Anti-phospholipid antibodies in COVID-19 are different from those detectable in the anti-phospholipid syndrome

  1. Maria Orietta Borghi
  2. Asmaa Beltagy
  3. Emirena Garrafa
  4. Daniele Curreli
  5. Germana Cecchini
  6. Caterina Bodio
  7. Claudia Grossi
  8. Simonetta Blengino
  9. Angela Tincani
  10. Franco Franceschini
  11. Laura Andreoli
  12. Maria Grazia Lazzaroni
  13. Silvia Piantoni
  14. Stefania Masneri
  15. Francesca Crisafulli
  16. Duilio Brugnoni
  17. Maria Lorenza Muiesan
  18. Massimo Salvetti
  19. Gianfranco Parati
  20. Erminio Torresani
  21. Michael Mahler
  22. Francesca Heilbron
  23. Francesca Pregnolato
  24. Martino Pengo
  25. Francesco Tedesco
  26. Nicola Pozzi
  27. Pier Luigi Meroni
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Abstract

Background

Critically ill patients with coronavirus disease 2019 (COVID-19) have a profound hypercoagulable state and often develop coagulopathy which leads to organ failure and death. Because of a prolonged activated partial-thromboplastin time (aPTT), a relationship with anti-phospholipid antibodies (aPL) has been proposed, but results are controversial. Functional assays for aPL (i.e., lupus anticoagulant) can be influenced by concomitant anticoagulation and/or high levels of C reactive protein. The presence of anti-cardiolipin (aCL), anti-beta2-glycoprotein I (anti-β2GPI) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies was not investigated systematically. Epitope specificity of anti-β2GPI antibodies was not reported.

Objective

To evaluate the prevalence and the clinical association of aPL in a large cohort of COVID-19 patients, and to characterize the epitope specificity of anti-β2GPI antibodies.

Methods

ELISA and chemiluminescence assays were used to test 122 sera of patients suffering from severe COVID-19. Of them, 16 displayed major thrombotic events.

Results

Anti-β2GPI IgG/IgA/IgM were the most frequent in 15.6/6.6/9.0% of patients, while aCL IgG/IgM were detected in 5.7/6.6% by ELISA. Comparable values were found by chemiluminescence. aPS/PT IgG/IgM were detectable in 2.5 and 9.8% by ELISA. No association between thrombosis and aPL was found. Reactivity against domain 1 and 4-5 of β2GPI was limited to 3/58 (5.2%) tested sera for each domain and did not correlate with aCL/anti-β2GPI nor with thrombosis.

Conclusions

aPL show a low prevalence in COVID-19 patients and are not associated with major thrombotic events. aPL in COVID-19 patients are mainly directed against β2GPI but display an epitope specificity different from antibodies in antiphospholipid syndrome.

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