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 (preprint)

Abstract Background Multimorbidity 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. Methods This 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. Results Within 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). Conclusion Younger 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: The Impact of Multimorbidity and Smoking Status on Vaccine Hesitancy, a Cohort Study of 25,111 Women in Wales, UK (preprint)

Background Multimorbidity 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. Methods This 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. Results Within 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 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). Conclusion Younger women, living without multimorbidity, 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 (preprint)

Background Vaccine hesitancy amongst pregnant women has been found to be a concern during past epidemics. This study aimed 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 women’s 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).Methods This was a 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). 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. Codebook thematic analysis was used to generate themes from an open-ended question on the survey.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 included 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.Conclusion Potentially 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. (preprint)

Background: To 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. Methods: : Survival 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. Results: : Compared 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. Conclusions: : Community 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 registration: Data 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.

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

Background: Vaccine hesitancy amongst pregnant women has been found to be a concern during past epidemics. Objectives: The 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). Design: A 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 participants: Objective 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. Outcomes: 1 (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. Conclusion: Potentially 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. (preprint)

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.

Pre-COVID-19 pandemic health-related behaviours in children (2018-2020) and association with being tested for SARS-CoV-2 and testing positive for SARS-CoV-2 (2020-2021): a retrospective cohort study using survey data linked with routine health data in Wales, UK (preprint)

ABSTRACT Objectives Examine if pre-COVID-19 pandemic (prior March 2020) health-related behaviours during primary school are associated with i) being tested for SARS-CoV-2 and ii) testing positive between 1 March 2020 to 31 August 2021. Design Retrospective cohort study using an online cohort survey (January 2018 to February 2020) linked to routine PCR SARS-CoV-2 test results. Setting Children attending primary schools in Wales (2018-2020), UK who were part of the HAPPEN school network. Participants Complete linked records of eligible participants were obtained for n=7,062 individuals. 39.1% (n=2,764) were tested (age 10.6±0.9, 48.9% girls) and 8.1% (n=569) tested positive for SARS-CoV-2 (age 10.6±1.0, 54.5% girls). Main outcome measures Logistic regression of health-related behaviours and demographics were used to determine Odds Ratios (OR) of factors associated with i) being tested for SARS-CoV-2 and ii) testing positive for SARS-CoV-2. Results Consuming sugary snacks (1-2 days/week OR=1.24, 95% CI 1.04 – 1.49; 5-6 days/week 1.31, 1.07 – 1.61; reference 0 days) can swim 25m (1.21, 1.06 – 1.39) and age (1.25, 1.16 – 1.35) were associated with an increased likelihood of being tested for SARS-CoV-2. Eating breakfast (1.52, 1.01 – 2.27), weekly physical activity ≥ 60 mins (1-2 days 1.69, 1.04 – 2.74; 3-4 days 1.76, 1.10 – 2.82, reference 0 days), out of school club participation (1.06, 1.02 – 1.10), can ride a bike (1.39, 1.00 – 1.93), age (1.16, 1.05 – 1.28) and girls (1.21, 1.00 – 1.46) were associated with an increased likelihood of testing positive for SARS-CoV-2. Living in least deprived quintiles 4 (0.64, 0.46 – 0.90) and 5 (0.64, 0.46 – 0.89) compared to the most deprived quintile was associated with a decreased likelihood. Conclusions Associations may be related to parental health literacy and monitoring behaviours. Physically active behaviours may include co-participation with others, and exposure to SARS-CoV-2. A risk versus benefit approach must be considered given the importance of health-related behaviours for development. STRENGTHS AND LIMITATIONS Investigation of the association of pre-pandemic child health-related behaviour measures with subsequent SARS-CoV-2 testing and infection. Reporting of multiple child health behaviours linked at an individual-level to routine records of SARS-CoV-2 testing data through the SAIL Databank. Child-reported health behaviours were measured before the COVID-19 pandemic (1 January 2018 to 28 February 2020) which may not reflect behaviours during COVID-19. Health behaviours captured through the national-scale HAPPEN survey represent children attending schools that engaged with the HAPPEN Wales primary school network and may not be representative of the whole population of Wales. The period of study for PCR-testing for and testing positive for SARS-CoV-2 includes a time frame with varying prevalence rates, approaches to testing children (targeted and mass testing) and restrictions which were not measured in this study.

