LAUSR

The COVID­19 pandemic has exacerbated pre­existing health inequalities between people with severe mental illness (SMI) and the general population. These inequalities are rightly re­ garded as a human rights issue. Rapidly accumulating evidence indicates that people with SMI are disproportionately affected by COVID­19 infection, showing increased risks of hospitalization and mortality. Attention has recently turned to equitable COVID­19 vaccine allocation. Drawing on ethical frameworks, there have been calls – the first one appearing in this journal – to prioritize people with SMI for vaccination. Having been severely affected by the pandemic, the UK has been among the fastest countries world­ wide to deploy its vaccination plan and one of the few countries to explicitly prioritize persons with SMI. Evidence on vaccine uptake among population subgroups in the UK is emerging. However, more fine­grained evidence of uptake among people with different psychiatric diagnoses is necessary to evaluate de­ livery of vaccination plans and inform mental health practition­ ers. We are investigating COVID­19 outcomes using de­identified electronic health record data from the Greater Manchester Care Record (GMCR), a shared care record for 2.8 million people, comprising real­time information from primary care, hospital admissions and mental health records. Using the GMCR, we compared vaccination rates in a sample of 1,152,831 adults with and without SMI. Individuals were followed up until June 30, 2021, ahead of the UK’s relaxation of COVID­19 restrictions on July 19, 2021. Approval was granted by GMCR’s secondary uses and research governance process. All patients who were registered with a general practitioner in Greater Manchester on January 31, 2020, aged 18 years or over, and with a lifetime diagnosis of SMI recorded in their primary care record, were eligible for inclusion in the SMI sample. This sample was divided into three hierarchically defined, mutually exclusive groups of individuals with schizophrenia or related psychotic disorders (N=46,859), bipolar disorder (N=3,461), and recurrent major depressive disorder (N=134,661). Alongside this, we also obtained a 10% sample of individuals with diagnoses of other depressive disorders, excluding all previously mentioned diagnoses (N=45,586). For comparison purposes, we obtained records for 922,264 age and gender­matched controls with no evidence of SMI or depressive disorders, sampled at a 4:1 ratio the different treatments. SSRIs mainly have direct beneficial effects on the two affective symptoms, which is in line with an individual patient meta­analysis comparing SSRIs to a placebo control condition. The most important indirect effects of SSRIs are found for all cognitive symptoms, including highly clinically relevant symptoms such as suicidal thoughts and loss of interest, and specific arousal/somatic symptoms. SSRIs have detrimental effects on two specific arousal symptoms (i.e., somatic anxiety and agitation), which are common side effects of SSRIs that can be captured by the HDRS. We also found that information from these networks could help in improving the identification of patients who were the most likely to benefit from one treatment relative to the other. That is, patients who suffered more from depressed mood and psychic anxiety and less from somatic anxiety and agitation were the most likely to benefit from SSRIs, whereas the opposite was true for CBT. It is, however, important to note that effect sizes were small (Cohen’s d ranging from .10 in Q1 to –.16 in Q4), somewhat limiting the relevance of findings for clinical practice. A symptom­specific approach is valuable, but also challeng­ ing, as more research is needed on the reliability and validity of assessing individual symptoms with individual (HDRS) items. In addition, the current categorization of symptoms – just like any categorization – may be overly simplistic, as, for example, affec­ tive symptoms may also comprise a cognitive component and cognitive symptoms an affective component. However, we do want to emphasize that a symptom­specific approach is highly promising in capturing the complex clinical response to depres­ sion treatments and in guiding the personalization of treatments.