Humoral and cellular immunity in patients with rare autoimmune rheumatic diseases following SARS-CoV-2 vaccination.

OBJECTIVES: COVID-19 vaccine responses in rare autoimmune rheumatic diseases (RAIRD) remain poorly understood, in particular there is little known about whether people develop effective T cell responses. We conducted an observational study to evaluate the short-term humoral and cell-mediated T cell response after the second SARS-CoV-2 vaccination in RAIRD patients compared with healthy controls (HC). METHODS: Blood samples were collected after the second dose and anti-spike, anti-nucleocapsid antibody levels and SARS-CoV-2 specific T cell responses were measured and compared with HC. Activation induced marker and deep phenotyping assays were used to identify differences in T cells between high and low/no antibody groups, followed by multi-dimensional clustering. RESULTS: 50 patients with RAIRD were included (31 with AAV, 4 with other systemic vasculitis, 9 with SLE and 6 with myositis). Median anti-spike levels were significantly lower in RAIRD compared with HC (p< 0.0001). 15 (33%) patients had undetectable and 26 (57%) had lower levels than the lowest HC. Rituximab in the last 12 months (p= 0.003) was associated with reduced immunogenicity compared with a longer pre-vaccination period. There was a significant difference in B cell percentages (p= 0.03) and spike-specific CD4+ T cells (p= 0.02) between no/low antibody vs. high antibody groups. Patients in the no/low antibody group had a higher percentage of terminally differentiated (exhausted) T cells. CONCLUSIONS: Following two doses, most RAIRD patients have lower antibody levels than the lowest HC and lower anti-spike T cells. RAIRD patients with low/no antibodies have diminished numbers and poor quality of memory T cells which lack proliferative and functional capacities.

Psychology Meets Biology in COVID-19: What We Know and Why It Matters for Public Health

Psychosocial factors are related to immune, viral, and vaccination outcomes. Yet, this knowledge has been poorly represented in public health initiatives during the COVID-19 pandemic. This review provides an overview of biopsychosocial links relevant to COVID-19 outcomes by describing seminal evidence about these associations known prepandemic as well as contemporary research conducted during the pandemic. This focuses on the negative impact of the pandemic on psychosocial health and how this in turn has likely consequences for critically relevant viral and vaccination outcomes. We end by looking forward, highlighting the potential of psychosocial interventions that could be leveraged to support all people in navigating a postpandemic world and how a biopsychosocial approach to health could be incorporated into public health responses to future pandemics.

A meta-analysis of the associations between insufficient sleep duration and antibody response to vaccination.

Vaccination is a major strategy to control a viral pandemic. Simple behavioral interventions that might boost vaccine responses have yet to be identified. We conducted meta-analyses to summarize the evidence linking the amount of sleep obtained in the days surrounding vaccination to antibody response in healthy adults. Authors of the included studies provided the information needed to accurately estimate the pooled effect size (ES) and 95% confidence intervals (95% CI) and to examine sex differences.1,2,3,4,5,6,7 The association between self-reported short sleep (<6 h/night) and reduced vaccine response did not reach our pre-defined statistical significant criteria (total n = 504, ages 18-85; overall ES [95% CI] = 0.29 [-0.04, 0.63]). Objectively assessed short sleep was associated with a robust decrease in antibody response (total n = 304, ages 18-60; overall ES [95% CI] = 0.79 [0.40, 1.18]). In men, the pooled ES was large (overall ES [95% CI] = 0.93 [0.54, 1.33]), whereas it did not reach significance in women (overall ES [95% CI] = 0.42 [-0.49, 1.32]). These results provide evidence that insufficient sleep duration substantially decreases the response to anti-viral vaccination and suggests that achieving adequate amount of sleep during the days surrounding vaccination may enhance and prolong the humoral response. Large-scale well-controlled studies are urgently needed to define (1) the window of time around inoculation when optimizing sleep duration is most beneficial, (2) the causes of the sex disparity in the impact of sleep on the response, and (3) the amount of sleep needed to protect the response.

Increases in stress hormone levels in a UK population during the COVID-19 pandemic: A prospective cohort study.

BACKGROUND: Research suggests that psychological factors may influence vulnerability to SARS-CoV-2 infection, although the mechanisms are unclear. PURPOSE: We examined whether the hypothalamic-pituitary-adrenal axis may be a possible mechanism, by measuring the relationship between indices of psychological distress and cortisone in hair (hairE) in a UK cohort during the COVID-19 pandemic. METHODS: Participants (N = 827) provided two 3 cm hair samples over a 6-month period between April-September 2020. Samples reflected hairE in the 3 months prior to the collection date. RESULTS: HairE in the first samples (T1: commenced April 2020) did not differ significantly from pre-pandemic population norms. However, hairE in the second samples (T2: commenced July 2020) were significantly higher than T1 and pre-pandemic population norms, with a 23% increase between T1 and T2. Linear regressions, controlling for age and gender, demonstrated that at both timepoints, hairE levels were greatest in people with a history of mental health difficulties. In addition, stress reported at T1 predicted greater hairE at T2 and a greater change in hairE between T1 and T2. CONCLUSIONS: These findings demonstrate that during the COVID-19 pandemic hairE was substantially elevated across a large community cohort, with greatest levels in those with a history of mental health difficulties and greatest changes in those reporting greatest levels of stress early in the pandemic. Further research is required with verified SARS-CoV-2 outcomes to determine whether the HPA axis is among the mechanisms by which a history of mental health difficulties and stress influence SARS-CoV-2 outcomes.

