Chris Robertson

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.

Estimating COVID-19 vaccine effectiveness (VE) by time since vaccination (TSV) is essential for understanding how protection may change over time and enables meaningful comparisons across studies. This is important for accurate comparisons of VE against different SARS-CoV-2 variants/sublineages, across age groups, during different periods post vaccination campaign, or by vaccine type/brand. We provide recommendations for case–control VE studies on estimating and reporting VE analyses by TSV, with the aim of improving quality of these estimates. Our recommendations cover study design and pre-analysis considerations, descriptive analyses, choice of categories of TSV, categorical and continuous modeling approaches, and best practices for reporting VE by TSV. Using a real-life case–control study, we apply these recommendations and include accompanying statistical scripts in R and Stata. These recommendations will serve as a practical resource for researchers conducting VE analyses by TSV. We encourage ongoing refinement of them through input from other study groups.

Background: Electronic health care databases are widely used for epidemiological studies. However, they may contain inactive records of individuals no longer participating in the health care system. These inactive records create a methodological challenge as they systematically appear as unexposed with no recorded outcomes. Given the widespread health care system engagement during the COVID-19 pandemic, the English National Health Service (NHS), which hosts a national pandemic planning and research dataset with linkage to COVID-19 vaccination and emergency care data, makes it an ideal setting to identify the extent of overrepresentation due to inactive health care records and assess ways to mitigate them. Objective: The objective of this study is to report any differences between the general practitioner–registered adult population size based on health care records compared to census estimates for England and to apply methodology that could be used to correct for such differences. Methods: We compared the number of adult patients within the General Practice Extraction Service Data for Pandemic Planning and Research (GDPPR) with a valid general practitioner registration as of 1st October 2021, with estimates published by the Office for National Statistics (ONS) for the English population. We used an approach adapted from a weighting method to correct for non-response bias in surveys and down-weighted individuals with no evidence of recent activity in their records. Results: There were 61,194,033 registered NHS patients (in the GDPPR) compared with 56,550,138 in the ONS census-based population. De-duplication on NHS number reduced the population to 57,876,641, including 46,835,968 adults, with the biggest overrepresented group aged 30‐45 years. Of the 46,835,986, 1,121,954 (2.4%) individuals had their initial weights down-weighted due to non-engagement with the health care system since January 2019. The down-weighting removed most of the differences between NHS and ONS populations. Conclusions: There are notable differences in the adult population size as per GDPPR when compared to census estimates. While the overall population size in the GDPPR data was seen to be inflated when compared to ONS census estimates, this was differential with respect to sociodemographic variables. A weighting-based approach can be applied to correct for the inflated denominator. Not correcting for it in large health care datasets, including the English NHS data, could introduce selection bias in epidemiological studies.

The interleukin-6 (IL-6) inhibitors tocilizumab and sarilumab have been repurposed for COVID-19 treatment. However, discrepancies still 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.

Early research into SARS-CoV-2 infection and COVID-19 in children and young people (CYP) primarily focused on clinical presentation, transmission patterns, viral load, diagnostic approaches, treatment strategies, and the debates surrounding vaccination in this age group [1,2]. Background information on vaccination of CYP to prevent COVID-19 and the related research on vaccine effectiveness (VE) and safety […]

In our previous two editorials, published in December 2021, we reviewed early research evidence into SARS-CoV-2 infection and the COVID-19 pandemic in children and young people (CYP) [1,2]. In 2020 and 2021, the research in many countries primarily focussed on clinical presentation, transmission patterns, viral load, diagnostic approaches, and treatment strategies [1]. In CYP, diagnostic […]

Background: The COVID-19 pandemic and the ensuing implementation of control measures caused widespread societal disruption. These disruptions may also have affected community transmission and seasonal circulation patterns of endemic respiratory viruses. Objective: We aimed to investigate the impact of COVID-19–related disruption on influenza-related emergency hospital admissions and deaths in Wales in the first 2 years of the pandemic. Methods: A descriptive analysis of influenza activity was conducted using anonymized pathology, hospitalization, and mortality data from the Secure Anonymised Information Linkage Databank in Wales. The annual incidence of emergency hospitalizations and deaths with influenza-specific diagnosis codes between January 1, 2015, and December 31, 2021, was estimated. Case definitions of emergency hospitalization and death required laboratory confirmation with a polymerase chain reaction test. Trends of admissions and deaths were analyzed monthly and yearly. We conducted 2 sensitivity analyses by extending case definitions to include acute respiratory illnesses with a positive influenza test and by limiting admissions to those with influenza as the primary diagnosis. We also examined yearly influenza testing trends to understand changes in testing behavior during the pandemic. Results: We studied a population of 3,235,883 Welsh residents in 2020 with a median age of 42.5 (IQR 22.9–61.0) years. Influenza testing in Wales increased notably in the last 2 months of 2020, and particularly in 2021 to 39,720 per 100,000 people, compared to the prepandemic levels (1343 in 2019). The percentage of influenza admissions matched to an influenza polymerase chain reaction test increased from 74.8% (1890/2526) in 2019 to 85.2% (98/115) in 2021. However, admissions with a positive test per 100,000 population decreased from 17.0 in 2019 to 2.7 and 0.6 in 2020 and 2021, respectively. Similarly, deaths due to influenza with a positive influenza test per 100,000 population decreased from 0.4 in 2019 to 0.0 in 2020 and 2021. Sensitivity analyses showed similar patterns of decreasing influenza admissions and deaths in the first 2 years of the COVID-19 pandemic. Conclusions: Nonpharmaceutical interventions to control COVID-19 were associated with a substantial reduction in the transmission of the influenza virus, with associated substantial reductions in hospital cases and deaths observed. Beyond the pandemic context, consideration should be given to the role of nonpharmaceutical community-driven interventions to reduce the burden of influenza.