COVID-19 Vaccination in Pregnancy: The Impact of Multimorbidity and Smoking Status on Vaccine Hesitancy, a Cohort Study of 25,111 Women in Wales, UK

BackgroundMultimorbidity and pregnancy are two risk factors for more severe outcomes after a SARS-CoV-2 infection, thus vaccination uptake is important for pregnant women living with multimorbidity. This study aimed to examine the impact of multimorbidity, smoking status, and demographics (age, ethnic group, area of deprivation) on vaccine hesitancy among pregnant women in Wales using electronic health records (EHR) linkage. MethodsThis cohort study utilised routinely collected, individual-level, anonymised population-scale linked data within the Secure Anonymised Information Linkage (SAIL) Databank. Pregnant women were identified from 13th April 2021 to 31st December 2021. Survival analysis was utilised to examine and compare the length of time to vaccination uptake in pregnancy by multimorbidity and smoking status, as well as depression, diabetes, asthma, and cardiovascular conditions independently. Variation in uptake by; multimorbidity, smoking status, and demographics was examined jointly and separately for the independent conditions using hazard ratios (HR) from the Cox regression model. A bootstrapping internal validation was conducted to assess the performance of the models. ResultsWithin the population cohort, 8,203 (32.7%) received at least one dose of the COVID-19 vaccine during pregnancy, with 8,572 (34.1%) remaining unvaccinated throughout the follow-up period, and 8,336 (33.2%) receiving the vaccine postpartum. Women aged 30 years or older were more likely to have the vaccine in pregnancy. Those who had depression were slightly but significantly more likely to have the vaccine compared to those without depression (HR = 1.08, 95% CI 1.03 to 1.14, p = 0.02). Women living with multimorbidity (> 1 health condition) were 1.12 times more likely to have the vaccine compared to those living without multimorbidity (HR = 1.12, 95% CI 1.04 to 1.19, p = 0.001). Vaccine uptakes were significantly lower among both current smokers and former smokers compared to never smokers (HR = 0.87, 95% CI 0.81 to 0.94, p < 0.001 and HR = 0.92, 95% CI 0.85 to 0.98, p = 0.015 respectively). Uptake was also lower among those living in the most deprived areas compared to those living in the most affluent areas (HR = 0.89, 95% CI 0.83 to 0.96, p = 0.002). The validated model had similar performance and revealed that multimorbidity, smoking status, age, and deprivation level together have a significant impact on vaccine hesitancy (p < 0.05 for all). ConclusionYounger women, living without multimorbidity (zero or only one health condition), current and former smokers, and those living in the more deprived areas are less likely to have the vaccine, thus, a targeted approach to vaccinations may be required for these groups. Women living with multimorbidity are slightly but significantly less likely to be hesitant about COVID-19 vaccination when pregnant.

COVID-19 vaccination in pregnancy: views and vaccination uptake rates in pregnancy, a mixed methods analysis from the Born In Wales study

BackgroundVaccine hesitancy amongst pregnant women has been found to be a concern during past epidemics. ObjectivesThe aims of this study were to 1) estimate COVID-19 vaccination rates among pregnant women in Wales and their association with age, ethnicity, and area of deprivation, using electronic health records (EHR) linkage, and 2) explore pregnant womens views on receiving the COVID-19 vaccine during pregnancy using data from a survey recruiting via social media (Facebook, Twitter), through midwives, and posters in hospitals (Born in Wales Cohort). DesignA mixed methods study utilising routinely collected linked data from the Secure Anonymised Information Linkage (SAIL) (Objective 1) and the Born In Wales Birth Cohort participants (Objective 2). SAIL combines data from general practice, hospital admissions, the national community child health dataset, maternal indicators dataset, and COVID-19 vaccination databases. Setting and participantsObjective 1) All women documented as being pregnant on or after 13th April 2021, aged 18 years or older, and eligible for COVID-19 vaccination were identified in routine health care. They were linked to the vaccination data up to and including 31st December 2021. Objective 2) Separately, a cross-section of pregnant women in Wales were invited to complete an online survey via social media advertising. The survey asked what their views were on having the COVID-19 vaccination during pregnancy, and if they had already received, or intended to receive, the COVID-19 vaccination during their pregnancies. They were also asked to give reasons for their decisions. Outcomes1 (a). Rate of vaccination uptake per month during pregnancy among women eligible for vaccination. 1 (b). Survival analysis was utilised to examine and compare the length of time to vaccination uptake in pregnancy, and variation in uptake by; age, ethnicity, and deprivation area was examined using hazard ratios (HR) from Cox regression. 2.Expectant mothers views of the COVID-19 vaccination during pregnancy. Results Population-level data linkage (objective 1)Within the population cohort, 32.7% (n = 8,203) were vaccinated (at least one dose of the vaccine) during pregnancy, 34.1% (n = 8,572) remained unvaccinated throughout follow-up period, and 33.2% (n = 8,336) received the vaccine postpartum. Younger women (<30 years) were less likely to have the vaccine and those living in areas of high deprivation were also less likely to have the vaccine (HR=0.88, 95% CI 0.82 to 0.95). Asian and other ethnic groups were 1.12 and 1.18 times more likely to have the vaccine in pregnancy compared to women of White ethnicity (HR=1.12, 95% CI 1.00 to 1.25) and (HR=1.18, 95% CI 1.03 to 1.37) respectively. Survey responses (objective 2)69% of participants stated that they would be happy to have the vaccine during pregnancy (n = 207). The remainder, 31%, indicated that they would not have the vaccine during pregnancy (n = 94). Reasons for having the vaccine related to protecting self and baby, perceived risk level, and receipt of sufficient evidence and advice. Reasons for vaccine refusal included lack of research about long-term outcomes for the baby, anxiety about vaccines, inconsistent advice/information, and preference to wait until after the pregnancy. ConclusionPotentially only 1 in 3 pregnant women would have the COVID-19 vaccine during pregnancy, even though 2 in 3 reported they would have the vaccination, thus it is critical to develop tailored strategies to increase its acceptance rate and to decrease vaccine hesitancy. A targeted approach to vaccinations may be required for groups such as younger people and those living in higher deprivation level areas.

