Group 2 Innate Lymphoid Cells: Team Players in Regulating Asthma.

Type 2 immunity helps protect the host from infection, but it also plays key roles in tissue homeostasis, metabolism, and repair. Unfortunately, inappropriate type 2 immune reactions may lead to allergy and asthma. Group 2 innate lymphoid cells (ILC2s) in the lungs respond rapidly to local environmental cues, such as the release of epithelium-derived type 2 initiator cytokines/alarmins, producing type 2 effector cytokines such as IL-4, IL-5, and IL-13 in response to tissue damage and infection. ILC2s are associated with the severity of allergic asthma, and experimental models of lung inflammation have shown how they act as playmakers, receiving signals variously from stromal and immune cells as well as the nervous system and then distributing cytokine cues to elicit type 2 immune effector functions and potentiate CD4+ T helper cell activation, both of which characterize the pathology of allergic asthma. Recent breakthroughs identifying stromal- and neuronal-derived microenvironmental cues that regulate ILC2s, along with studies recognizing the potential plasticity of ILC2s, have improved our understanding of the immunoregulation of asthma and opened new avenues for drug discovery.

RORα is a critical checkpoint for T cell and ILC2 commitment in the embryonic thymus.

Type 2 innate lymphoid cells (ILC2) contribute to immune homeostasis, protective immunity and tissue repair. Here we demonstrate that functional ILC2 cells can arise in the embryonic thymus from shared T cell precursors, preceding the emergence of CD4+CD8+ (double-positive) T cells. Thymic ILC2 cells migrated to mucosal tissues, with colonization of the intestinal lamina propria. Expression of the transcription factor RORα repressed T cell development while promoting ILC2 development in the thymus. From RNA-seq, assay for transposase-accessible chromatin sequencing (ATAC-seq) and chromatin immunoprecipitation followed by sequencing (ChIP-seq) data, we propose a revised transcriptional circuit to explain the co-development of T cells and ILC2 cells from common progenitors in the thymus. When Notch signaling is present, BCL11B dampens Nfil3 and Id2 expression, permitting E protein-directed T cell commitment. However, concomitant expression of RORα overrides the repression of Nfil3 and Id2 repression, allowing ID2 to repress E proteins and promote ILC2 differentiation. Thus, we demonstrate that RORα expression represents a critical checkpoint at the bifurcation of the T cell and ILC2 lineages in the embryonic thymus.

ILC2-derived LIF licences progress from tissue to systemic immunity.

Migration and homing of immune cells are critical for immune surveillance. Trafficking is mediated by combinations of adhesion and chemokine receptors that guide immune cells, in response to chemokine signals, to specific locations within tissues and the lymphatic system to support tissue-localized immune reactions and systemic immunity1,2. Here we show that disruption of leukaemia inhibitory factor (LIF) production from group 2 innate lymphoid cells (ILC2s) prevents immune cells leaving the lungs to migrate to the lymph nodes (LNs). In the absence of LIF, viral infection leads to plasmacytoid dendritic cells (pDCs) becoming retained in the lungs where they improve tissue-localized, antiviral immunity, whereas chronic pulmonary allergen challenge leads to marked immune cell accumulation and the formation of tertiary lymphoid structures in the lung. In both cases immune cells fail to migrate to the lymphatics, leading to highly compromised LN reactions. Mechanistically, ILC2-derived LIF induces the production of the chemokine CCL21 from lymphatic endothelial cells lining the pulmonary lymphatic vessels, thus licensing the homing of CCR7+ immune cells (including dendritic cells) to LNs. Consequently, ILC2-derived LIF dictates the egress of immune cells from the lungs to regulate tissue-localized versus systemic immunity and the balance between allergen and viral responsiveness in the lungs.

Identification of aceNKPs, a committed common progenitor population of the ILC1 and NK cell continuum.

