The immune status of migrant populations in Europe and implications for vaccine-preventable disease control: a systematic review and meta-analysis.

BACKGROUND: Ensuring vaccination coverage reaches established herd immunity thresholds (HIT) is the cornerstone of any vaccination programme. Diverse migrant populations in European countries have been associated with cases of vaccine-preventable diseases (VPD) and outbreaks, yet it is not clear to what extent they are an under-immunised group. METHODS: We did a systematic review and meta-analysis to synthesise peer-reviewed published primary research reporting data on the immune status of migrants in EU/EEA countries, the UK and Switzerland, calculating their pooled immunity coverage for measles, mumps, rubella, and diphtheria using random-effects models. We searched on Web of Science, Embase, Global Health and MEDLINE (January 1st 2000 to June 10th 2022), with no language restrictions. The protocol is registered with PROSPERO (CRD42018103666). FINDINGS: Of 1103 abstracts screened, 62 met eligibility criteria, of which 39 were included in the meta-analysis. The meta-analysis included 75 089 migrants, predominantly from outside Europe. Pooled immunity coverage among migrant populations was well below the recommended HIT for diphtheria (n = 7, 57.4% [95% CI: 43.1-71.7%] I2 = 99% vs HIT 83-86%), measles (n = 21, 83.7% [95% CI: 79.2-88.2] I2 = 99% vs HIT 93-95%), and mumps (n = 8, 67.1% [95% CI: 50.6-83.6] I2 = 99% vs HIT 88-93%), and midway for rubella (n = 29, 85.6% [95% CI: 83.1-88.1%] I2 = 99% vs HIT 83-94%), with high heterogeneity across studies. INTERPRETATION: Migrants in Europe are an under-immunised group for a range of important VPDs, with this study reinforcing the importance of engaging children, adolescents, and adults in 'catch-up' vaccination initiatives on arrival for vaccines, doses, and boosters they may have missed in their home countries. Co-designing strategies to strengthen catch-up vaccination across the life-course in under-immunised groups is an important next step if we are to meet European and global targets for VPD elimination and control and ensure vaccine equity.

Understanding the health system barriers and enablers to childhood MMR and HPV vaccination among disadvantaged, minority or underserved populations in middle- and high-income countries: a systematic review.

BACKGROUND: Child vaccinations are among the most effective public health interventions. However, wide gaps in child vaccination remain among different groups with uptake in most minorities or ethnic communities in Europe substantially lower compared to the general population. A systematic review was conducted to understand health system barriers and enablers to measles, mumps and rubella (MMR) and human papilloma virus (HPV) child vaccination among disadvantaged, minority populations in middle- and high-income countries. METHODS: We searched Medline, Cochrane, CINAHL, ProQuest and EMBASE for articles published from 2010 to 2021. Following title and abstract screening, full texts were assessed for relevance. Study quality was appraised using Critical Appraisal Skills Program checklists. Data extraction and analysis were performed. Health system barriers and enablers to vaccination were mapped to the World Health Organization health system building blocks. RESULTS: A total of 1658 search results were identified from five databases and 24 from reference lists. After removing duplicates, 1556 titles were screened and 496 were eligible. Eighty-six full texts were assessed for eligibility, 28 articles met all inclusion criteria. Factors that affected MMR and HPV vaccination among disadvantaged populations included service delivery (limited time, geographic distance, lack of culturally appropriate translated materials, difficulties navigating healthcare system), healthcare workforce (language and poor communication skills), financial costs and feelings of discrimination. CONCLUSION: Policymakers must consider health system barriers to vaccination faced by disadvantaged, minority populations while recognizing specific cultural contexts of each population. To ensure maximum policy impact, approaches to encourage vaccinations should be tailored to the unique population's needs. A one-size-fits-all approach is not effective.

Association between multiple sclerosis and urinary levels of toxic metals and organophosphates: A cross-sectional study in Israel.

