High-fat diet and aging-associated memory impairments persist in the absence of microglia in female rats.

Aging is associated with a priming of microglia such that they are hypersensitive to further immune challenges. As such high-fat diet during aging can have detrimental effects on cognition that is not seen in the young. However, conflicting findings also suggest that obesity may protect against cognitive decline during aging. Given this uncertainty we aimed here to examine the role of microglia in high-fat, high-sucrose diet (HFSD)-induced changes in cognitive performance in the aging brain. We hypothesised that 8 weeks of HFSD-feeding would alter microglia and the inflammatory milieu in aging and worsen aging-related cognitive deficits in a microglia-dependent manner. We found that both aging and HFSD reduced hippocampal neuron numbers and open field exploration; they also impaired recognition memory. However, the aging-related deficits occurred in the absence of a pro-inflammatory response and the deficits in memory performance persisted after depletion of microglia in the Cx3cr1-Dtr knock-in rat. Our data suggest that mechanisms additional to the acute microglial contribution play a role in aging- and HFSD-associated memory dysfunction.

Adapting care provision in family practice during the COVID-19 pandemic: a qualitative study exploring the impact of primary care reforms in four Canadian regions.

BACKGROUND: Over the past two decades, Canadian provinces and territories have introduced a series of primary care reforms in an attempt to improve access to and quality of primary care services, resulting in diverse organizational structures and practice models. We examine the impact of these reforms on family physicians' (FPs) ability to adapt their roles during the COVID-19 pandemic, including the provision of routine primary care. METHODS: As part of a larger case study, we conducted semi-structured qualitative interviews with FPs in four Canadian regions: British Columbia, Newfoundland and Labrador, Nova Scotia, and Ontario. During the interviews, participants were asked about their personal and practice characteristics, the pandemic-related roles they performed over different stages of the pandemic, the facilitators and barriers they experienced in performing these roles, and potential roles FPs could have filled. Interviews were transcribed and a thematic analysis approach was applied to identify recurring themes in the data. RESULTS: Sixty-eight FPs completed an interview across the four regions. Participants described five areas of primary care reform that impacted their ability to operate and provide care during the pandemic: funding models, electronic medical records (EMRs), integration with regional entities, interdisciplinary teams, and practice size. FPs in alternate funding models experienced fewer financial constraints than those in fee-for-service practices. EMR access enhanced FPs' ability to deliver virtual care, integration with regional entities improved access to personal protective equipment and technological support, and team-based models facilitated the implementation of infection prevention and control protocols. Lastly, larger group practices had capacity to ensure adequate staffing and cover additional costs, allowing FPs more time to devote to patient care. CONCLUSIONS: Recent primary care system reforms implemented in Canada enhanced FPs' ability to adapt to the uncertain and evolving environment of providing primary care during the pandemic. Our study highlights the importance of ongoing primary care reforms to enhance pandemic preparedness and advocates for further expansion of these reforms.

"Family doctors are also people": a qualitative analysis of how family physicians managed competing personal and professional responsibilities during the COVID-19 pandemic.

BACKGROUND: Family physicians (FPs) fill an essential role in public health emergencies yet have frequently been neglected in pandemic response plans. This exclusion harms FPs in their clinical roles and has unintended consequences in the management of concurrent personal responsibilities, many of which were amplified by the pandemic. The objective of our study was to explore the experiences of FPs during the first year of the COVID-19 pandemic to better understand how they managed their competing professional and personal priorities. METHODS: We conducted semi-structured interviews with FPs from four Canadian regions between October 2020 and June 2021. Employing a maximum variation sampling approach, we recruited participants until we achieved saturation. Interviews explored FPs' personal and professional roles and responsibilities during the pandemic, the facilitators and barriers that they encountered, and any gender-related experiences. Transcribed interviews were thematically analysed. RESULTS: We interviewed 68 FPs during the pandemic and identified four overarching themes in participants' discussion of their personal experiences: personal caregiving responsibilities, COVID-19 risk navigation to protect family members, personal health concerns, and available and desired personal supports for FPs to manage their competing responsibilities. While FPs expressed a variety of ways in which their personal experiences made their professional responsibilities more complicated, rarely did that affect the extent to which they participated in the pandemic response. CONCLUSIONS: For FPs to contribute fully to a pandemic response, they must be factored into pandemic plans. Failure to appreciate their unique role and circumstances often leaves FPs feeling unsupported in both their professional and personal lives. Comprehensive planning in anticipation of future pandemics must consider FPs' varied responsibilities, health concerns, and necessary precautions. Having adequate personal and practice supports in place will facilitate the essential role of FPs in responding to a pandemic crisis while continuing to support their patients' primary care needs.

