Combined intake of caffeine and low-dose glucose to reduce exercise-related hypoglycaemia in individuals with type 1 diabetes on ultra-long-acting insulin degludec: A randomized, controlled, double-blind, cross-over trial.

AIM: To evaluate whether caffeine combined with a moderate amount of glucose reduces the risk for exercise-related hypoglycaemia compared with glucose alone or control in adult people with type 1 diabetes using ultra-long-acting insulin degludec. MATERIALS AND METHODS: Sixteen participants conducted three aerobic exercise sessions (maximum 75 min) in a randomized, double-blind, cross-over design. Thirty minutes before exercise, participants ingested a drink containing either 250 mg of caffeine + 10 g of glucose + aspartame (CAF), 10 g of glucose + aspartame (GLU), or aspartame alone (ASP). The primary outcome was time to hypoglycaemia. RESULTS: There was a significant effect of the condition on time to hypoglycaemia (χ2 = 7.674, p = .0216). Pairwise comparisons revealed an 85.7% risk reduction of hypoglycaemia for CAF compared with ASP (p = .044). No difference was observed between GLU and ASP (p = .104) or between CAF and GLU (p = .77). While CAF increased glucose levels during exercise compared with GLU and ASP (8.3 ± 1.9 mmol/L vs. 7.7 ± 2.2 mmol/L vs. 5.8 ± 1.4 mmol/L; p < .001), peak plasma glucose levels during exercise did not differ between CAF and GLU (9.3 ± 1.4 mmol/L and 9.1 ± 1.6 mmol/L, p = .80), but were higher than in ASP (6.6 ± 1.1 mmol/L; p < .001). The difference in glucose levels between CAF and GLU was largest during the last 15 min of exercise (p = .002). Compared with GLU, CAF lowered perceived exertion (p = .023). CONCLUSIONS: Pre-exercise caffeine ingestion combined with a low dose of glucose reduced exercise-related hypoglycaemia compared with control while avoiding hyperglycaemia.

Effects of home-based exergaming on cardio-metabolic and cognitive health in physically inactive individuals.

AIMS: To examine the effects of a home-based exergame training over 6 weeks on cardio-metabolic and cognitive health, as well as training adherence, in physically inactive individuals. MATERIALS AND METHODS: Twenty participants were equipped with an exergame system specifically designed for use at home. Each participant performed at least three weekly exercise sessions at ≥80% of their individual maximum heart rate, over 6 weeks. Exercise duration increased biweekly until 75 min of vigorous exercise were performed in Weeks 5 and 6. Maximum oxygen uptake (VO2max), cardio-metabolic profiling, and neuro-cognitive tests were performed at baseline and study end. Additionally, training adherence was assessed via training diaries. RESULTS: After 6 weeks of home-based exergaming, VO2max increased significantly, while there was a significant decrease in heart rate (resting and maximum), blood pressure (systolic, diastolic and mean), and low-density lipoprotein cholesterol. Dynamic balance and reaction time improved after 6 weeks of exergaming. Training adherence was 88.4%. CONCLUSIONS: Home-based exergaming induced a clinically relevant increase in VO2max, a determinant of cardiovascular health, accompanied by further improvements in cardiovascular, metabolic and neuro-cognitive parameters. Exergaming may, therefore, offer an innovative approach to increasing regular physical activity, improving metabolic risk profile, and preventing chronic diseases.

Effects of postprandial exercise on blood glucose levels in adults with type 1 diabetes: a review.

