Bang Zheng

The interleukin-6 (IL-6) inhibitors tocilizumab and sarilumab have been repurposed for COVID-19 treatment. However, discrepancies exist across global and national COVID-19 guidelines, with limited data on the comparative effectiveness between these therapeutics especially during the delta/omicron periods. With the approval of NHS England and Public Health Scotland, we compared their effectiveness among adults hospitalised with COVID-19 using electronic health records data through the OpenSAFELY-TPP (England) and EAVE II (Scotland) platforms. Following the target trial emulation framework, 10,487 patients treated between July 2021 and February 2022, when both drugs were frequently prescribed, were included. In England, 1150 (20.1%) of 5710 participants receiving tocilizumab died by day 28 compared with 820 (20.4%) of 4025 participants receiving sarilumab (adjusted hazard ratio [aHR] 1.07, 95% CI 0.96-1.19). In Scotland, 114 (29.4%) of 388 participants receiving tocilizumab died by day 28 compared with 97 (27.0%) of 359 participants receiving sarilumab (aHR 0.92, 95% CI 0.68-1.23). There was no evidence of a difference in time to hospital discharge between the groups, and no credible effect modification by variant of concern, vaccination status, age, sex, ethnicity, body mass index, or comorbidities. Our findings provide supportive evidence for both drugs as alternative therapeutic options in COVID-19 in-patient management.

Background Between December 2021 and June 2023, COVID-19 medicine delivery units (CMDUs) in England offered antiviral medicines and neutralising monoclonal antibodies (paxlovid, sotrovimab, molnupiravir, remdesivir, and casirivimab/imdevimab) to non-hospitalised individuals with COVID-19, identified at high risk of developing severe outcomes. In order to prescribe and supply medicines CMDUs were required to notify NHS England of every prescription via an electronic form. This data was supplied to OpenSAFELY, a secure analytics platform for electronic patient records, as the COVID-19 “Therapeutics” dataset. We aimed to explore the analytic potential of the dataset for research into the use and effectiveness of these therapeutics offered by CMDUs. Methods Working on behalf of NHS England, we assessed the content and data quality of the COVID-19 Therapeutics dataset within OpenSAFELY. We focused on therapeutics provided in outpatient settings by CMDUs. We described for each field the: data format, completeness and summarised its content. Results The COVID-19 Therapeutics dataset contained 18 columns and 58,590 rows of data, for 54,435 distinct patient IDs (92.9%) treated in outpatient settings. The dataset was well-structured, with completeness of almost all fields of 100%. The dataset included details on the specific treatment received, date administered, high-risk group(s) to which the patient belonged and the region in which they were assessed. Conclusion The COVID-19 Therapeutics dataset is well-structured, complete, and is suitable for research. It is linked to other data sources in OpenSAFELY (e.g., primary care), enabling important research on the impact of treatment and health disparities.

Overcoming the COVID-19 pandemic, which resulted in great loss of life worldwide and shook the global economy, required individuals' willingness and ability to behave prosocially. To contribute to the understanding of predictors of prosociality, we used multilevel models to test three previously established pathways to prosocial behavior, which we call the “broaden and build”, compensation, and incapacity pathways. We also tested whether these three paths are mediated by general well-being, and moderated by collective disempowerment, i.e., individuals’ belief that external societal forces have made it harder for people like them to function effectively. Participants from 39 countries (N = 59987) were surveyed on their willingness to engage in prosocial behaviors in the context of the pandemic. The “broaden and build” pathway was supported: positive affect was associated with willingness to engage in prosocial behavior via higher well-being. Two (in)capacity paths were also supported: financial strain and negative affect were both negatively associated with prosociality via lower well-being. A compensation pathway was also observed: Controlling for lower well-being, negative affect was associated with greater prosociality. Finally, differences in disempowerment moderated the affective pathways: higher disempowerment strengthened the positive association of positive affect with prosociality via well-being, and buffered the negative affect incapacity path.

Objectives To examine the impact of the COVID-19 pandemic on deprivation-related inequalities in hospitalisations for cardiovascular disease (CVD) conditions in Denmark and England between March 2018 and December 2021. Design Time-series studies in England and Denmark. Setting With the approval of National Health Service England, we used English primary care electronic health records, linked to secondary care and death registry data through the OpenSAFELY platform and nationwide Danish health registry data. Participants We included adults aged 18 and over without missing age, sex or deprivation information. On 1 March 2020, 16 234 700 people in England and 4 491 336 people in Denmark met the inclusion criteria. Primary outcome measures Hospital admissions with the primary reason for myocardial infarction (MI), ischaemic or haemorrhagic stroke, heart failure and venous thromboembolism (VTE). Results We saw deprivation gradients in monthly CVD hospitalisations in both countries, with differences more pronounced in Denmark. Based on pre-pandemic trends, in England, there were an estimated 2608 fewer admissions than expected for heart failure in the most deprived quintile during the pandemic compared with an estimated 979 fewer admissions in the least deprived quintile. For all other outcomes, there was little variation by deprivation quintile. In Denmark, there were an estimated 1013 fewer admissions than expected over the pandemic for MI in the most deprived quintile compared with 619 in the least deprived quintile. Similar trends were seen for stroke and VTE, though absolute numbers were smaller. Heart failure admissions were similar to pre-pandemic levels with little variation by deprivation quintile. Conclusions Overall, we did not find that the pandemic substantially worsened pre-existing deprivation-related differences in CVD hospitalisations, though there were exceptions in both countries.

