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

Summary

In a nationwide matched test-negative design spanning >17 million tests, prior infection conferred strong protection against severe COVID-19 reinfection in both eras, but waned against asymptomatic/symptomatic Omicron reinfections. The study quantifies a clear severity-dependent protection gradient.

Key Findings

• Pre-Omicron prior infection reduced asymptomatic, symptomatic, severe, and critical reinfections by ~81%, 88%, 98%, and 100%, respectively.
• During Omicron, protection against asymptomatic and symptomatic reinfections fell to ~46% and ~53%, while protection against severe and critical reinfections remained ~100%.
• Protection waned over time for mild/asymptomatic Omicron reinfections, but remained strong for severe outcomes.

Clinical Implications

Clinicians can reassure that prior infection strongly protects against severe outcomes, while advising patients—especially high-risk—that mild/silent reinfections remain likely in Omicron circulation and that vaccination/boosters remain important.

Limitations

• Observational design subject to residual confounding and testing behavior biases
• Generalizability may vary with variant mix and public health measures

Future Directions

Integrate hybrid immunity (infection + vaccination) strata, variant-specific analyses, and modeling to optimize booster timing for protecting against severe disease while reducing transmission.