"Technology has allowed us to do a lot more but it's not necessarily the panacea for everybody": Family physician perspectives on virtual care during the COVID-19 pandemic and beyond.

INTRODUCTION: Early in the COVID-19 pandemic, Canadian primary care practices rapidly adapted to provide care virtually. Most family physicians lacked prior training or expertise with virtual care. In the absence of formal guidance, they made individual decisions about in-person versus remote care based on clinical judgement, their longitudinal relationships with patients, and personal risk assessments. Our objective was to explore Canadian family physicians' perspectives on the strengths and limitations of virtual care implementation for their patient populations during the COVID-19 pandemic and implications for the integration of virtual care into broader primary care practice. METHODS: We conducted semi-structured qualitative interviews with family physicians working in four Canadian jurisdictions (Vancouver Coastal health region, British Columbia; Southwestern Ontario; the province of Nova Scotia; and Eastern Health region, Newfoundland and Labrador). We analyzed interview data using a structured applied thematic approach. RESULTS: We interviewed 68 family physicians and identified four distinct themes during our analysis related to experiences with and perspectives on virtual care: (1) changes in access to primary care; (2) quality and efficacy of care provided virtually; (3) patient and provider comfort with virtual modalities; and (4) necessary supports for virtual care moving forward. CONCLUSIONS: The move to virtual care enhanced access to care for select patients and was helpful for family physicians to better manage their panels. However, virtual care also created access challenges for some patients (e.g., people who are underhoused or living in areas without good phone or internet access) and for some types of care (e.g., care that required access to medical devices). Family physicians are optimistic about the ongoing integration of virtual care into broader primary care delivery, but guidance, regulations, and infrastructure investments are needed to ensure equitable access and to maximize quality of care.

Acupuncture for primary insomnia: Effectiveness, safety, mechanisms and recommendations for clinical practice.

Primary insomnia (PI) is an increasing concern in modern society. Cognitive-behavioral therapy for insomnia is the first-line recommendation, yet limited availability and cost impede its widespread use. While hypnotics are frequently used, balancing their benefits against the risk of adverse events poses challenges. This review summarizes the clinical and preclinical evidence of acupuncture as a treatment for PI, discussing its potential mechanisms and role in reliving insomnia. Clinical trials show that acupuncture improves subjective sleep quality, fatigue, cognitive impairments, and emotional symptoms with minimal adverse events. It also positively impacts objective sleep processes, including prolonging total sleep time, improving sleep efficiency, reducing sleep onset latency and wake after sleep onset, and enhancing sleep architecture/structure, including increasing N3% and REM%, and decreasing N1%. However, methodological shortcomings in some trials diminish the overall quality of evidence. Animal studies suggest that acupuncture restores circadian rhythms in sleep-deprived rodents and improves their performance in behavioral tests, possibly mediated by various clinical variables and pathways. These may involve neurotransmitters, brain-derived neurotrophic factors, inflammatory cytokines, the hypothalamic-pituitary-adrenal axis, gut microbiota, and other cellular events. While the existing findings support acupuncture as a promising therapeutic strategy for PI, additional high-quality trials are required to validate its benefits.

Evaluating engagement with equity in Canadian provincial and territorial primary care policies: Results of a jurisdictional scan.

Equitable access to primary care is essential to achieving more equitable health outcomes, yet evidence suggests that structurally marginalized populations are less likely to have benefited from varied primary care reforms in Canada. Our objective is to determine how equity is incorporated in public primary care policy and strategy documents across Canada. We conducted string term and snowball searches for provincial/territorial primary care policy documents published between 01 January 2018 and 30 June 2022, extracted the policy objective, and applied a rubric to evaluate each document's engagement with equity. We performed content analysis of the documents which acknowledged inequities and articulated a related policy response. Of the 224 identified documents that discussed primary care policy: 63 (28 %) identified one or more structurally marginalized group(s) experiencing inequities related to primary care, 64 (29 %) identified a structurally marginalized group and articulated a policy response, and 16 (7 %) articulated a detailed policy response to address inequities. Even where policy responses were articulated, in most cases these did not directly address the acknowledged inequities. The absence of measurable goals, meaningful community consultation, and tenuous connections between the policy response and inequities mentioned may help explain persistent inequities in primary care across Canada.

