Elevated symptoms of depression and anxiety among family members and friends of critically ill COVID-19 patients - An observational study of five cohorts across four countries (preprint)

Background. Little is known regarding the mental health impact of having a significant person (family member and/or close friend) with COVID-19 of different severity. Methods. The study included five prospective cohorts from four countries (Iceland, Norway, Sweden, and the UK) with self-reported data on COVID-19 and symptoms of depression and anxiety during March 2020-March 2022. We calculated the prevalence ratio (PR) of depression and anxiety in relation to having a significant person with COVID-19 and performed a longitudinal analysis in the Swedish cohort to describe the temporal patterns of the results. Results. 162,237 and 168,783 individuals were included in the analysis of depression and anxiety, respectively, of whom 24,718 and 27,003 reported a significant person with COVID- 19. Overall, the PR was 1.07 (95% CI: 1.05-1.10) for depression and 1.08 (95% CI: 1.03-1.13) for anxiety among significant others of COVID-19 patients. The respective PRs for depression and anxiety were 1.04 (95% CI: 1.01-1.07) and 1.03 (95% CI: 0.98-1.07) if the significant person was never hospitalized, 1.15 (95% CI: 1.08-1.23) and 1.24 (95% CI: 1.14-1.34) if the patient was hospitalized, 1.42 (95% CI: 1.27-1.57) and 1.45 (95% CI: 1.31-1.60) if admitted to the ICU, and 1.34 (95% CI: 1.22-1.46) and 1.36 (95% CI: 1.22-1.51) if the significant person died. Individuals of hospitalized, ICU admitted, or deceased patients showed higher prevalence of depression and anxiety during the entire 12 months after the COVID-19 diagnosis of the significant person. Conclusions. Close friends and family members of critically ill COVID-19 patients show elevated prevalence of depression and anxiety throughout the first year after the diagnosis.

Acute COVID-19 severity and 16-month mental morbidity trajectories in patient populations of six nations (preprint)

BACKGROUND The aim of this multinational study was to assess the development of adverse mental health symptoms among individuals diagnosed with COVID-19 in the general population by acute infection severity up to 16 months after diagnosis. METHODS Participants consisted of 247 249 individuals from seven cohorts across six countries (Denmark, Estonia, Iceland, Norway, Scotland, and Sweden) recruited from April 2020 through August 2021. We used multivariable Poisson regression to contrast symptom-prevalence of depression, anxiety, COVID-19 related distress, and poor sleep quality among individuals with and without a diagnosis of COVID-19 at entry to respective cohorts by time (0-16 months) from diagnosis. We also applied generalised estimating equations (GEE) analysis to test differences in repeated measures of mental health symptoms before and after COVID-19 diagnosis among individuals ever diagnosed with COVID-19 over time. FINDINGS A total of 9979 individuals (4%) were diagnosed with COVID-19 during the study period and presented overall with a higher symptom burden of depression (prevalence ratio [PR] 1.18, 95% confidence interval [95% CI] 1.03-1.36) and poorer sleep quality (1.13, 1.03-1.24) but not with higher levels of symptoms of anxiety or COVID-19 related distress compared with individuals without a COVID-19 diagnosis. While the prevalence of depression and COVID-19 related distress attenuated with time, the trajectories varied significantly by COVID-19 acute infection severity. Individuals diagnosed with COVID-19 but never bedridden due to their illness were consistently at lower risks of depression and anxiety (PR 0.83, 95% CI 0.75-0.91 and 0.77, 0.63-0.94, respectively), while patients bedridden for more than 7 days were persistently at higher risks of symptoms of depression and anxiety (PR 1.61, 95% CI 1.27-2.05 and 1.43, 1.26-1.63, respectively) throughout the 16-month study period. CONCLUSION Acute infection severity is a key determinant of long-term mental morbidity among COVID-19 patients.

Development and validation of DNA Methylation scores in two European cohorts augment 10-year risk prediction of type 2 diabetes (preprint)

Type 2 diabetes mellitus (T2D) presents a major health and economic burden that could be alleviated with improved early prediction and intervention. While standard risk factors have shown good predictive performance, we show that the use of blood-based DNA methylation information leads to a significant improvement in the prediction of 10-year T2D incidence risk. Previous studies have been largely constrained by linear assumptions, the use of CpGs one-at-a-time, and binary outcomes. We present a flexible approach (via an R package, MethylPipeR ) based on a range of linear and tree-ensemble models that incorporate time-to-event data for prediction. Using the Generation Scotland cohort (training set n cases =374, n controls =9,461; test set n cases =252, n controls =4,526) our best-performing model (Area Under the Curve (AUC)=0.872, Precision Recall AUC (PRAUC)=0.302) showed notable improvement in 10-year onset prediction beyond standard risk factors (AUC=0.839, PRAUC=0.227). Replication was observed in the German-based KORA study (n=1,451, n cases = 142, p=1.6×10 -5 ).

