Neutralization Titers in Vaccinated Patients with SARS-CoV-2 Delta Breakthrough Infections

The continuous emergence of SARS-CoV-2 variants with increased transmission and immune evasion has caused breakthrough infections in the vaccinated population. It is important to determine the threshold of neutralizing antibody titers (NT₅₀) that permit breakthrough infections in humans. Here, we tested the neutralization titers of vaccinated patients who contracted Delta variant. All 64 patients with Delta breakthrough infections exhibited NT₅₀ of less than 70. When the breakthrough sera were tested against USA-WA1/2020 (a strain isolated in late January 2020), 82.8%, 15.6%, and 1.6% of them had the NT₅₀ ranges of <20, 20 to 50, and 50 to 69, respectively. When the same breakthrough sera were tested against Delta-spike SARS-CoV-2, 68.7%, 26.6%, and 4.7% of them had the NT₅₀ ranges of <20, 20 to 50, and 50 to 69, respectively. Overall, the results suggest NT₅₀ of 70 as a potential neutralizing threshold required to prevent Delta breakthrough infections. These clinical laboratory results have implications in vaccine strategy and public health policy. IMPORTANCE Given that neutralizing antibodies play a key role in protection of SARS-CoV-2 infection, it is important to define the neutralization levels in vaccinated individuals when they contracted breakthrough infections. In this study, we analyzed the neutralization levels from 64 vaccinated patients on days 0 to 5 before they tested positive for Delta breakthrough infections. The neutralization titers in these vaccinated individuals were all lower than 70 when they contracted breakthrough infections. The results suggest a neutralization titer of 70 as the potential threshold required to prevent breakthrough infections of Delta variant.