Ethnic inequalities in COVID-19 vaccine uptake and comparison to seasonal influenza vaccine uptake in Greater Manchester,UK: A cohort study

BackgroundCOVID-19 vaccine uptake is lower amongst most minority ethnic groups compared to the White British group in England, despite higher COVID-19 mortality rates. Here, we add to existing evidence by estimating inequalities for 16 minority ethnic groups, examining ethnic inequalities within population subgroups, and comparing the magnitudes of ethnic inequalities in COVID-19 vaccine uptake to those for routine seasonal influenza vaccine uptake.Methods and findingsWe conducted a retrospective cohort study using the Greater Manchester Care Record, which contains de-identified electronic health record data for the population of Greater Manchester, England. We used Cox proportional hazards models to estimate ethnic inequalities in time to COVID-19 vaccination amongst people eligible for vaccination on health or age (50+ years) criteria between 1 December 2020 and 18 April 2021 (138 days of follow-up). We included vaccination with any approved COVID-19 vaccine, and analysed first-dose vaccination only. We compared inequalities between COVID-19 and influenza vaccine uptake adjusting by age group and clinical risk, and used subgroup analysis to identify populations where inequalities were widest. The majority of individuals (871,231; 79.24%) were White British. The largest minority ethnic groups were Pakistani (50,268; 4.75%), ‘other White background’ (43,195; 3.93%), ‘other ethnic group’ (34,568; 3.14%), and Black African (18,802; 1.71%). In total, 83.64% (919,636/1,099,503) of eligible individuals received a COVID-19 vaccine. Uptake was lower compared to the White British group for 15 of 16 minority ethnic groups, with particularly wide inequalities amongst the groups ‘other Black background’ (hazard ratio [HR] 0.42, 95% CI 0.40 to 0.44), Black African (HR 0.43, 95% CI 0.42 to 0.44), Arab (HR 0.43, 95% CI 0.40 to 0.48), and Black Caribbean (HR 0.43, 95% CI 0.42 to 0.45). In total, 55.71% (419,314/752,715) of eligible individuals took up influenza vaccination. Compared to the White British group, inequalities in influenza vaccine uptake were widest amongst the groups ‘White and Black Caribbean’ (HR 0.63, 95% CI 0.58 to 0.68) and ‘White and Black African’ (HR 0.67, 95% CI 0.63 to 0.72). In contrast, uptake was slightly higher than the White British group amongst the groups ‘other ethnic group’ (HR 1.11, 95% CI 1.09 to 1.12) and Bangladeshi (HR 1.08, 95% CI 1.05 to 1.11). Overall, ethnic inequalities in vaccine uptake were wider for COVID-19 than influenza vaccination for 15 of 16 minority ethnic groups. COVID-19 vaccine uptake inequalities also existed amongst individuals who previously took up influenza vaccination. Ethnic inequalities in COVID-19 vaccine uptake were concentrated amongst older and extremely clinically vulnerable adults, and the most income-deprived. A limitation of this study is the focus on uptake of the first dose of COVID-19 vaccination, rather than full COVID-19 vaccination.ConclusionsEthnic inequalities in COVID-19 vaccine uptake exceeded those for influenza vaccine uptake, existed amongst those recently vaccinated against influenza, and were widest amongst those with greatest COVID-19 risk. This suggests the COVID-19 vaccination programme has created additional and different inequalities beyond pre-existing health inequalities. We suggest that further research and policy action is needed to understand and remove barriers to vaccine uptake, and to build trust and confidence amongst minority ethnic communities.

Ruth Elizabeth Watkinson and colleagues estimate inequalities in Covid-19 vaccine uptake for 16 minority ethnic groups and compare them to those in routine seasonal Influenza vaccine uptake.     

