187 - Cruise Ship Infectious Disease Outbreak

This chapter examines infectious disease outbreak on a cruise ship, including the outbreaks and handling of 2020 Sars-CoV-2 on cruise ships early in the COVID-19 pandemic.

Persistent memory despite rapid contraction of circulating T Cell responses to SARS-CoV-2 mRNA vaccination

Introduction While antibodies raised by SARS-CoV-2 mRNA vaccines have had compromised efficacy to prevent breakthrough infections due to both limited durability and spike sequence variation, the vaccines have remained highly protective against severe illness. This protection is mediated through cellular immunity, particularly CD8+ T cells, and lasts at least a few months. Although several studies have documented rapidly waning levels of vaccine-elicited antibodies, the kinetics of T cell responses have not been well defined. Methods Interferon (IFN)-γ enzyme-linked immunosorbent spot (ELISpot) assay and intracellular cytokine staining (ICS) were utilized to assess cellular immune responses (in isolated CD8+ T cells or whole peripheral blood mononuclear cells, PBMCs) to pooled peptides spanning spike. ELISA was performed to quantitate serum antibodies against the spike receptor binding domain (RBD). Results In two persons receiving primary vaccination, tightly serially evaluated frequencies of anti-spike CD8+ T cells using ELISpot assays revealed strikingly short-lived responses, peaking after about 10 days and becoming undetectable by about 20 days after each dose. This pattern was also observed in cross-sectional analyses of persons after the first and second doses during primary vaccination with mRNA vaccines. In contrast, cross-sectional analysis of COVID-19-recovered persons using the same assay showed persisting responses in most persons through 45 days after symptom onset. Cross-sectional analysis using IFN-γ ICS of PBMCs from persons 13 to 235 days after mRNA vaccination also demonstrated undetectable CD8+ T cells against spike soon after vaccination, and extended the observation to include CD4+ T cells. However, ICS analyses of the same PBMCs after culturing with the mRNA-1273 vaccine in vitro showed CD4+ and CD8+ T cell responses that were readily detectable in most persons out to 235 days after vaccination. Discussion Overall, we find that detection of spike-targeted responses from mRNA vaccines using typical IFN-γ assays is remarkably transient, which may be a function of the mRNA vaccine platform and an intrinsic property of the spike protein as an immune target. However, robust memory, as demonstrated by capacity for rapid expansion of T cells responding to spike, is maintained at least several months after vaccination. This is consistent with the clinical observation of vaccine protection from severe illness lasting months. The level of such memory responsiveness required for clinical protection remains to be defined.

Isolation and Characterization of Anti-Mycobacterial Natural Products from a Petrosia sp. Marine Sponge.

Tuberculosis (TB) is a dreadful infectious disease and a leading cause of mortality and morbidity worldwide, second in 2020 only to severe acute respiratory syndrome 2 (SARS-Cov-2). With limited therapeutic options available and a rise in multidrug-resistant tuberculosis cases, it is critical to develop antibiotic drugs that display novel mechanisms of action. Bioactivity-guided fractionation employing an Alamar blue assay for Mycobacterium tuberculosis strain H37Rv led to the isolation of duryne (13) from a marine sponge Petrosia sp. sampled in the Solomon Islands. Additionally, five new strongylophorine meroditerpene analogues (1-5) along with six known strongylophorines (6-12) were isolated from the bioactive fraction and characterized using MS and NMR spectroscopy, although only 13 exhibited antitubercular activity.

Persistent memory despite rapid contraction of circulating T Cell responses to SARS-CoV-2 mRNA vaccination.

