while retaining simplicity and suitability for existing manufacturing facilities. This improves upstream volumetric productivity of ChAdOx1 nCoV-19 by approximately fourfold and remains compatible with the existing downstream process, yielding drug substance sufficient for 10,000 doses from each liter of bioreactor capacity. This accelerated manufacturing process, along with other advantages such as thermal stability, supports the ongoing value of adenovirus-vectored vaccines as a rapidly adaptable and deployable platform for emergency response.

Cairo Consensus on Accreditation as the Basis for Future-Proofing the ART Laboratory.

An international consensus meeting was convened to discuss globally applicable strategies for 'future-proofing' ART laboratories. The central theme was how the application of the foundational principles of laboratory accreditation enables any centre to create an ethos and framework that will support future-proofing in all regards. Discussions focussed on ART laboratory services from egg retrieval and semen specimen receipt to embryo transfer, as well as pertinent cryobanking activities. Issues related to whether ART treatment should be considered an essential service, overall clinic operations, general patient care, and the provision of clinical treatment, were not included as they fall under the purview of physicians and public health authorities. This report details the 16 core consensus points reached, which are supported by extensive practical recommendations that cover the gamut of ART laboratory operations.

Inhibitors of Rickettsia prowazekii methionine aminopeptidase 1 identified from the Pandemic Response Box.

Methionine aminopeptidase (MetAp) enzymes catalyze the post-translational removal of the initiator methionine residue in newly synthesized proteins, a process that is often essential in the maturation of proteins. Consequently, these enzymes serve as important targets for drug development. Rickettsia prowazekii (Rp) is an obligate coccobacillus and the causative agent of the louse-borne epidemic typhus and despite adequate treatment causes a latent infection. This research aimed to identify potential anti-rickettsial agents by screening 400 compounds from the MMV Pandemic Response Box against RpMetAp1. Overall, 19 compounds were identified that possessed IC50 values from 10 µM to 340 nM. The most potent inhibitor was MMV 1580488 (17), which was observed to have an IC50 of 340 nM. The selected hits serve as chemical leads that can be used for the development of potent inhibitors of the RpMetAp1 enzyme.

HIV/AIDS, SARS, and COVID-19: the trajectory of China's pandemic responses and its changing politics in a contested world.

The COVID-19 pandemic has revealed the contested politics of global health governance, though we still don't know enough about the dynamics of domestic pandemic responses, or about the relationship between the politics of those responses and the politics of global health governance, both of which have changed significantly in recent decades. Focusing on three cases (HIV/AIDS, SARS, and COVID-19) of cross-border infectious diseases, this article explores the trajectory of China's pandemic responses in the context of globalization. Attending to changing politics at domestic, international, and global levels, I argue that those responses have been a complex combination of China's domestic politics (e.g., priorities, institutions, leadership, and timing), its international relations (especially with the US), and its engagements with global health governance. It is concluded that the increasing divergence of pandemic responses in a time of ubiquitous global health crisis demands urgent attention to the connections (including contestations) between domestic pandemic responses and the evolvement of global health governance from a broader perspective that considers changes in geopolitics.

The Dutch Citizen's Understanding and Perception of the Actors Involved in the Netherlands' COVID-19 Pandemic Response: A Focus Group Study During the First Pandemic Wave.

INTRODUCTION: The COVID-19 pandemic was a public health emergency (PHE) of unprecedented magnitude and impact. It provided the possibility to investigate the Dutch citizens' understanding and perception of the actors involved in the Dutch pandemic response as a PHE unfolded. METHODS: Three focus groups (FGs) were held with 16 Dutch citizens in June 2020. Citizens were recruited using the Dutch Health Care Consumer Panel. During the FGs, participants were asked to fill in a table with actors they thought were involved in the management of the COVID-19 pandemic. They also received information on actors involved in Dutch outbreak responses. Then, the actors named and omitted by the participants were discussed. RESULTS: An analysis of the FGs suggests that the Dutch citizens participating in the study were not fully aware of the scope of actors involved in the Dutch COVID-19 pandemic response. Some participants would have appreciated more information on the actors involved. This would help them have an informed opinion of the actors involved in the decision-making process, and accept non-pharmaceutical interventions implemented. Lastly, most participants recognised that they played a role in limiting the spread of the COVID-19 pandemic. Yet, very few spontaneously mentioned themselves as actors within the COVID-19 pandemic response. CONCLUSION: This study suggests that early in the COVID-19 pandemic, the Dutch citizens participating in this study's FG did not have a complete understanding of the scope of actors involved in the Dutch COVID-19 pandemic response, or the potential role of the citizen. Future research can build on these results to explore the citizen's perception of their role during PHEs of another origin, as well as other geographical and historical contexts. PATIENT OR PUBLIC CONTRIBUTION: The public participated in the focus groups and received a non-expert report summarising the outcomes of the focus groups.

