Prothrombotic autoantibodies in serum from patients hospitalized with COVID-19

Abstract

Patients with COVID-19 are at high risk for thrombotic arterial and venous occlusions. Lung histopathology often reveals fibrin-based blockages in the small blood vessels of patients who succumb to the disease. Antiphospholipid syndrome is an acquired and potentially life-threatening thrombophilia in which patients develop pathogenic autoantibodies targeting phospholipids and phospholipid-binding proteins (aPL antibodies). Case series have recently detected aPL antibodies in patients with COVID-19. Here, we measured eight types of aPL antibodies in serum samples from 172 patients hospitalized with COVID-19. These aPL antibodies included anticardiolipin IgG, IgM, and IgA; anti–β2 glycoprotein I IgG, IgM, and IgA; and anti-phosphatidylserine/prothrombin (aPS/PT) IgG and IgM. We detected aPS/PT IgG in 24% of serum samples, anticardiolipin IgM in 23% of samples, and aPS/PT IgM in 18% of samples. Antiphospholipid autoantibodies were present in 52% of serum samples using the manufacturer’s threshold and in 30% using a more stringent cutoff (≥40 ELISA-specific units). Higher titers of aPL antibodies were associated with neutrophil hyperactivity, including the release of neutrophil extracellular traps (NETs), higher platelet counts, more severe respiratory disease, and lower clinical estimated glomerular filtration rate. Similar to IgG from patients with antiphospholipid syndrome, IgG fractions isolated from patients with COVID-19 promoted NET release from neutrophils isolated from healthy individuals. Furthermore, injection of IgG purified from COVID-19 patient serum into mice accelerated venous thrombosis in two mouse models. These findings suggest that half of patients hospitalized with COVID-19 become at least transiently positive for aPL antibodies and that these autoantibodies are potentially pathogenic.

Antibody response and therapy in COVID-19 patients: what can be learned for vaccine development?

“…Another potential mechanism of antibody-mediated pathogenesis in COVID-19 patients may be the production of autoantibodies in severe and critically ill patients ( Figure 1B). Severe/critically ill patients with clinically significant coagulopathy were reported to have antiphospholipid (anticardiolipin (CL) and anti-β2-glycoprotein I (β2GPI)) IgA, IgM, and IgG antibodies (Sung and Anjum, 2020;Vlachoyiannopoulos et al, 2020;Zhang et al, 2020f;Zuo et al, 2020). Higher titers of antiphospholipid antibodies were associated with increased release of neutrophil extracellular traps (NETs) (Zuo et al, 2020).…”

“…Severe/critically ill patients with clinically significant coagulopathy were reported to have antiphospholipid (anticardiolipin (CL) and anti-β2-glycoprotein I (β2GPI)) IgA, IgM, and IgG antibodies (Sung and Anjum, 2020;Vlachoyiannopoulos et al, 2020;Zhang et al, 2020f;Zuo et al, 2020). Higher titers of antiphospholipid antibodies were associated with increased release of neutrophil extracellular traps (NETs) (Zuo et al, 2020). NETs infiltrate the lung airway, interstitial, and vascular compartments in severe COVID-19 patients and contribute to pathogenesis (Radermecker et al, 2020).…”

COVID-19 in patients with systemic lupus erythematosus: lessons learned from the inflammatory disease

“…112 In addition, IgG fractions of antiphospholipid antibodies promoted NET release in vitro and induced accelerated venous thrombosis in mice. 112 Nonetheless, there is still a lack of longitudinal studies assessing the persistence of antiphospholipid antibodies several weeks after COVID-19 diagnosis, 108 and it is possible that this represents a transient event as it has been demonstrated in the setting of other infections. [113][114][115] Dysregulation of the complement system.…”

Biomaterials-Based Opportunities to Engineer the Pulmonary Host Immune Response in COVID-19

“… 59 , 60 Activated neutrophils and high occurrence of prothrombotic autoantibodies that promote clotting events have been implicated in COVID-19 disease severity. 61 The impaired immune response, which includes the cytokine storm, otherwise known as hypercytokinemia, can result in plasma leakage, vascular permeability, and edema, all of which are commonly observed in severe COVID-19 patients ( Figure 1 J,K). The cytokine storm and the extent of recruitment of inflammatory cells are indicative of the severity of the COVID-19 infection.…”