Comparative effectiveness of one versus two doses of COVID-19 vaccines in Qatar: Evidence of converging protection over time

Background: Supply constraints during the coronavirus disease 2019 (COVID-19) pandemic led to vaccination strategies that prioritized first-dose coverage. To evaluate the merit of this approach, this study compared the development of protection gainst severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 following a single dose versus two doses across three widely used vaccine platforms. Methods: National, matched, test-negative case-control analyses were conducted in Qatar between December 1, 2020, and December 18, 2021, to evaluate vaccine effectiveness. The one-dose analysis included 227,309 cases and 4,170,786 controls; the two-dose analysis included 234,314 cases and 6,445,858 controls. Results: For BNT162b2, single-dose effectiveness against infection increased steadily from 9.9 % (95 % CI: 6.7-13.0 %) in the first two weeks post-vaccination to 71.5 % (95 % CI: 45.5-85.1 %) by month 3, closely approaching the 74.5 % (95 % CI: 72.9-76.0 %) effectiveness observed after the two-dose primary series. Similar trends were observed for mRNA-1273 and ChAdOx1 nCoV-19, with mRNA-1273 reaching two-dose levels of effectiveness as early as month 2. In contrast to the gradual buildup of protection against infection, single-dose effectiveness against severe, critical, or fatal COVID-19 increased rapidly for all three vaccines, exceeding 85 % by day 21 and closely matching the protection achieved after two doses. Conclusion: A single COVID-19 vaccine dose provides rapid, strong protection against severe outcomes, supporting first-dose prioritization during supply constraints. The slower development of protection against infection highlights the second dose's role in accelerating the immune response. Antigen dose appears to in-fluence the speed of protection buildup.