Ginsenosides enhance P2X7-dependent cytokine secretion from LPS-primed rodent macrophages.

The activation of P2X7 is a well-known stimulus for the NLRP3-caspase 1 inflammasome and subsequent rapid IL-1ß secretion from monocytes and macrophages. Here we show that positive allosteric modulators of P2X7, ginsenosides, can enhance the release of three important cytokines, IL-1ß, IL-6 and TNF-α from LPS-primed rodent macrophages using the J774 mouse macrophage cell line and primary rat peritoneal macrophages. We compared the immediate P2X7 responses in un-primed and LPS-primed macrophages and found no difference in calcium response amplitude or kinetics. These results suggest that under inflammatory conditions positive allosteric modulators are capable of increasing cytokine secretion at lower concentrations of ATP, thus boosting the initial pro-inflammatory signal. This may be important in the control of intracellular infections.

Practice- and System-Based Interventions to Reduce COVID-19 Transmission in Primary Care Settings: A Qualitative Study.

Using qualitative interviews with 68 family physicians (FPs) in Canada, we describe practice- and system-based approaches that were used to mitigate COVID-19 exposure in primary care settings across Canada to ensure the continuation of primary care delivery. Participants described how they applied infection prevention and control procedures (risk assessment, hand hygiene, control of environment, administrative control, personal protective equipment) and relied on centralized services that directed patients with COVID-19 to settings outside of primary care, such as testing centres. The multi-layered approach mitigated the risk of COVID-19 exposure while also conserving resources, preserving capacity and supporting supply chains.

Decoloniality and healthcare higher education: Critical conversations.

BACKGROUND: We explore the theoretical and methodological aspects of decolonising speech and language therapy (SLT) higher education in the United Kingdom. We begin by providing the background of the Rhodes Must Fall decolonisation movement and the engagement of South African SLTs in the decoloniality agenda. We then discuss the evolution of decoloniality in SLT, highlighting its focus on reimagining the relationships between participants, students, patients and the broader world. OBJECTIVE: The primary objective of this discussion is to fill a gap in professional literature regarding decoloniality in SLT education. While there is limited research in professional journals, social media platforms have witnessed discussions on decolonisation in SLT. This discussion aims to critically examine issues such as institutional racism, lack of belonging, inequitable services and limited diversity that currently affect the SLT profession, not just in the United Kingdom but globally. METHODS: The methods employed in this research involve the engagement of SLT academics in Critical conversations on decolonisation. These conversations draw on reflexivity and reflexive interpretation, allowing for a deeper understanding of the relationship between truth, reality, and the participants in SLT practice and education. The nature of these critical conversations is characterised by their chaotic, unscripted and fluid nature, which encourages the open discussion of sensitive topics related to race, gender, class and sexuality. DISCUSSION POINTS: We present our reflections as academics who participated in the critical conversations. We explore the discomfort experienced by an academic when engaging with decolonisation, acknowledging white privilege, and the need to address fear and an imposter syndrome. The second reflection focuses on the experiences of white academics in grappling with their complicity in a system that perpetuates racism and inequality. It highlights the need for self-reflection, acknowledging white privilege and working collaboratively with colleagues and students toward constructing a decolonised curriculum. Finally, we emphasise that while action is crucial, this should not undermine the potential of dialogue to change attitudes and pave the way for practical implementation. The paper concludes by emphasising the importance of combining dialogue with action and the need for a nuanced understanding of the complexities involved in decolonising SLT education. CONCLUSION: Overall, this paper provides a comprehensive overview of the background, objectives, methods and key reflections related to the decolonisation of SLT higher education in the United Kingdom. It highlights the challenges, discomfort and responsibilities faced by academics in addressing decoloniality and emphasizes the importance of ongoing critical conversations and collective action in effecting meaningful change. WHAT THIS PAPER ADDS: What is already known on this subject Prior to this paper, it was known that the decolonial turn in speech and language therapy (SLT) was a recent focus, building on a history of professional transformation in South Africa. However, there was limited literature on decoloniality in professional journals, with most discussions happening on social media platforms. This paper aims to contribute to the literature and provide a critical conversation on decolonising SLT education, via the United Kingdom. What this paper adds to existing knowledge This paper adds a critical conversation on decolonising SLT higher education. It explores theoretical and methodological aspects of decoloniality in the profession, addressing issues such as institutional racism, lack of sense of belonging, inequitable services and limited diversity. The paper highlights the discomfort experienced by academics in engaging with decolonisation and emphasizes the importance of reflection, collaboration and open dialogue for meaningful change. Notably we foreground deimperialisation (vs. decolonisation) as necessary for academics oriented in/with the Global North so that both processes enable each other. Deimperialisation is work that focuses the undoing of privilege exercised by academics in/with the Global North not only for localising their research and education agenda but checking their rite of passage into the lives of those in the Majority World. What are the potential or actual clinical implications of this work? The paper highlights the need for SLT practitioners and educators to critically examine their practices and curricula to ensure they are inclusive, decolonised and responsive to the diverse needs of communities. The discussions emphasise the importance of addressing institutional racism and promoting a sense of belonging for research participants, SLT students and patients. This paper offers insights and recommendations that can inform the development of more equitable and culturally responsive SLT services and education programmes.