Risk factors associated with SARS-CoV-2 infection in a multiethnic cohort of United Kingdom healthcare workers (UK-REACH): A cross-sectional analysis

BackgroundHealthcare workers (HCWs), particularly those from ethnic minority groups, have been shown to be at disproportionately higher risk of infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) compared to the general population. However, there is insufficient evidence on how demographic and occupational factors influence infection risk among ethnic minority HCWs.Methods and findingsWe conducted a cross-sectional analysis using data from the baseline questionnaire of the United Kingdom Research study into Ethnicity and Coronavirus Disease 2019 (COVID-19) Outcomes in Healthcare workers (UK-REACH) cohort study, administered between December 2020 and March 2021. We used logistic regression to examine associations of demographic, household, and occupational risk factors with SARS-CoV-2 infection (defined by polymerase chain reaction (PCR), serology, or suspected COVID-19) in a diverse group of HCWs. The primary exposure of interest was self-reported ethnicity.Among 10,772 HCWs who worked during the first UK national lockdown in March 2020, the median age was 45 (interquartile range [IQR] 35 to 54), 75.1% were female and 29.6% were from ethnic minority groups. A total of 2,496 (23.2%) reported previous SARS-CoV-2 infection. The fully adjusted model contained the following dependent variables: demographic factors (age, sex, ethnicity, migration status, deprivation, religiosity), household factors (living with key workers, shared spaces in accommodation, number of people in household), health factors (presence/absence of diabetes or immunosuppression, smoking history, shielding status, SARS-CoV-2 vaccination status), the extent of social mixing outside of the household, and occupational factors (job role, the area in which a participant worked, use of public transport to work, exposure to confirmed suspected COVID-19 patients, personal protective equipment [PPE] access, aerosol generating procedure exposure, night shift pattern, and the UK region of workplace). After adjustment, demographic and household factors associated with increased odds of infection included younger age, living with other key workers, and higher religiosity. Important occupational risk factors associated with increased odds of infection included attending to a higher number of COVID-19 positive patients (aOR 2.59, 95% CI 2.11 to 3.18 for ≥21 patients per week versus none), working in a nursing or midwifery role (1.30, 1.11 to 1.53, compared to doctors), reporting a lack of access to PPE (1.29, 1.17 to 1.43), and working in an ambulance (2.00, 1.56 to 2.58) or hospital inpatient setting (1.55, 1.38 to 1.75). Those who worked in intensive care units were less likely to have been infected (0.76, 0.64 to 0.92) than those who did not. Black HCWs were more likely to have been infected than their White colleagues, an effect which attenuated after adjustment for other known risk factors. This study is limited by self-selection bias and the cross sectional nature of the study means we cannot infer the direction of causality.ConclusionsWe identified key sociodemographic and occupational risk factors associated with SARS-CoV-2 infection among UK HCWs, and have determined factors that might contribute to a disproportionate odds of infection in HCWs from Black ethnic groups. These findings demonstrate the importance of social and occupational factors in driving ethnic disparities in COVID-19 outcomes, and should inform policies, including targeted vaccination strategies and risk assessments aimed at protecting HCWs in future waves of the COVID-19 pandemic.Trial registrationThe study was prospectively registered at ISRCTN (reference number: ISRCTN11811602).

Christopher A Martin and colleagues investigate associations of demographic, household and occupational risk factors with SARS-CoV-2 infection in a diverse group of healthcare workers in the UK.     

Seroprevalence of IgG antibodies against SARS-CoV-2 among the general population and healthcare workers in India,June–July 2021: A population-based cross-sectional study

