Project description:With vaccines for coronavirus disease 2019 (COVID-19) being introduced in countries across the world, policy makers are facing many practical considerations about how best to implement a vaccination programme. The supply of vaccines is insufficient for the global population, so decisions must be made as to which groups are prioritised for any vaccination and when. Furthermore, the aims of vaccination programmes will differ between countries, with some prioritising economic benefits that could stem from the relaxation of non-pharmaceutical interventions and others seeking simply to reduce the number of COVID-19 cases or deaths. This paper aims to share the experiences and lessons learned from conducting economic evaluations in Singapore and Thailand on hypothetical COVID-19 vaccines to provide a basis for other countries to develop their own contextualised economic evaluations, with particular focus on the key uncertainties, technical challenges, and characteristics that modellers should consider in partnership with key stakeholders. Which vaccines, vaccination strategies, and policy responses are most economically beneficial remains uncertain. It is therefore important for all governments to conduct their own analyses to inform local policy responses to COVID-19, including the implementation of COVID-19 vaccines in both the short and the long run. It is essential that such studies are designed, and ideally conducted, before vaccines are introduced so that policy decisions and implementation procedures are not delayed.
Project description:The SARS-CoV-2 Delta (B.1.617.2) variant is capable of infecting vaccinated persons. An open question remains as to whether deficiencies in specific vaccine-elicited immune responses result in susceptibility to vaccine breakthrough infection. We investigated 55 vaccine breakthrough infection cases (mostly Delta) in Singapore, comparing them against 86 vaccinated close contacts who did not contract infection. Vaccine breakthrough cases showed lower memory B cell frequencies against SARS-CoV-2 receptor binding domain (RBD). Compared to plasma antibodies, antibodies secreted by memory B cells retained a higher fraction of neutralizing properties against the Delta variant. Inflammatory cytokines including IL-1β and TNF were lower in vaccine breakthrough infections than primary infection of similar disease severity, underscoring the usefulness of vaccination in preventing inflammation. This report highlights the importance of memory B cells against vaccine breakthrough, and suggests that lower memory B cell levels may be a correlate of risk for Delta vaccine breakthrough infection.
Project description:Early in the COVID-19 pandemic, type 2 diabetes (T2D) was marked as a risk-factor for severe disease. Inflammation is central to the aetiology of both conditions where immune responses influence disease course. Identifying at-risk groups through immuno-inflammatory signatures can direct personalised care and help develop potential targets for precision therapy. This observational study characterised immunophenotypic variation associated with COVID-19 severity in T2D. Broad-spectrum immunophenotyping quantified 15 leukocyte populations in circulation from a cohort of 45 hospitalised COVID-19 patients with and without T2D. Lymphocytopenia, of CD8+ lymphocytes, was associated with severe COVID-19 and intensive care admission in non-diabetic and T2D patients. A morphological anomaly of increased monocyte size and monocytopenia of classical monocytes were specifically associated with severe COVID-19 in patients with T2D requiring intensive care. Over-expression of inflammatory markers reminiscent of the type-1 interferon pathway underlaid the immunophenotype associated with T2D. These changes may contribute to severity of COVID-19 in T2D. These findings show characteristics of severe COVID-19 in T2D as well as provide evidence that type-1 interferons may be actionable targets for future studies.