BACKGROUND: Multiple sclerosis (MS) is a multifactorial disease of uncertain etiology damaging myelin sheaths around axons of the central nervous system. Myelin protects the axon from potentially harmful exogenous factors. The aetiological role of environmental exposure metals and organophosphates is unclear. OBJECTIVE: Identify whether urinary levels of metals and organophosphates differed in MS patients and controls. METHODS: We recruited MS patients from Ziv Medical Centre and healthy controls. MS patients were evaluated according to Expanded Disability Status Scale into mild and moderate-severe conditions. Each participant provided a urine sample and completed epidemiological questionnaires. The levels of six metal (Aluminum, Cadmium, Chromium, Lead, Mercury, Nickel) and one metalloid (Arsenic) and common organophosphates pesticide metabolites (6 dialkylphosphates, DAP) were measured in urine using inductively coupled plasma-mass spectrometry and gas-chromatography mass-spectrometry. We compared cases with controls in terms of urinary levels of these compounds using Mann-Whitney and Kruskall-Wallis tests. RESULTS: Urinary cadmium and mercury levels were higher in the 49 MS patients than the 37 controls (p < 0.01). Cadmium levels were higher in moderate-severe MS patients (n = 24) than mild MS patients (n = 25) (p = 0.003). CONCLUSION: Urinary cadmium and mercury levels were higher among MS patients than controls. Cadmium levels correlated with disease severity. Further studies are needed to explore potential causal pathways between these compounds and MS pathogenesis.

B and T cell responses to the 3rd and 4th dose of the BNT162b2 vaccine in dialysis patients.

Patients on dialysis (PoD) are at high risk of severe morbidity and mortality from COVID-19. Characterizing long-term vaccine immune responses in these patients will help optimize vaccine schedule for PoD. This study aimed to determine whether long-term humoral and B and T cell-responses post 3rd and 4th dose of the BNT162b2 vaccine differed between PoD and controls. Non-infected PoD and controls vaccinated with BNT162b2 were recruited in Ziv Medical Center, Israel, between 2021 and 2022. Specimens were collected 1-2 months pre 3rd dose; 1-3 months post 3rd dose; 4-5 months post 3rd dose and 3-5 months post the 4th dose. Anti-SARS-CoV-2 spike (spike) specific antibodies, spike specific memory B cells, and spike specific CD154+ T cells as well as cytokines producing CD4+/CD8+ T cells were measured using standardized assays and compared between PoD and controls at each time point using Mann Whitney and Fisher's exact tests. We recruited 22 PoD and 20 controls. Antibody levels in PoD were lower compared to controls pre 3rd dose but not post 3rd and 4th doses. Frequencies of spike specific memory B cell populations were similar between PoD and controls overall. Frequencies of spike specific T cells, including those producing IFNγ and TNFα, were not lower in PoD. B and T cell mediated immune response in PoD following a 3rd and a 4th dose of the BNT162b2 vaccine was not inferior to controls up to 5 months post vaccination. Our results suggest that standard BNT162b2 vaccination is suitable for this group.

Barriers to HPV vaccination in marginalized Roma communities in Slovakia.

Introduction: Limited access to healthcare services leads to lower vaccination rates in marginalized Roma communities (MRCs). This study aimed to explore health system barriers to HPV vaccination faced by people from MRCs from multiple perspectives. Methods: The qualitative study was conducted in Slovakia in 2021/22 with 43 community members and health professionals. Data were analyzed using a combination of content analysis and consensual qualitative research. Results: A substantial barrier to vaccination is limited coverage of vaccination expenses for certain age categories by health insurance. Moreover, Slovakia faces a significant shortage of healthcare personnel, leading to work overload and a lack of capacity and motivation to address HPV vaccination. Impaired relationships between health care providers and people from MRCs lead to the avoidance of healthcare services, which contributes to insufficient delivery of information and a lack of awareness regarding HPV-related diseases and vaccination. Conclusion: Strengthening the capacities of health care providers, expanding the age group covered by health insurance and providing tailored information to people from MRCs are necessary prerequisites to increase the availability of HPV vaccination and enable people to make informed decisions about HPV vaccination.

Pediatric injury attendances in different population groups in Israel before, during, and after COVID-19 lockdowns: a descriptive study, 2018-2022.