Macrophage regulation of the "second brain": CD163 intestinal macrophages interact with inhibitory interneurons to regulate colonic motility - evidence from the Cx3cr1-Dtr rat model.

Intestinal macrophages are well-studied for their conventional roles in the immune response against pathogens and protecting the gut from chronic inflammation. However, these macrophages may also have additional functional roles in gastrointestinal motility under typical conditions. This is likely to occur via both direct and indirect influences on gastrointestinal motility through interaction with myenteric neurons that contribute to the gut-brain axis, but this mechanism is yet to be properly characterised. The CX3CR1 chemokine receptor is expressed in the majority of intestinal macrophages, so we used a conditional knockout Cx3cr1-Dtr (diphtheria toxin receptor) rat model to transiently ablate these cells. We then utilized ex vivo video imaging to evaluate colonic motility. Our previous studies in brain suggested that Cx3cr1-expressing cells repopulate by 7 days after depletion in this model, so we performed our experiments at both the 48 hr (macrophage depletion) and 7-day (macrophage repopulation) time points. We also investigated whether inhibitory neuronal input driven by nitric oxide from the enteric nervous system is required for the regulation of colonic motility by intestinal macrophages. Our results demonstrated that CD163-positive resident intestinal macrophages are important in regulating colonic motility in the absence of this major inhibitory neuronal input. In addition, we show that intestinal macrophages are indispensable in maintaining a healthy intestinal structure. Our study provides a novel understanding of the interplay between the enteric nervous system and intestinal macrophages in colonic motility. We highlight intestinal macrophages as a potential therapeutic target for gastrointestinal motility disorders when inhibitory neuronal input is suppressed.

Understanding Suicide Clusters Through Exploring Self-Harm Behaviors.

Background: There is little information about characteristics and long-term outcomes of individuals who self-harm during a suicide cluster. Aims: To compare characteristics of individuals who self-harmed during a suicide cluster in South Wales (∼10 deaths between December 2007 and March 2008) with others who self-harmed prior to the cluster and to evaluate 10-year self-harm and mortality outcomes. Method: Using records from the hospital serving the catchment area of the suicide cluster, enhanced by national routinely collected linked data, we created the following two groups: individuals who self-harmed (a) during the suicide cluster and (b) 1 year before. We compared individuals' characteristics and performed logistic regression to compute odds ratios of 10-year self-harm and mortality outcomes. Results: Individuals who self-harmed during the cluster were less likely to be hospitalized or have a mental health history than those who self-harmed prior to the cluster. No significant group differences were found for 10-year self-harm outcomes, but all-cause mortality was higher for males. Limitations: Sample size was small, and data were lacking on psychological and social proximity to individuals who died during the suicide cluster. Conclusion: Our findings highlight the importance of long-term healthcare follow-up of those who self-harm during a suicide cluster, particularly males.

Inhibiting microglia exacerbates the early effects of cuprizone in males in a rat model of multiple sclerosis, with no effect in females.

Hyper-activity of the brain's innate immune cells, microglia, is a hallmark of multiple sclerosis (MS). However, it is not clear whether this involvement of microglia is beneficial or detrimental or whether manipulating microglial activity may be therapeutic. We investigated if inhibiting microglial activity with minocycline prevents the early changes in oligodendrocyte and myelin-related markers associated with a demyelinating challenge in adult female and male rats. Cuprizone reduced the expression of myelin and oligodendrocyte genes in both females and males, reflective of cuprizone intoxication and the early phases demyelination, and reduced the number of oligodendrocytes in the corpus callosum. However, we see notable differences in the role for microglia in this response between females and males. In males, myelin and oligodendrocyte genes, as well as oligodendrocytes were also reduced by minocycline treatment; an effect that was not seen in females. In males, but not females, early changes in oligodendrocyte and myelin-related genes were associated with microglial proliferation in corpus callosum, and this increase was reversed by minocycline. These data indicate sex-specific effects of inhibiting microglia on the early changes leading to demyelination in an MS model and suggest microglia may play a key role in myelin stability in males but not in females. This highlights a strong need for sex-specific understanding of disease development in MS and suggest that treatments targeting microglia may be more effective in males than in females due to differing mechanisms of disease progression.