Health care use attributable to COVID-19: A propensity matched national electronic health records cohort study of 249,390 people in Wales, UK.

BackgroundTo determine the extent and nature of changes in infected patients healthcare utilization, we studied healthcare contact in the 1-4 weeks and 5-24 weeks following a COVID-19 diagnosis compared to propensity matched controls. MethodsSurvival analysis was used for time to death and first clinical outcomes including clinical terminology concepts for post-viral illness, fatigue, embolism, respiratory conditions, mental and developmental conditions, fit note, or hospital attendance. Increased instantaneous risk for the occurrence of an outcome for positive individuals was quantified using hazard ratios (HR) from Cox Regression and absolute risk was quantified using relative risk (RR) from life table analysis. ResultsCompared to matched individuals testing negative, surviving positive community-tested patients had a higher risk of post-viral illness (HR: 4.57, 95%CI: 1.77-11.80, p=0.002), fatigue (HR: 1.47, 95%CI: 1.24-1.75, p<0.001) and embolism (HR: 1.51, 95%CI: 1.13-2.02, p=0.005) at 5-24 weeks post-diagnosis. In the four weeks after COVID-19 higher rates of sick notes were being issued for community-tested (HR: 3.04, 95%CI: 0.88 to 10.50, p<0.079); the risk was reduced after four weeks, compared to controls. Overall healthcare attendance for anxiety, depression was less likely in those with COVID-19 in the first four weeks (HR: 0.83, 95%CI: 0.73-1.06, p=0.007). After four weeks, anxiety, depression is less likely to occur for the positive community-tested individuals (HR: 0.87, 95%CI: 0.77-1.00, p=0.048), but more likely for positive hospital-tested individuals (HR: 1.16, 95%CI: 1.00-1.45, p=0.053). Although statistical associations between positive infection and post-infection healthcare use are clear, the absolute use of healthcare is very. ConclusionsCommunity COVID-19 disease is associated with increased risks of post-viral illness, fatigue, embolism, depression, anxiety and respiratory conditions. Despite these elevated risks, the absolute healthcare burden is low. Either very small proportions of people experience adverse outcomes following COVID-19 or they are not presenting to healthcare. Trial registrationData held in SAIL databank are anonymised and therefore, no ethical approval is required. All data in SAIL has the permission from the relevant Caldicott Guardian or Data Protection Officer and SAIL-related projects are required to obtain Information Governance Review Panel (IGRP) approval. The IGRP approval number for this study is 1259.

Noninvasive Imaging for the Asymptomatic Patient: How to Use Imaging to Guide Treatment Goals?

Imaging subclinical atherosclerosis identifies individuals at higher risk of cardiovascular disease through direct visualization before events occur so that preventative measures can be taken. Coronary artery calcium (CAC) scans are the most widely used and studied to identify subclinical atherosclerosis and are most useful in men older than 40 years and women older than 50 years. Coronary computed tomography angiography has high prognostic value and might be the best modality for assessing subclinical atherosclerosis with incremental increase in predictive value over CAC. Ankle-brachial indexes are specific markers for cardiovascular risk but are a less sensitive tool for risk assessment.

