The incidence of COVID-19-related hospitalisation in migrants in the UK: Findings from the Virus Watch prospective community cohort study.

Background: Migrants in the United Kingdom (UK) may be at higher risk of SARS-CoV-2 exposure; however, little is known about their risk of COVID-19-related hospitalisation during waves 1-3 of the pandemic. Methods: We analysed secondary care data linked to Virus Watch study data for adults and estimated COVID-19-related hospitalisation incidence rates by migration status. To estimate the total effect of migration status on COVID-19 hospitalisation rates, we ran mixed-effect Poisson regression for wave 1 (01/03/2020-31/08/2020; wildtype), and mixed-effect negative binomial regressions for waves 2 (01/09/2020-31/05/2021; Alpha) and 3 (01/06/2020-31/11/2021; Delta). Results of all models were then meta-analysed. Results: Of 30,276 adults in the analyses, 26,492 (87.5 %) were UK-born and 3,784 (12.5 %) were migrants. COVID-19-related hospitalisation incidence rates for UK-born and migrant individuals across waves 1-3 were 2.7 [95 % CI 2.2-3.2], and 4.6 [3.1-6.7] per 1,000 person-years, respectively. Pooled incidence rate ratios across waves suggested increased rate of COVID-19-related hospitalisation in migrants compared to UK-born individuals in unadjusted 1.68 [1.08-2.60] and adjusted analyses 1.35 [0.71-2.60]. Conclusion: Our findings suggest migration populations in the UK have excess risk of COVID-19-related hospitalisations and underscore the need for more equitable interventions particularly aimed at COVID-19 vaccination uptake among migrants.

Linking migration and hospital data in England: linkage process and evaluation of bias.

Introduction: Difficulties ascertaining migrant status in national data sources such as hospital records have limited large-scale evaluation of migrant healthcare needs in many countries, including England. Linkage of immigration data for migrants and refugees, with National Health Service (NHS) hospital care data enables research into the relationship between migration and health for a large cohort of international migrants. Objectives: We aimed to describe the linkage process and compare linkage rates between migrant sub-groups to evaluate for potential bias for data on non-EU migrants and resettled refugees linked to Hospital Episode Statistics (HES) in England. Methods: We used stepwise deterministic linkage to match records from migrants and refugees to a unique healthcare identifier indicating interaction with the NHS (linkage stage 1 to NHS Personal Demographic Services, PDS), and then to hospital records (linkage stage 2 to HES). We calculated linkage rates and compared linked and unlinked migrant characteristics for each linkage stage. Results: Of the 1,799,307 unique migrant records, 1,134,007 (63%) linked to PDS and 451,689 (25%) linked to at least one hospital record between 01/01/2005 and 23/03/2020. Individuals on work, student, or working holiday visas were less likely to link to a hospital record than those on settlement and dependent visas and refugees. Migrants from the Middle East and North Africa and South Asia were four times more likely to link to at least one hospital record, compared to those from East Asia and the Pacific. Differences in age, sex, visa type, and region of origin between linked and unlinked samples were small to moderate. Conclusion: This linked dataset represents a unique opportunity to explore healthcare use in migrants. However, lower linkage rates disproportionately affected individuals on shorter-term visas so future studies of these groups may be more biased as a result. Increasing the quality and completeness of identifiers recorded in administrative data could improve data linkage quality.

Sexual and reproductive health and rights of migrant women attending primary care in England: A population-based cohort study of 1.2 million individuals of reproductive age (2009-2018).