BackgroundIndia began COVID-19 vaccination in January 2021, initially targeting healthcare and frontline workers. The vaccination strategy was expanded in a phased manner and currently covers all individuals aged 18 years and above. India experienced a severe second wave of COVID-19 during March–June 2021. We conducted a fourth nationwide serosurvey to estimate prevalence of SARS-CoV-2 antibodies in the general population aged ≥6 years and healthcare workers (HCWs).Methods and findingsWe did a cross-sectional study between 14 June and 6 July 2021 in the same 70 districts across 20 states and 1 union territory where 3 previous rounds of serosurveys were conducted. From each district, 10 clusters (villages in rural areas and wards in urban areas) were selected by the probability proportional to population size method. From each district, a minimum of 400 individuals aged ≥6 years from the general population (40 individuals from each cluster) and 100 HCWs from the district public health facilities were included. The serum samples were tested for the presence of IgG antibodies against S1-RBD and nucleocapsid protein of SARS-CoV-2 using chemiluminescence immunoassay. We estimated the weighted and test-adjusted seroprevalence of IgG antibodies against SARS-CoV-2, along with 95% CIs, based on the presence of antibodies to S1-RBD and/or nucleocapsid protein. Of the 28,975 individuals who participated in the survey, 2,892 (10%) were aged 6–9 years, 5,798 (20%) were aged 10–17 years, and 20,285 (70%) were aged ≥18 years; 15,160 (52.3%) participants were female, and 21,794 (75.2%) resided in rural areas. The weighted and test-adjusted prevalence of IgG antibodies against S1-RBD and/or nucleocapsid protein among the general population aged ≥6 years was 67.6% (95% CI 66.4% to 68.7%). Seroprevalence increased with age (p < 0.001) and was not different in rural and urban areas (p = 0.822). Compared to unvaccinated adults (62.3%, 95% CI 60.9% to 63.7%), seroprevalence was significantly higher among individuals who had received 1 vaccine dose (81.0%, 95% CI 79.6% to 82.3%, p < 0.001) and 2 vaccine doses (89.8%, 95% CI 88.4% to 91.1%, p < 0.001). The seroprevalence of IgG antibodies among 7,252 HCWs was 85.2% (95% CI 83.5% to 86.7%). Important limitations of the study include the survey design, which was aimed to estimate seroprevalence at the national level and not at a sub-national level, and the non-participation of 19% of eligible individuals in the survey.ConclusionsNearly two-thirds of individuals aged ≥6 years from the general population and 85% of HCWs had antibodies against SARS-CoV-2 by June–July 2021 in India. As one-third of the population is still seronegative, it is necessary to accelerate the coverage of COVID-19 vaccination among adults and continue adherence to non-pharmaceutical interventions.

Manoj Murhekar and co-workers report on the seroprevalence of anti-SARS-CoV-2 antibodies in India.     

Transmission of community- and hospital-acquired SARS-CoV-2 in hospital settings in the UK: A cohort study

BackgroundNosocomial spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been widely reported, but the transmission pathways among patients and healthcare workers (HCWs) are unclear. Identifying the risk factors and drivers for these nosocomial transmissions is critical for infection prevention and control interventions. The main aim of our study was to quantify the relative importance of different transmission pathways of SARS-CoV-2 in the hospital setting.Methods and findingsThis is an observational cohort study using data from 4 teaching hospitals in Oxfordshire, United Kingdom, from January to October 2020. Associations between infectious SARS-CoV-2 individuals and infection risk were quantified using logistic, generalised additive and linear mixed models. Cases were classified as community- or hospital-acquired using likely incubation periods of 3 to 7 days. Of 66,184 patients who were hospitalised during the study period, 920 had a positive SARS-CoV-2 PCR test within the same period (1.4%). The mean age was 67.9 (±20.7) years, 49.2% were females, and 68.5% were from the white ethnic group. Out of these, 571 patients had their first positive PCR tests while hospitalised (62.1%), and 97 of these occurred at least 7 days after admission (10.5%). Among the 5,596 HCWs, 615 (11.0%) tested positive during the study period using PCR or serological tests. The mean age was 39.5 (±11.1) years, 78.9% were females, and 49.8% were nurses. For susceptible patients, 1 day in the same ward with another patient with hospital-acquired SARS-CoV-2 was associated with an additional 7.5 infections per 1,000 susceptible patients (95% credible interval (CrI) 5.5 to 9.5/1,000 susceptible patients/day) per day. Exposure to an infectious patient with community-acquired Coronavirus Disease 2019 (COVID-19) or to an infectious HCW was associated with substantially lower infection risks (2.0/1,000 susceptible patients/day, 95% CrI 1.6 to 2.2). As for HCW infections, exposure to an infectious patient with hospital-acquired SARS-CoV-2 or to an infectious HCW were both associated with an additional 0.8 infection per 1,000 susceptible HCWs per day (95% CrI 0.3 to 1.6 and 0.6 to 1.0, respectively). Exposure to an infectious patient with community-acquired SARS-CoV-2 was associated with less than half this risk (0.2/1,000 susceptible HCWs/day, 95% CrI 0.2 to 0.2). These assumptions were tested in sensitivity analysis, which showed broadly similar results. The main limitations were that the symptom onset dates and HCW absence days were not available.ConclusionsIn this study, we observed that exposure to patients with hospital-acquired SARS-CoV-2 is associated with a substantial infection risk to both HCWs and other hospitalised patients. Infection control measures to limit nosocomial transmission must be optimised to protect both staff and patients from SARS-CoV-2 infection.