Introduction: While antibodies raised by SARS-CoV-2 mRNA vaccines have had compromised efficacy to prevent breakthrough infections due to both limited durability and spike sequence variation, the vaccines have remained highly protective against severe illness. This protection is mediated through cellular immunity, particularly CD8+ T cells, and lasts at least a few months. Although several studies have documented rapidly waning levels of vaccine-elicited antibodies, the kinetics of T cell responses have not been well defined. Methods: Interferon (IFN)-γ enzyme-linked immunosorbent spot (ELISpot) assay and intracellular cytokine staining (ICS) were utilized to assess cellular immune responses (in isolated CD8+ T cells or whole peripheral blood mononuclear cells, PBMCs) to pooled peptides spanning spike. ELISA was performed to quantitate serum antibodies against the spike receptor binding domain (RBD). Results: In two persons receiving primary vaccination, tightly serially evaluated frequencies of anti-spike CD8+ T cells using ELISpot assays revealed strikingly short-lived responses, peaking after about 10 days and becoming undetectable by about 20 days after each dose. This pattern was also observed in cross-sectional analyses of persons after the first and second doses during primary vaccination with mRNA vaccines. In contrast, cross-sectional analysis of COVID-19-recovered persons using the same assay showed persisting responses in most persons through 45 days after symptom onset. Cross-sectional analysis using IFN-γ ICS of PBMCs from persons 13 to 235 days after mRNA vaccination also demonstrated undetectable CD8+ T cells against spike soon after vaccination, and extended the observation to include CD4+ T cells. However, ICS analyses of the same PBMCs after culturing with the mRNA-1273 vaccine in vitro showed CD4+ and CD8+ T cell responses that were readily detectable in most persons out to 235 days after vaccination. Discussion: Overall, we find that detection of spike-targeted responses from mRNA vaccines using typical IFN-γ assays is remarkably transient, which may be a function of the mRNA vaccine platform and an intrinsic property of the spike protein as an immune target. However, robust memory, as demonstrated by capacity for rapid expansion of T cells responding to spike, is maintained at least several months after vaccination. This is consistent with the clinical observation of vaccine protection from severe illness lasting months. The level of such memory responsiveness required for clinical protection remains to be defined.

Reply to Bareille et al. Are Viscoelastometric Assays of Old Generation Ready for Disposal? Comment on "Volod et al. Viscoelastic Hemostatic Assays: A Primer on Legacy and New Generation Devices. J. Clin. Med. 2022, 11, 860".

We are pleased to see that Bareille et al. have written a Commentary: "Are viscoelastometric assays of old generation ready for disposal?" [...].

Time to return to school following ACL reconstruction: influence of the COVID-19 pandemic.

INTRODUCTION: ACL reconstruction is commonly performed in school-aged patients for whom missed time from school can have an impact on their education. Additionally, the COVID-19 pandemic has led to different ways of accessing school content. We sought to determine how many days of school school-aged patients should expect to miss following ACL reconstruction and how the availability of remote learning during the COVID-19 pandemic affected this. METHODS: We evaluated 53 ACL reconstruction patients in grades 7-12 undergoing surgery during the school year. Demographic, medical, and educational information were collected. Patients were placed into 1 of 2 cohorts: Group A (surgery before the COVID-19 pandemic) or Group B (surgery during the COVID-19 pandemic). We calculated days missed from school after surgery until return to either virtual or in-person school. RESULTS: Overall, patients returned to school after missing an average of 4.4 (SD, 3.0) days of school after ACL reconstruction surgery. Patients in Group A missed an average of 5.5 (SD, 2.9) school days, while patients in Group B missed an average of 2.3 (SD, 1.4) school days (p <.001). Eighty-nine percent of Group B patients first returned to school utilizing a virtual option. Among those returning virtually, these patients missed an average of 1.9 (SD, 0.9) school days. CONCLUSIONS: A virtual distance learning option results in fewer missed days of school post ACL reconstruction. When given this option, school-aged patients can expect to return to school within two days post-op. Otherwise, patients should expect to miss about one week of in-person schooling. In this regard, the COVID-19 pandemic has positively impacted educational opportunities for students post-surgery, and physicians should advocate for continuing virtual options for students receiving medical treatment.