For health or for profit? Understanding how private financing and for-profit delivery operate within Canadian healthcare (4H|4P): protocol for a multimethod knowledge mobilisation research project.

INTRODUCTION: Privatisation through the expansion of private payment and investor-owned corporate healthcare delivery in Canada raises potential conflicts with equity principles on which Medicare (Canadian public health insurance) is founded. Some cases of privatisation are widely recognised, while others are evolving and more hidden, and their extent differs across provinces and territories likely due in part to variability in policies governing private payment (out-of-pocket payments and private insurance) and delivery. METHODS AND ANALYSIS: This pan-Canadian knowledge mobilisation project will collect, classify, analyse and interpret data about investor-owned privatisation of healthcare financing and delivery systems in Canada. Learnings from the project will be used to develop, test and refine a new conceptual framework that will describe public-private interfaces operating within Canada's healthcare system. In Phase I, we will conduct an environmental scan to: (1) document core policies that underpin public-private interfaces; and (2) describe new or emerging forms of investor-owned privatisation ('cases'). We will analyse data from the scan and use inductive content analysis with a pragmatic approach. In Phase II, we will convene a virtual policy workshop with subject matter experts to refine the findings from the environmental scan and, using an adapted James Lind Alliance Delphi process, prioritise health system sectors and/or services in need of in-depth research on the impacts of private financing and investor-owned delivery. ETHICS AND DISSEMINATION: We have obtained approval from the research ethics boards at Simon Fraser University, University of British Columbia and University of Victoria through Research Ethics British Columbia (H23-00612). Participants will provide written informed consent. In addition to traditional academic publications, study results will be summarised in a policy report and a series of targeted policy briefs distributed to workshop participants and decision/policymaking organisations across Canada. The prioritised list of cases will form the basis for future research projects that will investigate the impacts of investor-owned privatisation.

Immunogenicity of High-Dose Egg-Based, Recombinant, and Cell Culture-Based Influenza Vaccines Compared With Standard-Dose Egg-Based Influenza Vaccine Among Health Care Personnel Aged 18-65 Years in 2019-2020.

Background: Emerging data suggest that second-generation influenza vaccines with higher hemagglutinin (HA) antigen content and/or different production methods may induce stronger antibody responses to HA than standard-dose egg-based influenza vaccines in adults. We compared antibody responses to high-dose egg-based inactivated (HD-IIV3), recombinant (RIV4), and cell culture-based (ccIIV4) vs standard-dose egg-based inactivated influenza vaccine (SD-IIV4) among health care personnel (HCP) aged 18-65 years in 2 influenza seasons (2018-2019, 2019-2020). Methods: In the second trial season, newly and re-enrolled HCPs who received SD-IIV4 in season 1 were randomized to receive RIV4, ccIIV4, or SD-IIV4 or were enrolled in an off-label, nonrandomized arm to receive HD-IIV3. Prevaccination and 1-month-postvaccination sera were tested by hemagglutination inhibition (HI) assay against 4 cell culture propagated vaccine reference viruses. Primary outcomes, adjusted for study site and baseline HI titer, were seroconversion rate (SCR), geometric mean titers (GMTs), mean fold rise (MFR), and GMT ratios that compared vaccine groups to SD-IIV4. Results: Among 390 HCP in the per-protocol population, 79 received HD-IIV3, 103 RIV4, 106 ccIIV4, and 102 SD-IIV4. HD-IIV3 recipients had similar postvaccination antibody titers compared with SD-IIV4 recipients, whereas RIV4 recipients had significantly higher 1-month-postvaccination antibody titers against vaccine reference viruses for all outcomes. Conclusions: HD-IIV3 did not induce higher antibody responses than SD-IIV4, but, consistent with previous studies, RIV4 was associated with higher postvaccination antibody titers. These findings suggest that recombinant vaccines rather than vaccines with higher egg-based antigen doses may provide improved antibody responses in highly vaccinated populations.

