COVID-BioB Cohort Study: the neutralizing antibody response to SARS-CoV-2 in symptomatic COVID-19 is persistent and critical for virus control and survival.

Dispinseri, S.; Secchi, M.; Pirillo, M. F.; Tolazzi, M.; Borghi, M.; Brigatti, C.; De Angelis, M. L.; Baratella, M.; Bazzigaluppi, E.; Venturi, G.; Sironi, F.; Canitano, A.; Marzinotto, I.; Tresoldi, C.; Ciceri, F.; Piemonti, L.; Negri, D.; Cara, A.; Lampasona, V.; Scarlatti, G.

Understanding how antibody to SARS-CoV-2 evolve during infection may provide important insight into therapeutic approaches to prevent fatal COVID-19 illness and vaccines. Here, we profile the antibody response of 162 well-characterized COVID-19 symptomatic patients followed longitudinally for up to eight months from symptom onset. Using two newly developed assays we detect SARS-CoV-2 neutralization and antibodies binding to Spike antigens and nucleoprotein as well as to Spike S2 antigen of seasonal beta-coronaviruses, and to hemagglutinin of the H1N1 flu virus. Presence of neutralizing antibodies withing the first weeks from symptom onset correlates with time to a negative swab result (p=0.002) while lack of neutralization with an increased risk of a fatal disease outcome (HR 2.918, 95%CI 1.321-6.449; p=0.008). Neutralizing antibody titers progressively drop after 5-8 weeks but are still detectable up to 8 months in the majority of recovered patients regardless of age or co-morbidities. IgG to Spike antigens are the best correlate of neutralization. Antibody responses to seasonal coronaviruses are temporary boosted and parallel those to SARS-CoV-2 without dampening the specific response or worsening disease progression. Thus, a compromised immune response to the Spike rather than an enhanced one is a major trait of patients with critical conditions. Patients should be promptly identified and immediately start therapeutic interventions aimed at restoring their immunity.