COVID-19 pandemic reveals challenges in engineering ethics education

Engineering ethics can be divided into three spheres, namely the technical, the professional, and the social. Ideally, engineering students should engage with all three spheres of ethics, but the literature suggests that this might not be the case. How do engineering students engage with the three spheres of engineering ethics during a global pandemic? The COVID-19 pandemic represents a dramatic and ongoing real-world challenge affecting many students personally. This research explores the extent to which engineering students engage with each sphere of engineering ethics by examining how engineering students understand their roles in addressing the pandemic and its implications. We conducted a survey with undergraduate engineering students (n = 410) at a university in the Midwest. Qualitative analysis suggests that there was low engagement with both social ethics and professional ethics among respondents, while there was higher engagement with technical ethics. Quantitative analysis suggests that non-conservative engineering students from less wealthy families in our study show higher engagement with technical ethics as compared to conservative engineering students from less wealthy families. Non-conservative engineering students from wealthy families, however, show similar engagement with technical ethics as compared to conservative engineering students from wealthy families. In addition, engineering students from both wealthy and less wealthy families show higher engagement with technical ethics if they reside in urban areas as compared to engineering students from both wealthy and less wealthy families in non-urban areas. In addition, the difference in terms of engagement with technical ethics between non-urban engineering students from less wealthy families and urban engineering students from less wealthy families is larger than the difference in terms of engagement with technical ethics between non-urban engineering students from wealthy families and urban engineering students from wealthy families. Further investigation will be needed to explain these findings. However, qualitative results confirm that, despite the potential for the pandemic to encourage engagement with all three spheres of ethics, there continues to be low engagement with ethics beyond the technical level. Supplementary Information The online version contains supplementary material available at 10.1007/s40889-022-00156-4.

Automated digital counselling with social network support as a novel intervention for patients with heart failure: protocol for randomised controlled trial.

INTRODUCTION: Heart failure (HF) symptoms improve through self-care, for which adherence remains low among patients despite the provision of education for these behaviours by clinical teams. Open Access Digital Community Promoting Self-Care, Peer Support and Health Literacy (ODYSSEE-vCHAT) combines automated digital counselling with social network support to improve mortality and morbidity, engagement with self-care materials, and health-related quality of life. METHODS AND ANALYSIS: Use of ODYSSEE-vCHAT via Internet-connected personal computer by 162 HF patients will be compared with a control condition over 22 months. The primary outcome is a composite index score of all-cause mortality, all-cause emergency department visits, and HF-related hospitalisation at trial completion. Secondary outcomes include individual components of the composite index, engagement with self-care materials, and patient-reported measures of physical and psychosocial well-being, disease management, health literacy, and substance use. Patients are recruited from tertiary care hospitals in Toronto, Canada and randomised on a 1:1 ratio to both arms of the trial. Online assessments occur at baseline (t=0), months 4, 8 and 12, and trial completion. Ordinal logistic regression analyses and generalised linear models will evaluate primary and secondary outcomes. ETHICS AND DISSEMINATION: The trial has been approved by the research ethics boards at the University Health Network (20-5960), Sunnybrook Hospital (5117), and Mount Sinai Hospital (21-022-E). Informed consent of eligible patients occurs in person or online. Findings will be shared with key stakeholders and the public. Results will allow for the preparation of a Canada-wide phase III trial to evaluate the efficacy of ODYSSEE-vCHAT in improving clinical outcomes and raising the standard of outpatient care. TRIAL REGISTRATION NUMBER: NCT04966104.

Trends in buprenorphine treatment disparities during the COVID pandemic in Massachusetts.

