Protection of natural infection against reinfection with SARS-CoV-2 JN.1 variant

Introduction: Evidence at the level of neutralizing antibodies suggests that the SARS-CoV-2 JN.1 variant demonstrates increased immune evasion compared to its parent lineage BA.2.86 and to recently circulating variants, such as XBB.1.5 and EG.5.1. JN.1 has also exhibited a growth advantage over other variants and triggered large SARS-CoV-2 waves in various countries. Methods: A national, matched, test-negative, case-control study was conducted on Qatar's population between December 4, 2023-February 12, 2024, to estimate the effectiveness of natural infection in preventing reinfection with JN.1. Subgroup analyses estimating effectiveness against specifically symptomatic reinfection, and by vaccination status, were conducted. Results: The overall effectiveness of previous infection in preventing reinfection with JN.1, regardless of symptoms, was estimated at 1.8% (95% CI: -9.3-12.6%). This effectiveness demonstrated a rapid decline over time since the previous infection, decreasing from 82.4% (95% CI: 40.9-94.7%) within 3 to less than 6 months after the previous infection to 50.9% (95% CI: -11.8-78.7%) in the subsequent 3 months, and further dropping to 18.3% (95% CI: -34.6-56.3) in the subsequent 3 months. Ultimately, it reached a negligible level after one year. The effectiveness was estimated at 49.1% (95% CI: 20.4-67.5%) during the first year and at -2.5% (95% CI: -13.5-9.0%) thereafter. The effectiveness against symptomatic reinfection with JN.1 demonstrated a similar pattern to that observed for any reinfection, estimated at -2.3% (95% CI: -14.4-10.3%). Subgroup analyses for unvaccinated and vaccinated individuals yielded results similar to those of the main analysis. Discussion: The protection of natural infection against reinfection was strong among those who were infected within the last 6 months, with variants such as XBB*. However, this protection waned rapidly and was entirely lost one year after the previous infection. These findings support a considerable immune evasion by JN.1, and that this immune evasion led to the observed rapid waning of the protection against JN.1, a pattern for the effect of immune evasion first characterized for SARS-CoV-2 following the omicron variant emergence at the end of 2021. Conclusions: The findings highlight the need for ongoing surveillance of SARS-CoV-2 variants and periodic assessment of COVID-19 vaccination strategies.