Antibody response and risk of reinfection over two years among the first wave of COVID-19 patients.

OBJECTIVES:To describe the dynamics and factors related with natural and hybrid humoral response against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and risk of reinfection among first wave patients. METHODS:A prospective longitudinal study with periodic serological follow-up after acute onset of all recovered patients with SARS-CoV-2 infection cared in Udine Hospital (March-May 2020). Nucleocapsid (N) protein and spike receptor-binding domain (S-RBD) antibody tests were used to distinguish natural and vaccine induced response. RESULTS:Overall, 153 patients (66 men, mean age 56 years) were followed for a median of 27.3 (IQR 26.9-27.8) months. Seroreversion was 98.5% (95% CI 96.8-99.4) for SARS-CoV-2-N IgM at 1 year and 57.4% (95% CI 51.5-63.5) for SARS-CoV-2-N IgG at 2 years. Initial serological response (HR 0.99, 95% CI 0.99-0.99, p=0.002 for IgM and HR 0.97, 95% CI 0.97-0.98, p<0.001 for IgG) and severity of acute infection (HR 0.62, 95% CI 0.39-0.96, p=0.033 for IgM and HR 0.60, 95% CI 0.37-0.99, p<0.001 for IgG) were independently associated with persistent SARS-CoV-2-N IgM/IgG response. Older age and smoker status were associated with long-term SARS-CoV-2-N IgM and SARS-CoV-2-N IgG respectively (HR 0.75, 95% CI 0.57-0.98, p=0.038; HR 1.77, 95% CI 1.19-2.61, p=0.004 respectively). All patients maintained SARS-CoV-2-S-RBD IgG response at 24 months follow-up. Reinfections occurred in 25/153 (16.3%) patients, mostly during the omicron circulation. Reinfection rates did not differ significantly between SARS-CoV-2-N IgG seronegative and seropositive patients (14/89, 15.7% vs 10/62, 16.1%, p=0.947). Unvaccinated patients had higher risk of reinfection (4/7, 57.1% vs vaccinated 21/146, 14.4%, p=0.014). CONCLUSIONS:First wave patients had durable natural humoral immunity in 40% and anti-S-RBD response in 100% up to two years after infection. Natural humoral response alone was not protective against reinfections with omicron SARS-CoV-2 variants, whereas vaccination was effective to reduce the risk of a new infection.