Background: Racial, sex, and age disparities in buprenorphine treatment have previously been demonstrated. We evaluated trends in buprenorphine treatment disparities before and after the onset of the COVID pandemic in Massachusetts. Methods: This cross-sectional study used data from an integrated health system comparing 12-months before and after the March 2020 Massachusetts COVID state of emergency declaration, excluding March as a washout period. Among patients with a clinical encounter during the study periods with a diagnosis of opioid use disorder or opioid poisoning, we extracted outpatient buprenorphine prescription rates by age, sex, race and ethnicity, and language. Generating univariable and multivariable Poisson regression models, we calculated the probability of receiving buprenorphine. Results: Among 4,530 patients seen in the period before the COVID emergency declaration, 57.9% received buprenorphine. Among 3,653 patients seen in the second time period, 55.1% received buprenorphine. Younger patients (<24) had a lower likelihood of receiving buprenorphine in both time periods (adjusted prevalence ratio (aPR), 0.56; 95% CI, 0.42-0.75 before vs. aPR, 0.76; 95% CI, 0.60-0.96 after). Male patients had a greater likelihood of receiving buprenorphine compared to female patients in both time periods (aPR: 1.05; 95% CI, 1.00-1.11 vs. aPR: 1.09; 95% CI, 1.02-1.16). Racial disparities emerged in the time period following the COVID pandemic, with non-Hispanic Black patients having a lower likelihood of receiving buprenorphine compared to non-Hispanic white patients in the second time period (aPR, 0.85; 95% CI, 0.72-0.99). Conclusions: Following the onset of the COVID pandemic in Massachusetts, ongoing racial, age, and gender disparities were evident in buprenorphine treatment with younger, Black, and female patients less likely to be treated with buprenorphine across an integrated health system.

A Spatio-temporal Study of Changes in Air Quality from Pre-COVID Era to Post-COVID Era in Chicago, USA

The COVID-19 pandemic has drastically changed human life and the world's environment. Most of the major cities of the USA went under full or partial lockdown in the first half of 2020. However, it started gradually reopening, and in 2021, most of the public activity restrictions were lifted. Many studies reported a significant improvement in air quality during the COVID-19 pandemic in the USA, corresponding with the reduced human activity. We hypothesized that this improved air quality was followed by the decline to air quality again due to the normalization of human activity in 2021. This study is a novel approach of studying air quality using spatio-temporal analysis at the finer spatial level within a city in the USA. It assessed the change in six air quality parameters from the pre-COVID era to the post-COVID era in Chicago city in Illinois, USA. The study found that reduced human activities during COVID-19, improved air quality by reducing the concentration of some air pollutants, especially PM2.5, NO2, and CO. However, this improvement was transitory, and it reverted in the post-COVID era. Therefore, policies should be formulated and practiced to improve air quality in the long term.

Reduced Cell Surface Levels of C-C Chemokine Receptor 5 and Immunosuppression in Long Coronavirus Disease 2019 Syndrome.

In an exploratory trial treating "long COVID" with the CCR5-binding antibody leronlimab, we observed significantly increased blood cell surface CCR5 in treated symptomatic responders but not in nonresponders or placebo-treated participants. These findings suggest an unexpected mechanism of abnormal immune downmodulation in some persons that is normalized by leronlimab. Clinical Trials Registration. NCT04678830.

CCR5 Receptor Occupancy Analysis Reveals Increased Peripheral Blood CCR5+CD4+ T Cells Following Treatment With the Anti-CCR5 Antibody Leronlimab.

CCR5 plays a central role in infectious disease, host defense, and cancer progression, thereby making it an ideal target for therapeutic development. Notably, CCR5 is the major HIV entry co-receptor, where its surface density correlates with HIV plasma viremia. The level of CCR5 receptor occupancy (RO) achieved by a CCR5-targeting therapeutic is therefore a critical predictor of its efficacy. However, current methods to measure CCR5 RO lack sensitivity, resulting in high background and overcalculation. Here, we report on two independent, flow cytometric methods of calculating CCR5 RO using the anti-CCR5 antibody, Leronlimab. We show that both methods led to comparable CCR5 RO values, with low background on untreated CCR5+CD4+ T cells and sensitive measurements of occupancy on both blood and tissue-resident CD4+ T cells that correlated longitudinally with plasma concentrations in Leronlimab-treated macaques. Using these assays, we found that Leronlimab stabilized cell surface CCR5, leading to an increase in the levels of circulating and tissue-resident CCR5+CD4+ T cells in vivo in Leronlimab-treated macaques. Weekly Leronlimab treatment in a chronically SIV-infected macaque led to increased CCR5+CD4+ T cells levels and fully suppressed plasma viremia, both concomitant with full CCR5 RO on peripheral blood CD4+ T cells, demonstrating that CCR5+CD4+ T cells were protected from viral replication by Leronlimab binding. Finally, we extended these results to Leronlimab-treated humans and found that weekly 700 mg Leronlimab led to complete CCR5 RO on peripheral blood CD4+ T cells and a statistically significant increase in CCR5+CD4+ T cells in peripheral blood. Collectively, these results establish two RO calculation methods for longitudinal monitoring of anti-CCR5 therapeutic antibody blockade efficacy in both macaques and humans, demonstrate that CCR5+CD4+ T cell levels temporarily increase with Leronlimab treatment, and facilitate future detailed investigations into the immunological impacts of CCR5 inhibition in multiple pathophysiological processes.