People with type 1 diabetes experience challenges in managing blood glucose around exercise. Previous studies have examined glycaemic responses to different exercise modalities but paid little attention to participants' prandial state, although this is an important consideration and will enhance our understanding of the effects of exercise in order to improve blood glucose management around activity. This review summarises available data on the glycaemic effects of postprandial exercise (i.e. exercise within 2 h after a meal) in people with type 1 diabetes. Using a search strategy on electronic databases, literature was screened until November 2022 to identify clinical trials evaluating acute (during exercise), subacute (≤2 h after exercise) and late (>2 h to ≤24 h after exercise) effects of postprandial exercise in adults with type 1 diabetes. Studies were systematically organised and assessed by exercise modality: (1) walking exercise (WALK); (2) continuous exercise of moderate intensity (CONT MOD); (3) continuous exercise of high intensity (CONT HIGH); and (4) interval training (intermittent high-intensity exercise [IHE] or high-intensity interval training [HIIT]). Primary outcomes were blood glucose change and hypoglycaemia occurrence during and after exercise. All study details and results per outcome were listed in an evidence table. Twenty eligible articles were included: two included WALK sessions, eight included CONT MOD, seven included CONT HIGH, three included IHE and two included HIIT. All exercise modalities caused consistent acute glycaemic declines, with the largest effect size for CONT HIGH and the smallest for HIIT, depending on the duration and intensity of the exercise bout. Pre-exercise mealtime insulin reductions created higher starting blood glucose levels, thereby protecting against hypoglycaemia, in spite of similar declines in blood glucose during activity between the different insulin reduction strategies. Nocturnal hypoglycaemia occurred after higher intensity postprandial exercise, a risk that could be diminished by a post-exercise snack with concomitant bolus insulin reduction. Research on the optimal timing of postprandial exercise is inconclusive. In summary, individuals with type 1 diabetes exercising postprandially should substantially reduce insulin with the pre-exercise meal to avoid exercise-induced hypoglycaemia, with the magnitude of the reduction depending on the exercise duration and intensity. Importantly, pre-exercise blood glucose and timing of exercise should be considered to avoid hyperglycaemia around exercise. To protect against late-onset hypoglycaemia, a post-exercise meal with insulin adjustments might be advisable, especially for exercise in the evening or with a high-intensity component.

Glycaemic patterns of male professional athletes with type 1 diabetes during exercise, recovery and sleep: Retrospective, observational study over an entire competitive season.

AIMS: To analyse glycaemic patterns of professional athletes with type 1 diabetes during a competitive season. MATERIALS AND METHODS: We analysed continuous glucose monitoring data of 12 professional male cyclists with type 1 diabetes during exercise, recovery and sleep on days with competitive exercise (CE) and non-competitive exercise (NCE). We assessed whether differences exist between CE and NCE days and analysed associations between exercise and dysglycaemia. RESULTS: The mean glycated haemoglobin was 50 ± 5 mmol/mol (6.7 ± 0.5%). The athletes cycled on 280.8 ± 28.1 days (entire season 332.6 ± 18.8 days). Overall, time in range (3.9-10 mmol/L) was 70.0 ± 13.7%, time in hypoglycaemia (<3.9 mmol/L) was 6.4 ± 4.7% and time in hyperglycaemia (>10 mmol/L) was 23.6 ± 12.5%. During the nights of NCE days, athletes spent 10.1 ± 7.4% of time in hypoglycaemia, particularly after exercise in the endurance zones. The CE days were characterized by a higher time in hyperglycaemia compared with NCE days (25.2 ± 12.5% vs. 22.2 ± 12.1%, p = .012). This was driven by the CE phase, where time in range dropped to 60.4 ± 13.0% and time in hyperglycaemia was elevated (38.5 ± 12.9%). Mean glucose was higher during CE compared with NCE sessions (9.6 ± 0.9 mmol/L vs. 7.8 ± 1.1 mmol/L, p < .001). The probability of hyperglycaemia during exercise was particularly increased with longer duration, higher intensity and higher variability of exercise. CONCLUSIONS: The analysis of glycaemic patterns of professional endurance athletes revealed that overall glycaemia was generally within targets. For further improvement, athletes, team staff and caregivers may focus on hyperglycaemia during competitions and nocturnal hypoglycaemia after NCE.

Clinical Considerations and Practical Advice for People Living With Type 2 Diabetes Who Undertake Regular Exercise or Aim to Exercise Competitively.

This article provides practical tips for advising people with type 2 diabetes on how to engage in regular exercise safely and effectively. Its focus is on individuals who wish to exceed the minimum physical activity recommendation of 150 minutes/week of moderate-intensity exercise or even compete in their chosen sport. Health care professionals who work with such individuals must have a basic understanding of glucose metabolism during exercise, nutritional requirements, blood glucose management, medications, and sport-related considerations. This article reviews three key aspects of individualized care for physically active people with type 2 diabetes: 1) initial medical assessment and pre-exercise screenings, 2) glucose monitoring and nutritional considerations, and 3) the combined glycemic effects of exercise and medications.