In a cohort study, Mo Yin and colleagues investigate transmission of community- and hospital-acquired SARS-CoV-2 in hospital settings in the UK.     

SARS-CoV-2 seroprevalence in health care workers from 10 hospitals in Quebec,Canada: a cross-sectional study

Background:The COVID-19 pandemic has disproportionately affected health care workers. We sought to estimate SARS-CoV-2 seroprevalence among hospital health care workers in Quebec, Canada, after the first wave of the pandemic and to explore factors associated with SARS-CoV-2 seropositivity.Methods:Between July 6 and Sept. 24, 2020, we enrolled health care workers from 10 hospitals, including 8 from a region with a high incidence of COVID-19 (the Montréal area) and 2 from low-incidence regions of Quebec. Eligible health care workers were physicians, nurses, orderlies and cleaning staff working in 4 types of care units (emergency department, intensive care unit, COVID-19 inpatient unit and non-COVID-19 inpatient unit). Participants completed a questionnaire and underwent SARS-CoV-2 serology testing. We identified factors independently associated with higher seroprevalence.Results:Among 2056 enrolled health care workers, 241 (11.7%) had positive SARS-CoV-2 serology. Of these, 171 (71.0%) had been previously diagnosed with COVID-19. Seroprevalence varied among hospitals, from 2.4% to 3.7% in low-incidence regions to 17.9% to 32.0% in hospitals with outbreaks involving 5 or more health care workers. Higher seroprevalence was associated with working in a hospital where outbreaks occurred (adjusted prevalence ratio 4.16, 95% confidence interval [CI] 2.63–6.57), being a nurse or nursing assistant (adjusted prevalence ratio 1.34, 95% CI 1.03–1.74) or an orderly (adjusted prevalence ratio 1.49, 95% CI 1.12–1.97), and Black or Hispanic ethnicity (adjusted prevalence ratio 1.41, 95% CI 1.13–1.76). Lower seroprevalence was associated with working in the intensive care unit (adjusted prevalence ratio 0.47, 95% CI 0.30–0.71) or the emergency department (adjusted prevalence ratio 0.61, 95% CI 0.39–0.98).Interpretation:Health care workers in Quebec hospitals were at high risk of SARS-CoV-2 infection, particularly in outbreak settings. More work is needed to better understand SARS-CoV-2 transmission dynamics in health care settings.

The COVID-19 pandemic has disproportionately affected health care workers. In France, Spain, Italy, Germany and the United States, at least 10% of cases reported in spring 2020 were in health care workers.¹ In Quebec, 25% (14 177 of 56 565) of all cases declared during the first wave of the pandemic, from March to July 2020, were in health care workers,² about one-third of whom were working in acute care hospitals.¹ The Montréal area was the most affected region in Quebec and Canada during the first wave, reaching a COVID-19 incidence rate of 1336 per 100 000 population.²The number of COVID-19 cases reported among health care workers underestimated the number of those infected with SARS-CoV-2 during that period, given limited testing leading to undiagnosed asymptomatic or paucisymptomatic infections.³ Seroprevalence studies are an important tool to determine the proportion of people infected with SARS-CoV-2, both in the general population and among health care workers.⁴ After the first wave in Quebec, SARS-CoV-2 seroprevalence in adults aged 18–69 years was found to be low (3.1% in Montréal and 1.3% in less affected regions), but this proportion could be much higher among health care workers who had to work despite the general shutdown of social and economic activities, especially if they were exposed to major outbreaks.⁵Only 2 other Canadian studies provide SARS-CoV-2 seroprevalence estimates among health care workers, and both studies were from a single centre.^6,7 Outside Canada, most seroprevalence studies among health care workers include a single site and do not provide a representative estimate for a defined region.⁸ Several studies have reported a higher seroprevalence among health care workers from units treating patients with COVID-19 (COVID-19 units) compared with other units (non–COVID-19 units), emergency departments or intensive care units.^9,10 Other studies have not identified such associations.^11,12 In this study, we aimed to assess the seroprevalence of SARS-CoV-2 antibody among hospital health care workers from a variety of settings after the first pandemic wave in Quebec, and to explore factors associated with SARS-CoV-2 seropositivity.     

