Long-term Specific IgG Response to SARS-CoV-2 Nucleocapsid Protein in Recovered COVID-19 Patients

This study monitored the long-term immune response to severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection in patients who had recovered from coronavirus disease (COVID)-19. Anti-nucleocapsid immunoglobulin G (anti-N IgG) titer in serum samples collected at a single (N=302) or multiple time points (N=229) 3–12 months after COVID-19 symptom onset or SARS-CoV-2 detection in respiratory specimens was measured by semiquantitative chemiluminescent microparticle immunoassay. The 531 patients (966 specimens) were classified according to the presence or absence of pneumonia symptoms. Anti‑N IgG was detected in 87.5% of patients (328/375) at 3 months, 38.6% (93/241) at 6 months, 23.7% (49/207) at 9 months, and 26.6% (38/143) at 12 months. The anti-N IgG seropositivity rate was significantly lower at 6, 9, and 12 months than at 3 months ( P <0.01) and was higher in the pneumonia group than in the non-pneumonia/asymptomatic group at 6 months ( P <0.01), 9 months ( P =0.04), and 12 months ( P =0.04). The rate started to decline 6–12 months after symptom onset. Anti-N IgG sample/cutoff index was positively correlated with age (r=0.192, P <0.01) but negatively correlated with interval between symptom onset and blood sampling (r=−0.567, P <0.01). These findings can guide vaccine strategies in recovered COVID-19 patients.