SARS-CoV-2 Evolution and Patient Immunological History Shape the Breadth and Potency of Antibody-Mediated Immunity.

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), humans have been exposed to distinct SARS-CoV-2 antigens, either by infection with different variants, and/or vaccination. Population immunity is thus highly heterogeneous, but the impact of such heterogeneity on the effectiveness and breadth of the antibody-mediated response is unclear. We measured antibody-mediated neutralization responses against SARS-CoV-2Wuhan, SARS-CoV-2α, SARS-CoV-2δ, and SARS-CoV-2ο pseudoviruses using sera from patients with distinct immunological histories, including naive, vaccinated, infected with SARS-CoV-2Wuhan, SARS-CoV-2α, or SARS-CoV-2δ, and vaccinated/infected individuals. We show that the breadth and potency of the antibody-mediated response is influenced by the number, the variant, and the nature (infection or vaccination) of exposures, and that individuals with mixed immunity acquired by vaccination and natural exposure exhibit the broadest and most potent responses. Our results suggest that the interplay between host immunity and SARS-CoV-2 evolution will shape the antigenicity and subsequent transmission dynamics of SARS-CoV-2, with important implications for future vaccine design.

Neutralizing antibodies provide protection against viruses and are generated because of vaccination or prior infections. The main target of anti-SARS-CoV-2 neutralizing antibodies is a protein called spike, which decorates the viral particle and mediates viral entry into cells. As SARS-CoV-2 evolves, mutations accumulate in the spike protein, allowing the virus to escape antibody-mediated immunity and decreasing vaccine effectiveness. Multiple SARS-CoV-2 variants have appeared since the start of the COVID-19 pandemic, causing various waves of infection through the population and infecting­in some cases­people that had been previously infected or vaccinated. Because the antibody response is highly specific, individuals infected with different variants are likely to have different repertoires of neutralizing antibodies. We studied the breadth and potency of the antibody-mediated response against different SARS-CoV-2 variants using sera from vaccinated people as well as from people infected with different variants. We show that potency of the antibody response against different SARS-CoV-2 variants depends on the particular variant that infected each person, the exposure type (infection or vaccination) and the number and order of exposures. Our study provides insight into the interplay between virus evolution and immunity, as well as important information for the development of better vaccination strategies.

The competitive athlete with type 1 diabetes.

Regular exercise is important for health, fitness and longevity in people living with type 1 diabetes, and many individuals seek to train and compete while living with the condition. Muscle, liver and glycogen metabolism can be normal in athletes with diabetes with good overall glucose management, and exercise performance can be facilitated by modifications to insulin dose and nutrition. However, maintaining normal glucose levels during training, travel and competition can be a major challenge for athletes living with type 1 diabetes. Some athletes have low-to-moderate levels of carbohydrate intake during training and rest days but tend to benefit, from both a glucose and performance perspective, from high rates of carbohydrate feeding during long-distance events. This review highlights the unique metabolic responses to various types of exercise in athletes living with type 1 diabetes. Graphical abstract.

Home-based high-intensity interval training reduces barriers to exercise in people with type 1 diabetes.