The development of innate lymphoid cell (ILC) transcription factor reporter mice has shown a previously unexpected complexity in ILC hematopoiesis. Using novel polychromic mice to achieve higher phenotypic resolution, we have characterized bone marrow progenitors that are committed to the group 1 ILC lineage. These common ILC1/NK cell progenitors (ILC1/NKP), which we call "aceNKPs", are defined as lineage-Id2+IL-7Rα+CD25-α4ß7-NKG2A/C/E+Bcl11b-. In vitro, aceNKPs differentiate into group 1 ILCs, including NK-like cells that express Eomes without the requirement for IL-15, and produce IFN-γ and perforin upon IL-15 stimulation. Following reconstitution of Rag2-/-Il2rg-/- hosts, aceNKPs give rise to a spectrum of mature ILC1/NK cells (regardless of their tissue location) that cannot be clearly segregated into the traditional ILC1 and NK subsets, suggesting that group 1 ILCs constitute a dynamic continuum of ILCs that can develop from a common progenitor. In addition, aceNKP-derived ILC1/NK cells effectively ameliorate tumor burden in a model of lung metastasis, where they acquired a cytotoxic NK cell phenotype. Our results identify the primary ILC1/NK progenitor that lacks ILC2 or ILC3 potential and is strictly committed to ILC1/NK cell production irrespective of tissue homing.

Discrimination, disadvantage and disempowerment during COVID-19: a qualitative intrasectional analysis of the lived experiences of an ethnically diverse healthcare workforce in the United Kingdom.

BACKGROUND: Healthcare workers (HCWs) in the United Kingdom (UK) have faced many challenges during the COVID-19 pandemic, some of these arising out of their social positions. Existing literature explicating these challenges (e.g., lack of appropriate PPE, redeployment, understaffing) have highlighted inequities in how these have been experienced by HCWs based on ethnicity, gender or, job role. In this paper, we move a step ahead and examine how the intersection of these social positions have impacted HCWs' experiences of challenges during the pandemic. METHODS: We collected qualitative data, using interviews and focus groups, from 164 HCWs from different ethnicities, gender, job roles, migration statuses, and regions in the United Kingdom (UK) between December 2020 and July 2021. Interviews and focus groups were conducted online or by telephone, and recorded with participants' permission. Recordings were transcribed and a hybrid thematic analytical approach integrating inductive data-driven codes with deductive ones informed by an intersectional framework was adopted to analyse the transcripts. RESULTS: Thematic analysis of transcripts identified disempowerment, disadvantage and, discrimination as the three main themes around which HCWs' experiences of challenges were centred, based on their intersecting identities (e.g., ethnicity gender, and/or migration status). Our analysis also acknowledges that disadvantages faced by HCWs were linked to systemic and structural factors at the micro, meso and macro ecosystemic levels. This merging of analysis which is grounded in intersectionality and considers the ecosystemic levels has been termed as 'intrasectionalism'. DISCUSSION: Our research demonstrates how an intrasectional lens can help better understand how different forms of mutually reinforcing inequities exist at all levels within the healthcare workforce and how these impact HCWs from certain backgrounds who face greater disadvantage, discrimination and disempowerment, particularly during times of crisis like the COVID-19 pandemic.

Coverage, completion and outcomes of COVID-19 risk assessments in a multi-ethnic nationwide cohort of UK healthcare workers: a cross-sectional analysis from the UK-REACH Study.

