Modelling the end of a Zero-COVID strategy using nirmatrelvir/ritonavir, vaccination and NPIs in Wallis and Futuna

BACKGROUND: Ending Zero-COVID is challenging, particularly when vaccine coverage is low. Considering Wallis and Futuna, a French Zero-COVID territory affected by reluctance to vaccination, low immunity and high levels of comorbidities, we investigate how targeted use of nirmatrelvir/ritonavir (brand name Paxlovid) can complement vaccination and non-pharmaceutical interventions (NPIs), and mitigate the epidemic rebound expected when Zero-COVID ends. METHODS: We developed a discrete age-stratified compartmental model describing SARS-CoV-2 spread and healthcare impact once Wallis and Futuna reopens. It accounts for comorbidity risk groups (CRG), vaccine coverage (2 doses, 3 doses), the effectiveness of vaccines (recent or old injection), treatments and NPIs. In our baseline scenario, cases aged 65+ in intermediate/high CRG and 40+ in high CRG are eligible for treatment. FINDINGS: The epidemic is expected to start 13–20 days after reopening with a doubling time of 1.6-3.7 days. For medium transmission intensity (R(0) = 5), 134 (115–156) hospital admissions are expected within 3 months, with no pharmaceutical measures. In our baseline scenario, admissions are reduced by 11%–21% if 50% of the target group receive treatment, with maximum impact when combined with NPIs and vaccination. The number of hospitalisations averted (HA) per patient treated (PT) is maximum when 65+ in high CRG are targeted (0.124 HA/PT), quickly followed by 65+ in intermediate/high CRG (0.097 HA/PT), and any 65+ (0.093 HA/PT). Expanding the target group increases both PT and HA, but marginal gains diminish. INTERPRETATION: Modelling suggests that test and treat may contribute to the mitigation of epidemic rebounds at the end of Zero-COVID, particularly in populations with low immunity and high levels of comorbidities. FUNDING: RECOVER, VEO, AXA, Groupama, SpF, IBEID, INCEPTION, EMERGEN.