Age-associated B cells predict impaired humoral immunity after COVID-19 vaccination in patients receiving immune checkpoint blockade.

Age-associated B cells (ABC) accumulate with age and in individuals with different immunological disorders, including cancer patients treated with immune checkpoint blockade and those with inborn errors of immunity. Here, we investigate whether ABCs from different conditions are similar and how they impact the longitudinal level of the COVID-19 vaccine response. Single-cell RNA sequencing indicates that ABCs with distinct aetiologies have common transcriptional profiles and can be categorised according to their expression of immune genes, such as the autoimmune regulator (AIRE). Furthermore, higher baseline ABC frequency correlates with decreased levels of antigen-specific memory B cells and reduced neutralising capacity against SARS-CoV-2. ABCs express high levels of the inhibitory FcγRIIB receptor and are distinctive in their ability to bind immune complexes, which could contribute to diminish vaccine responses either directly, or indirectly via enhanced clearance of immune complexed-antigen. Expansion of ABCs may, therefore, serve as a biomarker identifying individuals at risk of suboptimal responses to vaccination.

An analysis of policies supporting the roles of family physicians in four regions in Canada during the COVID-19 pandemic.

Policy supports are needed to ensure that Family Physicians (FPs) can carry out pandemic-related roles. We conducted a document analysis in four regions in Canada to identify regulation, expenditure, and public ownership policies during the COVID-19 pandemic to support FP pandemic roles. Policies supported FP roles in five areas: FP leadership, Infection Prevention and Control (IPAC), provision of primary care services, COVID-19 vaccination, and redeployment. Public ownership polices were used to operate assessment, testing and vaccination, and influenza-like illness clinics and facilitate access to personal protective equipment. Expenditure policies were used to remunerate FPs for virtual care and carrying out COVID-19-related tasks. Regulatory policies were region-specific and used to enact and facilitate virtual care, build surge capacity, and enforce IPAC requirements. By matching FP roles to policy supports, the findings highlight different policy approaches for FPs in carrying out pandemic roles and will help to inform future pandemic preparedness.

Disparities in access to primary care are growing wider in Canada.

Canadian provinces and territories have undertaken varied reforms to how primary care is funded, organized, and delivered, but equity impacts of reforms are unclear. We explore disparities in access to primary care by income, educational attainment, dwelling ownership, immigration, racialization, place of residence (metropolitan/non-metropolitan), and sex/gender, and how these have changed over time, using data from the Canadian Community Health Survey (2007/08 and 2015/16 or 2017/18). We observe disparities by income, educational attainment, dwelling ownership, recent immigration, immigration (regular place of care), racialization (regular place of care), and sex/gender. Disparities are persistent over time or increasing in the case of income and racialization (regular medical provider and consulted with a medical professional). Primary care policy decisions that do not explicitly consider existing inequities may continue to entrench them. Careful study of equity impacts of ongoing policy reforms is needed.

Accelerated waning of the humoral response to COVID-19 vaccines in obesity.

Obesity is associated with an increased risk of severe Coronavirus Disease 2019 (COVID-19) infection and mortality. COVID-19 vaccines reduce the risk of serious COVID-19 outcomes; however, their effectiveness in people with obesity is incompletely understood. We studied the relationship among body mass index (BMI), hospitalization and mortality due to COVID-19 among 3.6 million people in Scotland using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) surveillance platform. We found that vaccinated individuals with severe obesity (BMI > 40 kg/m2) were 76% more likely to experience hospitalization or death from COVID-19 (adjusted rate ratio of 1.76 (95% confidence interval (CI), 1.60-1.94). We also conducted a prospective longitudinal study of a cohort of 28 individuals with severe obesity compared to 41 control individuals with normal BMI (BMI 18.5-24.9 kg/m2). We found that 55% of individuals with severe obesity had unquantifiable titers of neutralizing antibody against authentic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus compared to 12% of individuals with normal BMI (P = 0.0003) 6 months after their second vaccine dose. Furthermore, we observed that, for individuals with severe obesity, at any given anti-spike and anti-receptor-binding domain (RBD) antibody level, neutralizing capacity was lower than that of individuals with a normal BMI. Neutralizing capacity was restored by a third dose of vaccine but again declined more rapidly in people with severe obesity. We demonstrate that waning of COVID-19 vaccine-induced humoral immunity is accelerated in individuals with severe obesity. As obesity is associated with increased hospitalization and mortality from breakthrough infections, our findings have implications for vaccine prioritization policies.