SARS-CoV-2: Targeted managements and vaccine development

Infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) results in diverse outcomes. The symptoms appear to be more severe in males older than 65 and people with underlying health conditions; approximately one in five individuals could be at risk worldwide. The virus’s sequence was rapidly established days after the first cases were reported and identified an RNA virus from the Coronaviridae family closely related to a Betacoronavirus virus found in bats in China. SARS-CoV-2 is the seventh coronavirus known to infect humans, and with the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS), the only ones to cause severe diseases. Lessons from these two previous outbreaks guided the identification of critical therapeutic targets such as the spike viral proteins promoting the virus’s cellular entry through the angiotensin-converting enzyme 2 (ACE2) receptor expressed on the surface of multiple types of eukaryotic cells. Although several therapeutic agents are currently evaluated, none seems to provide a clear path for a cure. Also, various types of vaccines are developed in record time to address the urgency of efficient SARS-CoV-2 prevention. Currently, 58 vaccines are evaluated in clinical trials, including 11 in phase III, and 3 of them reported efficacy above 90 %. The results so far from the clinical trials suggest the availability of multiple effective vaccines within months.     

Geographic concentration of SARS-CoV-2 cases by social determinants of health in metropolitan areas in Canada: a cross-sectional study

Background:Understanding inequalities in SARS-CoV-2 transmission associated with the social determinants of health could help the development of effective mitigation strategies that are responsive to local transmission dynamics. This study aims to quantify social determinants of geographic concentration of SARS-CoV-2 cases across 16 census metropolitan areas (hereafter, cities) in 4 Canadian provinces, British Columbia, Manitoba, Ontario and Quebec.Methods:We used surveillance data on confirmed SARS-CoV-2 cases and census data for social determinants at the level of the dissemination area (DA). We calculated Gini coefficients to determine the overall geographic heterogeneity of confirmed cases of SARS-CoV-2 in each city, and calculated Gini covariance coefficients to determine each city’s heterogeneity by each social determinant (income, education, housing density and proportions of visible minorities, recent immigrants and essential workers). We visualized heterogeneity using Lorenz (concentration) curves.Results:We observed geographic concentration of SARS-CoV-2 cases in cities, as half of the cumulative cases were concentrated in DAs containing 21%–35% of their population, with the greatest geographic heterogeneity in Ontario cities (Gini coefficients 0.32–0.47), followed by British Columbia (0.23–0.36), Manitoba (0.32) and Quebec (0.28–0.37). Cases were disproportionately concentrated in areas with lower income and educational attainment, and in areas with a higher proportion of visible minorities, recent immigrants, high-density housing and essential workers. Although a consistent feature across cities was concentration by the proportion of visible minorities, the magnitude of concentration by social determinant varied across cities.Interpretation:Geographic concentration of SARS-CoV-2 cases was observed in all of the included cities, but the pattern by social determinants varied. Geographically prioritized allocation of resources and services should be tailored to the local drivers of inequalities in transmission in response to the resurgence of SARS-CoV-2.

The COVID-19 epidemic in Canada has varied in size and trajectory across provinces and large cities.^1,2 At the national level³ and within regions,^4,5 the burden of confirmed SARS-CoV-2 cases and severe COVID-19 outcomes has fallen disproportionately on socially and economically marginalized communities. ⁶ Social determinants of health refer to nonmedical factors influencing health outcomes, and structural determinants encompass cultural norms, policies and institutions that generate social stratification and determine socioeconomic position.^7,8 In Canada and elsewhere, data have consistently highlighted the importance of determinants such as household size and density, work in essential services and structural racism (measured by proxy) in the relative risk of COVID-19.^9–17Understanding the factors associated with geographic patterns of transmission within cities can help identify the populations and, specifically, the contexts with the greatest risks. Geographic analyses can enable better allocation of resources, tailoring of policies and implementation of context-specific strategies to more effectively and efficiently curb local transmission. ¹⁸ Although respiratory virus transmission is often geographically clustered within a city,¹⁹ the early public health response to SARS-CoV-2 transmission in Canada did little to take within-city clustering into account.^20,21 Similarly, few studies have quantified and compared the geographic concentration of SARS-CoV-2 cases by social determinants across Canada, and the extent to which the magnitude of inequalities might vary among cities and provinces.^19,22 We therefore sought to quantify and compare the magnitude of geographic concentration of SARS-CoV-2 cases by area-level social determinants of health across metropolitan areas in British Columbia, Manitoba, Ontario and Quebec, Canada.     

