Disease severity dictates SARS-CoV-2-specific neutralizing antibody responses in COVID-19

Abstract

COVID-19 patients exhibit differential disease severity after SARS-CoV-2 infection. It is currently unknown as to the correlation between the magnitude of neutralizing antibody (NAb) responses and the disease severity in COVID-19 patients. In a cohort of 59 recovered patients with disease severity including severe, moderate, mild, and asymptomatic, we observed the positive correlation between serum neutralizing capacity and disease severity, in particular, the highest NAb capacity in sera from the patients with severe disease, while a lack of ability of asymptomatic patients to mount competent NAbs. Furthermore, the compositions of NAb subtypes were also different between recovered patients with severe symptoms and with mild-to-moderate symptoms. These results reveal the tremendous heterogeneity of SARS-CoV-2-specific NAb responses and their correlations to disease severity, highlighting the needs of future vaccination in COVID-19 patients recovered from asymptomatic or mild illness.

Fig. 1

Antibody responses to SARS-CoV-2 in COVID-19 recovered patients with different symptom severity. a–c ELISA binding assays of 100-fold diluted COVID-19 patient sera to ELISA plates after coating with SARS-CoV-2 S1 (a), RBD (b), and S2 (c) proteins. The dashed lines in a–c represent the average values of the healthy control groups. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001. ns not significant. Error bars in a–c indicate SEM

Fig. 2

Neutralizing antibody responses to SARS-CoV-2 in COVID-19 recovered patients. a Scores showing the COVID-19 patient serum-mediated inhibition of the SARS-CoV-2 RBD protein binding to ACE2 protein by ELISA. b Pie charts showing the proportions of patients with high (>50, green) or low (<50, red) RBD-ACE2-binding inhibition score in each indicated situations. c Patient serum-mediated blocking of luciferase-encoding SARS-CoV-2-typed pseudovirus into ACE2/293T cells. The dashed line indicates the cutoff value (7.121) determined by the ROC curve analysis. d Pie charts showing the proportions of patients with pseudovirus neutralization positive (<7.121, green) or negative (>7.121, red) in each indicated situations. e Patient serum-mediated blocking of SARS-CoV-2 virus into Vero E6 cells. f A table showing the fold change of SARS-CoV-2 viral RNA fold reduction between indicated two groups in e. *P < 0.05, **P < 0.01, and ****P < 0.0001. ns not significant. Error bars in a, c, e indicate SEM

Fig. 3

Subtypes of neutralizing antibodies to SARS-CoV-2 S proteins in COVID-19 recovered patients. a Blocking of luciferase-encoding SARS-CoV-2 typed pseudovirus into ACE2/293T cells by patient sera (no depletion) or S1 antibody-depleted sera (S1-Abs depletion) or S2 antibody-depleted sera (S2-Abs depletion). The dashed line indicates the cutoff value (6.749) determined by the ROC curve analysis. HC healthy control, NC negative control. b, c Pie charts showing the proportions of patients with different neutralizing antibody (NAb) subtype responses in the total 25 patients (b), 8 severe patients (c, left panel), and 17 moderate and mild patients (c, right panel) of pseudovirus neutralization positive. d Blocking of luciferase-encoding SARS-CoV-2 typed pseudovirus into ACE2/293T cells by “S1-NAbs only” patient sera with RBD antibody depletion (RBD-Abs depletion) or without RBD antibody depletion (no depletion). The dashed line indicates the cutoff value (6.034) determined by the ROC curve analysis. HC healthy control, NC negative control. e Pie chart showing the proportions of “S1-NAbs only” patients with RBD-Nab-dependent or -independent antibody response. Error bars in a, d indicate SEM