Exploring differences in perceived barriers and facilitators to COVID-19 vaccine uptake and testing intention by vaccination status and testing hesitancy among rural Latino communities in Southwest Florida.

BACKGROUND: Identifying factors impacting vaccination and testing for COVID-19 is crucial to reduce health disparities, especially for rural/agricultural, low access and high poverty Latino communities disproportionately affected by the pandemic. This study examined differences in perceived barriers and facilitators (such as values, beliefs, and concerns) to COVID-19 vaccine uptake and testing intention by vaccination status and testing hesitancy among rural Latino community members in Southwest Florida. METHODS: Rural Latino community members (N = 493) completed a cross-sectional survey in Spanish (86.0%) or English (14.0%) on perceived COVID-19 vaccine/testing barriers and facilitators, as well as demographics, mental health, medical history, health perceptions, and health literacy. RESULTS: At the time of the survey, approximately 43% of participants were unvaccinated and 46.4% were testing hesitant. Significantly more vaccinated participants acknowledged keeping their family (d = .25), community (d = .27), and themselves (d = .22) safe as facilitators to vaccination (ps < .001). Among the unvaccinated participants, the most common concerns for getting vaccinated were side effects (d = -.53) and lack of knowledge about how the vaccine works (d = -.35, ps < .001). Testing hesitant participants reported concerns including not knowing where to get tested (d = -.25, p = 0.01) and less confidence in a positive test result (d = -.40, p < 0.001). Doctors and faith leaders were ranked as the most trusted information sources across groups. In logistic regression models, vaccination was linked to age, gender, education, and protecting others, while concerns about needles and side effects reduced odds; testing was driven by education, anxiety, hope, and safety concerns. CONCLUSION: Promoting family and community safety may be effective facilitators influencing vaccine and testing intention in rural Latino communities. Enhanced education by trusted information sources, such as doctors and faith leaders may alleviate associated concerns. Our findings may inform actions for future pandemics. Further studies should determine the generalizability of our findings across other rural migrant communities and other vaccines.

Electricity consumption of Singaporean households reveals proactive community response to COVID-19 progression.

Understanding how populations' daily behaviors change during the COVID-19 pandemic is critical to evaluating and adapting public health interventions. Here, we use residential electricity-consumption data to unravel behavioral changes within peoples' homes in this period. Based on smart energy-meter data from 10,246 households in Singapore, we find strong positive correlations between the progression of the pandemic in the city-state and the residential electricity consumption. In particular, we find that the daily new COVID-19 cases constitute the most dominant influencing factor on the electricity demand in the early stages of the pandemic, before a lockdown. However, this influence wanes once the lockdown is implemented, signifying that residents have settled into their new lifestyles under lockdown. These observations point to a proactive response from Singaporean residents-who increasingly stayed in or performed more activities at home during the evenings, despite there being no government mandates-a finding that surprisingly extends across all demographics. Overall, our study enables policymakers to close the loop by utilizing residential electricity usage as a measure of community response during unprecedented and disruptive events, such as a pandemic.

