Absent or insufficient anti-SARS-CoV-2 S antibodies at ICU admission are associated to higher viral loads in plasma, antigenemia and mortality in COVID-19 patients

Martin-Vicente, M.; Almansa, R.; Martinez, I.; Tedim, A. P.; Bustamante, E.; Tamayo, L.; Aldecoa, C.; Gomez, J. M.; Renedo, G.; Berezo, J. A.; Cedeno, J. A.; Mamolar, N.; Garcia Olivares, P.; Herran, R.; Cicuendez, R.; Enriquez, P.; Ortega, A.; Jorge, N.; de la Fuente, A.; Bustamante-Munguira, J.; Munoz-Gomez, M. J.; Gonzalez-Rivera, M.; Puertas, C.; Mas, V.; Vazquez, M.; Perez-Garcia, F.; Rico-Feijoo, J.; Martin, S.; Motos, A.; Fernandez-Barat, L.; Eiros, J. M.; Dominguez-Gil, M.; Ferrer, R.; Barbe, F.; Kelvin, D.; Bermejo-Martin, J. F.; Resino, S.; Torres, A.

Purpose: to evaluate the association between anti-SARS-CoV-2 S IgM and IgG antibodies with viral RNA load in plasma, the frequency of antigenemia and with the risk of mortality in critically ill patients with COVID-19. Methods: anti-SARS-CoV-2 S antibodies levels, viral RNA load and antigenemia were profiled in plasma of 92 adult patients in the first 24 hours following ICU admission. The impact of these variables on 30-day mortality was assessed by using Kaplan-Meier curves and multivariate Cox regression analysis. Results: non survivors showed more frequently absence of anti-SARS-CoV-2 S IgG and IgM antibodies than survivors (26.3% vs 5.6% for IgM and 18.4% vs 5.6% for IgG), and a higher frequency of antigenemia (47.4% vs 22.2%) (p <0.05). Non survivors showed lower concentrations of anti-S IgG and IgM and higher viral RNA loads in plasma, which were associated to increased 30-day mortality and decreased survival mean time. [Adjusted HR (CI95%), p]: [S IgM (AUC [≥]60): 0.48 (0.24; 0.97), 0.040]; [S IgG (AUC [≥]237): 0.47 (0.23; 0.97), 0.042]; [Antigenemia (+): 2.45 (1.27; 4.71), 0.007]; [N1 viral load ([≥] 2.156 copies/mL): 2.21 (1.11; 4.39),0.024]; [N2 viral load ([≥] 3.035 copies/mL): 2.32 (1.16; 4.63), 0.017]. Frequency of antigenemia was >2.5-fold higher in patients with absence of antibodies. Levels of anti-SARS-CoV-2 S antibodies correlated inversely with viral RNA load. Conclusion: absence / insufficient levels of anti-SARS-CoV-2 S antibodies following ICU admission is associated to poor viral control, evidenced by increased viral RNA loads in plasma, higher frequency of antigenemia, and also to increased 30-day mortality.