More than 50% of patients with COVID-19 positive for antiphospholipid antibodies
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A significant proportion of patients with COVID-19 — up to 52% by one metric — are at least transiently positive for potentially pathogenic antiphospholipid autoantibodies, according to a speaker at ACR Convergence.
“Do COVID-19 patients get blood clots? Yes, they do,” Yu Zuo, MD, a physician scientist in the field of antiphospholipid syndrome and COVID-19 at the University of Michigan, told attendees at the virtual meeting. “According to Professor [Beverley Jane] Hunt, a world-renowned expert in thrombosis from the UK, she had never seen such sticky blood. There are now increasing reports of both arterial and venous thrombosis in patients with COVID-19. Histopathology from lung isthmus from patients with severe disease show not only characteristic findings of ARDS, but also evidence of occlusion of small vessels.”
“Antiphospholipid syndrome is an acquired thromboinflammatory disorder, characterized by recurrent thromboembolic events and pregnancy loss,” he added. “APS patients form antiphospholipid antibodies, and these antibodies can activate endothelial cells, platelets and neutrophils, thereby promoting thrombus formation. Catastrophic APS is the most severe type of APS and is frequently fatal. Clinically, it bears some similarities with severe COVID-19, such as cytokine storm and diffuse coagulopathy. There are small case reports and series that suggest that antiphospholipid autoantibodies might be present in COVID-19 patients, and they may contribute to thrombosis.”
To measure antiphospholipid autoantibodies in patients hospitalized with COVID-19 and analyze whether purified IgG fractions from these patients had prothrombotic properties in vitro and in vivo, Zuo and colleagues examined sera from 172 participants. Samples were assessed for eight types of antiphospholipid autoantibodies, including anticardiolipin IgG/IgM/IgA, anti-beta-2 glycoprotein I IgG/IgM/IgA, and anti-phosphatidylserine/prothrombin (PS/PT) IgG/IgM.
IgG fractions were then purified from patients with COVID-19 with various profiles of antiphospholipid autoantibodies. The researchers evaluated the prothrombotic potential of purified IgG fractions in neutrophil extracellular trap (NET) assays, as well as in two mouse models of inferior vena cava thrombosis.
According to the researchers, 23% of participants demonstrated anticardiolipin IgM antibodies, 24% had anti-PS/PT IgG and 18% had anti-PS/PT IgM. In all, 52% demonstrated any antiphospholipid autoantibodies, based on the manufacturer’s threshold, while 30% had them using a more stringent cutoff of at least 40 units. In addition, high antiphospholipid autoantibody levels were associated with more severe COVID-19. For example, anti-PS/PT IgM levels were significantly linked with neutrophil activation, circulating NETs and more severe respiratory disease (P = .03). The researchers reported similar correlations for anticardiolipin IgM.
Additionally, the presence of any antiphospholipid autoantibodies predicted impaired kidney function, defined by estimated glomerular filtration rate (P = .03). Purified IgG fractions from patients who were positive for antiphospholipid autoantibodies — either anti-2GPI IgG or anti-PS/PT IgG — promoted NET release from control neutrophils, similar to IgG isolated from individuals with established antiphospholipid syndrome.
Lastly, injecting COVID-19 IgG fractions — isolated from four different patients with high levels of anti-PS/PT IgG — into mice more than doubled thrombus extension and accretion in two separate models of inferior vena cava thrombosis. In addition, administration of the COVID-19 IgG also significantly increased circulating NET remnants in mice (P = .0004), similar to IgG from patients with catastrophic antiphospholipid syndrome (P = .001), the researchers wrote.
“More than half of hospitalized COVID-19 patients have positive antiphospholipid antibodies, particularly a non-criteria antiphospholipid antibodies anti- phosphatidylserine/prothrombin,” Zuo said. “COVID-19-associated antiphospholipid antibodies correlate with a neutrophil activation, impaired oxygenation and renal disfunction. Purified IgG fractions from some COVID-19 patients trigger neutrophil extracellular trap release from healthy neutrophils, and IgG fractions from some COVID-19 patients accelerate thrombosis in vivo.”
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Zuo Y. Abstract 0429. Presented at: ACR Convergence 2020; November 5-9, 2020 (virtual meeting).
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