The response of the Military Health System (MHS) to the COVID-19 pandemic: a summary of findings from MHS reviews.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic caused major disruptions to the US Military Health System (MHS). In this study, we evaluated the MHS response to the pandemic to understand the impact of the pandemic response in a large, national, integrated healthcare system providing care for ~ 9 million beneficiaries. METHODS: We performed a narrative literature review of 16 internal Department of Defense (DoD) reports, including reviews mandated by the US Congress in response to the pandemic. We categorized the findings using the Doctrine, Organization, Training, Materiel, Leadership, Personnel, Facilities, and Policy (DOTMLPF-P) framework developed by the DoD to assess system efficiency and effectiveness. RESULTS: The majority of the findings were in the policy, organization, and personnel categories. Key findings showed that the MHS structure to address surge situations was beneficial during the pandemic response, and the rapid growth of telehealth created the potential impact for improved access to routine and specialized care. However, organizational transition contributed to miscommunication and uneven implementation of policies; disruptions affected clinical training, upskilling, and the supply chain; and staffing shortages contributed to burnout among healthcare workers. CONCLUSION: Given its highly integrated, vertical structure, the MHS was in a better position than many civilian healthcare networks to respond efficiently to the pandemic. However, similar to the US civilian sector, the MHS also experienced delays in care, staffing and materiel challenges, and a rapid switch to telehealth. Lessons regarding the importance of communication and preparation for future public health emergency responses are relevant to civilian healthcare systems responding to COVID-19 and other similar public health crises.

A Qualitative Analysis of the Functions of Primary Care Nurses in COVID-19 Vaccination.

AIM: To describe vaccination roles of primary care nurses during the COVID-19 pandemic in Canada. DESIGN: This analysis was part of a larger mixed-methods case study. METHODS: We conducted semi-structured qualitative interviews from May 2022 to January 2023 with primary care nurses across four provinces: British Columbia, Ontario, Newfoundland and Labrador, and Nova Scotia. We asked participants to describe their roles during various stages of the pandemic, facilitators and challenges encountered and possible roles that nurses could have played. We used thematic analysis and analysed codes relevant to vaccination. RESULTS: We interviewed a total of 76 nurses and identified four key functions of primary care nurses' roles in COVID-19 vaccination: (1) education, (2) vaccine administration, (3) outreach and (4) advocacy. Themes outlined nurses' roles with respect to patient education, addressing vaccine hesitancy, partaking in vaccination roles outside of regular primary care practice and supporting accessibility in COVID-19 vaccination. Specific tasks varied by nursing professions. CONCLUSION: Primary care nurses fostered trust through existing patient-provider relationships to enhance roles and activities related to education, outreach and advocacy in COVID-19 vaccination. Some COVID-19 vaccine-related roles were more easily integrated into primary care, whereas others competed with routine primary care roles. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: Findings highlight the vital contributions of primary care nurses towards COVID-19 vaccination efforts in Canada. Leveraging nursing expertise can enhance future pandemic response efforts and improve patient care by addressing barriers to vaccination and promoting equitable access to vaccination services. IMPACT: This study addresses a knowledge gap by describing the vaccination-related roles of primary care nurses during the pandemic. Findings illustrate that nurses demonstrated adaptability through their engagement in vaccine education, administration, outreach and advocacy. This research informs resource allocation, policy development and workforce planning for future vaccination efforts during a pandemic response. REPORTING METHOD: The authors have adhered to the Standards for Reporting Qualitative Research (SRQR) guidelines included in the Empirical Research Qualitative reporting method. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. WHAT DOES THIS PAPER CONTRIBUTE TO THE WIDER GLOBAL CLINICAL COMMUNITY?: Provides insight into the pivotal roles of primary care nurses during the COVID-19 vaccination efforts in Canada, highlighting their diverse contributions towards education, vaccine administration, outreach and advocacy. Offers implications for future pandemic planning by informing resource allocation, policy development and workforce planning for vaccination efforts.

Emergency responses for a health workforce under pressure: Lessons learned from system responses to the first wave of the pandemic in Canada.