BACKGROUND: Lockdowns and quarantines during the COVID-19 pandemic influenced healthcare services' usage patterns such as emergency department (ED) attendance. During the pandemic, Israel issued three lockdowns (March-May 2020, September-October 2020, and December 2020-February 2021) to mitigate the spread of COVID-19. Little is known about the impact of these lockdowns on ED attendance for injuries in the diverse population of Northern Israel. METHODS: We described patterns of ED attendance before, during, and after COVID-19 lockdowns. We extracted data from medical records of all northern Israeli children aged 0-17 years old who attended Ziv Medical Center (ZMC) emergency department (ED) due to injury, between 01/01/2018 and 10/02/2022. We compared the volume and characteristics of ED attendance during lockdown periods to the same time periods in the 2 years before the pandemic and 1 year after the lockdowns, using chi-square tests. RESULTS: Seven thousand six hundred nineteen northern children attended ZMC ED during the time periods of the study for injuries and were analyzed. Mean attendance numbers during lockdowns decreased compared to previous years, with an increase in injuries proportion (67.8% (1502/2216) vs. 52.7% (2038/3868) p < 0.001). The proportion of 0-4-year-olds attending for injuries during the lockdown increased compared to pre-pandemic (39.68% vs. 30.7%, p < 0.0001). Minority population attendance decreased (27.47% vs. 30.71% p = 0.02). Hospitalization rates increased (13.21% vs. 10.65% p = 0.01). Post-lockdown periods saw a return to the pre-pandemic age and ethnicity distribution. CONCLUSIONS: Compared to previous years, the volume of injuries was lower during lockdowns for all ages, with a relative increase in the proportion of injuries among younger children attending the ED. A lower proportion of attendance from minority groups suggests different health-seeking behavior patterns during emergencies compared to the general population. Understanding these differences will help better plan for future emergencies.

Barriers and enablers to vaccination in the ultra-orthodox Jewish population: a systematic review.

Background: The Jewish Ultra-Orthodox (UO) population is an under-vaccinated minority group that has been disproportionally affected by outbreaks of vaccine-preventable diseases (VPD) such as measles and polio. Underlying reasons remain poorly characterized. We aimed to identify vaccination barriers and enablers in this population. Methods: We systematically reviewed the literature (PROSPERO: CRD42021273001), searching Pub-med, Web of science, Medline, PsychNet and Scopus from 1995 to 2021 for quantitative and qualitative primary research in English. Studies published outside the date range, not including barriers or enablers, or that were non-primary research were excluded. We assessed included publications for quality and extracted relevant data based on the 5As taxonomy: access, awareness, affordability, acceptance and activation. Results: We included nine qualitative and seven quantitative studies from the 125 studies identified. Access barriers included scheduling difficulties, inconvenient opening hours, and logistical difficulties related to having multiple young children. Acceptance barriers included safety concerns. Insufficient knowledge about the importance of vaccine and timely vaccination and the perception of being shielded from infections because of seclusion from wider society were key awareness barriers. Competing priorities, such as work and housework, were the main affordability barriers. Mainstream religious leadership's support for vaccination was an enabler, although recent studies suggest their influence on vaccination behavior is decreasing and influence of anti-vaccination messages is growing. Discussion: Barriers to vaccination among the UO were mainly logistical, with little religious framing. Safety and efficacy concerns were similar to those reported in the wider community. Decreasing influence of the traditionally pro-vaccine mainstream religious leadership and growing influence of anti-vaccination movements targeting the UO community are new phenomena that require close monitoring. Tailored interventions are required to protect the community and wider society against future VPD outbreaks. Systematic review registration: PROSPERO: CRD42021273001.

Association between BNT162b2 vaccination and health-related quality of life up to 18 months post-SARS-CoV-2 infection in Israel.

We determined whether COVID-19 vaccination was associated with Quality of Life (QoL) changes among individuals previously infected with SARS-CoV-2 in Israel. Using a validated questionnaire, we collected information about socio-demographics, SARS-CoV-2 infection, COVID-19 vaccination and QoL (using the EQ-5D-5L tool) 3-18 months post-infection among adults tested for SARS-CoV-2 by polymerase chain reaction in Northern Israel between March 2020-June 2022. We compared post-COVID QoL between those vaccinated against COVID-19 at the time of infection and those not, using an adjusted linear regression model, stratified by time elapsed since infection. Of 951 participants, mean EQ-5D Utility Index (EQ-5D UI) was 0.82 (SD = 0.26) and 0.83 (SD = 0.25) among the 227 double and 250 triple vaccinated respectively, compared to 0.76 (SD = 0.33) among those who received 0 dose (n = 243). The size of the effect of vaccination was small (Cohen's d = 0.2). In the adjusted model, previously infected individuals vaccinated with two or more doses reported a QoL score post- infection 0.05 points higher (CI = 0.01-0.10, p = 0.02) compared with those unvaccinated when infected. No association between vaccination and QoL was detected beyond 12 months post-infection. Vaccination with two or more doses of COVID19 vaccine, or at least the BNT162b2 vaccine, may modestly mitigate QoL losses associated with post-acute COVID-19 symptoms, at least in the first 12 months post-infection.