Background Between December 2021 and June 2023, COVID-19 medicine delivery units (CMDUs) in England offered antiviral medicines and neutralising monoclonal antibodies to non-hospitalised individuals with COVID-19, identified at high risk of developing severe outcomes. In order to prescribe and supply medicines CMDUs were required to notify NHS England of every prescription via an electronic form. This data was supplied to OpenSAFELY, a secure analytics platform for electronic patient records, as the COVID-19 “Therapeutics” dataset. We aimed to explore the analytic potential of the dataset for research into the use and effectiveness of these therapeutics offered by CMDUs. Methods Working on behalf of NHS England, we assessed the content and data quality of the COVID-19 Therapeutics dataset within OpenSAFELY. We focused on therapeutics provided in outpatient settings by CMDUs. We described for each field the: data format, completeness and summarised its content. Results The COVID-19 Therapeutics dataset contained 18 columns and 58,590 rows of data, for 54,435 distinct patient IDs (92.9%) treated in outpatient settings. The dataset was well-structured, with completeness of almost all fields of 100%. The dataset included details on the specific treatment received, date administered, high-risk group(s) to which the patient belonged and the region in which they were assessed. The values were largely plausible. Conclusion The COVID-19 Therapeutics dataset is well-structured, complete, and is suitable for research. The dataset is made available for all researchers in OpenSAFELY where it is linked to other data sources (e.g., primary care), enabling important research.

Background: In patients with COVID-19 requiring supplemental oxygen, dexamethasone reduces acute severity and improves survival, but longer-term effects are unknown. We hypothesised that systemic corticosteroid administration during acute COVID-19 would be associated with improved health-related quality of life (HRQoL) one year after discharge. Methods: Adults admitted to hospital between February 2020 and March 2021 for COVID-19 and meeting current guideline recommendations for dexamethasone treatment were included using two prospective UK cohort studies. HRQoL, assessed by EQ-5D-5L utility index, pre-hospital and one year after discharge were compared between those receiving corticosteroids or not after propensity weighting for treatment. Secondary outcomes included patient reported recovery, physical and mental health status, and measures of organ impairment. Sensitivity analyses were undertaken to account for survival and selection bias. Findings: In 1,888 participants included in the primary analysis, 1,149 received corticosteroids. There was no between-group difference in EQ-5D-5L utility index at one year (mean difference 0.004, 95% CI: -0.026 to 0.034, p = 0.77). A similar reduction in EQ-5D-5L was seen at one year between corticosteroid exposed and non-exposed groups (mean (SD) change -0.12 (0.22) vs -0.11 (0.22), p = 0.32). Overall, there were no differences in secondary outcome measures. After sensitivity analyses modelled using a larger cohort of 109,318 patients admitted to hospital with COVID-19, EQ-5D-5L utility index at one year remained similar between the two groups. Interpretation: Systemic corticosteroids for acute COVID-19 have no impact on the large reduction in HRQoL one year after hospital discharge. Treatments to address this are urgently needed. Take home message: Systemic corticosteroids given for acute COVID-19 do not affect health-related quality of life or other patient reported outcomes, physical and mental health outcomes, and organ function one year after hospital discharge

Background: Limited evidence is available regarding the anaphylaxis risk following the administration of COVID-19 therapeutics. Methods: With the approval of NHS England, we conducted a descriptive analysis of anaphylaxis events following COVID-19 treatment for non-hospitalised patients using routine clinical data from 24 million people in England in the OpenSAFELY-TPP database. Results: We found that the risk of anaphylaxis during the 29 days follow-up was 0.04% for sotrovimab users, 0.03% for Paxlovid users, <0.05% for molnupiravir users, and 0.02% for untreated high-risk patients. Conclusions: Our results suggest that anaphylaxis risks were similar between sotrovimab and Paxlovid users, which were not appreciably different from untreated patients.

Background: Due to limited inclusion of patients on kidney replacement therapy (KRT) in clinical trials, the effectiveness of coronavirus disease 2019 (COVID-19) therapies in this population remains unclear. We sought to address this by comparing the effectiveness of sotrovimab against molnupiravir, two commonly used treatments for non-hospitalised KRT patients with COVID-19 in the UK.Methods: With the approval of National Health Service England, we used routine clinical data from 24 million patients in England within the OpenSAFELY-TPP platform linked to the UK Renal Registry (UKRR) to identify patients on KRT. A Cox proportional hazards model was used to estimate hazard ratios (HRs) of sotrovimab versus molnupiravir with regards to COVID-19-related hospitalisations or deaths in the subsequent 28 days. We also conducted a complementary analysis using data from the Scottish Renal Registry (SRR).Results: Among the 2367 kidney patients treated with sotrovimab (n = 1852) or molnupiravir (n = 515) between 16 December 2021 and 1 August 2022 in England, 38 cases (1.6%) of COVID-19-related hospitalisations/deaths were observed. Sotrovimab was associated with substantially lower outcome risk than molnupiravir {adjusted HR 0.35 [95% confidence interval (CI) 0.17–0.71]; P = .004}, with results remaining robust in multiple sensitivity analyses. In the SRR cohort, sotrovimab showed a trend toward lower outcome risk than molnupiravir [HR 0.39 (95% CI 0.13–1.21); P = .106]. In both datasets, sotrovimab had no evidence of an association with other hospitalisation/death compared with molnupiravir (HRs ranged from 0.73 to 1.29; P > .05).Conclusions: In routine care of non-hospitalised patients with COVID-19 on KRT, sotrovimab was associated with a lower risk of severe COVID-19 outcomes compared with molnupiravir during Omicron waves.