Evolution of human antibody responses up to one year after SARS-CoV-2 infection (preprint)

Assessment of the kinetics of SARS-CoV-2 antibodies is essential to predict protection against reinfection and durability of vaccine protection. Here, we longitudinally measured Spike (S) and Nucleocapsid (N)-specific antibodies in 1,309 healthcare workers (HCW) including 393 convalescent COVID-19 and 916 COVID-19 negative HCW up to 405 days. From M1 to M7-9 after infection, SARS-CoV-2 antibodies decreased moderately in convalescent HCW in a biphasic model, with men showing a slower decay of anti-N (p=0.02), and a faster decay of anti-S (p=0.0008) than women. At M11-13, anti-N antibodies dramatically decreased (half-life: 210 days) while anti-S stabilized (half-life: 630 days) at a median of 2.41 log Arbitrary Units (AU)/mL (Interquartile Range (IQR): 2.11 -2.75). One case of reinfection was recorded in convalescent HCW (0.47 per 100 person-years) versus 50 in COVID-19 negative HCW (10.11 per 100 person-years). Correlation with live-virus neutralization assay revealed that variants D614G and B.1.1.7, but not B.1.351, were sensitive to anti-S antibodies at 2.3 log AU/mL, while IgG [≥] 3 log AU/mL neutralized all three variants. After SARS-CoV-2 vaccination, anti-S levels reached 4 logs regardless of pre-vaccination IgG levels, type of vaccine, and number of doses. Our study demonstrates a long-term persistence of anti-S IgG antibodies that may protect against reinfection. By significantly increasing cross-neutralizing antibody titers, a single-dose vaccination strengthens protection against escape mutants.

Sex differences in the decline of neutralizing antibodies to SARS-CoV-2 (preprint)

The evolution of SARS-CoV-2 humoral response in infected individuals remains poorly characterized. Here, we performed a longitudinal study of sera from 308 RT-qPCR+ individuals with mild disease, collected at two time-points, up to 6 months post-onset of symptoms (POS). We performed two anti-S and one anti-N serology assays and quantified neutralizing antibodies (NAbs). At month 1 (M1), males, individuals > 50 years of age or with a body mass index (BMI) > 25 exhibited higher levels of antibodies. Antibody levels decreased over time. At M3-6, anti-S antibodies persisted in 99% of individuals while anti-N IgG were measurable in only 59% of individuals. The decline in anti-S and NAbs was faster in males than in females, independently of age and BMI. Our results show that some serology tests are less reliable overtime and suggest that the duration of protection after SARS-CoV-2 infection or vaccination will be different in women and men.