User-Centered Design of A Novel Risk Prediction Behavior Change Tool Augmented With an Artificial Intelligence Engine (MyDiabetesIQ): A Sociotechnical Systems Approach.

BACKGROUND: Diabetes and its complications account for 10% of annual health care spending in the United Kingdom. Digital health care interventions (DHIs) can provide scalable care, fostering diabetes self-management and reducing the risk of complications. Tailorability (providing personalized interventions) and usability are key to DHI engagement/effectiveness. User-centered design of DHIs (aligning features to end users' needs) can generate more usable interventions, avoiding unintended consequences and improving user engagement. OBJECTIVE: MyDiabetesIQ (MDIQ) is an artificial intelligence engine intended to predict users' diabetes complications risk. It will underpin a user interface in which users will alter lifestyle parameters to see the impact on their future risks. MDIQ will link to an existing DHI, My Diabetes My Way (MDMW). We describe the user-centered design of the user interface of MDIQ as informed by human factors engineering. METHODS: Current users of MDMW were invited to take part in focus groups to gather their insights about users being shown their likelihood of developing diabetes-related complications and any risks they perceived from using MDIQ. Findings from focus groups informed the development of a prototype MDIQ interface, which was then user-tested through the "think aloud" method, in which users speak aloud about their thoughts/impressions while performing prescribed tasks. Focus group and think aloud transcripts were analyzed thematically, using a combination of inductive and deductive analysis. For think aloud data, a sociotechnical model was used as a framework for thematic analysis. RESULTS: Focus group participants (n=8) felt that some users could become anxious when shown their future complications risks. They highlighted the importance of easy navigation, jargon avoidance, and the use of positive/encouraging language. User testing of the prototype site through think aloud sessions (n=7) highlighted several usability issues. Issues included confusing visual cues and confusion over whether user-updated information fed back to health care teams. Some issues could be compounded for users with limited digital skills. Results from the focus groups and think aloud workshops were used in the development of a live MDIQ platform. CONCLUSIONS: Acting on the input of end users at each iterative stage of a digital tool's development can help to prioritize users throughout the design process, ensuring the alignment of DHI features with user needs. The use of the sociotechnical framework encouraged the consideration of interactions between different sociotechnical dimensions in finding solutions to issues, for example, avoiding the exclusion of users with limited digital skills. Based on user feedback, the tool could scaffold good goal setting, allowing users to balance their palatable future complications risk against acceptable lifestyle changes. Optimal control of diabetes relies heavily on self-management. Tools such as MDMW/ MDIQ can offer personalized support for self-management alongside access to users' electronic health records, potentially helping to delay or reduce long-term complications, thereby providing significant reductions in health care costs.