NEW FINDINGS: What is the topic of this review? This symposium review provides an overview of the recent work investigating whether a virtually monitored home-based high-intensity interval training (Home-HIT) intervention reduces the fear of hypoglycaemia and other common barriers to exercise in people with type 1 diabetes. What advances does it highlight? Home-HIT seems to offer a strategy to reduce fear of hypoglycaemia, while simultaneously removing other known barriers that prevent people with type 1 diabetes from taking up exercise, because it is time efficient, requires no travel time or costs associated with gym memberships, and allows people to exercise in their chosen environment. ABSTRACT: People with type 1 diabetes (T1D) are recommended to engage in regular exercise for a variety of health and fitness reasons. However, many lead a sedentary lifestyle and fail to meet the physical activity guidelines, in part because of the challenge of managing blood glucose concentration and fear of hypoglycaemia. A number of strategies designed to help people with T1D to manage their blood glucose during and after exercise have been investigated. Although many of these strategies show promise in facilitating blood glucose management during and after exercise, they do not target the many other common barriers to exercise that people with T1D face, such as difficulty with cost and travel time to gyms, limited access to exercise bikes and treadmills, and a possible dislike of exercising in front of others in public places. In this symposium review, we provide an overview of ongoing research into a virtually monitored home-based high-intensity interval training (Home-HIT) programme that is designed to reduce these other common barriers to exercise. The conclusion of this review is that Home-HIT seems to offer a strategy to reduce fear of hypoglycaemia, while simultaneously removing other known barriers preventing people with T1D from taking up exercise, such as being time efficient, requiring no travel time or costs associated with gym memberships, and giving them the opportunity to exercise in their chosen environment, reducing the embarrassment experienced by some when exercising in public.

Relative age and maturation selection biases in academy football.

This study examined the simultaneous effects of relative age and biological maturity status upon player selection in an English professional soccer academy. A total of 202 players from the U9 to U16 age groups, over an eight-year period (total of 566 observations), had their relative age (birth quarter) and biological maturity (categorised as late, on-time or early maturing based upon the Khamis-Roche method of percentage of predicted adult height at time of observation) recorded. Players born in the first birth quarter of the year (54.8%) were over-represented across all age groups. A selection bias towards players advanced in maturity status for chronological age emerged in U12 players and increased with age; 0% of players in the U15 and U16 age group were categorised as late maturing. A clear maturity selection bias for early maturing players was, however, only apparent when the least conservative criterion for estimating maturity status was applied (53.8% early and 1.9% late maturing in the U16 age group). Professional football academies need to recognise relative age and maturation as independent constructs that exist and operate independently. Thus, separate strategies should perhaps be designed to address the respective selection biases, to better identify, retain and develop players.

The psychology of bio-banding: a Vygotskian perspective.

CONTEXT: Bio-banding is the process of grouping players by their maturational status rather than chronological age. It is designed to limit the impact of maturational timing on talent identification and development and expose early and late maturing players to new learning experiences and challenges. A common criticism of bio-banding is that it does not consider age related differences in psychosocial and behaviour development. OBJECTIVE: The purpose of this case study is to describe how theory and research pertaining to the design and delivery of mixed-aged classrooms can be used to prepare early and late maturing players for bio-banding and optimise the benefits of this practice. METHOD: After placing the players in their bio-banded groups, one Elite Premier League Academy provided bespoke group psychology sessions for early and late maturing players for six weeks. RESULTS: Providing bespoke psychology sessions for players maturation age allows for the cognitive processes of both early and late maturity status to work within the zone of proximal development. CONCLUSION: Pedagogical practice associated with mixed age classrooms can be used in bio-banded contexts to benefit both early and late maturing players. Delivering psychological sessions alongside bio-banding permits learning and development to both ends of the maturity spectrum.

Home-hit improves muscle capillarisation and eNOS/NAD(P)Hoxidase protein ratio in obese individuals with elevated cardiovascular disease risk.

