Making a COVID-19 vaccine that works for everyone: ensuring equity and inclusivity in clinical trials

Coronavirus disease 2019 (COVID-19) mortality and morbidity have been shown to increase with deprivation and impact non-White ethnicities more severely. Despite the extra risk Black, Asian and Minority Ethnicity (BAME) groups face in the pandemic, our current medical research system seems to prioritise innovation aimed at people of European descent. We found significant difficulties in assessing baseline demographics in clinical trials for COVID-19 vaccines, displaying a lack of transparency in reporting. Further, we found that most of these trials take place in high-income countries, with only 25 of 219 trials (11.4%) taking place in lower middle- or low-income countries. Trials for the current best vaccine candidates (BNT162b2, ChadOx1, mRNA-173) recruited 80.0% White participants. Underrepresentation of BAME groups in medical research will perpetuate historical distrust in healthcare processes, and poses a risk of unknown differences in efficacy and safety of these vaccines by phenotype. Limiting trial demographics and settings will mean a lack of global applicability of the results of COVID-19 vaccine trials, which will slow progress towards ending the pandemic

Who funded the research behind the Oxford-AstraZeneca COVID-19 vaccine?

Objectives The Oxford-AstraZeneca COVID-19 vaccine (ChAdOx1 nCoV-19, Vaxzevira or Covishield) builds on two decades of research and development (R&D) into chimpanzee adenovirus-vectored vaccine (ChAdOx) technology at the University of Oxford. This study aimed to approximate the funding for the R&D of ChAdOx and the Oxford-AstraZeneca vaccine and to assess the transparency of funding reporting mechanisms. Methods We conducted a scoping review and publication history analysis of the principal investigators to reconstruct R&D funding the ChAdOx technology. We matched award numbers with publicly accessible grant databases. We filed freedom of information (FOI) requests to the University of Oxford for the disclosure of all grants for ChAdOx R&D. Results We identified 100 peer-reviewed articles relevant to ChAdOx technology published between January 2002 and October 2020, extracting 577 mentions of funding bodies from acknowledgements. Government funders from overseas (including the European Union) were mentioned 158 times (27.4%), the UK government 147 (25.5%) and charitable funders 138 (23.9%). Grant award numbers were identified for 215 (37.3%) mentions; amounts were publicly available for 121 (21.0%). Based on the FOIs, until December 2019, the biggest funders of ChAdOx R&D were the European Commission (34.0%), Wellcome Trust (20.4%) and Coalition for Epidemic Preparedness Innovations (17.5%). Since January 2020, the UK government contributed 95.5% of funding identified. The total identified R&D funding was £104 226 076 reported in the FOIs and £228 466 771 reconstructed from the literature search. Conclusion Our study approximates that public and charitable financing accounted for 97%-99% of identifiable funding for the ChAdOx vaccine technology research at the University of Oxford underlying the Oxford-AstraZeneca vaccine until autumn 2020. We encountered a lack of transparency in research funding reporting

Risks of metabolic syndrome in the ADVANCE and NAMSAL trials

IntroductionThe ADVANCE and NAMSAL trials evaluating antiretroviral drugs have both reported substantial levels of clinical obesity in participants. As one of the main risk factors for metabolic syndrome, growing rates of obesity may drive metabolic syndrome development. This study aims to evaluate the risk of metabolic syndrome in the ADVANCE and NAMSAL trials.MethodsThe number of participants with metabolic syndrome was calculated at baseline and week 192 as central obesity and any of the following two factors: raised triglycerides, reduced HDL-cholesterol, raised blood pressure and raised fasting glucose. Differences between the treatment arms were calculated using the χ2 test.ResultsAcross all visits to week 192, treatment-emergent metabolic syndrome was 15% (TAF/FTC + DTG), 10% (TDF/FTC + DTG) and 7% (TDF/FTC/EFV) in ADVANCE. The results were significantly higher in the TAF/FTC + DTG arm compared to the TDF/FTC/EFV arm (p < 0.001), and the TDF/FTC + DTG vs. the TDF/FTC/EFV arms (p < 0.05) in all patients, and in females. In NAMSAL, the incidence of treatment-emergent metabolic syndrome at any time point was 14% (TDF/3TC + DTG) and 5% (TDF/3TC + EFV) (p < 0.001). This incidence was significantly greater in the TDF/3TC/DTG arm compared to the TDF/3TC/EFV arm in all patients (p < 0.001), and in males (p < 0.001)ConclusionIn this analysis, we highlight treatment-emergent metabolic syndrome associated with dolutegravir, likely driven by obesity. Clinicians initiating or monitoring patients on INSTI-based ART must counsel for lifestyle optimisation to prevent these effects

Comparing prospective incident severe acute respiratory syndrome Coronavirus 2 infection rates during successive waves of Delta and Omicron in Johannesburg, South Africa

In high-risk individuals in Johannesburg, during the Delta coronavirus disease 2019 wave, 22% (125/561) were positive, with 33% symptomatic (2 hospitalizations; 1 death). During Omicron, 56% (232/411) were infected, with 24% symptomatic (no hospitalizations or deaths). The remarkable speed of infection of Omicron over Delta poses challenges to conventional severe acute respiratory syndrome coronavirus 2 control measures