Attitudinal and demographic predictors of measles-mumps-rubella vaccine (MMR) uptake during the UK catch-up campaign 2008-09: cross-sectional survey

Background and Objective

Continued suboptimal measles-mumps-rubella (MMR) vaccine uptake has re-established measles epidemic risk, prompting a UK catch-up campaign in 2008–09 for children who missed MMR doses at scheduled age. Predictors of vaccine uptake during catch-ups are poorly understood, however evidence from routine schedule uptake suggests demographics and attitudes may be central. This work explored this hypothesis using a robust evidence-based measure.

Design

Cross-sectional self-administered questionnaire with objective behavioural outcome.

Setting and Participants

365 UK parents, whose children were aged 5–18 years and had received <2 MMR doses before the 2008–09 UK catch-up started.

Main Outcome Measures

Parents'' attitudes and demographics, parent-reported receipt of invitation to receive catch-up MMR dose(s), and catch-up MMR uptake according to child''s medical record (receipt of MMR doses during year 1 of the catch-up).

Results

Perceived social desirability/benefit of MMR uptake (OR = 1.76, 95% CI = 1.09–2.87) and younger child age (OR = 0.78, 95% CI = 0.68–0.89) were the only independent predictors of catch-up MMR uptake in the sample overall. Uptake predictors differed by whether the child had received 0 MMR doses or 1 MMR dose before the catch-up. Receipt of catch-up invitation predicted uptake only in the 0 dose group (OR = 3.45, 95% CI = 1.18–10.05), whilst perceived social desirability/benefit of MMR uptake predicted uptake only in the 1 dose group (OR = 9.61, 95% CI = 2.57–35.97). Attitudes and demographics explained only 28% of MMR uptake in the 0 dose group compared with 61% in the 1 dose group.

Conclusions

Catch-up MMR invitations may effectively move children from 0 to 1 MMR doses (unimmunised to partially immunised), whilst attitudinal interventions highlighting social benefits of MMR may effectively move children from 1 to 2 MMR doses (partially to fully immunised). Older children may be best targeted through school-based programmes. A formal evaluation element should be incorporated into future catch-up campaigns to inform their continuing improvement.     

Plant-derived VLP: a worthy platform to produce vaccine against SARS-CoV-2

Biotechnology Letters - After its emergence in late 2019 SARS-CoV-2 was declared a pandemic by the World Health Organization on 11 March 2020 and has claimed more than 2.8 million lives. There has...     

A cross-sectional study of HPV vaccine acceptability in Gaborone, Botswana

Background

Cervical cancer is the most common cancer among women in Botswana and elsewhere in Sub-Saharan Africa. We sought to examine whether HPV vaccine is acceptable among parents in Botswana, which recently licensed the vaccine to prevent cervical cancer.

Methods and Findings

We conducted a cross-sectional survey in 2009, around the time the vaccine was first licensed, with adults recruited in general medicine and HIV clinics in Gaborone, the capital of Botswana. Although only 9% (32/376) of respondents had heard of HPV vaccine prior to the survey, 88% (329/376) said they definitely will have their adolescent daughters receive HPV vaccine. Most respondents would get the vaccine for their daughters at a public or community clinic (42%) or a gynecology or obstetrician''s office (39%), and 74% would get it for a daughter if it were available at her school. Respondents were more likely to say that they definitely will get HPV vaccine for their daughters if they had less education (OR = 0.20, 95% CI = 0.07–0.58) or lived more than 30 kilometers from the capital, Gaborone (OR = 2.29, 95% CI = 1.06–4.93). Other correlates of acceptability were expecting to be involved in the decision to get HPV vaccine, thinking the vaccine would be hard to obtain, and perceiving greater severity of HPV-related diseases.

Conclusions

HPV vaccination of adolescent girls would be highly acceptable if the vaccine became widely available to the daughters of healthcare seeking parents in Gaborone, Botswana. Potential HPV vaccination campaigns should provide more information about HPV and the vaccine as well as work to minimize barriers.     

