ABSTRACT
Aim: Evaluate the kinetics of antibody, plasmablasts (PB) and memory B cells (MBCs) from day 7 up to 8 months following mild COVID-19 Methods: This observational study enrolled 31 RT-PCR confirmed acute mild COVID-19 patients longitudinal followed ups at six visits: 0, +7, +14 +28, +56 and +200 days post onset of symptoms (dpos). Antibodies against S1 domain of the spike and N (nucleocapside) proteins of SARSCoV- 2 were evaluated using ELISA, while neutralization was quantified by a commercially available surrogate (sVNT) assay. Specific PB and MBC were assessed by ELISPOT Results: During mild COVID-19, anti-S1, anti-N as well as neutralizing antibodies were elicited during the first 3 weeks pos, reached a peak between 20-30 dpos and decayed slowly, however 80% of patients had detectable neutralizing antibodies at +200 dpos. S1-specific IgA and IgM PB reached their peak around +14 days while IgG slow increased. All patients developed anti-S1 IgG MBCs by one month that peaked at 49 dpos and remained stable up to 245dpos;anti-N IgG MBCs kinetics was similar but their magnitude was reduced. We next correlated humoral with cellular immune responses and found that anti-S1 IgG and IgA titers at visits +14 and +28 days correlated with plasmablast, while there was a poor correlation between antibody titers and MBCs at visit +56 days that was lost at visit +200 days Conclusion: Mild COVID-19 elicits early and long lasting neutralizing antibodies Antigen-specific PB correlated with early antibody titers, while specific MBCs frequencies were stable and independent of antibody titers up to 245 dpos.
ABSTRACT
OBJECTIVES: To evaluate longitudinally the persistence of humoral immunity for up to 6 months in a cohort of hospital employees with mild coronavirus disease 2019 (COVID-19). METHODS: We measured anti-RBD (receptor binding domain of viral spike protein), anti-N (viral nucleoprotein) and neutralizing antibodies at 1, 3 and 6 months after mostly mild COVID-19 in 200 hospital workers using commercial ELISAs and a surrogate virus neutralization assay. RESULTS: Antibodies specific for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persisted in all participants for up to 6 months. Anti-RBD geometric mean concentrations (GMCs) progressively increased between months 1 (74.2 U/mL, 95%CI: 62.7-87.8), 3 (103.2 U/mL, 95%CI: 87.9-121.2;p < 0.001), and 6 (123.3 U/mL, 95%CI: 103.4-147.0;p < 0.001) in the whole cohort. Anti-N antibodies were detectable in >97% at all times. Neutralizing antibodies were detectable in 99.5% of participants (195/196) at 6 months post infection. Their GMC progressively decreased between months 1 (20.1 AU/mL, 95%CI: 16.9-24.0), 3 (15.2 AU/mL, 95%CI: 13.2-17.6;p < 0.001) and 6 (9.4 AU/mL, 95%CI: 7.7-11.4;p < 0.001). RBD-ACE2-inhibiting antibody titres and anti-RBD antibody concentrations strongly correlated at each timepoint (all r > 0.86, p < 0.001). Disease severity was associated with higher initial anti-RBD and RBD-ACE2-inhibiting antibody titres, but not with their kinetics. CONCLUSIONS: Neutralizing antibodies persisted at 6 months in almost all participants, indicating more durability than initially feared. Anti-RBD antibodies persisted better and even increased over time, possibly related to the preferential detection of progressively higher-affinity antibodies.