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BACKGROUND: Both infection and vaccination, alone or in combination, generate antibody and T cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the maintenance of such responses-and hence protection from disease-requires careful characterization. In a large prospective study of UK healthcare workers (HCWs) (Protective Immunity from T Cells in Healthcare Workers [PITCH], within the larger SARS-CoV-2 Immunity and Reinfection Evaluation [SIREN] study), we previously observed that prior infection strongly affected subsequent cellular and humoral immunity induced after long and short dosing intervals of BNT162b2 (Pfizer/BioNTech) vaccination. METHODS: Here, we report longer follow-up of 684 HCWs in this cohort over 6-9 months following two doses of BNT162b2 or AZD1222 (Oxford/AstraZeneca) vaccination and up to 6 months following a subsequent mRNA booster vaccination. FINDINGS: We make three observations: first, the dynamics of humoral and cellular responses differ; binding and neutralizing antibodies declined, whereas T and memory B cell responses were maintained after the second vaccine dose. Second, vaccine boosting restored immunoglobulin (Ig) G levels; broadened neutralizing activity against variants of concern, including Omicron BA.1, BA.2, and BA.5; and boosted T cell responses above the 6-month level after dose 2. Third, prior infection maintained its impact driving larger and broader T cell responses compared with never-infected people, a feature maintained until 6 months after the third dose. CONCLUSIONS: Broadly cross-reactive T cell responses are well maintained over time-especially in those with combined vaccine and infection-induced immunity ("hybrid" immunity)-and may contribute to continued protection against severe disease. FUNDING: Department for Health and Social Care, Medical Research Council.

PhD Abstract: This project explores principles of “meaning” and “the meaningful” as active and embodied “gestures” or “lived-realities”, via concepts of “sharing” and communicative relationality. These concepts were ethnographically researched in the far northern, religiously-plural Indian state of Uttarakhand. This is a state with faith-based populations variously self-identifying as Hindu, Christian, Buddhist, Sikh, or Muslim. I met members of all of these faiths regularly, although my interlocutors were predominantly Christian and Hindu. Formerly a region of Uttar Pradesh, Uttarakhand is known for its close proximity to the Himalaya, the Indian borders with Tibet and Nepal, and for its religious sanctity as an area of devout (usually Hindu) pilgrimage. All of these diverse factors have led to the consistent and complex intermingling of a number of sub-communities and regional populations. This was evident within many of the larger towns, such as Mussoorie, found in the Garhwal district of Uttarakhand, and the central-base for my fieldwork. My methodology was ethnographic and qualitative, focusing on oral-verbal communications and person-to-person interactions. These processes defined my principal concepts within this project by demonstrating the lived-realities of religious identities, religious communities, and the prevalence of inter-faith communication (or “sharing”) within this region. Most significantly, my research highlighted the ongoing importance of meanings – as well as the notable variance in what “the meaningful” was actually considered to be across and between faiths. Such diversity in understanding was made even more complex by different meanings being expressed in the same language, forms, narratives, or verbal images. Within these communications, metaphor was a creative, commonly used, and actively-engaged principle, evidenced within the practice of (different) faiths. This demonstrated a form of “relationality” or “inter-relationality” that seemed to reinforce contemporary, anthropological concepts of embodied lived-realities being a fundamental aspect of the relational, but not the same as “definitionality” or as “meaning”. Yet, when in use in Uttarakhand, principles, concepts (and uses) of expressive form, representation, communication, “sharing”, and “meaning”, were frequently entangled . Many apparent “oral metaphors” and “descriptions” – including images of “sacrifice”, “heart-speech”, God, Gods, or the cosmological/transcendent – had extended-meanings and purposes in their Garhwali context. Such meanings and actions were in contrast to what I had previously understood metaphor “to be”. These were not solely representational-metaphors, they were, instead, acts of agency (via expression). These observations led to my own evolution of the term “ontological-metaphor”. The metaphorical was persistently utilised not only as a “symbolic- tool”, but as an overlapping, entwined lived-form that was capable of encapsulating the relational and definitional-meaningful. This was not merely in a simultaneous representation, but as a co-creational state-of-being or “ontology”.