KEY POINTS: Obesity and sedentary behaviour are associated with capillary rarefaction and impaired muscle microvascular vasoreactivity, due to reduced nitric oxide bioavailability. Low-volume high-intensity interval training (HIT) is a time-efficient alternative to traditional moderate-intensity continuous training (MICT), but its effect on the muscle microvasculature has not been studied. The applicability of current laboratory- and gym-based HIT protocols for obese individuals with low fitness and mobility has been disputed by public health experts, who cite the strenuous nature and complex protocols as major barriers. Therefore, we developed a virtually supervised HIT protocol targeting this group that can be performed at home without equipment (Home-HIT). This study is the first to show that 12 weeks of virtually supervised Home-HIT in obese individuals with elevated cardiovascular disease risk leads to similar increases in capillarisation and eNOS/NAD(P)Hoxidase protein ratio within the muscle microvascular endothelium as virtually supervised home-based MICT and laboratory-based HIT, while reducing many of the major barriers to exercise. ABSTRACT: This study investigated the effect of a novel virtually supervised home-based high-intensity interval training (HIT) (Home-HIT) intervention in obese individuals with elevated cardiovascular disease (CVD) risk on capillarisation and muscle microvascular eNOS/NAD(P)Hoxidase ratio. Thirty-two adults with elevated CVD risk (age 36 ± 10 years; body mass index 34.3 ± 5 kg m-2 ; V̇O2peak 24.6 ± 5.7 ml kg min-1 ), completed one of three 12-week training programmes: Home-HIT (n = 9), laboratory-based supervised HIT (Lab-HIT; n = 10) or virtually supervised home-based moderate-intensity continuous training (Home-MICT; n = 13). Muscle biopsies were taken before and after training to assess changes in vascular enzymes, capillarisation, mitochondrial density, intramuscular triglyceride content and GLUT4 protein expression using quantitative immunofluorescence microscopy. Training increased V̇O2peak (P < 0.001), whole-body insulin sensitivity (P = 0.033) and flow-mediated dilatation (P < 0.001), while aortic pulse wave velocity decreased (P < 0.001) in all three groups. Immunofluorescence microscopy revealed comparable increases in total eNOS content in terminal arterioles and capillaries (P < 0.001) in the three conditions. There was no change in eNOS ser1177 phosphorylation (arterioles P = 0.802; capillaries P = 0.311), but eNOS ser1177 /eNOS content ratio decreased significantly following training in arterioles and capillaries (P < 0.001). Training decreased NOX2 content (arterioles P < 0.001; capillaries P < 0.001), but there was no change in p47phox content (arterioles P = 0.101; capillaries P = 0.345). All measures of capillarisation increased (P < 0.05). There were no between-group differences. Despite having no direct supervision during exercise, virtually supervised Home-HIT resulted in comparable structural and endothelial enzymatic changes in the skeletal muscle microvessels to the traditional training methods. We provide strong evidence that Home-HIT is an effective novel strategy to remove barriers to exercise and improve health in an obese population at risk of CVD.

Premier League academy soccer players' experiences of competing in a tournament bio-banded for biological maturation.

Individual differences in the growth and maturation have been shown to impact player performance and development in youth soccer. This study investigated Premier League academy players' experiences of participating in a tournament bio-banded for biological maturation. Players (N = 66) from four professional soccer clubs aged 11 and 14 years and between 85-90% of adult stature participated in a tournament. Players competed in three 11 vs 11 games on a full size pitch with 25-min halves. Sixteen players participated in four 15-min focus groups and were asked to describe their experiences of participating in the bio-banded tournament in comparison to age group competition. All players described their experience as positive and recommended the Premier League integrate bio-banding into the existing games programme. In comparison to age-group competitions, early maturing players described the bio-banded games more physically challenging, and found that they had to adapt their style of play placing a greater emphasis on technique and tactics. Late maturing players considered the games to be less physically challenging, yet appreciated the having more opportunity to use, develop and demonstrate their technical, physical, and psychological competencies. Bio-banding strategies appear to contribute positively towards the holistic development of young soccer players.

Virtual Reality in Cancer Care: Enhancing Knowledge and Reducing Anxiety about Chemotherapy among Patients and Caregivers.

Virtual reality (VR) technology has evolved from entertainment to significant applications in healthcare and education. Despite its potential, there is limited research on the role of VR in cancer care. This study investigates VR's ability to simulate the chemotherapy process, aiming to enhance patients' knowledge and mitigate anxiety associated with chemotherapy. Utilizing a two-arm, mixed-methods pre/post-survey design, the study measured changes in patients' anxiety and knowledge before and after exposure to a VR simulation. Participants (n = 267) engaged with VR simulations or interactive 360-degree videos depicting the chemotherapy process. Data analyses revealed a significant median increase in chemotherapy knowledge post-exposure to the VR content (z = 12.511, p < 0.001). Demographic factSors significantly influenced perceptions of VR realism and usefulness (p < 0.05). Additionally, VR exposure was correlated with reduced anxiety levels and improved treatment expectations (p < 0.05). Participants with higher post-understanding chemotherapy scores considered VR a useful tool for managing anxiety about chemotherapy and recommended VR for other medical procedures (p < 0.001). These findings underscore VR technology's potential as a valuable tool in cancer treatment, suggesting it can enhance patient education and reduce anxiety, thereby improving patient outcomes during cancer therapy.