Manufacturing a chimpanzee adenovirus-vectored SARS-CoV-2 vaccine to meet global needs

Manufacturing has been the key factor limiting rollout of vaccination during the COVID-19 pandemic, requiring rapid development and large-scale implementation of novel manufacturing technologies. ChAdOx1 nCoV-19 (AZD1222, Vaxzevria) is an efficacious vaccine against SARS-CoV-2, based upon an adenovirus vector. We describe the development of a process for the production of this vaccine and others based upon the same platform, including novel features to facilitate very large-scale production. We discuss the process economics and the “distributed manufacturing” approach we have taken to provide the vaccine at globally-relevant scale and with international security of supply. Together, these approaches have enabled the largest viral vector manufacturing campaign to date, providing a substantial proportion of global COVID-19 vaccine supply at low cost.     

Prevalence and determinants of healthcare avoidance during the COVID-19 pandemic: A population-based cross-sectional study

BackgroundDuring the Coronavirus Disease 2019 (COVID-19) pandemic, the number of consultations and diagnoses in primary care and referrals to specialist care declined substantially compared to prepandemic levels. Beyond deferral of elective non-COVID-19 care by healthcare providers, it is unclear to what extent healthcare avoidance by community-dwelling individuals contributed to this decline in routine healthcare utilisation. Moreover, it is uncertain which specific symptoms were left unheeded by patients and which determinants predispose to healthcare avoidance in the general population. In this cross-sectional study, we assessed prevalence of healthcare avoidance during the pandemic from a patient perspective, including symptoms that were left unheeded, as well as determinants of healthcare avoidance.Methods and findingsOn April 20, 2020, a paper COVID-19 survey addressing healthcare utilisation, socioeconomic factors, mental and physical health, medication use, and COVID-19–specific symptoms was sent out to 8,732 participants from the population-based Rotterdam Study (response rate 73%). All questionnaires were returned before July 10, 2020. By hand, prevalence of healthcare avoidance was subsequently verified through free text analysis of medical records of general practitioners. Odds ratios (ORs) for avoidance were determined using logistic regression models, adjusted for age, sex, and history of chronic diseases. We found that 1,142 of 5,656 included participants (20.2%) reported having avoided healthcare. Of those, 414 participants (36.3%) reported symptoms that potentially warranted urgent evaluation, including limb weakness (13.6%), palpitations (10.8%), and chest pain (10.2%). Determinants related to avoidance were older age (adjusted OR 1.14 [95% confidence interval (CI) 1.08 to 1.21]), female sex (1.58 [1.38 to 1.82]), low educational level (primary education versus higher vocational/university 1.21 [1.01 to 1.46), poor self-appreciated health (per level decrease 2.00 [1.80 to 2.22]), unemployment (versus employed 2.29 [1.54 to 3.39]), smoking (1.34 [1.08 to 1.65]), concern about contracting COVID-19 (per level increase 1.28 [1.19 to 1.38]) and symptoms of depression (per point increase 1.13 [1.11 to 1.14]) and anxiety (per point increase 1.16 [1.14 to 1.18]). Study limitations included uncertainty about (perceived) severity of the reported symptoms and potentially limited generalisability given the ethnically homogeneous study population.ConclusionsIn this population-based cross-sectional study, 1 in 5 individuals avoided healthcare during lockdown in the COVID-19 pandemic, often for potentially urgent symptoms. Healthcare avoidance was strongly associated with female sex, fragile self-appreciated health, and high levels of depression and anxiety. These results emphasise the need for targeted public education urging these vulnerable patients to timely seek medical care for their symptoms to mitigate major health consequences.