The SRQR information for the paper titled: ‘Because people here are ignorant’: The failure of a community intervention to prevent mycetoma in Sudan

Funder: Medical Research Council, Funder: National Institute for Health Research (NIHR), Funder: Wellcome Trust, Funder: UK Health Security Agency, Funder: Cancer Research UK, OBJECTIVES: To investigate serological differences between SARS-CoV-2 reinfection cases and contemporary controls, to identify antibody correlates of protection against reinfection. METHODS: We performed a case-control study, comparing reinfection cases with singly infected individuals pre-vaccination, matched by gender, age, region and timing of first infection. Serum samples were tested for anti-SARS-CoV-2 spike (anti-S), anti-SARS-CoV-2 nucleocapsid (anti-N), live virus microneutralisation (LV-N) and pseudovirus microneutralisation (PV-N). Results were analysed using fixed effect linear regression and fitted into conditional logistic regression models. RESULTS: We identified 23 cases and 92 controls. First infections occurred before November 2020; reinfections occurred before February 2021, pre-vaccination. Anti-S levels, LV-N and PV-N titres were significantly lower among cases; no difference was found for anti-N levels. Increasing anti-S levels were associated with reduced risk of reinfection (OR 0·63, CI 0·47-0·85), but no association for anti-N levels (OR 0·88, CI 0·73-1·05). Titres >40 were correlated with protection against reinfection for LV-N Wuhan (OR 0·02, CI 0·001-0·31) and LV-N Alpha (OR 0·07, CI 0·009-0·62). For PV-N, titres >100 were associated with protection against Wuhan (OR 0·14, CI 0·03-0·64) and Alpha (0·06, CI 0·008-0·40). CONCLUSIONS: Before vaccination, protection against SARS-CoV-2 reinfection was directly correlated with anti-S levels, PV-N and LV-N titres, but not with anti-N levels. Detectable LV-N titres were sufficient for protection, whilst PV-N titres >100 were required for a protective effect. TRIAL REGISTRATION NUMBER: ISRCTN11041050.

Background: There is an urgent need to better understand whether individuals who have recovered from COVID-19 are protected from future SARS-CoV-2 infection.Methods: A large multi-centre prospective cohort was recruited from publicly funded hospital staff in the UK. Participants attended regular SARS-CoV-2 PCR and antibody testing (every 2-4 weeks) and completed fortnightly questionnaires on symptoms and exposures. At enrolment, participants were assigned to either the positive cohort (antibody positive or prior PCR/antibody test positive) or negative cohort (antibody negative, not previously known to be PCR/antibody positive). Potential reinfections were clinically reviewed and classified according to case definitions (confirmed, probable, possible (subdivided by symptom-status)) depending on hierarchy of evidence. Individuals in the primary infection were excluded from this analysis if infection was confirmed by antibody only. Reinfection rates in the positive cohort were compared against new PCR positives in the negative cohort using a mixed effective multivariable logistic regression analysis.Findings: Between 18 June and 09 November 2020, 44 reinfections (2 probable, 42 possible) were detected in the baseline positive cohort of 6,614 participants, collectively contributing 1,339,078 days of follow-up. This compares with 318 new PCR positive infections and 94 antibody seroconversions in the negative cohort of 14,173 participants, contributing 1,868,646 days of follow-up. The incidence density per 100,000 person days between June and November 2020 was 3.2 reinfections in the positive cohort, compared with 22.4 new PCR confirmed infections in the negative cohort. The adjusted odds ratio was 0.17 for all reinfections (95% CI 0.13-0.24) compared to PCR confirmed primary infections. The median interval between primary infection and reinfection was over 160 days.Interpretation: A prior history of SARS-CoV-2 infection was associated with an 83% lower risk of infection, with median protective effect observed five months following primary infection. This is the minimum likely effect as seroconversions were not included.Trial Registration: Trial registered with ISRCTN, Trial ID: ISRCTN11041050. https://www.isrctn.com/ISRCTN11041050.Funding Statement: Department of Health and Social Care and Public Health England, with contributions from the Scottish, Welsh and Northern Irish governments.Declaration of Interests: No conflicts of interest declared.Ethics Approval Statement: IRAS ID 284460, Berkshire Research Ethics Committee, Health Research Authority and Health and Care Research Wales approval granted 22 May 2020.