Background: Evidence on the sexual and reproductive health and rights (SRHR) of migrants is lacking globally. We describe SRHR healthcare resource use and long-acting reversible contraceptives (LARCs) prescriptions for migrant versus non-migrant women attending primary care in England (2009-2018). Methods: This population-based observational cohort study, using Clinical Practice Research Datalink (CPRD) GOLD, included females living in England aged 15 to 49. Migration was defined using a validated codelist. Rates per 100 person years at risk (pyar) and adjusted rate ratios (RRs) were measured in migrants versus non-migrants for consultations related to all-causes, six exemplar SRHR outcomes, and LARC prescriptions. Proportions of migrants and non-migrants ever prescribed LARC were calculated. Findings: There were 25,112,116 consultations across 1,246,353 eligible individuals. 98,214 (7.9 %) individuals were migrants. All-cause consultation rates were lower in migrants versus non-migrants (509 vs 583/100pyar;RR 0.9;95 %CI 0.9-0.9), as were consultations rates for emergency contraception (RR 0.7;95 %CI 0.7-0.7) and cervical screening (RR 0.96;95 %CI 0.95-0.97). Higher rates of consultations were found in migrants for abortion (RR 1.2;95 %CI 1.1-1.2) and management of fertility problems (RR 1.39;95 %CI 1.08-1.79). No significant difference was observed for chlamydia testing and domestic violence. Of 1,205,258 individuals eligible for contraception, the proportion of non-migrants ever prescribed LARC (12.2 %;135,047/1,107,894) was almost double that of migrants (6.91 %;6,728/97,364). Higher copper intrauterine devices prescription rates were found in migrants (RR 1.53;95 %CI 1.45-1.61), whilst hormonal LARC rates were lower for migrants: levonorgestrel intrauterine device (RR 0.63;95 %CI 0.60-0.66), subdermal implant (RR 0.72;95 %CI 0.69-0.75), and progesterone-only injection (RR 0.35;95 %CI 0.34-0.36). Interpretation: Healthcare resource use differs between migrant and non-migrant women of reproductive age. Opportunities identified for tailored interventions include access to primary care, LARCs, emergency contraception and cervical screening. An inclusive approach to examining health needs is essential to actualise sexual and reproductive health as a human right.

COVID-19 vaccination coverage for half a million non-EU migrants and refugees in England.

Despite evidence suggesting that some migrants are at risk of under-immunization and have experienced severe health inequities during the pandemic, data are limited on migrants' COVID-19 vaccine coverage globally. Here we linked data from non-European Union migrants and resettled refugees to the national COVID-19 vaccination dataset in England. We estimated patterns in second and third dose delays and overdue doses between 12 December 2020 and 20 April 2022 by age, visa type and ethnicity. Of the 465,470 linked records, 91.8% (427,073/465,470) of migrants received a second dose and 51.3% (238,721/465,470) received a third. Refugees had the highest risk of delayed second (adjusted odds ratio 1.66; 95% confidence interval 1.55-1.79) and third dose (1.55; 1.43-1.69). Black migrants were twice as likely to have a second dose delayed (2.37; 2.23-2.54) than white migrants, but this trend reversed for the third dose. Older migrants (>65 years) were four times less likely to have received their second or third dose compared with the general population in England aged >65 or older. Policymakers, researchers and practitioners should work to understand and address personal and structural barriers to vaccination for diverse migrant populations.

Deprivation, essential and non-essential activities and SARS-CoV-2 infection following the lifting of national public health restrictions in England and Wales.

Background: Individuals living in deprived areas in England and Wales undertook essential activities more frequently and experienced higher rates of SARS-CoV-2 infection than less deprived communities during periods of restrictions aimed at controlling the Alpha (B.1.1.7) variant. We aimed to understand whether these deprivation-related differences changed once restrictions were lifted. Methods: Among 11,231 adult Virus Watch Community Cohort Study participants multivariable logistic regressions were used to estimate the relationships between deprivation and self-reported activities and deprivation and infection (self-reported lateral flow or PCR tests and linkage to National Testing data and Second Generation Surveillance System (SGSS)) between August - December 2021, following the lifting of national public health restrictions. Results: Those living in areas of greatest deprivation were more likely to undertake essential activities (leaving home for work (aOR 1.56 (1.33 - 1.83)), using public transport (aOR 1.33 (1.13 - 1.57)) but less likely to undertake non-essential activities (indoor hospitality (aOR 0.82 (0.70 - 0.96)), outdoor hospitality (aOR 0.56 (0.48 - 0.66)), indoor leisure (aOR 0.63 (0.54 - 0.74)), outdoor leisure (aOR 0.64 (0.46 - 0.88)), or visit a hairdresser (aOR 0.72 (0.61 - 0.85))). No statistical association was observed between deprivation and infection (P=0.5745), with those living in areas of greatest deprivation no more likely to become infected with SARS-CoV-2 (aOR 1.25 (0.87 - 1.79). Conclusion: The lack of association between deprivation and infection is likely due to the increased engagement in non-essential activities among the least deprived balancing the increased work-related exposure among the most deprived. The differences in activities highlight stark disparities in an individuals' ability to choose how to limit infection exposure.