The global health workforce crisis, simmering for decades, was brought to a rolling boil by the COVID-19 pandemic in 2020. With scarce literature, evidence, or best practices to draw from, countries around the world moved to flex their workforces to meet acute challenges of the pandemic, facing demands related to patient volume, patient acuity, and worker vulnerability and absenteeism. One early hypothesis suggested that the acute, short-term pandemic phase would be followed by several waves of resource demands extending over the longer term. However, as the acute phase of the pandemic abated, temporary workforce policies expired and others were repealed with a view of returning to 'normal'. The workforce needs of subsequent phases of pandemic effects were largely ignored despite our new equilibrium resting nowhere near our pre-COVID baseline. In this paper, we describe Canada's early pandemic workforce response. We report the results of an environmental scan of the early workforce strategies adopted in Canada during the first wave of the COVID-19 pandemic. Within an expanded three-part conceptual framework for supporting a sustainable health workforce, we describe 470 strategies and policies that aimed to increase the numbers and flexibility of health workers in Canada, and to maximise their continued availability to work. These strategies targeted all types of health workers and roles, enabling changes to the places health work is done, the way in which care is delivered, and the mechanisms by which it is regulated. Telehealth strategies and virtual care were the most prevalent, followed by role expansion, licensure flexibility, mental health supports for workers, and return to practice of retirees. We explore the degree to which these short-term, acute response strategies might be adapted or extended to support the evolving workforce's long-term needs.

Forced displacement and the health workforce crisis: Venezuelan healthcare workers in Peru.

The migration of health workforces tends to be economically based benefiting high-income countries, while draining lower-income countries of workers and skills However, national instability or civil conflict may also have the effect of forcing out health workers. However, few articles focus on the experiences of these types of migrants. Peru has become the second largest Latin American destination for Venezuelan forced displaced migrants, a number of which are health workers. While the exact numbers of these workers is unknown, it is estimated that 4000 and 3000 doctors and about 2500 nurses and health technicians from Venezuela reside in Peru. These workers find entry into the heath system difficult due to bureaucratic and costly registration and qualification validation procedures. However, during Covid-19 these conditions were relaxed, and a large number of these heath workers entered the heath workforce. These workers were primarily doctors and worked in urban medical facilities, though there was some distribution across the country's departments. This avenue to the health workforce allowed the mobilisation of dormant health skills and lifted workforce density numbers. Nonetheless, it is too early to see if there have been sustainable improvements, and it remains uncertain how these policies have contributed to the country's UHC goals. Peru's experiences raise the issue of how to mobilise dormant displaced health worker migrants.

Evaluating emergency service response to COVID-19: A scoping review.

INTRODUCTION: The issue of how emergency services (police, fire, ambulance, local authorities) respond to pandemics has received greater research focus recently in relation to the COVID-19 outbreak, which saw agencies going beyond usual roles to support communities for prolonged periods. A critical appraisal is needed of this published evidence to take stock of what is known about the effectiveness of emergency service response to Covid-19. METHOD: A scoping review of scientific and grey literature identified 17 qualitative (N = 9), quantitative (N = 6), or mixed methods (N = 2) studies from across the UK and internationally that focus on the effectiveness of emergency service response to the Covid-19 outbreak. A narrative review was conducted using an interpretive approach. Papers were read, summarised, and then sorted into inductive themes that addressed some aspect of the review question. Eight critical themes emerged from the narrative review. RESULTS: Across countries, emergency services were required to quickly adapt working practices to reduce spread of infection, support partner agencies facing unprecedented demands, and make effective use of limited resources. Use of technology, access to timely, accurate and relevant information, strong leadership, prior experience, and emergency training were critical to this. However, most research is descriptive rather than evaluative. CONCLUSIONS: Overall, findings highlight the need for further research that examines what mechanisms facilitate and hinder emergency response to pandemics. This scoping review provides a knowledge framework for informing future research that can support emergency services in preparing for events of national and international significance.

Pandemic Action Plan: Phase 3-Lessons Learned from Implementation. "What Did We Learn?"