INTRODUCTION: There are limited data on the outcomes of COVID-19 risk assessment in healthcare workers (HCWs) or the association of ethnicity, other sociodemographic and occupational factors with risk assessment outcomes. METHODS: We used questionnaire data from UK-REACH (UK Research study into Ethnicity And COVID-19 outcomes in Healthcare workers), an ethnically diverse, nationwide cohort of UK HCWs. We derived four binary outcomes: (1) offered a risk assessment; (2) completed a risk assessment; (3) working practices changed as a result of the risk assessment; (4) wanted changes to working practices after risk assessment but working practices did not change.We examined the association of ethnicity, other sociodemographic/occupational factors and actual/perceived COVID-19 risk variables on our outcomes using multivariable logistic regression. RESULTS: 8649 HCWs were included in total. HCWs from ethnic minority groups were more likely to report being offered a risk assessment than white HCWs, and those from Asian and black ethnic groups were more likely to report having completed an assessment if offered. Ethnic minority HCWs had lower odds of reporting having their work change as a result of risk assessment. Those from Asian and black ethnic groups were more likely to report no changes to their working practices despite wanting them.Previous SARS-CoV-2 infection was associated with lower odds of being offered a risk assessment and having adjustments made to working practices. DISCUSSION: We found differences in risk assessment outcomes by ethnicity, other sociodemographic/occupational factors and actual/perceived COVID-19 risk factors. These findings are concerning and warrant further research using actual (rather than reported) risk assessment outcomes in an unselected cohort.

Correction: Salmonella escapes adaptive immune response via SIRT2 mediated modulation of innate immune response in dendritic cells.

[This corrects the article DOI: 10.1371/journal.ppat.1007437.].

Salmonella escapes adaptive immune response via SIRT2 mediated modulation of innate immune response in dendritic cells.

Salmonella being a successful pathogen, employs a plethora of immune evasion mechanisms. This contributes to pathogenesis, persistence and also limits the efficacy of available treatment. All these contributing factors call upon for new drug targets against Salmonella. For the first time, we have demonstrated that Salmonella upregulates sirtuin 2 (SIRT2), an NAD+ dependent deacetylase in dendritic cells (DC). SIRT2 upregulation results in translocation of NFκB p65 to the nucleus. This further upregulates NOS2 transcription and nitric oxide (NO) production. NO subsequently shows antibacterial activity and suppresses T cell proliferation. NOS2 mediated effect of SIRT2 is further validated by the absence of effect of SIRT2 inhibition in NOS2-/- mice. Inhibition of SIRT2 increases intracellular survival of the pathogen and enhances antigen presentation in vitro. However, in vivo SIRT2 inhibition shows lower bacterial organ burden and reduced tissue damage. SIRT2 knockout mice also demonstrate reduced bacterial organ burden compared to wild-type mice. Collectively, our results prove the role of SIRT2 in Salmonella pathogenesis and the mechanism of action. This can aid in designing of host-targeted therapeutics directed towards inhibition of SIRT2.

Navigating the infodemic: A qualitative study of university students' information strategies during the COVID-19 pandemic.

Objectives: We aimed to study the strategies which university students developed for vetting information during the COVID-19 pandemic and associated infodemic. Methods: We conducted semi-structured interviews with 34 students, using a piloted topic guide which explored several areas of pandemic experiences, including students' use of media. Transcripts were analysed inductively following the thematic approach. Higher order themes were finalised following a coding exercise undertaken by two of the authors. Results: Participants were acutely aware of misinformation during the pandemic. They rated legacy news media (print and broadcast media with pre-Internet origins) higher than social media for reliable information about the pandemic. However, strikingly, not all legacy media were automatically trusted and not all social media were uniformly distrusted. Participants identified a set of mechanisms for establishing whether a piece of information was truthful and accurate. These mechanisms had four main focal points: (1) the source, (2) the message, (3) individual media literacy and (4) the trustworthiness of others. Despite possessing a critical awareness of misinformation, participants avoided posting anything in relation to the pandemic for fear of becoming the target of online abuse. Conclusions: In addition to underscoring the role of media literacy, our research foregrounds the need to attend to the importance of fostering media confidence. We define media confidence as the ability of digital media users to challenge and interrogate questionable or inaccurate information safe in the knowledge that there are adequate regulatory mechanisms in place to curb abuse, trolling and intimidation.

Risk of vaccine preventable diseases in UK migrants: A serosurvey and concordance analysis.