Individuals living in deprived areas of England and Wales left home to go to work and used public transport more frequently than people living in less deprived areas of the country when under tight lockdown restrictions. They were also more likely to develop SARS-CoV-2 infection. Understanding whether these differences changed once restrictions were lifted is important to understand whether deprivation-related discrepancies in infection risk changed throughout the pandemic. We found that, after the removal of lockdown restrictions, people living in areas of the greatest deprivation continued to leave home for work or use public transport more frequently than those not living in areas of deprivation but they were less likely to visit either indoor or outdoor hospitality or leisure venues such as cafes, restaurants, bars, cinemas, theatres or visit a hairdresser or beautician than people living in areas with little deprivation. They were no longer more likely than those living in areas with little deprivation to become infected with SARS-CoV-2. This is likely because people living in areas with little deprivation were visiting hospitality and leisure venues more frequently than during lockdown and were increasing their exposure to infection in these settings, balancing out the increased infection risk posed through work and public transport to those living in deprived areas. The fact that people living in areas of deprivation were most likely exposed to SARS-CoV-2 infection through essential activities like work and public transport use while people living in areas with little deprivation were most likely exposed to infection through non-essential activities such as visiting a restaurant, pub, cinema or theatre, highlights stark disparities in an individuals' ability to choose how to limit infection exposure based on their deprivation status.

SARS-CoV-2 infections in migrants and the role of household overcrowding: a causal mediation analysis of Virus Watch data.

BACKGROUND: Migrants are over-represented in SARS-CoV-2 infections globally; however, evidence is limited for migrants in England and Wales. Household overcrowding is a risk factor for SARS-CoV-2 infection, with migrants more likely to live in overcrowded households than UK-born individuals. We aimed to estimate the total effect of migration status on SARS-CoV-2 infection and to what extent household overcrowding mediated this effect. METHODS: We included a subcohort of individuals from the Virus Watch prospective cohort study during the second SARS-CoV-2 wave (1 September 2020-30 April 2021) who were aged ≥18 years, self-reported the number of rooms in their household and had no evidence of SARS-CoV-2 infection pre-September 2020. We estimated total, indirect and direct effects using Buis' logistic decomposition regression controlling for age, sex, ethnicity, clinical vulnerability, occupation, income and whether they lived with children. RESULTS: In total, 23 478 individuals were included. 9.07% (187/2062) of migrants had evidence of infection during the study period vs 6.27% (1342/21 416) of UK-born individuals. Migrants had 22% higher odds of infection during the second wave (total effect; OR 1.22, 95% CI 1.01 to 1.47). Household overcrowding accounted for approximately 36% (95% CI -4% to 77%) of these increased odds (indirect effect, OR 1.07, 95% CI 1.03 to 1.12; proportion accounted for: indirect effect on log odds scale/total effect on log odds scale=0.36). CONCLUSION: Migrants had higher odds of SARS-CoV-2 infection during the second wave compared with UK-born individuals and household overcrowding explained 36% of these increased odds. Policy interventions to reduce household overcrowding for migrants are needed as part of efforts to tackle health inequalities during the pandemic and beyond.

A case-crossover study of the effect of vaccination on SARS-CoV-2 transmission relevant behaviours during a period of national lockdown in England and Wales.

BACKGROUND: Studies of COVID-19 vaccine effectiveness show increases in COVID-19 cases within 14 days of a first dose, potentially reflecting post-vaccination behaviour changes associated with SARS-CoV-2 transmission before vaccine protection. However, direct evidence for a relationship between vaccination and behaviour is lacking. We aimed to examine the association between vaccination status and self-reported non-household contacts and non-essential activities during a national lockdown in England and Wales. METHODS: Participants (n = 1154) who had received the first dose of a COVID-19 vaccine reported non-household contacts and non-essential activities from February to March 2021 in monthly surveys during a national lockdown in England and Wales. We used a case-crossover study design and conditional logistic regression to examine the association between vaccination status (pre-vaccination vs 14 days post-vaccination) and self-reported contacts and activities within individuals. Stratified subgroup analyses examined potential effect heterogeneity by sociodemographic characteristics such as sex, household income or age group. RESULTS: 457/1154 (39.60 %) participants reported non-household contacts post-vaccination compared with 371/1154 (32.15 %) participants pre-vaccination. 100/1154 (8.67 %) participants reported use of non-essential shops or services post-vaccination compared with 74/1154 (6.41 %) participants pre-vaccination. Post-vaccination status was associated with increased odds of reporting non-household contacts (OR 1.65, 95 % CI 1.31-2.06, p < 0.001) and use of non-essential shops or services (OR 1.50, 95 % CI 1.03-2.17, p = 0.032). This effect varied between men and women and different age groups. CONCLUSION: Participants had higher odds of reporting non-household contacts and use of non-essential shops or services within 14 days of their first COVID-19 vaccine compared to pre-vaccination. Public health emphasis on maintaining protective behaviours during this post-vaccination time period when individuals have yet to develop full protection from vaccination could reduce risk of SARS-CoV-2 infection.