The COVID-19 pandemic created critical challenges for hospitals and health care providers. Suddenly clinics were forced to close; elective procedures were delayed; scheduled visits were canceled; emergency rooms were overcrowded; hospital beds, equipment, and personal protective equipment (PPE) were in short supply; and staff were faced with rapidly changing circumstances, care protocols, trauma, and personal risk. To better address challenges of the ongoing COVID-19 pandemic and prepare for future pandemics, the National Telemedicine Technology Assessment Resource Center (TTAC) was asked to develop a Pandemic Response Action Plan that would allow its users to address critical issues with available telemedicine and related technologies. The project was constructed in 3 phases. Phase 1-Develop a Pandemic Response Action Plan and a Pandemic Response Action Plan Policy and Regulatory Summary, which identifies the regulatory challenges as well as policy recommendations. Phase 2-Publish the Action Plan and the Policy and Regulatory Summary. Phase 3-Look at health care providers who used the approaches, tools, and technology in the Pandemic Action Plan and document the results. This document represents Phase 3. This document is Phase 3. In this report we look back at health care providers who used the approaches in the Phase 1 Pandemic Response Action Plan as published in Phase 2. In this document we report on the challenges and results of implementing parts of the Pandemic Action Plan. It records the findings, conclusions, and recommendations resulting from the experience of health care providers and the professional experiences of the team and their organizations in implementing parts or all of the plan. Methods: The same multidisciplinary team that constructed Phase 1 and Phase 2 were engaged to develop this Phase 3 report. The members of the team represent leadership expertise and key stakeholders in health care delivery during a pandemic (administration, infection control, physicians, nurses, public health, contingency planning, disaster response, and information technology) as well as a facilitator. For Phase 3, the group used structured brainstorming to define the findings, issues, and results of their own organizations' digital health response to the pandemic. In addition, eight health care providers (hospitals) identified by the Telemedicine Resource Centers' (TRCs) organizations, who used the Pandemic response Plan (created in Phases 1 and 2), were interviewed. All interviews were conducted by the same facilitator with leaders (CEO, and leaders of the telemedicine programs) in each of the eight programs, using a standard questionnaire created by the team. Current literature references are included in this report to illustrate when findings are known to have broader applicability. Conclusions: The impact of the COVID-19 Pandemic was severe and identified multiple critical challenges and weaknesses. Applying the approaches, tools, and technology outlined in the Pandemic Response Action Plan proved to be effective in addressing critical provider challenges. However, implementing these tools during a crisis was difficult unless the organization had experience with the tools and necessary workflows in advance. Implementing these tools as part of standard workflows and everyday operations increased the capabilities and resilience of these organizations in the provision of care during this and for future pandemics.

Parents' and Caregivers' Support for in-School COVID-19 Mitigation Strategies: A Socioecological Perspective.

Informed by the social ecological model, which asserts that health behaviors and beliefs are the result of multiple levels of influence, we examined factors related to parents' support for in-school COVID-19 mitigation strategies. Using data from a survey of 567 parents/caregivers of public elementary and middle school students in eight Maryland counties, we employed regression models to examine relationships between parent-, child-, family-, school-, and community-level factors and acceptability of mitigation strategies. Acceptance of COVID-19 mitigation strategies was positively correlated with child- and family-level factors, including child racial identity (parents of Black children were more accepting than those of White children, odds ratio [OR]: 2.5, 95% confidence interval [CI] = [1.5, 4.1]), parent receipt of the COVID-19 vaccine (OR: 2.4, 95% CI = [1.5, 3.7]), and parent Democrat or Independent political affiliation (compared with Republican affiliation, OR: 4.2, 95% CI = [2.6, 6.7]; OR: 2.2, 95%CI = [1.3, 3.8], respectively). Acceptance was also positively associated with parents' perceptions of their school's mitigation approach, including higher school mitigation score, indicating more intensive mitigation policies (OR: 1.1, 95% CI = [1.0, 1.1]), better school communication about COVID-19 (OR: 1.7, 95% CI = [1.4, 1.9]) and better school capacity to address COVID-19 (OR: 1.9, 95% CI = [1.5, 2.4]). Community-level factors were not associated with acceptance. Child- and parent-level factors identified suggest potential groups for messaging regarding mitigation strategies. School-level factors may play an important role in parents' acceptance of in-school mitigation strategies. Schools' capacity to address public health threats may offer an underappreciated and modifiable setting for disseminating and reinforcing public health guidance.

Condition-Dependent and Dynamic Impacts of Indoor Masking Policies for Coronavirus Disease 2019 Mitigation: A Nationwide, Interrupted Time-Series Analysis.

