Antibody levels following vaccination against SARS-CoV-2: associations with post-vaccination infection and risk factors (preprint)

SARS-CoV-2 antibody levels can be used to assess humoral immune responses following SARS-CoV-2 infection or vaccination, and may predict risk of future infection. From cross-sectional antibody testing of 9,361 individuals from TwinsUK and ALSPAC UK population-based longitudinal studies (jointly in April-May 2021, and TwinsUK only in November 2021-January 2022), we tested associations between antibody levels following vaccination and: (1) SARS-CoV-2 infection following vaccination(s); (2) health, socio-demographic, SARS-CoV-2 infection and SARS-CoV-2 vaccination variables. Within TwinsUK, single-vaccinated individuals with the lowest 20% of anti-Spike antibody levels at initial testing had 3-fold greater odds of SARS-CoV-2 infection over the next six to nine months, compared to the top 20%. In TwinsUK and ALSPAC, individuals identified as at increased risk of COVID-19 complication through the UK "Shielded Patient List" had consistently greater odds (2 to 4-fold) of having antibody levels in the lowest 10%. Third vaccination increased absolute antibody levels for almost all individuals, and reduced relative disparities compared with earlier vaccinations. These findings quantify the association between antibody level and risk of subsequent infection, and support a policy of triple vaccination for the generation of protective antibodies.

Tracking population mental health before and across stages of the COVID-19 pandemic in young adults (preprint)

The SARS-CoV2 (COVID-19) pandemic has been associated with worsening mental health. Longitudinal studies have monitored changes in mental health from pre-pandemic levels, identifying critical points for mental health as COVID-19 restrictions evolve. Here we highlight changes in depression and anxiety in the UK from pre-pandemic across four pandemic occasions: April and June 2020, January, and July 2021 - corresponding to changes in COVID-19 restrictions. Data were from >5,000 27-29 year olds from the Avon Longitudinal Study of Parents and Children (ALSPAC). We found that anxiety almost doubled throughout the pandemic compared to pre-pandemic levels and remained high until July 2021 when COVID-19 restrictions were fully lifted. Depression was lower than pre-pandemic levels in April 2020 but increased as the pandemic evolved until July 2021. Women, those with existing mental/physical health conditions and those with economic hardship were most at risk of sustained poorer mental health across the pandemic. Our results highlight the importance of longitudinal studies for tracking mental health during the COVID-19 pandemic and across virus suppression policy changes.

Impact of voluntary risk-mitigation behaviour on transmission of the Omicron SARS-CoV-2 variant in England (preprint)

Abstract Background The Omicron variant of SARS-CoV-2 infection poses substantial challenges to public health. In England, "plan B" mitigation measures were introduced in December 2021 including increased home working and face coverings in shops, but stopped short of restrictions on social contacts. The impact of voluntary risk mitigation behaviours on future SARS-CoV-2 burden is unknown. Methods We developed a rapid online survey of risk mitigation behaviours during the winter 2021 festive period and deployed in two longitudinal cohort studies in the UK (Avon Longitudinal Study of Parents and Children (ALSPAC) and TwinsUK/Covid Symptom Study (CSS) Biobank) in December 2021. Using an individual-based, probabilistic model of COVID-19 transmission between social contacts with SARS-CoV-2 Omicron variant parameters and realistic vaccine coverage in England, we describe the potential impact of the SARS-CoV-2 Omicron wave in England in terms of the effective reproduction number and cumulative infections, hospital admissions and deaths. Using survey results, we estimated in real-time the impact of voluntary risk mitigation behaviours on the Omicron wave in England, if implemented for the entire epidemic wave. Results Over 95% of survey respondents (N_ALSPAC=2,686 and N_Twins=6,155) reported some risk mitigation behaviours, with being fully vaccinated and using home testing kits the most frequently reported behaviours. Less than half of those respondents reported that their behaviour was due to "plan B". We estimate that without risk mitigation behaviours, the Omicron variant is consistent with an effective reproduction number between 2.5 and 3.5. Due to the reduced vaccine effectiveness against infection with the Omicron variant, our modelled estimates suggest that between 55% and 60% of the English population could be infected during the current wave, translating into between 15,000 and 46,000 cumulative deaths, depending on assumptions about vaccine effectiveness. We estimate that voluntary risk reduction measures could reduce the effective reproduction number to between 1.8 and 2.2 and reduce the cumulative number of deaths by up to 24%. Conclusions We conclude that voluntary measures substantially reduce the projected impact of the SARS-CoV-2 Omicron variant, but that voluntary measures alone would be unlikely to completely control transmission.