Supported by the U.K. Health Security Agency, the U.K. Department of Health and Social Care (with contributions from the governments in Northern Ireland, Wales, and Scotland), the National Institute for Health Research, and grants from the Medical Research Council. Background: The duration and effectiveness of immunity from infection with and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are relevant to pandemic policy interventions, including the timing of vaccine boosters. Methods: We investigated the duration and effectiveness of immunity in a prospective cohort of asymptomatic health care workers in the United Kingdom who underwent routine polymerase-chain-reaction (PCR) testing. Vaccine effectiveness (≤10 months after the first dose of vaccine) and infection-acquired immunity were assessed by comparing the time to PCR-confirmed infection in vaccinated persons with that in unvaccinated persons, stratified according to previous infection status. We used a Cox regression model with adjustment for previous SARS-CoV-2 infection status, vaccine type and dosing interval, demographic characteristics, and workplace exposure to SARS-CoV-2. Results: Of 35,768 participants, 27% (9488) had a previous SARS-CoV-2 infection. Vaccine coverage was high: 95% of the participants had received two doses (78% had received BNT162b2 vaccine [Pfizer-BioNTech] with a long interval between doses, 9% BNT162b2 vaccine with a short interval between doses, and 8% ChAdOx1 nCoV-19 vaccine [AstraZeneca]). Between December 7, 2020, and September 21, 2021, a total of 2747 primary infections and 210 reinfections were observed. Among previously uninfected participants who received long-interval BNT162b2 vaccine, adjusted vaccine effectiveness decreased from 85% (95% confidence interval [CI], 72 to 92) 14 to 73 days after the second dose to 51% (95% CI, 22 to 69) at a median of 201 days (interquartile range, 197 to 205) after the second dose; this effectiveness did not differ significantly between the long-interval and short-interval BNT162b2 vaccine recipients. At 14 to 73 days after the second dose, adjusted vaccine effectiveness among ChAdOx1 nCoV-19 vaccine recipients was 58% (95% CI, 23 to 77) - considerably lower than that among BNT162b2 vaccine recipients. Infection-acquired immunity waned after 1 year in unvaccinated participants but remained consistently higher than 90% in those who were subsequently vaccinated, even in persons infected more than 18 months previously. Conclusions: Two doses of BNT162b2 vaccine were associated with high short-term protection against SARS-CoV-2 infection; this protection waned considerably after 6 months. Infection-acquired immunity boosted with vaccination remained high more than 1 year after infection. Publisher PDF

Scoping review protocol; Pre-data collection

OBJECTIVES: To investigate serological differences between SARS-CoV-2 reinfection cases and contemporary controls, to identify antibody correlates of protection against reinfection. METHODS: We performed a case-control study, comparing reinfection cases with singly infected individuals pre-vaccination, matched by gender, age, region and timing of first infection. Serum samples were tested for anti-SARS-CoV-2 spike (anti-S), anti-SARS-CoV-2 nucleocapsid (anti-N), live virus microneutralisation (LV-N) and pseudovirus microneutralisation (PV-N). Results were analysed using fixed effect linear regression and fitted into conditional logistic regression models. RESULTS: We identified 23 cases and 92 controls. First infections occurred before November 2020; reinfections occurred before February 2021, pre-vaccination. Anti-S levels, LV-N and PV-N titres were significantly lower among cases; no difference was found for anti-N levels. Increasing anti-S levels were associated with reduced risk of reinfection (OR 0•63, CI 0•47-0•85), but no association for anti-N levels (OR 0•88, CI 0•73-1•05). Titres >40 were correlated with protection against reinfection for LV-N Wuhan (OR 0•02, CI 0•001-0•31) and LV-N Alpha (OR 0•07, CI 0•009-0•62). For PV-N, titres >100 were associated with protection against Wuhan (OR 0•14, CI 0•03-0•64) and Alpha (0•06, CI 0•008-0•40). CONCLUSIONS: Before vaccination, protection against SARS-CoV-2 reinfection was directly correlated with anti-S levels, PV-N and LV-N titres, but not with anti-N levels. Detectable LV-N titres were sufficient for protection, whilst PV-N titres >100 were required for a protective effect. TRIAL REGISTRATION NUMBER: ISRCTN11041050.

This report provides an overview of the legal and policy framework of integration policies in the UK and explains the main contours of immigrant integration. The report looks into policies (macro-level), practices of stakeholders (meso-level) and experiences of immigrants (micro- level) in five thematic fields: a) labour market, b) education, c) housing and spatial integration, d) psychosocial health and e) citizenship and belonging. The report draws on interviews with asylum seekers and refugees at the micro level, and with stakeholders from NGOs and local authorities who are involved in the implementation of integration policies at the meso level. The main contribution of this study lies in its micro empirical focus by bringing in ethnographic insights from the perspective of asylum seekers and refugees based on their experiences vis- à-vis migration and integration policies. These individual accounts show us how asylum seekers and refugees are struggling to establish a new home in the UK and at a different level, in developing a belonging to a new place of living, while expressing their frustrations and hopes, their secondary traumas and resilience. In other words, they inform us about their integration experiences in society.