All had a confirmed SARS-CoV-2 infection and a record of symptoms onset. We profiled the humoral immune response of 162 patients within our COVID-BioB cohort. Our results indicate that early development of nAbs is critical for patient survival and virus control, supporting the early introduction of mAb therapy after infection in selected severely ill patients, and suggest that nAbs induced by prophylactic vaccination will most likely be long-lasting. We test 162 patients using a newly developed, robust lentiviral vector (LV)-based SARS-CoV-2 neutralization assay and the LIPS assay for the detection of IgG, IgM, and IgA to SARS-CoV-2 spike, RBD and nucleoprotein (NP) as well as IgG to the spike S2 protein of seasonal beta coronaviruses, and to H1N1 influenza virus hemagglutinin. Here we provide a comprehensive antibody profile of well-characterized COVID-19 symptomatic patients followed longitudinally for up to eight months from symptom onset. In light of the current timing of the pandemic, most published serological studies are predominantly cross-sectional or at most include a longitudinal follow-up of few months 3, 12– 14. Whether SARS-CoV-2 nAbs decline at a similar pace is yet to be conclusively established. In addition, studies dealing with infections carried out by MERS and SARS-CoV beta coronaviruses, two viruses closely related to SARS-CoV-2, suggest that the anti-viral humoral immunity, sometimes still detectable more than a year after hospitalization, wanes over time 10, 11. However, the impact of nAbs on COVID-19 course is still controversial with some studies even suggesting either a detrimental role for nAbs in disease progression 8, 9 or finding no nAbs differences among hospitalized patients who subsequently experienced varying disease outcomes 3. ![]() Furthermore, anti-spike neutralizing antibodies (nAbs) produced by COVID-19 patients can block viral infection of human cells in vitro and counter viral replication in vivo 3, 6, 8, 9. The spike glycoprotein mediates entry into target cells via the ACE2 receptor and clinical trials with monoclonal antibodies (mAbs) against its RBD decreased viral load in patients with recently diagnosed mild/moderate COVID-19 5– 7. Moreover, the early presence of anti-RBD IgG and anti-spike IgA positively correlated with patient survival and reduced persistence of SARS-CoV-2 RNA in naso-pharyngeal swabs, respectively. Using a newly developed Luciferase Immunoprecipitation System (LIPS) assay, we previously detected anti-RBD IgG in 95% of COVID-19 patients by the fourth week from symptom onset and observed that these antibodies increased throughout follow-up until the third month post-hospital discharge 4. Studies in large cohorts of SARS-CoV-2 infected individuals indicate that antibodies to the receptor-binding domain (RBD) of the viral spike glycoprotein appear within the first three weeks from symptoms onset and that IgG and/or IgA seroconversion occurs either sequentially or simultaneously with the appearance of IgM 2, 3. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can be fatal in a significant proportion of hospitalized Corona Virus Disease 19 (COVID-19) patients despite the development of an anti-viral antibody response 1. Our results thus suggest compromised immune responses to the SARS-CoV-2 spike to be a major trait of COVID-19 patients with critical conditions, and thereby inform on the planning of COVID-19 patient care and therapy prioritization. Antibody responses to seasonal coronaviruses are temporarily boosted, and parallel those to SARS-CoV-2 without dampening the specific response or worsening disease progression. ![]() ![]() 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, with IgG to spike antigens providing the best correlate of neutralization. The presence of neutralizing antibodies within the first weeks from symptoms onset correlates with time to a negative swab result (p = 0.002), while the lack of neutralizing capacity correlates with an increased risk of a fatal outcome (p = 0.008). Here we profile the antibody responses of 162 COVID-19 symptomatic patients in the COVID-BioB cohort followed longitudinally for up to eight months from symptom onset to find SARS-CoV-2 neutralization, as well as antibodies either recognizing SARS-CoV-2 spike antigens and nucleoprotein, or specific for S2 antigen of seasonal beta-coronaviruses and hemagglutinin of the H1N1 flu virus. ![]() Understanding how antibody responses to SARS-CoV-2 evolve during infection may provide important insight into therapeutic approaches and vaccination for COVID-19.
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