Background: Vaccine preventable diseases (VPDs) such as measles and rubella cause significant morbidity and mortality globally every year. The World Health Organization (WHO), reported vaccine coverage for both measles and rubella to be 71 % in 2019, indicating an immunity gap. Migrants in the EU/EEA may be at high risk of VPDs due to under-immunisation and poor living conditions. However, there are limited data on VPD seroprotection rates amongst migrants living in the United Kingdom (UK). Methods: We conducted an exploratory cross-sectional serosurvey amongst a sample of adult migrants living in Leicester, UK to: (a) determine seroprotection rates for measles, varicella zoster, and rubella in this group; (b) identify risk factors associated with seronegativity and, (c) understand if self-reported vaccine or diseases history is an effective measure of seroprotection. Participants gave a blood sample and completed a questionnaire asking basic demographic details and vaccine and disease history for the three VPDs. We summarised the data using median and interquartile range (IQR) for non-parametric continuous variables and count and percentage for categorical variables. We used logistic regression to establish predictors of seroprotection against these diseases. We examined the reliability of self-reported vaccination/disease history for prediction of seroprotection through a concordance analysis. Results: 149 migrants were included in the analysis. Seroprotection rates were: varicella zoster 98 %, rubella 92.6 % and measles 89.3 %. Increasing age was associated with seroprotection (OR 1.07 95 % CI 1.01-1.13 for each year increase in age). Migrants from Africa and the Middle East (aOR 15.16 95 % CI 1.31 - 175.06) and South/East Asia and Pacific regions (aOR 15.43 95 %CI 2.38 - 100.00) are significantly more likely to be seroprotected against measles as compared to migrants from Europe and Central Asia. The proportions of migrants unsure about their vaccination and disease history combined were 53.0 % for measles; 57.7 % for rubella; 43.0 % for varicella. There was no agreement between self-reported vaccination/disease history and serostatus. Conclusion: Our findings suggest lower levels of seroprotection against measles in migrants living in Leicester, UK, with younger migrants and those from Europe and Central Asia more likely to lack seroprotection. A high proportion of surveyed migrants were unaware of their vaccination/disease history and self-reported vaccine/disease was a poor predictor of seroprotection against VPDs which is important for clinical decision-making regarding catch-up vaccination in this population. Our results, although derived from a small sample, suggest that there may be gaps in seroimmunity for certain VPDs in particular migrant populations. These findings should inform future qualitative studies investigating barriers to vaccine uptake in migrants and population-level seroprevalence studies aimed at determining individualised risk profiles based on demographic and migration factors.

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis - update from 2017 to 2023.