BACKGROUND: The effectiveness and sustainability of masking policies as a pandemic control measure remain uncertain. Our aim was to evaluate different masking policy types on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) incidence and to identify factors and conditions impacting effectiveness. METHODS: Nationwide, retrospective cohort study of US counties from 4/4/2020-28/6/2021. Policy impacts were estimated using interrupted time-series models with the masking policy change date (eg, recommended-to-required, no-recommendation-to-recommended, no-recommendation-to-required) modeled as the interruption. The primary outcome was change in SARS-CoV-2 incidence rate during the 12 weeks after the policy change; results were stratified by coronavirus disease 2019 (COVID-19) risk level. A secondary analysis was completed using adult vaccine availability as the policy change. RESULTS: In total, N = 2954 counties were included (2304 recommended-to-required, 535 no-recommendation-to-recommended, 115 no-recommendation-to-required). Overall, indoor mask mandates were associated with 1.96 fewer cases/100 000/week (cumulative reduction of 23.52/100 000 residents during the 12 weeks after policy change). Reductions were driven by communities with critical and extreme COVID-19 risk, where masking mandated policies were associated with an absolute reduction of 5 to 13.2 cases/100 000 residents/week (cumulative reduction of 60 to 158 cases/100 000 residents over 12 weeks). Impacts in low- and moderate-risk counties were minimal (<1 case/100 000 residents/week). After vaccine availability, mask mandates were not associated with significant reductions at any risk level. CONCLUSIONS: Masking policy had the greatest impact when COVID-19 risk was high and vaccine availability was low. When transmission risk decreases or vaccine availability increases, the impact was not significant regardless of mask policy type. Although often modeled as having a static impact, masking policy effectiveness may be dynamic and condition dependent.

COVID-19 vaccine coverage targets to inform reopening plans in a low incidence setting.

Since the emergence of SARS-CoV-2 in 2019 through to mid-2021, much of the Australian population lived in a COVID-19-free environment. This followed the broadly successful implementation of a strong suppression strategy, including international border closures. With the availability of COVID-19 vaccines in early 2021, the national government sought to transition from a state of minimal incidence and strong suppression activities to one of high vaccine coverage and reduced restrictions but with still-manageable transmission. This transition is articulated in the national 're-opening' plan released in July 2021. Here, we report on the dynamic modelling study that directly informed policies within the national re-opening plan including the identification of priority age groups for vaccination, target vaccine coverage thresholds and the anticipated requirements for continued public health measures-assuming circulation of the Delta SARS-CoV-2 variant. Our findings demonstrated that adult vaccine coverage needed to be at least 60% to minimize public health and clinical impacts following the establishment of community transmission. They also supported the need for continued application of test-trace-isolate-quarantine and social measures during the vaccine roll-out phase and beyond.

Early coronavirus disease 2019 restrictive measures and changes in maternal characteristics, use of assisted reproductive technology, and stillbirth.

BACKGROUND: The initial COVID-19 pandemic response-related effects on conceptions following the use of assisted reproductive technologies (ART), and on changes in the maternal characteristics of women who conceived during the early vs. pre-pandemic period, have been understudied. OBJECTIVES: To examine the effects of ART clinic closures in the United States (US) in March 2020 on the frequency of ART-conceived live births, multiple births and stillbirths; and to describe changes in the characteristics of women who conceived in the early pandemic period. METHODS: Population-based cohort study including all births in the US from January 2015 to December 2020 (22,907,688 live births; 134,537 stillbirths). Interrupted time series (ITS) methodology was used to estimate rate ratios (RR) of expected versus observed rates in December 2020 (i.e., among births conceived mainly in March 2020). Demographic and clinical characteristics were compared between mothers who conceived in March 2020 versus March 2015-2019. RESULTS: Overall, 1.1% of live births and 1.7% of stillbirths were conceived by ART. ART-conceived live births decreased by 57.0% in December 2020 (observed vs. expected RR 0.43, 95% confidence interval [CI] 0.40, 0.45), and these declines occurred in all subgroups of women. Multiple births also declined in December 2020. Stillbirth rates increased in December 2020 in ART-conceived births (RR 2.55, 95% CI 1.63, 3.92) but remained unchanged in the non-ART group. Maternal characteristics of women who conceived in the early pandemic versus pre-pandemic period differed and included an increased prevalence of pre-pregnancy obesity class 3 and chronic hypertension. CONCLUSIONS: The early pandemic closure of ART clinics resulted in a substantial decline in ART-conceived live births and multiple births in December 2020 and an increase in the proportion of stillbirths among ART-conceived births. Women who conceived in the early pandemic period also had an increased prevalence of obesity and chronic hypertension.