Vaccine-induced and hybrid immunity to SARS-CoV-2 after three or four doses of BNT162b2 - results from 22 months follow-up of a healthcare workers cohort, Israel, 2020-2022.

OBJECTIVES: SARS-CoV-2 remains a global health concern 3 years after its emergence. Safe and effective vaccines mitigate the pandemic impact, but the optimal schedule remains unclear, especially in a context where a high proportion of the population is infected. METHODS: We periodically measured anti-spike SARS-CoV-2 immunoglobulin (Ig)G titers using a quantitative assay in an Israeli healthcare worker cohort who all received at least two BNT162b2 doses and either received further doses and/or were subsequently infected up to 22 months after dose two, and compared geometric mean concentrations according to number of doses received and infection status using analysis of variance. RESULTS: Among the 993 included participants, infection after dose two led to higher geometric mean concentration IgG titers than a third dose (4285 vs 2845 arbitrary unit/ml 1-2 months after infection/vaccination, P = 0.03). In 16-18 months after dose two, those infected and those who received three or four vaccine doses all had IgG geometric mean concentration levels above 500 arbitrary unit/ml with no significant differences among groups (P = 0.6). IgG levels plateaued 16-22 months after dose two. CONCLUSION: Three BNT162b2 doses provide long-term immunogenicity comparable to breakthrough infection after dose two. Dose four transiently increases IgG levels and may be especially important for providing additional protection to vulnerable individuals during periods of increased transmission risk.

Changes in Quality of Life Following SARS-CoV-2 Infection Among Jewish and Arab Populations in Israel: A Cross-Sectional Study.

Objectives: The long-term impact of COVID-19 on health inequalities is under-researched. We investigated changes in health-related inequalities following SARS-CoV-2 infection between the Jewish majority and the Arab/Druze minority in Israel. Methods: Patients with a positive SARS-CoV-2 RT-PCR test processed from one of the Northern-Israeli government hospitals between 03/2021 and 05/2022 were invited to participate. We collected socio-demographic, COVID-19-related, and health-related quality of life (HRQoL) information using a validated questionnaire. We compared pre- and post COVID-19 HRQoL changes between Jews and Arabs/Druze, up to 12+ months post-infection using an adjusted linear regression model. Results: Among the 881 included participants the average post-COVID HRQoL score was lower among Arabs/Druze than Jews (0.83 vs. 0.88; p = 0.005). Until 12 months post-infection, HRQoL changes were similar for Arabs/Druze and Jews. After 12 months, HRQoL dropped significantly more among Arabs/Druze than among Jews (0.11 points difference between the groups; p = 0.014), despite adjusting for socioeconomic variables. Conclusion: 12 months post-infection, COVID-19 affected the HRQoL of Arabs/Druze more than Jews, with the gap not fully explained by socio-economic differences. The COVID-19 pandemic may widen pre-existing long-term health inequalities.

Characterization of post-COVID syndromes by symptom cluster and time period up to 12 months post-infection: A systematic review and meta-analysis.

OBJECTIVES: The objective of this study was to characterize post-COVID condition symptoms and symptom clusters, their duration, and prevalence. METHODS: We conducted a systematic review and random-effects meta-analysis of studies reporting post-COVID-19 symptoms and clusters, respectively. We searched MEDLINE (via PubMed), Scopus, Web of Science, Science Direct, Google Scholar, EBSCOhost, EMBASE, PsycINFO, Cochrane Library, and Mednar for literature reporting on the post-COVID condition up to August 2022. RESULTS: In the 76 included studies, we found that although most symptoms were reported less frequently 7-12 months after infection compared to earlier, over 20% of patients reported at least one post-COVID condition-compatible symptom. In the seven studies reporting post-COVID symptom clusters, neurological clustering was consistently identified, followed by cardiorespiratory and systemic/inflammatory. CONCLUSION: Post-COVID symptom clustering provides direction for research into the etiology, diagnosis, and management of post-COVID conditions. Studies reporting post-COVID symptom clusters remain rare due to the focus on individual symptom reporting. Studies on post-COVID symptom clusters should replace individual symptom reporting to accelerate our understanding of this emerging public health issue.