Risk factors for long COVID: analyses of 10 longitudinal studies and electronic health records in the UK (preprint)

The impact of long COVID is increasingly recognised, but risk factors are poorly characterised. We analysed questionnaire data on symptom duration from 10 longitudinal study (LS) samples and electronic healthcare records (EHR) to investigate sociodemographic and health risk factors associated with long COVID, as part of the UK National Core Study for Longitudinal Health and Wellbeing. Methods Analysis was conducted on 6,899 adults self-reporting COVID-19 from 45,096 participants of the UK LS, and on 3,327 cases assigned a long COVID code in primary care EHR out of 1,199,812 adults diagnosed with acute COVID-19. In LS, we derived two outcomes: symptoms lasting 4+ weeks and symptoms lasting 12+ weeks. Associations of potential risk factors (age, sex, ethnicity, socioeconomic factors, smoking, general and mental health, overweight/obesity, diabetes, hypertension, hypercholesterolaemia, and asthma) with these two outcomes were assessed, using logistic regression, with meta-analyses of findings presented alongside equivalent results from EHR analyses. Results Functionally limiting long COVID for 12+ weeks affected between 1.2% (age 20), and 4.8% (age 63) of people reporting COVID-19 in LS. The proportion reporting symptoms overall for 12+ weeks ranged from 7.8 (mean age 28) to 17% (mean age 58) and for 4+ weeks 4.2% (age 20) to 33.1% (age 56). Age was associated with a linear increase in long COVID between age 20-70. Being female (LS: OR=1.49; 95%CI:1.24-1.79; EHR: OR=1.51 [1.41-1.61]), poor pre-pandemic mental health (LS: OR=1.46 [1.17-1.83]; EHR: OR=1.57 [1.47-1.68]) and poor general health (LS: OR=1.62 [1.25-2.09]; EHR: OR=1.26; [1.18-1.35]) were associated with higher risk of long COVID. Individuals with asthma also had higher risk (LS: OR=1.32 [1.07-1.62]; EHR: OR=1.56 [1.46-1.67]), as did those categorised as overweight or obese (LS: OR=1.25 [1.01-1.55]; EHR: OR=1.31 [1.21-1.42]) though associations for symptoms lasting 12+ weeks were less pronounced. Non-white ethnic minority groups had lower 4+ week symptom risk (LS: OR=0.32 [0.22-0.47]), a finding consistent in EHR. Associations were not observed for other risk factors. Few participants in the studies had been admitted to hospital (0.8-5.2%). Conclusions Long COVID is clearly distributed differentially according to several sociodemographic and pre-existing health factors. Establishing which of these risk factors are causal and predisposing is necessary to further inform strategies for preventing and treating long COVID.

Associations of socioeconomic position and adverse childhood experiences with health-related behaviour changes and changes to employment during the first COVID-19 lockdown in the UK (preprint)

Background Non-pharmaceutical interventions to reduce the spread of COVID-19 may have disproportionately affected already disadvantaged populations. Methods We analysed data from 2710 young adult participants of the Avon Longitudinal Study of Parents and Children. We assessed the associations of socioeconomic position (SEP) and Adverse Childhood Experiences (ACEs, e.g. abuse, neglect, measures of family dysfunction) with changes to health-related behaviours (meals, snacks, exercise, sleep, alcohol and smoking/vaping), and to financial and employment status during the first UK lockdown between March-June 2020. Results Experiencing 4 or more ACEs was associated with reporting decreased sleep quantity during lockdown (OR 1.53, 95% CI: 1.07-2.18) and increased smoking and/or vaping (OR 1.85, 95% CI: 0.99-3.43); no other associations were seen between ACEs or SEP and health-related behaviour changes. Adverse financial and employment changes were more likely for people with low SEP and for people who had experienced multiple ACEs; e.g. people who had been in the 'never worked or long-term unemployed' or 'routine and manual occupation' categories pre-lockdown were almost 3 times more likely to have stopped working during lockdown compared with people who were in a higher managerial, administrative or professional occupation pre-lockdown (OR 2.83, 95% CI: 1.45-5.50 and OR 2.68, 95% CI: 1.63-4.42 respectively). Conclusion Adverse financial and employment consequences of lockdown were more likely to be experienced by people who have already experienced socioeconomic deprivation or childhood adversity, thereby widening social inequalities. Despite this, in this sample of young adults, there was little evidence that lockdown worsened inequalities in health-related behaviours.

