Alternative epidemic indicators for COVID-19: a model-based assessment of COVID-19 mortality ascertainment in three settings with incomplete death registration systems (preprint)

Not all COVID-19 deaths are officially reported and, particularly in low-income and humanitarian settings the magnitude of such reporting gaps remain sparsely characterised. Alternative data sources, including burial site worker reports, satellite imagery of cemeteries and social-media-conducted surveys of infection, may offer solutions. By merging these data with independently conducted, representative serological studies within a mathematical modelling framework, we aim to better understand the range of under-reporting using the example of three major cities: Addis Ababa (Ethiopia), Aden (Yemen) and Khartoum (Sudan) during 2020. We estimate 69% - 100%, 0.8% - 8.0% and 3.0% - 6.0% of COVID-19 deaths were reported in these three settings, respectively. In future epidemics, and in settings where vital registrations systems are absent or limited, using multiple alternative data sources could provide critically-needed, improved estimates of epidemic impact. However, ultimately, functioning vital registration systems are needed to ensure that, in contrast to COVID-19, the impact of future pandemics or other drivers of mortality are reported and understood worldwide.

Estimating long-term vaccine effectiveness against SARS-CoV-2 variants: a model-based approach (preprint)

With the ongoing evolution of the SARS-CoV-2 virus, variant-adapted vaccines are likely to be required. Given the challenges of conducting clinical trials against a background of widespread infection-induced immunity, updated vaccines are likely to be adopted based on immunogenicity data. We extended a modelling framework linking immunity levels and protection and fitted the model to vaccine effectiveness data from England for three vaccines (Oxford/AstraZeneca AZD1222, Pfizer-BioNTech BNT162b2, Moderna mRNA-1273) and two variants (Delta and Omicron) to predict longer-term effectiveness against mild disease, hospitalisation and death. We use these model fits to predict the effectiveness of the Moderna bivalent vaccine (mRNA1273.214) against the Omicron variant using immunogenicity data. Our results suggest sustained protection against hospitalisation and death from the Omicron variant over the first six months following boosting with the monovalent vaccines but a gradual waning to moderate protection after 1 year (median predicted vaccine effectiveness at 1 year in 65+ age group: AZD1222 38.9%, 95% CrI 31.8%-46.8%; BNT162b2 53.3%, 95% CrI 49.1%-56.9%; mRNA-1273 60.0%, 95% CrI 56.0%-63.6%). Furthermore, we predict almost complete loss of protection against mild disease over this period (mean predicted effectiveness at 1 year 7.8% for AZD1222, 13.2% for BNT162b2 and 16.7% for mRNA-1273). Switching to a second booster with the bivalent mRNA1273.214 vaccine against Omicron BA.1/2 is predicted to prevent nearly twice as many hospitalisations and deaths over a 1-year period compared to administering a second booster with the monovalent mRNA1273 vaccine. Ongoing production and administration of variant-specific vaccines are therefore likely to play an important role in protecting against severe outcomes from the ongoing circulation of SARS-CoV-2.