Relative contribution of essential and non-essential activities to SARS-CoV-2 transmission following the lifting of public health restrictions in England and Wales.

PURPOSE: We aimed to understand which non-household activities increased infection odds and contributed greatest to SARS-CoV-2 infections following the lifting of public health restrictions in England and Wales. PROCEDURES: We undertook multivariable logistic regressions assessing the contribution to infections of activities reported by adult Virus Watch Community Cohort Study participants. We calculated adjusted weighted population attributable fractions (aPAF) estimating which activity contributed greatest to infections. FINDINGS: Among 11 413 participants (493 infections), infection was associated with: leaving home for work (aOR 1.35 (1.11-1.64), aPAF 17%), public transport (aOR 1.27 (1.04-1.57), aPAF 12%), shopping once (aOR 1.83 (1.36-2.45)) vs. more than three times a week, indoor leisure (aOR 1.24 (1.02-1.51), aPAF 10%) and indoor hospitality (aOR 1.21 (0.98-1.48), aPAF 7%). We found no association for outdoor hospitality (1.14 (0.94-1.39), aPAF 5%) or outdoor leisure (1.14 (0.82-1.59), aPAF 1%). CONCLUSION: Essential activities (work and public transport) carried the greatest risk and were the dominant contributors to infections. Non-essential indoor activities (hospitality and leisure) increased risk but contributed less. Outdoor activities carried no statistical risk and contributed to fewer infections. As countries aim to 'live with COVID', mitigating transmission in essential and indoor venues becomes increasingly relevant.

Migrants' primary care utilisation before and during the COVID-19 pandemic in England: An interrupted time series analysis.

Background: How international migrants access and use primary care in England is poorly understood. We aimed to compare primary care consultation rates between international migrants and non-migrants in England before and during the COVID-19 pandemic (2015-2020). Methods: Using data from the Clinical Practice Research Datalink (CPRD) GOLD, we identified migrants using country-of-birth, visa-status or other codes indicating international migration. We linked CPRD to Office for National Statistics deprivation data and ran a controlled interrupted time series (ITS) using negative binomial regression to compare rates before and during the pandemic. Findings: In 262,644 individuals, pre-pandemic consultation rates per person-year were 4.35 (4.34-4.36) for migrants and 4.60 (4.59-4.60) for non-migrants (RR:0.94 [0.92-0.96]). Between 29 March and 26 December 2020, rates reduced to 3.54 (3.52-3.57) for migrants and 4.2 (4.17-4.23) for non-migrants (RR:0.84 [0.8-0.88]). The first year of the pandemic was associated with a widening of the gap in consultation rates between migrants and non-migrants to 0.89 (95% CI 0.84-0.94) times the ratio before the pandemic. This widening in ratios was greater for children, individuals whose first language was not English, and individuals of White British, White non-British and Black/African/Caribbean/Black British ethnicities. It was also greater in the case of telephone consultations, particularly in London. Interpretation: Migrants were less likely to use primary care than non-migrants before the pandemic and the first year of the pandemic exacerbated this difference. As GP practices retain remote and hybrid models of service delivery, they must improve services and ensure primary care is accessible and responsive to migrants' healthcare needs. Funding: This study was funded by the Medical Research Council (MC_PC 19070 and MR/V028375/1) and a Wellcome Clinical Research Career Development Fellowship (206602).

Development and Validation of a Primary Care Electronic Health Record Phenotype to Study Migration and Health in the UK.

International migrants comprised 14% of the UK's population in 2020; however, their health is rarely studied at a population level using primary care electronic health records due to difficulties in their identification. We developed a migration phenotype using country of birth, visa status, non-English main/first language and non-UK-origin codes and applied it to the Clinical Practice Research Datalink (CPRD) GOLD database of 16,071,111 primary care patients between 1997 and 2018. We compared the completeness and representativeness of the identified migrant population to Office for National Statistics (ONS) country-of-birth and 2011 census data by year, age, sex, geographic region of birth and ethnicity. Between 1997 to 2018, 403,768 migrants (2.51% of the CPRD GOLD population) were identified: 178,749 (1.11%) had foreign-country-of-birth or visa -status codes, 216,731 (1.35%) non-English-main/first-language codes, and 8288 (0.05%) non-UK-origin codes. The cohort was similarly distributed versus ONS data by sex and region of birth. Migration recording improved over time and younger migrants were better represented than those aged ≥50. The validated phenotype identified a large migrant cohort for use in migration health research in CPRD GOLD to inform healthcare policy and practice. The under-recording of migration status in earlier years and older ages necessitates cautious interpretation of future studies in these groups.