Marije J. Splinter and colleagues assess the prevalence of healthcare avoidance during the COIVD-19 pandemic and investigate related determinants     

Vaccine effectiveness against SARS-CoV-2 infection,hospitalization, and death when combining a first dose ChAdOx1 vaccine with a subsequent mRNA vaccine in Denmark: A nationwide population-based cohort study

BackgroundThe recommendations in several countries to stop using the ChAdOx1 vaccine has led to vaccine programs combining different Coronavirus Disease 2019 (COVID-19) vaccine types, which necessitates knowledge on vaccine effectiveness (VE) of heterologous vaccine schedules. The aim of this Danish nationwide population-based cohort study was therefore to estimate the VE against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and COVID-19–related hospitalization and death following the first dose of the ChAdOx1 vaccine and the combination of the ChAdOx1/mRNA vaccines.Methods and findingsAll individuals alive in or immigrating to Denmark from 9 February 2021 to 23 June 2021 were identified in the Danish Civil Registration System. Information on exposure, outcomes, and covariates was obtained from Danish national registries. Poisson and Cox regression models were used to calculate crude and adjusted VE, respectively, along with 95% confidence intervals (CIs) against SARS-CoV-2 infection and COVID-19–related hospitalization or death comparing vaccinated versus unvaccinated individuals. The VE estimates were adjusted for calendar time as underlying time and for sex, age, comorbidity, country of origin, and hospital admission. The analyses included 5,542,079 individuals (97.6% of the total Danish population). A total of 144,360 individuals were vaccinated with the ChAdOx1 vaccine as the first dose, and of these, 136,551 individuals received an mRNA vaccine as the second dose. A total of 1,691,464 person-years and 83,034 SARS-CoV-2 infections were included. The individuals vaccinated with the first dose of the ChAdOx1 vaccine dose had a median age of 45 years. The study population was characterized by an equal distribution of males and females; 6.7% and 9.2% originated from high-income and other countries, respectively. The VE against SARS-CoV-2 infection when combining the ChAdOx1 and an mRNA vaccine was 88% (95% CI: 83; 92) 14 days after the second dose and onwards. There were no COVID-19–related hospitalizations or deaths among the individuals vaccinated with the combined vaccine schedule during the study period. Study limitations including unmeasured confounders such as risk behavior and increasing overall vaccine coverage in the general population creating herd immunity are important to take into consideration when interpreting the results.ConclusionsIn this study, we observed a large reduction in the risk of SARS-CoV-2 infection when combining the ChAdOx1 and an mRNA vaccine, compared with unvaccinated individuals.

Mie Agermose Gram and co-workers study the effectiveness of heterologous SARS-CoV-2 vaccine combinations in the Danish population.     

Modelling optimal vaccination strategy for SARS-CoV-2 in the UK

The COVID-19 outbreak has highlighted our vulnerability to novel infections.Faced with this threat and no effective treatment, in line with many other countries, the UK adopted enforced social distancing (lockdown) to reduce transmission—successfully reducing the reproductive number R below one. However, given the large pool of susceptible individuals that remain, complete relaxation of controls is likely to generate a substantial further outbreak. Vaccination remains the only foreseeable means of both containing the infection and returning to normal interactions and behaviour. Here, we consider the optimal targeting of vaccination within the UK, with the aim of minimising future deaths or quality adjusted life year (QALY) losses. We show that, for a range of assumptions on the action and efficacy of the vaccine, targeting older age groups first is optimal and may be sufficient to stem the epidemic if the vaccine prevents transmission as well as disease.     

A variant-proof SARS-CoV-2 vaccine targeting HR1 domain in S2 subunit of spike protein

The emerging SARS-CoV-2 variants, commonly with many mutations in S1 subunit of spike (S) protein are weakening the efficacy of the current vaccines and antibody therapeutics. This calls for the variant-proof SARS-CoV-2 vaccines targeting the more conserved regions in S protein. Here, we designed a recombinant subunit vaccine, HR121, targeting the conserved HR1 domain in S2 subunit of S protein. HR121 consisting of HR1–linker1–HR2–linker2–HR1, is conformationally and functionally analogous to the HR1 domain present in the fusion intermediate conformation of S2 subunit. Immunization with HR121 in rabbits and rhesus macaques elicited highly potent cross-neutralizing antibodies against SARS-CoV-2 and its variants, particularly Omicron sublineages. Vaccination with HR121 achieved near-full protections against prototype SARS-CoV-2 infection in hACE2 transgenic mice, Syrian golden hamsters and rhesus macaques, and effective protection against Omicron BA.2 infection in Syrian golden hamsters. This study demonstrates that HR121 is a promising candidate of variant-proof SARS-CoV-2 vaccine with a novel conserved target in the S2 subunit for application against current and future SARS-CoV-2 variants.Subject terms: Mechanisms of disease, Molecular modelling