Background: Antimicrobial resistance (AMR) is a critical global health concern. A previous systematic review showed that migrants in Europe are at increased risk of AMR. Since the COVID-19 pandemic there have been rapid changes in patterns of antibiotic use, AMR, and migration. We aimed to present an updated evidence synthesis on the current distribution of AMR among migrants in Europe. Methods: We carried out a systematic review and meta-analysis in accordance with PRISMA guidelines (PROSPERO ID: CRD42022343263). We searched databases (MEDLINE, Embase, PubMed and Scopus) from 18 January 2017 until 18 January 2023 to identify primary data from observational studies reporting any laboratory-confirmed AMR among migrants in the European Economic Area (EEA) and European Union-15 (EU-15) countries using over 7 key search terms for migrants and over 70 terms for AMR and countries in Europe. Outcomes were infection with, or colonisation of AMR bacteria. Methodological quality was assessed using Joanna Briggs Institute Critical Appraisal Checklist for Observational Studies. We meta-analysed the pooled-prevalence of infection and/or colonisation of AMR organisms. Findings: Among 630 articles, 21 observational studies met the inclusion criteria and were included in this review. The pooled prevalence for any detected AMR was 28.0% (95% CI 18.0%-41.0%, I 2  = 100%) compared to a 25.4% seen in the previous review; gram-negative bacteria 31.0% (95% CI 20.0%-44.0%, I 2  = 100%), and methicillin-resistant staphylococcus aureus 10.0% (95% CI 5.0%-16.0%, I 2  = 99%). Drug-resistant bacteria were more prevalent in community settings in large migrant populations (pooled prevalence: 41.0%, 95% CI 24.0%-60.0%, I 2  = 99%) than in hospitals (21.0%, 95% CI 12.0%-32.0%, I 2  = 99%). AMR estimates in 'other' migrants were 32.0%, (95% CI 12.0%-57.0%, I 2  = 100%) and 28.0% (95% CI 18.0%-38.0%, I 2 = 100%) in forced migrants. No firm evidence of AMR acquisition with arrival time or length of stay in the host country was found. Interpretation: Studies investigating AMR in migrants are highly heterogenous. However, since the COVID-19 pandemic, migrants may be at higher risk of acquiring resistant bacteria, particularly gram-negative bacteria, within community settings such as refugee camps and detention centres in Europe. Our study highlights the importance of infrastructure and hygiene measures within these settings, to mitigate transmission of resistant pathogens. Policy-makers should screen for AMR in migrants prior to departure from countries of origin, where feasible, and upon arrival to a new country to ensure optimal health screening, infection control and effective treatment. Funding: There was no funding source for this study.

Recipient tissue microenvironment determines developmental path of intestinal innate lymphoid progenitors.

Innate lymphoid cells (ILCs) are critical in maintaining tissue homeostasis, and during infection and inflammation. Here we identify, by using combinatorial reporter mice, a rare ILC progenitor (ILCP) population, resident to the small intestinal lamina propria (siLP) in adult mice. Transfer of siLP-ILCP into recipients generates group 1 ILCs (including ILC1 and NK cells), ILC2s and ILC3s within the intestinal microenvironment, but almost exclusively group 1 ILCs in the liver, lung and spleen. Single cell gene expression analysis and high dimensional spectral cytometry analysis of the siLP-ILCPs and ILC progeny indicate that the phenotype of the group 1 ILC progeny is also influenced by the tissue microenvironment. Thus, a local pool of siLP-ILCP can contribute to pan-ILC generation in the intestinal microenvironment but has more restricted potential in other tissues, with a greater propensity than bone marrow-derived ILCPs to favour ILC1 and ILC3 production. Therefore, ILCP potential is influenced by both tissue of origin and the microenvironment during development. This may provide additional flexibility during the tuning of immune reactions.

A qualitative study exploring healthcare workers' lived experiences of the impacts of COVID-19 policies and guidelines on maternal and reproductive healthcare services in the United Kingdom.

INTRODUCTION: During the COVID-19 pandemic, pregnant women were regarded as vulnerable to poor health outcomes if infected with the SARS-CoV-2 (COVID-19) virus. To protect the United Kingdom's (UK) National Health Service (NHS) and pregnant patients, strict infection control policies and regulations were implemented. This study aimed to understand the impact of the COVID-19 policies and guidelines on maternal and reproductive health services during the pandemic from the experiences of healthcare workers (HCWs) caring for these patients. METHODS: This qualitative study involved HCWs from the United Kingdom Research study into Ethnicity and COVID-19 outcomes in Healthcare workers (UK-REACH) project. Semi-structured interviews and focus groups were conducted online or by telephone with 44 diverse HCWs. Transcripts were thematically analyzed following Braun and Clarke's principles of qualitative analysis. RESULTS: Three key themes were identified during analysis. First, infection control policies impacted appointment availability, resulting in many cancellations and delays to treatment. Telemedicine was also used extensively to reduce risks from face-to-face consultations, disadvantaging patients from minoritized ethnicities. Secondly, staff shortages and redeployments reduced availability of consultations, appointments, and sonography scans. Finally, staff and patients reported challenges accessing timely, reliable and accurate information and guidance. CONCLUSIONS: COVID-19 demonstrated how a global health crisis can impact maternal and reproductive health services, leading to reduced service quality and surgical delays due to staff redeployment policies. Our findings underscore the implications of policy and future health crises preparedness. This includes tailored infection control policies, addressing elective surgery backlogs early and improved dissemination of relevant vaccine information.