Effect of volume of porogens on the porosity of PLGA scaffolds in pH-controlled environment.

Poly(lactic-co-glycolic acid) (PLGA) is a well-studied biodegradable polymer used in drug delivery and other medical applications such as in tissue regeneration. It is often necessary to impart porosity within the scaffold (microparticles) in order to promote the growth of tissue during the regeneration process. Sodium chloride and ammonium bicarbonate have been extensively used as porogens in the generation of porous microstructure. In this study, we compared the effect of volumes (250 µl, 500 µl and 750 µl) of two porogens, sodium chloride (1.71 M) and ammonium bicarbonate (1.71 M), on the porosity of PLGA microparticles.

A dual-application poly (dl-lactic-co-glycolic) acid (PLGA)-chitosan composite scaffold for potential use in bone tissue engineering.

The development of patient-friendly alternatives to bone-graft procedures is the driving force for new frontiers in bone tissue engineering. Poly (dl-lactic-co-glycolic acid) (PLGA) and chitosan are well-studied and easy-to-process polymers from which scaffolds can be fabricated. In this study, a novel dual-application scaffold system was formulated from porous PLGA and protein-loaded PLGA/chitosan microspheres. Physicochemical and in vitro protein release attributes were established. The therapeutic relevance, cytocompatibility with primary human mesenchymal stem cells (hMSCs) and osteogenic properties were tested. There was a significant reduction in burst release from the composite PLGA/chitosan microspheres compared with PLGA alone. Scaffolds sintered from porous microspheres at 37 °C were significantly stronger than the PLGA control, with compressive strengths of 0.846 ± 0.272 MPa and 0.406 ± 0.265 MPa, respectively (p < 0.05). The formulation also sintered at 37 °C following injection through a needle, demonstrating its injectable potential. The scaffolds demonstrated cytocompatibility, with increased cell numbers observed over an 8-day study period. Von Kossa and immunostaining of the hMSC-scaffolds confirmed their osteogenic potential with the ability to sinter at 37 °C in situ.

Monitoring model drug microencapsulation in PLGA scaffolds using X-ray powder diffraction.

The microencapsulation of three model drugs; metronidazole, paracetamol and sulphapyridine into Poly (dl-Lactide-Co-Glycolide) (PLGA) scaffolds were probed using X-ray Powder Diffraction (XRPD). Changes in the diffraction patterns of the PLGA scaffolds after encapsulation was suggestive of a chemical interaction between the pure drugs and the scaffolds and not a physical intermixture.

Physicomechanical properties of sintered scaffolds formed from porous and protein-loaded poly(DL-lactic-co-glycolic acid) microspheres for potential use in bone tissue engineering.

An injectable poly(DL-lactic-co-glycolic acid) (PLGA) system comprising both porous and protein-loaded microspheres capable of forming porous scaffolds at body temperature was developed for tissue regeneration purposes. Porous and non-porous (lysozyme loaded) PLGA microspheres were formulated to represent 'low molecular weight' 22-34 kDa, 'intermediate molecular weight' (IMW) 53 kDa and 'high molecular weight' 84-109 kDa PLGA microspheres. The respective average size of the microspheres was directly related to the polymer molecular weight. An initial burst release of lysozyme was observed from both microspheres and scaffolds on day 1. In the case of the lysozyme-loaded microspheres, this burst release was inversely related to the polymer molecular weight. Similarly, scaffolds loaded with 1 mg lysozyme/g of scaffold exhibited an inverse release relationship with polymer molecular weight. The burst release was highest amongst IMW scaffolds loaded with 2 and 3 mg/g. Sustained lysozyme release was observed after day 1 over 50 days (microspheres) and 30 days (scaffolds). The compressive strengths of the scaffolds were found to be inversely proportional to PLGA molecular weight at each lysozyme loading. Surface analysis indicated that some of the loaded lysozyme was distributed on the surfaces of the microspheres and thus responsible for the burst release observed. Overall the data demonstrates the potential of the scaffolds for use in tissue regeneration.