Neutralizing antibody responses to SARS-CoV-2 in symptomatic COVID-19 is persistent and critical for survival

Understanding how antibody responses to SARS-CoV-2 evolve during infection may provide important insight into therapeutic approaches and vaccination for COVID-19. 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. 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). 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. Antibody responses to seasonal coronaviruses are temporarily boosted, and parallel those to SARS-CoV-2 without dampening the specific response or worsening disease progression. 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.

• Figure 8: Variations of the SARS-CoV-2 neutralizing titers between the 2 nd and 3 rd out-patient visit.
• Figure 10. Schematic representation of plasmids used for the LIPS.
Supplementary Tables 1 to 5 • Table 1: Laboratory values at first Biobank blood sampling of the COVID-19 study population.
• Table 4: Characteristics of COVID-19 patients grouped according to their SARS-CoV-2 neutralizing antibody response. (provided as xls file) • Table 5: COVID-BioB study team and collaborators. spike neutralizing and RBD, S1+S2 antibodies during follow-up of the COVID-19 patients. Sera of 162 COVID-19 patients, collected at the indicated timepoints from symptoms onset, were assessed by LV-based neutralization assay (ID50) and the LIPS assay to the various antigens, as indicated in the panels. (a) Correlation matrix of the indicated variables at week 3-4. For each pair, the Pearson's correlation coefficient is shown as number and on a color scale. Statistically non-significant correlations are crossed. (b) Sera of COVID-19 patients, collected at the indicated timepoints from symptoms onset, were assessed by LV-based neutralization assay (ID50) and the LIPS assay, indicated in grey labels above each row/column. Boxes under the diagonal show each correlation plot of the ID50 reciprocal and arbitrary units after log10 conversion. Dots correspond to individual measurements; the black line represents the regression line and the grey area its 95%CI. Boxes on the diagonal show as histograms the distribution of values in each assay. Boxes above the diagonal show the corresponding Pearson correlation analysis coefficients. Asterisks correspond to the following p values: *** p ≤ 0.001; ** p ≤ 0.01; * p ≤ 0.05. Source data are provided as a Source Data file.  Table 1 the serum sample availability of the non-hospitalized COVID-19 patients is described. The clinical characteristics are described in Supplementary Table 3.

Weeks after symptoms onset
Footnote to Supplementary Table 2: No. = number. Neutralization is expressed as the inverse of the serum dilution at which the ID50 was obtained in the LV-based SARS-CoV-2 neutralization assay. A value of 10 was ascribed to the serum that displayed absence of neutralization at the first dilution used (1/40) for the assay. Antibody binding is expressed as arbitrary units. Sample category shows the number and percent of patient's sera tested at each visit according to time (in week intervals) from symptoms onset as depicted in Figure 2. NA= not applicable.  (