Risk Factors and Changes in Depression and Anxiety over Time in New Zealand during COVID-19: A Longitudinal Cohort Study

This longitudinal study investigated changes in and risk factors for anxiety and depression during the COVID-19 pandemic in a New Zealand cohort. Online surveys were distributed to 681 participants at three time-points: May 2020 (Time 1), August–September 2020 (Time 2), and March–April 2021 (Time 3). Participants completed measures of anxiety and depression, alongside measures of possible risk/protective factors. A total of 261 participants completed all three surveys and were included in analyses. Depression and anxiety reduced over time;however, levels were still significantly higher than pre-pandemic norms. Being younger, having a prior mental health disorder, experiencing negative life events due to COVID-19, and being a pet owner were risk factors for poorer depression and anxiety, whereas having higher positive mood was protective. This study demonstrates persisting negative effects of the pandemic on anxiety and depression in a context of low transmission and highlights the importance of providing psychological help to those most at risk.

Relationship Between Anxiety, Depression, and Susceptibility to Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Proof of Concept.

BACKGROUND: Psychological factors can influence susceptibility to viral infections. We examined whether such influences are evident in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: Participants (n = 102) completed measures of anxiety, depression, positive mood, and loneliness and provided a blood sample for the measurement of antibodies to the SARS-CoV-2 spike and nucleocapsid proteins. RESULTS: SARS-CoV-2 was significantly negatively associated with anxiety and depression. The model remained significant after adjustment for age and gender, although anxiety and depression were no longer significant independent predictors. CONCLUSIONS: These findings offer early support for the hypothesis that psychological factors may influence susceptibility to SARS-CoV-2 infection.

The prevalence, incidence, prognosis and risk factors for symptoms of depression and anxiety in a UK cohort during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has had profound consequences for population mental health. However, it is less clear for whom these effects are sustained. AIMS: To investigate the prevalence, incidence, prognosis and risk factors for symptoms of depression and anxiety in a UK cohort over three distinct periods in the pandemic in 2020. METHOD: An online survey was completed by a UK community cohort at three points (n = 3097 at baseline, n = 878 completed all surveys): April (baseline), July to September (time point 2) and November to December (time point 3). Participants completed validated measures of depression and anxiety on each occasion, and we prospectively explored the role of sociodemographic and psychological factors (loneliness, positive mood and perceived risk of and worry about COVID-19) as risk factors. RESULTS: Depression (Patient Health Questionnaire-9 means: baseline, 7.69; time point 2, 5.53; time point 3, 6.06) and anxiety scores (Generalised Anxiety Disorder-7 means: baseline, 6.59; time point 2, 4.60; time point 3, 4.98) were considerably greater than pre-pandemic population norms at all time points. Women reported greater depression and anxiety symptoms than men. Younger age, history of mental health disorder, more COVID-19-related negative life events, greater loneliness and lower positive mood at baseline were all significant predictors of poorer mental health at time point 3. CONCLUSIONS: The negative impact of the COVID-19 pandemic on mental health has persisted to some degree. Younger people and individuals with prior mental health disorders are at greatest risk. Easing of restrictions and resumption of social interaction could mitigate the risk factors of loneliness and positive mood.

Psychological Predictors of Self-reported COVID-19 Outcomes: Results From a Prospective Cohort Study.

BACKGROUND: Previous research has shown that psychological factors, such as stress and social support, are associated with greater susceptibility to viral respiratory illnesses and more severe symptoms. During the COVID-19 pandemic there has been a well-documented deterioration in psychological well-being and increased social isolation. This raises questions as to whether those experiencing psychological adversity during the pandemic are more at risk of contracting and/or experiencing COVID-19 symptoms. PURPOSE: To examine the relationship between psychological factors and the risk of COVID-19 self-reported infection and the symptomatic experience of SARS-CoV-2 (indicated by the number and severity of symptoms). METHODS: As part of a longitudinal prospective observational cohort study, 1,087 adults completed validated measures of psychological well-being during April 2020 and self-reported incidence of COVID-19 infection and symptom experience across the pandemic through to December 2020. Regression models were used to explore these relationships controlling for demographic and occupational factors. RESULTS: Greater psychological distress during the early phase of the pandemic was significantly associated with subsequent self-reported SARS-CoV-2 infection as well as the experience of a greater number and more severe symptoms. CONCLUSIONS: COVID-19 infection and symptoms may be more common among those experiencing elevated psychological distress. Further research to elucidate the mechanisms underlying these associations is needed.

