Single-dose BNT162b2 mRNA COVID-19 vaccine significantly boosts neutralizing antibody response in health care workers recovering from asymptomatic or mild natural SARS-CoV-2 infection

Vicenti, Ilaria; Gatti, Francesca; Scaggiante, Renzo; Boccuto, Adele; Zago, Daniela; Basso, Monica; Dragoni, Filippo; Zazzi, Maurizio; Parisi, Saverio Giuseppe

Objectives To measure SARS-CoV-2 neutralizing antibody (NtAb) titres in previously infected or uninfected healthcare workers (HCW) who received one or two doses of BNT162b2 mRNA COVID-19 vaccine. Methods NtAbs were titrated as dose inhibiting 50% virus replication (ID50) by live virus microneutralization. Forty-one HCW recovering from mild or asymptomatic infection were evaluated on the day of first-dose vaccination (T1_inf) and 21 days later (T2_inf). Sixteen uninfected HCW were evaluated 20 days after the first dose (T2_uninf) and 20 days after the second dose of vaccine (T3_inf). Results At T2_inf, but not at T1_inf, there was a significant correlation between days from diagnosis (median [IQR] 313 [285-322]) and NtAb levels (p = 0.011). NtAb titres increased at T2_inf with respect to T1_inf (1544 [732-2232] vs. 26 [10-88]; p < 0.001). Likewise, there was a significant increase in NtAb titres at T3_uninf with respect to T2_uninf (183 [111-301] vs. 5 [5-15]; p < 0001). However, NtAb levels at T2_inf were significantly higher than those at T2_uninf and T3_uninf (p < 0.0001 for both analyses). Conclusions A single vaccination in people with mild or asymptomatic previous infection further boosts SARS-CoV-2 humoral immunity to levels higher than those obtained by complete two-vaccination in uninfected subjects.