Maternal and Cord Anti-SARS-CoV-2-Spike IgG following COVID-19 Vaccination versus Infection during Pregnancy: A Prospective Study, Israel October 2021-March 2022.

OBJECTIVE: Defining how pregnant women respond to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination is critical to optimize vaccination strategies that protect mother and infant at the epidemic. This study aimed to compare anti-SARS-CoV-2-spike immunoglobulin G (IgG) of vaccinated versus infected women and to determine the optimal timing of maternal vaccination during pregnancy at the time of epidemic. STUDY DESIGN: We collected maternal/cord blood at delivery (October 2021-March 2022) and measured anti-SARS-CoV-2-spike IgG geometric mean concentrations (IgG-GMCs) using a quantitative immunoassay. We compared groups according to timing and number of doses and correlated maternal and fetal IgG levels. We described the proportion of women with IgG levels above the 150 AU/mL positivity threshold according to the timing of infection/vaccination and performed a subanalysis for maternal IgG-GMC levels pre- and during the Omicron wave. RESULTS: We included 238 vaccinated women, 125 who received two doses and 113 three doses, and 48 unvaccinated infected women. All groups infected/vaccinated in the second or third trimester had an IgG-GMC above the positivity threshold. Third-trimester vaccination (second/third dose) resulted in higher maternal and cord-blood IgG-GMC compared to the second trimester (maternal-IgG: 102,32 vs. 4,325 AU/mL, p < 0.001; cord-IgG: 12,113 vs. 8,112 AU/mL, p < 0.001). Compared with infected-only women, a higher proportion of vaccinated women with ≥2 doses and their newborns had IgG levels above the positivity threshold at all time points. In vaccinated women, there were higher maternal IgG-GMC levels during the Omicron wave than pre-Omicron. CONCLUSION: At the time of epidemic, receiving an additional COVID-19 vaccine dose in the third trimester resulted in a higher IgG-GMC compared to the second trimester. Relatively higher levels of maternal and cord IgG-GMC were achieved following vaccination than infection. Women infected during or before the first trimester might benefit from an additional third-trimester dose to prevent peripartum infection and to passively immunize their newborn. The higher levels of maternal IgG-GMC in the Omicron period are suggestive of hybrid immunity. KEY POINTS: · Higher maternal anti-SARS-IgGs in vaccinated → infected.. · Higher cord anti-SARS-IgGs in vaccinated → infected.. · Third-trimester vaccine resulted in high-cord IgG levels..

Addressing Determinants of Immunization Inequities Requires Objective Tools to Devise Local Solutions.

Universal immunization substantially reduces morbidity and mortality from vaccine-preventable diseases. In recent years, routine immunization coverage has varied considerably among countries across the WHO European Region, and among different populations and districts within countries. It has even declined in some countries. Sub-optimal immunization coverage contributes to accumulations of susceptible individuals and can lead to outbreaks of vaccine-preventable diseases. The European Immunization Agenda 2030 (EIA2030) seeks to build better health in the WHO European Region by ensuring equity in immunization and supporting immunization stakeholders in devising local solutions to local challenges. The factors that influence routine immunization uptake are context specific and multifactorial; addressing immunization inequities will require overcoming or removing barriers to vaccination for underserved individuals or populations. Local level immunization stakeholders must first identify the underlying causes of inequities, and based on this information, tailor resources, or service provision to the local context, as per the organization and characteristics of the health care system in their countries. To do this, in addition to using the tools already available to broadly identify immunization inequities at the national and regional levels, they will need new pragmatic guidance and tools to address the identified local challenges. It is time to develop the necessary guidance and tools and support immunization stakeholders at all levels, especially those at the subnational or local health centre levels, to make the vision of EIA2030 a reality.