Trajectories of child emotional and behavioural difficulties before and during the COVID-19 pandemic in a longitudinal UK cohort (preprint)

ImportanceCOVID-19 public health mitigation measures are likely to have detrimental effects on emotional and behavioural problems in children. However, longitudinal studies with pre-pandemic data are scarce. ObjectiveTo explore trajectories of childrens emotional and behavioural difficulties during the COVID-19 pandemic. Design and settingData were from children from the third generation of a birth cohort study; the Avon Longitudinal Study of Parents and Children - Generation 2 (ALSPAC-G2) in the southwest of England. ParticipantsThe study population comprised of 708 children (median age at COVID-19 data collection was 4.4 years, SD=2.9, IQR= [2.2 to 6.9]), whose parents provided previous pre-pandemic surveys and a survey between 26 May and 5 July 2020 that focused on information about the COVID-19 pandemic as restrictions from the first lockdown in the UK were eased. ExposuresWe employed multi-level mixed effects modelling with random intercepts and slopes to examine whether childrens trajectories of emotional and behavioural difficulties (a combined total difficulties score) during the pandemic differ from expected pre-pandemic trajectories. Main outcomesChildren had up to seven measurements of emotional and behavioural difficulties from infancy to late childhood, using developmentally appropriate scales such as the Emotionality Activity Sociability Temperament Survey in infancy and Strengths and Difficulties Questionnaire in childhood. ResultsThe observed normative pattern of childrens emotional and behavioural difficulties pre-pandemic, was characterised by an increase in scores during infancy peaking around the age of 2, and then declining throughout the rest of childhood. Pre-pandemic, the decline in difficulties scores after age 2 was 0.6 points per month; but was approximately one third of that in post-pandemic trajectories (there was a difference in mean rate of decline after age 2 of 0.2 points per month in pre vs during pandemic trajectories [95 % CI: 0.10 to 0.30, p <0.001]). This lower decline in scores over the years translated to older children having pandemic difficulty scores higher than would be expected from pre-pandemic trajectories (for example, an estimated 10.0 point (equivalent of 0.8 standard deviations) higher score (95% CI: 5.0 to 15.0) by age 8.5 years). Results remained similar although somewhat attenuated after adjusting for maternal anxiety and age. Conclusion and relevanceThe COVID-19 pandemic may be associated with greater persistence of emotional and behavioural difficulties after the age 2. Emotional difficulties in childhood predict later mental health problems. Further evidence and monitoring of emotional and behavioural difficulties are required to fully understand the potential role of the pandemic on young children. Key FindingsO_ST_ABSQuestionC_ST_ABSHow has the COVID-19 pandemic influenced emotional difficulties in young children? FindingsUsing repeated longitudinal data from before and during the pandemic we provide evidence that emotional difficulty scores of primary school aged children are higher by an estimated 10.0 points (0.8 standard deviations) (95% CI: 5.0 to 15.0) by age 8.5 years than would be expected based on pre pandemic data. MeaningThe level of difference in emotional difficulties found in the current study has been linked to increased likelihood of mental health problems in adolescence and adulthood. Therefore, this increase in difficulties needs careful monitoring and support.

Limits of lockdown: characterising essential contacts during strict physical distancing (preprint)

COVID-19 has exposed health inequalities within countries and globally. The fundamental determining factor behind an individuals risk of infection is the number of social contacts they make. In many countries, physical distancing measures have been implemented to control transmission of SARS-CoV-2, reducing social contacts to a minimum. Characterising unavoidable social contacts is key for understanding the inequalities behind differential risks and planning vaccination programmes. We utilised an existing English longitudinal birth cohort, which is broadly representative of the wider population (n=6807), to explore social contact patterns and behaviours when strict physical distancing measures were in place during the UKs first lockdown in March-May 2020. Essential workers, specifically those in healthcare, had 4.5 times as many contacts as non-essential workers [incident rate ratio = 4.42 (CI95%: 3.88-5.04)], whilst essential workers in other sectors, mainly teaching and the police force had three times as many contacts [IRR = 2.84 (2.58-3.13)]. The number of individuals in a household, which is conflated by number of children, increases essential social contacts by 40%. Self-isolation effectively reduces numbers of contacts outside of the home, but not entirely. Together, these findings will aid the interpretation of epidemiological data and impact the design of effective SARS-CoV-2 control strategies, such as vaccination, testing and contact tracing.