Anti-Toxoplasma gondii screening of MMV pandemic response box and evaluation of RWJ-67657 efficacy in chronically infected mice.

Toxoplasmosis is a significant public health concern with limited therapeutic options. The medicines for malaria venture (MMV) developed the pandemic response box (PRB) containing 400 drug-like molecules with broad pathogen activity. The aim of this work is to evaluate PRB compounds for their anti-Toxoplasma gondii activity and identify promising candidates for further evaluation. Screening identified 42 selective compounds with half effective concentration (EC50) ranging from 2.4 to 913.1 nm and half cytotoxic concentration (CC50) ranging from 6 µm to >50 µm. Selectivity index (SI) values (CC50/EC50) ranged from 11 to 17 708. Based on its in silico and in vitro profile and its commercial availability, RWJ-67657 was selected for further studies. Molecular docking analysis showed RWJ-67657 is predicted to bind to T. gondii p38 mitogen-activated protein kinase (TgMAPK). Oral administration of RWJ-67657 (20 mg kg day−1/10 days) significantly reduced parasite burden in chronically infected mice compared to mock-treated group (P < 0.01). These findings highlight the PRB as a promising source for anti-T. gondii compounds, with several showing favourable drug properties, including MMV1634492, MMV002731, MMV1634491, MMV1581551, MMV011565, MMV1581558, MMV1578577, MMV233495 and MMV1580482, firstly described here as anti-T. gondii agents. RWJ-67657 emerges as a valuable drug candidate for experimental chronic cerebral toxoplasmosis therapy.

COVID-19 prevention at institutions of higher education, United States, 2020-2021: implementation of nonpharmaceutical interventions.

BACKGROUND: In early 2020, following the start of the coronavirus disease 2019 (COVID-19) pandemic, institutions of higher education (IHEs) across the United States rapidly pivoted to online learning to reduce the risk of on-campus virus transmission. We explored IHEs' use of this and other nonpharmaceutical interventions (NPIs) during the subsequent pandemic-affected academic year 2020-2021. METHODS: From December 2020 to June 2021, we collected publicly available data from official webpages of 847 IHEs, including all public (n = 547) and a stratified random sample of private four-year institutions (n = 300). Abstracted data included NPIs deployed during the academic year such as changes to the calendar, learning environment, housing, common areas, and dining; COVID-19 testing; and facemask protocols. We performed weighted analysis to assess congruence with the October 29, 2020, US Centers for Disease Control and Prevention (CDC) guidance for IHEs. For IHEs offering ≥50% of courses in person, we used weighted multivariable linear regression to explore the association between IHE characteristics and the summated number of implemented NPIs. RESULTS: Overall, 20% of IHEs implemented all CDC-recommended NPIs. The most frequently utilized NPI was learning environment changes (91%), practiced as one or more of the following modalities: distance or hybrid learning opportunities (98%), 6-ft spacing (60%), and reduced class sizes (51%). Additionally, 88% of IHEs specified facemask protocols, 78% physically changed common areas, and 67% offered COVID-19 testing. Among the 33% of IHEs offering ≥50% of courses in person, having < 1000 students was associated with having implemented fewer NPIs than IHEs with ≥1000 students. CONCLUSIONS: Only 1 in 5 IHEs implemented all CDC recommendations, while a majority implemented a subset, most commonly changes to the classroom, facemask protocols, and COVID-19 testing. IHE enrollment size and location were associated with degree of NPI implementation. Additional research is needed to assess adherence to NPI implementation in IHE settings.