Associations between reported post-COVID-19 symptoms and subjective well-being, Israel, July 2021 - April 2022.

The impact of individual symptoms reported post-COVID-19 on subjective well-being (SWB) is unknown. We described associations between SWB and selected reported symptoms following SARS-CoV-2 infection. We analysed reported symptoms and subjective well being from 2295 participants (of which 576 reporting previous infection) in an ongoing longitudinal cohort study taking place in Israel. We estimated changes in SWB associated with reported selected symptoms at three follow-up time points (3-6, 6-12 and 12-18 months post infection) among participants reporting previous SARS-CoV-2 infection, adjusted for key demographic variables, using linear regression. Our results suggest that the biggest and most sustained changes in SWB stems from non-specific symptoms (fatigue -7.7 percentage points (pp), confusion/ lack of concentration -10.7 pp, and sleep disorders -11.5pp, P < 0.005), whereas the effect of system-specific symptoms, such as musculoskeletal symptoms (weakness in muscles and muscle pain) on SWB, are less profound and more transient. Taking a similar approach for other symptoms and following individuals over time to describe trends in SWB changes attributable to specific symptoms will help understand the post-acute phase of COVID-19 and how it should be defined and better managed. Post-acute COVID19 symptoms were associated with a significant decrease in subjective well being up to 18 months after initial infection.

Monitoring the COVID-19 immunisation programme through a national immunisation Management system - England's experience.

BACKGROUND: In England routine vaccinations are recorded in either the patients General Practice record or in series of sub-national vaccine registers that are not interoperable. During the COVID-19 pandemic it was established that COVID vaccines would need to be delivered in multiple settings where current vaccine registers do not exist. We describe how a national vaccine register was created to collect data on COVID-19 vaccines. METHODS: The National Immunisation Management System (NIMS) was developed by a range of health and digital government agencies. Vaccinations delivered are entered on an application which is verified by individual National Health Service number in a centralised system. UKHSA receive a feed of this data to use for monitoring vaccine coverage, effectiveness, and safety. To validate the vaccination data, we compared vaccine records to self-reported vaccination dose, manufacturer, and vaccination date from the enhanced surveillance system from 11 February 2021 to 24 August 2021. RESULTS: With the Implementation of NIMS, we have been able to successfully record COVID-19 vaccinations delivered in multiple settings. Of 1,129 individuals, 97.8% were recorded in NIMS as unvaccinated compared to those who self-reported as unvaccinated. One hundred percent and 99.3% of individuals recorded in NIMS as having at least one dose and two doses of the COVID-19 vaccine were also self-reported as having at least one and two doses, respectively. Of the 100% reporting at least one dose, 98.3% self-reported the same vaccination date as NIMS. A total of 98.8% and 99.3% had the same manufacturer information for their first dose and second dose as that which was self-reported, respectively. DISCUSSION: Daily access to individual-level vaccine data from NIMS has allowed UKHSA to estimate vaccine coverage and provide some of the world's first vaccine effectiveness estimates rapidly and accurately.

Equity of the Meningitis B vaccination programme in England, 2016-2018.

In England, the Meningitis B (MenB) vaccine is scheduled at eight and 16 weeks with a booster dose at one year of age and protects children against invasive bacterial meningococcal disease caused by Neisseria meningitidis serogroup B. Coverage of the second dose of MenB vaccine at 12 months was >92% in 2017/18, but this may mask inequalities in coverage in particular population groups. MenB vaccination records for children aged six, 12 and 18 months of age from December 2016 to May 2018 were routinely extracted from GP patient management systems every month in England via a web-based platform for national monitoring of vaccine coverage. We determined the association between ethnicity, deprivation and area of residence, vaccine coverage and drop-out rates (between dose one and dose two), using binomial regression. After adjusting for other factors, ethnic groups with lowest dose one coverage (Black or Black British-Caribbean, White-Any other White background, White-Irish) also had lowest dose two coverage, but in addition, these ethnic groups also had the largest drop-out rates between dose one and dose two. The drop-out rate for Black or Black British-Caribbean children was 5.7 percentage points higher than for White-British children. Vaccine coverage decreased with increasing deprivation quintile, and this was most marked for the booster coverage (6.2 percentage points lower in the most deprived compared to least deprived quintile, p < 0.001). To achieve high coverage for completed courses across all ethnic groups and deprivation quintiles both high initiation rates and a reduction in drop-out rates for ethnic groups with lowest coverage is necessary. A qualitative approach to better understand reasons behind lower coverage and higher drop-out rates in the most underserved ethnic groups is required to develop tailored approaches addressing these inequalities.