Brief Report: Predictors of Adolescent Mental Health and Wellbeing During the COVID-19 Pandemic (preprint)

Purpose: This study explored predictors of COVID-19-related stress and wellbeing of Scottish adolescents during the COVID-19 lockdown to identify potentially malleable risk and protective factors. Methods: 5,548 participants were surveyed regarding stress, loneliness, wellbeing, schoolwork, support from school, and interaction with friends and family. Multiple linear regressions within a structural equation modelling framework were fit to predict COVID-19-related stress and wellbeing during the UK’s first lockdown. Results: Loneliness, variables related to the ability to continue with schoolwork, and perceived support from school were important predictors of greater COVID-19-related stress and wellbeing during the first lockdown. Female adolescents were also more likely to show higher stress and poorer wellbeing. Conclusions: Facilitating meaningful social interaction and ensuring the ability to continue with schoolwork, and providing social support from school should be priority strategies to help protect the mental health and wellbeing of secondary school students during lockdowns and other disruptions to school attendance.

Pre-pandemic Cognitive Function and COVID-19 Vaccine Hesitancy: Prospective Cohort Study (preprint)

BackgroundWhereas several predictors of COVID-19 vaccine hesitancy have been examined, the role of cognitive function following the widely publicised development of an inoculation is unknown. ObjectiveTo test the association between scores from an array of cognitive function tests and self-reported vaccine hesitancy after the announcement of the successful testing of the Oxford University/AstraZeneca vaccine. Design, Setting, and ParticipantsWe used individual-level data from a pandemic-focused study (COVID Survey), a prospective cohort study nested within Understanding Society (Main Survey). In the week immediately following the announcement of successful testing of the first efficacious inoculation (November/December 2020), data on vaccine intentionality were collected in 11740 individuals (6702 women) aged 16-95. Pre-pandemic scores on general cognitive function, ascertained from a battery of six tests, were captured in 2011/12 wave of the Main Survey. MeasurementsSelf-reported intention to take up a vaccination for COVID-19. To summarise our results, we computed odds ratios with accompanying 95% confidence intervals for general cognitive function adjusted for selected covariates. ResultsOf the study sample, 17.2% (N=1842) indicated they were hesitant about having the vaccine. After adjustment for age, sex, and ethnicity, study members with a lower baseline cognition score were markedly more likely to be vaccine hesitant (odds ratio per standard deviation lower score in cognition; 95% confidence interval: 1.76; 1.62, 1.90). Adjustment for mental and physical health plus household shielding status had no impact on these results, whereas controlling for educational attainment led to partial attenuation but the probability of hesitancy was still elevated (1.52; 1.37, 1.67). There was a linear association for vaccine hesitancy across the full range of cognition scores (p for trend: p<0.0001). LimitationsOur outcome was based on intention rather than behaviour. ConclusionsErroneous social media reports might have complicated personal decision-making, leading to people with lower cognitive ability test scores being vaccine-hesitant. With people with lower cognition also experiencing higher rates of COVID-19 in studies conducted prior to vaccine distribution, these new findings are suggestive of a potential additional disease burden.

Face covering adherence is positively associated with better mental health and wellbeing: a longitudinal analysis of the CovidLife surveys (preprint)

Face masks or coverings are effective at reducing airborne infection rates, yet pandemic mitigation measures, including wearing face coverings, have been suggested to contribute to reductions in quality of life and poorer mental health. Longitudinal analyses of more than 11,000 participants across the UK found no association between lower adherence to face covering guidelines and poorer mental health. The opposite appears to be true. Even after controlling for behavioral, social, and psychological confounds, including measures of pre-pandemic mental health, individuals who wore face coverings "most of the time" or "always" had better mental health and wellbeing than those who did not. These results suggest that wearing face coverings more often will not negatively impact mental health.

Using symptom-based case predictions to identify host genetic factors that contribute to COVID-19 susceptibility (preprint)

Epidemiological and genetic studies on COVID-19 are hindered by inconsistent and limited testing policies to confirm SARS-CoV-2 infection. Recently, it was shown that it is possible to predict potential COVID-19 cases using cross-sectional self-reported disease-related symptoms. Using a previously reported COVID-19 prediction model, we show that it is possible to conduct a GWAS on predicted COVID-19 which benefits from a larger sample size in order to gain new insights into the genetic susceptibility of the disease. Furthermore, we find suggestive evidence that genetic variants for other viral infectious diseases do not overlap with COVID-19 susceptibility and that severity of COVID-19 may have a different genetic architecture compared to COVID-19 susceptibility. Our findings demonstrate the added value of using self-reported symptom assessments to quickly monitor novel endemic viral outbreaks in a scenario of limited testing. Should there be another outbreak of a novel infectious disease, then we recommend repeatedly collecting data of disease-related symptoms.

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.