Trajectories of Child Emotional and Behavioural Difficulties Before and During the COVID-19 Pandemic in a Longitudinal UK Cohort (preprint)

Background: There are concerns that the COVID-19 pandemic and its associated public health mitigation measures will have detrimental effects on emotional and behavioural problems in children. However, longitudinal studies with pre-pandemic data are scarce. In a UK cohort, we quantify the impact of the COVID-19 pandemic on trajectories of children’s emotional and behavioural difficulties measured before and during the pandemic.Methods: Data were from 708 children (Mean age = 3·45 years, SD = 3·13) part of the third generation of a birth cohort study, the Avon Longitudinal Study of Parents and Children (ALSPAC). Study sample comprised children whose parents provided previous pre-pandemic surveys and a survey between 26 May and 5 July 2020 that focused on the impact of the COVID-19 pandemic as restrictions in the UK were eased. The children had up to seven measurements of emotional and behavioural difficulties from infancy to late childhood (including the most recent measures during the pandemic). We employed multi-level mixed effects modelling with random intercepts and slopes to examine whether children’s trajectories of emotional and behavioural difficulties (a combined “total difficulties score”) during the pandemic differ from expected pre-pandemic trajectories. Findings: We found that children’s emotional and behavioural difficulties increased during infancy, peaked around the age of 2, and then declined throughout the rest of childhood. Pre-pandemic, the decline in difficulties scores after age 2 was 0·6 points per month; but was approximately one third of that in post-pandemic trajectories (there was a difference in mean rate of decline after age 2 of 0·2 points per month in pre vs during pandemic trajectories [95 % CI: 0·1 to 0·3, p <0·001]). This lower decline in scores over the years translated to older children having pandemic difficulty scores higher than would be expected from pre-pandemic trajectories (for example, an estimated 10-point higher score (95% CI: 5·0 to 15·0) by age 8·5 years). Results remained similar although somewhat attenuated after adjusting for maternal anxiety and age. Interpretation: The COVID-19 pandemic may be associated with greater persistence of emotional and behavioural difficulties after the age 2. Further evidence and monitoring of emotional and behavioural difficulties are required to fully understand the impact of the pandemic on this population, given ongoing and likely further periods of restrictions.Funding: This work was supported by the UK Medical Research Council and Wellcome (Grants 217065/Z/19/Z and 102215), the European Research Commission grant (Grant Ref: 758813 MHINT), the Elizabeth Blackwell Institute, University of Bristol, with funding from QR SPF (Quality-Related Strategic Priorities Fund), and UKRI Research England the Faculty Research Director’s discretionary fund and the University of Bristol. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf).Declaration of Interests: All authors declare no conflicts of interest.Ethics Approval Statement: Ethical approval for the study was obtained from the ALSPAC Ethics and Law Committee and the Local Research Ethics Committees. All participants provided fully informed consent and the study is GDPR compliant.

Mental health during the COVID-19 pandemic in two longitudinal UK population cohorts (preprint)

Background: The impact of COVID-19 on mental health is unclear. Evidence from longitudinal studies with pre pandemic data are needed to address (1) how mental health has changed from pre-pandemic levels to during the COVID-19 pandemic and (2), whether there are groups at greater risk of poorer mental health during the pandemic? Methods: We used data from COVID-19 surveys (completed through April/May 2020), nested within two large longitudinal population cohorts with harmonised measures of mental health: two generations of the Avon Longitudinal Study of Parents and Children (ALPSAC): the index generation ALSPAC-G1 (n= 2850, mean age 28) and the parents generation ALSPAC-G0 (n= 3720, mean age = 59) and Generation Scotland: Scottish Family Health Study (GS, (n= 4233, mean age = 59), both with validated pre-pandemic measures of mental health and baseline factors. To answer question 1, we used ALSPAC-G1, which has identical mental health measures before and during the pandemic. Question 2 was addressed using both studies, using pre-pandemic and COVID-19 specific factors to explore associations with depression and anxiety in COVID-19. Findings: In ALSPAC-G1 there was evidence that anxiety and lower wellbeing, but not depression, had increased in COVID-19 from pre-pandemic assessments. The percentage of individuals with probable anxiety disorder was almost double during COVID-19: 24% (95% CI 23%, 26%) compared to pre-pandemic levels (13%, 95% CI 12%, 14%), with clinically relevant effect sizes. In both ALSPAC and GS, depression and anxiety were greater in younger populations, women, those with pre-existing mental and physical health conditions, those living alone and in socio-economic adversity. We did not detect evidence for elevated risk in key workers or health care workers. Interpretation: These results suggest increases in anxiety and lower wellbeing that may be related to the COVID-19 pandemic and/or its management, particularly in young people. This research highlights that specific groups may be disproportionally at risk of elevated levels of depression and anxiety during COVID-19 and supports recent calls for increasing funds for mental health services. Funding: The UK Medical Research Council (MRC), the Wellcome Trust and University of Bristol.