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

  1. MarĂ­a Martin-Vicente
  2. Raquel Almansa
  3. Isidoro MartĂ­nez
  4. Ana P. Tedim
  5. Elena Bustamante
  6. Luis Tamayo
  7. CĂ©sar Aldecoa
  8. José Manuel Gómez
  9. Gloria Renedo
  10. Jose Ángel Berezo
  11. Jamil Antonio Cedeño
  12. Nuria Mamolar
  13. Pablo GarcĂ­a Olivares
  14. Rubén Herrån
  15. RamĂłn Cicuendez
  16. Pedro EnrĂ­quez
  17. Alicia Ortega
  18. Noelia Jorge
  19. Amanda de la Fuente
  20. Juan Bustamante-Munguira
  21. María José Muñoz-Gómez
  22. Milagros GonzĂĄlez-Rivera
  23. Carolina Puertas
  24. Vicente MĂĄs
  25. MĂłnica VĂĄzquez
  26. Felipe PĂ©rez-GarcĂ­a
  27. JesĂșs Rico-Feijoo
  28. Silvia MartĂ­n
  29. Anna Motos
  30. Laia Fernandez-Barat
  31. Jose MarĂ­a Eiros
  32. Marta Dominguez-Gil
  33. Ricard Ferrer
  34. Ferrån Barbé
  35. David J Kelvin
  36. JesĂșs F Bermejo-Martin
  37. Salvador Resino
  38. Antoni Torres
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Abstract

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.

Take-home message

absent or low levels of antibodies against the S protein of SARS-CoV- 2 at ICU admission is associated to an increased risk of mortality, higher frequency of antigenemia and higher viral RNA loads in plasma. Profiling anti-SARS-CoV-2 s antibodies at ICU admission could help to predict outcome and to better identify those patients potentially deserving replacement treatment with monoclonal or polyclonal antibodies.

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