The effect of sodium-glucose co-transporter 2 inhibitors on outcomes after cardiac resynchronization therapy.

AIMS: The trials upon which recommendations for the use of cardiac resynchronization therapy (CRT) in heart failure used optimal medical therapy (OMT) before sodium-glucose co-transporter 2 inhibitors (SGLT2i). Moreover, the SGLT2i heart failure trials included only a small proportion of participants with CRT, and therefore, it remains uncertain whether SGLT2i should be considered part of OMT prior to CRT. METHODS AND RESULTS: We compared electrocardiogram (ECG) and echocardiographic responses to CRT as well as hospitalization and mortality rates in consecutive patients undergoing implantation at a large tertiary centre between January 2019 to June 2022 with and without SGLT2i treatment. Three hundred seventy-four participants were included aged 74.0 ± 11.5 years (mean ± standard deviation), with a left ventricular ejection fraction (LVEF) of 31.8 ± 9.9% and QRS duration of 161 ± 29 ms. The majority had non-ischaemic cardiomyopathy (58%) and were in NYHA Class II/III (83.6%). These characteristics were similar between patients with (n = 66) and without (n = 308) prior SGLT2i treatment. Both groups demonstrated similar evidence of response to CRT in terms of QRS duration shortening, and improvements in LVEF, left ventricular end-diastolic inner-dimension (LVIDd) and diastolic function (E/A and e/e'). While there was no difference in rates of hospitalization (for heart failure or overall), mortality was significantly lower in patients treated with SGLT2i compared with those who were not (6.5 vs. 16.6%, P = 0.049). CONCLUSIONS: We observed an improvement in mortality in patients undergoing CRT prescribed SGLT2i compared with those not prescribed SGLT2i, despite similar degrees of reverse remodelling. The authors recommend starting SGLT2i prior to CRT implantation, where it does not delay implantation.

Increase in SARS-CoV-2 Seroprevalence in UK Domestic Felids Despite Weak Immunogenicity of Post-Omicron Variants.

Throughout the COVID-19 pandemic, SARS-CoV-2 infections in domestic cats have caused concern for both animal health and the potential for inter-species transmission. Cats are known to be susceptible to the Omicron variant and its descendants, however, the feline immune response to these variants is not well defined. We aimed to estimate the current seroprevalence of SARS-CoV-2 in UK pet cats, as well as characterise the neutralising antibody response to the Omicron (BA.1) variant. A neutralising seroprevalence of 4.4% and an overall seroprevalence of 13.9% was observed. Both purebred and male cats were found to have the highest levels of seroprevalence, as well as cats aged between two and five years. The Omicron variant was found to have a lower immunogenicity in cats than the B.1, Alpha and Delta variants, which reflects previous reports of immune and vaccine evasion in humans. These results further underline the importance of surveillance of SARS-CoV-2 infections in UK cats as the virus continues to evolve.

Immunological imprinting of humoral immunity to SARS-CoV-2 in children.

Omicron variants of SARS-CoV-2 are globally dominant and infection rates are very high in children. We measure immune responses following Omicron BA.1/2 infection in children aged 6-14 years and relate this to prior and subsequent SARS-CoV-2 infection or vaccination. Primary Omicron infection elicits a weak antibody response with poor functional neutralizing antibodies. Subsequent Omicron reinfection or COVID-19 vaccination elicits increased antibody titres with broad neutralisation of Omicron subvariants. Prior pre-Omicron SARS-CoV-2 virus infection or vaccination primes for robust antibody responses following Omicron infection but these remain primarily focussed against ancestral variants. Primary Omicron infection thus elicits a weak antibody response in children which is boosted after reinfection or vaccination. Cellular responses are robust and broadly equivalent in all groups, providing protection against severe disease irrespective of SARS-CoV-2 variant. Immunological imprinting is likely to act as an important determinant of long-term humoral immunity, the future clinical importance of which is unknown.

Ethnic differences in cellular and humoral immune responses to SARS-CoV-2 vaccination in UK healthcare workers: a cross-sectional analysis.