One virus, many lives: a qualitative study of lived experiences and quality of life of adults from diverse backgrounds living in the UK during the COVID-19 pandemic.

OBJECTIVES: The coronavirus disease 2019 (COVID-2019) pandemic has had far-reaching consequences for people's lives. In the UK, more than 23 million have been infected and nearly 185 000 have lost their lives. Previous research has looked at differential outcomes of COVID-19, based on socio-demographic factors such as age, sex, ethnicity and deprivation. We conducted a qualitative study with a diverse sample of adults living in the UK, to understand their lived experiences and quality of life (QoL) during the pandemic. METHODS: Participants were recruited with the help of civil society partners and community organisations. Semi-structured interviews were conducted between May and July 2021. Interviews were recorded with permission and transcribed. Transcripts were analysed following an inductive analytical approach as outlined in the Framework Method. RESULTS: 18 participants (≥16 years) representing different ethnicities, sexes, migration and employment statuses and educational qualifications took part. Five key themes and 14 subthemes were identified and presented using the QoL framework. The five key themes describe how COVID-19 affected the following aspects of QoL: (1) financial and economic, (2) physical health, (3) social, (4) mental health and (5) personal fulfilment and affective well-being. The narratives illustrated inequities in the impact of COVID-19 for individuals with intersecting social, economic, and health disparities. CONCLUSION: Our findings demonstrate the multidimensional and differential impact of the pandemic on different population groups, with most of the negative economic impacts being borne by people in low-paid and insecure jobs. Similarly, adverse social, physical and mental health impacts particularly affected people already experiencing displacement, violence, physical and mental illnesses or even those living alone. These findings indicate that COVID-19 impacts have been influenced by intersecting health and socioeconomic inequalities, which pre-existed. These inequities should be taken into consideration while designing pandemic recovery and rebuilding packages.

Migrants' living conditions, perceived health needs and implications for the use of antibiotics and antimicrobial resistance in the United Kingdom: A qualitative study.

Background and Aims: Antimicrobial resistance (AMR) is among the top public health concerns around the globe. Migrants, especially forced migrants, could be at higher risk of acquiring and transmitting AMR during their journeys or in host countries. There is limited understanding regarding migrants' living conditions and the wider factors contributing to their risk of acquiring infections, and behaviors around antimicrobial use, and AMR development. In this study, we aimed to explore transit experiences, living conditions, and antibiotic use of migrants living in the United Kingdom. Methods: We conducted semistructured qualitative interviews with 27 participants and identified five themes regarding migrants' journey and their living conditions during transit and after arriving in the United Kingdom, their access to water, sanitation and hygiene (WASH), and their use of antibiotics. Results: Migrants, particularly forced migrants, experienced unfavorable living conditions, poor access to WASH, and challenges in accessing healthcare, which further contributed to health conditions like urinary and skin problems. Isolation and difficulty in accessing healthcare played significant roles in migrants' perceived need for storing and using antibiotics as a safety net. Conclusion: The findings highlight the need for coordinated and multilevel interventions to address these challenges and contribute toward tackling AMR and improving the health of this population group.

Caring for Those Who Take Care of Others: Developing Systemic and Sustainable Mental Health Support for the Diverse Healthcare Workforce in the United Kingdom.