Home monitoring of vital signs and generation of alerts in a cohort of people living with dementia

BACKGROUND: People with dementia (PwD) are at increased risk of adverse medical events (e.g. infections and falls). These often cause clinical deterioration, and potentially preventable admissions. Remote home monitoring of vital signs using internet-of-things technology can identify risk factors for these events - something particular pertinent during the COVID-19 pandemic. We present data from an on-going UK Dementia Research Institute and Technology Integrated Health Management (DRI-TIHM) project. We aim to define algorithms that generate automated alerts, like the hospital-based NEWS system (Morgan, 1997, Clin Intensive Car), and provide more proactive care for PwD. METHOD: PwD recorded their systolic/diastolic blood pressure (SBP/DBP), heart rate (HR), temperature (BTM), bodyweight (BW) and oxygen saturation (Sats) daily (figure 1) and data were collected centrally. A 'monitoring team' followed algorithms in response to alerts and advised medical attention if required. Events such as infections, were logged and correlated with the data. The dataset was then used to calculate the number of alerts that would have been raised if different thresholds were used. RESULT: 52 PwD living at home were included. Patients had a range of dementia diagnoses, most commonly Alzheimer's disease. In total, 89,894 measurements were collected over 556 days (figure 2). During the pandemic, a sub-group were given Sats probes and these produced a significant number of false positive results (figure 4f). On sub-group analysis, PwD with Parkinson's disease dementia had significantly lower SBP and DBP (p=0.004 and p=0.01 respectively, Mann-Whitney U) (figure 3a), one of whom suffered from repeated falls (figure 3b). Pilot data were used to set alert thresholds. Average values and number of alerts for each domain are shown (table 1). We then modelled the effect of different thresholds, based on NEWS, to the number of alerts generated (figure 4, table 2). This is informative in optimising sensitivity and specificity of alerts whilst considering the burden on the monitoring service. CONCLUSION: Remote monitoring can be implemented for PwD. These data can be used to generate clinical alerts that may signify adverse medical outcomes. The thresholds need to be adjusted to optimise efficiency in the context of varying reliability of home monitoring devices. © 2021 the Alzheimer's Association.

Viscoelastic Hemostatic Assays: A Primer on Legacy and New Generation Devices.

Viscoelastic hemostatic assay (VHAs) are whole blood point-of-care tests that have become an essential method for assaying hemostatic competence in liver transplantation, cardiac surgery, and most recently, trauma surgery involving hemorrhagic shock. It has taken more than three-quarters of a century of research and clinical application for this technology to become mainstream in these three clinical areas. Within the last decade, the cup and pin legacy devices, such as thromboelastography (TEG® 5000) and rotational thromboelastometry (ROTEM® delta), have been supplanted not only by cartridge systems (TEG® 6S and ROTEM® sigma), but also by more portable point-of-care bedside testing iterations of these legacy devices (e.g., Sonoclot®, Quantra®, and ClotPro®). Here, the legacy and new generation VHAs are compared on the basis of their unique hemostatic parameters that define contributions of coagulation factors, fibrinogen/fibrin, platelets, and clot lysis as related to the lifespan of a clot. In conclusion, we offer a brief discussion on the meteoric adoption of VHAs across the medical and surgical specialties to address COVID-19-associated coagulopathy.

Significant cognitive impairment likely associated with COVID-19 infection with relatively nonsevere symptoms.

COVID-19 infection may involve the nervous system and has been associated with a number of neuropsychiatric complications, including impairment of cognition and dementia. Such complications are more likely to occur in (but are not limited to) patients with severe COVID-19 infections and those with concomitant risk factors. In this case report, the authors describe a normally functioning 51-year-old woman who developed cognitive impairment of a degree that rendered her unable to care for herself most likely related to a relatively nonsevere infection with COVID-19 about 2 months earlier. A detailed report of her deficits of different areas of cognitive functioning is provided. This report aims to make clinicians more aware of the potential for cognitive impairment in patients who have suffered from COVID-19, including those with infections that were not severe.

Breaking the cycle: A public-private partnership to combat the American opioid epidemic.

There has been an increased focus on the opioid epidemic in the United States, yet policy-based interventions such as prescription limits, restrictions on doctor shopping, and notification programs for high-volume prescribers have had no significant impact. In this paper, the authors explore a novel public health policy: a joint public-private partnership between the federal government and hospitals to establish long-term treatment centers for patients admitted to the emergency department after an overdose. These centers would provide medication for opioid use disorder, give individuals the necessary support for recovery, and reduce healthcare expenditures. Similar longitudinal strategies may be used in other areas of public health.