Background: Few studies have compared SARS-CoV-2 vaccine immunogenicity by ethnic group. We sought to establish whether cellular and humoral immune responses to SARS-CoV-2 vaccination differ according to ethnicity in UK Healthcare workers (HCWs). Methods: In this cross-sectional analysis, we used baseline data from two immunological cohort studies conducted in HCWs in Leicester, UK. Blood samples were collected between March 3, and September 16, 2021. We excluded HCW who had not received two doses of SARS-CoV-2 vaccine at the time of sampling and those who had serological evidence of previous SARS-CoV-2 infection. Outcome measures were SARS-CoV-2 spike-specific total antibody titre, neutralising antibody titre and ELISpot count. We compared our outcome measures by ethnic group using univariable (t tests and rank-sum tests depending on distribution) and multivariable (linear regression for antibody titres and negative binomial regression for ELISpot counts) tests. Multivariable analyses were adjusted for age, sex, vaccine type, length of interval between vaccine doses and time between vaccine administration and sample collection and expressed as adjusted geometric mean ratios (aGMRs) or adjusted incidence rate ratios (aIRRs). To assess differences in the early immune response to vaccination we also conducted analyses in a subcohort who provided samples between 14 and 50 days after their second dose of vaccine. Findings: The total number of HCWs in each analysis were 401 for anti-spike antibody titres, 345 for neutralising antibody titres and 191 for ELISpot. Overall, 25.4% (19.7% South Asian and 5.7% Black/Mixed/Other) were from ethnic minority groups. In analyses including the whole cohort, neutralising antibody titres were higher in South Asian HCWs than White HCWs (aGMR 1.47, 95% CI [1.06-2.06], P = 0.02) as were T cell responses to SARS-CoV-2 S1 peptides (aIRR 1.75, 95% CI [1.05-2.89], P = 0.03). In a subcohort sampled between 14 and 50 days after second vaccine dose, SARS-CoV-2 spike-specific antibody and neutralising antibody geometric mean titre (GMT) was higher in South Asian HCWs compared to White HCWs (9616 binding antibody units (BAU)/ml, 95% CI [7178-12,852] vs 5888 BAU/ml [5023-6902], P = 0.008 and 2851 95% CI [1811-4487] vs 1199 [984-1462], P < 0.001 respectively), increments which persisted after adjustment (aGMR 1.26, 95% CI [1.01-1.58], P = 0.04 and aGMR 2.01, 95% CI [1.34-3.01], P = 0.001). SARS-CoV-2 ELISpot responses to S1 and whole spike peptides (S1 + S2 response) were higher in HCWs from South Asian ethnic groups than those from White groups (S1: aIRR 2.33, 95% CI [1.09-4.94], P = 0.03; spike: aIRR, 2.04, 95% CI [1.02-4.08]). Interpretation: This study provides evidence that, in an infection naïve cohort, humoral and cellular immune responses to SARS-CoV-2 vaccination are stronger in South Asian HCWs than White HCWs. These differences are most clearly seen in the early period following vaccination. Further research is required to understand the underlying mechanisms, whether differences persist with further exposure to vaccine or virus, and the potential impact on vaccine effectiveness. Funding: DIRECT and BELIEVE have received funding from UK Research and Innovation (UKRI) through the COVID-19 National Core Studies Immunity (NCSi) programme (MC_PC_20060).

SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination.

BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. METHODS: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. FINDINGS: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. INTERPRETATION: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. FUNDING: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript.

A Brief Review on the Evolution of Technology in Exercise and Sport in Type 1 Diabetes: Past, Present, and Future.

One hundred years ago, insulin was first used to successfully lower blood glucose levels in young people living with what was then called juvenile diabetes. While insulin was not a cure for diabetes, it allowed individuals to resume a near normal life and have some freedom to eat more liberally and gain the strength they needed to live a more active lifestyle. Since then, a number of therapeutic and technical advances have arisen to further improve the health and wellbeing of individuals living with type 1 diabetes, allowing many to participate in sport at the local, regional, national or international level of competition. This review and commentary highlights some of the key advances in diabetes management in sport over the last 100 years since the discovery of insulin.