Low anti-SARS-CoV-2 S antibody levels predict increased mortality and dissemination of viral components in the blood of critical COVID-19 patients

Abstract

Background: Anti-SARS-CoV-2 S antibodies prevent viral replication. Critically ill COVID-19 patients show viral material in plasma, associated with a dysregulated host response. If these antibodies influence survival and viral dissemination in ICU-COVID patients is unknown.

Patients/methods: We studied the impact of anti-SARS-CoV-2 S antibodies levels on survival, viral RNA-load in plasma, and N-antigenaemia in 92 COVID-19 patients over ICU admission.

Results: Frequency of N-antigenaemia was >2.5-fold higher in absence of antibodies. Antibodies correlated inversely with viral RNA-load in plasma, representing a protective factor against mortality (adjusted HR [CI 95%], p): (S IgM [AUC ≥ 60]: 0.44 [0.22; 0.88], 0.020); (S IgG [AUC ≥ 237]: 0.31 [0.16; 0.61], <0.001). Viral RNA-load in plasma and N-antigenaemia predicted increased mortality: (N1-viral load [≥2.156 copies/ml]: 2.25 [1.16; 4.36], 0.016); (N-antigenaemia: 2.45 [1.27; 4.69], 0.007).

Conclusions: Low anti-SARS-CoV-2 S antibody levels predict mortality in critical COVID-19. Our findings support that these antibodies contribute to prevent systemic dissemination of SARS-CoV-2.

Keywords: COVID-19; RNA; antibodies; antigenaemia; mortality.

Fig. 1

Panel 1: Frequencies of patients with positive SARS‐CoV‐2 S antibodies (IgM, IgG) and antigenaemia by survival status 30 days following ICU admission. Panel 2: Levels of SARS‐CoV‐2 S antibodies (IgM, IgG) and viral RNA load (N1, N2) in plasma following ICU admission by survival status at day 30. Panel 3: Frequency of N‐antigenaemia in those patients with absence or presence of anti SARS‐CoV‐2 S IgM or anti SARS‐CoV‐2 S IgG antibodies. Panel 4: Heat map showing the correlation coefficients between anti SARS‐CoV‐2 S antibodies and viral RNA load in plasma.

Fig. 2

Upper panel: Kaplan–Meier curves to represent survival by day 30 following ICU admission depending on the presence or absence of SARS‐CoV‐2 S antibodies (IgM, IgG) (a and c), the presence or absence of antigenaemia (e), the presence of higher/lower levels of SARS‐CoV‐2 S antibodies (IgM, IgG) (b and d) or viral RNA load in plasma (N1,N2) (f and g). Lower panel: Cox regression analysis to assess risk of 30‐day mortality following ICU admission. Statistics: p‐values were calculated by univariate (a) and multivariate (b) analysis adjusted by the most relevant covariates (see Statistical Analysis section). Significant differences are shown in bold Abbreviations: 95% CI, 95% confidence interval; aHR, adjusted HR; HR, hazard ratio; p‐value, level of significance.