A Rare Deletion in SARS-CoV-2 ORF6 Dramatically Alters the Predicted Three-Dimensional Structure of the Resultant Protein

The function of the SARS-CoV-2 accessory protein p6, encoded by ORF6, is not fully known. Based upon its similarity to p6 from SARS-CoV, it may play a similar role, namely as an antagonist of type I interferon (IFN) signaling. Here we report the sequencing of a SARS-CoV-2 strain passaged six times after original isolation from a clinical patient in Hong Kong. The genome sequence shows a 27 nt in-frame deletion ({Delta}27,264-27,290) within ORF6, predicted to result in a 9 aa deletion ({Delta}FKVSIWNLD) from the central portion of p6. This deletion is predicted to result in a dramatic alteration in the three-dimensional structure of the resultant protein (p6{Delta}22-30), possibly with significant functional implications. Analysis of the original clinical sample indicates that the deletion was not present, while sequencing of subsequent passages of the strain identifies the deletion as a majority variant. This suggests that the deletion originated ab initio during passaging and subsequently propagated into the majority, possibly due to the removal of selective pressure through the IFN-deficient Vero E6 cell line. The specific function of the SARS-CoV-2 p6 N-terminus, if any, has not yet been determined. However, this deletion is predicted to cause a shift from N-endo to N-ecto in the transmembrane localization of the SARS-CoV-2 p6{Delta}22-30 N-terminus, possibly leading to the ablation of its native function.

Quantifying dynamics of SARS-CoV-2 transmission suggests that epidemic control and avoidance is feasible through instantaneous digital contact tracing

The newly emergent human virus SARS-CoV-2 is resulting in high fatality rates and incapacitated health systems. Preventing further transmission is a priority. We analysed key parameters of epidemic spread to estimate the contribution of different transmission routes and determine requirements for case isolation and contact-tracing needed to stop the epidemic. We conclude that viral spread is too fast to be contained by manual contact tracing, but could be controlled if this process was faster, more efficient and happened at scale. A contact-tracing App which builds a memory of proximity contacts and immediately notifies contacts of positive cases can achieve epidemic control if used by enough people. By targeting recommendations to only those at risk, epidemics could be contained without need for mass quarantines ( lock-downs) that are harmful to society. We discuss the ethical requirements for an intervention of this kind.

Phosphorylation releases constraints to domain motion in ERK2.

Protein motions control enzyme catalysis through mechanisms that are incompletely understood. Here NMR (13)C relaxation dispersion experiments were used to monitor changes in side-chain motions that occur in response to activation by phosphorylation of the MAP kinase ERK2. NMR data for the methyl side chains on Ile, Leu, and Val residues showed changes in conformational exchange dynamics in the microsecond-to-millisecond time regime between the different activity states of ERK2. In inactive, unphosphorylated ERK2, localized conformational exchange was observed among methyl side chains, with little evidence for coupling between residues. Upon dual phosphorylation by MAP kinase kinase 1, the dynamics of assigned methyls in ERK2 were altered throughout the conserved kinase core, including many residues in the catalytic pocket. The majority of residues in active ERK2 fit to a single conformational exchange process, with kex ≈ 300 s(-1) (kAB ≈ 240 s(-1)/kBA ≈ 60 s(-1)) and pA/pB ≈ 20%/80%, suggesting global domain motions involving interconversion between two states. A mutant of ERK2, engineered to enhance conformational mobility at the hinge region linking the N- and C-terminal domains, also induced two-state conformational exchange throughout the kinase core, with exchange properties of kex ≈ 500 s(-1) (kAB ≈ 15 s(-1)/kBA ≈ 485 s(-1)) and pA/pB ≈ 97%/3%. Thus, phosphorylation and activation of ERK2 lead to a dramatic shift in conformational exchange dynamics, likely through release of constraints at the hinge.

Ethics in practice: the state of the debate on promoting the social value of global health research in resource poor settings particularly Africa.

BACKGROUND: Promoting the social value of global health research undertaken in resource poor settings has become a key concern in global research ethics. The consideration for benefit sharing, which concerns the elucidation of what if anything, is owed to participants, their communities and host nations that take part in such research, and the obligations of researchers involved, is one of the main strategies used for promoting social value of research. In the last decade however, there has been intense debate within academic bioethics literature seeking to define the benefits, the beneficiaries, and the scope of obligations for providing these benefits. Although this debate may be indicative of willingness at the international level to engage with the responsibilities of researchers involved in global health research, it remains unclear which forms of benefits or beneficiaries should be considered. International and local research ethics guidelines are reviewed here to delineate the guidance they provide. METHODS: We reviewed documents selected from the international compilation of research ethics guidelines by the Office for Human Research Protections under the US Department of Health and Human Services. RESULTS: Access to interventions being researched, the provision of unavailable health care, capacity building for individuals and institutions, support to health care systems and access to medical and public health interventions proven effective, are the commonly recommended forms of benefits. The beneficiaries are volunteers, disease or illness affected communities and the population in general. Interestingly however, there is a divide between "global opinion" and the views of particular countries within resource poor settings as made explicit by differences in emphasis regarding the potential benefits and the beneficiaries. CONCLUSION: Although in theory benefit sharing is widely accepted as one of the means for promoting the social value of international collaborative health research, there is less agreement amongst major guidelines on the specific responsibilities of researchers over what is ethical in promoting the social value of research. Lack of consensus might have practical implications for efforts aimed at enhancing the social value of global health research undertaken in resource poor settings. Further developments in global research ethics require more reflection, paying attention to the practical realities of implementing the ethical principles in real world context.