Pressures such as high workload, stretched resources, and financial stress are resulting in healthcare workers experiencing high rates of mental health conditions, high suicide rates, high rates of staff absences from work, and high vacancy rates for certain healthcare professions. All of these factors point to the fact that a systematic and sustainable approach to mental health support at different levels and in different ways is more important than ever. In response, we present a holistic analysis of the mental health and wellbeing needs of healthcare workers across the United Kingdom healthcare ecosystem. We recommend that healthcare organisations should consider the specific circumstances of these staff and develop strategies to counter the negative impact of these factors and help safeguard the mental health of their staff.

University Students' Mental Health and Well-Being during the COVID-19 Pandemic: Findings from the UniCoVac Qualitative Study.

The worldwide spread of the coronavirus disease 2019 (COVID-19) pandemic in early 2020 affected all major sectors, including higher education. The measures to contain the spread of this deadly disease led to the closure of colleges and universities across the globe, disrupting the lives of millions of students and subjecting them to a new world of online learning. These sudden disturbances coupled with the demands of a new learning system and the experiences of living through a pandemic have placed additional strains on the mental health of university students. Research on university students' mental health, conducted during the pandemic, have found high levels of stress, anxiety and depression among students. In this qualitative study, we aimed to understand how pandemic experiences have affected student well-being by conducting in-depth interviews with 34 undergraduate students enrolled in a UK university. All interviews were conducted through Microsoft Teams and recorded with prior permission. Transcripts of recorded interviews were thematically analysed which identified two broad themes: (i) University students' mental health and well-being experiences during the pandemic; (ii) factors that influenced students' mental health and well-being. These factors were further distributed across six sub-themes: (a) isolation; (b) health and well-being; (c) bereavement; (d) academic concerns; (e) financial worries and; (f) support, coping, and resilience. Our study identifies the importance of mental health support to university students during pandemics and calls for measures to improve access to support services through these crisis points by universities. Findings can also inform students' mental health and risk assessments in the aftermath of the pandemic.

Healthcare Workers From Diverse Ethnicities and Their Perceptions of Risk and Experiences of Risk Management During the COVID-19 Pandemic: Qualitative Insights From the United Kingdom-REACH Study.

Introduction: Healthcare workers (HCWs) are at higher risk of being infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Previous studies have examined factors relating to infection amongst HCWs, including those from ethnic minority groups, but there is limited data regarding the lived experiences of HCWs in relation to self-protection and how they deal with SARS-CoV-2 infection prevention. In this study, we presented data from an ethnically diverse sample of HCWs in the United Kingdom (UK) to understand their perceptions of risks and experiences with risk management whilst working throughout the COVID-19 pandemic. Methods: We undertook a qualitative study as part of the United Kingdom Research study into Ethnicity and COVID-19 outcomes among Healthcare workers (United Kingdom-REACH) conducting semi-structured interviews and focus groups which were recorded with participants' permission. Recordings were transcribed and thematically analyzed. Findings: A total of 84 participants were included in the analysis. Five broad themes emerged. First, ethnic minority HCWs spoke about specific risks and vulnerabilities they faced in relation to their ethnicity. Second, participants' experience of risk assessments at work varied; some expressed satisfaction while many critiqued it as a "tick-box" exercise. Third, most participants shared about risks related to shortages, ambiguity in guidance, and inequitable distribution of Personal Protective Equipment (PPE), particularly during the start of the pandemic. Fourth, participants reported risks resulting from understaffing and inappropriate redeployment. Finally, HCWs shared the risk mitigation strategies which they had personally employed to protect themselves, their families, and the public. Conclusion: Healthcare workers identified several areas where they felt at risk and/or had negative experiences of risk management during the pandemic. Our findings indicate that organizational shortcomings may have exposed some HCWs to greater risks of infection compared with others, thereby increasing their emotional and mental burden. Ethnic minority HCWs in particular experienced risks stemming from what they perceived to be institutional and structural racism, thus leading to a loss of trust in employers. These findings have significance in understanding staff safety, wellbeing, and workforce retention in multiethnic staff groups and also highlight the need for more robust, inclusive, and equitable approaches to protect HCWs going forward.