Depression, anxiety and stress during the COVID-19 pandemic: results from a New Zealand cohort study on mental well-being.

OBJECTIVES: The COVID-19 pandemic has caused unprecedented disruption to daily life. This study investigated depression, anxiety and stress in New Zealand (NZ) during the first 10 weeks of the COVID-19 pandemic, and associated psychological and behavioural factors. It also compares the results with a similar cross-sectional study in the UK. DESIGN: Cross-sectional study. SETTING: NZ community cohort. PARTICIPANTS: N=681 adults (≥18 years) in NZ. The cohort was predominantly female (89%) with a mean age of 42 years (range 18-87). Most (74%) identified as NZ European and almost half (46%) were keyworkers. Most were non-smokers (95%) and 20% identified themselves as having clinical risk factors which would put them at increased or greatest risk of COVID-19. MAIN OUTCOME MEASURES: Depression, anxiety, stress, positive mood and engagement in health behaviours (smoking, exercise, alcohol consumption). RESULTS: Depression and anxiety significantly exceeded population norms (p<0.0001). Being younger (p<0.0001) and most at risk of COVID-19 (p<0.05) were associated with greater depression, anxiety and stress. Greater positive mood, lower loneliness and greater exercise were protective factors for all outcomes (p<0.0001). Smoking (p=0.037) and alcohol consumption (p<0.05) were associated with increased anxiety. Pet ownership was associated with lower depression (p=0.006) and anxiety (p=0.008). When adjusting for age and gender differences, anxiety (p=0.002) and stress (p=0.007) were significantly lower in NZ than in the UK. The NZ sample reported lower perceived risk (p<0.0001) and worry about COVID-19 (p<0.0001) than the UK sample. CONCLUSIONS: The NZ population had higher depression and anxiety compared with population norms. Younger people and those most at risk of COVID-19 reported poorer mental health. Interventions should promote frequent exercise, and reduce loneliness and unhealthy behaviours.

Young people, mental health and COVID-19 infection: the canaries we put in the coal mine.

OBJECTIVES: The number of people testing positive for Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) in the UK, particularly among young adults, is increasing. We report here on the mental health of young adults and related psychological and behavioural responses to the pandemic and consider the role of these factors in fuelling the increase in coronavirus disease 2019 (COVID-19) in this group. METHODS: An online survey was completed during the first six weeks of the first UK-wide lockdown by 3097 respondents, including data for 364 respondents aged 18-24 years. The survey included measures of mental health and indices capturing related psychological and behavioural responses to the pandemic. RESULTS: The mental health of 18- to 24-years-olds in the first 6 weeks of lockdown was significantly poorer than that of older respondents and previously published norms: with 84% reporting symptoms of depression and 72% reporting symptoms of anxiety. Young adults also reported significantly greater loneliness and reduced positive mood, both of which were also associated with greater mental health difficulties. CONCLUSIONS: We contend that the combination of mental health, social and economic considerations may have contributed to the rise of COVID-19 infections in young adults, and ascribing blame to this group will not aid our efforts to regain control of the disease.

Mental health in the UK during the COVID-19 pandemic: cross-sectional analyses from a community cohort study.

OBJECTIVES: Previous pandemics have resulted in significant consequences for mental health. Here, we report the mental health sequelae of the COVID-19 pandemic in a UK cohort and examine modifiable and non-modifiable explanatory factors associated with mental health outcomes. We focus on the first wave of data collection, which examined short-term consequences for mental health, as reported during the first 4-6 weeks of social distancing measures being introduced. DESIGN: Cross-sectional online survey. SETTING: Community cohort study. PARTICIPANTS: N=3097 adults aged ≥18 years were recruited through a mainstream and social media campaign between 3 April 2020 and 30 April 2020. The cohort was predominantly female (n=2618); mean age 44 years; 10% (n=296) from minority ethnic groups; 50% (n=1559) described themselves as key workers and 20% (n=649) identified as having clinical risk factors putting them at increased risk of COVID-19. MAIN OUTCOME MEASURES: Depression, anxiety and stress scores. RESULTS: Mean scores for depression ([Formula: see text] =7.69, SD=6.0), stress ([Formula: see text] =6.48, SD=3.3) and anxiety ([Formula: see text] = 6.48, SD=3.3) significantly exceeded population norms (all p<0.0001). Analysis of non-modifiable factors hypothesised to be associated with mental health outcomes indicated that being younger, female and in a recognised COVID-19 risk group were associated with increased stress, anxiety and depression, with the final multivariable models accounting for 7%-14% of variance. When adding modifiable factors, significant independent effects emerged for positive mood, perceived loneliness and worry about getting COVID-19 for all outcomes, with the final multivariable models accounting for 54%-57% of total variance. CONCLUSIONS: Increased psychological morbidity was evident in this UK sample and found to be more common in younger people, women and in individuals who identified as being in recognised COVID-19 risk groups. Public health and mental health interventions able to ameliorate perceptions of risk of COVID-19, worry about COVID-19 loneliness and boost positive mood may be effective.