COVID-19 mitigation measures in primary schools and association with infection and school staff wellbeing: an observational survey linked with routine data in Wales, UK (preprint)

IntroductionSchool-based COVID-19 mitigation strategies have greatly impacted the primary school day (children aged 3-11) including: wearing face coverings, 2-metre distancing, no mixing of children, and no breakfast clubs or extra-curricular activities. This study examines these mitigation methods and association with COVID-19 infection, respiratory infection, and school staff wellbeing between October to December 2020 in Wales, UK. MethodsA school staff survey captured self-reported COVID-19 mitigation measures in the school, participant anxiety and depression, and open-text responses regarding experiences of teaching and implementing measures. These survey responses were linked to national-scale COVID-19 test results data to examine association of measures in the school and the likelihood of a positive (staff or pupil) COVID-19 case in the school (clustered by school, adjusted for school size and free school meals using logistic regression). Linkage was conducted through the SAIL (Secure Anonymised Information Linkage) Databank. ResultsResponses were obtained from 353 participants from 59 primary schools within 15 of 22 local authorities. Having more direct non-household contacts was associated with a higher likelihood of COVID-19 positive case in the school (1-5 contacts compared to none, OR 2.89 (1.01, 8.31)) and a trend to more self-reported cold symptoms. Staff face covering was not associated with a lower odds of school COVID-19 cases (mask vs. no covering OR 2.82 (1.11, 7.14)) and was associated with higher self-reported cold symptoms. School staff reported the impacts of wearing face coverings on teaching, including having to stand closer to pupils and raise their voices to be heard. 67.1% were not able to implement 2-metre social distancing from pupils. We did not find evidence that maintaining a 2-metre distance was associated with lower rates of COVID-19 in the school. ConclusionsImplementing, adhering to and evaluating COVID-19 mitigation guidelines is challenging in primary school settings. Our findings suggest that reducing non-household direct contacts lowers infection rates. There was no evidence that face coverings, 2-metre social distancing or stopping children mixing was associated with lower odds of COVID-19 or cold infection rates in the school. Primary school staff found teaching challenging during COVID-19 restrictions, especially for younger learners and those with additional learning needs.

Telehealth Consultations in General Practice During a Pandemic Lockdown: Survey and Interviews on Patient Experiences and Preferences (preprint)

Background: During the first COVID-19 pandemic ‘lockdown’ in Aotearoa/New Zealand (March-May 2020, in which strict ‘stay at home’ measures were introduced), general practices were advised to use telephone and video consultations (telehealth) wherever possible instead of the usual in-person visits. This was a sudden change for most practices and patients. This research aimed to explore how patients accessed general practice during lockdown and evaluate their experiences with telehealth, to inform how telehealth could be most effectively used in the future. Methods: Using a mixed-method approach, we undertook an online survey and in-depth interviews with adults (>18 years) who had contact with practices during lockdown, recruited through social media and email lists. We present descriptive statistics from the survey data (n=1,010) and qualitative analysis of interview data (n=38) and open-ended survey questions, using a framework of access to health care, from the patient’s perspective. Results: In general, patients reported high satisfaction with telehealth in general practice during lockdown. Telehealth was convenient and allowed patients to safely access health care without having to weigh-up the fear of COVID-19 infection against the need to be seen. Telehealth worked best for routine and familiar health issues and when rapport was established between patients and clinicians. This was easier with a pre-existing clinical relationship, but not impossible without one. Telehealth was less suitable when a physical examination was needed, when the diagnosis was unknown or for patients who had a strong preference to be seen in-person. Conclusions: Even in this disruptive lockdown period, that prompted an unexpected and rapid implementation of telehealth services in general practices, most patients had positive experiences with telehealth. In the future, patients want the choice of consultation type to match their needs, circumstances, and preferences. Technological issues and funding barriers may need to be addressed, and clear communication for both patients and clinicians is needed about key aspects of telehealth (e.g. cost, appropriateness, privacy). Maintaining telehealth as an option post-lockdown has the potential to increase timely and safe access to primary health care for many patients.