Protection conferred by SARS-CoV-2 infection across a spectrum of reinfection symptoms and severities

Background SARS-CoV-2 infection is associated with protection against reinfection. This study analysed this protection across different reinfection symptoms and severities, comparing the preomicron and omicron eras.Methods A nationwide, matched, test-negative, case-control study was conducted in Qatar from 5 February 2020 to 12 March 2024. The preomicron analysis used a sample of 509 949 positive and 8 494 782 negative tests, while the omicron analysis included 682 257 positive and 6 904 044 negative tests. Data were sourced from Qatar's national databases for COVID-19 laboratory testing, vaccination, hospitalisation and death.Results Effectiveness of preomicron infection against preomicron reinfection was estimated at 80.9% (95% CI: 79.1% to 82.6%) for asymptomatic reinfection, 87.5% (95% CI: 86.1% to 88.9%) for symptomatic reinfection, 97.8% (95% CI: 95.7% to 98.9%) for severe COVID-19 reinfection, 100.0% (95% CI: 97.5% to 100.0%) for critical COVID-19 reinfection and 88.1% (95% CI: 50.3% to 97.2%) for fatal COVID-19 reinfection. For omicron infection against omicron reinfection, the estimates were 46.4% (95% CI: 36.9% to 54.4%) for asymptomatic reinfection, 52.8% (95% CI: 44.4% to 60.0%) for symptomatic reinfection, 100.0% (95% CI: 55.4% to 100.0%) for severe COVID-19 reinfection, 100.0% (95% CI: 15.1% to 100.0%) for critical COVID-19 reinfection, and 75.2% (95% CI: -58.8% to 97.5%) for fatal COVID-19 reinfection. Effectiveness over time since previous infection showed no discernible decline in protection against all forms of reinfection in the preomicron era, but a rapid decline against asymptomatic and symptomatic reinfections in the omicron era.Conclusions A gradient of protection against reinfection is evident, with the highest protection observed against severe forms of COVID-19. Over time, this gradient becomes more pronounced, as protection against asymptomatic and symptomatic reinfections decreases, while protection against severe outcomes remains strong.