Transmission dynamics of the 2016-18 outbreak of hepatitis A among men who have sex with men in England and cost-effectiveness analysis of vaccination strategies to prevent future outbreaks.

Background: Despite being vaccine-preventable, hepatitis A virus (HAV) outbreaks occur among men who have sex with men (MSM). We modelled the cost-effectiveness of vaccination strategies to prevent future outbreaks. Methods: A HAV transmission model was calibrated to HAV outbreak data for MSM in England over 2016-2018, producing estimates for the basic reproduction number (R0) and immunity levels (seroprevalence) post-outbreak. For a hypothetical outbreak in 2023 (same R0 and evolving immunity), the cost-effectiveness of pre-emptive (vaccination between outbreaks among MSM attending sexual health services (SHS)) and reactive (vaccination during outbreak among MSM attending SHS and primary care) vaccination strategies were modelled. Effectiveness in quality-adjusted life-years (QALYs) and costs were estimated (2017 UK pounds) from a societal perspective (10-year time horizon; 3% discount rate). The incremental cost-effectiveness ratio (ICER) was estimated. Findings: R0 for the 2016-2018 outbreak was 3·19 (95% credibility interval (95%CrI) 2·87-3·46); seroprevalence among MSM increased to 70·4% (95%CrI 67·3-72·8%) post-outbreak. For our hypothetical HAV outbreak in 2023, pre-emptively vaccinating MSM over the preceding five-years was cost-saving (compared to no vaccination) if the yearly vaccine coverage rate among MSM attending SHS was <9·1%. Reactive vaccination was also cost-saving compared to no vaccination, but was dominated by pre-emptive vaccination if the yearly vaccination rate was >8%. If the pre-emptive yearly vaccination rate fell below this threshold, it became cost-saving to add reactive vaccination to pre-emptive vaccination. Interpretation: Although highly transmissible, existing immunity limited the recent HAV outbreak among MSM in England. Pre-emptive vaccination between outbreaks, with reactive vaccination if indicated, is the best strategy for limiting future HAV outbreaks. Funding: NIHR.

Protective Effects of BNT162b2 Vaccination on Aerobic Capacity Following Mild to Moderate SARS-CoV-2 Infection: A Cross-Sectional Study Israel.

Patients previously infected with acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may experience post-acute adverse health outcomes, known as long COVID. The most reported symptoms are fatigue, headache and attention/concentration issues, dyspnea and myalgia. In addition, reduced aerobic capacity has been demonstrated in both mild and moderate COVID-19 patients. It is unknown whether COVID-19 vaccination mitigates against reduced aerobic capacity. Our aim was to compare the aerobic capacity of vaccinated and unvaccinated individuals previously infected with SARS-CoV-2. Methods: Individuals aged 18 to 65 years with laboratory-confirmed mild to moderate COVID-19 disease were invited to Ziv Medical Centre, Israel, three months after SARS-CoV-2 infection. We compared individuals unvaccinated at the time of infection to those vaccinated in terms of aerobic capacity, measured using symptom-limited cardiopulmonary exercise test (CPET). Results: We recruited 28 unvaccinated and 22 vaccinated patients. There were no differences in baseline demographic and pulmonary function testing (PFT) parameters. Compared with unvaccinated individuals, those vaccinated had higher V'O2/kg at peak exercise and at the anaerobic threshold. The V'O2/kg peak in the unvaccinated group was 83% of predicted vs. 100% in the vaccinated (p < 0.002). At the anaerobic threshold (AT), vaccinated individuals had a higher V'O2/kg than those unvaccinated. Conclusions: Vaccinated individuals had significantly better exercise performance. Compared with vaccinated individuals, a higher proportion of those unvaccinated performed substantially worse than expected on CPET. These results suggest that vaccination at the time of infection is associated with better aerobic capacity following SARS-CoV-2 infection.